Susan L. Calcaterra

National trends in pharmaceutical opioid related overdose deaths compared to other substance related overdose deaths: 1999–2009☆

BACKGROUND Pharmaceutical opioid related deaths have increased. This study aimed to place pharmaceutical opioid overdose deaths within the context of heroin, cocaine, psychostimulants, and pharmaceutical sedative hypnotics examine demographic trends, and describe common combinations of substances involved in opioid related deaths. METHODS We reviewed deaths among 15-64 year olds in the US from 1999-2009 using death certificate data available through the CDC Wide-Ranging Online Data for Epidemiologic Research (WONDER) Database. We identified International Classification of Disease-10 codes describing accidental overdose deaths, including poisonings related to stimulants, pharmaceutical drugs, and heroin. We used crude and age adjusted death rates (deaths/100,000 person years [p-y] and 95% confidence interval [CI] and multivariable Poisson regression models, yielding incident rate ratios; IRRs), for analysis. RESULTS The age adjusted death rate related to pharmaceutical opioids increased almost 4-fold from 1999 to 2009 (1.54/100,000 p-y [95% CI 1.49-1.60] to 6.05/100,000 p-y [95% CI 5.95-6.16; p<0.001). From 1999 to 2009, pharmaceutical opioids were responsible for the highest relative increase in overdose death rates (IRR 4.22, 95% CI 3.03-5.87) followed by sedative hypnotics (IRR 3.53, 95% CI 2.11-5.90). Heroin related overdose death rates increased from 2007 to 2009 (1.05/100,000 persons [95% CI 1.00-1.09] to 1.43/100,000 persons [95% CI 1.38-1.48; p<0.001). From 2005-2009 the combination of pharmaceutical opioids and benzodiazepines was the most common cause of polysubstance overdose deaths (1.27/100,000 p-y (95% CI 1.25-1.30). CONCLUSION Strategies, such as wider implementation of naloxone, expanded access to treatment, and development of new interventions are needed to curb the pharmaceutical opioid overdose epidemic.

A Review of Opioid Overdose Prevention and Naloxone Prescribing: Implications for Translating Community Programming Into Clinical Practice

BACKGROUND As physicians have increased opioid prescribing, overdose deaths from pharmaceutical opioids have substantially increased in the United States. Naloxone hydrochloride (naloxone), an opioid antagonist, is the standard of care for treatment of opioid induced respiratory depression. Since 1996, community-based programs have offered overdose prevention education and distributed naloxone for bystander administration to people who use opioids, particularly heroin. There is growing interest in translating overdose education and naloxone distribution (OEND) into conventional medical settings for patients who are prescribed pharmaceutical opioids. For this review, we summarized and classified existing publications on overdose education and naloxone distribution to identify evidence of effectiveness and opportunities for translation into conventional medical settings. METHODS For this review, we searched English language PubMed for articles on naloxone based on primary data collection from humans, including feasibility studies, program evaluations, surveys, qualitative studies, and studies comparing the effectiveness of different routes of naloxone administration. We also included cost-effectiveness studies. RESULTS We identified 41 articles that represented 5 categories: evaluations of OEND programs, effects of OEND programs on experiences and attitudes of participants, willingness of medical providers to prescribe naloxone, comparisons of different routes of naloxone administration, and the cost-effectiveness of naloxone. CONCLUSIONS Existing research suggests that people who are at risk for overdose and other bystanders are willing and able to be trained to prevent overdoses and administer naloxone. Counseling patients about the risks of opioid overdose and prescribing naloxone is an emerging clinical practice that may reduce fatalities from overdose while enhancing the safe prescribing of opioids.

Opioid Prescribing at Hospital Discharge Contributes to Chronic Opioid Use.

ABSTRACTBACKGROUNDChronic opioid therapy for chronic pain treatment has increased. Hospital physicians, including hospitalists and medical/surgical resident physicians, care for many hospitalized patients, yet little is known about opioid prescribing at hospital discharge and future chronic opioid use.OBJECTIVEWe aimed to characterize opioid prescribing at hospital discharge among ‘opioid naïve’ patients. Opioid naïve patients had not filled an opioid prescription at an affiliated pharmacy 1 year preceding their hospital discharge. We also set out to quantify the risk of chronic opioid use and opioid refills 1 year post discharge among opioid naïve patients with and without opioid receipt at discharge.DESIGNThis was a retrospective cohort study.PARTICIPANTSFrom 1 January 2011 to 31 December 2011, 6,689 opioid naïve patients were discharged from a safety-net hospital.MAIN MEASUREChronic opioid use 1 year post discharge.KEY RESULTSTwenty-five percent of opioid naïve patients (n = 1,688) had opioid receipt within 72 hours of discharge. Patients with opioid receipt were more likely to have diagnoses including neoplasm (6.3 % versus 3.5 %, p < 0.001), acute pain (2.7 % versus 1.0 %, p < 0.001), chronic pain at admission (12.1 % versus 3.3 %, p < 0.001) or surgery during their hospitalization (65.1 % versus 18.4 %, p < 0.001) compared to patients without opioid receipt. Patients with opioid receipt were less likely to have alcohol use disorders (15.7 % versus 20.7 %, p < 0.001) and mental health disorders (23.9 % versus 31.4 %, p < 0.001) compared to patients without opioid receipt. Chronic opioid use 1 year post discharge was more common among patients with opioid receipt (4.1 % versus 1.3 %, p < 0.0001) compared to patients without opioid receipt. Opioid receipt was associated with increased odds of chronic opioid use (AOR = 4.90, 95 % CI 3.22-7.45) and greater subsequent opioid refills (AOR = 2.67, 95 % CI 2.29-3.13) 1 year post discharge compared to no opioid receipt.CONCLUSIONOpioid receipt at hospital discharge among opioid naïve patients increased future chronic opioid use. Physicians should inform patients of this risk prior to prescribing opioids at discharge.

The association between social stressors and drug use/hazardous drinking among former prison inmates

Social stressors are associated with relapse to substance use among people receiving addiction treatment and people with substance use risk behaviors. The relationship between social stressors and drug use/hazardous drinking in former prisoners has not been studied. We interviewed former prisoners at baseline, 1 to 3 weeks post prison release, and follow up, between 2 and 9 months following the baseline interview. Social stressors were characterized by unemployment, homelessness, unstable housing, problems with family, friends, and/or significant others, being single, or major symptoms of depression. Associations between baseline social stressors and follow-up drug use and hazardous drinking were analyzed using multivariable logistic regression. Problems with family, friends, and/or significant others were associated with reported drug use (AOR 3.01, 95% CI 1.18-7.67) and hazardous drinking (AOR 2.69, 95% CI 1.05-6.87) post release. Further research may determine whether interventions and policies targeting social stressors can reduce relapse among former inmates.

National Trends in Psychostimulant-Related Deaths: 1999–2009

ABSTRACT Background: Increased methamphetamine use occurred during the last decade and little is known about factors associated with death. This study assesses trends in psychostimulant deaths in the United States. Methods: Using the Centers for Disease Control and Prevention (CDC) Wonder Database, the authors searched deaths among 15- to 64-year-olds from 1999 to 2009 for decedents who died with “psychostimulants with abuse potential, excluding cocaine.” The International Classification of Diseases (ICD) code T43.6 was used to identify methamphetamine-related deaths. Trends in death rates and the most common underlying causes of death were determined. For recent trends, age-adjusted death rates/100,000 person-years (p-y) and (95% confidence intervals [CIs]) among those who died with psychostimulants were calculated. Results: The rate of psychostimulant-related deaths increased 3-fold from 1999 (0.37/100,000 p-y; 95% CI: 0.354–0.39) to 2005 (1.05/100,000 p-y; 95% CI: 1.01–1.10). Deaths steadily declined from 2006 to 2008, but rose again in 2009 to 0.97/100,000 p-y (95% CI: 0.92–1.01). Across all age groups, men had a 2 to 3 times higher rate of death than women. American Indians/Alaska Natives were twice as likely to die a psychostimulant-related death as compared with non-Hispanic whites. The northwestern/western region of the US had the highest rates of psychostimulant-related deaths, whereas the northeastern region had the lowest death rates. “Accidental poisonings” (ICD-10: X40–49) was the most frequently listed cause of death among those who died with psychostimulants. Conclusions: Psychostimulant-related deaths increased from 1999 to 2006, declined from 2006 to 2008, but rebounded in 2009. Interventions targeting those at highest risk of death must be implemented and studied to prevent increasing deaths.

Prediction Model for Two-Year Risk of Opioid Overdose Among Patients Prescribed Chronic Opioid Therapy

BackgroundNaloxone is a life-saving opioid antagonist. Chronic pain guidelines recommend that physicians co-prescribe naloxone to patients at high risk for opioid overdose. However, clinical tools to efficiently identify patients who could benefit from naloxone are lacking.ObjectiveTo develop and validate an overdose predictive model which could be used in primary care settings to assess the need for naloxone.DesignRetrospective cohort.SettingDerivation site was an integrated health system in Colorado; validation site was a safety-net health system in Colorado.ParticipantsWe developed a predictive model in a cohort of 42,828 patients taking chronic opioid therapy and externally validated the model in 10,708 patients.Main MeasuresPotential predictors and outcomes (nonfatal pharmaceutical and heroin overdoses) were extracted from electronic health records. Fatal overdose outcomes were identified from state vital records. To match the approximate shelf-life of naloxone, we used Cox proportional hazards regression to model the 2-year risk of overdose. Calibration and discrimination were assessed.Key ResultsA five-variable predictive model showed good calibration and discrimination (bootstrap-corrected c-statistic = 0.73, 95% confidence interval [CI] 0.69–0.78) in the derivation site, with sensitivity of 66.1% and specificity of 66.6%. In the validation site, the model showed good discrimination (c-statistic = 0.75, 95% CI 0.70–0.80) and less than ideal calibration, with sensitivity and specificity of 82.2% and 49.5%, respectively.ConclusionsAmong patients on chronic opioid therapy, the predictive model identified 66–82% of all subsequent opioid overdoses. This model is an efficient screening tool to identify patients who could benefit from naloxone to prevent overdose deaths. Population differences across the two sites limited calibration in the validation site.

Improving the Safety of Opioid Use for Acute Noncancer Pain in Hospitalized Adults: A Consensus Statement From the Society of Hospital Medicine

Hospital-based clinicians frequently treat acute, noncancer pain. Although opioids may be beneficial in this setting, the benefits must be balanced with the risks of adverse events, including inadvertent overdose and prolonged opioid use, physical dependence, or development of opioid use disorder. In an era of epidemic opioid use and related harms, the Society of Hospital Medicine (SHM) convened a working group to develop a consensus statement on opioid use for adults hospitalized with acute, noncancer pain, outside of the palliative, end-of-life, and intensive care settings. The guidance is intended for clinicians practicing medicine in the inpatient setting (eg, hospitalists, primary care physicians, family physicians, nurse practitioners, and physician assistants). To develop the Consensus Statement, the working group conducted a systematic review of relevant guidelines, composed a draft Statement based on extracted recommendations, and obtained feedback from external experts in hospital-based opioid prescribing, SHM members, the SHM Patient-Family Advisory Council, other professional societies, and peer-reviewers. The iterative development process resulted in a final Consensus Statement consisting of 16 recommendations covering 1) whether to use opioids in the hospital, 2) how to improve the safety of opioid use during hospitalization, and 3) how to improve the safety of opioid prescribing at hospital discharge. As most guideline recommendations from which the Consensus Statement was derived were based on expert opinion alone, the working group identified key issues for future research to support evidence-based practice.

Psychostimulant-related deaths among former inmates.

Objectives:Psychostimulants are highly addictive and their use is increasing. Little is known about psychostimulant-related deaths. This study identified characteristics, risk factors, and contributing substances reported upon death among former prison inmates who died from a psychostimulant-related death. Methods:This retrospective cohort study of released inmates from 1999 to 2003 (N = 30,237) linked data from the Washington State Department of Corrections with the National Death Index. We examined characteristics of individuals who died with psychostimulants listed among their causes of death. These were categorized into 3 groups: (1) noncocaine psychostimulants, (2) cocaine only, and (3) all psychostimulants. Cox proportional hazards regression determined risk factors for death in each group, and the risk of death in the first 2 weeks after release from prison Results:Of the 443 inmates who died, 25 (6%) had noncocaine psychostimulants listed among their causes of death. Six of these 25 deaths had both noncocaine psychostimulants and cocaine listed among their causes-of-death. Most of the former inmates who died with noncocaine psychostimulants were male (n = 21, 84%) and non-Hispanic white (88%, n = 22). Cocaine only was listed among the causes-of-death for 49 former inmates; most were male (n = 35, 71%) and non-Hispanic white (n = 27, 55%). Longer length of incarceration was associated with a reduced risk of death from any psychostimulant use (hazard ratio = 0.76, confidence interval = 0.63–0.920 for each additional year of incarceration) and from use of noncocaine psychostimulants (hazard ratio = 0.42, 95% CI = 0.22–0.80). Risk of death was highest during the first 2 weeks postrelease for cocaine only–related deaths (incidence mortality ratio = 1224.0, confidence interval = 583–1865). Conclusions:Former prisoners have a significant risk of death from psychostimulants, especially within the first 2 weeks postrelease.

The Association Between Stimulant, Opioid, and Multiple Drug Use on Behavioral Health Care Utilization in a Safety-Net Health System

BACKGROUND Prior studies show an association between drug use and health care utilization. The relationship between specific drug type and emergent/urgent, inpatient, outpatient, and behavioral health care utilization has not been examined. We aimed to determine if multiple drug use was associated with increased utilization of behavioral health care. METHODS To assess health care utilization, we conducted a retrospective cohort study of patients who accessed health care at a safety-net medical center and affiliated clinics. Using electronic health records, we categorized patients who used stimulants, opioids, or multiple drugs based on urine toxicology screening tests and/or International Classification of Diseases, 9th Revision (ICD-9). Remaining patients were categorized as patients without identified drug use. Health care utilization by drug use group and visit type was determined using a negative binomial regression model. Associations were reported as incidence rate ratios. Utilization was described by rates of health care-related visits for inpatient, emergent/urgent, outpatient, and behavioral health care among patients who used drugs, categorized by drug types, compared with patients without identified drug use. RESULTS Of 95,198 index visits, 4.6% (n=4340) were by patients who used drugs. Opioid and multiple drug users had significantly higher rates of behavioral health care visits than patients without identified drug use (opioid incidence rate ratio [IRR]=7.2; 95% confidence interval [CI]: 3.8-13.8; multiple drug use IRR=5.6, 95% CI: 3.3-9.7). Patients who used stimulants were less likely to use behavioral health services (IRR=1.3, 95% CI: 0.9-2.0) when compared with opioid and multiple drug users, but were more likely to use inpatient (IRR=1.6, 95% CI: 1.4-1.8) and emergent/urgent care (IRR=1.4, 95% CI: 1.3-1.5) services as compared with patients without identified drug use. CONCLUSIONS Integrated medical and mental health care and drug treatment may reduce utilization of costly health care services and improve patient outcomes. How to capture and deliver primary care and behavioral health care to patients who use stimulants needs further investigation.

Safe Opioid Prescribing for Acute Noncancer Pain in Hospitalized Adults: A Systematic Review of Existing Guidelines

BACKGROUND Pain is common among hospitalized patients. Inpatient prescribing of opioids is not without risk. Acute pain management guidelines could inform safe prescribing of opioids in the hospital and limit associated unintended consequences. PURPOSE To evaluate the quality and content of existing guidelines for acute, noncancer pain management. DATA SOURCES The National Guideline Clearinghouse, MEDLINE via PubMed, websites of relevant specialty societies and other organizations, and selected international search engines. STUDY SELECTION Guidelines published between January 2010 and August 2017 addressing acute, noncancer pain management among adults were considered. Guidelines that focused on chronic pain, specific diseases, and the nonhospital setting were excluded. DATA EXTRACTION Quality was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. DATA SYNTHESIS Four guidelines met the selection criteria. Most recommendations were based on expert consensus. The guidelines recommended restricting opioids to severe pain or pain that has not responded to nonopioid therapy, using the lowest effective dose of short-acting opioids for the shortest duration possible, and co-prescribing opioids with nonopioid analgesics. The guidelines generally recommended checking the prescription drug monitoring program when prescribing opioids, developing goals for patient recovery, and educating patients regarding the risks and side effects of opioid therapy. Additional recommendations included using an opioid-dose conversion guide, avoidance of co-administration of parenteral and oral opioids, and using caution when co-prescribing opioids with other central nervous system depressants. CONCLUSIONS Guidelines, based largely on expert opinion, recommend judicious prescribing of opioids for severe, acute pain. Future work should assess the implications of these recommendations on hospital-based pain management.