Abstract
Purpose
The current epidemic of prescription opioid misuse has increased scrutiny of postoperative opioid prescribing. Some 6% to 8% of opioid-naïve patients undergoing noncancer procedures develop new persistent opioid use; however, it is unknown if a similar risk applies to patients with cancer. We sought to define the risk of new persistent opioid use after curative-intent surgery, identify risk factors, and describe changes in daily opioid dose over time after surgery.
Methods
Using a national data set of insurance claims, we identified patients with cancer undergoing curative-intent surgery from 2010 to 2014. We included melanoma, breast, colorectal, lung, esophageal, and hepato-pancreato-biliary/gastric cancer. Primary outcomes were new persistent opioid use (opioid-naïve patients who continued filling opioid prescriptions 90 to 180 days after surgery) and daily opioid dose (evaluated monthly during the year after surgery). Logistic regression was used to identify risk factors for new persistent opioid use.
Results
A total of 68,463 eligible patients underwent curative-intent surgery and filled opioid prescriptions. Among opioid-naïve patients, the risk of new persistent opioid use was 10.4% (95% CI, 10.1% to 10.7%). One year after surgery, these patients continued filling prescriptions with daily doses similar to chronic opioid users (P = .05), equivalent to six tablets per day of 5-mg hydrocodone. Those receiving adjuvant chemotherapy had modestly higher doses (P = .002), but patients with no chemotherapy still had doses equivalent to five tablets per day of 5-mg hydrocodone. Across different procedures, the covariate-adjusted risk of new persistent opioid use in patients receiving adjuvant chemotherapy was 15% to 21%, compared with 7% to 11% for those with no chemotherapy.
Conclusion
New persistent opioid use is a common iatrogenic complication in patients with cancer undergoing curative-intent surgery. This problem requires changes to prescribing guidelines and patient counseling during the surveillance and survivorship phases of care.
INTRODUCTION
Pain management is a crucial dimension of patient-centered cancer care.1,2 However, the recent increase in prescription opioid misuse, abuse, and overdose fatalities has highlighted the dangers of these medications.3-5 In 2015, 11.5 million adult Americans reported misusing prescription opioids, and 1.9 million met diagnostic criteria for prescription opioid abuse.6 Patients with cancer undergoing curative-intent therapies may be particularly vulnerable to opioid misuse or dependence because of psychological distress from their diagnosis, multiple invasive procedures, pain related to adjuvant therapies, and uncoordinated prescribing from multiple providers.1,7,8
Although guidelines exist for prescribing opioids to patients with cancer with advanced disease,1,7 little is known about opioid use among patients undergoing surgery for early-stage cancer. Previously opioid-naïve patients may convert to chronic opioid use, which is associated with substantial morbidity and mortality.3,4,9,10 Recent studies have evaluated the risk of new persistent opioid use after noncancer surgery11-13; however, the risk of new persistent opioid use after curative-intent cancer surgery is unknown.
To understand the risk of new persistent opioid use in this population, we performed a retrospective cohort study of privately insured patients undergoing curative-intent cancer surgery in the United States. We sought to define the risk of new persistent opioid use after curative-intent surgery, identify patient-level risk factors for new persistent opioid use, and describe the trend of daily opioid dose over time during the year after surgery.
METHODS
Data Source
We identified eligible patients by examining insurance claims from the Truven Health Marketscan Research Databases, including the Commercial Claims and Encounters Database and the Medicare Supplemental and Coordination of Benefits Database.14 These databases are obtained from employer health plans and include employees, Consolidated Omnibus Budget Reconciliation Act continuees, early retirees, Medicare-eligible retirees with employer-provided Medicare Supplemental plans, and dependents. The University of Michigan Institutional Review Board determined this study was exempt because all data were de-identified.
Study Sample
In this retrospective cohort study, we included patients age ≥ 18 years who underwent curative-intent surgery for a cancer diagnosis between January 1, 2010 and June 30, 2014 and filled an opioid prescription attributed to surgery. Figure 1 illustrates the study selection criteria. To ensure accurate assessment of preoperative and postoperative opioid use, we included only patients with continuous insurance enrollment for 1 year before and after surgery. To minimize confounding from postoperative complications, we excluded patients with hospital admissions > 30 days or a subsequent procedure within 180 days. In addition, we excluded patients discharged to home hospice care and those who died during their index hospitalization.
Fig 1.
Study cohort and sample criteria. Patients with cancer who underwent curative-intent surgery from January 1, 2010 to June 30, 2014 were included if they met the following criteria: age ≥ 18 years, continuous insurance enrollment from 1 year before surgery to 1 year after surgery, filled an opioid prescription attributable to surgery (between 30 days before surgery and 14 days after discharge). We also specifically excluded patients with an additional operation within 180 days, hospital length of stay > 30 days, and those who died during their index admission or were discharged to home hospice.
We selected patients undergoing the following curative-intent procedures: lumpectomy, mastectomy, wide local excision, colectomy, rectal resection, pancreatectomy, liver resection, gastric resection, esophagectomy, and lung resection. Patients were included if they had a claim with an eligible operation that was also associated with a cancer diagnosis. Procedures were identified using Current Procedural Terminology codes (Appendix Table A1, online only). Cancer diagnoses were identified using International Statistical Classification of Diseases and Related Health Problems, Ninth Revision codes (Appendix Table A2, online only).
Definitions of Opioid Prescriptions and Prescribing Patterns
Opioid prescription data were obtained from pharmacy claims and converted to oral morphine equivalents (OME) for comparison.15 Similar to previous work,13 we attributed an opioid prescription to surgery if it was filled between 30 days before surgery and 14 days after discharge. This window accounts for patients who developed cancer pain requiring opioids in the month before surgery and surgeons who provide patients with preoperative opioid prescriptions intended for postoperative use. For opioid prescriptions attributed to surgery, we evaluated two prescribing patterns: prescriptions filled by patients during the 30 days before surgery (preoperative opioid prescriptions) and quantity prescribed (OME) for the opioid prescription closest to the date of surgery (initial opioid prescribed).
Patients were defined as opioid-naïve if they filled no opioid prescriptions between 12 months and 31 days before surgery, a definition used in previous studies of surgical patients.11,13 Chronic opioid users were defined as patients who filled opioid prescriptions with at least 120 days supply between 12 months and 31 days before surgery or filled at least three opioid prescriptions in the three consecutive months before surgery. This level of opioid use was selected because it is associated with an increased risk of opioid overdose mortality.4 Intermittent opioid users were defined as those who filled opioid prescriptions less frequently than this threshold.
Outcomes
This study had two primary outcomes: new persistent opioid use, which was defined as previously opioid-naïve patients who filled an opioid prescription attributed to surgery, then filled at least one additional opioid prescription between 90 and 180 days after surgery; and daily opioid dose during the year after surgery, which was calculated every 30 days by dividing the quantity prescribed (OME) by the days supplied. Like other studies of surgical patients,11-13,16 we chose this definition of new persistent opioid use because normal surgical recovery would be expected by 90 days after surgery. This definition is more conservative than the 60-day threshold used by the International Association for the Study of Pain.17
Patient Covariates
We included information on age, sex, household income on the basis of metropolitan statistical area code, and insurance type. Data describing race and ethnicity are not available in the Truven Marketscan data sets. We used International Statistical Classification of Diseases and Related Health Problems, Ninth Revision, and Current Procedural Terminology codes to identify patients who underwent neoadjuvant chemotherapy or radiation during the 12 months before surgery and patients who underwent adjuvant chemotherapy or radiation during the 180 days after surgery (Appendix Table A3, online only). Comorbidities were captured using the Elixhauser comorbidity score.18 The Agency of Healthcare Research and Quality Clinical Classification System was used to assess for psychiatric diagnoses, including mood disorders, personality disorders, and substance use disorders. Substance use disorders included heroin use and nonmedical use of prescription opioids. This accounts for patients potentially misclassified as opioid-naïve by our definition, which is based on insurance claims for opioid prescriptions.
Statistical Analyses
Patients were stratified into four groups on the basis of perioperative opioid use: opioid-naïve patients who did not develop new persistent opioid use, opioid-naïve patients who developed new persistent opioid use, intermittent opioid users, and chronic opioid users. Opioid-naïve patients who developed new persistent use were further stratified by timing of chemotherapy. We then calculated the mean daily opioid dose for each group at 30-day intervals from 1 year before surgery to 1 year after surgery. Mixed linear models were used to adjust mean daily opioid dose for age, sex, preoperative opioid prescriptions, initial opioid prescribed, procedure type, neoadjuvant and adjuvant chemotherapy/radiation, psychiatric diagnoses, Elixhauser comorbidity score, insurance type, and median income. Daily opioid doses among patient groups were then compared using a χ2 test.
Multivariable logistic regression was used to identify variables associated with new persistent opioid use. Because our initial regression demonstrated a significant interaction between procedure type and timing of chemotherapy, a separate regression was performed for each procedure type. Using these models, we calculated the covariate-adjusted risk of new persistent opioid use for each procedure type stratified by timing of chemotherapy.
Analysis was conducted using SAS version 9.4 (SAS Institute, Cary, NC) Because of the large number of patients and statistical tests, two-sided P values < .01 were considered statistically significant. For our multivariable analyses, we evaluated for multicollinearity using variance inflation factors and found no significant multicollinearity in the variables included in our models. For logistic regression models, goodness of fit was evaluated using the c statistic and Hosmer-Lemeshow test.
Sensitivity Analysis
Because our initial analysis demonstrated patients receiving preoperative opioid prescriptions had a higher risk of new persistent opioid use, we performed a sensitivity analysis to evaluate the effect of these patients on the study results. Specifically, we excluded patients with preoperative opioid prescriptions from the cohort, then repeated our logistic regression models and recalculated covariate-adjusted rates of new persistent opioid use for each procedure type. These results were then compared with those including patients with preoperative opioid prescriptions.
RESULTS
During the study period, 68,463 patients underwent curative-intent surgery and were included in the analysis (Fig 1). Of these, 39,877 (58%) were opioid-naïve, 16,063 (23%) were intermittent opioid users, and 12,523 (18%) were chronic opioid users. Among previously opioid-naïve patients, 4,159 or 10% (95% CI, 10.1% to 10.7%) developed new persistent opioid use after curative-intent surgery. Table 1 lists characteristics of opioid-naïve patients stratified by whether they developed new persistent opioid use or not. Patients with new persistent opioid use were more likely to have received adjuvant chemotherapy (33% v 16%) and more likely to have filled preoperative opioid prescriptions (26% v 20%) but were initially prescribed the same quantity of opioids (200 ± 150 OME for both groups, equivalent to 40 tablets of 5-mg hydrocodone).
Table 1.
Characteristics of Opioid-Naïve Patients
For comparison, we also examined patients who did not fill a surgical opioid prescription. Compared with opioid-naïve patients who filled opioid prescriptions, patients with no opioid prescriptions were more likely to have undergone wide local excision for melanoma (38% v 17%) and less likely to have undergone lumpectomy/mastectomy (38% v 56%). They also had lower rates of adjuvant chemotherapy (8% v 18%) and radiation (4% v 24%) and higher rates of neoadjuvant chemotherapy (9% v 5%) and radiation (16% v 1%). They had similar rates of substance use disorders (4% v 5%).
Daily Opioid Dose During the Year After Surgery
Figure 2A shows the trajectory of mean daily opioid dose with patients stratified by perioperative opioid use. Mean daily opioid dose was adjusted for patient-level factors using mixed linear models. Three months after surgery, patients with new persistent opioid use continued to fill opioid prescriptions with high daily opioid doses, equivalent to six tablets per day of 5-mg hydrocodone (25 OME). Daily opioid doses remained at this high level even 1 year after surgery. When daily opioid doses were compared among groups, new persistent opioid users had similar daily doses compared with intermittent and chronic opioid users (P = .05).
Fig 2.
(A) Trajectory of daily opioid dose stratified by perioperative opioid use. Mean daily opioid dose for each group was calculated every 30 days from 1 year before surgery to 1 year after surgery, while adjusting for preoperative opioid prescriptions, initial opioid prescribed, procedure type, adjuvant and neoadjuvant therapy, and patient characteristics. One year after surgery, patients who developed new persistent opioid use continued filling opioid prescriptions with daily doses similar to intermittent and chronic opioid users (P = .05). (B) Trajectory of daily opioid dose stratified by timing of chemotherapy. Patients who developed new persistent opioid use and received adjuvant chemotherapy had higher daily opioid doses compared with those who received no chemotherapy (P = .002). All groups, however, continued filling prescriptions with high daily doses, equivalent to five to six tablets per day of 5-mg hydrocodone. OME, oral morphine equivalent.
Figure 2B shows patients who developed new persistent opioid use stratified by timing of chemotherapy. Those who received adjuvant chemotherapy filled prescriptions with modestly higher daily doses compared with those who did not (P = .002). This difference, however, was the equivalent of less than one tablet per day of 5-mg hydrocodone. All groups continued filling prescriptions with high daily doses 1 year after surgery, equivalent to five to six tablets per day of 5-mg hydrocodone (25 to 30 OME).
Risk Factors for New Persistent Opioid Use
Table 2 lists results from the logistic regression models for new persistent opioid use. Adjuvant chemotherapy was the only variable significantly associated with new persistent opioid use across all procedures (odds ratios [95% CI]: breast 2.4 [2.2 to 2.7]; melanoma 2.6 [1.5 to 4.5]; colorectal 2.3 [1.9 to 2.8]; hepato-pancreato-biliary/gastric 2.2 [1.5 to 3.3]; thoracic 2.1 [1.7 to 2.7]). Adjuvant radiation was a significant risk factor for melanoma (4.7 [2.4 to 9.2]) and thoracic (2.1 [1.4 to 3.0]) procedures. In addition, patients who filled preoperative opioid prescriptions had a significantly higher risk of new persistent opioid use for breast (1.2 [1.1 to 1.3]), melanoma (1.5 [1.2 to 1.9]), colorectal (2.1 [1.7 to 2.7]), and thoracic (1.7 [1.3 to 2.3]) procedures. In contrast, the initial quantity of opioid prescribed was not significant for any procedures. Age, sex, neoadjuvant chemotherapy/radiation, and insurance type had no consistent association with new persistent opioid use.
Table 2.
Logistic Regression Models for New Persistent Opioid Use
Effect of Procedure and Adjuvant Chemotherapy
Figure 3 shows the adjusted risk of new persistent opioid use across different procedures with 95% CIs and patients stratified by timing of chemotherapy. For each procedure group, the risk of new persistent opioid use was adjusted for patient-level factors using logistic regression models (Table 2). Patients undergoing adjuvant chemotherapy had a significantly higher risk of new persistent opioid use for all procedures (range, 15% to 21%), but those who did not receive adjuvant chemotherapy were still at risk (7% to 11%).
Fig 3.
Risk of new persistent opioid use stratified by procedure and timing of chemotherapy. We calculated the risk of new persistent opioid use by procedure with patients stratified by timing of chemotherapy. This figure shows 95% CIs with the risk of new persistent opioid use adjusted for preoperative opioid prescriptions, initial opioid prescribed, timing of chemotherapy, and patient characteristics. Patients receiving adjuvant chemotherapy had a higher risk of new persistent opioid use (15% to 21%), but those who received no chemotherapy were still at risk (7% to 11%). HPB, hepato-pancreato-biliary.
Sensitivity Analysis
After excluding patients with preoperative opioid prescriptions (n = 8,091), the overall risk of new persistent opioid use was 9.7% (95% CI, 9.4% to 10.1%), which was not substantially different from the initial cohort including these patients (10.4%; 95% CI, 10.1% to 10.7%). In addition, excluding these patients did not substantially affect the results of the logistic regression models (Appendix Table A4, online only) or the covariate-adjusted rates of new persistent opioid use (Appendix Fig A1, online only).
DISCUSSION
This study has two major findings. First, we found that 10% of opioid-naïve patients with cancer undergoing curative-intent surgery develop new persistent opioid use. These patients continue filling prescriptions with high daily doses even 1 year after surgery, equivalent to six tablets per day of 5-mg hydrocodone. This dose is similar to intermittent and chronic opioid users, suggesting that patients with new persistent opioid use may transition to chronic opioid use. Second, we found that adjuvant chemotherapy was a strong risk factor for new persistent opioid use for all procedures; however, new persistent opioid use was still common (7% to 11%) among patients with no adjuvant chemotherapy.
Similar to previous studies of surgical patients, we report the risk of new persistent opioid use among previously opioid-naïve patients.11-13,16 However, these studies were limited in that they did not focus on, or specifically excluded, patients with cancer. Our findings show the risk of new persistent opioid use for patients with cancer undergoing curative-intent surgery was 10%, which is higher than the 6% to 8% reported for noncancer surgery.11-13,16 Neurotoxicity from adjuvant chemotherapy may contribute to this increased risk, yet even patients who did not receive adjuvant chemotherapy had a 7% to 11% risk of new persistent opioid use. In addition, our study also describes changes in daily opioid dose after surgery, which has not been reported in previous studies of postoperative opioid use.11-13,16 We demonstrated patients with new persistent opioid use continue filling prescriptions with daily doses similar to chronic opioid users 1 year after surgery, equivalent to six tablets per day of 5-mg hydrocodone.
Patients with cancer who undergo curative-intent surgery have several potential reasons for persistently requiring opioids. Persistent postsurgical pain is a possible contributor, affecting 13% to 50% of patients undergoing mastectomy or thoracotomy.19,20 These patients are unlikely to achieve relief from opioids, however, and should be considered for nonopioid analgesics, behavioral therapies, or more aggressive procedural interventions.21-23 Neurotoxicity from adjuvant chemotherapy and radiation may also play a role and causes persistent pain in 13% to 26% of patients.20,24-27 In addition, 33% of patients develop new persistent opioid use after curative-intent chemoradiation.28 Other medications administered with adjuvant chemotherapy, such as aromatase inhibitors and granulocyte colony-stimulating factors, can also cause pain.29,30 The findings of this study, however, demonstrate that adjuvant chemotherapy does not account for all new persistent opioid use after curative-intent surgery. Furthermore, pain from chemotherapy-induced peripheral neuropathy is difficult to treat given the relative lack of effective pharmacologic therapies. Although opioids and gabapentin are often used to treat pain from chemotherapy-induced peripheral neuropathy, this practice is not supported by evidence,31 and duloxetine is the only medication with demonstrated efficacy for these patients.32 Another potential contributing factor is uncoordinated prescribing from multiple providers. Patients with cancer require multidisciplinary care, often from physicians in different health systems, and receive opioids from physicians who are accustomed to prescribing large quantities of opioids.33,34
New persistent opioid use after curative-intent surgery could be addressed by several strategies. First, further study is needed to develop evidence-based guidelines and reduce excessive opioid prescribing.35 Further study is also needed to develop effective screening tools to identify patients at risk for new persistent opioid use. For example, psychosocial factors are known to drive postoperative opioid consumption,36,37 and patients with cancer report high levels of psychosocial distress.38-40 This could contribute to higher rates of opioid use among patients undergoing curative-intent surgery. Alcoholism and tobacco use have also been associated with increased opioid use in patients with cancer.41
In addition, surgeons need to play a more active role in counseling patients on postoperative pain, potential risks of opioids, and minimizing postoperative opioid use.42 Given the high risk of new persistent opioid use in this population, physicians should consider universal precautions when prescribing opioids in this setting, including educating patients on safe use, storage, and disposal. More scrutiny is also needed on the use of opioids to treat neuropathic pain caused by adjuvant chemotherapy and persistent postsurgical pain, which is frequently unresponsive to opioids and may be better treated with nonopioid medications.21-23 Although a recent Cochrane review found insufficient evidence to evaluate the potential harm of treating neuropathic pain with opioids,43 the high rate of new persistent opioid use reported in our study suggests the risks of opioid use may outweigh the benefits for patients with cancer undergoing curative-intent surgery.
This study was limited by several factors. First, it only evaluated adults with continuous enrollment in employer-based insurance and did not adjust for race or ethnicity. These factors limit the generalizability of our findings. We did, however, adjust for income and insurance type in our analysis. This study also does not evaluate opioid consumption or the indications for opioid prescriptions. It is possible patients were filling prescriptions for pain unrelated to their cancer diagnosis. Previous work, however, suggests the rate of new persistent opioid use in nonsurgical populations is only 0.4%.13 In addition, our analysis adjusted for multiple potential contributing factors, including chemotherapy and psychiatric diagnoses.
Another limitation is the inability of claims data to capture the use of nonopioid analgesics, such as acetaminophen and ibuprofen, which are frequently filled over the counter. Nevertheless, given the high rate of new persistent opioid use reported in this study, all physicians should consider more aggressive use of nonopioid analgesics to minimize opioid use. This study also did not specifically adjust for postoperative complications. Nonetheless, we excluded patients with length of stay > 30 days or reoperation within 180 days, which should provide a more conservative estimate of opioid use. Finally, the database did not include information needed to identify which physician specialties were providing opioid prescriptions. However, given the high rate of new persistent opioid use reported in this study, all physicians caring for patients with cancer after curative-intent surgery should consider more judicious prescribing of opioids.
In conclusion, we found that 10% of patients with cancer develop new persistent opioid use after curative-intent surgery. These patients continue filling opioid prescriptions 1 year after surgery, with daily opioid doses similar to chronic opioid users. This iatrogenic complication is a substantial burden on cancer survivors and requires changes to prescribing guidelines, physician education, and patient counseling during the surveillance and survivorship phases of care.
Appendix
Fig A1.
Risk of new persistent opioid use stratified by procedure and timing of chemotherapy (excluding patients with preoperative opioid prescriptions within 30 days before surgery). Patients who received preoperative opioid prescriptions (within 30 days before surgery) were excluded from this analysis. We calculated the risk of new persistent opioid use by procedure with patients stratified by timing of chemotherapy. This figure shows 95% CIs with the risk of new persistent opioid use adjusted for initial opioid prescribed, timing of chemotherapy, and patient characteristics. Patients receiving adjuvant chemotherapy had a higher risk of new persistent opioid use (14% to 20%), but those who received no chemotherapy were still at risk (6% to 11%).
Table A1.
CPT Codes for Curative-Intent Surgery
Table A2.
ICD-9 Codes for Cancer Diagnoses
Table A3.
CPT and ICD-9 Codes for Chemotherapy and Radiation Therapy
Table A4.
Logistic Regression Models (Excluding Patients With Preoperative Opioid Prescriptions Within 30 Days Before Surgery)
Footnotes
Listen to the podcast by Dr Bruera at ascopubs.org/jco/podcasts
Supported by the National Research Service Award postdoctoral fellowship (No. 5T32 CA009672-23) (J.S.-J.L.), the National Institute on Drug Abuse (Research Project Grant No. R01 DA042859) (C.M.B., M.J.E., and J.F.W.), and the Michigan Department of Health and Human Services (C.M.B., M.J.E., and J.F.W.).
The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Michigan Department of Health and Human Services.
AUTHOR CONTRIBUTIONS
Conception and design: Jay Soong-Jin Lee, Anthony L. Edelman, Chad M. Brummett, Michael J. Englesbe, Jennifer F. Waljee, Lesly A. Dossett
Financial support: Chad M. Brummett
Provision of study materials or patients: Chad M. Brummett
Collection and assembly of data: Jay Soong-Jin Lee, Hsou Mei Hu
Data analysis and interpretation: Jay Soong-Jin Lee, Hsou Mei Hu, Chad M. Brummett, Michael J. Englesbe, Jennifer F. Waljee, Jeffrey B. Smerage, Jennifer J. Griggs, Hari Nathan, Jacqueline S. Jeruss
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
New Persistent Opioid Use Among Patients With Cancer After Curative-Intent Surgery
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc.
Jay Soong-Jin Lee
No relationship to disclose
Hsou Mei Hu
No relationship to disclose
Anthony L. Edelman
Employment: Anesthesia Associates of Ann Arbor
Leadership: Anesthesia Associates of Ann Arbor
Stock or Other Ownership: Anesthesia Associates of Ann Arbor
Chad M. Brummett
Research Funding: Neuros Medical
Patents, Royalties, Other Intellectual Property: Dexmedetomidine for peripheral nerve blocks
Expert Testimony: Medical malpractice expert
Michael J. Englesbe
No relationship to disclose
Jennifer F. Waljee
No relationship to disclose
Jeffrey B. Smerage
Research Funding: Merck
Jennifer J. Griggs
No relationship to disclose
Hari Nathan
No relationship to disclose
Jacqueline S. Jeruss
No relationship to disclose
Lesly A. Dossett
No relationship to disclose
REFERENCES
- 1.Swarm RA, Abernethy AP, Anghelescu DL, et al. : Adult cancer pain. J Natl Compr Canc Netw 11992-1022, 2013 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Temel JS, Greer JA, Muzikansky A, et al. : Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med 363:733-742, 2010 [DOI] [PubMed] [Google Scholar]
- 3.Bohnert AS, Valenstein M, Bair MJ, et al. : Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA 305:1315-1321, 2011 [DOI] [PubMed] [Google Scholar]
- 4.Bohnert AS, Ilgen MA, Trafton JA, et al. : Trends and regional variation in opioid overdose mortality among Veterans Health Administration patients, fiscal year 2001 to 2009. Clin J Pain 30:605-612, 2014 [DOI] [PubMed] [Google Scholar]
- 5.Kantor ED, Rehm CD, Haas JS, et al. : Trends in prescription drug use among adults in the United States from 1999-2012. JAMA 314:1818-1831, 2015 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Center for Behavioral Health Statistics and Quality: 2015 National Survey on Drug Use and Health: Detailed Tables. https://www.samhsa.gov/data/sites/default/files/NSDUH-DetTabs-2015/NSDUH-DetTabs-2015/NSDUH-DetTabs-2015.htm.
- 7.Portenoy RK: Treatment of cancer pain. Lancet 377:2236-2247, 2011 [DOI] [PubMed] [Google Scholar]
- 8.Tan PD, Barclay JS, Blackhall LJ: Do palliative care clinics screen for substance abuse and diversion? Results of a national survey. J Palliat Med 18:752-757, 2015 [DOI] [PubMed] [Google Scholar]
- 9.Compton WM, Jones CM, Baldwin GT: Relationship between nonmedical prescription-opioid use and heroin use. N Engl J Med 374:154-163, 2016 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Kern DM, Zhou S, Chavoshi S, et al. : Treatment patterns, healthcare utilization, and costs of chronic opioid treatment for non-cancer pain in the United States. Am J Manag Care 21:e222-e234, 2015 [PubMed] [Google Scholar]
- 11.Clarke H, Soneji N, Ko DT, et al. : Rates and risk factors for prolonged opioid use after major surgery: Population based cohort study. BMJ 348:g1251, 2014 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Soneji N, Clarke HA, Ko DT, et al. : Risks of developing persistent opioid use after major surgery. JAMA Surg 151:1083-1084, 2016 [DOI] [PubMed] [Google Scholar]
- 13.Brummett CM, Waljee JF, Goesling J, et al. : New persistent opioid use after minor and major surgical procedures in US adults. JAMA Surg 152:e170504, 2017 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Hansen L: The Truven Health MarketScan Databases for life sciences researchers. Ann Arbor, Michigan, Truven Health Analytics, 2017. [Google Scholar]
- 15.Gammaitoni AR, Fine P, Alvarez N, et al. : Clinical application of opioid equianalgesic data. Clin J Pain 19:286-297, 2003 [DOI] [PubMed] [Google Scholar]
- 16.Alam A, Gomes T, Zheng H, et al. : Long-term analgesic use after low-risk surgery: A retrospective cohort study. Arch Intern Med 172:425-430, 2012 [DOI] [PubMed] [Google Scholar]
- 17.Kehlet H, Rathmell JP: Persistent postsurgical pain: The path forward through better design of clinical studies. Anesthesiology 112:514-515, 2010 [DOI] [PubMed] [Google Scholar]
- 18.van Walraven C, Austin PC, Jennings A, et al. : A modification of the Elixhauser comorbidity measures into a point system for hospital death using administrative data. Med Care 47:626-633, 2009 [DOI] [PubMed] [Google Scholar]
- 19.Bayman EO, Brennan TJ: Incidence and severity of chronic pain at 3 and 6 months after thoracotomy: Meta-analysis. J Pain 15:887-897, 2014 [DOI] [PubMed] [Google Scholar]
- 20.Gärtner R, Jensen MB, Nielsen J, et al. : Prevalence of and factors associated with persistent pain following breast cancer surgery. JAMA 302:1985-1992, 2009 [DOI] [PubMed] [Google Scholar]
- 21.Bostick GP, Toth C, Carr EC, et al. : Physical functioning and opioid use in patients with neuropathic pain. Pain Med 16:1361-1368, 2015 [DOI] [PubMed] [Google Scholar]
- 22.Gaskell H, Derry S, Stannard C, et al. : Oxycodone for neuropathic pain in adults. Cochrane Database Syst Rev 7:CD010692, 2016 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Kehlet H, Jensen TS, Woolf CJ: Persistent postsurgical pain: Risk factors and prevention. Lancet 367:1618-1625, 2006 [DOI] [PubMed] [Google Scholar]
- 24.Jung BF, Herrmann D, Griggs J, et al. : Neuropathic pain associated with non-surgical treatment of breast cancer. Pain 118:10-14, 2005 [DOI] [PubMed] [Google Scholar]
- 25.Land SR, Kopec JA, Cecchini RS, et al. : Neurotoxicity from oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: NSABP C-07. J Clin Oncol 25:2205-2211, 2007 [DOI] [PubMed] [Google Scholar]
- 26.Mols F, Beijers T, Lemmens V, et al. : Chemotherapy-induced neuropathy and its association with quality of life among 2- to 11-year colorectal cancer survivors: Results from the population-based PROFILES registry. J Clin Oncol 31:2699-2707, 2013 [DOI] [PubMed] [Google Scholar]
- 27. Whelan TJ, Levine M, Julian J, et al: The effects of radiation therapy on quality of life of women with breast carcinoma: results of a randomized trial. Ontario Clinical Oncology Group. Cancer 88:2260-2266, 2000. [PubMed] [Google Scholar]
- 28.Kwon JH, Hui D, Chisholm G, et al. : Predictors of long-term opioid treatment among patients who receive chemoradiation for head and neck cancer. Oncologist 18:768-774, 2013 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Crew KD, Greenlee H, Capodice J, et al. : Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. J Clin Oncol 25:3877-3883, 2007 [DOI] [PubMed] [Google Scholar]
- 30.Kirshner JJ, Heckler CE, Janelsins MC, et al. : Prevention of pegfilgrastim-induced bone pain: A phase III double-blind placebo-controlled randomized clinical trial of the University of Rochester Cancer Center Clinical Community Oncology Program Research Base. J Clin Oncol 30:1974-1979, 2012 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Pachman DR, Watson JC, Lustberg MB, et al. : Management options for established chemotherapy-induced peripheral neuropathy. Support Care Cancer 22:2281-2295, 2014 [DOI] [PubMed] [Google Scholar]
- 32.Hershman DL, Lacchetti C, Dworkin RH, et al. : Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 32:1941-1967, 2014 [DOI] [PubMed] [Google Scholar]
- 33.http://www.chrt.org/publication/uncoordinated-prescription-opioid-use-in-michigan/ Dreyer T, Rontal R, Gabriel K, et al: Uncoordinated Prescription Opioid Use in Michigan. [Google Scholar]
- 34. doi: 10.1093/pm/pnx027. Weiner SG, Baker O, Rodgers AF, et al: Opioid prescriptions by specialty in Ohio, 2010-2014. Pain Med 10.1093/pm/pnx027 [epub ahead of print on March 6, 2017] [DOI] [PubMed] [Google Scholar]
- 35. doi: 10.1097/SLA.0000000000002198. Hill MV, Stucke RS, McMahon ML, et al: An educational intervention decreases opioid prescribing after general surgical operations. Ann Surg 10.1097/SLA.0000000000002198 [epub ahead of print on March 6, 2017] [DOI] [PubMed] [Google Scholar]
- 36.Brummett CM, Janda AM, Schueller CM, et al. : Survey criteria for fibromyalgia independently predict increased postoperative opioid consumption after lower-extremity joint arthroplasty: A prospective, observational cohort study. Anesthesiology 119:1434-1443, 2013 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Janda AM, As-Sanie S, Rajala B, et al. : Fibromyalgia survey criteria are associated with increased postoperative opioid consumption in women undergoing hysterectomy. Anesthesiology 122:1103-1111, 2015 [DOI] [PubMed] [Google Scholar]
- 38.Fann JR, Ell K, Sharpe M: Integrating psychosocial care into cancer services. J Clin Oncol 30:1178-1186, 2012 [DOI] [PubMed] [Google Scholar]
- 39.Mitchell AJ, Chan M, Bhatti H, et al. : Prevalence of depression, anxiety, and adjustment disorder in oncological, haematological, and palliative-care settings: A meta-analysis of 94 interview-based studies. Lancet Oncol 12:160-174, 2011 [DOI] [PubMed] [Google Scholar]
- 40.Zabora J, BrintzenhofeSzoc K, Curbow B, et al. : The prevalence of psychological distress by cancer site. Psychooncology 10:19-28, 2001 [DOI] [PubMed] [Google Scholar]
- 41.Dev R, Parsons HA, Palla S, et al. : Undocumented alcoholism and its correlation with tobacco and illegal drug use in advanced cancer patients. Cancer 117:4551-4556, 2011 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42. doi: 10.1016/j.jpain.2015.12.008. Chou R, Gordon DB, de Leon-Casasola OA, et al: Management of postoperative pain: A clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain 17:131-157, 2016 [Erratum: J Pain 17:508-510, 2016] [DOI] [PubMed] [Google Scholar]
- 43.Cooper TE, Chen J, Wiffen PJ, et al. : Morphine for chronic neuropathic pain in adults. Cochrane Database Syst Rev 5:CD011669, 2017 [DOI] [PMC free article] [PubMed] [Google Scholar]