Medications for Opioid Use Disorder and Mortality and Hospitalization Among People With Opioid Use-related Infections.

BACKGROUND: Severe skin and soft tissue infections related to injection drug use have increased in concordance with a shift to heroin and illicitly manufactured fentanyl. Opioid agonist therapy medications (methadone and buprenorphine) may improve long-term outcomes by reducing injection drug use. We aimed to examine the association of medication use with mortality among people with opioid use-related skin or soft tissue infections. METHODS: An observational cohort study of Medicaid enrollees aged 18 years or older following their first documented medical encounters for opioid use-related skin or soft tissue infections during 2007-2018 in North Carolina. The exposure was documented medication use (methadone or buprenorphine claim) in the first 30 days following initial infection compared with no medication claim. Using Kaplan-Meier estimators, we examined the difference in 3-year incidence of mortality by medication use, weighted for year, age, comorbidities, and length of hospital stay. RESULTS: In this sample, there were 13,286 people with opioid use-related skin or soft tissue infections. The median age was 37 years, 68% were women, and 78% were white. In Kaplan-Meier curves for the total study population, 12 of every 100 patients died during the first 3 years. In weighted models, for every 100 people who used medications, there were four fewer deaths over 3 years (95% confidence interval = 2, 6). CONCLUSION: In this study, people with opioid use-related skin and soft tissue infections had a high risk of mortality following their initial healthcare visit for infections. Methadone or buprenorphine use was associated with reductions in mortality.

Matching study design to prescribing intention: The prevalent new-user design for studying abuse-deterrent formulations of opioids.

PURPOSE: In drug studies, research designs requiring no prior exposure to certain drug classes may restrict important populations. Since abuse-deterrent formulations (ADF) of opioids are routinely prescribed after other opioids, choice of study design, identification of appropriate comparators, and addressing confounding by "indication" are important considerations in ADF post-marketing studies. METHODS: In a retrospective cohort study using claims data (2006-2018) from a North Carolina private insurer [NC claims] and Merative MarketScan [MarketScan], we identified patients (18-64 years old) initiating ADF or non-ADF extended-release/long-acting (ER/LA) opioids. We compared patient characteristics and described opioid treatment history between treatment groups, classifying patients as traditional (no opioid claims during prior six-month washout period) or prevalent new users. RESULTS: We identified 8415 (NC claims) and 147 978 (MarketScan) ADF, and 10 114 (NC claims) and 232 028 (MarketScan) non-ADF ER/LA opioid initiators. Most had prior opioid exposure (ranging 64%-74%), and key clinical differences included higher prevalence of recent acute or chronic pain and surgery among patients initiating ADFs compared to non-ADF ER/LA initiators. Concurrent immediate-release opioid prescriptions at initiation were more common in prevalent new users than traditional new users. CONCLUSIONS: Careful consideration of the study design, comparator choice, and confounding by "indication" is crucial when examining ADF opioid use-related outcomes.

Naloxone Accessibility by Standing Order in North Carolina Community Pharmacies.

BACKGROUND: According to a standing order in North Carolina (NC), naloxone can be purchased without a provider prescription. OBJECTIVE: The objective of this study is to examine whether same-day naloxone accessibility and cost vary by pharmacy type and rurality in NC. METHODS: A cross-sectional telephone audit of 202 NC community pharmacies stratified by pharmacy type and county of origin was conducted in March and April 2023. Trained "secret shoppers" enacted a standardized script and recorded whether naloxone was available and its cost. We examined the relationship between out-of-pocket naloxone cost, pharmacy type, and rurality. RESULTS: Naloxone could be purchased in 53% of the pharmacies contacted; 26% incorrectly noting that naloxone could be filled only with a provider prescription and 21% did not sell naloxone. Naloxone availability by standing order was statistically different by pharmacy type (chain/independent) (χ2 = 20.58, df = 4, P value < 0.001), with a higher frequency of willingness to dispense according to the standing order by chain pharmacies in comparison to independent pharmacies. The average quoted cost for naloxone nasal spray at chain pharmacies was $84.69; the cost was significantly more ($113.54; P < 0.001) at independent pharmacies. Naloxone cost did not significantly differ by pharmacy rurality (F2,136 = 2.38, P = 0.10). CONCLUSION: Approximately half of NC community pharmacies audited dispense naloxone according to the statewide standing order, limiting same-day access to this life-saving medication. Costs were higher at independent pharmacies, which could be due to store-level policies. Future studies should further investigate these cost differences, especially as intranasal naloxone transitions from a prescription only to over-the-counter product.

Identifying barriers and facilitators to COVID-19 vaccination uptake among People Who Use Drugs in Canada: a National Qualitative Study.

BACKGROUND: People Who Use Drugs (PWUD) have lower vaccination uptake than the general population, and disproportionately experience the burden of harms from vaccine-preventable diseases. We conducted a national qualitative study to: (1) identify the barriers and facilitators to receiving COVID-19 vaccinations among PWUD; and (2) identify interventions to support PWUD in their decision-making. METHODS: Between March and October 2022, semi-structured interviews with PWUD across Canada were conducted. Fully vaccinated (2 or more doses) and partially or unvaccinated (1 dose or less) participants were recruited from a convenience sample to participate in telephone interviews to discuss facilitators, barriers, and concerns about receiving COVID-19 vaccines and subsequent boosters, and ways to address concerns. A total of 78 PWUD participated in the study, with 50 participants being fully vaccinated and 28 participants partially or unvaccinated. Using thematic analysis, interviews were coded based on the capability, opportunity, and motivation-behavior (COM-B) framework. RESULTS: Many partially or unvaccinated participants reported lacking knowledge about the COVID-19 vaccine, particularly in terms of its usefulness and benefits. Some participants reported lacking knowledge around potential long-term side effects of the vaccine, and the differences of the various vaccine brands. Distrust toward government and healthcare agencies, the unprecedented rapidity of vaccine development and skepticism of vaccine effectiveness were also noted as barriers. Facilitators for vaccination included a desire to protect oneself or others and compliance with government mandates which required individuals to get vaccinated in order to access services, attend work or travel. To improve vaccination uptake, the most trusted and appropriate avenues for vaccination information sharing were identified by participants to be people with lived and living experience with drug use (PWLLE), harm reduction workers, or healthcare providers working within settings commonly visited by PWUD. CONCLUSION: PWLLE should be supported to design tailored information to reduce barriers and address mistrust. Resources addressing knowledge gaps should be disseminated in areas and through organizations where PWUD frequently access, such as harm reduction services and social media platforms.

Reducing the harms of xylazine: clinical approaches, research deficits, and public health context.

OBJECTIVES: Xylazine has emerged as a consistent part of the unregulated drug supply in recent months. We discuss major domains of xylazine's harm, current knowledge deficits, clinical and harm reduction strategies for minimizing harm, and xylazine's public health and policy context. As an interdisciplinary team from across the USA, we have pooled our knowledge to provide an overview of xylazine's current and emerging contexts. METHODS: To inform this essay, the pertinent literature was reviewed, clinical knowledge and protocols were shared by multiple clinicians with direct expertise, and policy and public health context were added by expert authors. RESULTS: We describe xylazine's major harm domains-acute poisoning, extended sedation, and wounds, along with anemia and hyperglycemia, which have been reported anecdotally but lack as clear of a connection to xylazine. Current successful practices for xylazine wound care are detailed. Understanding xylazine's epidemiology will also require greater investment in drug checking and surveillance. Finally, approaches to community-based wound care are discussed, along with an orientation to the larger policy and public health context. CONCLUSIONS: Addressing the harms of xylazine requires interdisciplinary participation, investment in community-based harm reduction strategies, and improved drug supply surveillance. The relatively unique context of xylazine demands buy-in from public health professionals, harm reduction professionals, clinicians, basic science researchers, policymakers and more.

Invited Commentary: Drug Checking for Novel Insights Into the Unregulated Drug Supply.

Tobias et al. (Am J Epidemiol. 2022;191 (2):241-247) present a novel analysis of time trends in fentanyl concentrations in the unregulated drug supply in British Columbia, Canada. The preexisting knowledge about unregulated drugs had come from law-enforcement seizures and postmortem toxicology. As both of these data sources are subject to selection bias, large-scale drug-checking programs are poised to be a crucial component of the public health response to the unrelenting increase in overdose in North America. As programs expand, we offer 2 guiding principles. First, the primary purpose of these programs is to deliver timely results to people who use drugs to mitigate health risks. Second, innovation is needed to go beyond criminal justice paradigms in laboratory analysis for a more nuanced understanding of health concerns. We provide examples of the role adulterants play in our understanding of drug harms. We also describe the applications and limitations of common laboratory assays, with implications for epidemiologic surveillance. While the research and direct service teams in British Columbia have taken groundbreaking steps, there is still a need to establish best practices for communicating results to sample donors in an approachable yet nonalarmist tone.

Impacts of Initial Prescription Length and Prescribing Limits on Risk of Prolonged Postsurgical Opioid Use.

BACKGROUND: In response to concerns about opioid addiction following surgery, many states have implemented laws capping the days supplied for initial postoperative prescriptions. However, few studies have examined changes in the risk of prolonged opioid use associated with the initial amount prescribed. OBJECTIVE: The objective of this study was to estimate the risk of prolonged opioid use associated with the length of initial opioid prescribed and the potential impact of prescribing limits. RESEARCH DESIGN: Using Medicare insurance claims (2007-2017), we identified opioid-naive adults undergoing surgery. Using G-computation methods with logistic regression models, we estimated the risk of prolonged opioid use (≥1 opioid prescription dispensed in 3 consecutive 30-d windows following surgery) associated with the varying initial number of days supplied. We then estimate the potential reduction in cases of prolonged opioid use associated with varying prescribing limits. RESULTS: We identified 1,060,596 opioid-naive surgical patients. Among the 70.0% who received an opioid for postoperative pain, 1.9% had prolonged opioid use. The risk of prolonged use increased from 0.7% (1 d supply) to 4.4% (15+ d). We estimated that a prescribing limit of 4 days would be associated with a risk reduction of 4.84 (3.59, 6.09)/1000 patients and would be associated with 2255 cases of prolonged use potentially avoided. The commonly used day supply limit of 7 would be associated with a smaller reduction in risk [absolute risk difference=2.04 (-0.17, 4.25)/1000]. CONCLUSIONS: The risk of prolonged opioid use following surgery increased monotonically with increasing prescription duration. Common prescribing maximums based on days supplied may impact many patients but are associated with relatively low numbers of reduced cases of prolonged use. Any prescribing limits need to be weighed against the need for adequate pain management.

Considerations for observational study design: Comparing the evidence of opioid use between electronic health records and insurance claims.

PURPOSE: Pharmacoepidemiology studies often use insurance claims and/or electronic health records (EHR) to capture information about medication exposure. The choice between these data sources has important implications. METHODS: We linked EHR from a large academic health system (2015-2017) to Medicare insurance claims for patients undergoing surgery. Drug utilization was characterized based on medication order dates in the EHR, and prescription fill dates in Medicare claims. We compared opioid use documented in EHR orders to prescription claims in four time periods: 1) Baseline (182 days before surgery); 2) Perioperative period; 3) Discharge date; 4) Follow-up (90 days after surgery). RESULTS: We identified 11 128 patients undergoing surgery. During baseline, 34.4% (EHR) versus 44.1% (claims) had evidence of opioid use, and 56.9% of all baseline use was reflected only in one data source. During the perioperative period, 78.8% (EHR) versus 47.6% (claims) had evidence of use. On the day of discharge, 59.6% (EHR) versus 45.5% (claims) had evidence of use, and 51.8% of all discharge use was reflected only in one data source. During follow-up, 4.3% (EHR) versus 10.4% (claims) were identified with prolonged opioid use following surgery with 81.4% of all prolonged use reflected only in one data source. CONCLUSIONS: When characterizing opioid exposure, we found substantial discrepancies between EHR medication orders and prescription claims data. In all time periods assessed, most patients' use was reflected only in the EHR, or only in the claims, not both. The potential for misclassification of drug utilization must be evaluated carefully, and choice of data source may have large impacts on key study design elements.

Accuracy and validity of reported opioid prescription days' supply.

PURPOSE: The primary objective of this study was to estimate the percentage of opioid analgesic (OA) prescriptions dispensed by Kentucky independent pharmacies with correctly entered days' supply in the state prescription drug monitoring program (PDMP) system in 2019. METHODS: Using a two-stage cluster design, pharmacies were sampled with probabilities proportional to the volume of dispensed OAs; 100 random OA prescriptions were sampled from PDMP records submitted by each pharmacy. Following recruitment, demographic information and hard-copy prescription data for sampled records were abstracted on-site. Days' supply was independently calculated by two pharmacists using a standard formula with disagreements adjudicated blindly by a third pharmacist. Adjudicated days' supply was compared with that submitted to the PDMP and classified as accurate/inaccurate. Descriptive statistics were used to characterize the sample and a multivariable logistic regression model was used to assess the relationship between accuracy and prescription/practice-related factors. RESULTS: A total of 1281 OA prescriptions were reviewed at 13 participating pharmacies. Accuracy of reported OA days' supply was 89.85%, (95% CI: 86.90, 92.80). Factors associated with accuracy were presence of special instructions from the prescriber (OR 3.13 [95% CI: 1.43, 6.82]), presence of 'as-needed' directions (OR 0.29 [95% CI: 0.18, 0.47]), and billing to a third-party payer (OR 1.43 [95% CI: 1.01, 2.02]). CONCLUSIONS: Accuracy of OA days' supply reported to the state PDMP was found to be moderately high. Certain prescription-related factors influence accuracy and should be accounted for in future studies. Patterns, including opioid 'split-billing' were identified and may impact validity of PDMP and administrative claims studies.

Kentucky pharmacists' experiences in dispensing abuse-deterrent opioid analgesics.

BACKGROUND: Despite pharmaceutical industry promise and enthusiasm, abuse-deterrent formulation (ADF) opioid use is relatively low. While some barriers to use have been addressed through state laws and policy, pharmacists' experiences with and opinions of ADF opioids are unclear. OBJECTIVES: The objective of this study was to evaluate pharmacists' perceptions of dispensing ADFs. METHODS: This was a cross-sectional survey of community pharmacists licensed and practicing in Kentucky conducted in late 2019. The survey asked about perception, experience dispensing, and insurance coverage of 5 ADF opioids available at the time. RESULTS: Most respondents (421/629, 67.9%) were familiar or very familiar with ADFs, and 63.1% agreed that all opioids should meet U.S. Food and Drug Administration standards for abuse deterrence. Aside from OxyContin, most ADF opioid formations were not stocked (range: 46.7%-73.6%). Third-party payer claims were occasionally or almost always rejected for most ADFs (range: 56.3%-75.4%). Contrary to intended mechanism of deterrence, ADFs were rated as the least effective strategy to reduce opioid misuse/abuse, with over half (51.2%) of respondents believing ADFs were not effective or somewhat effective. ADFs were rated as effective or very effective at reducing opioid abuse by swallowing intact by 37.4% of respondents. CONCLUSION: Pharmacists are familiar with ADFs but do not dispense them frequently. Pharmacists appear skeptical about the effectiveness of ADFs but support policies that could increase ADF uptake.

History and Future of Harm Reduction in North Carolina: Pragmatism and Innovation.

Harm reduction is a practice-oriented approach to reducing harms from drug use, including overdose and injection-related infections. North Carolina has a legacy of harm reduction innovation, yet our history includes sustained racist and harmful drug policies. People with lived experience are central to the creation of next-generation strategies for prevention.

Postsurgical Opioid Prescriptions and Risk of Long-term Use: An Observational Cohort Study Across the United States.

OBJECTIVE: The aim of this study was to evaluate differences in risk of long-term opioid therapy after surgery among an opioid-naive population using varying cutoffs based on days supplied (DS), total morphine milligram equivalents (MME) dispensed, and quantity of pills (QTY) dispensed. BACKGROUND: In response to the US opioid crisis, opioid prescription (Rx) limits have been implemented on a state-by-state basis beginning in 2016. However, there is limited evidence informing appropriate prescribing limits, and the effect of these policies on long-term opioid therapy. METHODS: Using the MarketScan claims databases, we identified all opioid-naive patients undergoing outpatient surgery between July 1, 2006 and June 30, 2015. We identified the initial postsurgical opioid prescribed, examining the DS, total MME, and QTY dispensed. We used Poisson to estimate adjusted risk differences and risk ratios of long-term opioid use comparing those receiving larger versus smaller volume of opioids. RESULTS: We identified 5,148,485 opioid-naive surgical patients. Overall, 55.5% received an opioid for postoperative pain, with median days supply = 5 and median total MME = 240. The proportion of patients receiving prescriptions above 7 DS increased from 11% in 2006 to 19% in 2015. Among those receiving postoperative opioids, 8% had long-term opioid use, and risk of long-term use was 1.16 times [95% confidence interval (CI), 1.10-1.25] higher among those receiving >7 days compared with those receiving ≤7 days. Those receiving >400 total MME (15% of patients) were at 1.17 times (95% CI, 1.10-1.25) the risk of long-term use compared with those receiving ≤400 MME. CONCLUSIONS: Between 2005 and 2015, the amounts of opioids prescribed for postoperative pain increased dramatically, and receipt of larger volume of opioids was associated with increased risk of long-term opioid therapy.

Day-of-Surgery Gabapentinoids and Prolonged Opioid Use: A Retrospective Cohort Study of Medicare Patients Using Electronic Health Records.

BACKGROUND: While preoperative gabapentinoids are commonly used in surgical multimodal analgesia protocols, little is known regarding the effects this therapy has on prolonged postsurgical opioid use. In this observational study, we used data from a large integrated health care system to estimate the association between preoperative day-of-surgery gabapentinoids and the risk of prolonged postsurgical opioid use. METHODS: We identified adults age ≥65 years undergoing major therapeutic surgical procedures from a large integrated health care system from 2016 to 2019. Exposure to preoperative gabapentinoids on the day of surgery was measured using inpatient medication administration records, and the outcome of prolonged opioid use was measured using outpatient medication orders. We used stabilized inverse probability of treatment-weighted log-binomial regression to estimate risk ratios and 95% confidence intervals (CIs) of prolonged opioid use, comparing patients who received preoperative gabapentinoids to those who did not and adjusting for relevant clinical factors. The main analysis was conducted in the overall surgical population, and a secondary analysis was conducted among procedures where at least 30% of all patients received a preoperative gabapentinoid. RESULTS: Overall, 13,958 surgical patients met inclusion criteria, of whom 21.0% received preoperative gabapentinoids. The observed 90-day risk of prolonged opioid use following surgery was 0.91% (95% CI, 0.77-1.08). Preoperative gabapentinoid administration was not associated with a reduced risk of prolonged opioid use in the main analysis conducted in a broad surgical population (adjusted risk ratio [adjRR], 1.19 [95% CI, 0.67-2.12]) or in the secondary analysis conducted in patients undergoing colorectal resection, hip arthroplasty, knee arthroplasty, or hysterectomy (adjRR, 1.01 [95% CI, 0.30-3.33]). CONCLUSIONS: In a large integrated health system, we did not find evidence that preoperative gabapentinoids were associated with reduced risk of prolonged opioid use in patients undergoing a broad range of surgeries.

Association Between Statewide Opioid Prescribing Interventions and Opioid Prescribing Patterns in North Carolina, 2006-2018.

OBJECTIVE: To examine the impact of three sequential statewide policy and legislative interventions on opioid prescribing practices among privately insured individuals in North Carolina. METHODS: An interrupted time series approach was used to examine level and trajectory changes of new and prevalent opioid prescription rates, days' supply, and daily morphine milligram equivalents before and after implementation of a 1) prescription drug monitoring program, 2) state medical board initiative, and 3) legislative action. Analyses were conducted using individual-level claims data from a large private health insurance provider serving North Carolina residents, ages 18-64 years, from January 2006 to August 2018. RESULTS: Rates of new and prevalent prescription opioid patients were relatively unaffected by the prescription monitoring program but sharply declined in the months immediately following both medical board (-3.7 new and -19.3 prevalent patients per 10,000 person months) and legislative (-14.1 new and -26.7 prevalent patients) actions. Among all opioid prescriptions, days' supply steadily increased on average over the study period but declined after legislative action (-1.5 days' supply per year). CONCLUSIONS: The voluntary prescription drug monitoring program launched in 2010 only marginally affected opioid prescribing patterns on its own, but its redeployment as an investigative and clinical tool in multifaceted public policy approaches by the state medical board and legislature later in the decade plausibly contributed to notable declines in prescription rates and days' supply. This study lends new emphasis to the importance of enforcement mechanisms for state and national policies seeking to reverse this critical public health crisis.

Implementation of mandatory opioid prescribing limits in North Carolina: healthcare administrator and prescriber perspectives.

BACKGROUND: Recent increases in state laws to reduce opioid prescribing have demonstrated a need to understand how they are interpreted and implemented in healthcare systems. The purpose of this study was to explore the systems, strategies, and resources that hospital administrators and prescribers used to implement the 2017 North Carolina Strengthen Opioid Prevention (STOP) Act opioid prescribing limits, which limited initial prescriptions to a five (for acute) or seven (for post-surgical) days' supply. METHODS: We interviewed 14 hospital administrators and 38 prescribers with degrees in medicine, nursing, pharmacy, business administration and public health working across North Carolina. Interview guides, informed by the Consolidated Framework for Implementation Research, explored barriers and facilitators to implementation. Interview topics included communication, resources, and hospital system support. Interviews were recorded and transcribed, then analyzed using flexible coding, integrating inductive and deductive coding, to inform analytic code development and identify themes. RESULTS: We identified three main themes around implementation of STOP act mandated prescribing limits: organizational communication, prescriber education, and changes in the electronic medical record (EMR) systems. Administrators reflected on implementation in the context of raising awareness and providing reminders to facilitate changes in prescriber behavior, operationalized through email and in-person communications as well as dedicated resources to EMR changes. Prescribers noted administrative communications about prescribing limits often focused on legality, suggesting a directive of the organization's policy rather than a passive reminder. Prescribers expressed a desire for more spaces to have their questions answered and resources for patient communications. While hospital administrators viewed compliance with the law as a priority, prescribers reflected on concerns for adequately managing their patients' pain and limited time for clinical care. CONCLUSIONS: Hospital administrators and prescribers approached implementation of the STOP act prescribing limits with different mindsets. While administrators were focused on policy compliance, prescribers were focused on their patients' needs. Strategies to implement the mandate then had to balance patient needs with policy compliance. As states continue to legislate to prevent opioid overdose deaths, understanding how laws are implemented by healthcare systems and prescribers will improve their effectiveness through tailoring and maximizing available resources.

Treatment experiences for skin and soft tissue infections among participants of syringe service programs in North Carolina.

INTRODUCTION: Bacterial and fungal infections, such as skin and soft tissue infections (SSTIs) and infective endocarditis (IE), are increasing among people who use drugs in the United States. Traditional healthcare settings can be inaccessible and unwelcoming to people who use drugs, leading to delays in getting necessary care. The objective of this study was to examine SSTI treatment experiences among people utilizing services from syringe services programs. This study was initiated by people with lived experience of drug use to improve quality of care. METHODS: We conducted a cross-sectional survey among participants of five syringe services programs in North Carolina from July through September 2020. Surveys collected information on each participant's history of SSTIs and IE, drug use and healthcare access characteristics, and SSTI treatment experiences. We examined participant characteristics using counts and percentages. We also examined associations between participant characteristics and SSTI history using binomial linear regression models. RESULTS: Overall, 46% of participants reported an SSTI in the previous 12 months and 10% reported having IE in the previous 12 months. Those with a doctor they trusted with drug use-related concerns had 27 fewer (95% confidence interval = - 51.8, - 2.1) SSTIs per every 100 participants compared to those without a trusted doctor. Most participants with a SSTI history reported delaying (98%) or not seeking treatment (72%) for their infections. Concerns surrounding judgment or mistreatment by medical staff and self-treating the infection were common reasons for delaying or not seeking care. 13% of participants used antibiotics obtained from sources other than a medical provider to treat their most recent SSTI. Many participants suggested increased access to free antibiotics and on-site clinical care based at syringe service programs to improve treatment for SSTIs. CONCLUSIONS: Many participants had delayed or not received care for SSTIs due to poor healthcare experiences. However, having a trusted doctor was associated with fewer people with SSTIs. Improved access to non-judgmental healthcare for people who use drugs with SSTIs is needed. Expansion of syringe services program-based SSTI prevention and treatment programs is likely a necessary approach to improve outcomes among those with SSTI and IE.

Medical Use of Long-term Extended-release Opioid Analgesics in Commercially Insured Adults in the United States.

OBJECTIVES: We examined the proportion of patients initiating extended-release (ER) opioids who become long-term users and describe how pain-related diagnoses before initiation of opioid therapy vary between drugs and over time. METHODS: Using MarketScan (2006-2015), a US national commercial insurance database, we examined pain-related diagnoses in the 182-day baseline period before initiation of ER opioid therapy to characterize indications for opioid initiation. We report the proportion who became long-term users, the median length of opioid therapy, and the proportion with cancer and other noncancer chronic pain, by active ingredient. RESULTS: Among 1,077,566 adults initiating ER opioids, 31% became long-term users, with a median length of use of 209 days. The most common ER opioids prescribed were oxycodone (26%) and fentanyl (23%), and the most common noncancer pain diagnoses were back pain (65%) and arthritis (48%). Among all long-term users, 16% had a diagnosis of cancer. We found notable variation by drug. Eighteen percent of patients initiating drugs approved by the Food and Drug Administration >10 years ago had evidence of cancer during baseline compared with only 8% of patients who received newer drugs. CONCLUSIONS: In a national sample of adults with private insurance, back pain was the most common diagnosis preceding initiation of opioid therapy. Opioids that have been approved within the last 10 years were more frequently associated with musculoskeletal pains and less frequently associated with cancer. Amid increasing concerns regarding long-term opioid therapy, our findings provide context regarding the conditions for which long-term opioid therapy is prescribed.

Opioid tolerance and clinically recognized opioid poisoning among patients prescribed extended-release long-acting opioids.

BACKGROUND: In recognition of potential for increased overdose risk, drug labels for extended-release and long-acting (ER/LA) opioids emphasize the need for established opioid tolerance prior to initiating high dosages. OBJECTIVES: Describe the proportion of patients with opioid tolerance prior to initiation of 90 morphine milligram equivalents (MME) ER/LA opioids and examine subsequent risk of opioid poisoning. METHODS: We used Truven Health Analytics' MarketScan Databases (2006-2015) to identify patients initiating ER/LA opioids ≥90 MME. We examined prescription histories and describe the proportion of initiators with opioid tolerance (defined as ≥7 days of 60 MME in the prior 14 days). We adjusted for age, sex, year of initiation, and baseline comorbidities using inverse probability of treatment weighted Cox proportional hazards models. We estimated adjusted hazard ratios and 95% confidence intervals for the effect of opioid tolerance on the risk of clinically recognized opioid poisoning (based on diagnosis codes) in specific periods (0-7, 8-30, 31-90, and 91-365 days) following initiation. RESULTS: Among 372 038 initiators, 38% did not meet opioid tolerance criteria. The proportion of nontolerant initiators was highest among those initiating methadone (44%) and fentanyl (42%). Nontolerant patients were 37% more likely to be diagnosed with opioid poisoning (adjusted hazard ratios = 1.37 [1.07, 1.76]) in the week following ER/LA initiation. CONCLUSIONS: Over one-third of patients initiating ≥90 MME ER/LA opioids did not have evidence of opioid tolerance. The 7 days following high dose ER/LA initiation may represent a high-risk period for clinically diagnosed opioid poisoning in patients who do not have prior opioid tolerance.