Letters
prior work showing no association with major or minor sur- Disclaimer: The content is solely the responsibility of the authors and does not
gery, persistent use was not explained by patient characteris-
tics or tooth impaction alone.3
Limitations include that the amount of opioid prescrip-
tions filled may not reflect actual consumption. The reasons
for opioid prescription refills (eg, whether for pain or a non-
prescribed reason, storage for later use, or diversion to an-
other person) were unknown. Persistent opioid use based on
prescription claims may underestimate overall and nonmedi-
cal use.
Dentists were the second-leading opioid prescribers for
children and adolescents in 2012.5 The American Dental As-
sociation recently mandated an opioid prescribing limit of 7
days or less.6 However, nonopioid analgesics may have equiva-
lent or superior efficacy for postextraction pain.2 The prac-
tice of any routine opioid prescribing must be questioned in
the face of the potential morbidity and long-term conse-
quences of opioid use.
Calista M. Harbaugh, MD
Romesh P. Nalliah, DDS, MHCM
Hsou Mei Hu, PhD, MBA
Michael J. Englesbe, MD
Jennifer F. Waljee, MD, MPH, MS
Chad M. Brummett, MD
Author Affiliations: Department of Surgery, University of Michigan Medical
School, Ann Arbor (Harbaugh, Englesbe, Waljee); College of Dentistry,
University of Michigan, Ann Arbor (Nalliah); Michigan Opioid Prescribing
Engagement Network, Ann Arbor (Hu); Department of Anesthesiology,
University of Michigan Medical School, Ann Arbor (Brummett).
Accepted for Publication: June 5, 2018.
Corresponding Author: Chad M. Brummett, MD, Division of Pain Medicine,
Department of Anesthesiology, University of Michigan Medical School, 1500 E
Medical Center Dr, Ste 1H247 UH, PO Box 5048, Ann Arbor, MI 48109
(cbrummet@umich.edu).
Author Contributions: Drs Harbaugh and Brummett had full access to all
of the data in the study and take responsibility for the integrity of the data
and the accuracy of the data analysis. Dr Hu conducted and is responsible for
the data analysis.
Concept and design: Harbaugh, Englesbe, Waljee, Brummett.
Acquisition, analysis, or interpretation of data: Harbaugh, Nalliah, Hu, Waljee.
Drafting of the manuscript: Harbaugh, Nalliah, Waljee, Brummett.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Hu.
Obtained funding: Englesbe, Brummett.
Administrative, technical, or material support: Hu, Englesbe.
Supervision: Englesbe, Waljee, Brummett.
Conflict of Interest Disclosures: The authors have completed and submitted
the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Waljee
reported receiving research funding from the Agency for Healthcare Research
and Quality (grant K08 1K08HS023313-01), the American College of Surgeons,
and the American Foundation for Surgery of the Hand; and serving as an unpaid
consultant for 3M Health Information Systems. Dr Brummett reported holding
a patent for peripheral perineural dexmedetomidine licensed to University
of Michigan; being a consultant for Recro Pharma and Heron Therapeutics;
and receiving research funding from Neuros Medical. No other
disclosures were reported.
Funding/Support: Funding was provided by the Substance Abuse and Mental
Health Services Administration, the Michigan Department of Health and Human
Services, and the University of Michigan Precision Health Initiative.
Role of the Funder/Sponsor: The funders 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.
506 JAMA August 7, 2018 Volume 320, Number 5 (Reprinted)
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necessarily represent the official views of the Substance Abuse and Mental
Health Services Administration or the Michigan Department of Health and
Human Services.
1. Moore PA, Nahouraii HS, Zovko JG, Wisniewski SR. Dental therapeutic
practice patterns in the US: I, anesthesia and sedation. Gen Dent. 2006;54(2):
92-98.
2. Moore PA, Dionne RA, Cooper SA, Hersh EV. Why do we prescribe Vicodin?
J Am Dent Assoc. 2016;147(7):530-533. doi:10.1016/j.adaj.2016.05.005
3. Brummett CM, Waljee JF, Goesling J, et al. New persistent opioid use after
minor and major surgical procedures in US adults. JAMA Surg. 2017;152(6):
e170504. doi:10.1001/jamasurg.2017.0504
4. Harbaugh CM, Lee JS, Hu HM, et al. Persistent opioid use among pediatric
patients after surgery. Pediatrics. 2018;141(1):e20172439. doi:10.1542/peds
.2017-2439
5. Groenewald CB, Rabbitts JA, Gebert JT, Palermo TM. Trends in opioid
prescriptions among children and adolescents in the United States: a nationally
representative study from 1996 to 2012. Pain. 2016;157(5):1021-1027. doi:10
.1097/j.pain.0000000000000475
6. American Dental Association. Statement on the use of opioids in the
treatment of dental pain. https://www.ada.org/en/press-room/news-releases
/2018-archives/february/american-dental-association-statement-on-opioids.
Accessed June 15, 2018.
COMMENT & RESPONSE
Opioids vs Nonopioids for Chronic Back, Hip,
or Knee Pain
To the Editor Dr Krebs and colleagues1 compared opioid with
nonopioid medications in improving pain-related function in
patients with chronic back pain or hip or knee osteoarthritis
pain. We have several concerns about the study design and gen-
eralizability of the results.
First, potentially eligible patients were identified by
searching the electronic health record for back, hip, or knee
pain diagnoses at a primary care visit. It is not clear that the
patients with knee or hip pain were truly painful due to
osteoarthritis. Osteoarthritic radiographic changes are com-
mon, but these radiographic manifestations of osteoarthritis
often are not the cause of the pain described by the patient.
Many other conditions can cause knee and hip pain. It
would be helpful if more detailed description of inclusion
criteria was given.
Second, other treatment modalities may confound the re-
sults. Patients were allowed to participate in nonpharmaco-
logical pain therapies. Injections and surgery are effective
methods of treating hip and knee osteoarthritis. The 2 groups
could be different from each other with regard to utilization
of other treatment modalities. Could the authors provide more
detailed information regarding other treatment modalities used
in each group?
Third, patient outcomes were improved in both groups.
The result may suggest that the patients did not get sufficient
nonopioid treatments before being enrolled in this study.
Fourth, treatment of chronic back pain is more compli-
cated and controversial than treatment of hip and knee osteo-
arthritis. Many conditions can cause chronic low back pain,
such as failed back surgical syndrome. Such patients may have
a history of multiple back surgeries and have failed multiple
nonopioid options and interventional procedures. Closely
monitored low-dose narcotics may be an option to improve
jama.com

their quality of life. Therefore, to generalize the results of this
study to all patients with chronic low back pain may not be ap-
propriate. A balanced approach to opioid prescribing is pre-
ferred so that access to opioids for patients who may benefit
from them is not limited.2
Wenbao Wang, MD
William Macaulay, MD
Author Affiliations: Baylor Institute for Rehabilitation, Dallas, Texas (Wang);
New York University Langone Medical Center, New York (Macaulay).
Corresponding Author: Wenbao Wang, MD, Baylor Institute for
Rehabilitation, 909 N Washington Ave, Dallas, TX 75246
(wenbao.wang@bswhealth.org).
Conflict of Interest Disclosures: The authors have completed and submitted
the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were
reported.
1. Krebs EE, Gravely A, Nugent S, et al. Effect of opioid vs nonopioid
medications on pain-related function in patients with chronic back pain or hip or
knee osteoarthritis pain: the SPACE randomized clinical trial. JAMA. 2018;319
(9):872-882. doi:10.1001/jama.2018.0899
2. Alford DP. Opioid prescribing for chronic pain–achieving the right balance
through education. N Engl J Med. 2016;374(4):301-303. doi:10.1056
/NEJMp1512932
To the Editor The Strategies for Prescribing Analgesics Com-
parative Effectiveness (SPACE) trial1,2 compared opioids with
nonopioid analgesics over 12 months in primary care patients
with chronic low back pain or osteoarthritis pain of the hip or
knee and concluded that the results do not support initiation
of opioid therapy for such patients. Further scientific discus-
sion of the study is necessary.
Most patients in the study were not representative
of patients who may be prescribed opioids long-term. 1,3
The mean baseline pain intensity of patients randomized
to opioids was 5.4 on an 11-point scale (SD, 1.5); thus more
than 95% had moderate pain (<7) and only a minority
had severe pain (≥7).1 Furthermore, patients randomized to
nonopioids could receive medications from various classes
and in combination (multimodal care), whereas the opioid
group received only opioids, which is not consistent with
guidelines.3 The nonopioid group received more than twice
as many drugs as the opioid group (mean of 3.8 vs 1.7,
respectively). A few of the nonopioid participants received
an opioid (tramadol).
In the nonopioid group, 21% of participants had moder-
ate or greater depressive symptoms vs 23% in the opioid
group.1 Antidepressants were available to the nonopioid group
patients,1 potentially contributing to pain improvement.4
Also, patients on long-term opioid therapy were excluded,
thereby excluding people that may have been benefitting from
and tolerating opioids.
Opioids should be prescribed in strict accordance with in-
dications approved by the US Food and Drug Administration.
Thus, opioids should rarely be the first analgesic for patients
with moderate pain intensity, as those included in this study.
Furthermore, opioids are not appropriate for every type of pain
or every patient who meets an indication. For example, Bigal
and Lipton5 showed that opioid use worsened outcomes in mi-
graineurs and should be avoided.
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Letters
Pragmatic trials emulate usual care, but they also pose a
dilemma by contrasting an often imperfect usual care against
an idealized optimized care. The SPACE trial supports the po-
sition that, for a mostly male population having moderate lev-
els of pain, multimodal chronic pain treatment with non-
opioid therapies is preferred over opioid therapy alone.
However, in an attempt to emulate guidelines, future studies
should test other situations, including multimodal care with
and without opioids in patients with severe pain for whom
other options are unsatisfactory.
Marcelo E. Bigal, MD, PhD
Author Affiliation: Purdue Pharma, Stamford, Connecticut.
Corresponding Author: Marcelo E. Bigal, MD, PhD, Purdue Pharma, 201 Tresser
Blvd, Stamford, CT 06901 (marcelo.bigal@pharma.com).
Conflict of Interest Disclosures: The author has completed and submitted the
ICMJE Form for Disclosure of Potential Conflicts of Interest and reported being
the chief medical officer for Purdue Pharma, the maker of oxycontin; and
previously being an employee of Teva.
1. Krebs EE, Gravely A, Nugent S, et al. Effect of opioid vs nonopioid
medications on pain-related function in patients with chronic back pain or hip or
knee osteoarthritis pain: the SPACE randomized clinical trial. JAMA. 2018;319
(9):872-882. doi:10.1001/jama.2018.0899
2. Krebs EE, Jensen AC, Nugent S, et al. Design, recruitment outcomes, and
sample characteristics of the Strategies for Prescribing Analgesics Comparative
Effectiveness (SPACE) trial. Contemp Clin Trials. 2017;62:130-139. doi:10.1016/j
.cct.2017.09.003
3. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for
chronic pain—United States, 2016. MMWR Recomm Rep. 2016;65(1):1-49.
doi:10.15585/mmwr.rr6501e1
4. Scott EL, Kroenke K, Wu J, Yu Z. Beneficial effects of improvement in
depression, pain catastrophizing, and anxiety on pain outcomes: a 12-month
longitudinal analysis. J Pain. 2016;17(2):215-222. doi:10.1016/j.jpain.2015.10.011
5. Bigal ME, Lipton RB. Excessive opioid use and the development of chronic
migraine. Pain. 2009;142(3):179-182. doi:10.1016/j.pain.2009.01.013
To the Editor The randomized clinical trial1 comparing opioid
and nonopioid medications reflects real-world use and was con-
ducted in a population with common reasons for chronic opi-
oid use. The prospective nature of this study is important given
the lack of correlation between patients’ actual benefit from
chronic opioids and their perceptions of benefit.2
The authors’ conclusions, however, that opioids are
not indicated for chronic low back or osteoarthritis pain,
are weakened by 3 important issues. First, a study that
helped to establish the efficacy of oxycodone3 found that
20 mg/d was not different from placebo, whereas 40 mg/d
produced sustained analgesia. The effective dose equates to
a morphine-equivalent dose of 80 mg. Because most
patients in the opioid group received less than 50 morphine-
equivalent mg, their lack of response may have resulted
from undertreatment.
Second, the interpretation of the nonopioid response is
confounded by the fact that 11% of the group was taking tra-
madol at 12 months. Tramadol’s major metabolite is an μ-opioid
receptor agonist. Therefore, 11% of the nonopioid group was
using an opioid. Third, both treatment groups demonstrated
analgesia and improved function.
Although prolonged opioid therapy has not yet been
adequately studied on a population basis, many individuals
(Reprinted) JAMA August 7, 2018 Volume 320, Number 5 507
 Letters
both tolerate and respond to this treatment, and it should
not be denied to patients with demonstrable benefit on the
basis of this study.
Edward Covington, MD
Charles Argoff, MD
Steven P. Stanos, DO
Author Affiliations: Cleveland Clinic Foundation, Shaker Heights, Ohio
(Covington); Albany Medical Center, Albany, New York (Argoff); Swedish
Medical Center, Seattle, Washington (Stanos).
Corresponding Author: Edward Covington, MD, Cleveland Clinic Foundation,
2864 Eaton Rd, Shaker Heights, OH 44122 (covinge@gmail.com).
Conflict of Interest Disclosures: The authors have completed and submitted
the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Covington
reported receiving personal fees from Purdue Pharma, Shionogi Medpace, Endo
Pharmaceuticals, Inspirion, AcelRx Pharmaceuticals, Intellipharmaceutics,
Indivior, and Braeburn Pharmaceuticals; and has the potential for equity in
Franklin Bioscience. Dr Argoff reported receiving a research grant from
Gruenenthal; serving on the speaker’s bureau or being a consultant to Allergan
Botox, Amgen, Astra Zeneca, BioDelivery Sciences International, Braeburn,
Collegium, Daiichi Sankyo, Depomed, Jazz Pharma, Kaleo, Nevro, Novartis,
Pfizer, Quest Diagnostics, Scilex, Seminur, and Teva; and receiving royalties
from Elsevier. Dr Stanos reported receiving personal fees from Collegium,
Depomed, Endo, and Teva.
1. Krebs EE, Gravely A, Nugent S, et al. Effect of opioid vs nonopioid
medications on pain-related function in patients with chronic back pain or hip or
knee osteoarthritis pain: the SPACE randomized clinical trial. JAMA. 2018;319
(9):872-882. doi:10.1001/jama.2018.0899
2. Goesling J, Moser SE, Lin LA, Hassett AL, Wasserman RA, Brummett CM.
Discrepancies between perceived benefit of opioids and self-reported patient
outcomes. Pain Med. 2018;19(2):297-306.
3. Roth SH, Fleischmann RM, Burch FX, et al. Around-the-clock,
controlled-release oxycodone therapy for osteoarthritis-related pain:
placebo-controlled trial and long-term evaluation. Arch Intern Med. 2000;160
(6):853-860. doi:10.1001/archinte.160.6.853
1 medications on pain-related function in patients with chronic back pain or hip or
To the Editor The study by Dr Krebs and colleagues compared
opioid with nonopioid medications for the treatment of pa-
tients with chronic back pain or hip or knee osteoarthritis pain
refractory to analgesic use in veterans. We have concerns about
the study’s methods and data interpretation.
The primary harms measure was a score derived from a
checklist of 19 items consisting mostly of mild, common ad-
verse events.2 This instrument captures relatively nonspe-
cific adverse events such as sleep, mood, fatigue, headache,
muscle aches, rash, incontinence, sexual problems, dizzi-
ness, and gastrointestinal symptoms. It does not capture se-
rious adverse events commonly associated with nonopioid an-
algesics, such as gastrointestinal bleeding, worsening of chronic
kidney disease, drug-induced liver injury, acute cardiac (eg,
myocardial infarction) or neurological events (eg, stroke). These
safety concerns limit nonopioid use for many patients, yet the
study did not acknowledge this possibility.
Opioids offer an occasional but necessary treatment op-
tion for certain subgroups of patients who have relative, if not
absolute, contraindications to nonopioid analgesics. In a co-
hort of 644 patients with rheumatic disease pain, prolonged
clinically meaningful pain reduction was achieved with opi-
oid use, and mostly mild adverse events were seen in 38% of
opioid users. There was minimal evidence of abuse behavior
(<1%).3 A similar observational study confirmed that in pa-
508 JAMA August 7, 2018 Volume 320, Number 5 (Reprinted)
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tients with back pain, opioids significantly reduced pain se-
verity with only mild adverse events.4
Because the authors did not examine important patient
subgroups with contraindications to nonopioids or serious non-
opioid-related toxicities, we were surprised by the authors’ con-
clusion that the “results do not support initiation of opioid
therapy” in patients with chronic arthritis pain. Such a broad
statement failed to acknowledge the complex spectrum of pa-
tients who require individualized pain treatment.
Jasvinder A. Singh, MBBS, MPH
Jeffrey R. Curtis, MD, MS, MPH
Kenneth G. Saag, MD, MSc
Author Affiliations: Department of Medicine, University of Alabama School of
Medicine, Birmingham.
Corresponding Author: Jasvinder A. Singh, MBBS, MPH, University of Alabama
School of Medicine, 510 20th St S, Faculty Office Tower 805B, Birmingham, AL
35294 (jsingh@uabmc.edu).
Conflict of Interest Disclosures: The authors have completed and
submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.
Dr Singh reported receiving grant funding from Takeda and Savient;
consulting fees for an investigator-initiated study funded by Horizon Pharma
through a grant to DINORA, a 501(c)(3) entity; being a member of the
executive committee of Outcome Measures in Rheumatology, a member of
the American College of Rheumatology’s (ACR) annual meeting planning
committee, the Veterans Affairs Rheumatology field advisory committee,
chair of the ACR Meet the Professor Workshop and Study Group subcommittee,
and editor and director of the University of Alabama at Birmingham Cochrane
Musculoskeletal Group Satellite Center on network meta-analysis. Dr Curtis
reported receiving grants and consulting fees from Pfizer. Dr Saag reported
receiving research grants from Amgen, Ironwood/AstraZeneca, Horizon,
Merck, Swedish Orphan Biovitrum, and Takeda and consultant fees from
Abbott, Amgen, Ironwood/AstraZeneca, Bayer, Bristol-Myers Squibb,
Horizon, Lilly, Merck, Pfizer, Radius, Roche/Genentech, Swedish Orphan
Biovitrum, and Takeda.
1. Krebs EE, Gravely A, Nugent S, et al. Effect of opioid vs nonopioid
knee osteoarthritis pain: the SPACE randomized clinical trial. JAMA. 2018;319
(9):872-882. doi:10.1001/jama.2018.0899
2. Weingart SN, Gandhi TK, Seger AC, et al. Patient-reported medication
symptoms in primary care. Arch Intern Med. 2005;165(2):234-240. doi:10.1001
/archinte.165.2.234
3. Ytterberg SR, Mahowald ML, Woods SR. Codeine and oxycodone use in
patients with chronic rheumatic disease pain. Arthritis Rheum. 1998;41(9):1603-
1612. doi:10.1002/1529-0131(199809)41:9<1603::AID-ART10>3.0.CO;2-U
4. Mahowald ML, Singh JA, Majeski P. Opioid use by patients in an orthopedics
spine clinic. Arthritis Rheum. 2005;52(1):312-321. doi:10.1002/art.20784
In Reply Drs Wang and Macaulay seek details about SPACE eli-
gibility and nonpharmacological therapies. Patients were
screened in 3 stages—automated diagnosis search, struc-
tured telephone interview, physician chart review—and en-
rolled only if documentation from prior evaluations supported
the qualifying diagnosis at the reported pain location.1 They
suggest patients may not have received “sufficient” preenroll-
ment nonopioid therapy. Consistent with our objective to com-
pare medication approaches, eligibility criteria required fail-
ure of prior medications, but not nonpharmacological
therapies. Prestudy treatments included spine injections (28%)
or surgery (20%) and knee or hip injections (45%) or surgery
(34%). Nonpharmacological therapies during SPACE were pre-
sented in eTable 10 in Supplement 2.
jama.com

Dr Bigal suggests SPACE patients had less-severe pain than
patients prescribed opioids; however, studies suggest moder-
ate severity pain is typical at opioid initiation in trials and prac-
tice. In 5 trials2 of oxycodone controlled release (CR) spon-
sored by Purdue, mean baseline 24-hour pain (scale range,
0-10) was 6.4 (SD, 1.6). In a prospective observational study,3
baseline pain (average of past-month worst, past-month av-
erage, and current pain) for new regular opioid users was 6.1
(95% CI, 5.9-6.4). In SPACE,1 baseline pain calculated as aver-
age of past-week worst, past-week average, and current pain
was 6.1 (SD 1.4).
We disagree with Bigal’s assertions that SPACE disadvan-
taged the opioid group. He incorrectly claims groups had dif-
ferential access to multimodal care and depression treatment;
in fact, groups had the same access to nonpharmacological
therapies and received the same depression symptom moni-
toring and treatment referral protocol. He correctly notes non-
opioid patients received more individual medications; how-
ever, this doesn’t reflect differences in treatment intensity.
Because opioid drugs are similar but optimal dosing varies
widely among patients, opioid medication adjustments were
more often dosage or scheduling changes than medication
switches. He suggests patients on long-term opioids should have
been included; however, this would have been inconsistent with
the primary study question and would have required a pro-
longed washout period to avoid confounding by opioid discon-
tinuation syndromes.4
Dr Covington and colleagues suggest opioid patients were
undertreated, citing a Purdue-sponsored, 2-week, 3-group oxy-
codone CR trial that randomized 133 patients (and retained only
47.3%).5 We disagree. Mean improvements in pain-related func-
tion in the SPACE opioid group appear similar to those in the
oxycodone high-dose group, suggesting similar benefit. Rather
than targeting a prespecified dosage, SPACE targeted the regi-
men that optimally balanced analgesia and tolerability for each
patient, the best way to avoid undertreatment while retain-
ing patients. Although both groups improved, we concluded
results did not support opioid initiation for chronic back pain
or osteoarthritis pain because opioids did not demonstrate any
treatment advantages that offset their well-known risks of
death and addiction.
Bigal and Covington and colleagues are concerned about
inclusion of tramadol in the nonopioid treatment strategy. We
reanalyzed data excluding tramadol-treated patients from the
nonopioid group. At 12 months, nonopioid patients who never
received tramadol (n = 99) had a mean Brief Pain Inventory
(BPI) interference of 3.0 (SD, 2.5) and BPI severity of 3.3
(SD, 1.8). Main repeated-measures model results were un-
changed: over 12 months, pain-related function did not differ
between groups (P = .19) and the nonopioid group had better
pain intensity (P = .01). Regardless, SPACE findings should be
interpreted as applying to overall treatment strategies.
Dr Singh and colleagues regret SPACE did not focus on se-
rious analgesic-related harms. The extensive literature on non-
opioid analgesic harms was considered in selecting medica-
tions for SPACE patients, many of whom had drug class
contraindications. We identified only 2 serious analgesic-
related events in SPACE, illustrating why larger cohorts are bet-
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Letters
ter for studying uncommon harms. Common adverse events
may be viewed as minor from a clinician perspective, but are
relevant to patients’ experience of medication treatment.
We agree about the importance of individualized pain care
and that our results should not be overgeneralized. SPACE results
should be used to inform individualized decision making.
Erin E. Krebs, MD, MPH
Amy Gravely, MA
Siamak Noorbaloochi, PhD
Author Affiliations: Center for Chronic Disease Outcomes Research,
Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota.
Corresponding Author: Erin E. Krebs, MD, MPH, Minneapolis Veterans Affairs
Health Care System (152), 1 Veterans Dr, Minneapolis, MN 55417
(erin.krebs@va.gov).
Conflict of Interest Disclosures: The authors have completed and submitted
the ICMJE Form for Disclosure of Potential Conflicts of Interest. Drs Krebs and
Noorbaloochi reported receiving grants from the Veterans Affairs Health
Services Research and Development. No other disclosures were reported.
1. Krebs EE, Jensen AC, Nugent S, et al. Design, recruitment outcomes, and
sample characteristics of the Strategies for Prescribing Analgesics Comparative
Effectiveness (SPACE) trial. Contemp Clin Trials. 2017;62:130-139. doi:10.1016/j
.cct.2017.09.003
2. Portenoy RK, Farrar JT, Backonja MM, et al. Long-term use of
controlled-release oxycodone for noncancer pain: results of a 3-year registry
study. Clin J Pain. 2007;23(4):287-299. doi:10.1097/AJP.0b013e31802b582f
3. Turner JA, Shortreed SM, Saunders KW, LeResche L, Von Korff M. Association
of levels of opioid use with pain and activity interference among patients
initiating chronic opioid therapy: a longitudinal study. Pain. 2016;157(4):849-857.
doi:10.1097/j.pain.0000000000000452
4. Ballantyne JC, Sullivan MD, Kolodny A. Opioid dependence vs addiction:
a distinction without a difference? Arch Intern Med. 2012;172(17):1342-1343.
doi:10.1001/archinternmed.2012.3212
5. Roth SH, Fleischmann RM, Burch FX, et al. Around-the-clock,
controlled-release oxycodone therapy for osteoarthritis-related pain:
placebo-controlled trial and long-term evaluation. Arch Intern Med. 2000;160
(6):853-860. doi:10.1001/archinte.160.6.853
Varicose Veins and Deep Venous Thrombosis
To the Editor Using a large database of 212 984 patients with
varicose veins and comparing them with a matched cohort
without varicose veins, Dr Chang and colleagues found a
higher incidence of deep vein thrombosis (DVT) among
patients with varicose veins.1 The article does not state what
percentage of patients with a diagnosis of varicose veins had
received any surgical treatment for them. If the patients had
received surgery, what types of treatment had they under-
gone? This information is important because DVT is a compli-
cation following venous surgery, either endovenous or open
procedures, with a higher incidence following radiofre-
quency ablation than other modalities2,3 and also after con-
comitant phlebectomy.3
In a large population database (261 629 procedures over
a 10-year period from 2003-2013) from the United Kingdom,
the incidence of DVT continued to increase among patients
who had undergone venous treatment up to 1 year after the
procedure.2 In the study by Chang and colleagues, the hazard
ratio for developing a DVT was higher within the first year af-
ter the diagnosis of varicose veins was made. Could these find-
ings be related to the patients having undergone endovenous
or open surgery for their varicose veins?
(Reprinted) JAMA August 7, 2018 Volume 320, Number 5 509