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4. National Center for Health Statistics, Centers for Disease Control and Prevention. National Health and Nutrition Examination Survey: questionnaires, datasets, and related documentation. http://www.cdc.gov/nchs/nhanes/nhanes _questionnaires.htm. Accessed March 31, 2014.
Table 1. Pain Characteristics and Medication Characteristics Among 2597 Army Infantry Soldiers, 2011 Variable
5. Navar-Boggan AM, Pencina MJ, Williams K, Sniderman AD, Peterson ED. Proportion of US adults potentially affected by the 2014 hypertension guideline. JAMA. 2014;311(14):1424-1429.
Pain severity (past month) None (0)
557 (22.2)
Chronic Pain and Opioid Use in US Soldiers After Combat Deployment
Mild (1-4) Moderate (5-6)
578 (23.0)
Chronic pain affects a quarter of people seeking primary health care.1,2 Opioid medications are prescribed for chronic pain, but recently, rates of opioid use and misuse have ballooned, leading to significant numbers of overdose-related hospitalizaInvited Commentary tions and deaths.3 The prevapage 1402 lence of chronic pain and opio i d u s e a s s o c i at e d w it h deployment is not well known, despite large numbers of wounded service members. To our knowledge, this is the first study to assess chronic pain prevalence and opioid use in a non– treatment-seeking, active duty infantry population following deployment.
Severe (7-10)
191 (7.6)
Results | The 2597 participants were predominantly male (93.1%), 18 to 24 years old (41.3%), high school educated (48.2%), married (54.9%), and junior enlisted rank (56.1%). Nearly half (45.4%) reported injuries during combat. The prevalences of PTSD, MDD, and alcohol misuse screening were 9.1%, 5.8%, and 16.4%, respectively. Past-month opioid use was reported by 15.1% of soldiers (Table 1); among these, 5.6% reported no past-month pain, and 38.5%, 37.7%, and 18.2% reported mild, moderate, and severe pain, respectively. Most using opioids (62.6%) reported few or several days’ use. Chronic pain was reported by 44.0%. Of these, 48.3% reported duration 1 year or longer, 55.6% reported nearly
1186 (47.2)
Opioid use (past month) Never Few or several days
2148 (84.9) 239 (9.4)
More than half the days
74 (2.9)
Nearly every day
69 (2.7)
Chronic pain (pain ≥3 mo) No
1440 (56.0)
Yes
1131 (44.0)
Among Those With Chronic Pain (n = 1131) Pain duration, mo 3-5
Methods | Institutional review board approval for the study was given by Walter Reed Army Institute of Research. Confidential surveys were collected in 2011 from 1 infantry brigade 3 months after return from Afghanistan under a protocol approved by the Walter Reed Army Institute of Research.4 Group recruitment briefings were attended by 80.3% of soldiers (3076 of 3832); 93.5% consented to participate (2876 of 3076). The final sample included 2597 soldiers who had been deployed to Afghanistan or Iraq. Participants provided written informed consent. Chronic pain was defined by soldiers reporting pain duration of at least 3 months (Table 1).5 Past-month pain frequency and severity (range, 0-10; none [0], mild [1-4], moderate [5-6], and severe [7-10])6 were also assessed (Table 1). Opioids and other pain medications were assessed by pastmonth frequency of use (never, few or several days, more than half the days, nearly every day) (Table 1). Standardized scales assessed injuries during combat, combat intensity, posttraumatic stress disorder (PTSD), major depressive disorder (MDD) and alcohol misuse.4 Multiple logistic regressions examined correlates of chronic pain and opioid use.
1400
No. (%)a
Among All Soldiers (N = 2597)
263 (23.3)
6-11
322 (28.5)
≥1 y
546 (48.3)
Pain frequency (past month) Few days/not at all
103 (9.1)
Several days
203 (18.0)
More than half the days
195 (17.3)
Nearly every day
350 (31.0)
Constantly
277 (24.6)
Pain severity (past month) None (0)
8 (0.7)
Mild (1-4)
535 (48.1)
Moderate (5-6)
417 (37.5)
Severe (7-10)
153 (13.7)
Medication use (any; past month) None
196 (17.3)
Over-the-counter pain medication
890 (79.0)
Nonopioid pain prescription
209 (18.8)
Opioid pain prescription
259 (23.2)
Opioid use (past month)
a
Never
855 (76.8)
Few or several days
150 (13.5)
More than half the days
49 (4.4)
Nearly every day
60 (5.4)
Percentages were adjusted for missing values.
daily or constant frequency, and 51.2% reported severity of moderate to severe; 23.2% reported past-month opioid use, and 57.9% of those reported few or several days use (Table 1). Chronic pain was significantly associated with age 30 years or older, being married or having been married previously, injury during combat, combat intensity, PTSD, and MDD (Table 2). Opioid use was associated with sex, age 25 years or older, being married, rank, injury during combat, chronic pain, and pain severity (Table 2).
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Table 2. Association of Demographic, Health, and Combat Factors With Chronic Pain and Opioid Use Among 2597 Army Soldiers, 2011
treating pain, particularly in those with combat-related injuries, must be balanced by careful assessment of risks, including the potential for misuse.
Adjusted OR (95% CI) Variable Female sexa
Chronic Pain 1.3 (0.9-1.8)
Opioid Use 1.9 (1.2-3.0)
Age, yb 25-29
1.0 (0.8-1.3)
1.6 (1.2-2.2)
≥30
1.4 (1.1-1.8)
2.0 (1.4-2.9)
Robin L. Toblin, PhD, MPH Phillip J. Quartana, PhD Lyndon A. Riviere, PhD Kristina Clarke Walper, MPH Charles W. Hoge, MD
Marital statusc Married
1.6 (1.3-1.9)
1.5 (1.1-2.0)
Previously married
1.7 (1.3-2.3)
1.2 (0.8-1.9)
Rankd Senior enlisted
0.8 (0.7-1.0)
0.7 (0.5-0.9)
(Warrant) Officer
0.6 (0.4-1.1)
0.4 (0.2-0.9)
2.8 (2.3-3.4)
1.9 (1.4-2.5)
Medium
1.3 (1.04-1.6)
1.1 (0.8-1.6)
High
1.4 (1.1-1.7)
1.2 (0.9-1.7)
0.8 (0.6-1.0)
1.0 (0.7-1.4)
Combat injury Combat experiencese
Alcohol misuse PTSD screen positive
1.7 (1.2-2.5)
1.1 (0.7-1.7)
MDD screen positive
2.3 (1.4-3.6)
1.0 (0.6-1.6)
NA
1.8 (1.3-2.3)
Moderate (5-6)
NA
2.0 (1.5-2.6)
Severe (7-10)
NA
3.2 (2.2-4.7)
Chronic pain Pain severityf
Abbreviations: MDD, major depressive disorder; NA, not applicable; OR, odds ratio; PTSD, posttraumatic stress disorder. a
Referent: Male.
b
Referent: Age 18 to 24 years.
c
Referent: Single.
d
Referent: Junior enlisted rank.
e
Referent: Low combat experiences.
f
Referent: No or mild pain (0-4).
Corresponding Author: Robin L. Toblin, PhD, MPH, Commissioned Corps of the US Public Health Service and Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD 20910 ([email protected]). Published Online: June 30, 2014. doi:10.1001/jamainternmed.2014.2726. Author Contributions: Dr Toblin had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Toblin, Hoge. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: All authors. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Toblin, Quartana. Administrative, technical, or material support: Riviere, Walper. Study supervision: Hoge. Conflict of Interest Disclosures: None reported. Funding/Support: The US Army Medical Research and Materiel Command (USAMRMC) provides intramural funding that supports enhancing the psychological resilience of the warfighter. Role of the Sponsor: The USAMRMC had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Disclaimer: The views reported herein are those of the authors only and do not represent the views of the US Army, Department of Defense, or any of the institutes listed.
Discussion | The prevalence of chronic pain (44.0%) and opioid use (15.1%) in this non–treatment-seeking infantry sample were higher than estimates in the general civilian population of 26.0% and 4.0%, respectively.2 These results are notable because this is an operational unit of young soldiers surveyed at their workplace and are likely, in part, related to deployment effects (including injuries, combat exposure, and mental health conditions). These findings suggest a large unmet need for assessment, management, and treatment of chronic pain and related opioid use and misuse in military personnel after combat deployments. Notably, 44.1% of soldiers reporting opioid use reported no or mild past-month pain, including 5.6% with no pain. This might imply that opioids are working to mitigate pain, but it is also possible that soldiers are receiving or using these medications unnecessarily. This is cause for concern because opioids should be prescribed generally for moderate to severe pain 1,3 and have high abuse and overdose potential.1-3 Prescription practices should be examined to ensure that opioid use is consistent with standards of care and practice guidelines and nonopioid alternatives are considered whenever possible.1,3 The benefits of opioids for jamainternalmedicine.com
Author Affiliations: Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, Maryland (Toblin, Quartana, Riviere, Walper, Hoge); Commissioned Corps of the US Public Health Service, Rockville, Maryland (Toblin).
Previous Presentation: Some data from this study were presented at the American Public Health Association Annual Meeting; October 29, 2012; San Francisco, California. Additional Information: Dr Riviere was the principal investigator of the study. Additional Contributions: We are grateful to the soldiers and leadership of the participating unit and the Land Combat Study team for assistance with data collection. 1. Department of Veteran Affairs; Department of Defense. VA/DoD Clinical practice guideline for management of opioid therapy for chronic pain. http://www.healthquality.va.gov/guidelines/Pain/cot/. Accessed January 31, 2014. 2. Toblin RL, Mack KA, Perveen G, Paulozzi LJ. A population-based survey of chronic pain and its treatment with prescription drugs. Pain. 2011;152(6):12491255. 3. Centers for Disease Control and Prevention. Prescription painkiller overdoses in the US. Vital Signs. http://www.cdc.gov/vitalsigns/painkilleroverdoses/. Accessed January 31, 2014. 4. Thomas JL, Wilk JE, Riviere LA, McGurk D, Castro CA, Hoge CW. Prevalence of mental health problems and functional impairment among active component and National Guard soldiers 3 and 12 months following combat in Iraq. Arch Gen Psychiatry. 2010;67(6):614-623. 5. International Association for the Study of Pain. Classification of Chronic Pain. 2nd ed. Seattle, WA: International Association for the Study of Pain; 1994. 6. Anderson KO. Role of cutpoints: why grade pain intensity? Pain. 2005;113(1-2): 5-6. JAMA Internal Medicine August 2014 Volume 174, Number 8
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Invited Commentary
Pain and Opioids in the Military: We Must Do Better In the documentary movie Escape Fire,1 a battle-weary and combat-wounded soldier falls out of his bunk during a medical evacuation flight from Afghanistan to Washington, DC. Disoriented from an overdose of opioid and psychoactive medications previously prescribed for his wounds, pain, and loss, he later embarks on a journey of self-healing in an effort to get off of the drugs. Unfortunately, he is not alone. In a study by Toblin et al2 of one of the Army’s leading units published in this issue of JAMA Internal Medicine, 44.0% of the soldiers had chronic pain, and 15.1% regularly used opioids. Even accounting for the ready availability of military care, these rates are much higher than the estimates of 26.0% and 4.0%, respectively, in the general civilian population. While chronic pain and opioid use have been a long-standing concern of the military leadership, this study is among the first to quantify the impact of recent wars on the prevalence of pain and narcotic use among soldiers. The nation’s defense rests on the comprehensive fitness of its service members—mind, body, and spirit. 3 Chronic pain and use of opioids carry the risk of functional impairment of America’s fighting force. In its landmark 2011 report Relieving Pain in America,4 the Institute of Medicine (IOM) called for a comprehensive pain management plan with specific goals, actions, and timeframes. They recommended that the goal should be nothing short of a “cultural transformation” in how we manage pain, noting that over 100 million people experience chronic pain at an annual cost of over $600 billion. Notably, they urged a plan that tailored pain management to each person and that more and better strategies for “self-management of pain be promoted.”4(p3) A year before this IOM report, in response to the growing prevalence of pain from a decade of continuous combat, the Department of Defense (DoD) took up this challenge. The Army, joined by the other Services, the Veterans Administration, and leading civilian pain experts, established a Pain Management Task Force. The DoD developed a comprehensive Pain Management Campaign with 109 specific action items with an aim to create an integrated approach to pain that is “…holistic, multidisciplinary, and multimodal in its approach, utilizes state of the art/science modalities and technologies, and provides optimal quality of life for soldiers and other patients with acute and chronic pain.”5 This campaign has continued unabated within the DoD. For example, the Army has moved forward with a variety of initiatives to improve treatment effectiveness and risk reduction related to polypharmacy, among them those aimed at reducing adverse outcomes due to prescription abuse. These include informed consent for polypharmacy, a sole health care provider program for frequent prescription drug users, limiting the authorized use of a prescription to 6 months following the fill date, adding hydrocodone and hydromorphone to the panel in random urine drug testing, and polypharmacy education and training. Drug take-back programs at hospital and clinic pharmacies have begun improving medical oversight and improving health record documentation. 1402
Among the first tasks needed to fully implement the IOM and DoD Pain Management Campaign recommendations was to examine the evidence basis for “self-management” strategies. The DoD commissioned Samueli Institute, a nonprofit research organization, to conduct a comprehensive set of systematic reviews on self-care and integrative approaches for pain. An expert committee called the Active Self-Care Therapies for Pain (PACT) Working Group was convened to make recommendations based on these reviews. The PACT included the director of the Defense and Veterans Center for Integrated Pain Management and 7 other subject matter experts. That PACT evidence review and recommendations were recently published in Pain Medicine.6 From the available literature, the committee recommended that several self-care modalities be adopted as effective for alleviating chronic pain, including yoga, t’ai chi, and music therapy. More than 10 other selfmanagement approaches had insufficient evidence to recommend them, primarily because of a lack of studies and poor research design. It was clear that much more investment was needed for understanding and delivering these modalities. But is that likely to happen? Achieving the IOM and DoD recommendations will require overcoming major obstacles, especially where we are investing our money for pain management. Despite the public costs of inadequately managed pain listed by IOM, the National Institutes of Health currently spends only 1% of its $30 billion budget for pain research. Compare this with private sector spending on pharmaceuticals, estimated at $48.5 billion for research and development and $57.5 billion for drug promotion.4 If only 1% of that is for pain, this amount dwarfs what goes into self-management. Although opioid medications are effective in treating acute pain, their use in chronic pain management is not well supported by the available evidence7 and is associated with clinically significant adverse events. In the Research Letter by Toblin et al2 in this issue, 44.1% of soldiers reporting opioid use had no or mild past-month pain, including 5.6% with no pain. As the authors point out,2 given the high abuse potential for opioids, this is also a cause for concern. Unless the “cultural transformation” called for by the IOM begins in earnest, our nation faces additional crises in the future. Many service members and veterans with pain also have comorbid conditions, such as posttraumatic stress syndrome or traumatic brain injury. Many of them are at risk for a lifetime progression of increasing disability unless the quality, variety, and accessibility of evidenced-based “self-management” skills are improved. Without more effective and less costly approaches to pain management, the estimated costs of care and disability to the country will approach $5 trillion.8 The loss of human potential is inestimable. This staggering cost will become the greatest threat to national defense as the nation is crushed under debt. Thus, for reasons of current and future national strength, and most important, the suffering of our service members and veterans, we must transform ourselves in the way we manage pain. We can and must do better. Wayne B. Jonas, MD, LTC (Ret) Eric B. Schoomaker, MD, PhD
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Author Affiliations: Samueli Institute, Alexandria, Virginia (Jonas); Uniformed Services University of the Health Sciences, Bethesda, Maryland (Schoomaker). Corresponding Author: Wayne B. Jonas, MD, LTC (Ret), US Army, Samueli Institute, 1737 King St, Ste 600, Alexandria, VA 22314 ([email protected]). Published Online: June 30, 2014. doi:10.1001/jamainternmed.2014.2114. Conflict of Interest Disclosures: None reported. Disclaimer: Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and should not be construed as an official Department of Defense or Uniformed Services University of the Health Sciences position, policy, or decision unless so designated by other documentation. 1. Heineman M. Escape Fire: The Fight to Rescue American Healthcare [film]. New York, NY: Our Time Projects; 2013. 2. Toblin RL, Quartana PJ, Riviere LA, Walper KC, Hoge CW. Chronic pain and opioid use in US soldiers after combat deployment [published online June 30, 2014]. JAMA Intern Med. doi:10.1001/jamainternmed.2014.2726. 3. Jonas WB, O'Connor F, Deuster P, Peck J, Shake C, Frost S, Why total force fitness? Military Med. 2010;175(8):6-13. 4. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington, DC: Institute of Medicine; 2011:1-3. 5. Lillis-Hearne PK. US Army MEDCOM Pain Management Initiative: Pain Task Force Overview, Findings, & Recommendations, Pain Management Campaign Plan Overview. March 2011. http://www.pdhealth.mil/education/2011 _Presentations/AFPCH%2011%20Pain%20Management%20Across%20the %20DoD.pdf. Accessed May 20, 2014. 6. Buckenmaier C III, Crawford C, Lee C, Schoomaker E. Are active self-care complementary and integrative therapies effective for management of chronic pain? a rapid evidence assessment of the literature and recommendations for the field. Pain Med. 2014;15(suppl):S1-S113. 7. Kissin I. Long-term opioid treatment of chronic nonmalignant pain: unproven efficacy and neglected safety? J Pain Res. 2013;6(6):513-529. 8. Bilmes L. The Financial Legacy of Iraq and Afghanistan: How Wartime Spending Decisions Will Constrain Future National Security Budgets. Cambridge, MA: Harvard Kennedy School Faculty Research Working Paper Series 13-006; 2013.
Effects of Ranolazine on Quality of Life Among Patients With Diabetes Mellitus and Stable Angina In the Type 2 Diabetes Evaluation of Ranolazine in Subjects with Chronic Stable Angina (TERISA) trial, ranolazine reduced the frequency of angina episodes and use of sublingual nitroglycerin in patients with type 2 diabetes mellitus (T2DM) and stable angina, as assessed by a daily diary.1 Using data from the same trial, we evaluated the effect of ranolazine on a broader range of patients’ health status and quality of life.
Methods | TERISA was approved by the national regulatory authority in each participating country and the institutional review board or local ethics committee for each site, and all participating patients provided written informed consent. TERISA was a randomized, double-blind, placebo-controlled trial in 104 sites in 14 countries in which patients with chronic stable angina receiving 1 to 2 antianginal medications and T2DM were randomized to placebo or ranolazine (Gilead Sciences; dosage goal, 1000 mg twice daily) for 8 weeks.1 Health status was assessed at baseline and at 8 weeks with the Seattle Angina Questionnaire (SAQ),2 Rose Dyspnea Scale,3 and the Medical Outcomes Short Form-36 (SF-36) component scores.4 A 10point increase in SAQ angina frequency represents a clinically important intraindividual change.2 Linguistically valid, country-specific instruments were used. Scores were compared using analysis of covariance, adjusted for baseline health status and prespecified stratification covariates.1 We tested interactions between treatment and baseline angina; number of antianginals; geography (Russia, Ukraine, and Belarus vs other [as prespecified in the TERISA analytic plan]), age, and sex. Results | Overall, 917 patients were randomized: mean age of 64 years, 61% men, 99% white, and mean hemoglobin A1c level of 7.3%. Both treatment groups had high symptom burden at baseline and experienced improvements in all health status measures at follow-up (Table). Compared with placebo, ranolazine significantly improved SAQ angina frequency, treatment satisfaction, and SF-36 physical component summary scale scores. These effects did not differ for all measures across each of the prespecified subgroups (geography, baseline angina episodes, number of antianginals, sex, and age [P > .05 for all interactions]), except the SF-36 mental component, which improved more with ranolazine in other countries (mean effect, 1.8; 95% CI, 0.01 to 3.5) than in Russia, Ukraine, and Belarus (mean effect, −0.9; 95% CI, −2.0 to 0.2 [P value for interaction, .009]). A greater percentage of patients treated with ranolazine vs placebo had at least a 10-point improvement in SAQ angina frequency scores (67% vs 58% [P = .004]; Figure), suggesting that 11 patients need to be treated with ranolazine for 1 to experience a clinically significant improvement in angina. The number needed to treat was lower among patients taking more
Table. Mean Change From Baseline in Disease-Specific Health Status and QOL Scores by Treatment Group LS Mean Change (95% CI)
Health Status/QOLa
Baseline Score, Mean (SD)
SAQ angina frequency
46.3 (19.0)
16.1 (14.0 to 18.1)
SAQ physical limitation
57.3 (19.2)
4.3 (2.8 to 5.9)
Ranolazine Group
Treatment Effect, Δ (95% CI)
P Value
13.3 (11.2 to 15.4)
2.8 (0.6 to 5.0)
.01
4.0 (2.4 to 5.5)
0.3 (−1.4 to 2.1)
.69
Placebo Group
SAQ QOL
50.2 (19.6)
9.6 (7.7 to 11.5)
7.8 (5.9 to 9.7)
1.8 (−0.2 to 3.9)
.08
SAQ treatment satisfaction
75.5 (15.4)
6.2 (4.7 to 7.6)
4.5 (3.0 to 6.0)
1.7 (0.1 to 3.3)
.04
SF-36 PCS
38.2 (6.8)
2.9 (2.3 to 3.5)
1.9 (1.3 to 2.5)
1.0 (0.3 to 1.6)
.005
SF-36 MCS
44.9 (10.1)
1.0 (0.2 to 1.8)
1.1 (0.3 to 1.9)
−0.1 (−1.0 to 0.8)
.77
Rose Dyspnea Scale score
Abbreviations: LS, least squares; MCS, mental component summary; PCS, physical component summary; QOL, quality of life; SAQ, Seattle Angina Questionnaire; SF-36, Medical Outcomes Short Form-36. a
2.0 (1.2)
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−0.28 (−0.39 to −0.17) −0.18 (−0.29 to −0.07) −0.11 (−0.23 to 0.01)
.08
Scores range from 0 to 100, with higher scores indicating improved health status/QOL for all measures except for dyspnea, where scores range from 0 to 4, with lower scores indicating less severe symptoms.
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4. National Center for Health Statistics, Centers for Disease Control and Prevention. National Health and Nutrition Examination Survey: questionnaires, datasets, and related documentation. http://www.cdc.gov/nchs/nhanes/nhanes _questionnaires.htm. Accessed March 31, 2014.
Table 1. Pain Characteristics and Medication Characteristics Among 2597 Army Infantry Soldiers, 2011 Variable
5. Navar-Boggan AM, Pencina MJ, Williams K, Sniderman AD, Peterson ED. Proportion of US adults potentially affected by the 2014 hypertension guideline. JAMA. 2014;311(14):1424-1429.
Pain severity (past month) None (0)
557 (22.2)
Chronic Pain and Opioid Use in US Soldiers After Combat Deployment
Mild (1-4) Moderate (5-6)
578 (23.0)
Chronic pain affects a quarter of people seeking primary health care.1,2 Opioid medications are prescribed for chronic pain, but recently, rates of opioid use and misuse have ballooned, leading to significant numbers of overdose-related hospitalizaInvited Commentary tions and deaths.3 The prevapage 1402 lence of chronic pain and opio i d u s e a s s o c i at e d w it h deployment is not well known, despite large numbers of wounded service members. To our knowledge, this is the first study to assess chronic pain prevalence and opioid use in a non– treatment-seeking, active duty infantry population following deployment.
Severe (7-10)
191 (7.6)
Results | The 2597 participants were predominantly male (93.1%), 18 to 24 years old (41.3%), high school educated (48.2%), married (54.9%), and junior enlisted rank (56.1%). Nearly half (45.4%) reported injuries during combat. The prevalences of PTSD, MDD, and alcohol misuse screening were 9.1%, 5.8%, and 16.4%, respectively. Past-month opioid use was reported by 15.1% of soldiers (Table 1); among these, 5.6% reported no past-month pain, and 38.5%, 37.7%, and 18.2% reported mild, moderate, and severe pain, respectively. Most using opioids (62.6%) reported few or several days’ use. Chronic pain was reported by 44.0%. Of these, 48.3% reported duration 1 year or longer, 55.6% reported nearly
1186 (47.2)
Opioid use (past month) Never Few or several days
2148 (84.9) 239 (9.4)
More than half the days
74 (2.9)
Nearly every day
69 (2.7)
Chronic pain (pain ≥3 mo) No
1440 (56.0)
Yes
1131 (44.0)
Among Those With Chronic Pain (n = 1131) Pain duration, mo 3-5
Methods | Institutional review board approval for the study was given by Walter Reed Army Institute of Research. Confidential surveys were collected in 2011 from 1 infantry brigade 3 months after return from Afghanistan under a protocol approved by the Walter Reed Army Institute of Research.4 Group recruitment briefings were attended by 80.3% of soldiers (3076 of 3832); 93.5% consented to participate (2876 of 3076). The final sample included 2597 soldiers who had been deployed to Afghanistan or Iraq. Participants provided written informed consent. Chronic pain was defined by soldiers reporting pain duration of at least 3 months (Table 1).5 Past-month pain frequency and severity (range, 0-10; none [0], mild [1-4], moderate [5-6], and severe [7-10])6 were also assessed (Table 1). Opioids and other pain medications were assessed by pastmonth frequency of use (never, few or several days, more than half the days, nearly every day) (Table 1). Standardized scales assessed injuries during combat, combat intensity, posttraumatic stress disorder (PTSD), major depressive disorder (MDD) and alcohol misuse.4 Multiple logistic regressions examined correlates of chronic pain and opioid use.
1400
No. (%)a
Among All Soldiers (N = 2597)
263 (23.3)
6-11
322 (28.5)
≥1 y
546 (48.3)
Pain frequency (past month) Few days/not at all
103 (9.1)
Several days
203 (18.0)
More than half the days
195 (17.3)
Nearly every day
350 (31.0)
Constantly
277 (24.6)
Pain severity (past month) None (0)
8 (0.7)
Mild (1-4)
535 (48.1)
Moderate (5-6)
417 (37.5)
Severe (7-10)
153 (13.7)
Medication use (any; past month) None
196 (17.3)
Over-the-counter pain medication
890 (79.0)
Nonopioid pain prescription
209 (18.8)
Opioid pain prescription
259 (23.2)
Opioid use (past month)
a
Never
855 (76.8)
Few or several days
150 (13.5)
More than half the days
49 (4.4)
Nearly every day
60 (5.4)
Percentages were adjusted for missing values.
daily or constant frequency, and 51.2% reported severity of moderate to severe; 23.2% reported past-month opioid use, and 57.9% of those reported few or several days use (Table 1). Chronic pain was significantly associated with age 30 years or older, being married or having been married previously, injury during combat, combat intensity, PTSD, and MDD (Table 2). Opioid use was associated with sex, age 25 years or older, being married, rank, injury during combat, chronic pain, and pain severity (Table 2).
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Table 2. Association of Demographic, Health, and Combat Factors With Chronic Pain and Opioid Use Among 2597 Army Soldiers, 2011
treating pain, particularly in those with combat-related injuries, must be balanced by careful assessment of risks, including the potential for misuse.
Adjusted OR (95% CI) Variable Female sexa
Chronic Pain 1.3 (0.9-1.8)
Opioid Use 1.9 (1.2-3.0)
Age, yb 25-29
1.0 (0.8-1.3)
1.6 (1.2-2.2)
≥30
1.4 (1.1-1.8)
2.0 (1.4-2.9)
Robin L. Toblin, PhD, MPH Phillip J. Quartana, PhD Lyndon A. Riviere, PhD Kristina Clarke Walper, MPH Charles W. Hoge, MD
Marital statusc Married
1.6 (1.3-1.9)
1.5 (1.1-2.0)
Previously married
1.7 (1.3-2.3)
1.2 (0.8-1.9)
Rankd Senior enlisted
0.8 (0.7-1.0)
0.7 (0.5-0.9)
(Warrant) Officer
0.6 (0.4-1.1)
0.4 (0.2-0.9)
2.8 (2.3-3.4)
1.9 (1.4-2.5)
Medium
1.3 (1.04-1.6)
1.1 (0.8-1.6)
High
1.4 (1.1-1.7)
1.2 (0.9-1.7)
0.8 (0.6-1.0)
1.0 (0.7-1.4)
Combat injury Combat experiencese
Alcohol misuse PTSD screen positive
1.7 (1.2-2.5)
1.1 (0.7-1.7)
MDD screen positive
2.3 (1.4-3.6)
1.0 (0.6-1.6)
NA
1.8 (1.3-2.3)
Moderate (5-6)
NA
2.0 (1.5-2.6)
Severe (7-10)
NA
3.2 (2.2-4.7)
Chronic pain Pain severityf
Abbreviations: MDD, major depressive disorder; NA, not applicable; OR, odds ratio; PTSD, posttraumatic stress disorder. a
Referent: Male.
b
Referent: Age 18 to 24 years.
c
Referent: Single.
d
Referent: Junior enlisted rank.
e
Referent: Low combat experiences.
f
Referent: No or mild pain (0-4).
Corresponding Author: Robin L. Toblin, PhD, MPH, Commissioned Corps of the US Public Health Service and Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD 20910 ([email protected]). Published Online: June 30, 2014. doi:10.1001/jamainternmed.2014.2726. Author Contributions: Dr Toblin had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Toblin, Hoge. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: All authors. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Toblin, Quartana. Administrative, technical, or material support: Riviere, Walper. Study supervision: Hoge. Conflict of Interest Disclosures: None reported. Funding/Support: The US Army Medical Research and Materiel Command (USAMRMC) provides intramural funding that supports enhancing the psychological resilience of the warfighter. Role of the Sponsor: The USAMRMC had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Disclaimer: The views reported herein are those of the authors only and do not represent the views of the US Army, Department of Defense, or any of the institutes listed.
Discussion | The prevalence of chronic pain (44.0%) and opioid use (15.1%) in this non–treatment-seeking infantry sample were higher than estimates in the general civilian population of 26.0% and 4.0%, respectively.2 These results are notable because this is an operational unit of young soldiers surveyed at their workplace and are likely, in part, related to deployment effects (including injuries, combat exposure, and mental health conditions). These findings suggest a large unmet need for assessment, management, and treatment of chronic pain and related opioid use and misuse in military personnel after combat deployments. Notably, 44.1% of soldiers reporting opioid use reported no or mild past-month pain, including 5.6% with no pain. This might imply that opioids are working to mitigate pain, but it is also possible that soldiers are receiving or using these medications unnecessarily. This is cause for concern because opioids should be prescribed generally for moderate to severe pain 1,3 and have high abuse and overdose potential.1-3 Prescription practices should be examined to ensure that opioid use is consistent with standards of care and practice guidelines and nonopioid alternatives are considered whenever possible.1,3 The benefits of opioids for jamainternalmedicine.com
Author Affiliations: Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, Maryland (Toblin, Quartana, Riviere, Walper, Hoge); Commissioned Corps of the US Public Health Service, Rockville, Maryland (Toblin).
Previous Presentation: Some data from this study were presented at the American Public Health Association Annual Meeting; October 29, 2012; San Francisco, California. Additional Information: Dr Riviere was the principal investigator of the study. Additional Contributions: We are grateful to the soldiers and leadership of the participating unit and the Land Combat Study team for assistance with data collection. 1. Department of Veteran Affairs; Department of Defense. VA/DoD Clinical practice guideline for management of opioid therapy for chronic pain. http://www.healthquality.va.gov/guidelines/Pain/cot/. Accessed January 31, 2014. 2. Toblin RL, Mack KA, Perveen G, Paulozzi LJ. A population-based survey of chronic pain and its treatment with prescription drugs. Pain. 2011;152(6):12491255. 3. Centers for Disease Control and Prevention. Prescription painkiller overdoses in the US. Vital Signs. http://www.cdc.gov/vitalsigns/painkilleroverdoses/. Accessed January 31, 2014. 4. Thomas JL, Wilk JE, Riviere LA, McGurk D, Castro CA, Hoge CW. Prevalence of mental health problems and functional impairment among active component and National Guard soldiers 3 and 12 months following combat in Iraq. Arch Gen Psychiatry. 2010;67(6):614-623. 5. International Association for the Study of Pain. Classification of Chronic Pain. 2nd ed. Seattle, WA: International Association for the Study of Pain; 1994. 6. Anderson KO. Role of cutpoints: why grade pain intensity? Pain. 2005;113(1-2): 5-6. JAMA Internal Medicine August 2014 Volume 174, Number 8
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Letters
Invited Commentary
Pain and Opioids in the Military: We Must Do Better In the documentary movie Escape Fire,1 a battle-weary and combat-wounded soldier falls out of his bunk during a medical evacuation flight from Afghanistan to Washington, DC. Disoriented from an overdose of opioid and psychoactive medications previously prescribed for his wounds, pain, and loss, he later embarks on a journey of self-healing in an effort to get off of the drugs. Unfortunately, he is not alone. In a study by Toblin et al2 of one of the Army’s leading units published in this issue of JAMA Internal Medicine, 44.0% of the soldiers had chronic pain, and 15.1% regularly used opioids. Even accounting for the ready availability of military care, these rates are much higher than the estimates of 26.0% and 4.0%, respectively, in the general civilian population. While chronic pain and opioid use have been a long-standing concern of the military leadership, this study is among the first to quantify the impact of recent wars on the prevalence of pain and narcotic use among soldiers. The nation’s defense rests on the comprehensive fitness of its service members—mind, body, and spirit. 3 Chronic pain and use of opioids carry the risk of functional impairment of America’s fighting force. In its landmark 2011 report Relieving Pain in America,4 the Institute of Medicine (IOM) called for a comprehensive pain management plan with specific goals, actions, and timeframes. They recommended that the goal should be nothing short of a “cultural transformation” in how we manage pain, noting that over 100 million people experience chronic pain at an annual cost of over $600 billion. Notably, they urged a plan that tailored pain management to each person and that more and better strategies for “self-management of pain be promoted.”4(p3) A year before this IOM report, in response to the growing prevalence of pain from a decade of continuous combat, the Department of Defense (DoD) took up this challenge. The Army, joined by the other Services, the Veterans Administration, and leading civilian pain experts, established a Pain Management Task Force. The DoD developed a comprehensive Pain Management Campaign with 109 specific action items with an aim to create an integrated approach to pain that is “…holistic, multidisciplinary, and multimodal in its approach, utilizes state of the art/science modalities and technologies, and provides optimal quality of life for soldiers and other patients with acute and chronic pain.”5 This campaign has continued unabated within the DoD. For example, the Army has moved forward with a variety of initiatives to improve treatment effectiveness and risk reduction related to polypharmacy, among them those aimed at reducing adverse outcomes due to prescription abuse. These include informed consent for polypharmacy, a sole health care provider program for frequent prescription drug users, limiting the authorized use of a prescription to 6 months following the fill date, adding hydrocodone and hydromorphone to the panel in random urine drug testing, and polypharmacy education and training. Drug take-back programs at hospital and clinic pharmacies have begun improving medical oversight and improving health record documentation. 1402
Among the first tasks needed to fully implement the IOM and DoD Pain Management Campaign recommendations was to examine the evidence basis for “self-management” strategies. The DoD commissioned Samueli Institute, a nonprofit research organization, to conduct a comprehensive set of systematic reviews on self-care and integrative approaches for pain. An expert committee called the Active Self-Care Therapies for Pain (PACT) Working Group was convened to make recommendations based on these reviews. The PACT included the director of the Defense and Veterans Center for Integrated Pain Management and 7 other subject matter experts. That PACT evidence review and recommendations were recently published in Pain Medicine.6 From the available literature, the committee recommended that several self-care modalities be adopted as effective for alleviating chronic pain, including yoga, t’ai chi, and music therapy. More than 10 other selfmanagement approaches had insufficient evidence to recommend them, primarily because of a lack of studies and poor research design. It was clear that much more investment was needed for understanding and delivering these modalities. But is that likely to happen? Achieving the IOM and DoD recommendations will require overcoming major obstacles, especially where we are investing our money for pain management. Despite the public costs of inadequately managed pain listed by IOM, the National Institutes of Health currently spends only 1% of its $30 billion budget for pain research. Compare this with private sector spending on pharmaceuticals, estimated at $48.5 billion for research and development and $57.5 billion for drug promotion.4 If only 1% of that is for pain, this amount dwarfs what goes into self-management. Although opioid medications are effective in treating acute pain, their use in chronic pain management is not well supported by the available evidence7 and is associated with clinically significant adverse events. In the Research Letter by Toblin et al2 in this issue, 44.1% of soldiers reporting opioid use had no or mild past-month pain, including 5.6% with no pain. As the authors point out,2 given the high abuse potential for opioids, this is also a cause for concern. Unless the “cultural transformation” called for by the IOM begins in earnest, our nation faces additional crises in the future. Many service members and veterans with pain also have comorbid conditions, such as posttraumatic stress syndrome or traumatic brain injury. Many of them are at risk for a lifetime progression of increasing disability unless the quality, variety, and accessibility of evidenced-based “self-management” skills are improved. Without more effective and less costly approaches to pain management, the estimated costs of care and disability to the country will approach $5 trillion.8 The loss of human potential is inestimable. This staggering cost will become the greatest threat to national defense as the nation is crushed under debt. Thus, for reasons of current and future national strength, and most important, the suffering of our service members and veterans, we must transform ourselves in the way we manage pain. We can and must do better. Wayne B. Jonas, MD, LTC (Ret) Eric B. Schoomaker, MD, PhD
JAMA Internal Medicine August 2014 Volume 174, Number 8
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Letters
Author Affiliations: Samueli Institute, Alexandria, Virginia (Jonas); Uniformed Services University of the Health Sciences, Bethesda, Maryland (Schoomaker). Corresponding Author: Wayne B. Jonas, MD, LTC (Ret), US Army, Samueli Institute, 1737 King St, Ste 600, Alexandria, VA 22314 ([email protected]). Published Online: June 30, 2014. doi:10.1001/jamainternmed.2014.2114. Conflict of Interest Disclosures: None reported. Disclaimer: Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and should not be construed as an official Department of Defense or Uniformed Services University of the Health Sciences position, policy, or decision unless so designated by other documentation. 1. Heineman M. Escape Fire: The Fight to Rescue American Healthcare [film]. New York, NY: Our Time Projects; 2013. 2. Toblin RL, Quartana PJ, Riviere LA, Walper KC, Hoge CW. Chronic pain and opioid use in US soldiers after combat deployment [published online June 30, 2014]. JAMA Intern Med. doi:10.1001/jamainternmed.2014.2726. 3. Jonas WB, O'Connor F, Deuster P, Peck J, Shake C, Frost S, Why total force fitness? Military Med. 2010;175(8):6-13. 4. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington, DC: Institute of Medicine; 2011:1-3. 5. Lillis-Hearne PK. US Army MEDCOM Pain Management Initiative: Pain Task Force Overview, Findings, & Recommendations, Pain Management Campaign Plan Overview. March 2011. http://www.pdhealth.mil/education/2011 _Presentations/AFPCH%2011%20Pain%20Management%20Across%20the %20DoD.pdf. Accessed May 20, 2014. 6. Buckenmaier C III, Crawford C, Lee C, Schoomaker E. Are active self-care complementary and integrative therapies effective for management of chronic pain? a rapid evidence assessment of the literature and recommendations for the field. Pain Med. 2014;15(suppl):S1-S113. 7. Kissin I. Long-term opioid treatment of chronic nonmalignant pain: unproven efficacy and neglected safety? J Pain Res. 2013;6(6):513-529. 8. Bilmes L. The Financial Legacy of Iraq and Afghanistan: How Wartime Spending Decisions Will Constrain Future National Security Budgets. Cambridge, MA: Harvard Kennedy School Faculty Research Working Paper Series 13-006; 2013.
Effects of Ranolazine on Quality of Life Among Patients With Diabetes Mellitus and Stable Angina In the Type 2 Diabetes Evaluation of Ranolazine in Subjects with Chronic Stable Angina (TERISA) trial, ranolazine reduced the frequency of angina episodes and use of sublingual nitroglycerin in patients with type 2 diabetes mellitus (T2DM) and stable angina, as assessed by a daily diary.1 Using data from the same trial, we evaluated the effect of ranolazine on a broader range of patients’ health status and quality of life.
Methods | TERISA was approved by the national regulatory authority in each participating country and the institutional review board or local ethics committee for each site, and all participating patients provided written informed consent. TERISA was a randomized, double-blind, placebo-controlled trial in 104 sites in 14 countries in which patients with chronic stable angina receiving 1 to 2 antianginal medications and T2DM were randomized to placebo or ranolazine (Gilead Sciences; dosage goal, 1000 mg twice daily) for 8 weeks.1 Health status was assessed at baseline and at 8 weeks with the Seattle Angina Questionnaire (SAQ),2 Rose Dyspnea Scale,3 and the Medical Outcomes Short Form-36 (SF-36) component scores.4 A 10point increase in SAQ angina frequency represents a clinically important intraindividual change.2 Linguistically valid, country-specific instruments were used. Scores were compared using analysis of covariance, adjusted for baseline health status and prespecified stratification covariates.1 We tested interactions between treatment and baseline angina; number of antianginals; geography (Russia, Ukraine, and Belarus vs other [as prespecified in the TERISA analytic plan]), age, and sex. Results | Overall, 917 patients were randomized: mean age of 64 years, 61% men, 99% white, and mean hemoglobin A1c level of 7.3%. Both treatment groups had high symptom burden at baseline and experienced improvements in all health status measures at follow-up (Table). Compared with placebo, ranolazine significantly improved SAQ angina frequency, treatment satisfaction, and SF-36 physical component summary scale scores. These effects did not differ for all measures across each of the prespecified subgroups (geography, baseline angina episodes, number of antianginals, sex, and age [P > .05 for all interactions]), except the SF-36 mental component, which improved more with ranolazine in other countries (mean effect, 1.8; 95% CI, 0.01 to 3.5) than in Russia, Ukraine, and Belarus (mean effect, −0.9; 95% CI, −2.0 to 0.2 [P value for interaction, .009]). A greater percentage of patients treated with ranolazine vs placebo had at least a 10-point improvement in SAQ angina frequency scores (67% vs 58% [P = .004]; Figure), suggesting that 11 patients need to be treated with ranolazine for 1 to experience a clinically significant improvement in angina. The number needed to treat was lower among patients taking more
Table. Mean Change From Baseline in Disease-Specific Health Status and QOL Scores by Treatment Group LS Mean Change (95% CI)
Health Status/QOLa
Baseline Score, Mean (SD)
SAQ angina frequency
46.3 (19.0)
16.1 (14.0 to 18.1)
SAQ physical limitation
57.3 (19.2)
4.3 (2.8 to 5.9)
Ranolazine Group
Treatment Effect, Δ (95% CI)
P Value
13.3 (11.2 to 15.4)
2.8 (0.6 to 5.0)
.01
4.0 (2.4 to 5.5)
0.3 (−1.4 to 2.1)
.69
Placebo Group
SAQ QOL
50.2 (19.6)
9.6 (7.7 to 11.5)
7.8 (5.9 to 9.7)
1.8 (−0.2 to 3.9)
.08
SAQ treatment satisfaction
75.5 (15.4)
6.2 (4.7 to 7.6)
4.5 (3.0 to 6.0)
1.7 (0.1 to 3.3)
.04
SF-36 PCS
38.2 (6.8)
2.9 (2.3 to 3.5)
1.9 (1.3 to 2.5)
1.0 (0.3 to 1.6)
.005
SF-36 MCS
44.9 (10.1)
1.0 (0.2 to 1.8)
1.1 (0.3 to 1.9)
−0.1 (−1.0 to 0.8)
.77
Rose Dyspnea Scale score
Abbreviations: LS, least squares; MCS, mental component summary; PCS, physical component summary; QOL, quality of life; SAQ, Seattle Angina Questionnaire; SF-36, Medical Outcomes Short Form-36. a
2.0 (1.2)
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−0.28 (−0.39 to −0.17) −0.18 (−0.29 to −0.07) −0.11 (−0.23 to 0.01)
.08
Scores range from 0 to 100, with higher scores indicating improved health status/QOL for all measures except for dyspnea, where scores range from 0 to 4, with lower scores indicating less severe symptoms.
JAMA Internal Medicine August 2014 Volume 174, Number 8
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