Andrew D. Wiese, PhD; Marie R. Griffin, MD, MPH; William Schaffner, MD; C. Michael Stein, MB, ChB; Robert A. Greevy, PhD; Edward F. Mitchel Jr., MS; Carlos G. Grijalva, MD, MPH
Note: The corresponding author affirms that he has listed everyone who contributed significantly to the work.
Acknowledgment: The authors thank the Tennessee Bureau of TennCare of the Department of Finance and Administration, as well as the Tennessee Department of Health for providing data for the study.
Grant Support: By NIH, National Institute on Aging, through grants R03 AG042981, R01 AG043471, and TL1TR000447.
Disclosures: Dr. Schaffner reports personal fees from Merck, Pfizer, Dynavax, Seqirus, Sutrovax, and Shionogi during the conduct of the study. Dr. Stein reports grants from NIH during the conduct of the study. Dr. Grijalva reports grants from NIH during the conduct of the study and consulting fees from Pfizer and Merck and grants from Sanofi-Pasteur, the Campbell Alliance, Centers for Disease Control and Prevention, U.S. Food and Drug Administration and Agency for Healthcare Research and Quality outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-1907.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol and statistical code: Available from Dr. Grijalva (firstname.lastname@example.org). Data set: Not available.
Requests for Single Reprints: Andrew D. Wiese, PhD Department of Health Policy, Vanderbilt University Medical Center, Suite 2600, Village at Vanderbilt, 1500 21st Avenue South, Nashville, TN 37212; e-mail, email@example.com.
Current Author Addresses: Drs. Wiese, Griffin, Schaffner, and Grijalva and Mr. Mitchel: Department of Health Policy, Vanderbilt University Medical Center, Suite 2600, Village at Vanderbilt, 1500 21st Avenue South, Nashville, TN 37212.
Dr. Stein: Department of Medicine, Vanderbilt University Medical Center, 2222 Pierce Avenue, Robinson Research Building, Suite 542, Nashville, TN 37232.
Dr. Greevy: Department of Biostatistics, Vanderbilt University Medical Center, 2525 West End, Suite 11000, Nashville, TN 37203.
Author Contributions: Conception and design: A.D. Wiese, M.R. Griffin, W. Schaffner, C.M. Stein, R.A. Greevy, E.F. Mitchel, C.G. Grijalva.
Analysis and interpretation of the data: A.D. Wiese, M.R. Griffin, W. Schaffner, C.M. Stein, R.A. Greevy, E.F. Mitchel, C.G. Grijalva.
Drafting of the article: A.D. Wiese.
Critical revision for important intellectual content: A.D. Wiese, M.R. Griffin, W. Schaffner, C.M. Stein, R.A. Greevy, E.F. Mitchel, C.G. Grijalva.
Final approval of the article: A.D. Wiese, M.R. Griffin, W. Schaffner, C.M. Stein, R.A. Greevy, E.F. Mitchel, C.G. Grijalva.
Statistical expertise: A.D. Wiese, R.A. Greevy, C.G. Grijalva.
Obtaining of funding: W. Schaffner, C.G. Grijalva.
Administrative, technical, or logistic support: E.F. Mitchel.
Collection and assembly of data: A.D. Wiese, W. Schaffner, E.F. Mitchel, C.G. Grijalva.
Although certain opioid analgesics have immunosuppressive properties and increase the risk for infections in animals, the clinical effects of prescription opioid use on infection risk among humans are unknown.
To test the hypothesis that prescription opioid use is an independent risk factor for invasive pneumococcal disease (IPD).
Nested case–control study.
Tennessee Medicaid database linked to Medicare and Active Bacterial Core surveillance system databases (1995 to 2014).
1233 case patients with IPD aged 5 years and older matched to 24 399 control participants by diagnosis date, age, and county of residence.
Opioid use was measured on the basis of pharmacy prescription fills. Invasive pneumococcal disease was defined by the isolation of Streptococcus pneumoniae from a normally sterile site. The odds of current opioid use were compared between the case and control groups, accounting for known IPD risk factors. Secondary analyses categorized opioid use by opioid characteristics, applied an IPD risk score to assure comparability between exposure groups, and analyzed pneumonia and nonpneumonia IPD cases separately.
Persons in the case group had greater odds than control participants of being current opioid users (adjusted odds ratio [aOR], 1.62 [95% CI, 1.36 to 1.92]). Associations were strongest for opioids that were long acting (aOR, 1.87 [CI, 1.24 to 2.82]), of high potency (aOR, 1.72 [CI, 1.32 to 2.25]), or were used at high dosages (50 to 90 morphine milligram equivalents [MME]/d: aOR, 1.71 [CI, 1.22 to 2.39]; ≥90 MME/d: aOR, 1.75 [CI, 1.33 to 2.29]). Results were consistent when the IPD risk score was taken into account and pneumonia and nonpneumonia IPD were analyzed separately.
Unmeasured confounding and measurement error, although sensitivity analyses suggested that neither was likely to affect results. Actual opioid use and other nonprescription use (such as illicit opioid use) were not measured.
Opioid use is associated with an increased risk for IPD and represents a novel risk factor for these diseases.
National Institutes of Health.
Wiese AD, Griffin MR, Schaffner W, et al. Opioid Analgesic Use and Risk for Invasive Pneumococcal Diseases: A Nested Case–Control Study. Ann Intern Med. 2018;168:396–404. [Epub ahead of print 13 February 2018]. doi: https://doi.org/10.7326/M17-1907
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Published: Ann Intern Med. 2018;168(6):396-404.
Published at www.annals.org on 13 February 2018
Infectious Disease, Streptococcal Infections.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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