The Opioid Analgesic Reduction Study (OARS) Pilot: A Double-Blind Randomized Multicenter Trial.

BACKGROUND: With addiction rates and opioid deaths increasing, health care providers are obligated to help stem the opioid crisis. As limited studies examine the comparative effectiveness of fixed-dose combination nonopioid analgesia to opioid-containing analgesia, a comparative effectiveness study was planned and refined by conducting a pilot study. METHODS: The Opioid Analgesic Reduction Study (OARS) pilot, a stratified, randomized, multisite, double-blind clinical trial, was designed to test technology and procedures to be used in the full OARS trial. Participants engaged in the full protocol, enabling the collection of OARS outcome data. Eligible participants reporting to 1 of 5 sites for partial or full bony impacted mandibular third molar extraction were stratified by biologic sex and randomized to 1 of 2 treatment groups, OPIOID or NONOPIOID. OPIOID participants were provided 20 doses of hydrocodone 5 mg/acetaminophen 300 mg. NONOPIOID participants were provided 20 doses of ibuprofen 400 mg/acetaminophen 500 mg. OARS outcomes data, including pain experience, adverse effects, sleep quality, pain interference, overall satisfaction, and remaining opioid tablets available for diversion, were collected via surveys, electronic medication bottles, eDiary, and activity/sleep monitor. RESULTS: Fifty-three participants were randomized with 50 completing the OARS pilot protocol. Across all outcome pain domains, in all but 1 time period, NONOPIOID was better in managing pain than OPIOID (P < 0.05 level). Other outcomes suggest less pain interference, less adverse events, better sleep quality, better overall satisfaction, and fewer opioid-containing tablets available for diversion. DISCUSSION: Results suggest patients requiring impacted mandibular third molar extraction would benefit from fixed-dose combination nonopioid analgesia. KNOWLEDGE TRANSFER STATEMENT: Study results suggest fixed-dose nonopioid combination ibuprofen 400 mg/acetaminophen 500 mg is superior to opioid-containing analgesic (hydrocodone 5 mg/acetaminophen 500 mg). This knowledge should inform surgeons and patients in the selection of postsurgical analgesia.

Selective Inhibition of NaV1.8 with VX-548 for Acute Pain.

BACKGROUND: The NaV1.8 voltage-gated sodium channel, expressed in peripheral nociceptive neurons, plays a role in transmitting nociceptive signals. The effect of VX-548, an oral, highly selective inhibitor of NaV1.8, on control of acute pain is being studied. METHODS: After establishing the selectivity of VX-548 for NaV1.8 inhibition in vitro, we conducted two phase 2 trials involving participants with acute pain after abdominoplasty or bunionectomy. In the abdominoplasty trial, participants were randomly assigned in a 1:1:1:1 ratio to receive one of the following over a 48-hour period: a 100-mg oral loading dose of VX-548, followed by a 50-mg maintenance dose every 12 hours (the high-dose group); a 60-mg loading dose of VX-548, followed by a 30-mg maintenance dose every 12 hours (the middle-dose group); hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. In the bunionectomy trial, participants were randomly assigned in a 2:2:1:2:2 ratio to receive one of the following over a 48-hour treatment period: oral high-dose VX-548; middle-dose VX-548; low-dose VX-548 (a 20-mg loading dose, followed by a 10-mg maintenance dose every 12 hours); oral hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. The primary end point was the time-weighted sum of the pain-intensity difference (SPID) over the 48-hour period (SPID48), a measure derived from the score on the Numeric Pain Rating Scale (range, 0 to 10; higher scores indicate greater pain) at 19 time points after the first dose of VX-548 or placebo. The main analysis compared each dose of VX-548 with placebo. RESULTS: A total of 303 participants were enrolled in the abdominoplasty trial and 274 in the bunionectomy trial. The least-squares mean difference between the high-dose VX-548 and placebo groups in the time-weighted SPID48 was 37.8 (95% confidence interval [CI], 9.2 to 66.4) after abdominoplasty and 36.8 (95% CI, 4.6 to 69.0) after bunionectomy. In both trials, participants who received lower doses of VX-548 had results similar to those with placebo. Headache and constipation were common adverse events with VX-548. CONCLUSIONS: As compared with placebo, VX-548 at the highest dose, but not at lower doses, reduced acute pain over a period of 48 hours after abdominoplasty or bunionectomy. VX-548 was associated with adverse events that were mild to moderate in severity. (Funded by Vertex Pharmaceuticals; VX21-548-101 and VX21-548-102 ClinicalTrials.gov numbers, NCT04977336 and NCT05034952.).

Serotonin syndrome from combination hydrocodone and cyclobenzaprine in a patient with cerebral palsy.

Aim: Serotonin syndrome (SS) is a life-threatening syndrome that occurs with the use of serotonergic drugs, most commonly due to two or more agents. Cerebral palsy is associated with mood disorders, and more commonly pain, with a prevalence of up to 50-80%. Case presentation: A 58-year-old female with cerebral palsy, metastatic malignancy and mood disorder who presented to the emergency department with acute-on-chronic pain, and signs of SS. She was initiated on iv. dilaudid, titrated off oral medications and scheduled for a left-sided sacroiliac joint injection. Results: It was suspected that due to additional doses of hydrocodone and cyclobenzaprine, she developed moderate-SS. Conclusion: Physicians need to be cognizant of comorbidities and uncommon pain medications that can predispose patients to SS.

Opioid prescribing patterns by drug type: The Pennsylvania experience.

OBJECTIVE: To explore the impact on opioid prescribing patterns and trends after implementing a prescription drug monitoring program (PDMP) in Pennsylvania from 2016 to 2020. DESIGN: A cross-sectional data analysis using deidentified data from Pennsylvania's PDMP delivered by the Pennsylvania Department of Health was undertaken. SETTING: Data were collected from the entire state of Pennsylvania, and statistics were run at Rothman Orthopedic Institute Foundation for Opioid Research & Education. INTERVENTIONS: Evaluating the effect on opioid prescriptions after introduction of the PDMP. MAIN OUTCOME MEASURE: In 2016, nearly 2 million opioid prescriptions were given to patients across the state. However, by the end of the study period in 2020, there was a 38 percent decrease in opioid prescriptions written. RESULTS: Beginning with Q3 2016, each subsequent quarter saw fewer opioids prescribed, decreasing on average by 3.4 ± 1.7 percent through Q1 2020. Specifically, over 700,000 fewer prescriptions were in the first quarter of 2020 compared to the third quarter in 2016. The opioids that were most frequently prescribed were oxycodone, hydrocodone, and morphine. CONCLUSION: While fewer prescriptions were being prescribed overall, the breakdown of drug type being prescribed remained similar in 2020 compared to 2016. Fentanyl and hydrocodone saw the largest decrease between 2016 and 2020.

Acute Renal Insufficiency Associated With Consumption of Hydrocodone- and Morphine-Adulterated Kratom (Mitragyna Speciosa).

BACKGROUND: Kratom (Mitragyna speciosa), an evergreen tree native to Southeast Asia, contains alkaloids that cause both stimulant and opioid-like effects. In the United States, its use continues to grow. Kratom products, however, are unregulated and nonstandardized, and reports of adulteration have been described previously. CASE REPORT: A 21-year-old African-American woman with a history of occasional headaches and self-treatment with internet-purchased kratom presented to the emergency department with the chief symptoms of nausea, vomiting, and left flank pain. Laboratory tests showed a markedly elevated serum creatinine of 4.25 mg/dL (reference range 0.6-1.2 mg/dL) and proteinuria. A computed tomography scan of the abdomen and pelvis was unrevealing. A standard urine screen for drugs of abuse was positive for opiates. A confirmatory testing revealed the presence of hydrocodone and morphine in the urine. Hydrocodone, morphine, and mitragynine were identified in a sample of kratom leaves provided by the patient. The patient's renal function improved with supportive care and normalized 1 month post discharge after kratom discontinuation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Despite widespread use, relatively little is known about kratom's adverse effects, particularly regarding its potential to cause renal insufficiency. This case illustrates the vital importance of recognizing that adulteration of unregulated products is certainly a possibility and clinicians may continue to see a rise in adverse effects, given kratom's increasing popularity.

Development of a potential opioid misuse measure from administrative dispensing data and contrasting opioid misuse among individuals on long-term tramadol, long-term short-acting hydrocodone or long-term short-acting oxycodone therapy in Arkansas.

OBJECTIVE: This study sought to: (1) construct and validate a composite potential opioid misuse score; and (2) compare potential opioid misuse among individuals prescribed long-term therapy on tramadol, short-acting hydrocodone or short-acting oxycodone. METHODS: A retrospective cohort study was conducted using Arkansas All-Payer Claims Database (APCD; 2013-2018) linked to Arkansas Prescription Drug Monitoring Program (PDMP; 2014-2017) and state death certificate data (2013-2018). The study subjects were ambulatory, cancer-free adults with incident long-term therapy on tramadol, short-acting hydrocodone or short-acting oxycodone. The number of opioid prescribers/pharmacies, cash payment for opioid prescriptions, overlapping prescribers/pharmacies and a composite misuse score (derived from opioid prescribers/pharmacies and cash payment) were assessed in two 180 day windows as potential measures of misuse. The composite score was developed based on associations observed with opioid overdose and opioid-related injuries. RESULTS: A total of 17,816 (tramadol), 23,660 (hydrocodone) and 4799 (oxycodone) persons were included. The composite score had modest discrimination for overdose (c-index = 0.65). In the first 180 day period, the average composite misuse scores were 1.28 (tramadol), 1.93 (hydrocodone) and 2.18 (oxycodone). Compared to long-term hydrocodone, long-term tramadol had lower misuse (IRR [95% CI]: 0.75 [0.73-0.76]), and long-term oxycodone had higher misuse (1.09 [1.07-1.11]) in adjusted analyses. Qualitatively similar associations were observed for nearly all individual component measures of misuse. CONCLUSION: A composite measure of potential opioid misuse had modest levels of discrimination in detecting overdose. In comparison to long-term hydrocodone therapy, long-term oxycodone had higher and tramadol had lower risk of potential opioid misuse.

Quantification of opioid dependence and abuse prevalence in the United States between 2017 and 2018.

OBJECTIVES: To quantify the prevalence of opioid drug dependence and abuse in United States between 2017 and 2018 and identify which opioid molecules are associated with a higher level of dependence and abuse. DESIGN: National Survey on Drug Use and Health (NSDUH) data for 2017 and 2018 have been extracted. The variables related to painkillers were studied, the most important ones were selected, and several variable crosses were made. After the data were extracted, they were analyzed using Microsoft Excel and PivotTables, calculating the relative prevalence and percentages of patients with abuse and dependence. RESULTS: In total, 1.4 million people had dependence on pain relievers (PRs) in 2018. The last PR used was mostly hydrocodone (33 percent) and oxycodone (24 percent). The main reasons for using a PR without a doctor's prescription were relieving pain (48 percent), feel good (16 percent), and relax or relieve tension (15 percent). Among patients who used a PR with a medical prescription, 1.5 million used it more frequently than prescribed, 1.2 million used it longer than prescribed, and 1.9 million used it in higher amounts than prescribed. CONCLUSIONS: Abuse and dependence to PRs is lower than expected with over 1.4 million people in the United States having dependence in 2018 (0.6 percent point prevalence). Most cases of dependence are associated with misuse or abuse of prescriptions without medical supervision or the use of medications without a prescription of their own. Oxycodone and hydrocodone are the molecules most associated with dependence, misuse, abuse, and use without prescription. The age of onset of oxycodone misuse is very early (14 years old). Fentanyl does not seem relevant in any of the variables studied.

Opioid-related overdose and chronic use following an initial prescription of hydrocodone versus oxycodone.

BACKGROUND: Hydrocodone and oxycodone are prescribed commonly to treat pain. However, differences in risk of opioid-related adverse outcomes after an initial prescription are unknown. This study aims to determine the risk of opioid-related adverse events, defined as either chronic use or opioid overdose, following a first prescription of hydrocodone or oxycodone to opioid naïve patients. METHODS: A retrospective analysis of multiple linked public health datasets in the state of Oregon. Adult patients ages 18 and older who a) received an initial prescription for oxycodone or hydrocodone between 2015-2017 and b) had no opioid prescriptions or opioid-related hospitalizations or emergency department visits in the year preceding the prescription were followed through the end of 2018. First-year chronic opioid use was defined as ≥6 opioid prescriptions (including index) and average ≤30 days uncovered between prescriptions. Fatal or non-fatal opioid overdose was indicated from insurance claims, hospital discharge data or vital records. RESULTS: After index prescription, 2.8% (n = 14,458) of individuals developed chronic use and 0.3% (n = 1,480) experienced overdose. After adjustment for patient and index prescription characteristics, patients receiving oxycodone had lower odds of developing chronic use relative to patients receiving hydrocodone (adjusted odds ratio = 0.95, 95% confidence interval (CI) 0.91-1.00) but a higher risk of overdose (adjusted hazard ratio (aHR) = 1.65, 95% CI 1.45-1.87). Oxycodone monotherapy appears to greatly increase the hazard of opioid overdose (aHR 2.18, 95% CI 1.86-2.57) compared with hydrocodone with acetaminophen. Oxycodone combined with acetaminophen also shows a significant increase (aHR 1.26, 95% CI 1.06-1.50), but not to the same extent. CONCLUSIONS: Among previously opioid-naïve patients, the risk of developing chronic use was slightly higher with hydrocodone, whereas the risk of overdose was higher after oxycodone, in combination with acetaminophen or monotherapy. With a goal of reducing overdose-related deaths, hydrocodone may be the favorable agent.

Opioid Misuse Among American Indian Adolescents.

Objectives. To present data for opioid misuse among US reservation-based American Indian (AI) adolescents and to compare these data with national rates from Monitoring the Future (MTF).Methods. Data were from a national sample of 33 schools participating in a substance use epidemiological survey of reservation-based AI adolescents during 2018 and 2019. Participants were 8th-, 10th-, and 12th-grade AI students (n = 1592). Measures included 12-month and 30-day use of OxyContin, Vicodin, heroin, and narcotics. We computed prevalence and compared it with MTF national prevalence.Results. Across grades, AI youths demonstrated significantly greater past 12-month and 30-day opioid use relative to a national sample. Significant absolute differences in 12-month and 30-day prevalence levels ranged from 1.6% (8th-grade heroin) to 4.7% (12th-grade narcotics) and from 1.6% (12th-grade narcotics) to 1.8% (12th-grade heroin), respectively.Conclusions. Opioid misuse prevalence levels were significantly greater for reservation-based AI adolescents relative to national prevalence levels.Public Health Implications. Findings suggest that implementation of evidence-based efforts, adapted or developed to be culturally appropriate, should be significantly increased in tribal communities, along with policies to address the unique social, economic, and health issues they face.

Reduction of Drug-Drug Interaction Risk; CDC Guidelines Influence on Opiate Benzodiazepine Prescribing.

We examined the results of 1.3 million drug tests performed on patients being monitored for compliance with pain medications and substance abuse rehabilitation to determine if the 2016 CDC prescribing guidelines had any impact on opiate benzodiazepine use. We observed that the combination of the opiate drugs morphine, oxycodone, and hydrocodone with the benzodiazepine metabolites oxazepam, alphahydroxyalprazolam, and 7-aminoclonazepam showed many patients were on a combination of these drugs. This ranged from approximately 9 to 16%. There was considerable variability between opiate drug pairs, but there was a general trend to fewer patients on the combination of opiate-benzodiazepine over the 2016 to 2019 time frame.

Online Conversation Monitoring to Understand the Opioid Epidemic: Epidemiological Surveillance Study.

BACKGROUND: Between 2016 and 2017, the national mortality rate involving opioids continued its escalation; opioid deaths rose from 42,249 to 47,600, bringing the public health crisis to a new height. Considering that 69% of adults in the United States use online social media sites, a resource that builds a more complete understanding of prescription drug misuse and abuse could supplement traditional surveillance instruments. The Food and Drug Administration has identified 5 key risks and consequences of opioid drugs-misuse, abuse, addiction, overdose, and death. Identifying posts that discuss these key risks could lead to novel information that is not typically captured by traditional surveillance systems. OBJECTIVE: The goal of this study was to describe the trends of online posts (frequency over time) involving abuse, misuse, addiction, overdose, and death in the United States and to describe the types of websites that host these discussions. Internet posts that mentioned fentanyl, hydrocodone, oxycodone, or oxymorphone were examined. METHODS: Posts that did not refer to personal experiences were removed, after which 3.1 million posts remained. A stratified sample of 61,000 was selected. Unstructured data were classified into 5 key risks by manually coding for key outcomes of misuse, abuse, addiction, overdose, and death. Sampling probabilities of the coded posts were used to estimate the total post volume for each key risk. RESULTS: Addiction and misuse were the two most commonly discussed key risks for hydrocodone, oxycodone, and oxymorphone. For fentanyl, overdose and death were the most discussed key risks. Fentanyl had the highest estimated number of misuse-, overdose-, and death-related mentions (41,808, 42,659, and 94,169, respectively). Oxycodone had the highest estimated number of abuse- and addiction-related mentions (3548 and 12,679, respectively). The estimated volume of online posts for fentanyl increased by more than 10-fold in late 2017 and 2018. The odds of discussing fentanyl overdose (odds ratios [OR] 4.32, 95% CI 2.43-7.66) and death (OR 5.05, 95% CI 3.10-8.21) were higher for social media, while the odds of discussing fentanyl abuse (OR 0.10, 95% CI 0.04-0.22) and addiction (OR 0.24, 95% CI 0.15-0.38) were higher for blogs and forums. CONCLUSIONS: Of the 5 FDA-defined key risks, fentanyl overdose and death has dominated discussion in recent years, while discussion of oxycodone, hydrocodone, and oxymorphone has decreased. As drug-related deaths continue to increase, an understanding of the motivations, circumstances, and consequences of drug abuse would assist in developing policy responses. Furthermore, content was notably different based on media origin, and studies that exclusively use either social media sites (such as Twitter) or blogs and forums could miss important content. This study sets out sustainable, ongoing methodology for surveilling internet postings regarding these drugs.

Implementation of Opioid-Free Thyroid and Parathyroid Procedures: A Single Center Experience.

BACKGROUND: Initial opioid exposure for most individuals with substance use disorder comes from the healthcare system, and overprescription of opioids in ambulatory operations is common. This report describes an academic medical center's experience implementing opioid-free thyroid and parathyroid operations. MATERIALS AND METHODS: This is a retrospective chart review of patients undergoing a thyroid or parathyroid operation before and after implementation of an opioid-free analgesia protocol. The primary endpoint was new postoperative opioid prescription. Secondary endpoints included prescription characteristics and predictors of new opioid prescription. RESULTS: A total of 515 patients were enrolled in the study: 240 in the control or "pre-intervention" cohort (May through October 2017) and 275 in the intervention or "post" cohort (May through October 2018). Patients in the intervention cohort were significantly less likely to receive an opioid prescription (12.0% versus 59.6%, P < 0.001). When opioids were prescribed, they were used for shorter durations and at lower doses in the intervention cohort. Among the patients prescribed opioids in the intervention cohort (N = 33), the only significant predictor of postoperative opioid use was preoperative opioid use (P = 0.001). CONCLUSIONS: Opioids may not be required after thyroidectomy and parathyroidectomy, especially for opioid-naïve patients. Future research should examine patient satisfaction with opioid-sparing analgesia.

Palladium causes bizarre skin hyperpigmentation in long-term dihydrocodeinone 'Braun' abusers.

BACKGROUND: 'Braun' is an illegal injectable dihydrocodeinone-enriched drug mixture of semi-synthetic opioids. It is prepared by palladium-catalysed hydrogenation from codeine-containing tablets. OBJECTIVE: We aimed to characterize the dermatologic consequences of long-term abuse of 'Braun'. METHODS: Skin biopsies of two long-term 'Braun' abusers were evaluated histopathologically, immunohistochemically and ultrastructurally. Palladium skin content was assessed by X-ray fluorescence (XRF) spectrometry. RESULTS: Both patients showed generalized diffuse dark blue-grey hyperpigmentation of the skin. In both, an abnormal population of cells containing intracytoplasmic brownish granular material was identified in the papillary dermis by light microscopy. Electron microscopy revealed a dense and minimally structured material that predominantly accumulated in macrophages, fibroblasts and vascular endothelial cells. XRF analysis confirmed elevated levels of palladium in the patient's skin in comparison to healthy controls. CONCLUSION: Long-term abuse of palladium-contaminated dihydrocodeinone ('Braun') results in excessive accumulation of granular material in various dermal cell types and causes generalized diffuse skin hyperpigmentation.

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.

The Vicodin abuse problem: A mathematical approach.

The prescription drug epidemic in the United States has gained attention in recent years. Vicodin, along with its generic version, is the country's mostly widely prescribed pain reliever, and it contains a narcotic component that can lead to physical and chemical dependency. The majority of Vicodin abusers were first introduced via prescription, unlike other drugs which are often experienced for the first time due to experimentation. Most abusers report obtaining their supply from a prescription, either their own or someone else's. Although the problem with prescription drug abuse is well known, there is no standard method of addressing the problem. To better understand how to do this, we develop and analyze a mathematical model of Vicodin use and abuse, considering only those patients who were initially prescribed the drug. Through global sensitivity analysis, we show that focusing efforts on abuse prevention rather than treatment has greater success at reducing the population of Vicodin abusers. Our results demonstrate that relying solely on rehabilitation and other treatment programs is not enough to combat the prescription drug problem in the United States. We anticipate that implementing preventative measures in both prescribers and patients will reduce the number of Vicodin abusers.

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.

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.

Impact of rescheduling hydrocodone-combination products in an urban Texas county healthcare system.

OBJECTIVE: The objective of this study was to examine the rescheduling of hydrocodone-combination products (HCPs) and associated changes in prescriber patterns in an urban county healthcare system in Texas. METHODS: Pharmacy data were obtained electronically for tramadol, hydrocodone-acetaminophen, and acetaminophen-codeine from 180 days before and after the schedule change on October 6, 2014. x2 and t tests were used to calculate the significance of changes between the medications over the studied time. RESULTS: Hydrocodone-acetaminophen saw a decline in dispense events and pills dispensed of 80.2 and 67.9 percent, respectively, in the immediate 30-day period following the scheduling change with a total decrease of 80.8 and 67.5 percent, respectively, in the 180-day period. Acetaminophen-codeine dispense events and total pills dispensed increased by 302.3 and 288.9 percent, respectively, in the immediate 30-day period while 180-day results experienced an increase of 215.1 and 209.8 percent, respectively. There were no major changes with tramadol. Additionally, an increase of 69.5 percent in pills per dispense event of hydroco-done-acetaminophen was noted in the 180-day period following the schedule change. CONCLUSION: The scheduling change of HCPs is associated with an immediate decrease in hydrocodone-acetaminophen use at our institution while a simultaneous rise in acetaminophen-codeine products was observed.

Evaluating drugged driving: Effects of exemplar pain and anxiety medications.

OBJECTIVE: Distracted and drug-influenced driving presents a major risk for traffic safety morbidity and mortality. As part of an ongoing research program, we examined the effects of a commonly prescribed combination of medications for pain relief: alprazolam, a benzodiazepine, and a hydrocodone preparation, a combination opiate and acetaminophen, on a simulated driving protocol. METHODS: Utilizing a within-subjects design, we recruited 8 healthy experienced drivers without major physical and psychological histories. Using a double-blind, placebo-controlled crossover design, we administered placebo, alprazolam alone, hydrocodone/acetaminophen, and the combination of the 2 drugs in a standardized simulated driving protocol. Measures of lateral and longitudinal control were collected and the data were reduced and statically analyzed. RESULTS: The study observed clear detrimental effects of alprazolam on driving measures of lateral control and longitudinal control. Driving appeared to more aberrant at higher speeds and in rural scenarios. There were no statistical differences between hydrocodone and placebo. A measure of sedation showed that subjects rated alprazolam as more sedating than both hydrocodone and placebo. CONCLUSIONS: The findings suggest that impairing effects of this commonly prescribed combination of pharmacologic agents impact simulated driving performance. Negative changes in driving performance included measures of lateral and longitudinal control, although the deleterious effects on lateral control measures such as standard deviation of lane position (SDLP) were larger and more robust. Although the number of subjects was small, thus making it more difficult to draw conclusions on the narcotic effects, these results suggest that in this combination of central nervous system (CNS)-active drugs the benzodiazepine alprazolam accounted for the majority of impairing drug effects. The effect sizes associated with the hydrocodone preparation ranged from very small to medium. These results have potential implications for prescribing physicians and dispensing pharmacists, traffic safety experts, law enforcement officers, and patients themselves.