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Context: People with spasticity that occurred between 30 days and one year after stroke onset with a baseline Modified Ashworth Scale (MAS) ≥1.Objectives: To determine the practicality of a pragmatic parallel-group open-labeled randomized controlled trial and to collect preliminary data of effectiveness and safety of electroacupuncture (EA) for poststroke spasticity.Methods: Eligible participants were randomly allocated to the intervention group (EA plus usual care) or the control group (usual care alone) at a 1:1 ratio with block sizes of six. Participants received EA three times a week for four weeks, then were followed up for another four weeks. Participants' retention and adherence in the trial were assessed to determine the practicality of trial design. Clinical outcome measures were the change scores of MAS, Fugl-Meyer Assessment of motor performance and Barthel Index, and adverse events.Results: Seventy-two people were screened for eligibility, and 30 of them were recruited and randomized. At the end, 25 participants followed the trial protocol and were included in our final data analyses using an intention-to-treat approach. No significant between-group difference was detected for the change scores of MAS, Fugl-Meyer Assessment, or Barthel Index at the end of treatment or end of follow-up. Eighteen participants reported 37 adverse events, but none of the participants was deemed related to EA.Conclusion: It is feasible to conduct a full-scale trial to precisely evaluate the effectiveness and safety of EA for treating poststroke spasticity; however, longer treatment and follow-up phases should be considered in the full-scale trial. [ABSTRACT FROM AUTHOR]

Context: Chronic breathlessness is a clinical syndrome that results in significant distress and disability. Morphine can reduce chronic breathlessness when the contributing etiologies are optimally treated.Objectives: Does oxycodone reduce chronic breathlessness compared with placebo?Methods: A multisite, randomized, placebo-controlled, double-blind, parallel-arm, fixed-dose trial of oral controlled-release oxycodone 15 mg (5 mg, eight hourly) or placebo (ACTRN12609000806268 at www.anzctr.org.au). As-needed immediate-release morphine (2.5 mg per dose; six and less doses/day) was available for both arms as required by one ethics committee overseeing the trial. Recruitment occurred from 2010 to 2014 in 14 inpatient and outpatient respiratory, cardiology, and palliative care services across Australia. Participants were adults, with chronic breathlessness (modified Medical Research Council Scale 3 or 4), who were opioid naive. The primary end point was the proportion of people with greater than 15% reduction from baseline in the intensity of breathlessness now (0-100 mm visual analogue scale) comparing arms Days 5-7. Secondary end points were average and worst breathlessness, quality of life, function, and harms.Results: Of 157 participants randomized, 155 were included (74 oxycodone and 81 placebo), but the study did not reach target recruitment. There was difference in neither between groups for the primary outcome (P = 0.489) nor any of the prespecified secondary outcomes. Placebo participants used more as-needed morphine (mean 7.0 vs. 4.2 doses; P ≤ 0.001). Oxycodone participants reported more nausea (P < 0.001).Conclusion: There was no signal of benefit from oxycodone over placebo. Future research should focus on investigating the existence of an opioid class effect on the reduction of chronic breathlessness. [ABSTRACT FROM AUTHOR]

Context: The optimal dose of fentanyl sublingual spray (FSS) for exertional dyspnea has not been determined.Objectives: We examined the effect of two doses of prophylactic FSS on exertional dyspnea.Methods: In this parallel, dose-finding, double-blind randomized clinical trial, opioid-tolerant cancer patients completed a shuttle walk test at baseline. Patients completed a second shuttle walk test 10 minutes after a single dose of FSS equivalent to either 35%-45% (high dose) or 15%-25% (low dose) of the total daily opioid dose. The primary outcome was change in modified dyspnea Borg scale (0-10) between the first and second shuttle walk tests. Secondary outcomes included adverse events as well as changes in walk distance, vital signs, and neurocognitive function.Results: Thirty of the 50 enrolled patients completed the study. High-dose FSS (n = 13) resulted in significantly lower dyspnea (mean change -1.42; 95% CI -2.37, -0.48; P = 0.007) and greater walk distance (mean change 44 m; P = 0.001) compared to baseline. Low-dose FSS (n = 17) resulted in a nonsignificant reduction in dyspnea (mean change -0.47; 95% CI -1.26, 0.32; P = 0.24) and significant increase in walk distance (mean change 24 m; P = 0.01) compared to baseline. Global evaluation showed high-dose group was more likely to report at least somewhat better improvement (64% vs. 24%; P = 0.06). No significant adverse events or detriment to vital signs or neurocognitive function was detected.Conclusion: Prophylactic FSS was well tolerated and demonstrated a dose-response relationship in improving both dyspnea and walk distance. High-dose FSS should be tested in confirmatory trials. [ABSTRACT FROM AUTHOR]

Context: Although opioids and pregabalin are widely used for cancer-related neuropathic pain (CNP), no clinical trials exist to determine which medications are effective when an opioid-pregabalin combination therapy fails.Objectives: We investigated the efficacy of duloxetine for CNP nonresponsive or intolerant to opioid-pregabalin combination therapy.Methods: A multicenter, randomized, double-blind, placebo-controlled trial was performed at 12 specialized palliative care services in Japan. Patients with CNP average pain scores (Brief Pain Inventory [BPI]-Item 5) ≥ 4 in the previous 24 hours and nonresponsive or intolerant to opioid-pregabalin combination therapy were eligible. Patients with chemotherapy-induced peripheral neuropathies were excluded. Patients were administered duloxetine 20 mg/day titrated to 40 mg/day or placebo for 10 days. The primary endpoint was BPI-Item 5 on Day 10. Responder analysis measured proportions of patients with 30% and 50% pain decreases.Results: Seventy patients were enrolled. Complete case analysis revealed mean BPI-Item 5 on Day 10 of 4.03 for Group D vs. 4.88 for Group P (P = 0.053). Baseline observation carried forward analysis revealed mean BPI-Item 5 on Day 10 of 4.06 and 4.91 for Groups D and P, respectively (P = 0.048). Clinically meaningful pain improvement (≥30%) was reported by 44.1% (n = 15) of patients in Group D vs. 18.2% (n = 6) in Group P (P = 0.02); 32.4% (n = 11) vs. 3.0% (n = 1) of patients in Groups D and P, respectively, reported pain reduction ≥ 50% (P = 0.002).Conclusion: Adding duloxetine to opioid-pregabalin therapy might have clinical benefit in alleviating refractory CNP. Further studies are needed to conclude the efficacy of adding duloxetine. [ABSTRACT FROM AUTHOR]

Context: Pulmonary arterial hypertension (PAH) affects people of all ages and is associated with poor prognosis. Chronic breathlessness affects almost all people with PAH.Objectives: This randomized, placebo-controlled, double-blind, crossover study aimed to evaluate the effects of regular, low-dose, extended-release (ER) morphine for PAH-associated chronic breathlessness.Methods: Participants with PAH-associated chronic breathlessness were randomized to 1) seven days of ER morphine 20 mg, 2) seven-day washout, and 3) seven days of identically looking placebo, or vice versa. Primary end points were breathlessness "right now"-morning and evening-measured with a Visual Analogue Scale. Secondary end points included additional breathlessness measures, quality of life, function, harms, and blinded treatment preference (ACTRN12609000209291).Results: Within a period of seven years, 50 patients were assessed in detail and 23 (46%) were randomized (despite broad eligibility criteria). Four participants withdrew while taking morphine. Nineteen participants completed the study. Breathlessness "right now" was higher on morphine compared with placebo both for morning [mean (M) ± SD 31.7 ± 25 mm vs. 26.9 ± 22 mm; effect size (80% CI) = -0.22 (-0.6 to 0.2)] and evening [(M ± SD 33.5 ± 28 mm vs. 25.6 ± 21 mm; effect size (80% CI) = -0.33 (-0.8 to 0.1)]. All secondary measures of breathlessness were higher with morphine as were nausea and constipation.Conclusion: This study does not support a Phase III study of ER morphine for people with PAH-associated chronic breathlessness. Recruiting to the target sample size was difficult, the direction of effect in every measure of breathlessness favored placebo and morphine generated more harms. [ABSTRACT FROM AUTHOR]

Context: Dyspnea is a common distressing symptom among patients with advanced cancer.Objective: The objective of this study was to determine the effect of fan therapy on dyspnea in patients with terminally ill cancer.Methods: This parallel-arm, randomized controlled trial included 40 patients with advanced cancer from a palliative care unit at the National Cancer Center Hospital in Japan. All patients experienced dyspnea at rest with a score of at least three points on a subjective 0- to 10-point Numerical Rating Scale (NRS), showed peripheral oxygen saturation levels of ≥90%, had an Eastern Cooperative Oncology Group grade of 3 or 4, and were aged 20 years or more. In one group, a fan was directed to blow air on the patient's face for five minutes. This group was compared to a control group wherein air was blown to the patient's legs. Patients were randomly assigned to each group. The main outcome measure was the difference in dyspnea NRS scores between fan-to-face and fan-to-legs groups.Results: No significant differences were seen in baseline dyspnea NRS between groups (mean score, 5.3 vs. 5.1, P = 0.665). Mean dyspnea changed by -1.35 points (95% CI, -1.86 to -0.84) in patients assigned to receive fan-to-face and by -0.1 points (-0.53 to 0.33) in patients assigned to receive fan-to-legs (P < 0.001). The proportion of patients with a one-point reduction in dyspnea NRS was significantly higher in the fan-to-face arm than in the fan-to-legs arm (80% [n = 16] vs. 25% [n = 5], P = 0.001).Conclusion: Fan-to-face is effective in alleviating dyspnea in patients with terminally ill cancer. [ABSTRACT FROM AUTHOR]

Context: Provision of home-based palliative care (PC) for seriously ill patients is important, yet few home-based PC services specifically or exclusively focus on end-stage heart failure (ESHF) patients.Objectives: This study aimed to examine the effect of a home-based palliative heart failure (HPHF) program on quality of life (QOL), symptoms burden, functional status, patient satisfaction, and caregiver burden among patients with ESHF.Methods: This study was a two-group randomized controlled trial undertaken in three hospitals. We recruited a total of 84 hospitalized ESHF patients who were referred to PC. They were randomized to the intervention or control group. The intervention group received a 12-week structured program with regular home visits/telephone calls provided by the nurse case managers. Data were collected at baseline (T1) and at four (T2) and 12 weeks (T3) after discharge.Results: A statistically significant between-group effect was found, with the HPHF group having significantly higher McGill QOL total score than the control group (P = 0.016) and there was significant group × time interaction effect (P = 0.032). There was no significant between-group effects detected for the measures of symptom distress or functional status at 12 weeks. The intervention group had higher satisfaction (P = 0.001) and lower caregiver burden (P = 0.024) than the control group at 12 weeks.Conclusion: The HPHF program is effective in enhancing the QOL of ESHF patients, satisfaction with care, and caregiver burden. The program has potential to reduce distress for some of the symptoms. [ABSTRACT FROM AUTHOR]

Context: Physical exercise can alleviate cancer-related fatigue. Randomized controlled trials in patients with advanced cancer are scarce.Objectives: We test the impact of a structured, individual sports program on fatigue in patients with advanced cancer.Methods: Seventy-seven patients were invited to participate in this randomized controlled trial exploring the effects of physical exercises on fatigue 12 and 24 weeks after baseline. Patients were randomized into three groups. Group A received treatment as usual, Group B was taught a structured, individual sports program, and Group C received additional ambulatory physiotherapeutical supervision. Primary outcome was general fatigue, secondary outcomes included rate of severe general fatigue, further dimensions of the Multidimensional Fatigue Inventory (MFI), as well as walking distance.Results: Mean score of general fatigue as well as other MFI subdimensions differed nonsignificantly between all groups at 12 weeks. However, the mental fatigue score demonstrated a statistically significant difference between the three groups. The rate of severe general fatigue was significantly reduced within Intervention Group C. Significant longitudinal change of MFI-dimension mental fatigue was found and reached the threshold for minimal clinically important difference, while all MFI-dimensions increased in Group A.Conclusion: Our results imply that tumor-patients' severe general fatigue can be reduced when patients conduct appropriate physical exercise. This study amends previous knowledge, as it describes the impact of outpatient physical exercise on fatigue in a heterogeneous patient cohort with various advanced cancer entities. Furthermore, this trial differentiates between patients with only a self-directed exercise program versus those receiving additional partially professional supervision. [ABSTRACT FROM AUTHOR]

Context: Relaxation interventions are frequently used to promote symptom relief in palliative care settings, but little is known about the underlying mechanisms.Objectives: The present analysis aimed at examining the psychophysiological pathways of terminally ill patients' cardiovascular response to a live music therapy vs. prerecorded mindfulness exercise.Methods: Eighty-four patients of a palliative care unit were randomly assigned to either of the two interventions. Multilevel modeling was used to analyze trajectories of physiological change. Vagally mediated heart rate variability (VM-HRV) and blood volume pulse amplitude (BVP-A) served as indices of autonomic nervous system response. Participants' gender, age, baseline scores, self-rated pain, and assignment to treatment were entered to the models as predictors.Results: Both VM-HRV and BVP-A showed significant linear and quadratic trends over time, as well as substantial heterogeneity among individuals' trajectories. Baseline scores, pain, and treatment significantly accounted for random variation in VM-HRV intercepts. BVP-A levels were significantly higher in women than in men. Moreover, assignment to treatment significantly accounted for differences in the linear slopes of peripheral blood flow.Conclusion: Higher levels of VM-HRV in the music therapy group highlight the importance of a therapeutic relationship for the effectiveness of relaxation interventions in end-of-life care settings. Music therapy caused significantly stronger reductions of vascular sympathetic tone and, therefore, may be indicated in the treatment of pain and stress-related symptoms in palliative care. Initial self-ratings of pain moderated patients' physiological response and need to be taken into account in clinical practice and future theory building. [ABSTRACT FROM AUTHOR]

Context: Audits have been proposed for estimating possible recruitment rates to randomized controlled trials (RCTs), but few studies have compared audit data with subsequent recruitment rates.Objectives: To compare the accuracy of estimates of potential recruitment from a retrospective consecutive cohort audit of actual participating sites and recruitment to four Phase III multisite clinical RCTs.Methods: The proportion of potentially eligible study participants estimated from an inpatient chart review of people with life-limiting illnesses referred to six Australian specialist palliative care services was compared with recruitment data extracted from study prescreening information from three sites that participated fully in four Palliative Care Clinical Studies Collaborative RCTs. The predominant reasons for ineligibility in the audit and RCTs were analyzed.Results: The audit overestimated the proportion of people referred to the palliative care services who could participate in the RCTs (pain 17.7% vs. 1.2%, delirium 5.8% vs. 0.6%, anorexia 5.1% vs. 0.8%, and bowel obstruction 2.8% vs. 0.5%). Approximately 2% of the referral base was potentially eligible for these effectiveness studies. Ineligibility for general criteria (language, cognition, and geographic proximity) varied between studies, whereas the reasons for exclusion were similar between the audit and pain and anorexia studies but not for delirium or bowel obstruction.Conclusion: The retrospective consecutive case note audit in participating sites did not predict realistic recruitment rates, mostly underestimating the impact of study-specific inclusion criteria. These findings have implications for the applicability of the results of RCTs. Prospective pilot studies are more likely to predict actual recruitment. [ABSTRACT FROM AUTHOR]

Context Pediatric palliative care randomized controlled trials (PPC-RCTs) are uncommon. Objectives To evaluate the feasibility of conducting a PPC-RCT in pediatric cancer patients. Methods This was a cohort study embedded in the Pediatric Quality of Life and Evaluation of Symptoms Technology Study (NCT01838564). This multicenter PPC-RCT evaluated an electronic patient-reported outcomes system. Children aged two years and older, with advanced cancer, and potentially eligible for the study were included. Outcomes included: pre-inclusion attrition (patients not approached, refusals); post-inclusion attrition (drop-out, elimination, death, and intermittent attrition (IA; missing surveys) over nine months of follow-up); child/teenager self-report rates; and, reasons to enroll/participate. Results Over five years, of the 339 identified patients, 231 were eligible (in 22, we could not verify eligibility); 84 eligible patients were not approached and 43 declined participation. Patients not approached were more likely to die or have brain tumors. We enrolled 104 patients. Average enrollment rate was one patient per site per month; shortening follow-up from nine to three months (with optional re-enrollment) increased recruitment by 20%. A total of 87 patients completed the study (24 died) and 17 dropped out. Median IA was 41% in the first 20 weeks of follow-up and more than 60% in the eight weeks preceding death. Child/teenager self-report was 94%. Helping others, low burden procedures, incentives, and staff attitude were frequent reasons to enroll/participate. Conclusion A PPC-RCT in children with advanced cancer was feasible, post-inclusion retention adequate; many families participated for altruistic reasons. Strategies that may further PPC-RCT feasibility include: increasing target population through large multicenter studies, approaching sicker patients, preventing exclusion of certain patient groups, and improving data collection at end of life. [ABSTRACT FROM AUTHOR]

Context Does octreotide reduce vomiting in cancer-associated bowel obstruction? Objectives To evaluate the net effect of adding octreotide or placebo to standardized therapies on the number of days free of vomiting for populations presenting with vomiting and inoperable bowel obstruction secondary to cancer or its treatment. Methods Twelve services enrolled people with advanced cancer presenting with vomiting secondary to bowel obstruction where surgery or anti-cancer therapies were not indicated immediately. In a double-blind study, participants were randomized to placebo or octreotide (600 μg/24 hours by infusion). Both arms received standardized supportive therapy (infusion of ranitidine [200 mg/24 hours], dexamethasone [8 mg/24 hours], and parenteral hydration [10–20 mL/kg/24 hours]). The primary outcome was patient-reported days free of vomiting at 72 hours. Results In a study that recruited to the numbers identified in its power calculation, 87 participants provided data at 72 hours (45, octreotide arm). Seventeen people (octreotide) and 14 (placebo) were free of vomiting for 72 hours ( P = 0.67). Mean days free of vomiting were 1.87 (SD 1.10; octreotide) and 1.69 (SD 1.15; placebo; P = 0.47). An adjusted multivariate regression of the incidence of vomiting over the study showed a reduced number of episodes of vomiting in the octreotide group (incidence rate ratio = 0.40; 95% CI: 0.19–0.86; P = 0.019); however, people in the octreotide arm were 2.02 times more likely to be administered hyoscine butylbromide ( P = 0.004), potentially reflecting increased colicky pain. Conclusion Although there was no reduction in the number of days free of vomiting, the multivariate analysis suggests that further study of somatostatin analogues in this setting is warranted. [ABSTRACT FROM AUTHOR]

Context. The difference in patient-reported outcomes between study arms can often be difficult to ascertain in randomized controlled trials (RCTs) using a parallel design because of wide interindividual variations in baseline characteristics and how patients interpret the outcome measures. Furthermore, the minimal clinically significant difference is often not available for many outcomes, and even when available, not individualized for each patient. Crossover RCTs are designed for intraindividual comparisons, which can address these issues by asking patients to directly compare the interventions with regard to effectiveness, adverse effects, and ease of use and to provide an overall choice. Objectives. We discuss the key design elements for crossover trials, their advantages and disadvantages relative to parallel designs, and their utility in palliative care research using a number of case examples. Methods. This is a narrative review. Results. Crossover studies randomize patients to a sequence of treatments. In addition to facilitating intraindividual comparisons, they often require a smaller sample size for the same statistical power compared with parallel designs and are thus less costly. However, crossover studies are only feasible when the condition being studied is relatively stable and the intervention has a short-term effect. Crossover studies with inadequate washout periods may be difficult to interpret. The risk of attrition also may increase because of prolonged study duration. Conclusion. By facilitating intraindividual comparisons and eliciting patient preferences, crossover studies can provide unique information on the superior intervention. Crossover designs should be considered for selected palliative care studies. [ABSTRACT FROM AUTHOR]

We report the challenges of the Working to Improve Discussions About Defibrillator Management trial, our novel, multicenter trial aimed at improving communication between cardiology clinicians and their patients with advanced heart failure (HF) who have implantable cardioverter defibrillators (ICDs). The study objectives are (1) to increase ICD deactivation conversations, (2) to increase the number of ICDs deactivated, and (3) to improve psychological outcomes in bereaved caregivers. The unit of randomization is the hospital, the intervention is aimed at HF clinicians, and the patient and caregiver are the units of analysis. Three hospitals were randomized to usual care and three to intervention. The intervention consists of an interactive educational session, clinician reminders, and individualized feedback. We enroll patients with advanced HF and their caregivers, and then we regularly survey them to evaluate whether the intervention has improved communication between them and their HF providers. We encountered three implementation barriers. First, there were institutional review board concerns at two sites because of the palliative nature of the study. Second, we had difficulty in creating entry criteria that accurately identified an HF population at high risk of dying. Third, we had to adapt our entry criteria to the changing landscape of ventricular assist devices and cardiac transplant eligibility. Here we present our novel solutions to the difficulties we encountered. Our work has the ability to enhance conduct of future studies focusing on improving care for patients with advanced illness. [ABSTRACT FROM AUTHOR]

When conducting research on pain and symptom management interventions for seriously ill individuals, randomized controlled trials are not always feasible or ethical to conduct. Secondary analyses of observational data sets that include information on treatments experienced and outcomes for individuals who did and did not receive a given treatment can be conducted, but confounding because of selection bias can obscure the treatment effect in which one is interested. Propensity scores provide a way to adjust for observable characteristics that differ between treatment and comparison groups. This article provides conceptual guidance in addition to an empirical example to illustrate two areas of propensity score analysis that often lead to confusion in practice: covariate selection and interpretation of resultant treatment effects. [ABSTRACT FROM AUTHOR]

Abstract: Context: Lung cancer patients experience multiple, simultaneous symptoms related to their disease and treatment that impair functioning and health-related quality of life (HRQL). Computer technology can reduce barriers to nonsystematic, infrequent symptom assessment and potentially contribute to improved patient care. Objectives: To evaluate the efficacy of technology-based symptom monitoring and reporting in reducing symptom burden in patients with advanced lung cancer. Methods: This was a prospective, multisite, randomized controlled trial. Two hundred fifty-three patients were enrolled at three sites and randomized to monitoring and reporting (MR) or monitoring alone (MA). Patients completed questionnaires at baseline, 3, 6, 9, and 12 weeks and symptom surveys via interactive voice response weekly for 12 weeks. MR patients' clinically significant symptom scores generated an e-mail alert to the site nurse for management. The primary endpoint was overall symptom burden; secondary endpoints included HRQL, treatment satisfaction, symptom management barriers, and self-efficacy. Results: This randomized controlled trial failed to demonstrate efficacy of symptom monitoring and reporting in reducing symptom burden compared with monitoring alone in lung cancer. HRQL declined over 12 weeks in both groups (P < 0.006 to P < 0.025); at week 12, treatment satisfaction was higher in MA than MR patients (P < 0.012, P < 0.027). Adherence to weekly calls was good (82%) and patient satisfaction was high. Conclusion: Feasibility of using a technology-based system for systematic symptom monitoring in advanced lung cancer patients was demonstrated. Future research should focus on identifying patients most likely to benefit and other patient, provider, and health system factors likely to contribute to the system's success. [Copyright &y& Elsevier]

Abstract: Context: Dyspnea is one of the most distressing symptoms in patients with cancer, and often worsens with breakthrough episodes on exertion. We hypothesized that fentanyl given prophylactically may alleviate breakthrough dyspnea. Objectives: To determine the feasibility of conducting a randomized trial of subcutaneous fentanyl in patients with cancer, and examine the effects of fentanyl on dyspnea, walk distance, vital signs, and adverse events. Methods: In this double-blind, randomized, controlled trial, we asked ambulatory patients with breakthrough dyspnea to perform a baseline six minute walk test (6MWT), and then assigned them to either subcutaneous fentanyl or placebo 15 minutes before a second 6MWT. We documented the change in dyspnea Numeric Rating Scale (NRS) score, walk distance, vital signs, and adverse events between the first and second 6MWT. Results: A total of 20 patients were enrolled (1:1 ratio) without attrition. Comparison between baseline and second walk showed that fentanyl was associated with significant improvements in dyspnea NRS score at the end of the 6MWT (mean [95% CI] −1.8 [−3.2, −0.4]), dyspnea NRS score at rest of 15 minutes after drug administration (−0.9 [−1.8, −0.04]), Borg Scale fatigue score at the end of the 6MWT (−1.3 [−2.4, −0.2]), 6MWT distance (+37.2m [5.8, 68.6]), and respiratory rate (−2.4 [−4.5, −0.3]). Nonstatistically significant improvements also were observed in the placebo arm, with no difference between the two study arms. No significant adverse effects were observed. Conclusion: Prophylactic fentanyl was safe and improved dyspnea, fatigue, walk distance, and respiratory rate. We also observed a large placebo effect. Our results justify larger randomized controlled trials with higher fentanyl doses (clinicaltrials.gov registration: NCT01515566). [Copyright &y& Elsevier]

Abstract: Context: Treatment of pain in palliative care patients is challenging. Adjunctive methods of pain management are desirable. Music therapy offers a nonpharmacologic and safe alternative. Objectives: To determine the efficacy of a single music therapy session to reduce pain in palliative care patients. Methods: Two hundred inpatients at University Hospitals Case Medical Center were enrolled in the study from 2009 to 2011. Patients were randomly assigned to one of two groups: standard care alone (medical and nursing care that included scheduled analgesics) or standard care with music therapy. A clinical nurse specialist administered pre- and post-tests to assess the level of pain using a numeric rating scale as the primary outcome, and the Face, Legs, Activity, Cry, Consolability Scale and the Functional Pain Scale as secondary outcomes. The intervention incorporated music therapist-guided autogenic relaxation and live music. Results: A significantly greater decrease in numeric rating scale pain scores was seen in the music therapy group (difference in means [95% CI] −1.4 [−2.0, −0.8]; P <0.0001). Mean changes in Face, Legs, Activity, Cry, Consolability scores did not differ between study groups (mean difference −0.3, [95% CI] −0.8, 0.1; P >0.05). Mean change in Functional Pain Scale scores was significantly greater in the music therapy group (difference in means −0.5 ([95% CI] −0.8, 0.3; P <0.0001). Conclusion: A single music therapy intervention incorporating therapist-guided autogenic relaxation and live music was effective in lowering pain in palliative care patients. [Copyright &y& Elsevier]

Abstract: Context: Multiple complex symptoms from cancer treatment can interfere with functioning. Objectives: To evaluate the efficacy of an “energy and sleep enhancement” (EASE) intervention to relieve fatigue and sleep disturbance and improve health-related functional status. Methods: Individuals receiving chemotherapy (CTX) were randomized to the EASE (n =153) or a control intervention (n =139). The EASE intervention included information and behavioral skills taught by an oncology nurse in three telephone sessions. The primary outcomes of fatigue, sleep disturbance, and functional status were measured before CTX, Day 4 after first treatment (baseline), and 43–46 or 57–60 days later (follow-up), depending on the CTX cycle length. Results: The sample was primarily female (82%) and non-Hispanic white (89%), with mean age of 53.9 years. Fatigue and patient-reported sleep disturbance were elevated in both groups at baseline and follow-up. Actigraphy revealed that the total sleep time was almost eight hours, and sleep percent was greater than 85% for both groups at both time points (normal range). Physical functioning was diminished and at the same level as a sample with serious illness. Mental functioning was in normal range. A repeated-measures analysis of variance revealed no statistically significant group-by-time effects for fatigue, sleep disturbance, or functional status. Unemployed individuals showed greater benefit from the EASE intervention, reporting less pain and symptom interference. Conclusion: Potential explanations include high variability and/or floor effect for fatigue, incorrect timing of measures, insufficient amount or dose of the intervention, and confounding effects of gender. Future research should consider screening for symptom severity and tailoring interventions. [ABSTRACT FROM AUTHOR]

Abstract: Context: Published literature has not defined the effectiveness of standardized educational tools that can be self-administered in the general oncology population with pain. Objectives: We sought to determine if an educational intervention consisting of a video and/or booklet for adults with cancer pain could improve knowledge and attitudes about cancer pain management, pain levels, pain interference, anxiety, quality of life, and analgesic use. Methods: Eligible participants had advanced cancer, a pain score ≥2 of 10 in the last week, English proficiency, an estimated prognosis of more than one month, and were receiving outpatient cancer treatment at participating hospitals. Participants completed baseline assessments and then were randomly allocated to receive a booklet, a video, both, or neither, in addition to standard care. Outcome measures at two and four weeks included the Barriers Questionnaire (BQ), Brief Pain Inventory, Global Quality of Life Scale, and Hospital Anxiety and Depression Scale. Adequacy of analgesia and severity of pain were assessed with the Pain Management Index and a daily pain diary. Results: One hundred fifty-eight participants were recruited from 21 sites over 42 months. Baseline mean barriers scores were lower than reported in previous Australian studies at 1.33 (standard deviation: 0.92). Mean average pain and worst pain scores improved significantly in patients receiving both the video and booklet by 1.17 (standard error [SE]: 0.51, P =0.02) and 1.12 (SE: 0.57, P =0.05), respectively, on a 0–10 scale. The addiction subscale of the BQ score was improved by 0.44 (SE: 0.19) for participants receiving any part of the intervention (P =0.03). Conclusion: Provision of a video and/or booklet for people with cancer pain was a feasible and effective adjunct to the management of cancer pain. [Copyright &y& Elsevier]

Abstract: This study investigates whether using an HIV/AIDS symptom management manual with self-care strategies for 21 common symptoms, compared to a basic nutrition manual, had an effect on reducing symptom frequency and intensity. A 775-person, repeated measures, randomized controlled trial was conducted over three months in 12 sites from the United States, Puerto Rico, and Africa to assess the relationship between symptom intensity with predictors for differences in initial symptom status and change over time. A mixed model growth analysis showed a significantly greater decline in symptom frequency and intensity for the group using the symptom management manual (intervention) compared to those using the nutrition manual (control) (t =2.36, P =0.018). The models identified three significant predictors for increased initial symptom intensities and in intensity change over time: (1) protease inhibitor-based therapy (increased mean intensity by 28%); (2) having comorbid illness (nearly twice the mean intensity); and (3) being Hispanic receiving care in the United States (increased the mean intensity by 2.5 times). In addition, the symptom manual showed a significantly higher helpfulness rating and was used more often compared to the nutrition manual. The reduction in symptom intensity scores provides evidence of the need for palliation of symptoms in individuals with HIV/AIDS, as well as symptoms and treatment side effects associated with other illnesses. The information from this study may help health care providers become more aware of self-management strategies that are useful to persons with HIV/AIDS and help them to assist patients in making informed choices. [Copyright &y& Elsevier]

Abstract: Cardiac pain arising from chronic stable angina (CSA) is a cardinal symptom of coronary artery disease and has a major negative impact on health-related quality of life (HRQL), including pain, poor general health status, and inability to self-manage. Current secondary prevention approaches lack adequate scope to address CSA as a multidimensional ischemic and persistent pain problem. This trial evaluated the impact of a low-cost six-week angina psychoeducation program, entitled The Chronic Angina Self-Management Program (CASMP), on HRQL, self-efficacy, and resourcefulness to self-manage anginal pain. One hundred thirty participants were randomized to the CASMP or three-month wait-list usual care; 117 completed the study. Measures were taken at baseline and three months. General HRQL was measured using the Medical Outcomes Study 36-Item Short Form and the disease-specific Seattle Angina Questionnaire (SAQ). Self-efficacy and resourcefulness were measured using the Self-Efficacy Scale and the Self-Control Schedule, respectively. The mean age of participants was 68 years, 80% were male. Analysis of variance of change scores yielded significant improvements in treatment group physical functioning [F =11.75(1,114), P <0.001] and general health [F =10.94(1,114), P =0.001] aspects of generic HRQL. Angina frequency [F =5.57(1,115), P =0.02], angina stability [F =7.37(1,115), P =0.001], and self-efficacy to manage disease [F =8.45(1,115), P =0.004] were also significantly improved at three months. The CASMP did not impact resourcefulness. These data indicate that the CASMP was effective for improving physical functioning, general health, anginal pain symptoms, and self-efficacy to manage pain at three months and provide a basis for long-term evaluation of the program. [Copyright &y& Elsevier]

Context: Promoting patient value-concordant end-of-life care is a priority in health care systems but has rarely been examined in randomized clinical trials.Objectives: To examine the effectiveness of an advance care planning intervention in facilitating concordance between cancer patients' preferred and received life-sustaining treatment (LST) states and to explore modifiable factors facilitating or impeding such concordance.Methods: Terminal cancer patients (N = 460) were randomly assigned 1:1 to the experimental and control arms of a randomized clinical trial, with 430 deceased participants comprising the final sample. States of preferred LSTs (cardiopulmonary resuscitation, intensive care unit care, chest compression, intubation with mechanical ventilation, intravenous nutrition, and nasogastric tube feeding) and LSTs received in the last month were examined by hidden Markov modeling. Concordance and its modifiable predictors were evaluated by kappa and multivariate logistic regression, respectively.Results: We identified three LST-preference states (uniformly preferring LSTs, rejecting LSTs except intravenous nutrition support, and mixed LST preferences) and three received LST states (uniformly receiving LSTs, received intravenous nutrition only, and selectively receiving LSTs). Concordance was not significantly higher in the experimental than the control arm (kappa [95% CI]: 0.126 [0.032, 0.221] vs. 0.050 [-0.028, 0.128]; arm difference: odds ratio [95% CI]: 1.008 [0.675, 1.5001]). Preferred-received LST-state concordance was facilitated by accurate prognostic awareness, better quality of life, and more depressive symptoms, whereas concordance was impeded by more anxiety symptoms.Conclusions: Our advance care planning intervention did not facilitate concordance between terminally ill cancer patients' preferred and received LST states, but patient value-concordant end-of-life care may be facilitated by interventions to cultivate accurate prognostic awareness, improve quality of life, support depressive patients, and clarify anxious patients' overexpectations of LST efficacy. [ABSTRACT FROM AUTHOR]

Context Dignity therapy (DT) is a psychotherapeutic intervention with increasing evidence of acceptability and utility in palliative care settings. Objectives The aim of this study was to evaluate the legacy creation component of DT by comparing this intervention with life review (LR) and waitlist control (WC) groups. Methods Seventy adults with advanced terminal disease were randomly allocated to DT, LR, or WC followed by DT, of which 56 completed the study protocol. LR followed an identical protocol to DT except that no legacy document was created in LR. Primary outcome measures were the Brief Generativity and Ego-Integrity Questionnaire, Patient Dignity Inventory, Functional Assessment of Cancer Therapy-General, version 4, and treatment evaluation questionnaires. Results Unlike LR and WC groups, DT recipients demonstrated significantly increased generativity and ego-integrity scores at study completion. There were no significant changes for dignity-related distress or physical, social, emotional, and functional well-being among the three groups. There were also no significant changes in primary outcomes after the provision of DT after the waiting period in the WC group. High acceptability and satisfaction with interventions were noted for recipients of both DT and LR and family/carers of DT participants. Conclusion This study provides initial evidence that the specific process of legacy creation is able to positively affect sense of generativity, meaning, and acceptance near end of life. High acceptability and satisfaction rates for both DT and LR and positive impacts on families/carers of DT participants provide additional support for clinical utility of these interventions. Further evaluation of specific mechanisms of change post-intervention is required given DT's uncertain efficacy on other primary outcomes. [ABSTRACT FROM AUTHOR]

Context: Somatostatin analogues are commonly used to relieve symptoms in malignant bowel obstruction (MBO) but are more expensive than other antisecretory agents.Objectives: To evaluate the evidence of effectiveness of somatostatin analogues compared with placebo and/or other pharmacologic agents in relieving vomiting in patients with inoperable MBO.Methods: MEDLINE, EMBASE, CINAHL, and The Cochrane Controlled Trials Register databases were systematically searched; reference lists of relevant articles were hand searched. Cochrane risk of bias tool was used.Results: The search identified 420 unique studies. Seven randomized controlled trials (RCTs) met the inclusion criteria (six octreotide studies and one lanreotide); 220 people administered somatostatin analogues and 207 placebo or hyoscine butylbromide. Three RCTs compared a somatostatin analogue with placebo and four with hyoscine butylbromide. Two adequately powered multicenter RCTs with a low Cochrane risk of bias reported no significant difference between somatostatin analogues and placebo in their primary end points. Four RCTs with a high/unclear Cochrane risk of bias reported that somatostatin analogues were more effective than hyoscine butylbromide in reducing vomiting.Conclusion: There is low-level evidence of benefit with somatostatin analogues in the symptomatic treatment of MBO. However, high-level evidence from trials with low risk of bias found no benefit of somatostatin analogues for their primary outcome. There is debate regarding the clinically relevant study end point for symptom control in MBO and when it should be measured. The role of somatostatin analogues in this clinical situation requires further adequately powered, well-designed trials with agreed clinically important end points and measures. [ABSTRACT FROM AUTHOR]

Context Episodic breathlessness is common and debilitating in cancer patients. Objectives In this pilot study, we examined the effect of prophylactic fentanyl pectin nasal spray (FPNS) on exercise-induced dyspnea, physiologic function, and adverse events. Methods In this parallel, double-blind randomized placebo-controlled trial, opioid-tolerant patients performed three six-minute walk tests (6MWTs) to induce dyspnea. They were randomized to receive either FPNS (15%–25% of total daily opioid dose each time) or placebo 20 minutes before the second and third 6MWTs. We compared dyspnea Numeric Rating Scale (NRS, 0–10, primary outcome), walk distance, vital signs, neurocognitive function, and adverse events between the first and second 6MWTs (T2-T1) and between the first and third 6MWTs (T3-T1). Results Twenty-four patients enrolled, with 96% completion. FPNS was associated with significant within-arm reduction in dyspnea NRS at rest (T2-T1: −0.9 [95% CI −1.7, −0.1]; T3-T1: −1.3 [95% CI −2.0, −0.5]) and at the end of a 6MWT (T2-T1: −2.0 [95% CI −3.5, −0.6]; T3-T1: −2.3 [95% CI −4.0, −0.7]), and longer walk distance (T2-T1 +23.8 m [95% CI +1.3, +46.2 m]; T3-T1: +23.3 m [95% CI −1.7, +48.2]). In the placebo arm, we observed no significant change in walk distance nor dyspnea NRS at rest, but significant reduction in dyspnea NRS at six minutes (T2-T1: −1.7 [95% CI −3.3, −0.1]; T3-T1: −2.5 [95% CI −4.2, −0.9]). Vital signs, neurocognitive function, and adverse effects did not differ significantly. Conclusion FPNS was safe, reduced dyspnea at rest, and increased walk distance in before-after comparison. The placebo effect was substantial, which needs to be factored in future study designs. Trial Registration ClinicalTrials.gov NCT01832402 . [ABSTRACT FROM AUTHOR]

Context: Dexamethasone is often used to treat dyspnea in cancer patients, but evidence is lacking.Objectives: We determined the feasibility of conducting a randomized trial of dexamethasone in cancer patients and estimated the efficacy of dexamethasone in the treatment of dyspnea.Methods: In this double-blind, randomized, controlled trial, patients with dyspnea ≥4 were randomized to receive either dexamethasone 8 mg twice daily × four days then 4 mg twice daily × three days or placebo for seven days, followed by an open-label phase for seven days. We documented the changes in dyspnea (0-10 numeric rating scale), spirometry measures, quality of life, and toxicities.Results: A total of 41 patients were randomized and 35 (85%) completed the blinded phase. Dexamethasone was associated with a significant reduction in dyspnea numeric rating scale of -1.9 (95% CI -3.3 to -0.5, P = 0.01) by Day 4 and -1.8 (95% CI -3.2 to -0.3, P = 0.02) by Day 7. In contrast, placebo was associated with a reduction of -0.7 (95% CI -2.1 to 0.6, P = 0.38) by Day 4 and -1.3 (95% CI -2.4 to -0.2, P = 0.03) by Day 7. The between-arm difference was not statistically significant. Drowsiness improved with dexamethasone. Dexamethasone was well tolerated with no significant toxicities.Conclusion: A double-blind, randomized, controlled trial of dexamethasone was feasible with a low attrition rate. Our preliminary data suggest that dexamethasone may be associated with rapid improvement in dyspnea and was well tolerated. Further studies are needed to confirm our findings.Trial Registration: ClinicalTrials.govNCT01670097. [ABSTRACT FROM AUTHOR]

Abstract: Context: With many medications available for the management of breakthrough cancer pain (BTCP), physicians may require additional guidance in selecting an appropriate medication to suit an individual patient's needs. Objectives: To identify all the evidence and assess the relative clinical value of currently approved BTCP medications. Methods: Following a systematic literature search (2007–2010), the results of 10 randomized controlled trials investigating the effects of BTCP medications (intranasal fentanyl spray [INFS], fentanyl pectin nasal spray, fentanyl sublingual tablets, fentanyl buccal soluble film, fentanyl buccal tablets, oral transmucosal fentanyl citrate, and morphine sulfate immediate release) were synthesized using a network meta-analysis. The main outcome was pain intensity difference (PID) relative to placebo up to 60 minutes after the intake of medication. Results: INFS, fentanyl pectin nasal spray, fentanyl buccal tablet, and oral transmucosal fentanyl citrate showed greater PIDs relative to placebo than other BTCP medications 15 minutes after intake. All other medications showed greater PIDs relative to placebo at 30 minutes, except morphine sulfate immediate release, which did not show efficacy over placebo until 45 minutes. Only INFS produced clinically meaningful pain relief (absolute PID ≥2) at 15 minutes. Conclusion: From current evidence, although all BTCP medications provided pain relief within the time frames assessed, transmucosal fentanyl medications achieved a greater level of pain relief in a shorter time frame than placebo or oral morphine. [Copyright &y& Elsevier]