Janet L. Williams

Methylphenidate and/or a Nursing Telephone Intervention for Fatigue in Patients With Advanced Cancer: A Randomized, Placebo-Controlled, Phase II Trial

PURPOSE Cancer-related-fatigue (CRF) is common in advanced cancer. The primary objective of the study was to compare the effects of methylphenidate (MP) with those of placebo (PL) on CRF as measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) fatigue subscale. The effect of a combined intervention including MP plus a nursing telephone intervention (NTI) was also assessed. PATIENTS AND METHODS Patients with advanced cancer with a fatigue score of ≥ 4 out of 10 on the Edmonton Symptom Assessment Scale (ESAS) were randomly assigned to one of the following four groups: MP+NTI, PL+NTI, MP + control telephone intervention (CTI), and PL+CTI. Methylphenidate dose was 5 mg every 2 hours as needed up to 20 mg per day. The primary end point was the median difference in FACIT-F fatigue at day 15. Secondary outcomes included anxiety, depression, and sleep. RESULTS One hundred forty-one patients were evaluable. Median FACIT-F fatigue scores improved from baseline to day 15 in all groups: MP+NTI (median score, 4.5; P = .005), PL+NTI (median score, 8.0; P < .001), MP+CTI (median score, 7.0; P = .004), and PL+CTI (median score, 5.0; P = .03). However, there were no significant differences in the median improvement in FACIT-F fatigue between the MP and PL groups (5.5 v 6.0, respectively; P = .69) and among all four groups (P = .16). Fatigue (P < .001), nausea (P = .01), depression (P = .02), anxiety (P = .01), drowsiness (P < .001), appetite (P = .009), sleep (P < .001), and feeling of well-being (P < .001), as measured by the ESAS, significantly improved in patients who received NTI. Grade ≥ 3 adverse events did not differ between MP and PL (40 of 93 patients v 29 of 97 patients, respectively; P = .06). CONCLUSION MP and NTI alone or combined were not superior to placebo in improving CRF.

Measuring the symptom burden associated with the treatment of chronic myeloid leukemia

We developed a module of the MD Anderson Symptom Inventory (MDASI) for patients with chronic myeloid leukemia (CML). To develop the MDASI-CML, we identified CML-specific symptoms from qualitative interviews with 35 patients. A list of candidate symptoms was reduced by a panel of patients, caregivers, and clinicians to the 13 core MDASI symptom items and 6 CML-specific items; these items were subsequently administered to 30 patients. Cognitive debriefing confirmed that the items were clear, relevant, and easy to use. One additional CML-specific symptom item was added, for a total of 7. The refined MDASI-CML was administered to 152 patients once every 2 weeks for 1 year. The content, concurrent, known-group, and construct validity of the MDASI-CML were evaluated. The internal consistency and test-retest reliabilities of the module were adequate. Longitudinal analysis showed relatively stable symptom severity scores over time. The most severe symptoms were fatigue, drowsiness, disturbed sleep, muscle soreness and cramping, and trouble remembering things. Approximately one-third of the patients who completed the MDASI-CML reported persistent moderate-to-severe symptoms. The MDASI-CML is a valid and reliable symptom assessment instrument that can be used in clinical studies of symptom status in patients with CML.

Avoidable and unavoidable visits to the emergency department among patients with advanced cancer receiving outpatient palliative care.

CONTEXT Admissions to the emergency department (ED) can be distressing to patients with advanced cancer receiving palliative care. There is limited research about the clinical characteristics of these patients and whether these ED visits can be categorized as avoidable or unavoidable. OBJECTIVES To determine the frequency of potentially avoidable ED visits (AvEDs) for patients with advanced cancer receiving outpatient palliative care in a large tertiary cancer center, identify the clinical characteristics of the patients receiving palliative care who visited the ED, and analyze the factors associated with AvEDs and unavoidable ED visits (UnAvEDs). METHODS We randomly selected 200 advanced cancer patients receiving treatment in the outpatient palliative care clinic of a tertiary cancer center who visited the ED between January 2010 and December 2011. Visits were classified as AvED (if the problem could have been managed in the outpatient clinic or by telephone) or UnAvED. RESULTS Forty-six (23%) of 200 ED visits were classified as AvED, and 154 (77%) of 200 ED visits were classified as UnAvED. Pain (71/200, 36%) was the most common chief complaint in both groups. Altered mental status, dyspnea, fever, and bleeding were present in the UnAvED group only. Infection, neurologic events, and cancer-related dyspnea were significantly more frequent in the UnAvED group, whereas constipation and running out of pain medications were significantly more frequent in the AvED group (P < 0.001). In a multivariate analysis, AvED was associated with nonwhite ethnicity (odds ratio [OR] 2.66; 95% CI 1.26, 5.59) and constipation (OR 17.08; 95% CI 3.76, 77.67), whereas UnAvED was associated with ED referral from the outpatient oncology or palliative care clinic (OR 0.24; 95% CI 0.06, 0.88) and the presence of baseline dyspnea (OR 0.46; 95% CI 0.21, 0.99). CONCLUSION Nearly one-fourth of ED visits by patients with advanced cancer receiving palliative care were potentially avoidable. Proactive efforts to improve communication and support between scheduled appointments are needed.

Patterns of Storage, Use, and Disposal of Opioids Among Cancer Outpatients

PURPOSE Improper storage, use, and disposal of prescribed opioids can lead to diversion or accidental poisoning. Our objective was to determine the patterns of storage, utilization, and disposal of opioids among cancer outpatients. PATIENTS AND METHODS We surveyed 300 adult cancer outpatients receiving opioids in our supportive care center and collected information regarding opioid use, storage, and disposal, along with scores on the CAGE (cut down, annoyed, guilty, eye-opener) alcoholism screening questionnaire. Unsafe use was defined as sharing or losing opioids; unsafe storage was defined as storing opioids in plain sight. RESULTS The median age was 57 years. CAGE was positive in 58 of 300 patients (19%), and 26 (9%) had a history of illicit drug use. Fifty-six (19%) stored opioids in plain sight, 208 (69%) kept opioids hidden but unlocked, and only 28 (9%) locked their opioids. CAGE-positive patients (p = .007) and those with a history of illicit drug use (p = .0002) or smoking (p = .03) were more likely to lock their opioids. Seventy-eight (26%) reported unsafe use by sharing (9%) or losing (17%) their opioids. Patients who were never married or single (odds ratio: 2.92; 95% confidence interval: 1.48-5.77; p = .006), were CAGE positive (40% vs. 21%; p = .003), or had a history of illicit drug use (42% vs. 23%; p = .031) were more likely to use opioids unsafely. Overall, 223 of 300 patients (74%) were unaware of proper opioid disposal methods, and 138 (46%) had unused opioids at home. CONCLUSION A large proportion of cancer patients improperly and unsafely use, store, and dispose of opioids, highlighting the need for establishment of easily accessed patient education and drug take-back programs.

Frequency, Predictors, and Medical Record Documentation of Chemical Coping Among Advanced Cancer Patients

BACKGROUND In this prospective study, we determined the frequency of opioid-related chemical coping among advanced cancer patients, as diagnosed by palliative medicine specialists. We also determined predictors for chemical coping and the concordance between the physicians diagnosis and documentation in the medical records. PATIENTS AND METHODS Palliative medicine specialists evaluated and diagnosed consecutive patients seen for chemical coping. The proportion of patients identified as chemically coping was compared with the proportion documented in the medical records. Demographic data; cancer diagnosis; history of smoking; substance abuse; psychiatric disease; morphine equivalent daily dosage; Cut-down, Annoyed, Guilty, and Eye-opener (CAGE) questionnaire scores; and Edmonton Symptom Assessment System scores were also collected. RESULTS A total of 432 patients were evaluated. Overall, 76 patients (18%; 95% confidence interval [CI]: 14%-21%) were diagnosed as chemically coping. Documentation of chemical coping in the medical records was reported for only 15 patients (4%; 95% CI: 2%-6%). CAGE positivity (odds ratio [OR]: 2.89), younger age (OR: 0.97 per year), better performance status (OR: 0.68 per point), pain (OR: 1.20 per point), and well-being (OR: 1.28 per point) were found to be significant predictors of chemical coping by protocol definition. After recursive partitioning, 21 of 50 patients (42%) who were CAGE positive and had an Eastern Cooperative Oncology Group performance status ≤2 were diagnosed as chemically coping. CONCLUSION Approximately 18% of palliative care patients seen were diagnosed as chemically coping by palliative medicine specialists. The frequency of documentation in the medical records was significantly lower. Better and safer ways for physicians to assess and report chemical coping are needed. IMPLICATIONS FOR PRACTICE Cancer pain is a multidimensional symptom for which opioids are the mainstay of treatment. However, opioids can have a double effect resulting in drug-seeking behaviors. Chemical coping occurs when a patient uses opioids in a nonprescribed way to cope with various stressful events. This can lead to misuse of opioids and complications including neurotoxicities, respiratory depression, and death. Proper diagnosis and documentation is needed to ensure proper management of pain and to avoid unnecessary harm. The findings of this study suggest that ∼18% of advanced cancer patients seen by a palliative care service were diagnosed as chemical coping, but only 4% were documented in the medical records.

Use of Palliative Care Services in a Tertiary Cancer Center

This study analyzed palliative/supportive care use in a single cancer center over 8 years. Billing data showed the inpatient consultations as a percentage of hospital admissions and the ratio of inpatient consultations to hospital beds almost doubled. In the outpatient setting, data revealed earlier access to outpatient referrals to palliative care service (from 4.8 months to 7.9 months; p = .001) during the study period.

Association Between Tobacco Use, Symptom Expression, and Alcohol and Illicit Drug Use in Advanced Cancer Patients

CONTEXT Limited knowledge exists examining the association between smoking status, symptom expression, and alcohol or illicit drug use. OBJECTIVES The goal of this study was to clarify these associations in patients with advanced cancer. METHODS We retrospectively reviewed 560 charts and identified 300 consecutive advanced cancer patients who completed a comprehensive smoking questionnaire. Data including the Edmonton Symptom Assessment System, Cut down/Annoyed/Guilty/Eye opener (CAGE) alcoholism screening questionnaire, illicit drug use history, and daily opioid requirements-morphine equivalent daily dose-were collected. RESULTS Among 300 patients, 119 (40%) were never smokers, 148 (49%) former smokers, and 33 (11%) current smokers. The most common malignancies were gastrointestinal (28%) and lung (20%). Current smokers were more likely to be single (P < 0.01) and significantly younger than former smokers (P < 0.001) but did not differ in age from never smokers. Never smokers were more likely to be female (P < 0.001). Current smokers reported significantly higher pain expression than former and never smokers (median 7 vs. 5.5 vs. 5, respectively, P = 0.02), higher CAGE positivity (42% vs. 21% vs. 3%, P < 0.001) and were more likely to have a history of illicit drug use (33% vs. 16% vs. 3%, P < 0.001). The morphine equivalent daily dose was not significantly different according to smoking status. CONCLUSION In advanced cancer, patients who were former or current smokers were significantly more likely to have a history of CAGE positivity and illicit drug use compared with never smokers. Current smokers expressed significantly higher pain. A smoking history may be a marker of an increased risk of opioid misuse.

Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care: A Randomized Clinical Trial

Importance The use of benzodiazepines to control agitation in delirium in the last days of life is controversial. Objective To compare the effect of lorazepam vs placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium in the setting of advanced cancer. Design, Setting, and Participants Single-center, double-blind, parallel-group, randomized clinical trial conducted at an acute palliative care unit at MD Anderson Cancer Center, Texas, enrolling 93 patients with advanced cancer and agitated delirium despite scheduled haloperidol from February 11, 2014, to June 30, 2016, with data collection completed in October 2016. Interventions Lorazepam (3 mg) intravenously (n = 47) or placebo (n = 43) in addition to haloperidol (2 mg) intravenously upon the onset of an agitation episode. Main Outcomes and Measures The primary outcome was change in Richmond Agitation-Sedation Scale (RASS) score (range, −5 [unarousable] to 4 [very agitated or combative]) from baseline to 8 hours after treatment administration. Secondary end points were rescue neuroleptic use, delirium recall, comfort (perceived by caregivers and nurses), communication capacity, delirium severity, adverse effects, discharge outcomes, and overall survival. Results Among 90 randomized patients (mean age, 62 years; women, 42 [47%]), 58 (64%) received the study medication and 52 (90%) completed the trial. Lorazepam + haloperidol resulted in a significantly greater reduction of RASS score at 8 hours (−4.1 points) than placebo + haloperidol (−2.3 points) (mean difference, −1.9 points [95% CI, −2.8 to −0.9]; P < .001). The lorazepam + haloperidol group required less median rescue neuroleptics (2.0 mg) than the placebo + haloperidol group (4.0 mg) (median difference, −1.0 mg [95% CI, −2.0 to 0]; P = .009) and was perceived to be more comfortable by both blinded caregivers and nurses (caregivers: 84% for the lorazepam + haloperidol group vs 37% for the placebo + haloperidol group; mean difference, 47% [95% CI, 14% to 73%], P = .007; nurses: 77% for the lorazepam + haloperidol group vs 30% for the placebo + haloperidol group; mean difference, 47% [95% CI, 17% to 71%], P = .005). No significant between-group differences were found in delirium-related distress and survival. The most common adverse effect was hypokinesia (3 patients in the lorazepam + haloperidol group [19%] and 4 patients in the placebo + haloperidol group [27%]). Conclusions and Relevance In this preliminary trial of hospitalized patients with agitated delirium in the setting of advanced cancer, the addition of lorazepam to haloperidol compared with haloperidol alone resulted in a significantly greater reduction in agitation at 8 hours. Further research is needed to assess generalizability and adverse effects. Trial Registration clinicaltrials.gov Identifier: NCT01949662

The Impact of an Educational Program on Patient Practices for Safe Use, Storage, and Disposal of Opioids at a Comprehensive Cancer Center

BACKGROUND Improper use, storage, and disposal of prescribed opioids can lead to diversion or accidental poisoning. Our previous study showed a large proportion of cancer patients have unsafe opioid practices. Our objective was to determine whether an improvement occurred in the patterns of use, storage, and disposal of opioids among cancer outpatients after the implementation of a patient educational program. PATIENTS AND METHODS Our palliative care (PC) clinic provides every patient with educational material (EM) on safe opioid use, storage, and disposal every time they receive an opioid prescription. We prospectively assessed 300 adult cancer outpatients receiving opioids in our PC clinic, who had received the EM, and compared them with 300 patients who had not received the EM. The previously used surveys pertaining to opioid use, storage, and disposal were administered, and demographic information was collected. Sharing or losing their opioids was defined as unsafe use. RESULTS Patients who received EM were more aware of the proper opioid disposal methods (76% vs. 28%; p ≤ .0001), less likely to share their opioids with someone else (3% vs. 8%; p = .0311), less likely to practice unsafe use of opioids (18% vs. 25%; p = .0344), and more likely to be aware the danger of their opioids when taken by others (p = .0099). Patients who received the EM were less likely to have unused medication at home (38% vs. 47%; p = .0497) and more likely to keep their medications in a safe place (hidden, 75% vs. 70%; locked, 14% vs. 10%; p = .0025). CONCLUSION The use of EM on opioid safety for patients with advanced cancer was associated with improved patient-reported safe opioid use, storage, and disposal. The Oncologist 2017;22:115-121Implications for Practice: Prescription opioid abuse is a fast-growing epidemic that has become more prominent recently, even in the cancer pain population. A previous study reported that 26% of cancer outpatients seen in the supportive care center either lose their pain medications or share their pain medications with someone else. This study demonstrates that the implementation of an opioid educational program and distribution of educational material on opioid safety brings about an improvement in opioid storage, use, and disposal practices in patients being prescribed opioids for cancer-related pain. Our study highlights the importance of consistent and thorough opioid education at every instance in which opioids are prescribed.

Frequency, predictors, and outcomes of urine drug testing among patients with advanced cancer on chronic opioid therapy at an outpatient supportive care clinic

Data are limited on the use and outcomes of urine drug tests (UDTs) among patients with advanced cancer. The main objective of this study was to determine the factors associated with UDT ordering and results in outpatients with advanced cancer.