Annual Causes of Death in the United States

1. Deaths Attributed To Drug Overdose In The US In 2018

"● In 2018, there were 67,367 drug overdose deaths in the United States, a 4.1% decline from 2017 (70,237 deaths).

"● The age-adjusted rate of drug overdose deaths in 2018 (20.7 per 100,000) was 4.6% lower than in 2017 (21.7).

"● For 14 states and the District of Columbia, the drug overdose death rate was lower in 2018 than in 2017.

"● The rate of drug overdose deaths involving synthetic opioids other than methadone (drugs such as fentanyl, fentanyl analogs, and tramadol) increased by 10%, from 9.0 in 2017 to 9.9 in 2018.

"● From 2012 through 2018, the rate of drug overdose deaths involving cocaine more than tripled (from 1.4 to 4.5) and the rate for deaths involving psychostimulants with abuse potential (drugs such as methamphetamine) increased nearly 5-fold (from 0.8 to 3.9)."

Hedegaard H, Miniño AM, Warner M. Drug overdose deaths in the United States, 1999–2018. NCHS Data Brief, no 356. Hyattsville, MD: National Center for Health Statistics. 2020.
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2. Deaths in 2017 in the US Attributed to Drug Overdose

"• In 2017, there were 70,237 drug overdose deaths in the United States.

"• The age-adjusted rate of drug overdose deaths in 2017 (21.7 per 100,000) was 9.6% higher than the rate in 2016 (19.8).

"• Adults aged 25–34, 35–44, and 45–54 had higher rates of drug overdose deaths in 2017 than those aged 15–24, 55–64, and 65 and over.

"• West Virginia (57.8 per 100,000), Ohio (46.3), Pennsylvania (44.3), and the District of Columbia (44.0) had the highest age-adjusted drug overdose death rates in 2017.

"• The age-adjusted rate of drug overdose deaths involving synthetic opioids other than methadone (drugs such as fentanyl, fentanyl analogs, and tramadol) increased by 45% between 2016 and 2017, from 6.2 to 9.0 per 100,000."

Hedegaard H, Miniño AM, Warner M. Drug overdose deaths in the United States, 1999–2017. NCHS Data Brief, no 329. Hyattsville, MD: National Center for Health Statistics. 2018.
https://www.cdc.gov/nchs/produ...
https://www.cdc.gov/nchs/data/...

3. Drug Overdose Deaths In 2018 - Demographic Details and Changes from 2017

"During 2018, drug overdoses resulted in 67,367 deaths in the United States, a 4.1% decrease from 2017. Among these drug overdose deaths, 46,802 (69.5%) involved an opioid. From 2017 to 2018, opioid-involved death rates decreased 2.0%, from 14.9 per 100,000 population to 14.6 (Table 1); decreases occurred among females; persons aged 15–34 years and 45–54 years; non-Hispanic whites; and in small metro, micropolitan, and noncore areas; and in the Midwest and South regions. Rates during 2017–2018 increased among persons aged ≥65 years, non-Hispanic blacks, and Hispanics, and in the Northeast and the West regions. Rates decreased in 11 states and DC and increased in three states, with the largest relative (percentage) decrease in Iowa (–30.4%) and the largest absolute decrease (difference in rates) in Ohio (–9.6); the largest relative and absolute increase occurred in Missouri (18.8%, 3.1). The highest opioid-involved death rate in 2018 was in West Virginia (42.4 per 100,000).

"Prescription opioid-involved death rates decreased by 13.5% from 2017 to 2018. Rates decreased in males and females, persons aged 15–64 years, non-Hispanic whites, Hispanics, non-Hispanic American Indian/Alaska Natives, and across all urbanization levels. Prescription opioid–involved death rates remained stable in the Northeast and decreased in the Midwest, South, and the West. Seventeen states experienced declines in prescription opioid–involved death rates, with no states experiencing significant increases. The largest relative decrease occurred in Ohio (–40.5%), whereas the largest absolute decrease occurred in West Virginia (–4.1), which also had the highest prescription opioid-involved death rate in 2018 (13.1 per 100,000).

"Heroin-involved death rates decreased 4.1% from 2017 to 2018; reductions occurred among males and females, persons aged 15–34 years, non-Hispanic whites, and in large central metro and large fringe metro areas (Table 2). Rates decreased in the Midwest and increased in the West. Rates decreased in seven states and DC and increased in three states from 2017 to 2018. The largest relative decrease occurred in Kentucky (50.0%), and the largest absolute decrease occurred ††† Z-tests were used if the number of deaths was ≥100; a p-value of <0.05 was considered to be statistically significant. Nonoverlapping confidence intervals based on the gamma method were used if the number of deaths was <100 in 2017 or 2018. This method of comparing confidence intervals is a conservative method for estimating statistical significance; caution should be observed when interpreting a nonsignificant difference when the lower and upper limits being compared overlap only slightly. https://www.cdc.gov/nchs/data/.... in DC (–7.1); the largest relative and absolute increase was in Tennessee (18.8%, 0.9). The highest heroin-involved death rate in 2018 was in Vermont (12.5 per 100,000).

"Death rates involving synthetic opioids increased from 9.0 per 100,000 population in 2017 to 9.9 in 2018 and accounted for 67.0% of opioid-involved deaths in 2018. These rates increased from 2017 to 2018 among males and females, persons aged ≥25 years, non-Hispanic whites, non-Hispanic blacks, Hispanics, non-Hispanic Asian/Pacific Islanders, and in large central metro, large fringe metro, medium metro, and small metro counties. Synthetic opioid–involved death rates increased in the Northeast, South and West and remained stable in the Midwest. Rates increased in 10 states and decreased in two states. The largest relative increase occurred in Arizona (92.5%), and the largest absolute increase occurred in Maryland and Missouri (4.4 per 100,000 in both states); the largest relative and absolute decrease was in Ohio (–20.7%, –6.7). The highest synthetic opioid–involved death rate in 2018 occurred in West Virginia (34.0 per 100,000)."

Wilson N, Kariisa M, Seth P, Smith H IV, Davis NL. Drug and Opioid-Involved Overdose Deaths — United States, 2017–2018. MMWR Morb Mortal Wkly Rep 2020;69:290–297. DOI: http://dx.doi.org/10.15585/mmw...
https://www.cdc.gov/...

4. Drug Overdose Deaths in the US Involving Cocaine and Psychostimulants On the Rise

"Deaths involving cocaine and psychostimulants have increased in the United States in recent years; among 70,237 drug overdose deaths in 2017, nearly a third (23,139 [32.9%]) involved cocaine, psychostimulants, or both. From 2016 to 2017, death rates involving cocaine and psychostimulants each increased by approximately one third, and increases occurred across all demographic groups, Census regions, and in several states. In 2017, nearly three fourths of cocaine-involved and roughly one half of psychostimulant-involved overdose deaths, respectively, involved at least one opioid. After initially peaking in 2006, trends in overall cocaine-involved death rates declined through 2012, when they began to rise again. The 2006–2012 decrease paralleled a decline in cocaine supply coupled with an increase in cost. Similar patterns in death rates involving both cocaine and opioids were observed, with increases for cocaine- and synthetic opioid-involved deaths occurring from 2012 to 2017. From 2010 to 2017, increasing rates of deaths involving psychostimulants occurred and persisted even in the absence of opioids."

Kariisa M, Scholl L, Wilson N, Seth P, Hoots B. Drug Overdose Deaths Involving Cocaine and Psychostimulants with Abuse Potential — United States, 2003–2017. MMWR Morb Mortal Wkly Rep 2019;68:388–395. DOI: http://dx.doi.org/10.15585/mmw...
https://www.cdc.gov/mmwr/volum...

5. Changes in Types of Opioids Involved in Overdose Deaths in the US

"• The rate of drug overdose deaths involving synthetic opioids other than methadone, which include drugs such as fentanyl, fentanyl analogs, and tramadol, increased from 0.3 per 100,000 in 1999 to 1.0 in 2013, 1.8 in 2014, 3.1 in 2015, 6.2 in 2016, and 9.0 in 2017 (Figure 4). The rate increased on average by 8% per year from 1999 through 2013 and by 71% per year from 2013 through 2017.

"• The rate of drug overdose deaths involving heroin increased from 0.7 in 1999 to 1.0 in 2008 to 4.9 in 2016. The rate in 2017 was the same as in 2016 (4.9).

"• The rate of drug overdose deaths involving natural and semisynthetic opioids, which include drugs such as oxycodone and hydrocodone, increased from 1.0 in 1999 to 4.4 in 2016. The rate in 2017 was the same as in 2016 (4.4).

"• The rate of drug overdose deaths involving methadone increased from 0.3 in 1999 to 1.8 in 2006, then declined to 1.0 in 2016. The rate in 2017 was the same as in 2016 (1.0)."

Hedegaard H, Miniño AM, Warner M. Drug overdose deaths in the United States, 1999–2017. NCHS Data Brief, no 329. Hyattsville, MD: National Center for Health Statistics. 2018.
https://www.cdc.gov/nchs/produ...
https://www.cdc.gov/nchs/data/...

6. Drugs Most Frequently Mentioned in Overdose Deaths in the US 2011-2016

"The number of drug overdose deaths per year increased 54%, from 41,340 deaths in 2011 to 63,632 deaths in 2016 (Table A). From the literal text analysis, the percentage of drug overdose deaths mentioning at least one specific drug or substance increased from 73% of the deaths in 2011 to 85% of the deaths in 2016. The percentage of drug overdose deaths that mentioned only a drug class but not a specific drug or substance declined from 5.1% of deaths in 2011 to 2.5% in 2016. Review of the literal text for these deaths indicated that the deaths that mentioned only a drug class frequently involved either an opioid or an opiate (ranging from 54% in 2015 to 60% in 2016). The percentage of deaths that did not mention a specific drug or substance or a drug class declined from 22% of drug overdose deaths in 2011 to 13% in 2016."

Hedegaard H, Bastian BA, Trinidad JP, Spencer M, Warner M. Drugs most frequently involved in drug overdose deaths: United States, 2011–2016. National Vital Statistics Reports; vol 67 no 9. Hyattsville, MD: National Center for Health Statistics. 2018.
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7. Drugs Most Frequently Involved in Drug Overdose Deaths in the US 2011–2016

"For the top 15 drugs:

"• Among drug overdose deaths that mentioned at least one specific drug, oxycodone ranked first in 2011,heroin from 2012 through 2015, and fentanyl in 2016.

"• In 2011 and 2012, fentanyl was mentioned in approximately 1,600 drug overdose deaths each year, but mentions increased in 2013 (1,919 deaths),2014 (4,223 deaths), 2015 (8,251 deaths), and 2016(18,335 deaths). In 2016, 29% of all drug overdose deaths mentioned involvement of fentanyl.

"• The number of drug overdose deaths involving heroin increased threefold, from 4,571 deaths or 11% of all drug overdose deaths in 2011 to 15,961 deaths or 25% of all drug overdose deaths in 2016.

"• Throughout the study period, cocaine ranked second or third among the top 15 drugs. From 2014 through 2016, the number of drug overdose deaths involving cocaine nearly doubled from 5,892 to 11,316.

"• The number of drug overdose deaths involving methamphetamine increased 3.6-fold, from 1,887 deaths in 2011 to 6,762 deaths in 2016.

"• The number of drug overdose deaths involving methadone decreased from 4,545 deaths in 2011 to 3,493 deaths in 2016."

Hedegaard H, Bastian BA, Trinidad JP, Spencer M, Warner M. Drugs most frequently involved in drug overdose deaths: United States, 2011–2016. National Vital Statistics Reports; vol 67 no 9. Hyattsville, MD: National Center for Health Statistics. 2018.
https://www.cdc.gov/nchs/produ...
https://www.cdc.gov/nchs/data/...

8. Drugs Most Frequently Involved in Drug Overdose Deaths in the US 2011–2016

"The percentage of deaths with concomitant involvement of other drugs varied by drug. For example, almost all drug overdose deaths involving alprazolam or diazepam (96%) mentioned involvement of other drugs. In contrast, 50% of the drug overdose deaths involving methamphetamine, and 69% of the drug overdose deaths involving fentanyl mentioned involvement of one or more other specific drugs.

"Table D shows the most frequent concomitant drug mentions for each of the top 10 drugs involved in drug overdose deaths in 2016.

"• Two in five overdose deaths involving cocaine also mentioned fentanyl.

"• Nearly one-third of drug overdose deaths involving fentanyl also mentioned heroin (32%).

"• Alprazolam was mentioned in 26% of the overdose deaths involving hydrocodone, 22% of the deaths involving methadone, and 25% of the deaths involving oxycodone.

"• More than one-third of the overdose deaths involving cocaine also mentioned heroin (34%).

"• More than 20% of the overdose deaths involving methamphetamine also mentioned heroin."

Hedegaard H, Bastian BA, Trinidad JP, Spencer M, Warner M. Drugs most frequently involved in drug overdose deaths: United States, 2011–2016. National Vital Statistics Reports; vol 67 no 9. Hyattsville, MD: National Center for Health Statistics. 2018.
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https://www.cdc.gov/nchs/data/...

9. Annual Number of Deaths By Selected Causes in the US, Including Deaths Attributed to Alcohol, Tobacco, and Other Drug Use


Cause of death (Data from 2016 unless otherwise noted) Number
All Causes 2,744,248
Major Cardiovascular Diseases [MCD] 835,947
   Diseases of Heart [subset of MCD]    635,260
   Cerebrovascular Diseases [subset of MCD]    142,142
Malignant Neoplasms [Cancer] 598,038
Deaths Attributed to Tobacco Smoking (Each year from 2005 through 2009)1 480,320
Accidents (Unintentional Injuries) [Total] 161,374
   Motor Vehicle Accidents [subset of Total Accidents]    40,327
Chronic Lower Respiratory Diseases 154,596
Alzheimer's Disease 116,103
Diabetes Mellitus 80,058
Drug-Induced Deaths2 67,265
Influenza and Pneumonia 51,537
Nephritis, Nephrotic Syndrome and Nephrosis 50,046
Intentional Self-Harm (Suicide) 44,965
Septicemia 40,613
Chronic Liver Disease and Cirrhosis 40,545
   Alcoholic Liver Disease [subset of Chronic Liver Disease]    21,815
Injury by Firearms 38,658
Alcohol-Induced Deaths 34,865
Parkinson's Disease 29,697
Pneumonitis Due to Solids and Liquids 19,715
Assault (Homicide) 19,362
Viral Hepatitis 6,421
Human Immunodeficiency Virus (HIV) Disease 6,160
All Illicit Drugs Combined (2000)3 17,0002
Cannabis (Marijuana)4 0

2016 Data Detailing Drug-Induced Deaths,
Breaking Out Specific Data for Natural and Semi-Synthetic Opioids (including Oxycodone), Synthetic Opioids (including Fentanyl), and Heroin,
as Reported by the CDC7
Total Deaths Attributed to Drug Overdose 63,632
Overdose Deaths Involving Any Opioid 42,249
Overdose Deaths Involving Heroin 15,469
Overdose Deaths Involving Natural and Semi-Synthetic Opioids 14,487
Overdose Deaths Involving Methadone 3,373
Overdose Deaths Involving Synthetic Opioids Other Than Methadone 19,413

2014 Data Detailing Drug-Induced Deaths,
Breaking Out Specific Data for Prescription Analgesics and Heroin,
as Reported by the CDC5
Drug Overdose Total 47,055
Deaths Involving Pharmaceutical Opioid Analgesics 18,893
Deaths Involving Heroin 10,574

2010 Drug Overdose Mortality Data In Detail,
Reported By Paulozzi et al.6
Drug Overdose Total 38,329
Deaths Involving Pharmaceutical Drugs 22,134
Deaths Involving Pharmaceutical Opioids 16,651

1 Estimated number of deaths annually 2005-2009. U.S. Department of Health and Human Services. The Health Consequences of Smoking: 50 Years of Progress. A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014.
2 "Drug" includes both legal and illegal drugs.

3 Mokdad, Ali H., PhD, James S. Marks, MD, MPH, Donna F. Stroup, PhD, MSc, Julie L. Gerberding, MD, MPH, "Actual Causes of Death in the United States, 2000," Journal of the American Medical Association, (March 10, 2004), G225 Vol. 291, No. 10, 1242.

4 No recorded cases of overdose deaths from cannabis have been found in extensive literature reviews, see for example Gable, Robert S., "The Toxicity of Recreational Drugs," American Scientist (Research Triangle Park, NC: Sigma Xi, The Scientific Research Society, May-June 2006) Vol. 94, No. 3, p. 207.

5 CDC/NCHS, National Vital Statistics System, Mortality File, 2015, last accessed Dec. 11, 2015.

6 Paulozzi et al analyzed mortality figures and found that of 38,329 drug overdose deaths then reported in 2010, pharmaceutical drugs accounted for 22,134 deaths, of which 16,651 were opiod analgesic overdoses. The data were apparently revised slightly between the time the research letter was published in JAMA (February 2013) and release of the CDC's Deaths: Final Data for 2010 publication report, officially dated May 8, 2013.
7 Hedegaard H, Warner M, Miniño AM. Drug overdose deaths in the United States, 1999–2016. NCHS Data Brief, no 294. Hyattsville, MD: National Center for Health Statistics. 2017.

Xu JQ, Murphy SL, Kochanek KD, Bastian B, Arias E. Deaths: Final data for 2016. National Vital Statistics Reports; vol 67 no 5. Hyattsville, MD: National Center for Health Statistics. 2018.
https://www.cdc.gov/nchs/nvss/...
https://www.cdc.gov/nchs/data/...
Hedegaard H, Warner M, Miniño AM. Drug overdose deaths in the United States, 1999–2016. NCHS Data Brief, no 294. Hyattsville, MD: National Center for Health Statistics. 2017.
https://www.cdc.gov/nchs/produ...
https://www.cdc.gov/nchs/data/...
https://www.cdc.gov/nchs/data/...
CDC/NCHS, National Vital Statistics System, Mortality File, 2015, last accessed Dec. 11, 2015.
http://www.cdc.gov/nchs/data/h...
Hedegaard H, Chen LH, Warner M. Drug poisoning deaths involving heroin: United States, 2000–2013. NCHS data brief, no 190. Hyattsville, MD: National Center for Health Statistics. 2015.
http://www.cdc.gov/nchs/data/d...
http://www.cdc.gov/nchs/data/d...
Chen LH, Hedegaard H, Warner M. Drug-poisoning deaths involving opioid analgesics: United States, 1999–2011. NCHS data brief no. 166.
Hyattsville, MD: US Department of Health and Human Services, CDC; 2014, p. 1.
http://www.cdc.gov/nchs/data/d....
http://www.cdc.gov/nchs/data/h...
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Christopher M. Jones, PharmD, Karin A. Mack, PhD, and Leonard J. Paulozzi, MD, "Pharmaceutical Overdose Deaths, United States, 2010," Journal of the American Medical Association, February 20, 2013, Vol 309, No. 7, p. 658.
http://jama.jamanetwork.com/ar...
U.S. Department of Health and Human Services. The Health Consequences of Smoking: 50 Years of Progress. A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014. Printed with corrections, January 2014, p. 660, Table 12.4
https://www.surgeongeneral.gov...
https://www.surgeongeneral.gov...

10. Deaths from Drug Overdose in the United States in 2015

"During 2015, drug overdoses accounted for 52,404 U.S. deaths, including 33,091 (63.1%) that involved an opioid. There has been progress in preventing methadone deaths, and death rates declined by 9.1%. However, rates of deaths involving other opioids, specifically heroin and synthetic opioids other than methadone (likely driven primarily by illicitly manufactured fentanyl) (2,3), increased sharply overall and across many states."

Rudd RA, Seth P, David F, Scholl L. Increases in Drug and Opioid-Involved Overdose Deaths — United States, 2010–2015. MMWR Morb Mortal Wkly Rep 2016;65:1445–1452. DOI: dx.doi.org/10.15585/mmwr.mm655051e1
https://www.cdc.gov/mmwr/volum...
https://www.cdc.gov/mmwr/volum...

11. Deaths Attributed to Drug Overdose in the US, 2017

According to the Centers for Disease Control, using data available for analysis on September 5, 2018, there were a reported 70,652 deaths attributed to drug overdose in the US for the year ending December 2017. Some deaths were still under investigation. The CDC projects that the total for 2017 will be 72,222.

Of these:
Opioids were detected in 47,863 reported deaths, and are predicted to be involved in 49,031 deaths.
Synthetic opioids, excluding methadone, were detected in 28,644 reported deaths, and are predicted to be involved in 28,644 deaths.
Heroin was detected in 15,585 reported deaths, and is predicted to be involved in 15,941 deaths.
Natural and semi-synthetic opioids were detected in 14,553 reported deaths, and are predicted to be involved in 14,940 deaths.
Cocaine was detected in 14,065 reported deaths, and is predicted to be involved in 14,612 deaths.
Psychostimulants with abuse potential were detected in 10,420 reported deaths, and are predicted to be involved in 10,703 deaths.
Methadone was detected in 3,209 reported deaths, and is predicted to be involved in 3,286 deaths.

Note: Categories are not mutually exclusive because deaths may involve more than one drug.

Ahmad FB, Rossen LM, Spencer MR, Warner M, Sutton P. Provisional drug overdose death counts. National Center for Health Statistics, Centers for Disease Control. 2018. Last accessed September 13, 2018.
https://www.cdc.gov/nchs/nvss/...

12. Opioid Involvement in Deaths in the US Attributed to Drug Overdose, 2016

According to the US Centers for Disease Control, in 2016, there were 63,632 drug overdose deaths in the United States. The CDC further estimates that of those, 42,249 deaths involved any opioid.

The CDC reports that in 2016, 15,469 deaths involved heroin; 14,487 deaths involved natural and semi-synthetic opioids; 3,373 deaths involved methadone; and 19,413 deaths involved synthetic opioids other than methadone, a category which includes fentanyl. The sum of those numbers is greater than the total opioid involved deaths because, as noted by the CDC, "Deaths involving more than one opioid category (e.g., a death involving both methadone and a natural or semisynthetic opioid such as oxycodone) are counted in both categories."

Hedegaard H, Warner M, Miniño AM. Drug overdose deaths in the United States, 1999–2016. NCHS Data Brief, no 294. Hyattsville, MD: National Center for Health Statistics. 2017.
https://www.cdc.gov/nchs/produ...
https://www.cdc.gov/nchs/data/...
https://www.cdc.gov/nchs/data/...

13. Provisional Counts of Overdose Deaths Can Be Misleading

The federal Centers for Disease Control reported on December 21, 2017, that there had been a total of 63,600 deaths attributed to drug overdose in the US in 2016. Based on data available for analysis on Oct. 1, 2017, the CDC's provisional count of drug overdose deaths in the US for the 12-month period ending in December 2016 had been 71,135. The difference is attributed to data quality: provisional counts are by definition incomplete, which means they can be misleading.

The CDC compiles and publishes official data on annual causes of death in the United States. Demand for data on drug overdose deaths, and on drug overdoses generally, is so great that the CDC is now making raw data on these subjects available to the public. Those data are provisional, not final, and so can be misleading. Several caveats that must be understood before examining the numbers. According to the CDC:

"Provisional counts are often incomplete and causes of death may be pending investigation (see table Notes). Data quality measures, such as percent completeness in overall death reporting and percentage of deaths pending investigation, are included to aid interpretation of provisional data, because both data completeness and the percentage of records pending investigation are related to the accuracy of provisional counts (see Technical Notes). Provisional data are based on available records that meet certain data quality criteria at the time of analysis and may not include all deaths that occurred during a given time period. Therefore, they should not be considered comparable with final data and are subject to change. Reporting of specific drugs and drug classes varies by jurisdiction, and comparisons across selected states should not be made (see Technical Notes)."

Hedegaard H, Warner M, Miniño AM. Drug overdose deaths in the United States, 1999–2016. NCHS Data Brief, no 294. Hyattsville, MD: National Center for Health Statistics. 2017.
https://www.cdc.gov/nchs/produ...
https://www.cdc.gov/nchs/data/...
https://www.cdc.gov/nchs/data/...
"Provisional Drug Overdose Death Counts," U.S. Centers for Disease Control, Atlanta, GA, based on data available for analysis on Oct. 1, 2017, last accessed Oct. 19, 2017 at https://www.cdc.gov/nchs/...

14. Changes in Synthetic Opioid Involvement in Overdose Deaths in the US and Involvement of Other Drugs in Combination

"Among the 42 249 opioid-related overdose deaths in 2016, 19,413 involved synthetic opioids, 17,087 involved prescription opioids, and 15,469 involved heroin. Synthetic opioid involvement in these deaths increased significantly from 3007 (14.3% of opioid-related deaths) in 2010 to 19,413 (45.9%) in 2016 (P for trend <.01). Significant increases in synthetic opioid involvement in overdose deaths involving prescription opioids, heroin, and all other illicit or psychotherapeutic drugs were found from 2010 through 2016 (Table).

"Among synthetic opioid–related overdose deaths in 2016, 79.7% involved another drug or alcohol. The most common co-involved substances were another opioid (47.9%), heroin (29.8%), cocaine (21.6%), prescription opioids (20.9%), benzodiazepines (17.0%), alcohol (11.1%), psychostimulants (5.4%), and antidepressants (5.2%) (Figure)."

Jones CM, Einstein EB, Compton WM. Changes in Synthetic Opioid Involvement in Drug Overdose Deaths in the United States, 2010-2016. JAMA. 2018;319(17):1819–1821. doi:10.1001/jama.2018.2844
https://jamanetwork.com/journa...

15. Factors That May Skew Estimates of Overdose Deaths Attributed to Specific Drugs, Particularly Opioids

"First, factors related to death investigation might affect rate estimates involving specific drugs. At autopsy, the substances tested for, and circumstances under which tests are performed to determine which drugs are present, might vary by jurisdiction and over time. Second, the percentage of deaths with specific drugs identified on the death certificate varies by jurisdiction and over time. Nationally, 19% (in 2014) and 17% (in 2015) of drug overdose death certificates did not include the specific types of drugs involved. Additionally, the percentage of drug overdose deaths with specific drugs identified on the death certificate varies widely by state, ranging from 47.4% to 99%. Variations in reporting across states prevent comparison of rates between states. Third, improvements in testing and reporting of specific drugs might have contributed to some observed increases in opioid-involved death rates. Fourth, because heroin and morphine are metabolized similarly (9), some heroin deaths might have been misclassified as morphine deaths, resulting in underreporting of heroin deaths. Finally the state-specific analyses of opioid deaths are restricted to 28 states, limiting generalizability."

Rudd RA, Seth P, David F, Scholl L. Increases in Drug and Opioid-Involved Overdose Deaths — United States, 2010–2015. MMWR Morb Mortal Wkly Rep 2016;65:1445–1452. DOI: http://dx.doi.org/10.15585/mmw...
https://www.cdc.gov/mmwr/volum...
https://www.cdc.gov/mmwr/volum...

16. Growth of Fentanyl Related Deaths in the US

"Preliminary estimates of U.S. drug overdose deaths exceeded 60,000 in 2016 and were partially driven by a fivefold increase in overdose deaths involving synthetic opioids (excluding methadone), from 3,105 in 2013 to approximately 20,000 in 2016 (1,2). Illicitly manufactured fentanyl, a synthetic opioid 50–100 times more potent than morphine, is primarily responsible for this rapid increase (3,4). In addition, fentanyl analogs such as acetylfentanyl, furanylfentanyl, and carfentanil are being detected increasingly in overdose deaths (5,6) and the illicit opioid drug supply (7). Carfentanil is estimated to be 10,000 times more potent than morphine (8). Estimates of the potency of acetylfentanyl and furanylfentanyl vary but suggest that they are less potent than fentanyl (9). Estimates of relative potency have some uncertainty because illicit fentanyl analog potency has not been evaluated in humans."

Julie K. O’Donnell, PhD; John Halpin, MD; Christine L. Mattson, PhD; Bruce A. Goldberger, PhD; R. Matthew Gladden, PhD. Deaths Involving Fentanyl, Fentanyl Analogs, and U-47700 — 10 States, July–December 2016. Morbidity and Mortality Weekly Report. Vol. 66. Centers for Disease Control. October 27, 2017.
https://www.cdc.gov/mmwr/volum...

17. Estimated Economic Impact of Illegal Opioid Use and Opioid-Related Overdose Deaths

The White House Council of Economic Advisers [CEA] released its analysis of the economic costs of illegal opioid use, related overdoses, and overdose mortality in November 2017. It reported a dramatically higher estimate than previous analyses, largely due to a change in methodology. Previous analyses had used a person's estimated lifetime earnings to place a dollar value on that person's life. According to the CEA, "We diverge from the previous literature by quantifying the costs of opioid-related overdose deaths based on economic valuations of fatality risk reduction, the “value of a statistical life” (VSL)."

The CEA noted that "According to a recent white paper prepared by the U.S. Environmental Protection Agency’s (EPA) Office of Policy for review by the EPA’s Science Advisory Board (U.S. EPA 2016), the EPA’s current guidance calls for using a VSL estimate of $10.1 million (in 2015 dollars), updated from earlier estimates based on inflation, income growth, and assumed income elasticities. Guidance from the U.S. Department of Health and Human Services (HHS) suggests using the range of estimates from Robinson and Hammitt (2016) referenced earlier, ranging from a low of $4.4 million to a high of $14.3 million with a central value of $9.4 million (in 2015 dollars). The central estimates used by these three agencies, DOT, EPA, and HHS, range from a low of $9.4 million (HHS) to a high of $10.1 million (EPA) (in 2015 dollars)."

In addition, the CEA assumed that the number of opioid-related overdoses in the US in 2015 was significantly under-reported. According to its report, "However, recent research has found that opioids are underreported on death certificates. Ruhm (2017) estimates that in 2014, opioid-involved overdose deaths were 24 percent higher than officially reported.4 We apply this adjustment to the 2015 data, resulting in an estimated 41,033 overdose deaths involving opioids. We apply this adjustment uniformly over the age distribution of fatalities."

The combination of that assumption with the methodology change resulted in a dramatically higher cost estimate than previous research had shows. According to the CEA, "CEA’s preferred cost estimate of $504.0 billion far exceeds estimates published elsewhere. Table 3 shows the cost estimates from several past studies of the cost of the opioid crisis, along with the ratio of the CEA estimate to each study’s estimate in 2015 dollars. Compared to the recent Florence et al. (2016) study—which estimated the cost of prescription opioid abuse in 2013—CEA’s preferred estimate is more than six times higher, reported in the table’s last column as the ratio of $504.0 billion to $79.9 billion, which is Florence et al.’s estimate adjusted to 2015 dollars. Even CEA’s low total cost estimate of $293.9 billion is 3.7 times higher than Florence et al.’s estimate."

In contrast, the CEA noted that "Among the most recent (and largest) estimates was that produced by Florence et al. (2016), who estimated that prescription opioid overdose, abuse, and dependence in the United States in 2013 cost $78.5 billion. The authors found that 73 percent of this cost was attributed to nonfatal consequences, including healthcare spending, criminal justice costs and lost productivity due to addiction and incarceration. The remaining 27 percent was attributed to fatality costs consisting almost entirely of lost potential earnings." According to the CDC, there were 25,840 deaths in 2013 related to an opioid overdose.

According to the CEA, "We also present cost estimates under three alternative VSL assumptions without age-adjustment: low ($5.4 million), middle ($9.6 million), and high ($13.4 million), values suggested by the U.S. DOT and similar to those used by HHS. For example, our low fatality cost estimate of $221.6 billion is the product of the adjusted number of fatalities, 41,033, and the VSL assumption of $5.4 million. Our fatality cost estimates thus range from a low of $221.6 billion to a high of $549.8 billion."

"The Underestimated Cost of the Opioid Crisis," Council of Economic Advisers, Executive Office of the President of the United States, November 2017.
https://www.whitehouse.gov/sit...
Warner M, Trinidad JP, Bastian BA, et al. Drugs most frequently involved in drug overdose deaths: United States, 2010–2014. National vital statistics reports; vol 65 no 10. Hyattsville, MD: National Center for Health Statistics. 2016. Table B, p. 64.
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18. Drug-Induced Mortality in the US, by Gender and Race/Ethnicity

"In 2016, a total of 67,265 persons died of drug-induced causes in the United States (Tables 5, 6, 8, and I–1). This category includes deaths from poisoning and medical conditions caused by use of legal or illegal drugs, as well as deaths from poisoning due to medically prescribed and other drugs. It excludes deaths indirectly related to drug use, as well as newborn deaths due to the mother's drug use. (For a list of drug-induced causes, see Technical Notes.)

"In 2016, the age-adjusted death rate for drug-induced causes for the total population increased significantly, by 20.9% from 17.2 in 2015 to 20.8 in 2016 (Tables 5, 10, and I–1). For males in 2016, the age-adjusted death rate for drug-induced causes was 1.9 times the rate for females. The rate for drug-induced causes increased 26.0% for males and 13.6% for females in 2016 from 2015. The age-adjusted death rate for non-Hispanic white males was 28.9% higher than for non-Hispanic black males and 131.8% higher than for Hispanic males. The rate for non-Hispanic white females was 71.6% higher than for non-Hispanic black females and 252.8% higher than for Hispanic females.

"Among the major race–ethnicity–sex groups, the age-adjusted death rates for drug-induced causes increased significantly in 2016 from 2015 for non-Hispanic white males (24.7%), non-Hispanic white females (12.0%), non-Hispanic black males (42.2%), non-Hispanic black females (29.8%), Hispanic males (26.5%), and Hispanic females (12.8%)."

Xu JQ, Murphy SL, Kochanek KD, Bastian B, Arias E. Deaths: Final data for 2016. National Vital Statistics Reports; vol 67 no 5. Hyattsville, MD: National Center for Health Statistics. 2018.
https://www.cdc.gov/nchs/data/...
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19. Alcohol-Induced Mortality in the US, by Gender and Race/Ethnicity

"In 2016, a total of 34,865 persons died of alcohol-induced causes in the United States (Tables 5, 6, 8, and I–2). This category includes deaths from dependent and nondependent use of alcohol, as well as deaths from accidental poisoning by alcohol. It excludes unintentional injuries, homicides, and other causes indirectly related to alcohol use, as well as deaths due to fetal alcohol syndrome. For a list of alcohol-induced causes, see Technical Notes.

"The age-adjusted death rate for alcohol-induced causes for the total population increased significantly, by 4.4% from 9.1 in 2015 to 9.5 in 2016 (Tables 5, 10, and I–2). For males, the age-adjusted death rate for alcohol-induced causes in 2016 was 2.7 times the rate for females. The rate for alcohol-induced causes increased 3.7% for males and 4.0% for females in 2016 from 2015. The age-adjusted death rate for non-Hispanic white males was 32.1% higher than for non-Hispanic black males and 16.3% lower than for Hispanic males. The rate for non-Hispanic white females was 66.7% higher than for non-Hispanic black females and 62.2% higher than for Hispanic females.

"Among the major race–ethnicity–sex groups, the age- adjusted rate for alcohol-induced death increased significantly in 2016 from 2015 for non-Hispanic white males (4.3%) and non-Hispanic white females (7.1%). The rates for non-Hispanic black males, non-Hispanic black females, Hispanic males, and Hispanic females did not change significantly."

Xu JQ, Murphy SL, Kochanek KD, Bastian B, Arias E. Deaths: Final data for 2016. National Vital Statistics Reports; vol 67 no 5. Hyattsville, MD: National Center for Health Statistics. 2018.
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20. Drug Overdose Deaths in the US, Polydrug Use, and Involvement of Prescription Pharmaceutical Drugs

"Of the 36,667 drug overdose deaths with at least one mention of a specific drug, 52% mentioned only one specific drug (18,931 deaths), 26% mentioned two (9,351 deaths), 12% mentioned three (4,521 deaths), 6% mentioned four (2,041 deaths), and 5% mentioned five or more (1,823 deaths). Among drug overdose deaths with at least one mention of a specific drug, the average number of specific drugs mentioned was 1.9.

"Table C shows the percentage of drug overdose deaths with concomitant drugs for drug overdose deaths involving the top 10 drugs in 2014. The percentage of deaths involving concomitant drugs varied by referent drug. For example, the majority of the drug overdose deaths involving methamphetamine did not involve other drugs. In contrast, among deaths involving alprazolam and diazepam, more than 95% involved other drugs.

"The average number of concomitant drugs involved (excluding the referent drug) also varied among the top 10 drugs involved in drug overdose deaths. For example, drug overdose deaths involving diazepam or alprazolam had on average more than two additional drugs involved in death. Drug overdose deaths involving fentanyl, heroin, cocaine, or methamphetamine had on average fewer than two additional drugs involved in death.

"Figure 5 shows the percent distribution of the number of concomitant drugs for overdose deaths involving the top 10 drugs in 2014 (Table 5). For example, for drug overdose deaths involving methamphetamine, 55% had no concomitant mentions, 25% mentioned one other drug, 18% mentioned two to four other drugs, and 1% mentioned five or more drugs. In contrast, for drug overdose deaths involving diazepam, 3% had no concomitant mentions, 22% mentioned one other drug, 62% mentioned two to four other drugs, and 13% mentioned five or more other drugs.

"Table D shows the most frequent concomitant drugs for each of the top 10 drugs involved in drug overdose deaths in 2014.

"• One in five drug overdose deaths involving heroin also involved cocaine.
"• Alprazolam was involved in 26% of the drug overdose deaths involving hydrocodone, 23% of the deaths involving oxycodone, and 18% of the deaths involving methadone.
"• More than one-third (37%) of the drug overdose deaths involving cocaine also involved heroin.
"• Nearly 20% of the overdose deaths involving methamphetamine also involved heroin."

Warner M, Trinidad JP, Bastian BA, et al. Drugs most frequently involved in drug overdose deaths: United States, 2010–2014. National vital statistics reports; vol 65 no 10. Hyattsville, MD: National Center for Health Statistics. 2016, pp. 5-6.
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21. Alcohol as a Factor in Overdose Deaths Attributed to Other Drugs in the US

"In 2014, alcohols, including ethanol and isopropyl alcohol, were involved in 15% of all drug overdose deaths and 17% of the drug overdose deaths that mentioned involvement of at least one specific drug. Table E shows the frequency of alcohol involvement among drug overdose deaths involving specific drugs.

"• Alcohol involvement was mentioned in 12%–22% of the drug overdose deaths involving fentanyl, heroin, hydrocodone, morphine, oxycodone, alprazolam, diazepam, or cocaine.

"• Alcohol involvement was mentioned in less than 10% of the drug overdose deaths involving methadone and methamphetamine."

Warner M, Trinidad JP, Bastian BA, et al. Drugs most frequently involved in drug overdose deaths: United States, 2010–2014. National vital statistics reports; vol 65 no 10. Hyattsville, MD: National Center for Health Statistics. 2016, pp. 5-6.
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22. Alcohol Overdose Deaths in the US

"On average, 6 people died every day from alcohol poisoning in the US from 2010 to 2012. Alcohol poisoning is caused by drinking large quantities of alcohol in a short period of time. Very high levels of alcohol in the body can shutdown critical areas of the brain that control breathing, heart rate, and body temperature, resulting in death. Alcohol poisoning deaths affect people of all ages but are most common among middle-aged adults and men."

Alcohol Poisoning Deaths. CDC Vital Signs, January 2015. US Centers for Disease Control, Atlanta, GA.
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23. Estimated Annual Number of Deaths Caused by Tobacco Use in the US - Mortality Data

"The 2014 Surgeon General's report estimates that cigarette smoking causes more than 480,000 deaths each year in the United States.1 This widely cited estimate of the mortality burden of smoking may be an underestimate, because it considers deaths only from the 21 diseases that have been formally established as caused by smoking (12 types of cancer, 6 categories of cardiovascular disease, diabetes, chronic obstructive pulmonary disease [COPD], and pneumonia including influenza). Associations between smoking and the 30 most common causes of death in the United Kingdom in the Million Women Study suggest that the excess mortality observed among current smokers cannot be fully explained by these 21 diseases.2

Brian D. Carter, M.P.H., Christian C. Abnet, Ph.D., et al., "Smoking and Mortality — Beyond Established Causes," New England Journal of Medicine, Feb 12, 2015;372:631-40. DOI: 10.1056/NEJMsa1407211.
http://www.nejm.org/doi/full/1...

24. Alternative Estimate of Total Number of Deaths In the US Caused By Tobacco Use

"Our results suggest that the Surgeon General's recent estimate of smoking-attributable mortality may have been an underestimate. The Surgeon General's estimate, which took into account only the 21 diseases formally established as caused by smoking, was that approximately 437,000 deaths among adults are caused each year by active smoking (not including secondhand smoke). However, the Surgeon General’s report presents an alternative estimate of 556,000 deaths among adults on the basis of the excess mortality from all causes. The difference between these two estimates is nearly 120,000 deaths.1 If, as suggested by the results in our cohort, at least half of this difference is due to associations of smoking with diseases that are causal but are not yet formally established as such, then at least 60,000 additional deaths each year among U.S. men and women may be caused by cigarette smoking."

Brian D. Carter, M.P.H., Christian C. Abnet, Ph.D., et al., "Smoking and Mortality - Beyond Established Causes," New England Journal of Medicine, Feb 12, 2015;372:631-40. DOI: 10.1056/NEJMsa1407211.
http://www.nejm.org/doi/full/1...

25. Drug Poisoning Deaths In The US 2013, and Trends 1999-2013

"In 2013, a total of 43,982 deaths in the United States were attributed to drug poisoning, including 16,235 deaths (37%) involving opioid analgesics. From 1999 to 2013, the drug poisoning death rate more than doubled from 6.1 to 13.8 per 100,000 population, and the rate for drug poisoning deaths involving opioid analgesics nearly quadrupled from 1.4 to 5.1 per 100,000. For both drug poisoning and drug poisoning involving opioid analgesics, the death rate increased at a faster pace from 1999 to 2006 than from 2006 to 2013."

Li-Hui Chen, PhD; Holly Hedegaard, MD; Margaret Warner, PhD. Rates of Deaths from Drug Poisoning and Drug Poisoning Involving Opioid Analgesics — United States, 1999–2013. Centers for Disease Control. Morbidity and Mortality Weekly Report. Vol. 64, No. 1. January 16, 2015, p. 32.
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26. Increasing Involvement Of Benzodiazepines In Opioid Overdose Mortality In The US

"In 2011, 5,188 opioid-analgesic poisoning deaths also involved benzodiazepines (sedatives used to treat anxiety, insomnia, and seizures), up from 527 such deaths in 1999 (Figure 3). From 2006 through 2011, the number of opioid-analgesic poisoning deaths involving benzodiazepines increased 14% on average each year, while the number of opioid-analgesic poisoning deaths not involving benzodiazepines did not change significantly."

Chen, LH, Hedegaard, H, and Warner, M. Drug-poisoning deaths involving opioid analgesics: United States, 1999–2011. NCHS data brief, No. 166. Hyattsville, MD: National Center for Health Statistics, 2014, p. 3.
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27. Polydrug Involvement in Pharmaceutical Overdose Deaths in the US

"Opioids were frequently implicated in overdose deaths involving other pharmaceuticals. They were involved in the majority of deaths involving benzodiazepines (77.2%), antiepileptic and antiparkinsonism drugs (65.5%), antipsychotic and neuroleptic drugs (58.0%), antidepressants (57.6%), other analgesics, antipyretics, and antirheumatics (56.5%), and other psychotropic drugs (54.2%). Among overdose deaths due to psychotherapeutic and central nervous system pharmaceuticals, the proportion involving only a single class of such drugs was highest for opioids (4903/16 651; 29.4%) and lowest for benzodiazepines (239/6497; 3.7%)."

Christopher M. Jones, PharmD, Karin A. Mack, PhD, and Leonard J. Paulozzi, MD, "Pharmaceutical Overdose Deaths, United States, 2010," Journal of the American Medical Association, February 20, 2013, Vol 309, No. 7, p. 658.
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28. The Burden of Opioid-Related Mortality in the United States

"Over the 15-year study period, 335,123 opioid-related deaths in the United States met our inclusion criteria, with an increase of 345% from 9489 in 2001 (33.3 deaths per million population) to 42,245 in 2016 (130.7 deaths per million population). By 2016, men accounted for 67.5% of all opioid-related deaths (n = 28,496), and the median (interquartile range) age at death was 40 (30-52) years. The proportion of deaths attributable to opioids increased over the study period, rising 292% (from 0.4% [1 in 255] to 1.5% [1 in 65]), and increased steadily over time in each age group studied (P < .001 for all age groups) (Figure). The largest absolute increase between 2001 and 2016 was observed among those aged 25 to 34 years (15.8% increase from 4.2% in 2001 to 20.0% in 2016), followed by those aged 15 to 24 years (9.4% increase from 2.9% to 12.4%). However, the largest relative increases occurred among adults aged 55 to 64 years (754% increase from 0.2% to 1.7%) and those aged 65 years and older (635% increase from 0.01% to 0.07%). Despite the fact that confirmed opioid-related deaths represent a small percentage of all deaths in these older age groups, the absolute number of deaths is moderate. In 2016, 18.4% (7762 of 42,245) of all opioid-related deaths in the United States occurred among those aged 55 years and older.

"In our analysis of the burden of early loss of life from opioid overdose, we found that opioid-related deaths were responsible for 1,681,359 YLL [Years of Life Lost] (5.2 YLL per 1000 population) in the United States in 2016 (Table); however, this varied by age and sex. In particular, when stratified by age, adults aged 25 to 34 years and those aged 35 to 44 years experienced the highest burden from opioid-related deaths (12.9 YLL per 1000 population and 9.9 YLL per 1000 population, respectively). We also found that the burden of opioid-related death was higher among men (1,125,711 YLL; 7.0 YLL per 1000 population) compared with women (555,648 YLL; 3.4 YLL per 1000 population). Importantly, among men aged 25 to 34 years, this rate increased to 18.1 YLL per 1000 population, and the total YLL in this population represented nearly one-quarter of all YLL in the United States in 2016 (411,805 of 1,681,359 [24.5%])."

Gomes T, Tadrous M, Mamdani MM, Paterson JM, Juurlink DN. The Burden of Opioid-Related Mortality in the United States. JAMA Network Open. 2018;1(2):e180217. doi:10.1001/jamanetworkopen.2018.0217
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29. Role of Psychopharmaceuticals in Overdose Deaths

"This analysis confirms the predominant role opioid analgesics play in pharmaceutical overdose deaths, either alone or in combination with other drugs. It also, however, highlights the frequent involvement of drugs typically prescribed for mental health conditions such as benzodiazepines, antidepressants, and antipsychotics in overdose deaths. People with mental health disorders are at increased risk for heavy therapeutic use, nonmedical use, and overdose of opioids.4-6 Screening, identification, and appropriate management of such disorders is an important part of both behavioral health and chronic pain management."

Christopher M. Jones, PharmD, Karin A. Mack, PhD, and Leonard J. Paulozzi, MD, "Pharmaceutical Overdose Deaths, United States, 2010," Journal of the American Medical Association, February 20, 2013, Vol 309, No. 7, p. 659.
http://jama.jamanetwork.com/ar...

30. Opioid Overdose Deaths In The US, 1999-2007

"From 1999 to 2007, the number of U.S. poisoning deaths involving any opioid analgesic (e.g., oxycodone, methadone, or hydrocodone) more than tripled, from 4,041 to 14,459, or 36% of the 40,059 total poisoning deaths in 2007. In 1999, opioid analgesics were involved in 20% of the 19,741 poisoning deaths. During 1999–2007, the number of poisoning deaths involving specified drugs other than opioid analgesics increased from 9,262 to 12,790, and the number involving nonspecified drugs increased from 3,608 to 8,947."

"Number of Poisoning Deaths* Involving Opioid Analgesics and Other Drugs or Substances — United States, 1999–2007," Morbidity and Mortality Weekly Report, August 20, 2010, Vol. 59, No. 32 (Atlanta, GA: US Centers for Disease Control), p. 1026.
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