The impact of more restrictive hydrocodone rescheduling on unintentional pediatric opioid exposures.

PURPOSE: To evaluate the impact of rescheduling hydrocodone combination products (HCPs) from schedule III of the Controlled Substances Act to the more restrictive schedule II on unintentional pediatric exposures (≤5 years old). METHODS: Using U.S. data on outpatient retail pharmacy dispensing, emergency department (ED) visits, and poison center (PC) exposure cases, we assessed trends in prescriptions dispensed and unintentional pediatric exposure cases involving hydrocodone (rescheduled from III to II) compared to oxycodone (schedule II) and codeine (schedule III for combination products) using descriptive and interrupted time-series (ITS) analyses during the 16 quarters before and after the October 2014 rescheduling of HCPs. RESULTS: Dispensing of hydrocodone products was declining before rescheduling but declined more steeply post-rescheduling. In ITS analyses, both hydrocodone and oxycodone had significant slope decreases in PC case rates in the post versus pre-period that was larger for hydrocodone, while codeine had a small but significant slope increase in PC case rates. An estimated 4202 ED visits for pediatric hydrocodone exposures occurred in the pre-period and 2090 visits occurred in the post-period, a significant decrease of 50.3%. Oxycodone exposures showed no significant decrease. CONCLUSIONS: Pediatric hydrocodone unintentional exposure ED visits and PC cases decreased after HCP rescheduling more than would be expected had the pre-rescheduling trend continued; the acceleration in the decrease in hydrocodone PC cases was partially offset by a slowing in the decrease in codeine-involved cases. The trend changes were likely due to multiple factors, including changes in dispensing that followed the rescheduling. Unintentional pediatric medication exposures and poisonings remain a public health concern requiring ongoing, multifaceted mitigation efforts.

Higher First 30-Day Dose of Buprenorphine for Opioid Use Disorder Treatment Is Associated With Decreased Mortality.

OBJECTIVE: Buprenorphine is a medication for opioid use disorder that reduces mortality. This study aims to investigate the less well-understood relationship between the dose in the early stages of treatment and the subsequent risk of death. METHODS: We used Kentucky prescription monitoring data to identify adult Kentucky residents initiating transmucosal buprenorphine medication for opioid use disorder (January 2017 to November 2019). Average daily buprenorphine dose for days covered in the first 30 days of treatment was categorized as ≤8 mg, >8 to ≤16 mg, and >16 mg. Patients were followed for 365 days after the first 30 days of buprenorphine treatment. Endpoints were opioid-involved overdose death and death from other causes. Causes and dates of death were obtained using Kentucky death certificate records. Associations were evaluated using multivariable Fine and Gray models adjusting for patient baseline characteristics. RESULTS: In the cohort of 49,857 patients, there were 227 opioid-involved overdose deaths and 459 deaths from other causes. Compared with ≤8 mg, the adjusted subdistribution hazard ratio (aSHR) of opioid-involved overdose death decreased by 55% (aSHR, 0.45; 95% confidence interval [CI], 0.34-0.60) and 64% (aSHR, 0.36; 95% CI, 0.25-0.52) for patients receiving doses of >8 to ≤16 mg and >16 mg, respectively. The incidence of death from other causes was lower in patients receiving >8 to ≤16 mg (aSHR, 0.78; 95% CI, 0.62-0.98) and >16 mg (aSHR, 0.62; 95% CI, 0.47-0.80) versus ≤8 mg dose. CONCLUSIONS: Higher first 30-day buprenorphine doses were associated with reduced opioid-involved overdose death and death from other causes, supporting benefit of higher dosing in reducing mortality.

Drugs involved in Kentucky drug poisoning deaths and relation with antecedent controlled substance prescription dispensing.

BACKGROUND: The shift from prescription to illicit drugs involved in drug poisoning deaths raises questions about the current utility of prescription drug monitoring program (PDMP) data to inform drug poisoning (overdose) prevention efforts. In this study, we describe relations between specific drugs involved in Kentucky drug poisoning deaths and antecedent controlled substance (CS) dispensing. METHODS: The study used linked death certificates and PDMP data for 2,248 Kentucky resident drug poisoning deaths in 2021. Death certificate literal text analysis identified drugs mentioned with involvement (DMI) in drug poisoning deaths. We characterized the concordance between each DMI and the CS dispensing history for this drug at varying timepoints since 2008. RESULTS: Overall, 25.5% of all decedents had dispensed CS in the month before fatal drug poisoning. Over 80% of decedents were dispensed opioid(s) since 2008; the percentage was similar regardless of opioid involvement in the poisoning death. One-third of decedents had dispensed buprenorphine for treatment of opioid use disorder since 2008, but only 6.1% had dispensed buprenorphine in the month preceding death. Fentanyl/fentanyl analogs were DMI in 1,568 (69.8%) deaths, yet only 3% had received a fentanyl prescription since 2008. The highest concordance in the month preceding death was observed for clonazepam (43.6%). CONCLUSION: Overall, concordance between CS dispensing history and the drugs involved in poisoning deaths was low, suggesting a need to reevaluate the complex relationships between prescription medication exposure and overdose death and to expand harm reduction interventions both within and outside the healthcare system to reduce drug poisoning mortality.

Characteristics and Prescribing Patterns of Clinicians Waivered to Prescribe Buprenorphine for Opioid Use Disorder Before and After Release of New Practice Guidelines.

Importance: In April 2021, the US Department of Health and Human Services (HHS) released practice guidelines exempting educational requirements to obtain a Drug Addiction Treatment Act (DATA) waiver to treat up to 30 patients with opioid use disorder with buprenorphine. Objective: To compare demographic and practice characteristics of clinicians who received traditional DATA waivers before and after release of the education-exempted HHS practice guidelines and those who were approved under the guidelines. Design, Setting, and Participants: This survey study was conducted electronically from February 1 to March 1, 2022. Eligible survey recipients were US clinicians who obtained an initial DATA waiver between April 2020 and November 2021. Exposure: DATA waiver approval pathway. Main Outcome and Measures: The outcomes were clinician demographic and practice characteristics, buprenorphine prescribing barriers, and strategies to treat patients with opioid use disorder, measured using χ2 tests and z tests to assess for differences among the waivered groups. Results: Of 23 218 eligible clinicians, 4519 (19.5%) responded to the survey. This analysis was limited to 2736 respondents with a 30-patient limit at the time of survey administration who identified their DATA waiver approval pathway. Among these respondents, 1365 (49.9%; female, 831 [61.9%]; male, 512 [38.1%]) received their DATA waiver prior to the education-exempted practice guidelines (prior DATA waiver), 550 (20.1%; female, 343 [63.4%]; male, 198 [36.6%]) received their waiver after guidelines were released but met education requirements (concurrent DATA waiver), and 821 (30.0%; female, 396 [49.2%]; male, 409 [50.8%]) received the waiver under the education-exempted guidelines (practice guidelines). Among practice guidelines clinicians, 500 (60.9%) reported that traditional DATA waiver educational requirements were a reason for not previously obtaining a waiver. Demographic and practice characteristics differed by waiver approval type. Across all groups, a large minority had not prescribed buprenorphine since obtaining a waiver (prior DATA waiver, 483 [35.7%]; concurrent DATA waiver, 226 [41.2%]; practice guidelines, 359 [44.3%]; P < .001). Clinicians who prescribed buprenorphine in the past 6 months reported treating few patients in an average month: 27 practice guidelines clinicians (6.0%) prescribed to 0 patients and 338 (75.1%) to 1 to 4 patients compared with 16 (2.2%) and 435 (59.9%) for prior and 11 (3.6%) and 166 (55.0%) for concurrent DATA waiver clinicians, respectively (P < .001). Across waiver types, clinicians reported multiple challenges to buprenorphine prescribing. Conclusions and Relevance: In this survey of DATA-waivered clinicians, clinician- and systems-level challenges that limit buprenorphine prescribing were observed, even among clinicians approved under the education-exempted guidelines pathway. The findings suggest that as implementation of legislation removing the DATA waiver begins, addressing these barriers could be essential to increasing buprenorphine access.

The impact of hydrocodone rescheduling on utilization, abuse, misuse, and overdose deaths.

PURPOSE: To evaluate the impact of increased federal restrictions on hydrocodone combination product (HCP) utilization, misuse, abuse, and overdose death. METHODS: We assessed utilization, misuse, abuse, and overdose death trends involving hydrocodone versus select opioid analgesics (OAs) and heroin using descriptive and interrupted time-series (ITS) analyses during the nine quarters before and after the October 2014 rescheduling of HCPs from a less restrictive (CIII) to more restrictive (CII) category. RESULTS: Hydrocodone dispensing declined >30% over the study period, and declines accelerated after rescheduling. ITS analyses showed that immediately postrescheduling, quarterly hydrocodone dispensing decreased by 177M dosage units while codeine, oxycodone, and morphine dispensing increased by 49M, 62M, and 4M dosage units, respectively. Postrescheduling, hydrocodone-involved misuse/abuse poison center (PC) case rates had a statistically significant immediate drop but a deceleration of preperiod declines. There were small level increases in codeine-involved PC misuse/abuse and overdose death rates immediately after HCP's rescheduling, but these were smaller than level decreases in rates for hydrocodone. Heroin-involved PC case rates and overdose death rates increased across the study period, with exponential increases in PC case rates beginning 2015. CONCLUSIONS: HCP rescheduling was associated with accelerated declines in hydrocodone dispensing, only partially offset by smaller increases in codeine, oxycodone, and morphine dispensing. The net impact on hydrocodone and other OA-involved misuse/abuse and fatal overdose was unclear. We did not detect an immediate impact on heroin abuse or overdose death rates; however, the dynamic nature of the crisis and data limitations present challenges to causal inference.

Patient-Reported Opioid Analgesic Use After Discharge from Surgical Procedures: A Systematic Review.

OBJECTIVE: This systematic review synthesizes evidence on patient-reported outpatient opioid analgesic use after surgery. METHODS: We searched PubMed (February 2019) and Web of Science and Embase (June 2019) for U.S. studies describing patient-reported outpatient opioid analgesic use. Two reviewers extracted data on opioid analgesic use, standardized the data on use , and performed independent quality appraisals based on the Cochrane Risk of Bias Tool and an adapted Newcastle-Ottawa scale. RESULTS: Ninety-six studies met the eligibility criteria; 56 had sufficient information to standardize use in oxycodone 5-mg tablets. Patient-reported opioid analgesic use varied widely by procedure type; knee and hip arthroplasty had the highest postoperative opioid use, and use after many procedures was reported as <5 tablets. In studies that examined excess tablets, 25-98% of the total tablets prescribed were reported to be excess, with most studies reporting that 50-70% of tablets went unused. Factors commonly associated with higher opioid analgesic use included preoperative opioid analgesic use, higher inpatient opioid analgesic use, higher postoperative pain scores, and chronic medical conditions, among others. Estimates also varied across studies because of heterogeneity in study design, including length of follow-up and inclusion/exclusion criteria. CONCLUSION: Self-reported postsurgery outpatient opioid analgesic use varies widely both across procedures and within a given procedure type. Contributors to within-procedure variation included patient characteristics, prior opioid use, intraoperative and perioperative factors, and differences in the timing of opioid use data collection. We provide recommendations to help minimize variation caused by study design factors and maximize interpretability of forthcoming studies for use in clinical guidelines and decision-making.

Emergency Department Visits Attributed to Adverse Events Involving Benzodiazepines, 2016-2017.

INTRODUCTION: Characterization of emergency department visits attributed to adverse events involving benzodiazepines can be used to guide preventive interventions. This study describes U.S. emergency department visits attributed to adverse events involving benzodiazepines by intent, patient characteristics, and clinical manifestations. METHODS: Data from the 2016-2017 National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project were analyzed in 2019 to calculate estimated annual numbers and rates of emergency department visits attributed to adverse events involving benzodiazepines, by intent of benzodiazepine use. RESULTS: Based on 6,148 cases, there were an estimated 212,770 (95% CI=167,163, 258,377) emergency department visits annually attributed to adverse events involving benzodiazepines. More than half were visits involving nonmedical use of benzodiazepines (119,008; 55.9%, 95% CI=50.0%, 61.9%), one third were visits involving self-harm with benzodiazepines (64,721; 30.4%, 95% CI=25.6%, 35.2%), and a smaller proportion of visits involved therapeutic use of benzodiazepines (29,041; 13.6%, 95% CI=11.4%, 15.9%). The estimated population rate of visits was highest for nonmedical use of benzodiazepines by patients aged 15-34 years (7.4 visits per 10,000 people). Among visits involving nonmedical use of benzodiazepines, 54.8% (95% CI=49.8%, 59.8%) were made by patients aged 15-34 years, 82.7% (95% CI=80.1%, 85.4%) involved concurrent use of other substances (illicit drugs, alcohol, prescription opioids, and/or other pharmaceuticals), and 24.2% (95% CI=17.7%, 30.6%) involved cardiorespiratory arrest or unresponsiveness. CONCLUSIONS: These findings support recommendations to assess for and address substance use disorder before initiating or continuing benzodiazepines and reinforce the need for validated self-harm risk assessment tools for clinicians.

A comparison of opioid-involved fatalities captured in the National Poison Data System to data derived from US death certificate literal text.

PURPOSE: The purpose of the study is to describe and compare the number and characteristics of opioid-involved fatal cases captured in the National Poison Data System (NPDS) and in US death certificates. METHODS: NPDS, which collects data on all calls to US poison control centers, and Drug-Involved Mortality (DIM), which combines information from literal text of US death certificates and National Vital Statistics Systems, were queried for opioid-involved fatal cases from 2010 to 2015. Characteristics of the two case series were compared. RESULTS: DIM contained 154 016 opioid-involved overdose deaths, and NPDS contained 2524 fatal opioid exposures, a ratio of 61:1. The number of opioid deaths remained stable in NPDS but increased in DIM over the 6-year period. On average, deaths involving opioids with higher mean dosage strength (in morphine milligram equivalents) per unit among dispensed prescriptions were more likely to be captured in DIM relative to NPDS, as compared with those with a lower mean dosage strength per unit. The increase in fentanyl-related deaths seen in DIM since 2013 was not observed in NPDS. CONCLUSIONS: NPDS is a valuable drug safety surveillance resource due to its timeliness and drug specificity. However, it captures only a small fraction of opioid-involved fatal poisonings, and comparisons with data derived from death certificate literal text indicate that caution is warranted in making inferences about opioid-involved fatality trends over time or comparisons across opioids.

U.S. Emergency Department Visits Resulting From Nonmedical Use of Pharmaceuticals, 2016.

INTRODUCTION: National data on morbidity from nonmedical use of pharmaceuticals are limited. This study used nationally representative, public health surveillance data to characterize U.S. emergency department visits for acute harms from nonmedical use of pharmaceuticals and to guide prevention efforts. METHODS: Data collected in 2016 from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project were analyzed in 2018 to calculate national estimates of emergency department visits for harms from nonmedical use of pharmaceuticals. RESULTS: Based on 5,130 surveillance cases, there were an estimated 358,247 emergency department visits (95% CI=280,675, 435,819) in 2016 for harms from nonmedical use of pharmaceuticals and 41.1% resulted in hospitalization (95% CI=32.3%, 49.8%). One half (50.9%, 95% CI=46.6%, 55.3%) of estimated visits involved patients aged ≤34 years; more than one half of estimated visits also involved non-pharmaceutical substances (52.9%, 95% CI=49.7%, 56.1%), including illicit drugs in 34.1% (95% CI=30.9%, 37.2%) and alcohol in 21.8% (95% CI=19.8%, 23.9%). Overall, benzodiazepines were implicated in 46.9% (95% CI=42.5%, 51.2%) of estimated emergency department visits for nonmedical use of pharmaceuticals but were the only substance implicated in just 6.5% (95% CI=5.1%, 7.9%). Prescription opioids were implicated in 36.2% (95% CI=30.8%, 41.7%) of estimated emergency department visits and were the only substance implicated in 11.3% (95% CI=8.6%, 14.0%). CONCLUSIONS: Although prescription opioids or benzodiazepines are frequently implicated in emergency department visits for nonmedical use, because other substances and additional pharmaceuticals are most often involved, prescribing clinicians should consider implementing specific screening to address polysubstance use and, when warranted, treatment interventions.

Important statistical considerations in the evaluation of post-market studies to assess whether opioids with abuse-deterrent properties result in reduced abuse in the community.

PURPOSE: Abuse, misuse, addiction, overdose, and death associated with non-medical use of prescription opioids have become a serious public health concern. Reformulation of these products with abuse-deterrent properties is one approach for addressing this problem. FDA has approved several extended-release opioid analgesics with abuse-deterrent labeling, the bases of which come from pre-market studies. As all opioid analgesics must be capable of delivering the opioid in order to reduce pain, abuse-deterrent properties do not prevent abuse, nor do pre-market evaluations ensure that there will be reduced abuse in the community. Utilizing data from various surveillance systems, some recent post-market studies suggest a decline in abuse of extended-release oxycodone after reformulation with abuse-deterrent properties. We discuss challenges stemming from the use of such data. METHODS: We quantify the relationship between the sample, the population, and the underlying sampling mechanism and identify the necessary conditions if valid statements about the population are to be made. The presence of other interventions in the community necessitates the use of comparators. We discuss the principles under which the use of comparators can be meaningful. CONCLUSIONS: Results based on surveillance data need to be interpreted with caution as the underlying sampling mechanisms can bias the results in unpredictable ways. The use of comparators has the potential to disentangle the effect due to the abuse-deterrence properties from those due to other interventions. However, identifying a comparator that is meaningful can be very difficult.

Trends in dextromethorphan cough and cold products: 2000-2015 National Poison Data System intentional abuse exposure calls.

CONTEXT: Recent restrictions in access to and availability of dextromethorphan (DXM) cough and cold medications may correlate with changes in abuse exposures. OBJECTIVE: To extend and update existing knowledge about DXM abuse, we describe recent trends and patterns of calls to poison control centers involving DXM abuse, by demographics, geography, common brands, and medical outcomes. METHODS: We utilized data from the National Poison Data System (NPDS) maintained by the American Association of Poison Control Centers (AAPCC), which captures data on calls to U.S. poison centers on a near real-time basis. We analyzed demographic, geographic, brand and medical outcome data for single-substance DXM cough and cold product intentional abuse exposure calls in multiple age groups reported to NPDS from 2000 to 2015. RESULTS: The annual rate of single-substance DXM intentional abuse calls tripled from 2000 to 2006 and subsequently plateaued from 2006 to 2015. The highest abuse call rate was observed among adolescents 14-17 years old, where the mean annual number of calls was 1761 per year, corresponding to an annual rate of 103.6 calls per million population. From 2006 to 2015, the rate for single-substance DXM abuse calls among adolescents 14-17 years decreased by 56.3%, from 143.8 to 80.9 calls per million population. CONCLUSION: DXM intentional abuse exposure call rates have declined among adolescents 14-17 years, since their peak in 2006. The observed decline in DXM abuse call rates corresponds to a period of growing public health efforts to curtail the abuse of over-the-counter (OTC) DXM containing products, particularly among adolescents. Further evaluation of state-level sales and abuse trends among adolescents would be valuable to better understand how restricted availability of OTC DXM cough and cold products and other efforts may affect abuse rates.

Patterns of Immediate-Release and Extended-Release Opioid Analgesic Use in the Management of Chronic Pain, 2003-2014.

Importance: Many stakeholders are working to improve the safe use of immediate-release (IR) and extended-release/long-acting (ER/LA) opioid analgesics. However, little information exists regarding the relative use of these 2 formulations in chronic pain management. Objectives: To describe the distribution of IR and ER/LA opioid analgesic therapy duration and examine adding and switching patterns among patients receiving long-term IR opioid analgesic therapy, defined as at least 90 consecutive days of IR formulation use. Design, Setting, and Participants: A retrospective cohort study of 169 million individuals receiving opioid analgesics from across 90% of outpatient retail pharmacies in the United States from January 1, 2003, to December 31, 2014, using the IQVIA Health Vector One: Data Extract Tool. Analyses were conducted from March 2015 to June 2017. Exposures: Receipt of dispensed IR or ER/LA opioid analgesic prescription. Main Outcomes and Measures: Distribution of therapy frequency and duration of IR and ER/LA opioid analgesic use, and annual proportions of patients receiving long-term IR opioid analgesic therapy who added an ER/LA formulation while continuing to use an IR formulation, switched to an ER/LA formulation, or continued receiving IR opioid analgesic therapy only. Results: Among the 169 280 456 patients included in this analysis, 168 315 458 patients filled IR formulations and 10 216 570 patients filled ER/LA formulations. A similar percentage of women received ER/LA (55%) and IR (56%) formulations, although those receiving ER/LA formulations (72%) were more likely to be aged 45 years or older compared with those receiving IR formulations (46%). The longest opioid analgesic episode duration was 90 days or longer for 11 563 089 patients (7%) filling IR formulations and 3 103 777 patients (30%) filling ER/LA formulations. The median episode duration was 5 days (interquartile range, 3-10 days) for patients using IR formulations and 30 days (interquartile range, 21-74 days) for patients using ER/LA formulations. From January 1, 2003, to December 31, 2014, a small and decreasing proportion of patients with long-term IR opioid analgesic therapy added (3.8% in 2003 to 1.8% in 2014) or switched to (1.0% in 2003 to 0.5% in 2014) an ER/LA formulation. Conclusions and Relevance: Most patients receiving opioid analgesics, whether for short or extended periods, use IR formulations. Once receiving long-term IR opioid analgesic therapy, patients are unlikely to add or switch to an ER/LA formulation.

Adverse event detection using the FDA post-marketing drug safety surveillance system: Cardiotoxicity associated with loperamide abuse and misuse.

OBJECTIVE: The purpose of this investigation was to identify and characterize post-marketing reports of cardiotoxicity, including torsades de pointes (TdP), associated with loperamide use. METHODS: We searched the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database for post-marketing reports of serious cardiac adverse events associated with loperamide use from December 28, 1976 (U.S. drug approval date), through December 14, 2015. We also conducted a Pubmed and Google Scholar search to identify additional published reports of cardiotoxicity associated with loperamide in the medical literature through February 11, 2016. RESULTS: Forty-eight cases of serious cardiac adverse events associated with loperamide use composed the case series. The most frequently reported cardiac adverse events were syncope (n = 24), cardiac arrest (n = 13), QT-interval prolongation (n = 13), ventricular tachycardia (n = 10), and TdP (n = 7). There were 10 cases that resulted in death. Of the 48 cases, the most commonly reported reasons for use can be characterized as drug abuse (n = 22) and diarrhea treatment (n = 17). More than one-half of the 48 cases were reported after 2010. Of the 22 drug abuse cases, the median daily dose was 250 mg (range 70 mg to 1600 mg) and events occurred as early as 6 hours after a dose and as long as 18 months after initiation of loperamide. Thirteen of the 22 cases reported using loperamide for euphoric or analgesic effects, and 9 reported use to prevent opioid withdrawal symptoms. CONCLUSION: The FAERS case reports provide evidence to suggest that high doses of loperamide are associated with TdP and other serious cardiac adverse events. The majority of cases in this series occurred in the setting of drug abuse for the purpose of preventing opioid withdrawal or to produce euphoric effects. It is important for both clinicians and patients to be aware of this potential risk, because prompt therapy and discontinuation of the offending agent are often essential to management and prevention of loperamide-induced cardiac arrhythmias.

Trends in the Concomitant Prescribing of Opioids and Benzodiazepines, 2002-2014.

INTRODUCTION: Although many clinical guidelines caution against the combined use of opioids and benzodiazepines, overdose deaths and emergency department visits involving the co-ingestion of these drugs are increasing. METHODS: In this ecologic time series study, the IMS Health Total Patient Tracker was used to describe nationally projected trends of patients receiving opioids and benzodiazepines in the U.S. outpatient retail setting between January 2002 and December 2014. The IMS Health Data Extract Tool was used to examine trends in the concomitant prescribing of these two medication classes among 177 million individuals receiving opioids during this period. The annual proportion of opioid recipients who were prescribed benzodiazepines concomitantly was calculated and stratified by gender, age, duration of opioid use, immediate-release versus extended-release/long-acting opioids, and benzodiazepine molecule. The proportion of patients with concomitancy receiving opioids and benzodiazepines from the same prescriber was also analyzed. Analyses were conducted from April to June 2015. RESULTS: The nationally projected number of patients receiving opioids and benzodiazepines increased by 8% and 31%, respectively, from 2002 to 2014. During this period, the annual proportion of opioid recipients dispensed a benzodiazepine concomitantly increased from 6.8% to 9.6%, which corresponded to a relative increase of 41%. Approximately half of these patients received both prescriptions from the same prescriber on the same day. Concomitancy was more common in patients receiving opioids for ≥90 days, women, and the elderly. CONCLUSIONS: Concomitant prescribing of opioids and benzodiazepines is increasing and may play a growing role in adverse patient outcomes related to these medications.

Emergency Department Visits and Overdose Deaths From Combined Use of Opioids and Benzodiazepines.

INTRODUCTION: Opioid analgesics and benzodiazepines are the prescription drugs most commonly associated with drug overdose deaths. This study was conducted to assess trends in nonmedical use-related emergency department (ED) visits and drug overdose deaths that involved both opioid analgesics and benzodiazepines in the U.S. from 2004 to 2011. METHODS: Opioid analgesic and benzodiazepine nonmedical use-related ED visits from the Drug Abuse Warning Network and drug overdose deaths from the National Vital Statistics System were analyzed for 2004-2011 to determine trends and demographic-specific rates. Data were analyzed from March 2014 to June 2014. RESULTS: From 2004 to 2011, the rate of nonmedical use-related ED visits involving both opioid analgesics and benzodiazepines increased from 11.0 to 34.2 per 100,000 population (p-trend<0.0001). During the same period, drug overdose deaths involving both drugs increased from 0.6 to 1.7 per 100,000 (p-trend<0.0001). Statistically significant increases in ED visits occurred among males and females, non-Hispanic whites, non-Hispanic blacks, and Hispanics, and all age groups except 12- to 17-year-olds. For overdose deaths, statistically significant increases were seen in males and females, all three race/ethnicity groups, and all age groups except 12- to 17-year-olds. Benzodiazepine involvement in opioid analgesic overdose deaths increased each year, increasing from 18% of opioid analgesic overdose deaths in 2004 to 31% in 2011 (p-trend<0.0001). CONCLUSIONS: ED visits and drug overdose deaths involving both opioid analgesics and benzodiazepines increased significantly between 2004 and 2011. Interventions to improve the appropriate prescribing and use of these medications are needed.

Higher psychological distress is associated with unintentional injuries in US adults.

BACKGROUND: Links between mental illness, self-inflicted injury and interpersonal violence are well recognised, but the association between poor mental health and unintentional injuries is not well understood. METHODS: We used the 2010 National Health Interview Survey to assess the association between psychological distress and unintentional non-occupational injuries among US adults. Psychological distress was measured by the Kessler Psychological Distress Scale, a symptom scale shown to identify community-dwelling persons with mental illness. Multivariable logistic regression was used to estimate adjusted ORs (AOR) and 95% CIs. RESULTS: Of the 26,776 individuals analysed, 2.5% reported a medically attended unintentional injury in the past 3 months. Those with moderate and severe psychological distress had 1.5 (1.2 to 1.8) and 2.0 (1.4 to 2.8) times higher odds of injury, respectively, as compared to those with low distress levels, after adjusting for age, sex, race, marital status, education level, alcohol use, physical functional limitation, medical comorbidity, employment status and health insurance status. Psychological distress was significantly associated with falls (AOR 1.4 (1.1 to 1.9)) and sprain/strain injuries (AOR 2.0 (1.5 to 2.8)), but not transportation-related injuries (AOR 1.2 (0.7 to 1.9)) or fractures (AOR 1.1 (0.8 to 1.6)). CONCLUSIONS: Among community-dwelling US adults, psychological distress is significantly associated with unintentional non-occupational injury, and the magnitude of association increases with severity of distress. The association between psychological distress and injury may be particularly strong for falls and sprain/strain injuries. These findings draw attention to a large group of at-risk individuals that may merit further targeted research, including longitudinal studies.