JOURNAL OF PALLIATIVE MEDICINE Volume 17, Number 9, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/jpm.2013.0593
Original Articles
Response to Pain Management among Patients with Active Cancer, No Evidence of Disease, or Chronic Nonmalignant Pain in an Outpatient Palliative Care Clinic Cara Jennings, MD,1,2 Brian Cassel, PhD,1,2 Devon Fletcher, MD,1,2 Aiping Wang,3 Kellie J. Archer, PhD,3 Nevena Skoro,1 Leanne Yanni, MD,4 and Egidio Del Fabbro, MD1,2
Abstract
Background: Outpatient palliative care clinics may be required to manage patients not typically seen by palliative care. These include patients treated for cancer who no longer have evidence of disease (NED) and patients with chronic pain but no life-limiting illness (NLLI). Treatment response may differ among these groups. Objectives: Our aim was to determine treatment response by change in pain scores and morphine equivalent daily dose (MEDD) between initial visit and first follow-up in patients with active cancer (AC), NED, and those with NLLI. Methods: A retrospective review of 143 consecutive outpatients referred to a clinic staffed by the palliative care program was conducted. Pain treatment response was defined by a ‡ 2 point difference on the Numerical Rating Scale (NRS) or ‡ 30% reduction from baseline score. Results: Ninety-four patients had pain scores at both initial and follow-up visits after a median of 29.0 days. Fifty percent had AC, 27% NED, and 23% NLLI. Mean (standard deviation [SD]) pain scores at baseline were not significantly different among AC 6.0 (2.5), NED 5.6 (2.5), and NLLI 6.8 (2.2) patients ( p = 0.22), but were significant at follow-up between AC 4.2 (2.7) and NLLI 6.0 (2.6) ( p = 0.03) groups. The percent of responders differed significantly between AC 57.4% and NED 20% groups ( p = 0.002). MEDD increased by 17.2 mg in AC, 40.9 mg in NED, and 18.1mg in NLLI patients ( p = 0.88).Benzodiazepine use was significantly more frequent in the NLLI group than the AC ( p = 0.025) and NED ( p = 0.002) groups. Conclusions: Although median pain scores improved at follow-up, less than half of patients were responders. Patients with AC had a significantly better response rate than NED patients and a lower pain score than NLLI patients at follow-up.
Introduction
P
alliative care programs are becoming more common, with 85% of large hospitals offering inpatient palliative care services.1 Despite the growth in palliative care programs, there is still a gap between the availability of inpatient and outpatient care2 and only 59% of National Cancer Institute (NCI)-designated cancer centers have an outpatient palliative care clinic.3 These clinics have improved a number of clinical outcomes including patient and caregiver satisfaction,4 symptoms,5 and survival.6 The structure of clinics may vary depending on the number of days per week they are
staffed, the referral sources, the main patient populations they serve, and the administrative home of the program. The Virginia Commonwealth University (VCU) palliative care program within the Division of Oncology, Hematology, and Palliative care staffs a palliative care clinic at Massey Cancer Center. Although most of the patients referred to the clinic have active cancer (AC), other groups are also referred including patients with no evidence of disease (NED) who have completed treatment for cancer, and patients with chronic pain but no life-limiting illness (NLLI).The expertise of the palliative care team in pain management and the absence of survivorship or chronic pain clinics within the
1 Massey Cancer Center, 2Division of Hematology, Oncology, and Palliative Care, Department of Internal Medicine, 3Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia. 4 Palliative Medicine, Bon Secours Richmond Health System, Richmond, Virginia. Accepted March 7, 2013.
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PAIN RESPONSE AMONG GROUPS IN AN AMBULATORY CLINIC
institution are among the factors driving the ‘‘mixed’’ referrals to this ambulatory clinic. The objective of the study was to evaluate the response to pain management among the different patient groups seen in the palliative care clinic. Changes in pain scores and the morphine equivalent daily dose (MEDD) were measured from the initial visit to first follow-up. We hypothesized that patients with AC would derive greater benefit from outpatient palliative care, compared with those with NED or NLLI. Design Patient selection
A retrospective chart review of 143 consecutive patients referred to the VCU palliative care clinic from July 1, 2009 to June 30, 2012 was conducted. One hundred four patients had an initial visit and follow-up after a median of 29.0 days. Among these 104, 102 had MEDD documented and 94 had pain scores recorded at both initial and follow-up visits. Analysis was restricted to patients having both initial and follow-up values. The inception date was chosen because the clinic came to be fully staffed with a board-certified palliative care physician and palliative care fellows, and an electronic health record was implemented. Prior to this date patient records were not easily accessible. The end date for the study was chosen because after that date, the clinic routinely accepted referrals only for patients with a life-limiting illness. The study was approved by the VCU Institutional Review Board. Setting
The palliative care clinic within the NCI-designated Massey Cancer Center at VCU operates 2 days a week with a palliative care physician, a registered nurse, and palliative care fellows. In addition, psychology, occupational therapy, social work, and chaplain services are available on the same day if required. During the study period, the palliative care clinic was staffed only one day per week. Measures Demographic data. Demographic data included age, race, gender, date of initial visit, date of first follow-up, referring specialty, cancer diagnosis, presence of AC, and pain from a noncancer cause. Other assessments included the type of opioids, benzodiazepine use, and a history of tobacco or illicit drugs. Morphine Equivalent Daily Dose. The MEDD is the total dose of opioids administered in 24 hours converted to an equivalent dose of oral morphine. The MEDD was calculated for all opioids including morphine, hydromorphone, oxycodone, methadone, oxymorphone, and fentanyl. Standard conversion ratios7 were used for all opioids and a conversion factor of 5 was used for methadone.8 Pain response. The pain scores from the Numerical Rating Scale (NRS) were collected at both visits. Similar to pain scoring used by Yennurajalingam and colleagues9and Farrar and coworkers,10 an improvement in pain was considered to be a ‡ 2-point or a ‡ 30% reduction from baseline on a 0 to 10 NRS. These patients were identified as ‘‘responders.’’ Yennurajalingam et al. recorded the pain score at
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the initial visit and then at the first follow-up evaluation 1 to 4 weeks later. This brief time frame was chosen because cancer progression may worsen symptoms during a longer interval. We used the same premise, but allowed a first follow-up visit regardless of the duration after the initial visit. The change in pain score and MEDD was measured between initial visit and follow-up visit. Statistical analysis
Descriptive statistics were provided for demographic characteristics of the clinic patients. Continuous variables were summarized using means and standard deviations (SDs), whereas categorical variables were summarized by reporting frequencies and percentages. For categorical variables, such as classifying subjects with and without a follow-up visit or as responders/nonresponders, the three groups were compared using a v2 test. When comparing MEDD and pain scores among the three groups, the analysis was restricted to patients having both initial and follow-up values. Analysis of variance (ANOVA) methods were used to compare the three groups (AC, NED, and NLLI) with respect to pain scores and MEDD on initial and follow-up visits. Paired comparisons were made using a v2 or Tukey test when the overall test was significant. Results
During the study period 143 patients were seen at initial visit, 104 had a follow-up visit, 102 had both their initial and follow-up MEDD recorded, and 94 had both initial and follow-up pain score recorded. Baseline characteristics are reported in Table 1. Of the 143 patients, 80 (55.9%) had AC, 35 (24.5%) had a prior history of cancer but currently NED, and 28 (19.6%) had NLLI. Referrals were most commonly from hematology-oncology (35.7%), otolaryngology (11.2%), and internal medicine (9.8%). Back pain (39%) and osteoarthritis (25%) were the main reasons for treatment of noncancer pain and hydromorphone (n = 29, 20.3%) and oxycodone (n = 42, 29.4%) were the most frequently prescribed opioids. Thirtynine of the 143 patients did not have a follow-up appointment after the initial visit. Of these patients, 24.5% were ‘‘no-shows’’ and others were referred back to their primary care provider, were enrolled in hospice, or died before their next visit. The primary analysis was restricted to the 102 subjects having measures recorded at both initial and follow-up; 74.1% of patients had their first palliative contact in the clinic, whereas the remaining patients were initially seen by palliative care as an inpatient consult and then referred to the clinic. There was no significant difference among the three groups with respect to frequency of follow-up ( p = 0.065). The mean MEDD (SD) was 310.4 mg (452.5 mg) at initial visit and was increased by 24.2 mg (213.2 mg) at follow-up. At first visit, patients with AC, NED, and NLLI had a MEDD of 393.1 mg (463.1), 208.7 mg (205.2), and 258.9 mg (613.9) ( p = 0.18),respectively. The MEDD increased between visits by 17.2 mg (285.8 mg) in the AC group, 40.9 mg (123.2 mg) in the NED group, and 18.1 mg (82.7 mg) in the NLLI group, although there was no difference between the groups with respect to milligram increase ( p = 0.88). For patients with recorded initial and follow-up measures, the mean pain score (SD) on initial visit was 6.1 (2.4) (n = 94) and pain decreased by 1.3 points (3.0) to 4.8 (2.6) ( p = < 0.0001) on the NRS. AC, NED, and NLLI groups had
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Table 1. Baseline Patient Characteristics Patient characteristics, n = 143 Total N = 143
AC N = 80 (55.9%)
NED N = 35 (24.5%)
Race Tumor site
Female: 77 (53.9%) Mean: 51 Median: 52 Range: 19–83 Caucasian: 101 (70.6%) Breast: 11 (7.7) Gastrointestinal: 25 (17.5) Genitourinary: 14 (9.8) Head and neck: 22 (15.4) Lung: 14 (9.8) Other: 18 (12.6)
Benzodiazepine use Tobacco use History of Illicit drug use
45 (31.5) 45 (31.5) 15 (10.5)
42 (52.5%) 52.7 53 24–83 57 (71.2%) 9 (11%) 19 (24%) 7 (9%) 14 (18%) 4 (5%) 12 (15%) 15 (19%) 24 (30%) 22 (27.5%) 7 (8.8%)
21 (60%) 49.6 52 26–76 23 (65.7%) 2 (6%) 6 (17%) 7 (20%) 8 (23%) 7 (20%) 2 (6%) 3 (9%) 6 (17.1%) 15 (42.9%) 4 (11.4%)
Patient group Gender Age
NLLI N = 28 (19.6%) 14 (50%) 48.1 47 19–82 21 (75%)
15 (53.6%) 8 (28.6%) 4 (14.3%)
AC, active cancer; NED, no evidence of disease, past history of cancer treatment; NLLI, no life-limiting illness.
initial pain scores of 6.0 (2.5), 5.6 (2.5), and 6.8 (2.2) ( p = 0.22), respectively (Table 2). The follow-up mean pain scores were lower in the AC (4.2 [2.7]) than the NLLI (6.0 [2.6]) group ( p = 0.03). In the AC group, 57.4% (27/47) of patients were responders, compared with 20% (5/25) in the NED group ( p = 0.002). At first visit, patients in the AC, NED, and NLLI groups had MEDDs of 393.1 mg (463.1 mg), 208.7 mg (205.2 mg), and 258.9 mg (613.9 mg) ( p = 0.18), respectively. The MEDD increased between visits by 17.2 mg (285.8 mg) in the AC group, 40.9 mg (123.2 mg) in the NED group, and 18.1 mg (82.7) in the NLLI group ( p = 0.88). Benzodiazepine use was significantly more frequent in the NLLI group than the AC ( p = 0.025) and NED ( p = 0.002) groups; however, there was no difference in the frequency of benzodiazepine use between responders (n = 4) and nonre-
sponders(n = 8) in the NLLI group ( p = 0.67). The frequency of illicit drug use or tobacco was not significantly different among the three groups ( p = 0.29 and P = 0.15, respectively). Discussion
Patients with AC had a higher response rate than patients with NED, and had a lower pain score on follow-up than NLLI patients. There may be a number of reasons for the difference between these groups. Patients with NED and NLLI may have had a longer duration of chronic pain and therefore developed greater opioid tolerance than patients with AC. The etiology of the chronic pain (e.g., neuropathic pain11 due to chemotherapy in NED patients) and frequency of substance use disorders in NLLI patients12 may be additional factors that increase the potential of nonresponse in
Table 2. One Hundred Two Patients Who Had MEDD Both at Initial and Follow-Up Visits and 94 Patients Who Had Pain Scores Both at Initial and Follow-Up Visits Treatment outcomes among groups Total N = 102
AC N = 50
NED N = 29
NLLI N = 23
Days between initial and follow-up (Mean and SD) 52.4 (81.0) 39.5 (40.7) 45.3 (29.5) 89.6 (153.0) Initial MEDD 310.4 (452.5) 393.1 (463.1) 208.7 (205.2) 258.9 (613.9) Follow-up MEDD 334.6 (472.4) 410.3 (475.9) 249.6 (233.9) 277 (651.4) MEDD difference 24.2 (213.2) 17.2 (285.8) 40.9 (123.2) 18.1 (82.7) N = 94 N = 47 N = 25 N = 22 Initial pain score 6.1 (2.4) 6.0 (2.5) 5.6 (2.5) 6.8 (2.2) Follow-up pain score 4.9 (2.6) 4.2 (2.7) 5.0 (2.2) 6.0 (2.6) Pain score difference - 1.3 (3.0) - 1.8 (3.2) - 0.5 (2.4) - 0.9 (2.9) Responders 41 27 (57.4%) 5 (20%) 9 (41%) Nonresponders 53 20 (42.6%) 20 (80%) 13 (59%) a
P value 0.0401a 0.1807a 0.2799a 0.8842a 0.2153a 0.0339a 0.1756a 0.0091b 0.0091b
From analysis of variance (ANOVA). From v2 analysis. AC, active cancer; MEDD, morphine equivalent daily dose; NED, no evidence of disease, past history of cancer treatment; NLLI, no lifelimiting illness; SD, standard deviation. b
PAIN RESPONSE AMONG GROUPS IN AN AMBULATORY CLINIC
these groups. Although there was no difference in the reported use of illicit drugs between the three groups, and no difference in the use of benzodiazepines among responders and nonresponders, the frequency of benzodiazepine use was significantly higher in NLLI patients compared with the AC and NED groups. The use of benzodiazepines and benzodiazepine-like drugs is known to be a risk factor for opioid addiction in patients with chronic nonmalignant pain,13 and in a large population based study the use of benzodiazepines was an even stronger predictor of later opioid use than self-reported pain.14 Nonpharmacological therapies such as counseling by the palliative program’s psychologist or chaplain that address ‘‘total pain’’15 may also have played a role in the treatment response of AC patients. Only 43.6% of patients were considered to be responders. However, our response rate of 57.4% in patients with AC is consistent with other larger palliative care populations. Yennurajalingam and colleagues9 used the same pain treatment response outcomes and found 45% of patients were responders after a mean of 15 days from initial visit. Another study showed a ‡ 1 point pain score improvement in 58% of patients referred to a palliative care clinic.16 To our knowledge, there are no other studies evaluating the response of AC, NED, and NLLI groups to pain management by the same outpatient palliative care team. Our results suggest that symptomatic patients with a life-limiting illness will benefit the most from interdisciplinary outpatient palliative care. The relatively long interval between initial and first follow-up should have favored the groups without AC because disease progression in patients with AC could increase symptom burden and decrease the treatment response rate. In an effort to encourage patient volume and demonstrate sustainability to hospital administrators, palliative care clinics based in an oncology division may be willing to accept referrals for patients who have NED or NLLI. These patients may be more challenging to manage because palliative care specialists are often not trained to manage chronic nonmalignant pain. Patients with NED are likely to require treatment for a longer duration and will limit outpatient clinics’ capacity to enroll new palliative care patients. Although inadequate funding and reimbursement2 are still issues for outpatient palliative care clinics, a recent survey reported many clinics being ‘‘overwhelmed’’ by the volume of referrals.17 In the absence of robust survivorship clinics or primary physicians who are comfortable with prescribing strong opioids, outpatient palliative care clinics may be expected to continue co-managing survivors with their primary oncologists. Given the limited funding for palliative care and the expected shortage of palliative care providers,18 these finite resources should be used thoughtfully by hospital systems and palliative care programs. Since July 2013, our outpatient palliative care clinic has reached full capacity, and any new referrals have been restricted to patients with AC or other life-limiting illnesses such as congestive heart failure. Patients with NED are co-managed by request of the referring physician for a limited period of less than three visits before being discharged from the palliative care clinic to be managed by their primary physician. Finding solutions to manage these different populations of patients with chronic pain may require institution-specific strategies. Our study has several limitations. This is a retrospective study of a relatively small number of patients with no control
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group for comparison (e.g., patients managed by a chronic pain service) and 39 (27%) patients who did not return for a follow-up visit. The use of adjuvant pharmacological agents for pain such as tricyclic antidepressants or gabapentin was not included in our study and the relative contributions of individual interdisciplinary team (IDT) members to patient care may have differed among the three groups. Patientrelated factors that influence pain and its expression19 such as depression, somatization, and ‘‘chemical coping’’ may respond to nonpharmacological interventions delivered by an IDT. Unfortunately, the detailed records of patient care delivered by these team members were not available in electronic form during the study period. Additional information regarding nonpain symptoms or risk for ‘‘chemical coping’’20 are also not available because a screening assessment tool had not been implemented in the clinic at that time. Finally, our preliminary findings from a single institution should be validated by other ambulatory care clinics that provide pain management to both ‘‘palliative’’ and ‘‘nonpalliative’’ patients. Conclusions
Although median pain scores improved at follow-up, less than half of patients were responders. Patients with AC had a significantly better response rate than NED patients and a lower pain score than NLLI patients at follow-up. NED and NLLI patients with chronic pain may derive less benefit from outpatient palliative care than AC patients. Acknowledgments
The views expressed in this article are the authors’ own and not an official position of the institution or funder. Author Disclosure Statement
No competing financial interests exist. References
1. Center to Advance Palliative Care, National Palliative Care Research Center: Report Card: America’s Care of Serious Illness: A State-by-State Report Card on Access to Palliative Care in Our Nation’s Hospitals. Center to Advance Palliative Care, New York, NY, 2011. www.capc .org/reportcard/findings (Last accessed August 13, 2013). 2. Meier DE, Beresford L: Outpatient clinics are a new frontier for palliative care. J Palliat Med 2008;11:823–828. 3. Hui D, Elsayem A, De la Cruz M, Berger A, Zhukovsky DS, Palla S, Evans A, Fadul N, Palmer JL, Bruera E: Availability and integration of palliative care at US cancer centers. JAMA 2010;303:1054–1061. 4. Follwell M, Burman D, Le LW, Wakimoto K, Seccareccia D, Bryson J, Rodin G, Zimmerman C: Phase II study of an outpatient palliative care intervention in patients with metastatic cancer. J Clin Oncol 2009;27:206–213. 5. Kang JH, Kwon JH, Hui D, Yennurajalingam S, Bruera E: Changes in symptom intensity among cancer patients receiving outpatient palliative care. J Pain Symptom Manage 2013;46:652–660. 6. Temel JS, Greer JA, Muzikansky A, Gallagher ER, Admane S, Jackson VA, Dahlin CM, Blinderman CD, Jacobsen J, Pirl WF, Billings JA, Lynch TJ: Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med 2010;363:733–742.
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7. Elsayem A, Bruera E (eds): The MD Anderson Symptom Control and Palliative Care Handbook. Houston, TX: University of Texas Health Science Center, 2008. 8. Walker PW, Palla S, Pei BL, Kaur G, Zhang K, Hanohano J, Munsell M, Bruera E: Switching from methadone to a different opioid: What is the equianalgesic dose ratio? J Palliat Med 2008;11:1103–1108. 9. Yennurajalingam S, Kang JH, Hui D, Kang DH, Kim SH, Bruera E: Clinical response to an outpatient palliative care consultation in patients with advanced cancer and cancer pain. J Pain Symptom Manage 2012;44:340–350. 10. Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole RM: Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001;94:149–158. 11. Baron R: Neuropathic pain: a clinical perspective. Handb Exp Pharmacol 2009;194:3–30. 12. Kissin I: Long-term opioid treatment of chronic nonmalignant pain: Unproven efficacy and neglected safety? J Pain Res 2013;6:513–529. 13. Højsted J, Ekholm O, Kurita GP, Juel K, Sjøgren P: Addictive behaviors related to opioid use for chronic pain: A population-based study. Pain 2013;154:2677–2683. 14. Skurtveit S, Furu K, Bramness J, Selmer R, Tverdal A: Benzodiazepines predict use of opioids—A follow-up study of 17,074 men and women. Pain Med 2010;11:805–814. 15. Clark D: ‘Total pain’, disciplinary power and the body in the work of Cicely Saunders 1958–1967. Soc Sci Med 1999;49:727–736.
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16. Bischoff K, Weinberg V, Rabow MW: Palliative and oncologic co-management: Symptom management for outpatients with cancer. Support Care Cancer 2013;21:3031–3037. 17. Smith AK, Thai JN, Bakitas MA, Meier DE, Spragens LH, Temel JS, Weissman DE, Rabow MW: The diverse landscape of palliative care clinics. J Palliat Med 2013;16: 661–668. 18. Lupu D, American Academy of Hospice and Palliative Medicine Workforce Task Force: Estimate of current hospice and palliative medicine physician workforce shortage. J Pain Symptom Manage 2010;40:899–911. 19. Bruera E, Schoeller T, Wenk R, MacEachern T, Marcelino S, Hanson J, Suarez-Almazor M: A prospective multicenter assessment of the Edmonton staging system for cancer pain. J Pain Symptom Manage 1995;10:348–355. 20. Dev R, Parsons HA, Palla S, Palmer JL, Del Fabbro E, Bruera E: Undocumented alcoholism and its correlation with tobacco and illegal drug use in advanced cancer patients. Cancer 2011;117:4551–4556.
Address correspondence to: Egidio Del Fabbro, MD Internal Medicine Virginia Commonwealth University 1101 East Marshall Street Richmond, VA 23223 E-mail: [email protected]
Original Articles
Response to Pain Management among Patients with Active Cancer, No Evidence of Disease, or Chronic Nonmalignant Pain in an Outpatient Palliative Care Clinic Cara Jennings, MD,1,2 Brian Cassel, PhD,1,2 Devon Fletcher, MD,1,2 Aiping Wang,3 Kellie J. Archer, PhD,3 Nevena Skoro,1 Leanne Yanni, MD,4 and Egidio Del Fabbro, MD1,2
Abstract
Background: Outpatient palliative care clinics may be required to manage patients not typically seen by palliative care. These include patients treated for cancer who no longer have evidence of disease (NED) and patients with chronic pain but no life-limiting illness (NLLI). Treatment response may differ among these groups. Objectives: Our aim was to determine treatment response by change in pain scores and morphine equivalent daily dose (MEDD) between initial visit and first follow-up in patients with active cancer (AC), NED, and those with NLLI. Methods: A retrospective review of 143 consecutive outpatients referred to a clinic staffed by the palliative care program was conducted. Pain treatment response was defined by a ‡ 2 point difference on the Numerical Rating Scale (NRS) or ‡ 30% reduction from baseline score. Results: Ninety-four patients had pain scores at both initial and follow-up visits after a median of 29.0 days. Fifty percent had AC, 27% NED, and 23% NLLI. Mean (standard deviation [SD]) pain scores at baseline were not significantly different among AC 6.0 (2.5), NED 5.6 (2.5), and NLLI 6.8 (2.2) patients ( p = 0.22), but were significant at follow-up between AC 4.2 (2.7) and NLLI 6.0 (2.6) ( p = 0.03) groups. The percent of responders differed significantly between AC 57.4% and NED 20% groups ( p = 0.002). MEDD increased by 17.2 mg in AC, 40.9 mg in NED, and 18.1mg in NLLI patients ( p = 0.88).Benzodiazepine use was significantly more frequent in the NLLI group than the AC ( p = 0.025) and NED ( p = 0.002) groups. Conclusions: Although median pain scores improved at follow-up, less than half of patients were responders. Patients with AC had a significantly better response rate than NED patients and a lower pain score than NLLI patients at follow-up.
Introduction
P
alliative care programs are becoming more common, with 85% of large hospitals offering inpatient palliative care services.1 Despite the growth in palliative care programs, there is still a gap between the availability of inpatient and outpatient care2 and only 59% of National Cancer Institute (NCI)-designated cancer centers have an outpatient palliative care clinic.3 These clinics have improved a number of clinical outcomes including patient and caregiver satisfaction,4 symptoms,5 and survival.6 The structure of clinics may vary depending on the number of days per week they are
staffed, the referral sources, the main patient populations they serve, and the administrative home of the program. The Virginia Commonwealth University (VCU) palliative care program within the Division of Oncology, Hematology, and Palliative care staffs a palliative care clinic at Massey Cancer Center. Although most of the patients referred to the clinic have active cancer (AC), other groups are also referred including patients with no evidence of disease (NED) who have completed treatment for cancer, and patients with chronic pain but no life-limiting illness (NLLI).The expertise of the palliative care team in pain management and the absence of survivorship or chronic pain clinics within the
1 Massey Cancer Center, 2Division of Hematology, Oncology, and Palliative Care, Department of Internal Medicine, 3Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia. 4 Palliative Medicine, Bon Secours Richmond Health System, Richmond, Virginia. Accepted March 7, 2013.
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PAIN RESPONSE AMONG GROUPS IN AN AMBULATORY CLINIC
institution are among the factors driving the ‘‘mixed’’ referrals to this ambulatory clinic. The objective of the study was to evaluate the response to pain management among the different patient groups seen in the palliative care clinic. Changes in pain scores and the morphine equivalent daily dose (MEDD) were measured from the initial visit to first follow-up. We hypothesized that patients with AC would derive greater benefit from outpatient palliative care, compared with those with NED or NLLI. Design Patient selection
A retrospective chart review of 143 consecutive patients referred to the VCU palliative care clinic from July 1, 2009 to June 30, 2012 was conducted. One hundred four patients had an initial visit and follow-up after a median of 29.0 days. Among these 104, 102 had MEDD documented and 94 had pain scores recorded at both initial and follow-up visits. Analysis was restricted to patients having both initial and follow-up values. The inception date was chosen because the clinic came to be fully staffed with a board-certified palliative care physician and palliative care fellows, and an electronic health record was implemented. Prior to this date patient records were not easily accessible. The end date for the study was chosen because after that date, the clinic routinely accepted referrals only for patients with a life-limiting illness. The study was approved by the VCU Institutional Review Board. Setting
The palliative care clinic within the NCI-designated Massey Cancer Center at VCU operates 2 days a week with a palliative care physician, a registered nurse, and palliative care fellows. In addition, psychology, occupational therapy, social work, and chaplain services are available on the same day if required. During the study period, the palliative care clinic was staffed only one day per week. Measures Demographic data. Demographic data included age, race, gender, date of initial visit, date of first follow-up, referring specialty, cancer diagnosis, presence of AC, and pain from a noncancer cause. Other assessments included the type of opioids, benzodiazepine use, and a history of tobacco or illicit drugs. Morphine Equivalent Daily Dose. The MEDD is the total dose of opioids administered in 24 hours converted to an equivalent dose of oral morphine. The MEDD was calculated for all opioids including morphine, hydromorphone, oxycodone, methadone, oxymorphone, and fentanyl. Standard conversion ratios7 were used for all opioids and a conversion factor of 5 was used for methadone.8 Pain response. The pain scores from the Numerical Rating Scale (NRS) were collected at both visits. Similar to pain scoring used by Yennurajalingam and colleagues9and Farrar and coworkers,10 an improvement in pain was considered to be a ‡ 2-point or a ‡ 30% reduction from baseline on a 0 to 10 NRS. These patients were identified as ‘‘responders.’’ Yennurajalingam et al. recorded the pain score at
991
the initial visit and then at the first follow-up evaluation 1 to 4 weeks later. This brief time frame was chosen because cancer progression may worsen symptoms during a longer interval. We used the same premise, but allowed a first follow-up visit regardless of the duration after the initial visit. The change in pain score and MEDD was measured between initial visit and follow-up visit. Statistical analysis
Descriptive statistics were provided for demographic characteristics of the clinic patients. Continuous variables were summarized using means and standard deviations (SDs), whereas categorical variables were summarized by reporting frequencies and percentages. For categorical variables, such as classifying subjects with and without a follow-up visit or as responders/nonresponders, the three groups were compared using a v2 test. When comparing MEDD and pain scores among the three groups, the analysis was restricted to patients having both initial and follow-up values. Analysis of variance (ANOVA) methods were used to compare the three groups (AC, NED, and NLLI) with respect to pain scores and MEDD on initial and follow-up visits. Paired comparisons were made using a v2 or Tukey test when the overall test was significant. Results
During the study period 143 patients were seen at initial visit, 104 had a follow-up visit, 102 had both their initial and follow-up MEDD recorded, and 94 had both initial and follow-up pain score recorded. Baseline characteristics are reported in Table 1. Of the 143 patients, 80 (55.9%) had AC, 35 (24.5%) had a prior history of cancer but currently NED, and 28 (19.6%) had NLLI. Referrals were most commonly from hematology-oncology (35.7%), otolaryngology (11.2%), and internal medicine (9.8%). Back pain (39%) and osteoarthritis (25%) were the main reasons for treatment of noncancer pain and hydromorphone (n = 29, 20.3%) and oxycodone (n = 42, 29.4%) were the most frequently prescribed opioids. Thirtynine of the 143 patients did not have a follow-up appointment after the initial visit. Of these patients, 24.5% were ‘‘no-shows’’ and others were referred back to their primary care provider, were enrolled in hospice, or died before their next visit. The primary analysis was restricted to the 102 subjects having measures recorded at both initial and follow-up; 74.1% of patients had their first palliative contact in the clinic, whereas the remaining patients were initially seen by palliative care as an inpatient consult and then referred to the clinic. There was no significant difference among the three groups with respect to frequency of follow-up ( p = 0.065). The mean MEDD (SD) was 310.4 mg (452.5 mg) at initial visit and was increased by 24.2 mg (213.2 mg) at follow-up. At first visit, patients with AC, NED, and NLLI had a MEDD of 393.1 mg (463.1), 208.7 mg (205.2), and 258.9 mg (613.9) ( p = 0.18),respectively. The MEDD increased between visits by 17.2 mg (285.8 mg) in the AC group, 40.9 mg (123.2 mg) in the NED group, and 18.1 mg (82.7 mg) in the NLLI group, although there was no difference between the groups with respect to milligram increase ( p = 0.88). For patients with recorded initial and follow-up measures, the mean pain score (SD) on initial visit was 6.1 (2.4) (n = 94) and pain decreased by 1.3 points (3.0) to 4.8 (2.6) ( p = < 0.0001) on the NRS. AC, NED, and NLLI groups had
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Table 1. Baseline Patient Characteristics Patient characteristics, n = 143 Total N = 143
AC N = 80 (55.9%)
NED N = 35 (24.5%)
Race Tumor site
Female: 77 (53.9%) Mean: 51 Median: 52 Range: 19–83 Caucasian: 101 (70.6%) Breast: 11 (7.7) Gastrointestinal: 25 (17.5) Genitourinary: 14 (9.8) Head and neck: 22 (15.4) Lung: 14 (9.8) Other: 18 (12.6)
Benzodiazepine use Tobacco use History of Illicit drug use
45 (31.5) 45 (31.5) 15 (10.5)
42 (52.5%) 52.7 53 24–83 57 (71.2%) 9 (11%) 19 (24%) 7 (9%) 14 (18%) 4 (5%) 12 (15%) 15 (19%) 24 (30%) 22 (27.5%) 7 (8.8%)
21 (60%) 49.6 52 26–76 23 (65.7%) 2 (6%) 6 (17%) 7 (20%) 8 (23%) 7 (20%) 2 (6%) 3 (9%) 6 (17.1%) 15 (42.9%) 4 (11.4%)
Patient group Gender Age
NLLI N = 28 (19.6%) 14 (50%) 48.1 47 19–82 21 (75%)
15 (53.6%) 8 (28.6%) 4 (14.3%)
AC, active cancer; NED, no evidence of disease, past history of cancer treatment; NLLI, no life-limiting illness.
initial pain scores of 6.0 (2.5), 5.6 (2.5), and 6.8 (2.2) ( p = 0.22), respectively (Table 2). The follow-up mean pain scores were lower in the AC (4.2 [2.7]) than the NLLI (6.0 [2.6]) group ( p = 0.03). In the AC group, 57.4% (27/47) of patients were responders, compared with 20% (5/25) in the NED group ( p = 0.002). At first visit, patients in the AC, NED, and NLLI groups had MEDDs of 393.1 mg (463.1 mg), 208.7 mg (205.2 mg), and 258.9 mg (613.9 mg) ( p = 0.18), respectively. The MEDD increased between visits by 17.2 mg (285.8 mg) in the AC group, 40.9 mg (123.2 mg) in the NED group, and 18.1 mg (82.7) in the NLLI group ( p = 0.88). Benzodiazepine use was significantly more frequent in the NLLI group than the AC ( p = 0.025) and NED ( p = 0.002) groups; however, there was no difference in the frequency of benzodiazepine use between responders (n = 4) and nonre-
sponders(n = 8) in the NLLI group ( p = 0.67). The frequency of illicit drug use or tobacco was not significantly different among the three groups ( p = 0.29 and P = 0.15, respectively). Discussion
Patients with AC had a higher response rate than patients with NED, and had a lower pain score on follow-up than NLLI patients. There may be a number of reasons for the difference between these groups. Patients with NED and NLLI may have had a longer duration of chronic pain and therefore developed greater opioid tolerance than patients with AC. The etiology of the chronic pain (e.g., neuropathic pain11 due to chemotherapy in NED patients) and frequency of substance use disorders in NLLI patients12 may be additional factors that increase the potential of nonresponse in
Table 2. One Hundred Two Patients Who Had MEDD Both at Initial and Follow-Up Visits and 94 Patients Who Had Pain Scores Both at Initial and Follow-Up Visits Treatment outcomes among groups Total N = 102
AC N = 50
NED N = 29
NLLI N = 23
Days between initial and follow-up (Mean and SD) 52.4 (81.0) 39.5 (40.7) 45.3 (29.5) 89.6 (153.0) Initial MEDD 310.4 (452.5) 393.1 (463.1) 208.7 (205.2) 258.9 (613.9) Follow-up MEDD 334.6 (472.4) 410.3 (475.9) 249.6 (233.9) 277 (651.4) MEDD difference 24.2 (213.2) 17.2 (285.8) 40.9 (123.2) 18.1 (82.7) N = 94 N = 47 N = 25 N = 22 Initial pain score 6.1 (2.4) 6.0 (2.5) 5.6 (2.5) 6.8 (2.2) Follow-up pain score 4.9 (2.6) 4.2 (2.7) 5.0 (2.2) 6.0 (2.6) Pain score difference - 1.3 (3.0) - 1.8 (3.2) - 0.5 (2.4) - 0.9 (2.9) Responders 41 27 (57.4%) 5 (20%) 9 (41%) Nonresponders 53 20 (42.6%) 20 (80%) 13 (59%) a
P value 0.0401a 0.1807a 0.2799a 0.8842a 0.2153a 0.0339a 0.1756a 0.0091b 0.0091b
From analysis of variance (ANOVA). From v2 analysis. AC, active cancer; MEDD, morphine equivalent daily dose; NED, no evidence of disease, past history of cancer treatment; NLLI, no lifelimiting illness; SD, standard deviation. b
PAIN RESPONSE AMONG GROUPS IN AN AMBULATORY CLINIC
these groups. Although there was no difference in the reported use of illicit drugs between the three groups, and no difference in the use of benzodiazepines among responders and nonresponders, the frequency of benzodiazepine use was significantly higher in NLLI patients compared with the AC and NED groups. The use of benzodiazepines and benzodiazepine-like drugs is known to be a risk factor for opioid addiction in patients with chronic nonmalignant pain,13 and in a large population based study the use of benzodiazepines was an even stronger predictor of later opioid use than self-reported pain.14 Nonpharmacological therapies such as counseling by the palliative program’s psychologist or chaplain that address ‘‘total pain’’15 may also have played a role in the treatment response of AC patients. Only 43.6% of patients were considered to be responders. However, our response rate of 57.4% in patients with AC is consistent with other larger palliative care populations. Yennurajalingam and colleagues9 used the same pain treatment response outcomes and found 45% of patients were responders after a mean of 15 days from initial visit. Another study showed a ‡ 1 point pain score improvement in 58% of patients referred to a palliative care clinic.16 To our knowledge, there are no other studies evaluating the response of AC, NED, and NLLI groups to pain management by the same outpatient palliative care team. Our results suggest that symptomatic patients with a life-limiting illness will benefit the most from interdisciplinary outpatient palliative care. The relatively long interval between initial and first follow-up should have favored the groups without AC because disease progression in patients with AC could increase symptom burden and decrease the treatment response rate. In an effort to encourage patient volume and demonstrate sustainability to hospital administrators, palliative care clinics based in an oncology division may be willing to accept referrals for patients who have NED or NLLI. These patients may be more challenging to manage because palliative care specialists are often not trained to manage chronic nonmalignant pain. Patients with NED are likely to require treatment for a longer duration and will limit outpatient clinics’ capacity to enroll new palliative care patients. Although inadequate funding and reimbursement2 are still issues for outpatient palliative care clinics, a recent survey reported many clinics being ‘‘overwhelmed’’ by the volume of referrals.17 In the absence of robust survivorship clinics or primary physicians who are comfortable with prescribing strong opioids, outpatient palliative care clinics may be expected to continue co-managing survivors with their primary oncologists. Given the limited funding for palliative care and the expected shortage of palliative care providers,18 these finite resources should be used thoughtfully by hospital systems and palliative care programs. Since July 2013, our outpatient palliative care clinic has reached full capacity, and any new referrals have been restricted to patients with AC or other life-limiting illnesses such as congestive heart failure. Patients with NED are co-managed by request of the referring physician for a limited period of less than three visits before being discharged from the palliative care clinic to be managed by their primary physician. Finding solutions to manage these different populations of patients with chronic pain may require institution-specific strategies. Our study has several limitations. This is a retrospective study of a relatively small number of patients with no control
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group for comparison (e.g., patients managed by a chronic pain service) and 39 (27%) patients who did not return for a follow-up visit. The use of adjuvant pharmacological agents for pain such as tricyclic antidepressants or gabapentin was not included in our study and the relative contributions of individual interdisciplinary team (IDT) members to patient care may have differed among the three groups. Patientrelated factors that influence pain and its expression19 such as depression, somatization, and ‘‘chemical coping’’ may respond to nonpharmacological interventions delivered by an IDT. Unfortunately, the detailed records of patient care delivered by these team members were not available in electronic form during the study period. Additional information regarding nonpain symptoms or risk for ‘‘chemical coping’’20 are also not available because a screening assessment tool had not been implemented in the clinic at that time. Finally, our preliminary findings from a single institution should be validated by other ambulatory care clinics that provide pain management to both ‘‘palliative’’ and ‘‘nonpalliative’’ patients. Conclusions
Although median pain scores improved at follow-up, less than half of patients were responders. Patients with AC had a significantly better response rate than NED patients and a lower pain score than NLLI patients at follow-up. NED and NLLI patients with chronic pain may derive less benefit from outpatient palliative care than AC patients. Acknowledgments
The views expressed in this article are the authors’ own and not an official position of the institution or funder. Author Disclosure Statement
No competing financial interests exist. References
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Address correspondence to: Egidio Del Fabbro, MD Internal Medicine Virginia Commonwealth University 1101 East Marshall Street Richmond, VA 23223 E-mail: [email protected]
