Journal of Pain and Symptom Management - Articles in Press

Gaps in the Evidence Base of Opioids for Refractory Breathlessness. A Future Work Plan? - Corrected Proof

Miriam J. Johnson, Amy P. Abernethy, David C. Currow — 2012-01-30

Abstract: Breathlessness or “shortness of breath,” medically termed dyspnea, remains a devastating problem for many people and those who care for them. As a treatment intervention, administration of opioids to relieve breathlessness is an area where progress has been made with the development of an evidence base. As evidence in support of opioids has accumulated, so has our collective understanding about trial methodology, research collaboration, and infrastructure that is crucial to generate reliable research results for palliative care clinical settings. Analysis of achievements to date and what it takes to accomplish these studies provides important insights into knowledge gaps needing further research and practical insight into design of pharmacological and nonpharmacological intervention trials in breathlessness and palliative care. This article presents the current understanding of opioids for treating breathlessness, what is still unknown as priorities for future research, and highlights methodological issues for consideration in planned studies.

Is Oxycodone Efficacy Reflected in Serum Concentrations? A Multicenter, Cross-Sectional Study in 456 Adult Cancer Patients - Corrected Proof

2012-01-30

Abstract: Context: The relationship between oxycodone and metabolite serum concentrations and clinical effects has not previously been investigated in cancer pain patients.Objectives: The aim of this study was to assess whether there is a relationship between oxycodone concentrations and pain intensity, cognitive functioning, nausea, or tiredness in cancer patients. Also, oxymorphone and noroxymorphone contributions to analgesia and the adverse effects of oxycodone were assessed.Methods: Four hundred fifty-six cancer patients receiving oxycodone for cancer pain were included. Pain was assessed using the Brief Pain Inventory. The European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-C30 was used to assess the symptoms of tiredness, nausea, constipation, and depression. Cognitive function was assessed using the Mini-Mental State Examination. Associations were examined by multiple linear or ordinal logistic regressions. Whether patients classified as being a “treatment success” or a “treatment failure” had different serum concentrations of oxycodone or metabolites was assessed using Mann-Whitney U-tests.Results: Serum concentrations of oxycodone and metabolites were not associated with pain intensity, nausea, tiredness, or cognitive function, with the exception that increased pain intensity was associated with higher oxymorphone concentrations. Patients with poor pain control and side effects had higher serum concentrations of the oxycodone metabolites, noroxycodone and noroxymorphone, compared with those with good pain relief and without side effects.Conclusion: This study of patients receiving oxycodone for cancer pain confirms previous observations that there is most likely no association between serum concentrations of opioid analgesics and clinical effects.

Parent Perceptions of Child Vulnerability Are Associated With Functioning and Health Care Use in Children With Chronic Pain - Corrected Proof

Mark Connelly, Kelly K. Anthony, Laura E. Schanberg — 2012-01-30

Abstract: Background: The extent to which parent variables are associated with the level of disability experienced by children with persistent pain has been an area of increasing research.Measures: To evaluate the extent to which parent perceptions of their child’s vulnerability are associated with functioning and health care utilization among children with persistent pain. We also evaluated whether perceptions of child vulnerability contribute to an indirect relationship between parent distress and child functioning and/or child health care utilization.Intervention: The study sample comprised 87 patients aged 6–18 years and a parent attending a chronic pain clinic. Children completed questionnaires on functional limitations, and parents completed questionnaires on parent distress, perceptions of child vulnerability, and extent of the child’s pain-related health care utilization. Hierarchical regression and bootstrapping mediation analyses were used to test study hypotheses.Outcomes: Perceptions of child vulnerability were found to be clinically elevated in nearly half (46%) of parents/caregivers, and average child functional ability for the sample was substantially lower than healthy norms. Parent perceptions of greater child vulnerability were significantly associated with poorer child functioning and more child pain-related health care utilization regardless of child age, sex, and duration of persistent pain. Parent distress was found to be indirectly related to child health care utilization through parent perceptions of child vulnerability but directly related to child functioning.Conclusions/Lessons Learned: Parent perceptions of child vulnerability appear important for understanding levels of child functional limitations and health care utilization among children with chronic pain.

Dyspnea in Idiopathic Pulmonary Fibrosis: A Systematic Review - Corrected Proof

Christopher J. Ryerson, DorAnne Donesky, Steven Z. Pantilat, Harold R. Collard — 2012-01-30

Abstract: Context: Little is known about the treatment and correlates of dyspnea in idiopathic pulmonary fibrosis (IPF).Objectives: The objective of this systematic review was to summarize the literature regarding the treatment and correlates of dyspnea in IPF.Methods: MEDLINE, EMBASE, and all Evidence-Based Medicine Reviews were searched for publications that evaluated treatment or correlates of dyspnea in IPF. Reference lists and recent review articles also were searched.Results: The heterogeneity of included studies did not permit meta-analysis. Dyspnea improved in studies of sildenafil, pulmonary rehabilitation, and prednisone with colchicine. Additional studies of these three treatments, however, found discordant results. One study suggested that assisted ventilation delivered by facemask improved exertional dyspnea. Oxygen and opioids improve dyspnea in other chronic lung diseases, but data in IPF are limited. Correlates of dyspnea included functional and physiological measures and comorbid diseases.Conclusion: Sildenafil and pulmonary rehabilitation should be considered as potential therapies for dyspnea in selected patients with IPF. Supplemental oxygen and opioids may be additional potential therapies; however, the evidence supporting their use is weak. Additional research should focus on the management of functional status and comorbidities as potential treatments for dyspnea.

It Is “Too Late” or Is It? Bereaved Family Member Perceptions of Hospice Referral When Their Family Member Was on Hospice for Seven Days or Less - Corrected Proof

Joan M. Teno, David Casarett, Carol Spence, Stephen Connor — 2012-01-30

Abstract: Context: Many family members of patients enrolled in hospice for less than seven days state that the hospice referral was made “at the right time.”Objectives: To examine bereaved family members’ perceptions of the timing of hospice referral to identify aspects of the referral process that can be improved.Methods: Open-ended interviews were conducted in seven hospice programs, interviewing bereaved family members of hospice patients who died within the first week of hospice enrollment.Results: Of the 100 narrative interviews, 99 respondents stated that their family member was either referred “too late” (n=41) or “at the right time” (n=58) to hospice services. When families stated that referral was “at the right time,” their perceptions were based on the patient having refused earlier referral (n=8), a rapid decline in the patient’s condition resulting in the late referral (n=20), or a belief in all things coming together as they were meant to (n=11). In contrast, when families stated that referral was “too late,” their reasons were centered on concerns with the health care providers’ role in decision making (n=24), with the leading concerns being inadequate physician communication (n=7), not recognizing the patient as dying (n=11), or problematic hospice delays in referral from the nursing home or home health agency (n=4). Despite the patient refusing an earlier hospice referral, five family members believed the referral was “too late.”Conclusion: Whereas family members identified expected concerns with communication, more than one in three stated an earlier hospice referral was not possible.

Illness Perceptions, Adjustment to Illness, and Depression in a Palliative Care Population - Corrected Proof

2012-01-30

Abstract: Context: Representations of illness have been studied in several populations, but research is limited in palliative care.Objectives: To describe illness representations in a population with advanced disease receiving palliative care and to examine the relationship between illness perceptions, adaptive coping, and depression.Methods: A cross-sectional survey of 301 consecutive eligible patients recruited from a palliative care service in south London, U.K. Measures used included the Brief Illness Perception Questionnaire (Brief IPQ), the Mental Adjustment to Cancer (MAC) Scale, and the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire-9.Results: Scores were not normally distributed for most questions on the Brief IPQ. The correlations found between items on the Brief IPQ were understandable in the context of advanced disease. MAC helplessness-hopelessness and fighting spirit were highly correlated with items on the Brief IPQ in opposite directions. The Brief IPQ domains of consequences, identity, concern, personal control, and emotion were associated with depression, a relationship that was not explained by adaptive coping. Seven causal attribution themes were identified: don’t know, personal responsibility, exposure, pathological process, intrinsic personal factors, chance, fate or luck, and other. Both lung cancer diagnosis and gender were found to be independently associated with personal responsibility attribution. None of the attribution themes were associated with the presence of depression.Conclusion: Assessment of illness perceptions in palliative care is likely to yield important information about risk of depression and will help clinicians to personalize management of advanced disease.

Unique Manifestations of Catecholamine Release in Malignant Pheochromocytoma: An Experience Within an Inpatient Palliative Care Unit - Corrected Proof

Nicholas Anthony Coupe, Judith Lacey, Christine Sanderson — 2012-01-30

Abstract: Malignant pheochromocytoma is a rare disorder. We describe the case of a 41-year-old female with disseminated metastatic pheochromocytoma who was admitted for ongoing palliative and supportive care within an inpatient palliative care unit. Predominant symptoms included severe gastrointestinal pseudo-obstruction and orthostatic hypotension Pseudo-obstruction management included percutaneous enterogastric and percutaneous enterojejunostomy tubes for gastric decompression and delivery of nutrition, respectively. Debilitating symptoms of orthostatic hypotension were mitigated with judicious fluid balance and appropriate use of adrenergic blocking agents. The potential for metoclopramide to worsen symptoms also was a significant component of management. The case presents rare features of this unusual disease and is unique for its setting within the confines of a palliative care unit.

All’s Well That Ends Well? Quality of Life and Physical Symptom Clusters in Long-Term Cancer Survivors Across Cancer Types - Corrected Proof

Alison C. Zucca, Allison W. Boyes, Wolfgang Linden, Afaf Girgis — 2012-01-27

Abstract: Context: Little is known about the presentation of multiple concurrent symptoms (symptom clusters) in long-term cancer survivors, with few studies adequately powered to compare quality of life (QoL) and symptom presentation by cancer type.Objectives: This research aimed to 1) assess patient-reported QoL and 2) identify clusters of cancer-related physical symptoms by cancer type among long-term breast, prostate, colorectal, and melanoma cancer survivors.Methods: A population-based cross-sectional sample of 863 adult cancer survivors five to six years post-diagnosis completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), assessing global QoL and frequency of presentation of cancer-related physical symptoms.Results: Long-term survivors reported higher levels of global QoL than 1) the general population (age-adjusted mean=79.4 vs. 71.1, small clinical difference) and 2) cancer patients early in the care trajectory (age-adjusted mean=77.1 vs. 61.3, moderate clinical difference). The majority (71%) did not report any cancer-related physical symptoms; 18% reported multiple (two or more) symptoms in the past month. Factor analysis found that cognitive functioning, fatigue, insomnia, pain, dyspnea, appetite loss, constipation, diarrhea, nausea, and vomiting formed a cluster (α=0.48). No symptom clusters were identified that were specific to just one cancer type. However, individual symptoms (including diarrhea, pain, constipation, and insomnia) modestly discriminated between cancer types.Conclusion: Contrary to expectations, no symptom clusters specific to one type of cancer were identified and survivors reported few cancer-related symptoms and high QoL. These results convey a strong “good news” message, providing health professionals with a sound foundation for making encouraging predictions about their patients’ long-term physical recovery after cancer. Cancer patients also will welcome the news that only a minority of five-year survivors experience long-term and late effects.

Palliative Medicine Fellowship: A Study of Resident Choices - Corrected Proof

Susan B. LeGrand, Jessica B. Heintz — 2012-01-24

Abstract: Context: There are no data on the motives or characteristics of physicians choosing fellowship training in Hospice and Palliative Medicine (HPM).Objectives: To understand more about the residents who choose HPM and what leads them to this decision.Methods: An electronic survey of HPM fellows initiating training in July 2009.Results: Seventy-six physicians began the study, with 62 responders (82%) completing all questions. Fifty-five percent were aged 30–40 years, and 61% were female. Sixty-eight percent were non-Hispanic Caucasian, 24% were Asian, and none were African American. Fifty-five percent were trained in internal medicine. Most (86%) asserted that the care of a dying, critically ill, or symptomatic person impacted their decision to enter the field of HPM. Sixty-three percent did not feel prepared to manage dying patients, and 41% felt personal regret about the care they delivered. The major reasons for choosing the specialty were a desire to contribute to relief of suffering (79%), enhance end-of-life care (73%), and improve communication (78%). Ninety-five percent received negative comments about their career choice. Fifty-nine percent had no exposure to hospice or palliative medicine in medical school, whereas 61% had an exposure available during residency. Forty-seven percent decided to enter a fellowship in the third year of residency, and 33% applied after practicing in their primary specialty for a median of 10 years. Accreditation, strength of education, and a hospital palliative medicine service were required by the majority for selection of a fellowship program.Conclusion: Negative experiences with end-of-life care in residency, particularly in the intensive care unit, continue to be a factor in selection of HPM as a specialty. Many residents make their decision to enter the field and apply during Postgraduate Year 3. Most received negative comments about the choice. Fellows require a broad range of experience when selecting a fellowship program.

The Catalonia World Health Organization Demonstration Project for Palliative Care Implementation: Quantitative and Qualitative Results at 20 Years - Corrected Proof

2012-01-24

Abstract: Catalonia (Spain) has a total population of 7.3 million citizens for whom the National Health Service (NHS) provides health care that is free at the point of access. The prevalence of terminally ill patients is between 30,100 and 39,600. Twenty years ago, the World Health Organization (WHO), in collaboration with the Catalan Department of Health and the Catalan Institute of Oncology, began a demonstration project (WHO Demonstration Project) in palliative care (PC) with the aim of implementing specialist PC services, generating experience in this field, identifying areas for improvement, and introducing educative procedures (clinical and nonclinical). Over the past 20 years, 237 PC clinical services (72 home care support teams, 49 hospital support teams, 60 units with 742 dedicated beds, 50 outpatient clinics, and six psychosocial support teams) have been implemented. In the five years since the previous evaluation, 57 new clinical services (15 new hospital support teams, 36 outpatient clinics, and six psychosocial support teams among others) and four nonclinical services (education, research, WHO Collaborating Center, and planning) have been implemented. During the year 2010, a total of 46,200 processes were undertaken for the care of 23,100 patients, of whom 12,100 (52%) had cancer and 11,000 (48%) had other chronic advanced diseases. The overall yearly costs are around €52,568,000, with an overall savings of €69,300,000 (€2275 per patient, net savings to the NHS of €16,732,000). In the last five years, three qualitative evaluations and a benchmarking process have been performed to identify weak points and inequities in care provision among districts. Systematic assessments indicate high cost-effectiveness of care as well as high levels of satisfaction by patients and their relatives, thus reinforcing the principle that access to PC under the auspices of the NHS at the end of life is a basic human right.

Physical Activity Monitoring: A Responsive and Meaningful Patient-Centered Outcome for Surgery, Chemotherapy, or Radiotherapy? - Corrected Proof

2012-01-24

Abstract: Context: In surgical and clinical oncology, there is a growing need for patient-centered outcomes that are responsive, meaningful, and fit for purpose.Objectives: The aim of this study was to validate physical activity (PA) monitoring as a responsive outcome measure at different stages of disease and treatment, by verifying correlations between PA, performance score, and quality of life (QoL).Methods: Daily life PA of 162 cancer patients, monitored by a device that records time sitting/lying, time standing, time walking, number of steps taken, and walking cadence, was compared with 20 healthy volunteers. In a subgroup of patients, functional status and QoL were assessed using the World Health Organization/Eastern Cooperative Oncology Group and the Karnofsky Performance Status scores and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) questionnaire.Results: The PA of patients with resectable gastrointestinal cancer did not differ significantly from controls. In contrast, patients with advanced cancer took 45% fewer steps and spent an extra 2.8 hours/day lying/sitting (P=0.001). Patients undergoing neoadjuvant chemotherapy and surgery (5–6 weeks after operation) experienced a similar reduction in PA. There were significant correlations between PA and the physical and role domains as well as fatigue subscale of the EORTC QLQ-C30 scale.Conclusion: Objective PA scores correlate significantly with disease stage, functional status, and QoL of patients with cancer. Therefore, activity monitoring can make meaningful objective estimates of patient function in response to cancer and its treatment and may provide surrogate outcomes of QoL.

Exploring Hospice Patients’ Views About Participating in Research - Corrected Proof

2012-01-03

A study examining the pharmacokinetics and pharmacodynamics of cyclizine in palliative care patients was carried out at Nurse Maude Hospice, Christchurch, New Zealand. It involved intensive blood sampling over five days and is reported on elsewhere in this issue. As this was the first such study in our institution, qualitatively examining the impact of such research on this population was thought to be appropriate to inform future studies.

Improving Outcomes for People With Progressive Cancer: Interrupted Time Series Trial of a Needs Assessment Intervention - Corrected Proof

2012-01-03

Abstract: Context: Improving the effectiveness of cancer care delivery has become a major focus of research.Objectives: This study assessed the uptake and impact of the Palliative Care Needs Assessment Guidelines and Needs Assessment Tool: Progressive Disease—Cancer (NAT: PD-C) on the outcomes of people with advanced cancer.Methods: Given widely varying survival in people with advanced cancer, an interrupted time series design was used, with data on unmet needs, depression, anxiety, and quality of life collected from 195 patients using telephone interviews every two months, for up to 18 months. Patients completed at least two baseline interviews before health professionals were academically detailed in the use of the Palliative Care Needs Assessment Guidelines and NAT: PD-C. Health professionals completed the NAT: PD-C with patients approximately monthly for the remainder of the study. Changes in patients’ outcomes were compared prior to and following the introduction of the NAT: PD-C using General Estimating Equations.Results: Moderate to high needs across all domains were frequently seen in the preintervention phase. The use of the NAT: PD-C was associated with a significant reduction in health system and information and patient care and support needs.Conclusion: These resources have the potential as an efficient and acceptable strategy for supporting needs-based cancer care. Further work is required to determine their unique contribution to improvements in patient outcomes.

The Pharmacokinetics and Pharmacogenetics of the Antiemetic Cyclizine in Palliative Care Patients - Corrected Proof

2012-01-03

Abstract: Context: Cyclizine, an antihistaminic antiemetic, is commonly used in palliative care. Its pharmacokinetics have been poorly studied, and its metabolic pathway is unknown but may involve the genetically controlled cytochrome P450 2D6 (CYP2D6). If this is the case, the metabolic ratio of cyclizine to norcyclizine and efficacy/adverse effects may vary between patients according to their CYP2D6 genotype.Objectives: To deduce the pharmacokinetics and antiemetic/sedative effects of cyclizine and relate these and its metabolic ratio to the CYP2D6 genotype in palliative care patients.Methods: Palliative care patients initiated on continuous cyclizine subcutaneous (SC) infusions had blood samples taken and efficacy/toxicity scores measured during the approach to steady state. Another group of patients at steady state receiving oral cyclizine had a single blood sample taken. Samples were analyzed to elucidate pharmacokinetic parameters and CYP2D6 genetics.Results: SC dosing group: The median (interquartile range) cyclizine half-life, volume of distribution, and clearance were 13 (7–48) hours, 23 (12–30)L/kg, and 15 (11–26)mL/min/kg, respectively. Nausea and sedation scores were 3.0 (1.2–5.7) and 5.0 (2.6–8.1), respectively, overall and did not vary with genotype (P=0.76 and 0.11, respectively). The median overall metabolic ratio at steady state was 4.9 (3.8–9.2) and did vary with CYP2D6 genotype (P=0.02). Oral dosing group: The median metabolic ratio was 2.1 (1.5–2.9) and did not vary with CYP2D6 genotype (P=0.37).Conclusion: Palliative care patients have similar cyclizine pharmacokinetics to those reported in other patient groups. Cyclizine metabolism to norcyclizine may include CYP2D6 as the metabolic ratio varied with CYP2D6 genotype in the SC group.

Inhaled Fentanyl Citrate Improves Exercise Endurance During High-Intensity Constant Work Rate Cycle Exercise in Chronic Obstructive Pulmonary Disease - Corrected Proof

2011-12-15

Abstract: Context: Activity limitation and dyspnea are the dominant symptoms of chronic obstructive pulmonary disease (COPD). Traditionally, efforts to alleviate these symptoms have focused on improving ventilatory mechanics, reducing ventilatory demand, or both of these in combination. Nevertheless, many patients with COPD remain incapacitated by dyspnea and exercise intolerance despite optimal therapy.Objectives: To determine the effect of single-dose inhalation of nebulized fentanyl citrate (a μ-opioid agonist drug) on exercise tolerance and dyspnea in COPD.Methods: In a randomized, double-blind, placebo-controlled, crossover study, 12 stable patients with COPD (mean±standard error of the mean post-β2-agonist forced expiratory volume in one second [FEV1] and FEV1 to forced vital capacity ratio of 69%±4% predicted and 49%±3%, respectively) received either nebulized fentanyl citrate (50mcg) or placebo on two separate days. After each treatment, patients performed pulmonary function tests and a symptom-limited constant work rate cycle exercise test at 75% of their maximum incremental work rate.Results: There were no significant postdose differences in spirometric parameters or plethysmographic lung volumes. Neither the intensity nor the unpleasantness of perceived dyspnea was, on average, significantly different at isotime (5.0±0.6 minutes) or at peak exercise after treatment with fentanyl citrate vs. placebo. Compared with placebo, fentanyl citrate was associated with 1) increased exercise endurance time by 1.30±0.43 minutes or 25%±8% (P=0.01); 2) small but consistent increases in dynamic inspiratory capacity by ∼0.10L at isotime and at peak exercise (both P≤0.03); and 3) no concomitant change in ventilatory demand, breathing pattern, pulmonary gas exchange, and/or cardiometabolic function during exercise. The mean rate of increase in dyspnea intensity (1.2±0.3 vs. 2.9±0.8 Borg units/minute, P=0.03) and unpleasantness ratings (0.5±0.2 vs. 2.9±1.3 Borg units/minute, P=0.06) between isotime and peak exercise was less after treatment with fentanyl citrate vs. placebo.Conclusion: Single-dose inhalation of fentanyl citrate was associated with significant and potentially clinically important improvements in exercise tolerance in COPD. These improvements were accompanied by a delay in the onset of intolerable dyspnea during exercise near the limits of tolerance.

Pain and Physical and Psychological Symptoms in Ambulatory HIV Patients in the Current Treatment Era - Corrected Proof

2011-11-24

Abstract: Context: HIV infection has become a manageable chronic disease. There are few studies of pain and symptoms in the current treatment era.Objectives: Our primary objective was to determine the prevalence of and risk factors for pain and physical and psychological symptoms in a population of ambulatory HIV patients.Methods: We performed a cross-sectional study using the Brief Pain Inventory and the Memorial Symptom Assessment Scale.Results: We evaluated 156 individuals with a median age of 47.5 years (range 21–71), median time since HIV diagnosis of 11 years (range <1 to 25), and median CD4+ cell count of 502 cells/mm3 (interquartile range [IQR] 308–683). Most (125, 80.6%) of the patients had an undetectable viral load. Seventy-six (48.7%) patients reported pain, of whom 39 (51.3%) had moderate to severe pain, and 43 (57.3%) had pain that caused moderate to severe interference with their lives. The median number of symptoms was eight (IQR 5–14.5) of 32 queried. In multivariable analyses, patients with psychiatric illness were 39.8% more likely to have pain (P<0.001). Psychiatric illness was associated with 0.7 and 1.2 point higher Memorial Symptom Assessment Scale Short Form subscale scores, and IV drug use was associated with 0.4 and 0.5 higher subscale scores (out of four).Conclusion: Pain and other physical and psychological symptoms were common among ambulatory HIV patients. Pain and symptoms were strongly associated with psychiatric illness and IV drug use. Future investigation should evaluate interventions that include psychiatric and substance abuse components for HIV patients with pain.

The Lack of Standard Definitions in the Supportive and Palliative Oncology Literature - Corrected Proof

2011-11-21

Abstract: Context: Multiple organizations have raised concerns about the lack of standard definitions for terminology in the supportive and palliative oncology literature.Objectives: We aimed to determine 1) the frequency of 10 commonly used terms in the supportive and palliative oncology literature, 2) the proportion of articles that provided definitions for each term, and 3) how each term was defined.Methods: We systematically searched MEDLINE, PubMed, PsycINFO, the Cochrane Library, Embase, ISI Web of Science, and Cumulative Index to Nursing and Allied Health Literature for original studies, review articles, and systematic reviews related to palliative care and cancer in the first six months of 2004 and 2009. We counted the number of occurrences for “palliative care,” “supportive care,” “best supportive care,” “hospice care,” “terminal care,” “end-of-life,” “terminally ill,” “goals of care,” “actively dying,” and “transition of care” in each article, reviewed them for the presence of definitions, and documented the journal characteristics.Results: Among the 1213 articles found, 678 (56%) were from 2009. “Palliative care” and “end-of-life” were the most frequently used terms. “Palliative care,” “end-of-life,” and “terminally ill” appeared more frequently in palliative care journals, whereas “supportive care” and “best supportive care” were used more often in oncology journals (P<0.001). Among 35 of 601 (6%) articles with a definition for “palliative care,” there were 16 different variations (21 of 35 articles used the World Health Organization definition). “Hospice care” had 13 definitions among 13 of 151 (9%) articles. “Supportive care” and other terms were rarely defined (less than 5% of articles that used the term).Conclusion: Our findings highlight the lack of definitional clarity for many important terms in the supportive and palliative oncology literature. Standard definitions are needed to improve administrative, clinical, and research operations.

Quality of Life and Experience of Care in Women With Metastatic Breast Cancer: A Cross-Sectional Survey - Corrected Proof

Elizabeth Reed, Peter Simmonds, Joanne Haviland, Jessica Corner — 2011-11-17

Abstract: Context: Despite developments in the medical management of metastatic breast cancer, little is known about the quality of life (QoL) and experience of care in women with it.Objectives: To explore QoL, experience of care, and support needs of women living with metastatic breast cancer in the U.K.Methods: Questionnaire-based, cross-sectional study, undertaken in two U.K. cancer centers and online via the Breast Cancer Care Web site, assessing QoL and experience of care in 235 women with metastatic breast cancer.Results: QoL was assessed using the Functional Assessment of Cancer Therapy—Breast QoL measure. Overall, QoL was low (mean 89.0, standard deviation 21.8) for total score. Low scores were seen uniformly in physical, social, emotional, and functional well-being domains. Symptom burden was a significant problem, with over one-third of women (34%) reporting high levels of pain and other uncontrolled symptoms. In multiple regression analysis, social well-being was significantly better for older women (P<0.001) but was lower in those with bone metastases only (P=0.002). Functional well-being was significantly higher in women without children (P=0.004). Satisfaction with experience of care was low and appeared to be predominantly in the hospital setting, with little evidence of involvement of general practitioners and palliative care services.Conclusion: Despite improvements in treatment and survival of women with metastatic breast cancer, this group reports high symptom burden and dissatisfaction with elements of their care, indicating that alternative models of service delivery should be explored.

Impact of Infections on the Survival of Hospitalized Advanced Cancer Patients - Corrected Proof

Vincent Thai, Francis Lau, Gary Wolch, Ju Yang, Hue Quan, Konrad Fassbender — 2011-11-10

Abstract: Context: Advanced cancer patients remain highly susceptible to infections, leading to significant morbidity and mortality. A lack of consensus on the management of infections in this population stems from the heterogeneity of the patient group, divergent goals of care, and unknown prognosis with antibiotic treatment.Objectives: This prospective single cohort study examined the impact of infection and its treatment on the survival of hospitalized advanced cancer patients compared with a similar cohort without infection.Methods: A total of 441 patients were referred to the palliative care (PC) consult service in a tertiary hospital over a 12-month period. The occurrence of sepsis, organ-related infection, and antibiotic use were recorded on initial PC consult. Survival was calculated from the point of PC consult to the date of death.Results: Of these patients, 16.6% suffered a recent episode of sepsis (with or without an identifiable organ-related infection) and 23.4% had a recent episode of organ-related infection without clinically evident sepsis. Among the patients with sepsis, organ-related infection, or both, 89.7% received antibiotics (intravenous, oral, or both). Median survival of septic and nonseptic patients was 15 and 42 days, respectively. Septic patients who responded poorly to treatment (nonresponders) had a median survival of five days vs. 142 days in good responders. This equates with a hazard ratio of 9.74 for death in antibiotic nonresponders (P<0.05). Median survival for patients with an untreated organ-related infection (no sepsis) was 27 days compared with 48 days in a similar cohort receiving antibiotic therapy. Among patients on IV antibiotics, nonresponders had a median survival of six days vs. 108 days in responders. For patients on oral antibiotics, nonresponders had a median survival of six days vs. 70 days in responders.Conclusion: These findings suggest that a recent episode of sepsis and/or organ-related infection significantly reduces overall patient survival. Favorable antibiotic response is associated with an increase in median survival. These findings suggest that antibiotic treatment may prolong survival, and a time-limited trial may be indicated contingent on goals of care.

Self-Compassion in Patients With Persistent Musculoskeletal Pain: Relationship of Self-Compassion to Adjustment to Persistent Pain - Corrected Proof

2011-11-10

Abstract: Context: Self-compassion entails qualities such as kindness and understanding toward oneself in difficult circumstances and may influence adjustment to persistent pain. Self-compassion may be a particularly influential factor in pain adjustment for obese individuals who suffer from persistent pain, as they often experience heightened levels of pain and lower levels of psychological functioning.Objectives: The purpose of the present study was to examine the relationship of self-compassion to pain, psychological functioning, pain coping, and disability among patients who have persistent musculoskeletal pain and who are obese.Methods: Eighty-eight obese patients with persistent pain completed a paper-and-pencil self-report assessment measure before or after their appointment with their anesthesiologist.Results: Hierarchical linear regression analyses demonstrated that even after controlling for important demographic variables, self-compassion was a significant predictor of negative affect (β=−0.48, P<0.001), positive affect (β=0.29, P=0.01), pain catastrophizing (β=−0.32, P=0.003), and pain disability (β=−0.24, P<0.05).Conclusion: The results of this study indicate that self-compassion may be important in explaining the variability in pain adjustment among patients who have persistent musculoskeletal pain and are obese.

Development of a Prognostic Model for Six-Month Mortality in Older Adults With Declining Health - Corrected Proof

2011-11-10

Abstract: Context: Estimation of six-month prognosis is essential in hospice referral decisions, but accurate, evidence-based tools to assist in this task are lacking.Objectives: To develop a new prognostic model, the Patient-Reported Outcome Mortality Prediction Tool (PROMPT), for six-month mortality in community-dwelling elderly patients.Methods: We used data from the Medicare Health Outcomes Survey linked to vital status information. Respondents were 65 years old or older, with self-reported declining health over the past year (n=21,870), identified from four Medicare Health Outcomes Survey cohorts (1998–2000, 1999–2001, 2000–2002, and 2001–2003). A logistic regression model was derived to predict six-month mortality, using sociodemographic characteristics, comorbidities, and health-related quality of life (HRQOL), ascertained by measures of activities of daily living and the Medical Outcomes Study Short Form-36 Health Survey; k-fold cross-validation was used to evaluate model performance, which was compared with existing prognostic tools.Results: The PROMPT incorporated 11 variables, including four HRQOL domains: general health perceptions, activities of daily living, social functioning, and energy/fatigue. The model demonstrated good discrimination (c-statistic=0.75) and calibration. Overall diagnostic accuracy was superior to existing tools. At cut points of 10%–70%, estimated six-month mortality risk sensitivity and specificity ranged from 0.8% to 83.4% and 51.1% to 99.9%, respectively, and positive likelihood ratios at all mortality risk cut points ≥40% exceeded 5.0. Corresponding positive and negative predictive values were 23.1%–64.1% and 85.3%–94.5%. Over 50% of patients with estimated six-month mortality risk ≥30% died within 12 months.Conclusion: The PROMPT, a new prognostic model incorporating HRQOL, demonstrates promising performance and potential value for hospice referral decisions. More work is needed to evaluate the model.

Validation of the Symptom and Problem Checklist of the German Hospice and Palliative Care Evaluation (HOPE) - Corrected Proof

2011-11-10

Abstract: Context: The German Hospice and Palliative Care Evaluation (HOPE) is a national, long-term quality assurance project. Every year, German hospice and palliative care institutions document a core data set for their patients for a period of three months.Objectives: To validate the multidimensional symptom and problem checklist (HOPE-SP-CL) of the core data set and report details on reliability and validity.Methods: Data from yearly evaluation periods between 2002 and 2009 were used to calculate construct and convergent validity, internal consistency, test-retest reliability, and documentation discipline and acceptance of the core documentation system.Results: The HOPE-SP-CL includes items on physical, nursing, psychological, and social symptoms and problems. Factor analysis extracted four low to moderately intercorrelating factors with eigen values greater than 1.0 explaining 56% of the total variance. Discriminant validity of the HOPE-SP-CL showed good properties in detecting patient groups with different symptom intensities and overall symptom burden using the Eastern Cooperative Oncology Group performance status and primary cancer diagnosis as external validation criteria. The global sum score of the HOPE-SP-CL correlated most closely with the Palliative Outcome Scale staff version (r=0.750). Internal consistencies ranged between α=0.768–0.801 at three different times of assessment. Test-retest coefficients showed moderate to high correlations at one-week intervals.Conclusion: Analyses of reliability and validity of the HOPE-SP-CL showed satisfactory to good psychometric properties; therefore, the HOPE-SP-CL can be recommended for standard implementation in German hospice and palliative care institutions.

Preferred and Actual Involvement of Advanced Lung Cancer Patients and Their Families in End-of-Life Decision Making: A Multicenter Study in 13 Hospitals in Flanders, Belgium - Corrected Proof

2011-11-03

Abstract: Context: Death is often preceded by medical decisions that potentially shorten life (end-of-life decisions [ELDs]), for example, the decision to withhold or withdraw treatment. Respect for patient autonomy requires physicians to involve their patients in this decision making.Objectives: The objective of this study was to examine the involvement of advanced lung cancer patients and their families in ELD making and compare their actual involvement with their previously stated preferences for involvement.Methods: Patients with Stage IIIb/IV non-small cell lung cancer were recruited by physicians in 13 hospitals and regularly interviewed between diagnosis and death. When the patient died, the specialist and general practitioner were asked to fill in a questionnaire.Results: Eighty-five patients who died within 18 months of diagnosis were studied. An ELD was made in 52 cases (61%). According to the treating physician, half of the competent patients were not involved in the ELD making, one-quarter shared the decision with the physician, and one-quarter made the decision themselves. In the incompetent patients, family was involved in half of cases. Half of the competent patients were involved less than they had previously preferred, and 7% were more involved. Almost all of the incompetent patients had previously stated that they wanted their family involved in case of incompetence, but half did not achieve this.Conclusion: In half of the cases, advanced lung cancer patients—or their families in cases of incompetence—were not involved in ELD making, despite the wishes of most of them. Physicians should openly discuss ELDs and involvement preferences with their advanced lung cancer patients.

A Spicamycin Derivative (KRN5500) Provides Neuropathic Pain Relief in Patients With Advanced Cancer: A Placebo-Controlled, Proof-of-Concept Trial - Corrected Proof

2011-10-10

Abstract: Context: Neuropathic pain in patients with cancer can be difficult to treat effectively.Objectives: The purpose of the study was to determine safety and efficacy of KRN5500, a novel, spicamycin-derived, nonopioid analgesic agent, in patients with advanced cancer and neuropathic pain of any etiology.Methods: The study was a Phase 2a, multicenter, double-blind, placebo-controlled, dose escalation clinical trial. Patients with refractory neuropathic pain and advanced cancer were randomly assigned 2:1 to receive a maximum of eight single escalating doses of KRN5500 or placebo, ranging from 0.6 to 2.2mg/m2. The primary objective was safety and tolerability. The secondary objective was efficacy, measured by change in average pain intensity on a 0–10 numeric rating scale administered one week after the patient’s final dose.Results: Nineteen patients received treatment (KRN5500 n=12; placebo n=7). The most frequently reported adverse events were gastrointestinal symptoms, which were more frequent and severe with KRN5500 than placebo; two (17%) KRN5500 patients discontinued the study because of nausea and vomiting. At study end point, KRN5500 exhibited a significant median decrease in pain intensity from baseline of 24% compared with 0% for placebo (P=0.03). The median for largest weekly reduction in target pain intensity was 29.5% for KRN5500 and 0% for placebo patients (P=0.02).Conclusion: This proof-of-concept study for KRN5500 in patients with advanced cancer and any type of neuropathic pain found gastrointestinal adverse events to be the predominant safety concern. The results also provided the first indication of clinical and statistical efficacy in reducing pain intensity.

In-Hospital Mortality in Patients Older Than 60 Years with Very Low Albumin Levels - Corrected Proof

Jodi L. Hannan, Steven M. Radwany, Terry Albanese — 2011-09-19

Abstract: Context: Low albumin levels have been associated with increased mortality, but few studies have looked at the mortality rates of patients with very low albumin levels.Objectives: The objective of this study was to determine the in-hospital mortality rates for patients older than 60 years with albumin levels <2.0g/dL.Methods: This was a retrospective study of 543 consecutive patients older than the age of 60 who had an albumin level <2.0g/dL while admitted to Summa Akron City Hospital between July and November 2008. Data were obtained from hospital databases. Mortality rates were calculated for each albumin level and compared with the overall inpatient mortality for patients older than 60 years. Rates of discharge to home were calculated by albumin level. Cross-tabulations and correlations were conducted to determine the association between albumin level and mortality, and to assess the independent effects of total parenteral nutrition, dialysis, cancer, and end-stage renal disease.Results: Patients with albumin levels between 1.0 and 1.4 had a 41% in-hospital mortality rate, with only 16% of the patients being discharged to home. Patients with albumin levels between 1.5 and 1.9 had a 21% mortality rate, with 33% of patients discharged to home. Overall hospital mortality for patients older than 60 years was 6% during the study period. Total parenteral nutrition, cancer, dialysis, and end-stage renal disease were not independent risk factors for mortality in this study.Conclusion: An albumin level is readily obtained across all areas of the hospital and provides a simple and useful aid in identifying patients at high risk of a poor hospital outcome.

Corticosteroid Rotation to Alleviate Dexamethasone-Induced Hiccup: A Case Series at a Single Institution - Corrected Proof

2011-09-19

Abstract: Dexamethasone, one of the key medications for the prevention of chemotherapy-induced nausea and vomiting (CINV), may cause hiccups as an adverse effect. In this case series, we present five patients who developed hiccups after receiving dexamethasone for CINV. We successfully switched dexamethasone to an equipotent dosage of either methylprednisolone or prednisolone, which resolved the hiccups while maintaining adequate control of CINV. This was achieved without changing the rest of the antiemetic regimen, chemotherapy doses, or the use of other medications such as baclofen, haloperidol, and metoclopramide for hiccups. Further studies on switching dexamethasone to alternative corticosteroids in patients developing hiccups after administration of dexamethasone are warranted.