Julio Allo

Parenteral Hydration in Patients With Advanced Cancer: A Multicenter, Double-Blind, Placebo-Controlled Randomized Trial

PURPOSE The vast majority of patients with cancer at the end of life receive parenteral hydration in hospitals and no hydration in hospice, with limited evidence supporting either practice. In this randomized controlled trial, we determined the effect of hydration on symptoms associated with dehydration, quality of life, and survival in patients with advanced cancer. PATIENTS AND METHODS We randomly assigned 129 patients with cancer from six hospices to receive parenteral hydration (normal saline 1 L per day) or placebo (normal saline 100 mL per day) daily over 4 hours. The primary outcome was change in the sum of four dehydration symptoms (fatigue, myoclonus, sedation and hallucinations, 0 = best and 40 = worst possible) between day 4 and baseline. Secondary outcomes included Edmonton Symptom Assessment Scale (ESAS), Memorial Delirium Assessment Scale (MDAS), Nursing Delirium Screening Scale (NuDESC), Unified Myoclonus Rating Scale (UMRS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Dehydration Assessment Scale, creatinine, urea, and overall survival. Intention-to-treat analysis was conducted to examine the change by day 4 ± 2 and day 7 ± 2 between groups. RESULTS The hydration (n = 63) and placebo (n = 66) groups had similar baseline characteristics. We found no significant differences between the two groups for change in the sum of four dehydration symptoms (-3.3 v -2.8, P = .77), ESAS (all nonsignificant), MDAS (1 v 3.5, P = .084), NuDESC (0 v 0, P = .13), and UMRS (0 v 0, P = .54) by day 4. Results for day 7, including FACIT-F, were similar. Overall survival did not differ between the two groups (median, 21 v 15 days, P = .83). CONCLUSION Hydration at 1 L per day did not improve symptoms, quality of life, or survival compared with placebo.

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.

The Association Between Autonomic Dysfunction and Survival in Male Patients with Advanced Cancer: A Preliminary Report

CONTEXT Autonomic nervous system dysfunction (AD) is a common syndrome in patients with advanced cancer. It is associated with decreased survival in several patient populations, including diabetes mellitus, heart failure, and neurological diseases. Based on this evidence, we hypothesized that autonomic dysfunction is associated with decreased survival in patients with advanced cancer. OBJECTIVES The objective of this preliminary study was to test the association between AD, as measured by the standardized Ewing test and heart rate variability (HRV) measures, and survival in this patient population. METHODS We examined the relationship between survival and parameters of AD in subjects who participated in a prospective study of autonomic dysfunction and hypogonadism in male patients with advanced cancer. Eligibility criteria were defined based on the prospective study protocol. We collected demographic information, date of death (obtained from the online Social Security Death Index database), date of study entry, and Ewing and HRV scores. We defined survival as the interval between study entry and date of death. A survival analysis was used to test the association between survival (in days) and Ewing test (0-5) and measures of HRV, including time domain (standard deviation of normal to normal beat interval [SDNN]) and frequency domain (ultra low, very low, low, and high). Four patients were still alive at the time of this study and included in the survival analysis as being censored. RESULTS Forty-seven male patients were included in this study. Median age was 59 years (range: 20-79), and 30 out of 47 (63%) were Caucasians. AD, defined as Ewing score greater than 2, was present in 38 out of 47 (80%) of the patients. Median Ewing score was 3 (1-5), indicating moderate to severe AD. Spearman correlation for Ewing score and SDNN was 0.44 (P = 0.002). There was a significant association between abnormal Ewing score and survival (P < 0.0001) and abnormal SDNN HRV and survival (P = 0.056). CONCLUSION AD is associated with shorter survival in male patients with advanced cancer. Further longitudinal research in a large cohort is justified based on.

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.

The Role of Thalidomide and Placebo for the Treatment of Cancer-Related Anorexia-Cachexia Symptoms: Results of a Double-Blind Placebo-Controlled Randomized Study

OBJECTIVES To determine the effects of thalidomide and placebo on anorexia-cachexia and its related symptoms, body composition, resting metabolic rate, and serum cytokines and their receptors in patients with advanced cancer. METHODS Included in the study were patients with advanced cancer with weight loss greater than 5% in 6 months and who reported anorexia, fatigue, and one of the following: anxiety, depression, or sleep disturbances. Patients on chemotherapy within 2 weeks prior or during the study were excluded from the study. Patients were randomly assigned to either 100 mg thalidomide or placebo once a day for 14 days. The Edmonton Symptom Assessment Scale (ESAS), Functional Assessment of Anorexia/Cachexia Therapy (FAACT), Functional Assessment of Cancer Illness Therapy (FACIT-F), Hospital Anxiety Depression Scale (HADS) Pittsburgh Sleep Quality Index (PSQI) were utilized, and in addition body composition, Resting Energy Expenditure (REE), and serum cytokine levels were assessed. RESULTS Of the 31 patients entered in the study, 15 were assigned to the thalidomide group and 16 to the placebo group. However only 21/31 patients were able to complete the study. Compared with their baseline values, both the thalidomide and the placebo groups showed significant reduction in cytokines. Tumor necrosis factor (TNF)-α (p=0.04) and its receptors TNFR1 (p=0.04), TNFR2 (p=0.04), and interleukin (IL)-8 (p=0.04) were statistically significant in the thalidomide group. In the placebo group, TNF-α (p=0.008), TNFR1 (p=0.005), TNFR2 (p=0.005), IL-RA (p=0.005), IL-6 (p=0.005), and IL-8 (p=0.005) were statistically significant. However, improvement in these symptoms and cytokine levels were not significantly different in the thalidomide group compared with the placebo group. None of the patients withdrew from the study because of toxicity of either thalidomide or placebo. CONCLUSIONS Based on the poor accrual rate and attrition observed in this study, it is important that future research on thalidomide as a treatment for cancer-related anorexia-cachexia symptoms (ACS) in patients with advanced cancer use less stringent entry criteria and less exhaustive outcome measures.

Characteristics and Outcomes of Patients Admitted to the Acute Palliative Care Unit From the Emergency Center

CONTEXT Most patients admitted to acute palliative care units (APCUs) are transferred from inpatient oncology units. We hypothesized that patients admitted to APCUs from emergency centers (ECs) have symptom burdens and outcomes that differ from those of transferred inpatients. OBJECTIVES The purpose of this retrospective cohort study was to compare the symptom burdens and survival rate of patients admitted to an APCU from an EC with those of inpatients transferred to the APCU. METHODS Among the 2568 patients admitted to our APCU between September 1, 2003 and August 31, 2008, 312 (12%) were EC patients. We randomly selected 300 inpatients transferred to the APCU as controls (The outcome data were unavailable for two patients). We retrieved data on patient demographics, cancer diagnosis, Edmonton Symptom Assessment System scores, discharge outcomes, and overall survival from time of admission to the APCU. RESULTS The EC patients had higher rates of pain, fatigue, nausea, and insomnia and were less likely to be delirious. They were more than twice as likely to be discharged alive than transferred inpatients. Kaplan-Meier plot tests for product-limit survival estimate from admission to APCU for EC patients and inpatients were statistically significant (median survival 34 vs. 31 days, P<0.0001). In multivariate analysis, EC admission (odds ratio [OR]=1.8593, 95% confidence interval [CI] 1.1532-2.9961), dyspnea (OR=0.8533, 95% CI 0.7892-0.9211), well-being (OR=1.1192, 95% CI 1.0234-1.2257), and delirium (OR=0.3942, 95% CI 0.2443-0.6351) were independently associated with being discharged alive. CONCLUSION The EC patients have a higher acute symptom burden and are more likely to be discharged alive than transferred inpatients. The APCU was successful at managing symptoms and facilitating the discharge of both inpatients and EC patients to the community although the patients had severe symptoms on admission.

Frequency and outcome of neuroleptic rotation in the management of delirium in patients with advanced cancer

Purpose The response to haloperidol as a first-line neuroleptic and the pattern of neuroleptic rotation after haloperidol failure have not been well defined in palliative care. The purpose of this study was to determine the efficacy of haloperidol as a first-line neuroleptic and the predictors associated with the need to rotate to a second neuroleptic. Materials and Methods We conducted a retrospective review of the charts of advanced cancer patients admitted to our acute palliative care unit between January 2012 and March 2013. Inclusion criteria were a diagnosis of delirium and first-line treatment with haloperidol. Results Among 167 patients with delirium, 128 (77%) received only haloperidol and 39 (23%) received a second neuroleptic. Ninety-one patients (71%) who received haloperidol alone improved and were discharged alive. The median initial haloperidol dose was 5 mg (interquartile ranges [IQR], 3 to 7 mg) and the median duration was 5 days (IQR, 3 to 7 days). The median final haloperidol dose was 6 mg (IQR, 5 to 7 mg). A lack of treatment efficacy was the most common reason for neuroleptic rotation (87%). Significant factors associated with neuroleptic rotation were inpatient mortality (59% vs. 29%, p=0.001), and being Caucasian (87% vs. 62%, p=0.014). Chlorpromazine was administered to 37 patients (95%) who were not treated successfully by haloperidol. The median initial chlorpromazine dose was 150 mg (IQR, 100 to 150 mg) and the median duration was 3 days (IQR, 2 to 6 days). Thirteen patients (33%) showed reduced symptoms after the second neuroleptic. Conclusion Neuroleptic rotation from haloperidol was only required in 23% of patients with delirium and was associated with inpatient mortality and white race.

A prospective study: Hypodermoclysis performed by caregivers in the home setting.

128 Background: Decreased oral intake is very common at the end of life. Dehydration can aggravate symptoms like fatigue, myoclonus, and confusion. Intravenous (iv) hydration at home can be uncomfortable and expensive. Hypodermoclysis (HDC) is a comfortable and inexpensive but rarely used way to provide hydration at the end of life in the home setting. The purpose of this study was to evaluate a program of HDC at home by the caregivers. METHODS All caregivers underwent a 45 minute training session on HDC administration and assessment of infusion site delivered by a specially trained nurse. Caregivers received daily calls and on site evaluation on day 8. RESULTS A total of 21 patient/caregivers dyads were admitted to this preliminary study: 10 (47%) female patients and 16 (76%) female caregivers. All patients had advanced cancer receiving hospice care at home. All caregivers who received training were able to start the infusion. Side effects were minimal with 1 (5%) care of the needle difficulty and leakage. CONCLUSIONS This preliminary study suggests that subcutaneous hydration can be administered by caregivers at home with minimal burden. It can be easily done by just gravity or weight. It will avoid the use of expensive iv pump devices or need of special technical support. [Table: see text].

Clinical characteristics and outcomes of advanced cancer patients referred to outpatient supportive care who missed their appointment.

79 Background: Supportive Care Outpatient Clinics (SCOC) offer comprehensive care and symptom management to patients with advanced cancer (AdCa). Missed appointments (MA) are important source of problems to patient care and clinic operations. But there are no studies on the clinical outcomes of patients who fail to show for consultation. METHODS We determined the frequency of MA, including clinical and demographic data, and reviewed clinic appointment records for 218 consecutive kept (KA) and 218 MA for distinct patients referred to SCOC from January to December 2011. RESULTS 218/1,352(16%) AdCa who were referred to our SCOC, missed their appointment. Median age was 57 years (interquartile range 49-67). The mean(range) time between referral and appointment was 7.4 days(0-71) for KA vs. 9.1 days(0-89) for MA (p=0.0062). Age, gender, marital status, and cancer types or stages, and reasons for referral to SCOC were not significantly different between MA and KA patients. The reasons for MA were: admission to the hospital 17/218(8%), death 4/218(2%), appointment with primary oncologist 37/218(18%), other appointments 19/218(9%), visits to emergency room(ER) 9/218(9%), and unknown 111/218(54%). MA patients visited more the ER at 2 weeks 16/214(7%) vs. 5/217(2%), p=0.01, and 4 weeks 17/205(8%) vs. 8/217(4%), p=0.06. Median survival for MA patients was 177 days (range:127-215) vs. 253 days (range:192-347) for KA patients (p=0.013). Multivariate analysis showed that MA were associated to the time between referral and scheduled appointment (OR: 1.026/day, p=0.03), referral from targeted therapy services (OR:2.177, p=0.004), living at Texas/Louisiana regions (OR;2.345, p=0.002), having advanced directives (OR:0.154, P<0.0001), and being referred for symptom control(OR:0.024, p=0.0003). CONCLUSIONS AdCa with MA have worse survival and increased ER utilization. We identified AdCa at higher risk for MA who should undergo more aggressive follow up. More research on MA prevention is needed.

A Comparative Analysis of Academic and Nonacademic Hospitals on Outcome Measures and Patient Satisfaction

Academic hospitals contribute to health care through patient care, research, and teaching; however, their outcomes may not be equivalent to nonacademic hospitals. Multivariate analysis of variance is used to compare publicly reported data on patient satisfaction, readmission rates, mortality rates, and hospital-acquired injury scores between 1906 academic and nonacademic hospitals, while controlling for hospital-level covariates. Results show that academic hospitals have higher levels of patient satisfaction on 7 of the 11 measures and are equivalent to nonacademic hospitals on the remaining 4 measures. Academic hospitals have lower pneumonia mortality rates than nonacademic hospitals, with no difference for other mortality or disease-specific readmissions. However, academic hospitals have a slightly higher overall readmission rate. Infection rates were equivalent between academic and nonacademic hospitals for central line-associated bloodstream infections, pressure ulcers, and wound dehiscence for abdominal and pelvic injuries, but academic hospitals have higher catheter-associated urinary tract infection rates.