Association of Opioids Prescribed to Family Members With Opioid Overdose Among Adolescents and Young Adults.
ABSTRACT: Importance:Family members are cited as a common source of prescription opioids used for nonmedical reasons. However, the overdose risk associated with exposure to opioids prescribed to family members among adolescents and young adults is not well established. Objective:To assess the association of opioids prescribed to family members with pharmaceutical opioid overdose among youth. Design, Setting, and Participants:This cohort study included 45?145 family units with a total of 72?040 adolescents and young adults aged 11 to 26 years enrolled in a Kaiser Permanente Colorado health plan in 2006 and observed through June 2018. Exposures:Opioid prescriptions and dosage dispensed to family members and youth in the past month. Main Outcomes and Measures:Fatal pharmaceutical opioid overdoses identified in vital records and nonfatal pharmaceutical opioid overdoses identified in emergency department and inpatient settings. Time to first overdose was modeled using Cox regression. Results:The study population consisted of 72?040 adolescents and young adults (mean [SD] age across follow-up, 19.3 [3.7] years; 36?646 [50.9%] girls and women) nested in 45?145 family units. Youth were more commonly exposed to prescription opioids dispensed to a family member than through their own prescriptions. During follow-up, 26?284 youth (36.5%) filled at least 1 opioid prescription, and 47?461 youth (65.9%) had at least 1 family member with a prescription. Exposure to family members with opioid prescriptions in the past month was associated with increased risk of pharmaceutical opioid overdose (adjusted hazard ratio [aHR], 2.17; 95% CI, 1.24-3.79) independent of opioids prescribed to youth (aHR, 6.62; 95% CI, 3.39-12.91). Concurrent exposure to opioid prescriptions from youth and family members was associated with substantially increased overdose risk (aHR, 12.99; 95% CI, 5.08-33.25). High dosage of total morphine milligram equivalents (MME) prescribed to family members in the past month was associated with youth overdose (0 MME vs >0 to <200 MME: aHR, 1.39; 95% CI, 0.51-3.81; 0 MME vs 200 to <600 MME: aHR, 1.49; 95% CI, 0.59-3.77; 0 MME vs ?600 MME: aHR, 2.93; 95% CI, 1.55-5.56). Conclusions and Relevance:In this study of youth linked to family members, exposure to family members' prescribed opioids was associated with increased risk of pharmaceutical opioid overdose, independent of opioids prescribed to youth. Further interventions targeting youth and families are needed, including counseling patients about the risks of opioids to youth in their families.
Project description:Importance:Prescription opioid misuse is a public health problem that leads to overdose. Although existing interventions focus on limiting prescribing to patients at high risk, individuals may still access prescription opioids dispensed to family members. Objective:To determine whether opioid prescriptions to family members were associated with overdose for individuals who themselves did not have an opioid prescription. Design, Setting, and Participants:We conducted a 1:4 matched case-control study using health care utilization data from 2004 through 2015 from a large US commercial insurance company. Eligible individuals were required to have at least 12 months of continuous enrollment and 1 or more family members in the database. Individuals who experienced overdose were identified by their first opioid overdose after the baseline period and matched to control participants by time in the database, calendar time, age, sex, and number of individuals in the family unit. Both groups were restricted to individuals with no prior opioid dispensing of their own. Data analysis was conducted from January 2018 to August 2018. Exposures:Any prior opioid dispensing to a family member, total morphine milligram equivalents dispensed to family members, and the type of opioid product dispensed. Main Outcomes and Measures:Individual odds of opioid overdose resulting in an emergency department visit or hospitalization were the primary end point. The primary analysis evaluated the odds of overdose among individuals whose family members had been dispensed an opioid. Sensitivity analyses examined the odds stratified by age and timing relative to the dispensing of opioids to family members. Results:A total of 2303 individuals who experienced opioid overdose and 9212 matched control individuals were identified. The mean (SD) age was 23.2 (18.1) years; 1158 affected individuals and 4632 control individuals (50.3%) were female. The mean (SD) time in the database before an overdose case was 3.2 (3.3) years. Prior opioid dispensing to family members was associated with individual overdose (odds ratio [OR], 2.89 [95% CI, 2.59-3.23]). There was a significant dose-response association between increasing amounts of opioids dispensed to family members and odds of overdose (>0-<50 morphine milligram equivalents per day: OR, 2.71 [95% CI, 2.42-3.03]; 50-<90 morphine milligram equivalents per day: OR, 7.80 [95% CI, 3.63-16.78]; ?90 morphine milligram equivalents per day: OR, 15.08 [95% CI, 8.66-26.27]). Conclusions and Relevance:In this analysis, opioid prescriptions to family members were associated with overdose among individuals who do not receive opioid prescriptions. Interventions may focus on expanding access to opioid antagonists, locking prescription opioids in the home, and providing greater patient education to limit fatal overdose among family members.
Project description:BACKGROUND:Potentially inappropriate prescribing (PIP) may contribute to opioid overdose. OBJECTIVE:To examine the association between PIP and adverse events. DESIGN:Cohort study. PARTICIPANTS:Three million seventy-eight thousand thirty-four individuals age ≥ 18, without disseminated cancer, who received prescription opioids between 2011 and 2015. MAIN MEASURES:We defined PIP as (a) morphine equivalent dose ≥ 100 mg/day in ≥ 3 months; (b) overlapping opioid and benzodiazepine prescriptions in ≥ 3 months; (c) ≥ 4 opioid prescribers in any quarter; (d) ≥ 4 opioid-dispensing pharmacies in any quarter; (e) cash purchase of prescription opioids on ≥ 3 occasions; and (f) receipt of opioids in 3 consecutive months without a documented pain diagnosis. We used Cox proportional hazards models to identify PIP practices associated with non-fatal opioid overdose, fatal opioid overdose, and all-cause mortality, controlling for covariates. KEY RESULTS:All six types of PIP were associated with higher adjusted hazard for all-cause mortality, four of six with non-fatal overdose, and five of six with fatal overdose. Lacking a documented pain diagnosis was associated with non-fatal overdose (adjusted hazard ratio [AHR] 2.21, 95% confidence interval [CI] 2.02-2.41), as was high-dose opioids (AHR 1.68, 95% CI 1.59-1.76). Co-prescription of benzodiazepines was associated with fatal overdose (AHR 4.23, 95% CI 3.85-4.65). High-dose opioids were associated with all-cause mortality (AHR 2.18, 95% CI 2.14-2.23), as was lacking a documented pain diagnosis (AHR 2.05, 95% CI 2.01-2.09). Compared to those who received opioids without PIP, the hazard for fatal opioid overdose with one, two, three, and ≥ four PIP subtypes were 4.24, 7.05, 10.28, and 12.99 (test of linear trend, p < 0.001). CONCLUSIONS:PIP was associated with higher hazard for all-cause mortality, fatal overdose, and non-fatal overdose. Our study implies the possibility of creating a risk score incorporating multiple PIP subtypes, which could be displayed to prescribers in real time.
Project description:<h4>Background</h4>Over the last 2 decades, medical providers have increasingly prescribed pharmaceutical opioids for chronic non-cancer pain, while opioid overdose death rates have quadrupled. Naloxone, an opioid antagonist, can be prescribed to patients with chronic pain to reverse an opioid overdose, yet little is known about how patients perceive this emerging practice.<h4>Objective</h4>This study assessed the knowledge and attitudes toward naloxone prescribing among non-cancer patients prescribed opioids in primary care.<h4>Design</h4>Qualitative study design using semi-structured interviews.<h4>Participants</h4>Adults (N?=?24) prescribed high-dose (?100 morphine mg equivalent daily dose) chronic opioid therapy in eight primary care internal medicine, family medicine and HIV practices in three large Colorado health systems.<h4>Approach</h4>Inductive and deductive methods were used to analyze interview transcripts.<h4>Key results</h4>Themes emerged related to knowledge of and benefits, barriers and facilitators to naloxone in primary care. Patients reported receiving limited education about opioid medication risks from providers and limited knowledge of naloxone. When provided with a description of naloxone, patients recognized its ability to reverse overdoses. In addition to pragmatic barriers, such as medication cost, barriers to naloxone acceptance included the perception that overdose risk stems from medication misuse and that providers might infer that they were misusing their opioid medication if they accepted a naloxone prescription, prompting an opioid taper. Facilitators to the acceptance of naloxone included medical providers' using empowering, non-judgmental communication practices, framing naloxone for use in "worst case scenarios" and providing education and training about opioids and naloxone.<h4>Conclusions</h4>While patients recognized the utility of naloxone prescribing, we identified important barriers to patient acceptance of naloxone prescribing. To improve the naloxone prescribing acceptability in primary care practice, medical providers and health systems may need to enhance patient education, employ empowering, non-judgmental communication styles and adequately frame discussions about naloxone to address patients' fears.
Project description:Opioid prescribing has increased 15-fold in Australia in the past two decades, alongside increases in a range of opioid-related harms such as opioid dependence and overdose. However, despite concerns about increasing opioid use, extramedical use and harms, there is a lack of population-level evidence about the drivers of long-term prescribed opioid use, dependence, overdose and other harms. We will form a cohort of all adult residents in New South Wales (NSW), Australia, who initiated prescribed opioids from 2002 using Pharmaceutical Benefits Scheme dispensing records. This cohort will be linked to a wide range of other datasets containing information on sociodemographic and clinical characteristics, health service use and adverse outcomes (eg, opioid dependence and non-fatal and fatal overdose). Analyses will initially examine patterns and predictors of prescribed opioid use and then apply regression and survival analysis to quantify the risks and risk factors of adverse outcomes associated with prescribed opioid use. This study has received full ethical approval from the Australian Institute of Health and Welfare Ethics Committee, the NSW Population and Health Services Research Committee and the ACT Health Human Research Ethics Committee. This will be the largest postmarketing surveillance study of prescribed opioids undertaken in Australia, linking exposure and outcomes and examining risk factors for adverse outcomes of prescribed opioids. As such, this work has important translational promise, with direct relevance to regulatory authorities and agencies worldwide. Project findings will be disseminated at scientific conferences and in peer-reviewed journals. We will also conduct targeted dissemination with policy makers, professional bodies and peak bodies in the pain, medicine and addiction fields through stakeholder workshops and advisory groups. Results will be reported in accordance with the REporting of studies Conducted using Observational Routinely collected Data (RECORD) Statement.
Project description:BACKGROUND:Opioid overdose deaths occur in civilian and military populations and are the leading cause of accidental death in the USA. OBJECTIVE:To determine whether ECHO Pain telementoring regarding best practices in pain management and safe opioid prescribing yielded significant declines in opioid prescribing. DESIGN:A 4-year observational cohort study at military medical treatment facilities worldwide. PARTICIPANTS:Patients included 54.6% females and 46.4% males whose primary care clinicians (PCCs) opted to participate in ECHO Pain; the comparison group included 39.9% females and 60.1% males whose PCCs opted not to participate in ECHO Pain. INTERVENTION:PCCs attended 2-h weekly Chronic Pain and Opioid Management TeleECHO Clinic (ECHO Pain), which included pain and addiction didactics, case-based learning, and evidence-based recommendations. ECHO Pain sessions were offered 46 weeks per year. Attendance ranged from 1 to 3 sessions (47.7%), 4-19 (32.1%, or >?20 (20.2%). MAIN MEASURES:This study assessed whether clinician participation in Army and Navy Chronic Pain and Opioid Management TeleECHO Clinic (ECHO Pain) resulted in decreased prescription rates of opioid analgesics and co-prescribing of opioids and benzodiazepines. Measures included opioid prescriptions, morphine milligram equivalents (MME), and days of opioid and benzodiazepine co-prescribing per patient per year. KEY RESULTS:PCCs participating in ECHO Pain had greater percent declines than the comparison group in (a) annual opioid prescriptions per patient (-?23% vs. -?9%, P?<?0.001), (b) average MME prescribed per patient/year (-28% vs. -7%, p?<?.02), (c) days of co-prescribed opioid and benzodiazepine per opioid user per year (-53% vs. -1%, p?<?.001), and (d) the number of opioid users (-20.2% vs. -8%, p?<?.001). Propensity scoring transformation-adjusted results were consistent with the opioid prescribing and MME results. CONCLUSIONS:Patients treated by PCCs who opted to participate in ECHO Pain had greater declines in opioid-related prescriptions than patients whose PCCs opted not to participate.
Project description:<h4>Objective</h4>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.<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
Project description:<h4>Background</h4>Dentists are regular prescribers of opioid analgesic medications; however, there are few published data on their prescribing practices for children. The aim of this study was to assess opioid prescribing practices of dentists for pediatric patients.<h4>Methods</h4>We conducted a retrospective study (2011/12 to 2017/18) using administrative health data of opioid prescribing practices of dentists in Nova Scotia for children and adolescents (age < 18 yr). The main variables of interest were opioid "type" and "load" dentists prescribed (number of dispensed prescriptions/yr, days supplied/prescription and dosage/d per prescription in milligrams of morphine equivalents [MME]).<h4>Results</h4>Dentists accounted for a mean of 18.3% (standard deviation 1.5%) of all opioid prescribers for the pediatric population annually but were responsible for 59.9% of all opioid prescriptions and 48.6% of total MME dispensed during the 7-year study period. Oral and maxillofacial surgeons were responsible for 80.7% of all dental-related opioids dispensed. Codeine was most frequently prescribed (78.6% of total MME), followed by oxycodone (11.1%). There were significant downward trends over the study period in the total amount of opioid analgesics dispensed (<i>r</i> = -0.903, <i>p</i> < 0.01), primarily due to a reduction in the total amount of codeine dispensed and number of days supplied per prescription (<i>r</i> = -0.837, <i>p</i> < 0.05). Few opioids were dispensed to children less than 12 years.<h4>Interpretation</h4>Dentists in Nova Scotia reduced prescriptions of opioids in the pediatric population between 2011/12 and 2017/18, which may indicate that current opioid prescribing principles are influencing dentists' prescribing habits. Nonetheless, patients and parents should receive appropriate counselling as to the proper use, risks, storage and potential for misuse of opioids when prescribed.
Project description:BACKGROUND AND AIMS:While prescribed and illicit opioid use are primary drivers of the national surges in overdose deaths, opioid overdose deaths in which stimulants are also present are increasing in the U.S. We determined the social determinants and sociodemographic factors associated with opioid-only versus polysubstance opioid overdose deaths in Massachusetts. Particular attention was focused on the role of stimulants in opioid overdose deaths. METHODS:We analyzed all opioid-related overdose deaths from 2014 to 2015 in an individually-linked population database in Massachusetts. We used linked postmortem toxicology data to identify drugs present at the time of death. We constructed a multinomial logistic regression model to identify factors associated with three mutually exclusive overdose death groups based on toxicological results: opioid-related deaths with (1) opioids only present, (2) opioids and other substances not including stimulants, and (3) opioids and stimulants with or without other substances. RESULTS:Between 2014 and 2015, there were 2,244 opioid-related overdose deaths in Massachusetts that had accompanying toxicology results. Toxicology reports indicated that 17% had opioids only, 36% had opioids plus stimulants, and 46% had opioids plus another non-stimulant substance. Persons older than 24 years, non-rural residents, those with comorbid mental illness, non-Hispanic black residents, and persons with recent homelessness were more likely than their counterparts to die with opioids and stimulants than opioids alone. CONCLUSIONS:Polysubstance opioid overdose is increasingly common in the US. Addressing modifiable social determinants of health, including barriers to mental health services and homelessness, is important to reduce polysubstance use and overdose deaths.
Project description:Importance:Risk of opioid use disorder, overdose, and death from prescription opioids increases as dosage, duration, and use of extended-release and long-acting formulations increase. States are well suited to respond to the opioid crisis through legislation, regulations, enforcement, surveillance, and other interventions. Objective:To estimate temporal trends and geographic variations in 6 key opioid prescribing measures in 50 US states and the District of Columbia. Design, Setting, and Participants:Population-based cross-sectional analysis of opioid prescriptions filled nationwide at US retail pharmacies between January 1, 2006, and December 31, 2017. Data were obtained from the IQVIA Xponent database. All US residents who had an opioid prescription filled at a US retail pharmacy were included. Main Outcomes and Measures:Primary outcomes were annual amount of opioids prescribed in morphine milligram equivalents (MME) per person; mean duration per prescription in days; and 4 separate prescribing rates-for prescriptions 3 or fewer days, those 30 days or longer, those with a high daily dosage (≥90 MME), and those with extended-release and long-acting formulations. Results:Between 2006 and 2017, an estimated 233.7 million opioid prescriptions were filled in retail pharmacies in the United States each year. For all states combined, 4 measures decreased: (1) mean (SD) amount of opioids prescribed (mean [SD] decrease, 12.8% [12.6%]) from 628.4 (178.0) to 543.4 (158.6) MME per person, a statistically significant decrease in 23 states; (2) high daily dosage (mean [SD] decrease, 53.1% [13.6%]) from 12.3 (3.4) to 5.6 (1.7) per 100 persons, a statistically significant decrease in 49 states; (3) short-term (≤3 days) duration (mean [SD] decrease, 43.1% [9.4%]) from 18.0 (5.4) to 10.0 (2.5) per 100 persons, a statistically significant decrease in 48 states; and (4) extended-release and long-acting formulations (mean [SD] decrease, 14.7% [13.7%]) from 7.2 (1.9) to 6.0 (1.7) per 100 persons, a statistically significant decrease in 27 states. Two measures increased, each associated with the duration of prescription dispensed: (1) mean (SD) prescription duration (mean [SD] increase, 37.6% [6.9%]) from 13.0 (1.2) to 17.9 (1.4) days, a statistically significant increase in every state; and (2) prescriptions for a term of 30 days or longer (mean [SD] increase, 37.7% [28.9%]) from 18.3 (7.7) to 24.9 (10.7) per 100 persons, a statistically significant increase in 39 states. Two- to 3-fold geographic differences were observed across states, measured by comparing the ratio of each state's 90th to 10th percentile for each measure. Conclusions and Relevance:In this study, across 12 years, the mean duration and prescribing rate for long-term prescriptions of opioids increased, whereas the amount of opioids prescribed per person and prescribing rate for high-dosage prescriptions, short-term prescriptions, and extended-release and long-acting formulations decreased. Some decreases were significant, but results were still high. Two- to 3-fold state variation in 5 measures occurred in most states. This information may help when state-specific intervention programs are being designed.
Project description:BACKGROUND:A long-term opioid use has been associated with hypermethylation of the opioid receptor mu 1 (OPRM1) promoter. Very little is currently known about the early epigenetic response to therapeutic opioids. Here, we examine whether we can detect DNA methylation changes associated with a few days' use of prescribed opioids. Genome-wide DNA methylation was assayed in a cohort of 33 opioid-naïve participants who underwent standard dental surgery followed by opioid self-administration. Saliva samples were collected before surgery (visit 1), and at two postsurgery visits at 2.7 ± 1.5?days (visit 2), and 39 ± 10?days (visit 3) after the discontinuation of opioid analgesics. RESULTS:The perioperative methylome underwent significant changes over the three visits that were primarily due to postoperative inflammatory response and cell heterogeneity. To specifically examine the effect of opioids, we started with a candidate gene approach and evaluated 10 CpGs located in the OPRM1 promoter. There was a significant cross-sectional variability in opioid use, and for participants who self-administered the prescribed drugs, the total dosage ranged from 5-210 morphine milligram equivalent (MME). Participants were categorized by cumulative dosage into three groups: < 25 MME, 25-90 MME, and ? 90 MME. Using mixed-effects modeling, 4 CpGs had significant positive associations with opioid dose at two-tailed p value < 0.05, and overall, 9 of the 10 OPRM1 promoter CpGs showed the predicted higher methylation in the higher dose groups relative to the lowest dose group. After adjustment for age, cellular heterogeneity, and past tobacco use, the promoter mean methylation also had positive associations with cumulative MME (regression coefficient = 0.0002, one-tailed p value = 0.02) and duration of opioid use (regression coefficient = 0.003, one-tailed p value = 0.001), but this effect was significant only for visit 3. A preliminary epigenome-wide association study identified a significant CpG in the promoter of the RAS-related signaling gene, RASL10A, that may be predictive of opioid dosage. CONCLUSION:The present study provides evidence that the hypermethylation of the OPRM1 promoter is in response to opioid use and that epigenetic differences in OPRM1 and other sites are associated with a short-term use of therapeutic opioids.