PC-FACS (Fast Article Critical Summaries for Clinicians in Palliative Care) provides hospice and palliative care clinicians with concise summaries of the most important findings from more than 100 medical and scientific journals. If you have colleagues who would benefit from receiving PC-FACS, please encourage them to join the AAHPM at aahpm.org. Comments from readers are welcomed at [email protected] PC-FACS (Fast Article Critical Summaries for Clinicians in Palliative Care) provides hospice and palliative care clinicians with concise summaries of the most important findings from more than 100 medical and scientific journals. If you have colleagues who would benefit from receiving PC-FACS, please encourage them to join the AAHPM at aahpm.org. Comments from readers are welcomed at [email protected] Furuno JP, Noble BN, Horne KN, et al. Frequency of outpatient antibiotic prescription on discharge to hospice care. Antimicrob Agents Chemother 2014;58:5473-5477. Rosenberg AR, Orellana L, Kang TI, et al. Differences in parent-provider concordance regarding prognosis and goals of care among children with advanced cancer. J Clin Oncol 2014 Jul 14. [Epub ahead of print]. Kitzninger C, Kitzinger J. Withdrawing artificial nutrition and hydration from minimally conscious and vegetative patients: family perspectives. J Med Ethics 2014 Jan 14. [Epub ahead of print]. Grenklo TB, Kreicbergs U, Valdimarsdottir UA, et al. Self-injury in youths who lost a parent to cancer: nationwide study of the impact of family-related and healthcare-related factors. Psychooncology 2014;23:989-997. Pahor M, Guralnik JM, Ambrosius WT, et al. Effect of structured physical activity on prevention of major mobility disability in older adults. JAMA 2014;311:2387-2396. Kir S, White JP, Kleiner S, et al. Tumor-derived PTH-related protein triggers adipose tissue browning and cancer cachexia. Nature 2014;513:100-104. Antibiotic administration is common for patients discharged to hospice despite no conclusive evidence of its effectiveness.1,2 What are the characteristics of patients discharged to hospice with antibiotic prescriptions? This was a cross-sectional study examining antibiotic prescription rates in hospitalized patients discharged directly to hospice. Eligible participants were adult patients with a first hospice admission from one academic healthcare institution in Oregon from 2010 through 2012. Demographics, clinical information, and discharge disposition data were collected from electronic institutional databases. Primary outcome was receipt of an outpatient antibiotic prescription on discharge, with exposures of interest being documented infection and receipt of a palliative care consultation during hospital admission. Participants (N = 845) were 55% male, 51% older than 65 years, and 90% white; diagnoses were 58% cancer and 65% heart failure or cardiovascular disease; mean Charlson Comorbidity Index score was 6.9. Prevalence of an antibiotic prescription on hospital discharge was 21% (178/845). Seventy-two percent of patients had a documented infection, with bloodstream, bacteremia or endocarditis (40%), and pneumonia (39%) the most common sources. Independent risk factors for receipt of antibiotic prescription were documented infection during the index admission (adjusted odds ratio [AOR], 7.0; 95% CI, 4.7-20.5), discharge to home hospice care (AOR, 2.9; 95% CI, 1.9-4.3), and having a cancer diagnosis (AOR, 2.2; 95% CI, 1.5-3.2), but not palliative care consultation (AOR, 0.8; 95% CI, 0.5-1.3). Fluoroquinolones (36%) and penicillins (22%) were the most frequently prescribed antibiotics; 17% of patients received prescriptions for multiple antibiotics. This study begs the question, “Is antibiotic treatment (AT) of infections inconsistent with patients' and families' goals of care (GOCs)?” AT may promote quality of life (QOL) by palliating symptoms and may support patients' longevity despite incurability. Other pertinent questions relate to responsible antimicrobial stewardship, healthcare quality and safety, fiduciary responsibility,3,4 and effect on patient access. Were the prescribed antibiotics the most cost effective of available choices? Was there communication with the prescriber about GOCs? Were they prescribed for an appropriate duration? What was the rationale for AT for those without a documented infection? How many suffered from poorly controlled symptoms due to lack of AT? How many declined hospice care due to the limitation many hospices place on antibiotics? Most patients discharged from hospital to hospice with AT have a documented infection; areas ripe for research include the impact of AT and other medications on QOL, hospice access, and fiduciary responsibility. Donna S. Zhukovsky, MD, FACP, FAAHPM, University of Texas M, D. Anderson Cancer Center, Houston, TX. Furuno JP, Noble BN, Horne KN, et al. Frequency of outpatient antibiotic prescription on discharge to hospice care. Antimicrob Agents Chemother 2014;58:5473-5477. 1.Albrecht JS, McGregor JC, Fromme EK, Bearden DT, Furuno JP. A nationwide analysis of antibiotic use in hospice care in the final week of life. J Pain Symptom Manage 2013;46:483-490.2.Nagy-Agren S, Haley H. Management of infections in palliative care patients with advanced cancer. J Pain Symptom Manage 2002;24:64-70.3.Society for Healthcare Epidemiology of America, Infectious Diseases Society of America, Pediatric Infectious Diseases Society. Policy statement on antimicrobial stewardship by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), and the Pediatric Infectious DiseasesSociety (PIDS). Infect Control Hosp Epidemiol 2012;33:322-327.4.Ford PJ, Fraser TG, Davis MP, Kodish E. Anti-infective therapy at end of life: ethical decision-making in hospice-eligible patients. Bioethics 2005;19:379-392. Parents of children with serious illness often have overly optimistic expectations of prognosis.1 Is there discordance between the expectations of parents of children with advanced cancer and their providers regarding care? This survey study assessed parent-provider concordance about prognosis and goals of care (GOCs) as part of a randomized controlled trial of a supportive care intervention for children with advanced cancer conducted at three large pediatric cancer centers. Eligible children were aged 2 years and older and had a 2-week or longer history of progressive, recurrent, or nonresponsive cancer or a decision made to not pursue cancer-targeted treatment. At baseline, parents and providers completed a 4-point Likert scale assessing likelihood of cure (from “very unlikely” to “very likely”) and a 5-point scale assessing primary goal of current medical treatment (from “cure” to “lessen suffering”). Participating children (N = 77) were mean (SD) age 13 (6) years, 60% non-CNS solid tumors, and 26 (20) months from diagnosis. Participating parents (N = 77) were mean (SD) age 44 (8) years, 86% mothers, 66% some college education. Participating providers (N = 54) were mean (SD) age 38 (7) years, mean (SD) years of experience 10 (7), 77% female. Parents reported a higher likelihood of cure than did providers (49% vs. 22%, P < 0.001) and were more likely to report cure as the GOC (64% vs. 38%, P = 0.03). The most common goal reported by providers was extending life without hope of cure. Parent-provider concordance was poor for both prognosis and GOC (κ = 0.2; 95% CI, 0.1-0.4, and κ = 0.1; 95% CI, 0.05-0.2, respectively). We do not know whether parents or providers were more accurate in their prognosis; evidence suggests that parents tend to be overly optimistic and clinicians overly pessimistic. Still, lack of consensus about prognosis, particularly in advanced disease, undermines meaningful discussions about goals. Interestingly, providers in this study were relatively young, suggesting that communication gaps persist even as medical training increasingly emphasizes communication skills. The study results should help clinicians anticipate prognostic discordance; developing skills to explore the meaning of prognosis with families is an important training opportunity. Hope may be central to parental identity in the face of their child's illness, and clinicians need skills to help parents hope for what is possible given the likely prognosis. Provider-parent concordance about prognosis is often absent in pediatric oncology, particularly for some disease types; clinicians should expect and address this discordance as we help parents hope for what is possible. Renee D. Boss, MD, MHS, Johns Hopkins University School of Medicine, Baltimore MD. Rosenberg AR, Orellana L, Kang TI, et al. Differences in parent-provider concordance regarding prognosis and goals of care among children with advanced cancer. J Clin Oncol 2014 Jul 14. [Epub ahead of print]. 1.Wolfe J, Klar N, Grier HE, et al. Understanding of prognosis among parents of children who died of cancer: impact on treatment goals and integration of palliative care. JAMA 2012;284:2469-2475. Since the case W v. M in 2011, extensive controversy has surrounded withdrawal of artificial nutrition and hydration (ANH) from patients in permanent vegetative (PVS) or minimally conscious states (MCS). What are the real-life views and experiences of their families? This qualitative study of relatives of individuals with PVS or MCS regarding withdrawal of ANH was drawn from a larger study of families describing experiences with a severely brain-injured relative. Participants (N = 51) were recruited from social contacts of the two qualitative interviewers, sisters who had a severely brain-injured sister, via brain injury support groups, and by the snowball technique until thematic saturation was achieved. Approximately one-third of interviewees believed that their family member would prefer to be kept alive in PVS or MCS and were almost universally within the first 2 years of the precipitating event. Families who believed the patient would rather be dead tended to arrive at this view only after they felt that all possibilities of recovery to an acceptable quality of life had been exhausted, by which time the patient had been stabilized and ANH was the only life-sustaining treatment. Thus the opportunity to allow death by any other means was no longer available. Most families were strongly opposed to withdrawal of ANH because of the proposed manner of death by “starvation and dehydration,” but were willing to allow a natural death by placing a ceiling on the level of care provided to the patient, for example by instituting a “do-not-resuscitate” policy. The strength and weakness of this study comes from the unique situation of its authors, who have a sister with a brain injury. They provide little description of their subjects, many of whom they knew, and they did the analysis themselves, raising concerns for bias. The different legal environment in England surrounding ANH also limits generalizability. These caveats notwithstanding, the authors' personal experiences allow them a fascinating insider's view. The most sensitive revelation is that many families have thought about killing the patient, believing euthanasia more humane than stopping ANH. This not only reignites the debate about physician aid in dying2,3 but also gives helpful insight for clinicians navigating these conversations. Some families accept limiting escalation of care but continue ANH in patients in PVS/MCS, not because they think the patients want to live but because they believe stopping ANH is cruel and do not see any other option. Gordon J. Wood, MD, MSci, FAAHPM, Midwest Palliative & Hospice CareCenter, Glenview IL, and Northwestern University Feinberg School of Medicine, Chicago, IL. Kitzninger C, Kitzinger J. Withdrawing artificial nutrition and hydration from minimally conscious and vegetative patients: family perspectives. J Med Ethics 2014 Jan 14. [Epub ahead of print]. 1.W v. M (2011) EWHC 2443 (Fam).2.Seigel AM, Sisti DA, Caplan AL. Pediatric euthanasia in Belgium: disturbing developments. JAMA 2014;311:1963-1964.3.Quill TE. Death and dignity—A case of individualized decision making. N Engl J Med 1991;324:691-694. The rate of self-injury is increased in children who lost a parent to cancer.1 What are the risk factors for self-harm in this population? This was a nation-wide population-based study of Swedish youths who had lost a parent aged 64 years or older to cancer. Eligibility included age 18 to 26 years at time of survey and 13 to 16 years at bereavement, living with both parents at time of loss, and other parent still alive. An anonymous survey, developed according to established methods, that evaluated four family and 15 healthcare-related potential predictors, was mailed to consenting individuals and included questions about self-injury, issues relating to their family, and parental health care. Participants (N = 622) were 50% male, 80% high school educated, and 54% bereaved of father. Participation rate was 73%. Nineteen percent of participants reported a history of postbereavement self-injury. Univariate analysis revealed significant associations with poor cohesion before (relative risk [RR], 3.4; 95% CI, 2.5-4.6) and after the loss (RR, 3.3; 95% CI, 2.4-4.4), distrust in provided health care (RR, 1.7; 95% CI, 1.2-2.4), perceived poor healthcare efforts to cure the parent (RR, 1.5; 95% CI, 1.1-2.1), perceived poor efforts to prevent suffering (RR, 1.6; 95% CI, 1.1-2.4), history of depression or life troubles in at least one parent (RR, 1.5; 95% CI, 1.1-2.1), and belief in cure 3 days before the death (RR, 1.6; 95% CI, 1.1-2.3). In multivariable analysis, only poor family cohesion before and after parental loss were associated with self-injury. End-of-life situations can stress families to the point of crisis. This study suggests that the lack of family cohesion prior to or following a parent's death can herald self-injurious behavior in teenagers. Extrapolations from the data may be limited by the lack of definition of cohesion or information about the cultural context, as well as lack of an established minimally important difference. P-values, although statistically significant, may not be clinically significant. The findings may, however, lead palliative care clinicians to pay closer attention to teenagers whose family relationships may be perceived by the teen as brittle or fractured. Palliative care teams may not be able to “fix” families in crisis; they may, nonetheless, be able to provide more support or referrals to families with teens at risk for self-injurious behavior after parental loss. Teenagers may be at increased risk of self-injurious behavior during bereavement if their family cohesion is compromised before or after the death of their parent. Jane E. Loitman, MD, MBA, FAAHPM, Washington University School of Medicine, St. Louis, MO. Grenklo TB, Kreicbergs U, Valdimarsdottir UA, et al. Self-injury in youths who lost a parent to cancer: nationwide study of the impact of family-related and healthcare-related factors. Psychooncology 2014;23:989-997. 1.Bylund Grenklo T, Kreicbergs U, Hauksdottir A, et al. Self-injury in teenagers who lost a parent to cancer: a nationwide, population-based, long-term follow-up. JAMA Pediatr 2013;167:133-140. http://www.ncbi.nlm.nih.gov/pubmed?term=2013%5bpdat%5d+AND+Guon+J%5bauthor%5d&cmd=detailssearch In older patients, reduced mobility is a risk factor for disability, morbidity, and mortality.1 Is a long-term structured physical activity program more effective than a health education program at reducing the risk of major mobility disorder (MMD)? This multicenter, single-blind, parallel randomized trial examined the impact of physical activity on MMD. Eligible participants were sedentary, aged 70 to 89 years, at high risk for MMD, could walk 400 meters within 15 minutes, and had no major cognitive impairment. The primary outcome was inability to walk 400 meters within 15 minutes without assistance. The intervention group (n = 818) received a structured, moderate-intensity physical activity program (center-based twice weekly and home-based 3 to 4 times/week) with 150 minutes/week of aerobic, resistance, and flexibility training exercises. The control group (n = 817) received weekly, followed by monthly, programs focused on “successful aging.” Participants (N = 1635) were mean age 79 years, 67% female, 17% African American, and mean body mass index of 30. Mean duration of follow-up was 2.6 years. The physical activity group attended a median (% [IQR]) of 71% [50%-83%] of sessions after excluding medical leave, and the control group, 82% [63%-90%]. MMD occurred in 30% of the intervention vs. 35% of the control group (hazard ratio [HR], 0.8; 95% CI, 0.7-1.0; P = 0.03), with persistent MMD in 15% of the physical activity group and 20% of the health education group (HR, 0.7; 95% CI, 0.6-0.9; P = 0.006). There was no significant difference in frequency of serious adverse events between the groups. This randomized trial demonstrates that a low-intensity, structured exercise program for sedentary older adults reduces risk of disability in the next few years. The study uses rigorous methods and compared the intervention to an attention control of in-person health education—likely to bias toward a negative trial. The target population was sedentary but not seriously ill; nonetheless, 59% had to take “medical leave” for acute illnesses during the study. The intervention is simple to replicate and costs $1815 per person per year. Exercise is an essential intervention to maintain mobility for sedentary older persons—a structured program with paid transportation makes the difference! Laura C. Hanson, MD, MPH, FAAHPM, University of North Carolina–Chapel Hill, Chapel Hill, NC. Pahor M, Guralnik JM, Ambrosius WT, et al. Effect of structured physical activity on prevention of major mobility disability in older adults. JAMA 2014;311:2387-2396. 1.Newman AB, Simonsick EM, Naydeck BL, et al. Association of long-distance corridor walk performance with mortality, cardiovascular disease, mobility limitation, and disability. JAMA 2006;295:2018-2026. Cancer cachexia is characterized by higher energy expenditure levels, which have been linked to increased brown fat thermogenesis.1 What mechanism explains the link between thermogenesis and tissue loss in cachexia? This preclinical study used a Lewis lung carcinoma (LLC) mouse model to examine the molecular characteristics of cancer cachexia. First, a gene expression profile was created of genes involved in adipose thermogenesis and energy metabolism. Subclone lines of single-cell isolates from an LLC population were assayed for their effect on thermogenic activity in adipose cells, and microarray analysis was performed. Candidate molecules from this screen were subjected to in vitro and in vivo assays and finally explored in clinical samples of patients diagnosed with cancer. In this cancer cachexia mouse model, tissue loss resulted from increased fat metabolism independent of physical activity or food intake. Adipose thermogenesis genes were up-regulated in the model, and reduced thermogenic potential was correlated with less adipose tissue wasting. The subclone screen revealed that thermogenesis genes were up-regulated in the presence of a g-protein coupled receptor, tumor-derived parathyroid-hormone-related protein (PTHrP), which is involved in the cellular respiration pathway. Antibody experiments revealed that adipocyte browning, indicative of thermogenesis, was dependent on PTHrP. In vivo, weight loss of tumor-bearing mice was exacerbated by exposure to PTHrP, whereas anti-PTHrP treatment reduced weight loss to insignificant levels. Finally, PTHrP expression was examined in a cohort of patients diagnosed with cancer; expression of PTHrP correlated with lower lean body mass and higher resting energy expenditure. Prior studies show cachectic cancer patients have a higher prevalence of brown fat.1 White fat contains pockets of “beige” cells that can be stimulated by cold exposure or sympathetic activation via a process termed “browning”. In this study, PTHrP caused wasting of fat and muscle in mice through increased expression of genes involved in adipose tissue thermogenesis. Blockage of PTHrP by antibody prevented fat browning and muscle wasting, and increased physical activity, with no effect on tumor growth. In a subset of cancer patients with detectable PTHrP levels, PTHrP was associated with increased resting energy expenditure and decreased muscle but no change in calorie intake or inflammatory markers. Although PTHrP is known to cause hypercalcemia-associated cachexia, this study is the first to demonstrate direct effects on fat and increased metabolism. Based on this mouse model, neutralizing antibody to PTHrP may prove to be effective anticachexia therapy for patients. Egidio Del Fabbro, MD, Virginia Commonwealth University Massey Cancer Center, Richmond, VA. Kir S, White JP, Kleiner S, et al. Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia. Nature 2014;513:100-104. 1.Shellock FG, Riedinger MS, Fishbein MC. Brown adipose tissue in cancer patients: possible cause of cancer-induced cachexia. J Cancer Res Clin Oncol 2014;111:82-85. PC-FACS Feedback We appreciate your feedback. Help us help you—send your comments to [email protected] PC-FACS was created in 2005 by Founding Editor-in-Chief Amy P. Abernethy, MD, PhD, FACP, FAAHPM. The Academy is deeply grateful to Dr. Abernethy for creating this important publication and for her many contributions to the field of hospice and palliative medicine. PC-FACS is edited by Editor-in-Chief, Donna S. Zhukovsky, MD, FACP, FAAHPM, of the University of Texas M. D. Anderson Cancer Center, and Associate Editor-in-Chief, Mellar P. Davis, MD, FCCP, FAAHPM, of the Taussig Cancer Institute at Cleveland Clinic. All critical summaries are written by Jane Wheeler, MPH. AAHPM thanks the following PC-FACS Editorial Board members for their review of the critical summaries and preparatio of the commentaries: Basic Science Egidio Del Fabbro, MD, Senior Section Editor Fidel Davila, MD, MSMM Rony Dev, DO, MS Khurram J. Khan, MD Eric Prommer, MD, FAAHPM Bioethics, Humanities, and Spirituality Francine Rainone, DO, PhD, MS, FAAHPM, Senior Section Editor Robert M. Arnold, MD, FAAHPM Ira Byock, MD, FAAHPM Valencia Clay, MD Hunter Groninger, MD, FAAHPM Jessica A. Moore, DHCE, MA Alan J. Nixon, MD, FAAHPM Gordon Wood, MD, MSci, FAAHPM Geriatrics and Care Transitions Paul Tatum, MD, MSPH, AGSF, CMD, FAAHPM, Senior Section Editor David B. Brecher, MD, FAAFP, FAAHPM Laura C. Hanson, MD, MPH, FAAHPM Sandra Sanchez-Reilly, MD, MSc, AGSF, FAAHPM Eric Widera, MD Hospice, Hospice and Palliative Medicine Interface, and Regulatory Issues Tommie W. Farrell, MD, Senior Section Editor Janet H. Bull, MD, FAAHPM Charles S. Mills, MD, FACP J. Cameron Muir, MD, FAAHPM Joel S. Policzer, MD, FACP, FAAHPM Pediatrics Christina Ullrich, MD, MPH, Senior Section Editor Rene D. Boss, MD, MHS Marcia Levetown, MD, FAAP, FAAHPM Robert C. Macauley, MD, FAAHPM Psychosocial Thomas B. Strouse, MD, Senior Section Editor Steven J. Baumrucker, MD, FAAFP, FAAHPM Myra Glajchen, DSW Stephanie M. Harman, MD, FACP Jane E. Loitman, MD, MBA, FAAHPM David Nowels, MD, MPH Symptom Assessment and Management Stephen J. Bekanich, MD, Senior Section Editor Amy P. Abernethy, MD, FACP, FAAHPM Michael A. Ashburn, MD, MBA, MPH James T. D'Olimpio, MD, FACP, FAAHPM Daniel L. Handel, MD Dana Lustbader, MD, FCCM, FCCP, FAAHPM Aaron Olden, MD, MS Eric Roeland, MD Ad Hoc Reviewers Mary Braun, MD Jeanne-Marie Maher, MD, FACP Lisa E. Thompson, MD Denise G. Waugh, MD, FACEP, FAAHPM PC-FACS is partially supported through an unrestricted educational grant from Purdue Pharma, LP. The views expressed herein are those of the individual authors and are not necessarily those of the Academy. Information included herein is not medical advice and is not intended to replace the judgment of a practitioner with respect to particular patients, procedures or practices. To the extent permissible under applicable laws, the Academy disclaims responsibility for any injury and / or damage to persons or property as a result of any actual or alleged libelous statements, infringement of intellectual property or other proprietary or privacy rights, or from use or operation of any ideas, instructions, procedures, products or methods contained in this publication. American Academy of Hospice and Palliative Medicine 8735 W. Higgins Road, Suite 300 Chicago, IL 60631, USA Phone: 847-375-4712 Fax: 877-734-8671 E-mail: Website: www.aahpm.org