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The current opioid epidemic has dramatically increased the number of children who are prenatally exposed to opioids, including oxycodone. A number of social and cognitive abnormalities have been documented in these children as they reach young adulthood. However, little is known about the mechanisms underlying developmental effects of prenatal opioid exposure. Microglia, the resident immune cells of the brain, respond to acute opioid exposure in adulthood. Moreover, microglia are known to sculpt neural circuits during healthy development. Indeed, we recently found that microglial phagocytosis of dopamine D1 receptors (D1R) in the nucleus accumbens (NAc) is required for the natural developmental decline in NAc-D1R that occurs between adolescence and adulthood in rats. This microglial pruning occurs only in males, and is required for the normal developmental trajectory of social play behavior. However, virtually nothing is known as to whether this developmental program is altered by prenatal exposure to opioids. Here, we show in rats that maternal oxycodone self-administration during pregnancy leads to reduced adolescent microglial phagocytosis of D1R and subsequently higher D1R density within the NAc in adult male, but not female, offspring. Finally, we show that prenatal opioid exposure abolishes the extinction of oxycodone-conditioned place preference in these male offspring. This work demonstrates for the first time that microglia play a key role in translating prenatal opioid exposure to long-term changes in neural systems and behavior.HighlightsPrenatal opioid exposure decreases offspring viability and body weight in males and femalesPrenatal opioid exposure decreases microglial phagocytosis of D1R in the nucleus accumbens in males onlyPrenatal opioid exposure increases nucleus accumbens dopamine D1 receptor expression in males but not femalesAdult males fail to extinguish oxycodone-conditioned place preference following prenatal oxycodone exposure

AIMS Community pharmacists could contribute to identify people misusing prescription opioids, which may be associated with hospitalizations, substance use disorders, and death. This study investigated prescription opioid misuse in community pharmacy patients and the factors potentially associated with high Prescription Opioid Misuse Index (POMI) scores. METHODS In this cross-sectional study, pharmacy students asked patients with opioids prescriptions to fill in a questionnaire (including the POMI) in community pharmacies in a French region, in April 2019. Eligible patients were adults with chronic non-cancer pain who consented to participate. RESULTS In total, 414 patients (62.4% of women; mean age: 58.00 years ± 16.00) were included. The prescribed opioids were mainly weak opioids (73.2%; paracetamol/tramadol: 35%). Strong opioids (32.6%) included oxycodone (11.95%), fentanyl (9%), and morphine (9%). The median morphine milligram equivalent (MME) was 40 mg/day [IQR25-75 : 20-80]. The POMI score (0 to 6) was ≥4 in 16% of patients who were younger (p 100 mg, OR: 2.65 [95%CI: 1.14-4.41, p=0.0194) were significantly associated with POMI scores ≥4. CONCLUSIONS The high proportion of patients with high POMI scores underlines the interest of prescription opioid misuse screening in community pharmacies, in order to help these patients and refer them to pain specialists, if needed.

OBJECTIVES/HYPOTHESIS Surgeons have a critical role in the current opioid epidemic, and there is a need to prospectively understand patterns of pain and opioid use among patients undergoing endoscopic sinus surgery (ESS). STUDY DESIGN Prospective observational cohort. METHODS This was a prospective, observational cohort study that included patients undergoing ESS from November 2019 to March 2020. Demographic data were collected at baseline, as was respondent information regarding preoperative anxiety, pain, and postoperative pain expectations. Opioid use was converted to milligram morphine equivalents (MME). All patients received 10 tablets of 5 mg oxycodone (75 MME). Patients quantified postoperative pain and opioid consumption via telephone follow-up every 48 hours. The primary outcome was total MME utilized. RESULTS There were 91 patients included in the final cohort. Mean opioid use was 35.2 ± 47.3 MME. There were 29 (32%) patients who did not use any opioids after surgery, and six (7%) patients who required opioid refills. Postoperative opioid use was associated with increased preoperative anxiety (r = 0.41, P

The United States is facing an opioid epidemic that has only worsened with the COVID-19 pandemic. There is little evidence regarding patterns of opioid use among patients with total hip replacement (THR). Although the Centers for Disease Control and Prevention has put forward guidelines for prescribing opioids, it does not include guidance specifically for THR patients suffering from presurgical and postsurgical pain. The purpose of this study was to (1) compare presurgical and postsurgical opioid rates, (2) compare presurgical and postsurgical morphine milligram equivalents (MME), and (3) determine whether having a presurgical opioid prescription predicts the receipt of postsurgical opioid prescriptions among patients undergoing THR surgery. Retrospective cohort analysis of 4,405 patients undergoing THR at a major academic medical center in the United States from April 30, 2015, to April 30, 2018, was done. Patient characteristics, opioid rates, and average MME/day/person were described. Logistic regression was used to determine whether presurgical opioid prescription and opioid risk level predicted postsurgical opioid prescribing. Median age was 64 years (range = 18-85 years); patients were primarily Caucasian/White (78.8%) and female (54.7%). Opioid prescription rates in this sample for the 12-month presurgical and postsurgical periods were 66.1% and 95.6%, respectively. Oxycodone was the most common opioid prescribed in both periods. Among those prescribed an opioid, moderate/high risk for overdose and/or death was 6.3% presurgery and 19.8% postsurgery. Patients with a comorbidity were two times more likely to receive an opioid prescription in the postsurgical period. The median average MME/day/person was 26.5 (range = 0.3-180.0) for patients with an opioid prescribed during the presurgery period and 40.4 (range = 1.5-270.0) during the postsurgery period. Opioid use, regardless of strength, in the presurgical period as well as having one or more comorbidities predicted opioid use in the postsurgical period.

Publisher Copyright: © 2021 The Authors Objective: Airway management to ensure sufficient gas exchange is of major importance in emergency care. Prehospital endotracheal intubation (ETI) by paramedics is a widely debated method to ensure a patent airway. ETI is performed with procedural sedation in comatose patients because of the regulation. The use of medications increases the rate of successful airway management compared with nonmedication ETI and may also improve outcomes in patients with traumatic brain injury. In the absence of an operative emergency physician and with long distances, paramedic-induced airway management may increase the survival of patients in selected scenarios. A paramedic-staffed helicopter emergency medical system in Northern Finland operates in a rural area without an emergency physician and paralytic medications and treats critically ill patients using basic or advanced life support ground units. The aim of this study was to evaluate the success rates of ETI performed by a small, appropriately trained, and experienced group of 8 nurse paramedics in an out-of-hospital setting. Methods: The inclusion criterion for the study was an attempted intubation in patients with medical or traumatic indication for airway management by nurse paramedic. Results: Fifty-one patients were treated with ETI. The first-pass success rate was 72.5%, the second-pass success rate was 94.1%, and the overall success rate was 100% within 4 attempts. The median on-scene time was 54 minutes, and there were no signs of aspiration during laryngoscopy or after successful ETI. The primary mortality rate was 11.7%. Conclusion: The use of a rigid standard operating procedure for paramedic rapid sequence induction, paralytics, a video laryngoscope, and a gum elastic bougie might positively affect the ETI first-pass success rate. A follow-up study after these future modifications is needed. This small study suggests that intubation might be 1 option for airway management by an experienced nonanesthesiologist in Lapland.

To evaluate the effects of dexmedetomidine (Dex) and oxycodone (Oxy) on neurocognitive and inflammatory response after tourniquet-induced ischemia–reperfusion (I/R) injury. C57/BL6 mice were used to construct the mouse model of tourniquet-induced I/R injury. Mice (n = 48) were randomly divided into sham, I/R, Dex or Oxy group. Morris water maze test was performed to assess the spatial learning and memory function. The expression of NF-κB, TLR4, NR2B, M1 (CD68 and TNF-α) and M2 (CD206 and IL-10) polarization markers in mice hippocampus were detected by western blot or immunofluorescent staining. Spontaneous excitatory post-synaptic currents (sEPSCs) were recorded by electrophysiology. Dex treatment alleviated I/R-induced declines in learning and memory (p

Background Residents report that faculty preference is a significant driver of opioid prescribing practices. This study compared opioid prescribing preferences of surgical residents and faculty against published guidelines and actual practice and assessed perceptions in communication and transparency around these practices. Methods Surgical residents and faculty were surveyed to evaluate the number of oxycodone tablets prescribed for common procedures. Quantities were compared between residents, faculty, Opioid Prescribing Engagement Network guidelines, and actual opioids prescribed. Frequency with which faculty communicate prescribing preferences and the desire for feedback and transparency in prescription practices were assessed. Results Fifty-six (72%) residents and 57 (59%) faculty completed the survey. Overall, faculty preferred a median number of tablets greater than recommended by Opioid Prescribing Engagement Network in 5 procedures, while residents did so in 9 of 14 procedures. On average, across all operations, faculty reported prescribing practices compliant with Opioid Prescribing Engagement Network 56.1% of the time, whereas residents did so 47.6% of the time (P = .40). Interestingly, opioids actually prescribed were significantly less than recommended in 7 procedures. Among faculty, 62% reported often or always specifying prescription preferences to residents, while only 9% of residents noted that faculty often did so. Residents (80%) and faculty (75%) were amenable to seeing regular reports of personal opioid prescription practices, and 74% and 65% were amenable to seeing practices compared with peers. Only 34% of residents and 44% of faculty wanted prescription practices made public. Conclusion There is a disconnect between opioid prescribing preferences and practice among surgical residents and faculty. Increased transparency through individualized reports and education regarding Opioid Prescribing Engagement Network guidelines with incorporation into the electronic medical record as practice advisories may reduce prescription variability.

ZusammenfassungIm vorliegenden Fallbericht wird die Situation einer 67-jährigen chronischen Schmerzpatientin geschildert, die aufgrund eines Zufallsbefundes mit der Diagnose eines metastasierten kleinzelligen Bronchialkarzinoms konfrontiert wird. Bisher hatte sie mit einer chronischen Lumboischialgie zu kämpfen. Im Verlauf traten zunehmend therapieresistente Tumorschmerzen in den Vordergrund. Es wird beschrieben, wie wichtig es ist, die veränderte Schmerzqualität zu erkennen. Der Tumorschmerz mit neuropathischer Komponente beziehungsweise „mixed pain“ erschwerte im vorliegenden Fallbeispiel eine zufriedenstellende Symptomkontrolle. Es erfolgte ein Wechsel von transdermal appliziertem Fentanyl zu einem subkutanen Perfusorsystem mit Morphin und kurz darauf, aufgrund fehlender Schmerzkontrolle, auf ein orales retardiertes Oxycodonpräparat. Diese zweifache Opioidrotation wird im Folgenden diskutiert. Aspekte wie Resistenzentwicklung, inkomplette Kreuztoleranz und genetische Polymorphismen werden mithilfe wissenschaftlicher Literaturrecherche beleuchtet.

Sex differences in opioid analgesia occur in rodents and humans, and could be due to differences in drug and metabolite levels. Thus, we investigated the sex and cycle differences in analgesia (nociception) from oxycodone in rats and related these to sex and cycle differences in brain and plasma oxycodone and metabolite levels. Since numerous opioids are CYP2D enzyme substrates and variation in CYP2D alters opioid drug levels and response, we also initiated studies to see if the sex and cycle differences observed might be due to differences in brain CYP2D activity. Across oxycodone doses, females in diestrus had higher analgesia (using tail flick latency) compared to males and females in estrus; we also demonstrated a direct effect of estrous cycle on analgesia within females. Consistent with the analgesia, females in diestrus had highest brain oxycodone levels (assessed using microdialysis) compared to males and females in estrus. Analgesia correlated with brain oxycodone, but not brain oxymorphone or noroxycodone levels, or plasma drug or metabolite levels. Propranolol (a CYP2D mechanism-based inhibitor), versus vehicle pre-treatments, increased brain oxycodone, and decreased brain oxymorphone/oxycodone drug level ratios (an in vivo CYP2D activity phenotype in the brain) in males and females in estrus, but not in females in diestrus. Brain oxymorphone/oxycodone inversely correlated with analgesia. Together, both sex and estrous cycle impact oxycodone analgesia and brain oxycodone levels, likely through regulation of brain CYP2D oxycodone metabolism. As CYP2D6 is expressed in human brain, perhaps similar sex and cycle influences also occur in humans.

Background Several opioids have pharmacogenomic associations impacting analgesic efficacy. However, germline pharmacogenomic testing is not routinely incorporated into supportive oncology. We hypothesized that CYP2D6 profiling would correlate with opioid prescribing and hospitalizations. Materials and Methods We analyzed 61,572 adult oncology patients from 2012 to 2018 for opioid exposures. CYP2D6 metabolizer phenotype (ultra-rapid [UM], normal metabolizer [NM], intermediate [IM], or poor [PM]), the latter two of which may cause inefficacy of codeine, tramadol, and standard-dose hydrocodone, was determined for patients genotyped for reasons unrelated to pain. The primary endpoint was number of opioid medications received during longitudinal care (IM/PMs vs. NMs). Secondary endpoint was likelihood of pain-related hospital encounters. Results Most patients with cancer (n = 34,675, 56%) received multiple opioids (average 2.8 ± 1.6/patient). Hydrocodone was most commonly prescribed (62%), followed by tramadol, oxycodone, and codeine. In the CYP2D6 genotyped cohort (n = 105), IM/PMs received a similar number of opioids (3.4 ± 1.4) as NMs (3.3 ± 1.9). However, IM/PMs were significantly more likely to experience pain-related hospital encounters compared with NMs, independent of other variables (odds ratio [OR] = 5.4; 95% confidence interval [CI], 1.2–23.6; p = .03). IM/PMs were also more likely to be treated with later-line opioids that do not require CYP2D6 metabolism, such as morphine and hydromorphone (OR = 3.3; 95% CI, 1.1–9.8; p = .03). Conclusion CYP2D6 genotype may identify patients with cancer at increased risk for inadequate analgesia when treated with typical first-line opioids like codeine, tramadol, or standard-dose hydrocodone. Palliative care considerations are an integral part of optimal oncology care, and these findings justify prospective evaluation of preemptive genotyping as a strategy to improve oncology pain management. Implications for Practice Genomic variation in metabolic enzymes can predispose individuals to inefficacy when receiving opioid pain medications. Patients with intermediate and/or poor CYP2D6 metabolizer status do not adequately convert codeine, tramadol, and hydrocodone into active compounds, with resulting increased risk of inadequate analgesia. This study showed that patients with cancer frequently receive CYP2D6-dependent opioids. However, patients with CYP2D6 intermediate and poor metabolizer status had increased numbers of pain-related hospitalizations and more frequently required the potent non-CYP2D6 opioids morphine and hydromorphone. This may reflect inadequate initial analgesia with the common “first-line” CYP2D6-metabolized opioids. Preemptive genotyping to guide opioid prescribing during cancer care may improve pain-related patient outcomes.

Patients with chronic or acute/postoperative pain frequently use opioids. However, opioids may cause considerable adverse reactions (ARs), such as respiratory depression, which could be lethal. Unfortunately, only 5% of drug-related ARs (including those to opioids) are reported to health authorities. Therefore, little is known regarding the occurrence of opioid-related ARs at the population level. The aim of this study was to investigate how the rates of reported opioid-related ARs have changed in Canada since 1965. Our retrospective study examined trends of reported opioid-related ARs occurring in hospitalized and outpatients. Data on opioid-related ARs and mortality between 1965 and 2019 were obtained from the Canada Vigilance and Statistics Canada databases. Descriptive and Joinpoint regression analyses were performed. Oxycodone and normethadone were the most and least involved opioid agents, respectively, among the 18,407 reported ARs. The highest rate of reported opioid ARs (3.8 per 100,000 person-years) was recorded in 2012, whereas the lowest was recorded in 1965 (0.1 per 100,000 person-years). Between 1965 and 2019, annual rates climbed by 4.2% (95% confidence interval [CI] 3.1–5.2), and many fluctuations were observed: 1965–1974: +22.3% (95% CI 12.0–33.6); 1974–2000: − 4.1% (95% CI − 5.3 to − 2.9); 2000–2008: +30.3% (95% CI 22.6–38.4); 2008–2014: +4.1% (95% CI − 1.5 to 10.1); 2014–2017: −26.0% (95% CI − 44.7 to − 0.9); and, finally, 2017–2019: +35.4% (95% CI 3.8–76.7). Reported opioid-related ARs have increased since 1965, although fluctuations were observed in recent decades. The absolute number of opioid-related ARs might be seriously underestimated. Future studies should look into how to close this gap.

Urine drug testing (UDT) is a tool for monitoring drug use, including oxycodone. While variation in cytochrome P450 (CYP) genes is known to alter oxycodone metabolism, its impact on UDT results of oxycodone and its metabolites has not been well-studied. Here, multivariate analysis was performed on retrospective UDT results of 90,379 specimens collected from 14,684 genotyped patients prescribed oxycodone. Genetic variation in CYP2D6 and CYP2C19 had a significant impact on oxymorphone/oxycodone ratios, with a 6.9-fold difference between CYP2D6 ultrarapid metabolizers (UMs) and poor metabolizers (PMs; p < 10-300) and a 1.6-fold difference between CYP2C19 UMs and PMs (p = 1.50 × 10-4). CYP2D6 variation also significantly impacted noroxycodone/oxycodone ratios (p = 6.95 × 10-38). Oxycodone-positive specimens from CYP2D6 PMs were ~5-fold more likely to be oxymorphone-negative compared to normal metabolizers. These findings indicate that multivariate analysis of UDT data may be used to reveal the real-world impact of genetic and non-genetic factors on drug metabolism.

Oral care providers frequently prescribe analgesics for the management of dental pain. To get an overview of the analgesics prescribed in the Netherlands from 2016 through 2020, we collected data from the Stichting Farmaceutische Kengetallen (foundation [for] pharmaceutical indicators). Annually, more than 300,000 analgesics are prescribed by dentists in general practice and dental specialists. The largest group concerns NSAIDs (88%), followed by weak opioids (9%), acetaminophen (2%) and strong opioids (1%). Of the NSAIDs, ibuprofen is the most prescribed by all groups of oral care providers (84-91%). Of the weak opioids, dentists and oral and maxillofacial surgeons mainly prescribe codeine and codeine/ acetaminophen (64% and 78%, respectively), while orthodontists mainly prescribe tramadol (53%). Of the strong opioids, oxycodone is the most frequently prescribed by all groups of oral care providers (77-87%). Analgesics are a large part of the prescription medications in Dutch oral care and mainly concern NSAIDs (ibuprofen) and weak opioids (codeine/ acetaminophen). There are no major differences in prescription behaviour among different oral care providers.Mondzorgverleners schrijven frequent pijnstillers voor om dentogene pijn te bestrijden. Om inzicht te krijgen in de pijnstillers die van 2016 tot en met 2020 werden voorgeschreven, werden gegevens van de Stichting Farmaceutische Kengetallen opgevraagd. Jaarlijks worden er ruim 300.000 pijnstillers verstrekt door tandartsen-algemeen practici en tandarts-specialisten. De grootste groep betreft NSAID’s (88%), gevolgd door zwakwerkende opioïden (9%), paracetamol (2%) en sterkwerkende opioïden (1%). Van de NSAID’s wordt ibuprofen door alle mondzorgverleners het meest voorgeschreven (84-91%). Van de zwakwerkende opioïden schrijven tandartsen en mka-chirurgen vooral codeïne en codeïne/paracetamol voor (respectievelijk 64% en 78%), terwijl orthodontisten vooral tramadol voorschrijven (53%). Van de sterkwerkende opioïden wordt oxycodon door alle mondzorgverleners het meest voorgeschreven (77-87%). Pijnstillers maken een groot deel uit van de voorgeschreven geneesmiddelen in de mondzorg. Het betreffen vooral NSAID’s (ibuprofen) en zwakwerkende opioïden (codeïne/paracetamol). Er zijn geen grote verschillen in het voorschrijfgedrag tussen verschillendemondzorgverleners.

Background Limiting opioid use in perioperative pain management is currently an important focus in orthopedic surgery. The ability of acetaminophen to reduce postoperative opioid consumption while providing acceptable pain management has not been thoroughly investigated in patients undergoing rotator cuff repair (RCR). Methods Patients undergoing primary arthroscopic RCR were prospectively randomized to 1 of 3 treatment groups: Group 1 (control) received both 5 mg of oxycodone every 6 hours as needed and 1000 mg of acetaminophen orally every 6 hours as needed after surgery and had the option to take either medication or both. Group 2 (control) received only 5 mg of oxycodone every 6 hours as needed without any additional acetaminophen after surgery. Group 3 received 1000 mg of acetaminophen orally every 6 hours for 1 day prior to and after surgery, which was subsequently decreased to administration every 8 hours during postoperative days 2-5. Group 3 patients were also allowed to take 5 mg of oxycodone every 6 hours as needed after surgery. All patients received interscalene blocks with liposomal bupivacaine (Exparel). Opioid use, pain scores, side effects, and overall satisfaction were assessed daily for the first week after surgery. Results A total of 57 patients (mean age, 57.8 ± 9.55 years) were included in this study. Baseline demographic characteristics including age, sex, and body mass index were similar between the groups (P > .05). Patients in group 3 took significantly fewer narcotics overall (P = .017) and took significantly fewer pills each day compared with group 2. Group 3 also reported significantly better overall pain control compared with the other groups (P = .040). There were no significant differences in overall patient satisfaction between the groups (P > .05). Additionally, there were no significant differences between groups regarding postoperative medication-associated side effects (P > .05). Conclusion Perioperative acetaminophen represents an important component of multimodal analgesia in appropriately selected patients undergoing shoulder surgery. In this study, the use of perioperative acetaminophen significantly decreased opioid consumption and improved overall pain control after primary arthroscopic RCR.

1. Priyadarshani Giri, MD* 2. Philip Roth, MD, PhD* 1. *Staten Island University Hospital/Northwell, Zucker School of Medicine at Hofstra Northwell, Staten Island, NY Neonatal abstinence syndrome (NAS), often used interchangeably with neonatal opioid withdrawal syndrome, is a constellation of clinical signs and symptoms of withdrawal that occurs when neonates are removed from long-term in utero substance exposure. The incidence of NAS rose fourfold from 2004 to 2013, in parallel with a similar increase in opioid use during pregnancy (1999 to 2014), resulting in prolonged length of stay (LOS) in the NICU and increasing hospital costs. NAS has changed in complexity over time from multiple factors, including an increase in illicit drug use (eg, heroin), prescription of opioid agonist therapy for maternal opioid use disorder (eg, methadone and buprenorphine), use or misuse of prescribed opioids (eg, oxycodone, hydrocodone), the proliferation of illicit synthetic opioids with long half-lives and high potencies, as well as prescription of anxiolytics and antidepressants. In an effort to decrease the overprescription of opioids, programs have been introduced to monitor prescribing practices. Similarly, a recent systematic review found that using a nonjudgmental and open-ended approach during the interview with women who use substances improved relationships with perinatal providers. Currently, medication for opioid use disorder, either methadone or buprenorphine, in combination with counseling and behavioral therapy, is recommended for management of opioid use in pregnancy to prevent risks associated with withdrawal. In fact, perinatal counseling of the mother and family is critical to establishing a good rapport and safe environment to improve maternal and infant management. Although the exact pathophysiology of NAS and the basis for symptom variability is not well understood, infants with NAS are clearly at increased risk for admission to the NICU, birth complications (low birthweight, jaundice, feeding intolerance), preterm …

PurposeOpioids are recommended for moderate-to-severe cancer pain; however, in patients with cancer, impaired hepatic function can affect opioid metabolism. The aim of this systematic review was to evaluate the evidence for the use of opioids in patients with cancer with hepatic impairment.MethodsA systematic review was conducted and the following databases searched: AMED (−2021), MEDLINE (−2021), EMBASECLASSIC + EMBASE (−2021) and Cochrane Central Register of Controlled Trials (−2021). Eligible studies met the following criteria: patients with cancer-related pain, taking an opioid (as defined by the WHO Guidelines for the pharmacological and radiotherapeutic management of cancer pain in adults and adolescents); >18 years of age; patients with hepatic impairment defined using recognised or study-defined definitions; clinical outcome hepatic impairment related; and primary studies. All eligible studies were appraised using the Grading of Recommendations Assessment, Development and Evaluation system.ResultsThree studies (n=95) were eligible but heterogeneity meant meta-analysis was not possible. Each individual study focused on only one each of oxycodone±hydrocotarnine, oxycodone/naloxone and morphine. No recommendations could be formulated on the preferred opioid in patients with hepatic impairment.ConclusionsMorphine is the preferred opioid in hepatic impairment owing to clinical experience and pharmacokinetics. This review, however, found little clinical evidence to support this. Dose adjustments of morphine and the oxycodone formulations reviewed remain necessary in the absence of quality evidence. Overall, the quality of existing evidence on opioid treatments in cancer pain and hepatic impairment is low and there remains a need for high-quality clinical studies examining this.

Objectives Health systems (nonfederal hospitals and clinics) are the second major source for drug expenditure in the United States. Opioids prescribed in these healthcare settings are commonly short-acting opioids that can lead to persistent opioid use. Nevertheless, there are no national data that describe trends in opioid use and the associated expenditure in health systems. Therefore, the objective of this article was to describe opioid use and expenditures in US health systems from 2015 to 2019. Methods We used data from IQVIA National Sales Perspectives to describe prescription opioid expenditure and use in health systems (nonfederal hospitals and clinics). Results Over the 5-year study period, health systems dispensed a total of 6.55 billion units of opioids (26.88% decrease) with an associated expenditure of $3.33 billion (26.78% decrease). Relative to all opioid formulations in our study, oxycodone, hydrocodone, and fentanyl were the opioids with the highest use in US health systems. All opioid prescriptions decreased except fentanyl use, which increased by 29.80% in clinics. The use of abuse-deterrent formulations of opioids decreased by 51.00% over the study period, although the decrease seems to be driven mainly by long-acting oxycodone (brand name Oxycontin). Conclusions Opioid use and expenditures in health systems have been decreasing following national trends from retail pharmacies. Nevertheless, fentanyl use increased in clinics and was prescribed at higher proportions in nonfederal hospitals than other opioids, which warrants further investigation.

Introduction In the United States, the opioid epidemic claims over 130 lives per day due to overdoses. While the use of opioids in trauma patients has been well-described in the literature, it is unknown whether prescription opioid use is associated with mortality after trauma. We hypothesized that legally obtained prescription opioid consumption would be positively associated with injury-related deaths in the United States. Methods Cross-sectional time-series data was compiled using state-level mortality data from the Centers for Disease Control and Prevention Multiple Causes of Death database and prescription opioid shipping data to each state using the US Department of Justice Automated Reports and Consolidated Ordering System Retail Drug Summary reports from 2006 to 2017, with opioids shipped used as a proxy for local opioid consumption. Oxycodone and hydrocodone amounts were converted to morphine equivalent doses (MEDs). Our primary outcome was an association between MEDs and injury mortality rates at the state-level. We analyzed total injury-related deaths and subgroups of unintentional deaths, suicides, and homicides. We modeled the data using fixed effects regression to reduce bias from unmeasured differences between states. Results Data were available for all states and the District of Columbia. Opioid deliveries increased through 2012 and then declined. Total injury-related mortalities have been increasing steadily since 2012. Opioid MEDs did not show a consistent or statistically significant relationship with injury-related mortality, including with any subgroups of unintentional deaths, suicides, and homicides. Conclusion In every state examined, there was no consistent relationship between the amount of prescription opioids delivered and total injury-related mortality or any subgroups, suggesting that there is not a direct association between prescription opioids and injury-related mortality. This is the first study to combine national mortality and opioid data to investigate the relationship between legally obtained opioids and injury-related mortality. The US opioid epidemic remains a significant challenge that requires ongoing attention from all stakeholders in our medical and public health systems.

Background: Currently, in the United States, there is an epidemic of opioid abuse. While this problem is well known to the public due to significant media and political attention, patients are poorly educated on the proper handling and disposal of unused opioids. Instead, the onus has fallen on the healthcare provider to minimize the number of opioids prescribed. Study objective: To improve proper opioid disposal rates after gynecologic surgery by providing educational materials along with a disposal bag. Study design: We performed a prospective study evaluating baseline understanding of medication disposal using a questionnaire given to the patients during their preoperative visit. Subsequently, patients were provided written information on proper disposal of their medications and an activated charcoal medication disposal bag. Study patients completed a survey about disposal of their unused opioids at their last post-operative visit. The success of education and proper disposal of opioid medications were evaluated. Results: Thirty-five patients, average age of 45 (range 20-77), were enrolled, and 31 patients successfully completed both surveys. The surgeries performed included hysterectomy 23 percent (n = 7), laparoscopic excision of endometriosis 32 percent (n = 10), laparoscopic ovarian cystectomy 23 percent (n = 7), prolapse repair 3 percent (n = 1), and midurethral sling procedures 19 percent (n = 6). Chronic pelvic pain was identified in 39 percent (n = 12) of our patient population. Prior to education, 52 percent (n = 16) of patients did not dispose of their opioids. Furthermore, 71 percent (n = 22) of patients stated they had never been educated by a medical provider regarding appropriate disposal. Nineteen percent (n = 6) confirmed they have used an opioid medication prescribed to someone else. Demographic data show 65 percent (n = 20) of these patients had completed a college degree or greater. After education and being given a reliable option for medication disposal with the Deterra ® bag, 94 percent (n = 29) of patients properly disposed of their opioids after surgery, demonstrating a 45 percent (p < 0.001) increase in proper disposal. In our study alone, 491 tablets of 5mg oxycodone were properly disposed. The majority of patients, 77 percent (n = 24) used the drug disposal bag, and when queried, stated they would be willing to pay on average $7.70 (range 0-20) per bag. Without education and a simple option for disposal, 422 tablets prescribed may have been subject to inappropriate diversion. Conclusion: This study clearly shows that patient education, coupled with a reliable option for opioid disposal, is effective. We strongly encourage other surgical institutions to implement similar practices not only for our surgical patients’ safety, but also for the tens of thousands of patients who died of opioid abuse in the last year.

Objective: To evaluate the prescribing practices and opioid consumption in an ambulatory setting to inform the development of evidence-based guidelines. Design: A prospective study of adults undergoing outpatient open and laparoscopic surgeries over 3 months. One week after discharge, a telephonic interview quantified the number of opioids prescribed and consumed, degree of pain control and satisfaction, and whether additional pain medication was requested. Setting: Community hospital ambulatory surgery center in Westchester County, New York. Participants: This study included 304 adults undergoing a variety of procedures by surgeons from multiple specialties. Main outcome measures: Quantify surgeons’ postoperative opioid prescribing compared with patient opioid consumption. Results: Eighty-one percent (N = 245) responded to the survey, of which 64 percent were prescribed opioids. Males and females were equally represented with the mean age of 59.4 years. Of those prescribed opioids, 92 percent filled the prescription. The most commonly prescribed opioids reported by the patients that filled their prescription (N = 145) were oxycodone (36.5 percent), oxycodone/acetaminophen (28.9 percent), and tramadol (22.7 percent). The mean number of opioid pills prescribed was 20 and the mean consumption was 6.7 pills, resulting in an average of 13 retained pills. Only 3.8 percent of the patients prescribed opioids at discharge called their provider for additional analgesia. Despite the low opioid consumption patients reported high satisfaction (4.5 on scale of 0-5) with pain control. Only 10.4 percent reported that the surgeon recommended an over the counter (OTC) analgesic option. There was variability in the amount of opioids prescribed within each surgical category. Conclusions: One week after outpatient surgery, patients consumed one-third of physician-prescribed opioids, yet they reported high pain management satisfaction. Our study will inform the development of a patient-centered interdisciplinary perioperative education program to more effectively tailor multimodal pain management in ambulatory surgical patients and collaterally reduce the number of retained opioids.

Supplemental Digital Content is Available in the Text., Opioids relieve acute pain, but there is little evidence to support the stability of the benefit over long-term treatment of chronic noncancer pain. Previous systematic reviews consider only group level published data which did not provide adequate detail. Our goal was to use patient-level data to explore the stability of pain, opioid dose, and either physical function or pain interference in patients treated for 12 months with abuse deterrent formulations of oxycodone and hydrocodone. All available studies in the Food and Drug Administration Document Archiving, Reporting, and Regulatory Tracking System were included. Patient-level demographics, baseline data, exposure, and outcomes were harmonized. Individual patient slopes were calculated from a linear model of pain, physical function, and pain interference to determine response over time. Opioid dose was summarized by change between baseline and the final month of observation. Patients with stable or less pain, stable or lower opioid dose, and stable or better physical function (where available) met our prespecified criteria for maintaining long-term benefit from chronic opioids. Of the complete data set of 3192 patients, 1422 (44.5%) maintained their pain level and opioid dose. In a secondary analysis of 985 patients with a measured physical function, 338 (34.3%) maintained their physical function in addition to pain and opioid dose. Of 2040 patients with pain interference measured, 788 (38.6%) met criteria in addition. In a carefully controlled environment, about one-third of patients successfully titrated on opioids to treat chronic noncancer pain demonstrated continued benefit for up to 12 months.

OBJECTIVE To evaluate whether viewing an educational video on pain management reduces opioid use after cesarean delivery. METHODS We conducted a randomized, controlled trial of women aged 18 years or older who underwent cesarean delivery at a tertiary care center. Eligible women were randomized in a 1:1 ratio to usual discharge pain medication instructions plus an educational video on pain management or to usual discharge pain medication instructions alone. All women received the same opioid prescription at discharge: Twenty 5-mg oxycodone tablets. Participants were contacted at 7 days and at 14 days after delivery to assess the number of oxycodone tablets used, adjunct medication (acetaminophen and ibuprofen) use, pain scores, and overall satisfaction of pain control. The primary outcome was the number of oxycodone tablets used from discharge through postpartum day 14. A sample size of 23 per group (n=46) was planned to detect a 25% difference in mean number of oxycodone tablets used between groups, as from 20 to 15. RESULTS From July 2019 through December 2019, 61 women were screened and 48 were enrolled-24 in each group. Women who viewed the educational video used significantly fewer opioid tablets from discharge through postpartum day 14 compared with women who received usual pain medication instructions (median 1.5, range 0-20 vs median 10, range 0-24, P

Background Immunoassays provide a rapid tool for the screening of drugs-of-abuse (DOA). However, results are presumptive and confirmatory testing is warranted. To reduce associated cost and delay, laboratories should employ assays with high positive and negative predictive values (PPVs and NPVs). Here, we compared the results of urine drug screens on cobas 6000 (cobas) and ARCHITECTi2000 (ARCHITECT) platforms for six drugs against LC-MS/MS to assess the analytical performance of these assays. Methods Eighty nine residual urine specimens, which tested positive for amphetamine , THC-COOH, benzoylecgonine , EDDP, opiates and/or oxycodone during routine drug testing, were stored frozen until later confirmation by LC-MS/MS. Immunoassays were performed on cobas and ARCHITECT using a split sample. A third aliquot from these samples was tested by LC-MS/MS to assess the percentage of false positive, false negative , true positive and true negative results and calculate the PPVs and NPVs for each immunoassay. Results The PPVs of THC-COOH and EDDP assays were 100% on both platforms. Suboptimal PPVs were achieved for oxycodone (cobas, 57.1% vs ARCHITECT, 66.7%), amphetamine (77.8 vs. 100%), opiates (80.0 vs. 84.6%) and benzoylecgonine (88.9 vs. 84.2%) assays. The NPV was 100% for cobas and ARCHITECT oxycodone assays. Lower NPVs were achieved for THC-COOH (cobas, 28.6% vs ARCHITECT, 25.0%), EDDP (72.7% for both assays), benzoylecgonine (74.4% vs 73.8%), amphetamine (83.3% vs 82.8%) and opiates (100% vs 85.3%). Conclusion Overall, cobas and ARCHITECT urine drug screens have comparable analytical performance. Confirmatory testing is warranted for positive test results especially for oxycodone, amphetamine, opiates and cocaine. Negative drug screen results must be interpreted with caution especially for THC-COOH, EDDP, benzoylecgonine, amphetamine and opiates.

Objective: Guidelines for opioid prescription post-operatively exist; however, the majority of these are for adults. Nevertheless, opioid risks are present for pediatric patients also. This study investigates the effect of a single institution's guidelines on post-operative opioid prescribing for pediatric orthopedic patients undergoing knee surgery. We hypothesized that a standardized set of prescribing guidelines would result in a decrease in opioids prescribed at discharge home after these surgeries. Design: Retrospective observational. Setting: Urban, tertiary care, academic orthopedic hospital. Patients: Pediatric, sports knee surgery, 23-month period. Interventions: Guidelines were implemented institutionally for post-operative opioid prescribing practices. We reviewed all post-operative opioid prescriptions for pediatric patients undergoing sports knee surgery with two pediatric sports surgeons for the 11 months prior to the guidelines and 12 months afterwards, totaling 316 surgeries. Main outcome measure: Oral morphine equivalents (OMEs) prescribed on discharge from the hospital before and after implementation of guidelines. Results: There was a significant reduction in OMEs from 229 OMEs to 175 OMEs before and after opioid prescribing guidelines (p < 0.001). This is a decrease in approximately seven 5 mg oxycodone tablets per patient. Conclusions: This study demonstrates that at our institution, with a pediatric patient population having sports knee surgery, prescribing guidelines reduced the number of opioids prescribed at discharge.

BACKGROUND: Short bowel syndrome is a disorder with several complications such as malnutrition and failure of drug therapy. Treatment with opioids is needed in many patients, and oral medication is preferred. However, optimal dosing is a difficult task as current guidelines are based on an intact gastrointestinal tract. Hence, the aim of this explorative case study was to assess the pharmacokinetics of orally administered oxycodone in patients with short bowel syndrome.METHODS: Six patients with short bowel syndrome were administered 10 mg oral solution oxycodone after an overnight fast. Oxycodone plasma concentrations were determined over a 6-hour period. Pharmacokinetic profiles were visually inspected. Pharmacokinetic parameters: maximum plasma concentration, time of maximum concentration and area under the curve were calculated. Data were also compared to mean values obtained in healthy participants.RESULTS: A clinically relevant concentration of oxycodone was found in all patients, although with large inter-individual variation. The absorption fraction tended to correlate positively with total intestinal length. Additionally, preservation of some or the entire colon seemed further to increase the absorption fraction. Time of maximum concentration varied from 30 min to approximately 90 min.CONCLUSIONS: Oxycodone is absorbed in a clinically relevant extent in patients with short bowel syndrome, but bioavailability varies greatly between patients, which shall be taken into consideration. Absorption is related to functional small intestinal length, but preservation of colon is also beneficial. Still, optimal therapeutic dosing must be individualized, and other factors such as those related to malnutrition and motility shall also be taken into consideration.

Background: Pharmacological management of chronic neuropathic pain (CNP) still represents a major clinical challenge. Collective harnessing of both the scientific evidence base and clinical experience (of clinicians and patients) can play a key role in informing treatment pathways and contribute to the debate on specific treatments (e.g., cannabinoids). A group of expert clinicians (pain specialists and psychiatrists), scientists, and patient representatives convened to assess the relative benefit-safety balance of 12 pharmacological treatments, including orally administered cannabinoids/cannabis-based medicinal products, for the treatment of CNP in adults. Methods: A decision conference provided the process of creating a multicriteria decision analysis (MCDA) model, in which the group collectively scored the drugs on 17 effect criteria relevant to benefits and safety and then weighted the criteria for their clinical relevance. Findings: Cannabis-based medicinal products consisting of tetrahydrocannabinol/cannabidiol (THC/CBD), in a 1:1 ratio, achieved the highest overall score, 79 (out of 100), followed by CBD dominant at 75, then THC dominant at 72. Duloxetine and the gabapentinoids scored in the 60s, amitriptyline, tramadol, and ibuprofen in the 50s, methadone and oxycodone in the 40s, and morphine and fentanyl in the 30s. Sensitivity analyses showed that even if the pain reduction and quality-of-life scores for THC/CBD and THC are halved, their benefit-safety balances remain better than those of the noncannabinoid drugs. Interpretation: The benefit-safety profiles for cannabinoids were higher than for other commonly used medications for CNP largely because they contribute more to quality of life and have a more favorable side effect profile. The results also reflect the shortcomings of alternative pharmacological treatments with respect to safety and mitigation of neuropathic pain symptoms. Further high-quality clinical trials and systematic comprehensive capture of clinical experience with cannabinoids is warranted. These results demonstrate once again the complexity and multimodal mechanisms underlying the clinical experience and impact of chronic pain.

Polypharmacy is common among patients taking prescription opioids long-term, and the codispensing of interacting medications may further increase opioid overdose risk. To identify nonopioid medications that may increase opioid overdose risk in this population, we conducted a case-crossover-based screening of electronic claims data from IBM MarketScan and Optum Clinformatics Data Mart spanning 2003 through 2019. Eligible patients were 18 years of age or older and had at least 180 days of continuous enrollment and 90 days of prescription opioid use immediately before an opioid overdose resulting in an emergency room visit or hospitalization. The main analysis quantified the odds ratio (OR) between opioid overdose and each nonopioid medication dispensed in the 90 days immediately before the opioid overdose date after adjustment for prescription opioid dosage and benzodiazepine codispensing. Additional analyses restricted to patients without cancer diagnoses and individuals who used only oxycodone for 90 days immediately before the opioid overdose date. The false discovery rate (FDR) was used to account for multiple testing. We identified 24,866 individuals who experienced opioid overdose. Baclofen (OR 1.56; FDR < 0.01; 95% confidence interval (CI), 1.29 to 1.89), lorazepam (OR 1.53; FDR < 0.01; 95% CI, 1.25 to 1.88), and gabapentin (OR 1.16; FDR = 0.09; 95% CI, 1.04 to 1.28), among other nonopioid medications, were associated with opioid overdose. Similar patterns were observed in noncancer patients and individuals who used only oxycodone. Interventions may focus on prescribing safer alternatives when a potential for interaction exists.

Opioids are commonly prescribed following childbirth, but data are lacking on trends in postpartum opioid prescribing over time. We examined whether a highly-publicized 2006 case report questioning the safety of codeine during lactation was associated with changes in postpartum opioid prescribing. We conducted a cross-sectional time series analysis of all publicly-funded prescriptions for opioids to postpartum women in Ontario, Canada from April 1, 2000 to March 31, 2017. The intervention was the publication of a case report in 2006 attributing the death of a breastfeeding neonate to maternal codeine use. The primary outcome was the rate of opioid prescribing to postpartum women. Among postpartum women eligible for prescription drug coverage, 17.5% filled an opioid prescription in the third quarter of 2006 (immediately prior to publication of the case report), with codeine representing 89.8% of all prescriptions. By the fourth quarter of 2010, only 12.2% of postpartum women filled an opioid prescription, representing a decline of 30% (p

Objective This study sought to prospectively validate an institutional prescribing guideline based on previously defined opioid consumption patterns following inpatient colorectal operations. Background In light of the opioid epidemic, reducing excess prescription quantities is key while still tailoring to patient needs. Methods This is a cohort study of elective colorectal operations (colectomies, proctectomies, and ostomy reversals) at a single tertiary care medical center. Opioid prescribing and consumption patterns (quantified as Equianalgesic 5 mg Oxycodone Pills, EOP) were compared before and after adoption of a tiered opioid prescribing guideline. Tiers were divided based on opioid consumption in the 24-hours prior to discharge: Tier 1 (0 EOP), Tier 2 (0.1-3 EOP), and Tier 3 (>3 EOP). Our guideline recommended maximum prescriptions of 0 EOP for Tier 1, 12 EOP for Tier 2, and 30 EOP for Tier 3. Results The study included 100 patients before and 101 after guideline adoption. Demographic and operative characteristics were similar between cohorts. Guideline adherence was 85%. Overall, there was a 41% reduction in mean prescription quantity and 53% reduction in excess pills per prescription. No change in opioid consumption or refill rates was observed. Conclusion Adoption of a tiered opioid prescribing guideline significantly reduced opioid prescription quantity with no change in consumption or refill rates. Standardization of discharge prescriptions based on patient consumption in the 24-hours prior to discharge may be an important step towards minimizing excess prescribing.

Background The changing of opioids during the transition of care from hospital to home may be associated with harm. Objective To compare patients receiving tapentadol IR versus oxycodone IR following orthopaedic surgery during hospitalisation with regard to the changing of opioids at hospital discharge. Setting A major metropolitan tertiary referral hospital in Australia. Methods This is a retrospective cohort study. Participants included adult orthopaedic surgery patients receiving postoperative tapentadol IR or oxycodone IR during hospitalisation between 1 January 2018 and 30 June 2019. Main outcome measure The proportion of patients for whom the opioid prescribed was changed at hospital discharge. Results The study cohort included 199 patients. Of these, 100 patients received oxycodone and 99 patients received tapentadol post-operatively during hospitalisation. The mean age was 66 years (SD, 12 years) and 111 (56%) were female. The most common surgeries were total knee arthroplasty (91, 46%), total hip arthroplasty (63, 32%) and shoulder surgery (26, 13%). Patients in the tapentadol group were more likely to be changed to a different opioid upon hospital discharge than the oxycodone group (57% versus 9%, difference 48% [95% CI 36–59%, p

The interindividual variability in opioid response is an issue that contributes to the ongoing opioid crisis. Current evidence suggests this variability can be attributed to genetic factors. The pharmacogenetics of Opioid Treatment for acute post-operative Pain (OTP) project was a prospective study that aimed to identify genetic markers associated with opioid treatment outcomes. Healthy patients undergoing third-molar extractions were recruited from dental offices located within the Greater Toronto Area. Participants were evaluated using the Brief Pain Inventory Short Form, the Opioid Related Symptom Distress Scale, and the Leeds Dependence Questionnaire. Seventy-two participants had an active opioid prescription. Participants were prescribed one of the following opioids: codeine, morphine, hydromorphone, tramadol, or oxycodone. The majority of participants were female (57%), ranging from 16 to 44 years of age. Pain severity, pain interference, and side effects declined over the seven-day post-operative period. Additionally, 4% of participants displayed medium to high risk of dependence. It is anticipated that OTP will enable the development of a genetic test for opioid use and facilitate the introduction of this test into routine healthcare practice. The OTP study represents a novel approach to opioid treatment and has significant implications for future interventions targeting the ongoing opioid crisis. Employing a pharmacogenomic-guided strategy for prescribing opioids may improve patients' response to this treatment and, in so doing, increase adherence to the target treatment plan. Optimized prescriptions may also provide public healthcare systems with beneficial savings and reduce the risks associated with opioid use.

To examine opioid prescribing and consumption patterns after hysterectomy and identify factors associated with postoperative opioid consumption.Prospective cohort study.Single university medical center.Women undergoing hysterectomy for benign, nonobstetric indications.Participant preoperative and surgical characteristics were obtained through chart review and patient report of baseline pain score. During the third postoperative week, participants completed a telephone interview, including a direct count of remaining opioid pills and assessment of satisfaction with pain management. We assessed factors associated with opioid consumption in oral morphine equivalents (OME) using a linear regression model.Of the 129 participants, 113 (88%) completed the postoperative survey after hysterectomy: 16 vaginal, 43 robotic-assisted, 42 conventional laparoscopic, and 12 abdominal hysterectomies. The median amount of opioid prescribed was 150 OME (interquartile range [IQR] 113-200), while the median amount consumed was 75 (IQR 10-135), reflecting an average consumption of about 50% of the prescription. Opioid prescription size was associated with consumption; for every additional oral morphine equivalent prescribed, on average, an additional 0.5 was consumed (p.001). If the indication for hysterectomy was related to pain, participants consumed 25.3 additional OME (p = .04). The amount of opioid prescribed was inversely correlated with pain management satisfaction; every additional point on a 1 through 5 Likert scale of increasing satisfaction was associated with 44 fewer OME prescribed (standard error 9 OME, p.001). For the 1464 total unused pills among the 104 participants with leftover opioids, only 20% reported an Food and Drug Administration -compliant opioid disposal plan.Gynecologic surgeons can respond to the opioid epidemic by reducing excess opioid pills after hysterectomy by providing both the smallest effective prescription size and concrete resources for safe opioid disposal. These actions may contribute to a reduction in opioid use disorder cases or overdose deaths.

Purpose To determine whether differences in total morphine equivalent doses (MEDs) prescribed after arthroscopic rotator cuff repair (RCR) existed because of age younger than or older than 55 years and sex and to characterize potential risk factors for needing an opioid medication refill, visiting a provider other than the surgeon (either in the emergency department or ambulatory settings), and postoperative pain control requiring opioids approximately 6 weeks from the date of surgery. Methods A retrospective cohort study of 100 patients who underwent arthroscopic RCR between July 1, 2018, to November 30, 2018, in a single institution was performed. Data including demographics, perioperative treatments, and postoperative opioid prescriptions were recorded. Our primary hypotheses were evaluated with the Wilcoxon-Mann-Whitney test. Univariate and multivariate analyses assessed potential risk factors for the 3 outcomes of interest. Results were given in adjusted odds ratios (aORs), 95% confidence intervals (CIs), and P values. Results There was a difference (P = .038) in total MEDs used (in 5 mg oxycodone tablets) between males (median 56 tablets; interquartile range, 50-98 tablets) and females (median 78 tablets; interquartile range, 56-116 tablets). Age younger than 55 years was a risk factor for seeking an opioid refill (OR = 2.51; CI, 1.11-5.66; P = .026). A significant risk factor for visiting another provider was preoperative opiate use (OR = 15.0; CI, 1.79-125.8; P = .013). Age younger than than 55 years (aOR = 2.51; CI, 1.01-6.02; P = .047), body mass index (aOR = 1.08; CI, 1.01-1.17; P = .046), and shorter surgical duration (aOR = 0.97; CI, 0.95-0.99, P =.007) were independent predictive factors for requiring opioids for pain control 6 weeks after surgery. Conclusions After arthroscopic RCR, MED prescription is higher for females than males. The risk factors for requesting opioid prescription refill for pain control 6 weeks after surgery were age younger than 55 years and shorter surgical duration. Level of Evidence Level III, retrospective comparative study.

OBJECTIVES To describe the perioperative opioid demand in a large population of patients undergoing lower extremity fracture fixation and to evaluate mental disorders such as substance abuse as risk factors for increased use. DESIGN Retrospective, observational. SETTING National insurance claims database. PATIENTS/PARTICIPANTS Twenty-three four hundred forty-one patients grouped by mental disorders such as depression, psychoses, alcohol abuse, tobacco abuse, drug abuse, and preoperative opioid filling undergoing operative treatment of lower extremity fractures (femoral shaft through ankle) between 2007 and 2017. INTERVENTION Operative treatment of lower extremity fractures. MAIN OUTCOME MEASURES The primary outcome was filled opioid prescription volume converted to oxycodone 5-mg pill equivalents. Secondary outcomes included the number of filled prescriptions and the risk of obtaining 2 or more opioid prescriptions. RESULTS Of 23,441 patients, 16,618 (70.9%), 8862 (37.8%), and 18,084 (77.1%) filled opioid prescriptions within 1-month preop to 90-day postop, 3-month postop to 1-year postop, and 1-month preop to 1-year postop, respectively. On average, patients filled 104, 69, and 173 oxycodone 5-mg pills at those time intervals. Alcohol, tobacco, drug abuse, and preoperative opioid filling were associated with increased perioperative opioid demand. Psychoses had a small effect on opioid demand, and depression had no significant impact. CONCLUSIONS This study reports the rate and volume of opioid prescription filling in patients undergoing lower extremity fracture surgery. Substance use and abuse were the main risk factors for increased perioperative opioid prescription filling. Providers should recognize these risk factors for increased use and be judicious when prescribing opioids. Enhanced patient education, increased nonopioid pain management strategies, and referral for substance use and abuse treatment may be helpful for these patients. LEVEL OF EVIDENCE Level III. See Instructions for Authors for a complete description of levels of evidence. LEVEL OF EVIDENCE Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background Prolonged opioid use can lead to suboptimal outcomes after total shoulder arthroplasty (TSA), and thus, reduced consumption is desirable. Our primary aims were to determine if differences in total morphine equivalent doses existed owing to (1) age less than or greater than 65 years, (2) sex, and (3) TSA type – reverse or anatomic total shoulder arthroplasty. We also characterized potential risk factors for (1) visiting another provider for pain, (2) pain control 6 weeks postoperatively, and (3) needing an opioid refill. Methods A retrospective cohort study of 100 patients who underwent TSA (reverse total shoulder arthroplasty N1 = 50; anatomic total shoulder arthroplasty N2 = 50) between 1 July 2018 and 31 December 2018 was performed. Demographics, perioperative treatments, and postoperative opioid prescriptions were recorded. Primary hypotheses were evaluated with Wilcoxon-Mann-Whitney testing. Univariate and multivariate analyses assessed potential risk factors for the 3 outcomes of interest. Results were given in adjusted odds ratios (aORs), 95% confidence intervals (CIs), and P values. Results There was a difference (P = .009) in total morphine equivalent doses used (in 5-milligram oxycodone tablets) between patients who were younger than 65 years of age (median: 83 tablets, interquartile range: 62-140) and those who were older than 65 years of age (median: 65 tablets, interquartile range: 52-90). Unemployment (aOR = 4.68, CI: 1.5-14.2, P = .006) and age less than 65 years (aOR = 4.18, CI: 1.6-11.2, P = .004) were independent risk factors for inadequate pain control 6 weeks postoperatively. Two independent risk factors for needing an opiate prescription refill after discharge were unemployment (aOR = 4.56, CI: 1.5-13.8, P = .007) and preoperative opiate use (aOR = 3.95, CI: 1.4-11.0, P = .009). Conclusion After TSA, morphine equivalent dose usage is higher for patients younger than 65 years of age, and several risk factors exist for requiring a refill and having inadequate pain control 6 weeks postoperatively. Prospective studies using these data to guide interventions may be beneficial.

BACKGROUND Better alignment of opioid prescription quantities with patient need could help reduce excessive prescribing. OBJECTIVE The study sought to develop an institutional prescribing guideline based on defined opioid consumption patterns after inpatient colorectal operations. DESIGN This was a retrospective cohort study. SETTINGS The study was conducted at a single tertiary care center. PATIENTS Patients who underwent elective major colorectal procedures between July 2018 and January 2019 were included. MAIN OUTCOME MEASURES The study measured prescription and consumption quantities measured as equianalgesic oxycodone 5-mg pills. RESULTS Patients were categorized into 3 groups based on consumption in the 24-hour period before discharge: tier 1 consumed 0 equianalgesic oxycodone 5-mg pills (n = 53), tier 2 consumed 0.1 to 3.0 equianalgesic oxycodone 5-mg pills (n = 25), and tier 3 consumed >3.0 equianalgesic oxycodone 5-mg pills (n = 22). Average prescription quantity was 17.5 ± 10.5 equianalgesic oxycodone 5-mg pills (range, 0-78). Patients consumed a mean of 6.7 ± 10.9 equianalgesic oxycodone 5-mg pills after discharge and had 10.8 ± 10.2 equianalgesic oxycodone 5-mg pill excess, whereas 51% of patients consumed no pills. Opioid consumption was significantly different between each tier (p < 0.001). A prescribing guideline was developed to satisfy the majority of patients: 0 equianalgesic oxycodone 5-mg pills if tier 1, 12 pills if tier 2, and 30 pills if tier 3. Tiered guideline adoption could reduce prescribed pills by 45% and excess pills per prescription by 73%. Patient history of IBD was independently associated with increased odds of exceeding the guideline (adjusted OR = 7.2 (95% CI, 1.6-32.6)). LIMITATIONS The study was limited by its single-center, retrospective design and that outpatient opioid consumption was self-reported. CONCLUSIONS Following hospital discharge after major colorectal surgery, more than half of patients consumed no opioid pills, and 62% of prescribed opioids were in excess. Outpatient opioid consumption was highly associated with inpatient opioid use in the 24 hours before discharge. Prospective validation of this prescribing guideline is needed, but adoption could reduce excessive prescribing. See Video Abstract at http://links.lww.com/DCR/B575. DESARROLLO DE UNA GUA PRCTICA PARA LA PRESCRIPCIN DE OPIOIDES AL EGRESO DESPUS DE UNA CIRUGA COLORRECTAL MAYOR ANTECEDENTES:Una mejor alineacion de las cantidades de prescripcion de opioides con las necesidades del paciente podria ayudar a reducir la prescripcion excesiva.OBJETIVO:El estudio busco desarrollar una guia institucional de prescripcion basada en patrones definidos de consumo de opioides luego de cirugias colorrectales hospitalarias.DISENO:Estudio de cohorte retrospectivo.ENTORNO CLINICO:El estudio se llevo a cabo en un solo centro de atencion terciaria.PACIENTES:Pacientes que se sometieron a procedimientos colorrectales mayores electivos entre julio de 2018 y enero de 2019.PRINCIPALES MEDIDAS DE RESULTADO:El estudio midio las cantidades de prescripcion y consumo medidas como pildoras de 5 mg de oxicodona equianalgesica (EOP).RESULTADOS:Los pacientes se clasificaron en tres grupos segun el consumo en el periodo de 24 horas antes del egreso: el nivel 1 consumio 0 EOP (n = 53), el nivel 2 consumio 0,1-3 EOP (n = 25) y el nivel 3 consumio mas de 3 EOP (n = 22). La cantidad promedio de prescripcion fue 17,5 (± 10,5) EOP (rango: 0-78). Los pacientes consumieron una media de 6,7 (± 10,9) EOP posterior al egreso y tuvieron un exceso de 10,8 (± 10,2) EOP, mientras que el 51% de los pacientes no consumieron pildoras. El consumo de opioides fue significativamente diferente entre cada nivel (p

Objective To assess the analgesic efficacy and safety of single-dose oral cannabidiol (CBD) as an adjunct to standard care for patients presenting to an emergency department with acute low back pain. Design Randomised, double blinded, placebo-controlled clinical trial. Setting The tertiary emergency department of Austin Hospital, Melbourne. Participants Patients who presented with acute, non-traumatic low back pain between 21 May 2018 and 13 June 2019. Intervention One hundred eligible patients were randomised to receiving 400 mg CBD or placebo in addition to standard emergency department analgesic medication. Main outcome measures Pain score two hours after administration of study agent, on a verbal numerical pain scale (range, 0-10). Secondary outcomes were length of stay, need for rescue analgesia, and adverse events. Results The median age of the 100 participants was 47 years (IQR, 34-60 years); 44 were women. Mean pain scores at two hours were similar for the CBD (6.2 points; 95% CI, 5.5-6.9 points) and placebo groups (5.8 points; 95% CI, 5.1-6.6 points; absolute difference, -0.3 points; 95% CI, -1.3 to 0.6 points). The median length of stay was 9.0 hours (IQR, 7.4-12 hours) for the CBD group and 8.5 hours (IQR, 6.5-21 hours) for the placebo group. Oxycodone use during the four hours preceding and the four hours after receiving CBD or placebo was similar for the two groups, as were reported side effects. Conclusion CBD was not superior to placebo as an adjunct medication for relieving acute non-traumatic low back pain in the emergency department. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12618000487213 (prospective).

Opioids are one of the most prescribed classes of analgesic medications. Their narrow therapeutic index and metabolism through cytochrome p450 (CYP) enzymes can result in a drug interaction when used concomitantly with rifamycins. In clinical scenarios where concurrent therapy with an opioid and a rifamycin occurs, there is no standardized guidance for managing the interaction. The objective of this review was to examine literature which evaluates the concomitant use of opioids and rifamycins with clinically relevant CYP-inducing properties. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria was performed. PubMed, Scopus, and OVID Embase were queried for studies from database inception to January 2020 related to rifamycin and opioid medications. Only full-text, peer-reviewed, English language articles addressing clinical outcomes from concomitant rifamycin and opioid therapy were included. The review isolated 12 articles for data extraction from an original 2260 citations identified. Rifampin (11; 92%) and rifabutin (2; 17%) were the rifamycins studied along with seven different opioids. Decreased effect of opioids with concomitant rifampin therapy manifested as withdrawal in numerous patients on methadone and a decreased analgesic effect from tramadol, morphine, and, most notably, oxycodone. Only the combinations of rifampin with buccal fentanyl and rifabutin with buprenorphine and methadone were found to have no clinically measurable interaction. Available literature suggests that a decrease in opioid clinical effects is appreciated with concomitant rifamycin therapy. Further research is needed to focus on specific mitigation strategies beyond opioid agent selection, such as dosing adjustment recommendations.

Background Opioid overprescription for acute postoperative pain is an inadvertent contributor to the opioid epidemic via pill diversion and misuse. In response, the surgical community advocates for evidence-based postoperative opioid prescribing guidelines. The objective of this study is to evaluate patient-reported opioid consumption after lower extremity bypass surgery. Methods We conducted a retrospective review of a prospectively maintained database of infrainguinal bypass operations from 2016 to 2019. For patients receiving an opioid prescription at discharge, a telephone survey was administered questioning the percentage of pills used. Exclusion criteria included chronic opioid use and reoperations or amputations within 30 days. The primary outcome was the difference in opioids prescribed versus opioids consumed. Results Forty-nine patients met inclusion criteria. Forty-one (84%) were prescribed opioids at discharge, and 27 (65.9%) completed the survey. The average age was 65.8 ± 7.7 years; 29.6% were women. Oxycodone immediate-release was most commonly prescribed (78%). On average, patients received 318 ± 156 morphine milligram equivalent. A total of 940 opioid pills were prescribed (36.0 ± 11.3 per patient), but only 37% were consumed. This difference resulted in 568 unused pills. Conclusions This is the first study to specifically evaluate opioid use in a strictly lower extremity bypass population. Over 60% of pills were unused, which poses significant societal risk for misuse. Our findings contribute to knowledge of operation-specific opioid use, which may shape practice recommendations and reduce opioid overprescription after vascular surgery.

Nausea is a typical adverse event associated with opioids. In this study, we performed logistic regression analysis with the aim of clarifying the risk factors for nausea induced by extended-release oxycodone (ER-OXY). Furthermore, we constructed a decision tree (DT) model, a typical data mining method, to estimate the risk of oxycodone-induced nausea by combining multiple factors. A retrospective study was conducted on patients who newly received ER-OXY for cancer pain during hospitalization at Hokkaido University Hospital in Japan from April 2015 to March 2018. In logistic regression and DT analyses, the dependent variable was the presence or absence of nausea. Independent variables were the potential risk factors. First, univariate analyses were performed to screen potential factors associated with oxycodone-induced nausea. Then, multivariate and DT analyses were performed using factors with p-values

With an ongoing opioid epidemic in the United States, it is important to examine if decreased opioid prescribing can affect patient experience, namely satisfaction with pain control.The purpose of this study was to investigate what effect, if any, decreased opioid prescribing after total shoulder arthroplasty had on Press Ganey satisfaction surveys.A retrospective review was conducted on patients who underwent primary anatomic or reverse total shoulder arthroplasty between October 2014 and October 2019. Patients with complete Press Ganey survey information and no history of trauma, fracture, connective tissue disease, or prior shoulder arthroplasty surgery were included in the analysis. Patients were segregated into 2 groups, pre-protocol and post-protocol, based on the date of surgery relative to implementation of an institutional opioid reduction protocol, which occurred in October 2018. Prescriptions were converted to morphine milligram equivalents (MME) for direct comparison between different opioid medications.A total of 201 patients met inclusion criteria, and there were 110 reverse total shoulder arthroplasties and 91 anatomic total shoulder arthroplasties. Average opioids prescribed on discharge for the pre-protocol group were 426.3 ± 295 MME (equivalent to 56.8 tablets of oxycodone 5 mg), whereas after the initiation of the protocol, they were 193.8 ± 199 MME (equivalent to 25.8 tablets of oxycodone 5 mg); P.0001. Average satisfaction with pain control did not change significantly between pre-protocol and post-protocol (4.71 ± 0.65 pre-protocol and 4.74 ± 0.44 post-protocol, P = .82).A reduction in opioids prescribed after a total shoulder replacement is not associated with any negative effects on patient satisfaction, as measured by the Press Ganey survey.

Purpose To investigate what effect decreased opioid prescribing following hip arthroscopy had on Press–Ganey satisfaction survey scores. Methods A retrospective review of prospectively collected data was conducted on patients who underwent primary hip arthroscopy for femoroacetabular impingement between October 2014 and October 2019. Inclusion criteria consisted of complete Press–Ganey survey information, no history of trauma, fracture, connective tissue disease, developmental hip dysplasia, autoimmune disease, or previous hip arthroscopy. Groups were separated based on date of surgery relative to implementation of an institutional opioid reduction policy that occurred in October 2018. Prescriptions were converted to milligram morphine equivalents (MME) for direct comparison between different opioids. Results A total of 113 patients met inclusion criteria, 88 preprotocol and 25 postprotocol. There were no statistically significant differences between groups with respect to patient demographics or intraoperative pathologies (P > .05). Average opioid prescription dropped from 249.6 ± 152 MME (equivalent to 33.3 tablets of oxycodone 5 mg) preprotocol to 108.6 ± 84.7 MME (equivalent to 14.5 tablets of oxycodone 5 mg) postprotocol; P = .0002. There were no statistically significant differences in Press–Ganey survey scores between pre- and postprotocol groups (P > .05). Conclusions A reduction in opioids prescribed after a hip arthroscopy is not associated with any statistically significant difference in patient satisfaction with pain management, as measured by the Press–Ganey survey. Level of Evidence Level III, retrospective comparative study.

Objectives Dentists are independent prescribers that can prescribe subsidised medicines under the Australian Pharmaceutical Benefits Scheme (PBS). It is hypothesised that increased dental prescribing can partly be accounted for by the growth in both the Australian population and the number of practising dentists. This pharmacoepidemiological study aims to determine the dispensing patterns of medications amongst dentists and to identify trends over time. Materials and methods Data on dental medications under PBS from 2006 to 2018 were accessed. All the dentist-prescribed concessional medicines dispensed at pharmacies in 2018 were included for time trend analysis. Cumulative dispensing counts and defined daily dose (DDD) per 1,000 concessional population days (DPD) were analysed for time trend analysis. Results Out of the 56 medications within the dental PBS schedule, the top 20 medicines had a total cumulative dispensing count of 5,058,556, which accounts for 97.4% of the total dispensing count. Eleven out of 20 medicines were antibiotics. Overall, increases were observed for seven out of 20 medicines (amoxicillin + clavulanic acid, clindamycin, ibuprofen, diazepam, oxycodone, tramadol, naproxen) in both dispensing count and trend, as expressed per DPD. Conclusion This study highlights the increasing dispensing pattern and trends of dentist-prescribed antibiotics, opioids and benzodiazepines. Further investigation may be required to determine whether the medicine use is appropriate. In the future, this could provide new educational opportunities on the appropriate use of medicines for dentists.

A 41-year-old male presented for pain treated with oxycodone. A zone-2 thoracic endovascular aortic repair with distal PETTICOAT (provisional extension to induce complete attachment) for complicated Type-IIIB aortic dissection was performed 18 months before. Repeated hospitalizations did not show any issues to justify the recurrent pain. The aortic nature of the pain was suspected considering the plug as a pain trigger. Through a left thoracoabdominal incision in the eighth intercostal space, the candy plug was removed. Pain diminished after thoracoabdominal surgery steadily.

Study design This is a prospective observational study. Objective The aim was to record daily opioid use and pain levels after 1-level or 2-level anterior cervical discectomy and fusion (ACDF) or cervical disc arthroplasty (CDA). Summary of background data Data to inform opioid prescription guidelines following ACDF or CDA is lacking. Understanding postoperative opioid consumption behaviors is critical to provide appropriate postdischarge prescriptions. Methods Patients undergoing 1-level or 2-level primary ACDF or CDA were consecutively enrolled at 2 participating institutions between March 2018 and March 2019. Patients with opioid dependence (defined as daily use ≥6 mo before surgery) were excluded. Starting postoperative day 1, daily opioid use and numeric pain rating scale pain levels were collected through a Health Insurance Portability and Accountability Act-compliant, automated text-messaging system. To facilitate clinical applications, opioid use was converted from oral morphine equivalents into "pills" (oxycodone 5 mg equivalents). After 6 weeks or upon patient-reported cessation of opioid use, final survey questions were asked. Refill data were verified from the state prescription registry. Risk factors for patients in top quartile of consumption were analyzed. Results Of 57 patients, 48 completed the daily queries (84.2%). Mean age of the patient sample was 50.2±10.9 years. Thirty-two patients (66.7%) underwent ACDF and 16 CDA (33.3%); 64.6% one level; 35.4% two levels. Median postdischarge use was 6.7 pills (range: 0-160). Cumulative opioid use did not vary between the 1-level and 2-level groups (median pill consumption, 10 interquartile range: 1.3-31.3 vs. 4 interquartile range: 0-18, respectively, P=0.085). Thirteen patients (27.1%) did not use any opioids after discharge. Of those patients that took opioids after discharge, half ceased opioids by postoperative day 8. Preoperative intermittent opioid use was associated with the top quartile of opioid consumption (9.1% vs. 50%, P=0.006). Conclusion Given that most patients use few opioids, patients could be offered the option of a 12 oxycodone 5 mg (90 oral morphine equivalents) discharge prescription, accompanied by education on appropriate opioid use and disposal.

We estimated the prevalence of potentially actionable pharmacogenetic (PGx) variants related to symptom control medications (SCMs) based on institutional prescribing patterns and correlated presenting symptoms with SCM prescribing. This was a retrospective study of adult ambulatory cancer patients undergoing electronic distress screening (EDS) within 90 days of intake to the cancer hospital. We estimated the proportion prescribed SCM(s) with PGx evidence within 90 days of intake. Those with potentially actionable variants were estimated using population frequency data from 1000 genomes. The expected number at risk of altered drug response was estimated. The associations between symptom scores and SCM(s) were estimated with logistic regression and threshold analyses performed with receiver operating characteristic (ROC) curves. Of 6985 patients, 3222 (46%) received ≥ one SCM. Of these, 2760 (86%) received SCM(s) with PGx evidence for CYP2B6, CYP2C19, CYP2D6, or SLC6A4; 2719 (84%) received a drug metabolized by CYP2D6, most commonly hydrocodone (40.4%), ondansetron (35.6%), oxycodone (24.2%), and/or tramadol (7.1%). Based on this, about one quarter were expected to have altered metabolism and/or drug response. One third were prescribed two or more SCMs with PGx evidence. About half reported at least one severe symptom, which significantly correlated with SCM prescribing (p < 0.001). Threshold scores were identified that highly correlated with SCM prescribing for anxiety, depression, nausea, neuropathy, pain, and sleep. About half presented with significant symptom burden, which highly correlated with SCM prescribing. Most received SCMs with PGx evidence. Preemptive PGx testing for these variants should be evaluated in prospective trials to evaluate the impact on symptom control.

Pain is a common problem for children, and pain management comprises both pharmacologic and nonpharmacologic measures. For moderate to severe pain, oral opioids have been a popular choice for the last few decades. Codeine has historically been the best-known oral opioid for use in children. However, availability and use of codeine have sharply declined due to safety concerns. A variety of other opioids have been used in place of codeine, but data are limited regarding their efficacy and safety in children. While the same pathways metabolize oral oxycodone as codeine, oxycodone’s pharmacokinetics varies widely. There are also limited data on the safety and efficacy of oral hydromorphone and tramadol use for children. Oral morphine is the opiate alternative to codeine for which there is the most evidence of safety and efficacy in children. Research is needed to investigate both other opioids and non-opioid approaches to guide evidence-based analgesic therapy and treatment for moderate-to-severe pain in children.

Background Cardiac bypass surgery patients have early postoperative interventions that elicit breakthrough pain. We evaluated the use of intranasal fentanyl for breakthrough pain management in these patients. Methods Multimodal analgesia (paracetamol 1 g three times a day, oxycodone 2–3 mg boluses with a patient-controlled intravenous pump) was used in 16 patients (age 49–70 years, weight 59–129 kg) after cardiac bypass surgery. Intranasal fentanyl 100 µg or 200 µg was used to manage breakthrough pain on the first and third postoperative mornings in a randomised order. Blood samples were collected for up to 3 h after fentanyl administration, pain was assessed with a numeric rating scale of 0–10. Plasma fentanyl concentration was assayed using liquid chromatography-mass spectrometry. Body composition was measured with a bioelectrical impedance device. Results Bioavailability of intranasal fentanyl was high (77%), absorption half-time short (< 2 min) and an analgesic plasma concentration ≥ 0.5 ng/mL was achieved in 31 of 32 administrations. Fentanyl exposure correlated inversely with skeletal muscle mass and total body water. Fentanyl analgesia was effective both on the first postoperative morning with chest pleural tube removal and during physiotherapy on the third postoperative morning. The median time of subsequent oxycodone administration was 1.1 h after intranasal fentanyl 100 µg and 2.1 h after intranasal fentanyl 200 µg, despite similar oxycodone concentrations (median 13.8, range 5.2–35 ng/mL) in both fentanyl dose groups. Conclusions Intranasal fentanyl 100 µg provided rapid-onset analgesia within 10 min and is an appropriate starting dose for incidental breakthrough pain in the first 3 postoperative days after cardiac bypass surgery. Clinical Trial Registration EudraCT Number: 2018-001280-22. Supplementary Information The online version contains supplementary material available at 10.1007/s40262-021-01002-4.

Background Patients undergoing upper extremity fracture surgery often have postoperative pain that can be mitigated with opioid pain medications. Opioid misuse and abuse are growing concerns regarding the liberal use of opioids in the perioperative setting. The impact of mental health disorders and substance abuse on perioperative opioid demand is largely unknown. The purpose of this study is to describe perioperative opioid filling and risk factors for increased filling after upper extremity fractures. The study hypothesis is that poor mental health and substance abuse will be associated with increased opioid demand. Methods This is a retrospective, cohort study of 26,283 patients undergoing operative fixation of upper extremity fractures involving the proximal humerus through distal radius using a commercially available insurance database. Opioid prescription filling in oxycodone 5-mg equivalents and refills were tabulated from 1 month preoperation to 1 year postoperation. Multivariable linear and logistic regression models were constructed in R (Statistical Analysis Software) to evaluate associations between mental health and substance use disorders and opioid-related outcomes with adjustment for baseline patient and treatment factors such as age, sex, comorbidities, and fracture location. Results Of the 26,283 patients in the cohort, 79.9%, 32.6%, and 83.1% filled at least 1 opioid prescription in the 1-month preoperative to 90-day postoperative, 3-month postoperative to 1-year postoperative, and 1-month preoperative to 1-year postoperative time frames, respectively. Mean opioid volume prescribed during those time frames was 103.7, 53.5, and 156.9 oxycodone 5-mg equivalents, respectively. Drug abuse, psychoses, and preoperative opioid filling were significant mental health–related drivers of increased postoperative opioid demand. Discussion This study reports the rate and volume of opioid prescription filling in patients undergoing upper extremity fracture surgery. Mental health and substance use disorders were significant drivers of perioperative opioid demand. These study findings can guide surgeons to anticipate expected perioperative opioid demand and identify patients who may benefit from collaboration with pain management specialists during the perioperative period.

Supplemental Digital Content is available in the text., Background: It is unclear whether confounding accounts for the increased risk of preterm birth and small for gestational age (SGA) birth in opioid analgesic exposed pregnancies. Methods: Using universal coverage health data for Ontario, we assembled a cohort of mother–infant pairs without opioid use disorder (627,172 pregnancies and 509,522 women). We estimated risk ratios (RRs) between opioid analgesics and preterm birth, SGA birth, and stillbirth; neonatal abstinence syndrome was a secondary outcome. We used high-dimensional propensity scores and sensitivity analyses for confounding adjustment. Results: 4% of pairs were exposed, mainly to codeine (2%), morphine (1%), and oxycodone (1%). Compared with unexposed, the adjusted risk of preterm birth was higher with any (1.3, 95% confidence interval [CI] = 1.2, 1.3), first- (RR: 1.2, 95% CI = 1.2, 1.3), and second-trimester (RR: 1.3, 95% CI = 1.2, 1.4) opioid analgesic exposure. Preterm birth risk was higher for first- and second-trimester codeine, morphine, and oxycodone exposure, and for third-trimester morphine. There was a small increase in SGA with first-trimester exposure to any opioid analgesic or to codeine. Exposed pregnancies had an elevated stillbirth risk with any (RR: 1.6, 95% CI = 1.4, 1.8), first- and second-trimester exposure. Few infants had neonatal abstinence syndrome (N = 143); the risk was higher in exposed (RR: 3.6, 95% CI = 2.1, 6.0). In sensitivity analyses of unmeasured confounding, an elevated risk in exposed pregnancies persisted for preterm birth but not SGA. Conclusions: Opioid analgesic-exposed pregnancies had a small increased risk of preterm birth and possibly stillbirth after accounting for confounding by indication and sociodemographic factors.