PC-FACS

Abstract

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]. Houben CH, Spruit MA, Groenen MTJ, Wouters EFM, Janssen DJA. Efficacy of advance care planning: a systematic review and meta-analysis. J Am Med Dir Assoc 2014;15: 477-489. Grinnell SG, Majumdar S, Narayan A, et al. Pharmacologic characterization in the rat of a potent analgesic lacking respiratory depression, IBNtxA. J Pharmacol Exp Ther 2014;350:710-718. Tietze AL, Zernikow B, Michel E, Blankenburg M. Sleep disturbances in children, adolescents, and young adults with severe psychomotor impairment: impact on parental quality of life and sleep. Dev Med Child Neurol 2014;56:1187-1193. Mehnert A, Brahler E, Faller H, et al. Four-week prevalence of mental disorders in patients with cancer across major tumor entities. J Clin Oncol 2014;32:3540-3546. Paulsen O, Klepstad P, Rosand JH, et al. Efficacy of methylprednisolone on pain, fatigue, and appetite loss in patients with advanced cancer using opioids: a randomized, placebo-controlled, double-blind trial. J Clin Oncol 2014;32:3221-3228. Aaltonen M, Raitanen J, Forma L, et al. Burdensome transitions at the end of life among long-term care residents with dementia. J Am Med Dir Assoc 2014;15: 643-648. In the past 20 years multiple interventions to improve advance care planning (ACP) have been published. What has been the efficacy of ACP in different adult patient populations? This systematic review of ACP interventions searched Medline/PubMed and Cochrane Central Register of Controlled Trials from 1966 through September 2013, supplemented by hand searches. Eligible studies were English-language randomized controlled trials. Meta-analysis was conducted with a random effects model. Methodological quality was assessed by the Physiotherapy Evidence-Based Database (PEDro) scale.1 Interventions were classified into those directed exclusively at completion of advance directives (AD) and those that also included communication about ACP. Primary outcome measures were AD completion and occurrence of end-of-life (EOL) discussions. Secondary outcomes included concordance between care preferred and care delivered. Fifty-six studies were identified; 37 (66%) recruited outpatients, 15 (27%) inpatients, and four (7%) both. Twenty-six trials focused on ADs alone; 30 included communication about ACP. The median PEDro score was 5; 31 studies (55%) scored less than 6 and were designated as low quality. Interventions focusing on AD and those including communication about ACP were associated with an increased likelihood of AD completion (OR, 3.3; 95% CI, 2.0-5.3; P = 0.00001) and EOL care discussions between providers and patients (OR, 2.8; 95% CI, 2.2-3.8; P < 0.00001), compared with usual care. Interventions including ACP communication also were associated with an increased likelihood of receiving EOL care concordant with patient preferences, compared with usual care (OR, 4.7; 95% CI, 1.2-18.1; P = 0.03). This is a relevant systematic review of ADs and ACP in different patient populations. Unfortunately it lacks power due to lack of blinding, validity, and ability to accurately compare studies in different venues. The reviewers have done great statistical work to arrive at their conclusions regarding primary and secondary outcomes. Clearly an AD alone is unlikely to lead to the desired outcome for patient, family, and caregivers. As the reviewers iterate, there need to be further studies appropriately blinded and comparing usual care and ACP and effect on EOL outcome (i.e., meeting patients' physical, emotional, and spiritual needs and those of their nearest and dearest). AD discussion alone is unlikely to enhance EOL care without discussion of ACP and communication. This is a process, not an event. Further prospective studies are needed. Alan J. Nixon, MB, BCh, BAO, CCFP(C), FAAHPM, University of British Columbia, BC, Canada. Houben CH, Spruit MA, Groenen MTJ, Wouters EFM, Janssen DJA. Efficacy of advance care planning: a systematic review and meta-analysis. J Am Med Dir Assoc 2014;15: 477-489. 1.Sherrington C, Herbert RD, Maher CG, Mosely AM. PEDro. A database of randomized trials and systematic reviews in physiotherapy. Man Ther 2000;5:223-226. IBNtxA is a potent unique opioid analgesic in animal models.1-2 What characteristics of IBNtxA pharmacology may be clinically important? This preclinical study used an in vitro and in vivo rat model to evaluate the pharmacodynamics of rats subcutaneously injected with IBNtxA. Rats were tested for analgesia using the radiant heat tail-flick assay1,3 following escalating doses every 30 minutes. Mice were made cross-tolerant to morphine by implanted free-base pellets and tested for IBNtxA analgesia. The influence of IBNtxA on respiratory function was separately assayed by oximetry in freely moving rats. Oxygen saturation value was measured every 5 minutes. Binding affinity of [125I]IBNtxA was assayed in brain membrane homogenates in the presence of mu-, kappa-, and delta-opioid receptor antagonists. IBNtxA administration produced analgesia (ED50 of 0.9 mg/kg [95% CI, 0.7-1.2]) fourfold more potent than morphine with no respiratory depression at levels up to five times the ED50. IBNtxA analgesia was less sensitive to naloxone than morphine. Rats cross-tolerant to morphine displayed no reduction in IBNtxA analgesia. The IBNtxA binding profile was distinctly different from traditional opioid receptors and involved the exon 11 mu subtype receptor, which is a six- rather than seven-transmembrane receptor.4 This is an encouraging preclinical study of IBNtxA, which provides four times more potent analgesia than morphine without accompanying respiratory depression. In addition, IBNtxA does not produce physical dependence or reward behavior with chronic administration, has minimal effects on gastrointestinal transit, and shows no cross-tolerance to morphine in mice. Clinical trials of IBNtxA are needed to evaluate the potential of this synthetic opioid, because the same splice variant mu receptors also are found in humans. Future applications of this agent for palliative care patients include the relief of pain and dyspnea with lower doses and fewer adverse effects, as well as reduced risk of allodynia, hyperalgesia, and chemical coping with long-term opioid use. This preclinical study suggests that using different site-specific binding strategies on mu-opioid receptors can lead to the development of a potent analgesic agent with a favorable pharmacologic profile and possibly no tolerance and addiction. Khurram J. Khan, MD, Keck School of Medicine of University of Southern California, Los Angeles, CA. Grinnell SG, Majumdar S, Narayan A, et al. Pharmacologic characterization in the rat of a potent analgesic lacking respiratory depression, IBNtxA. J Pharmacol Exp Ther 2014;350:710-718. 1.Majumdar S, Grinell S, Le Rouzic V, et al. Truncated G protein-coupled mu opioid receptor MOR-1 splice variants are targets for highly potent opioid analgesics lacking side effects. Proc Natl Acad Sci USA 2001;108:19778-19783.2.Majumdar S, Saubrath J, Le Rouzic V, et al. Synthesis and evaluation of aryl-naloxamide opiate analgesics targeting truncated exon 11-associated mu opioid receptor (MOR-1) splice variants. J Med Chem 2012;55:6352-6362.3.Ling GSF, Spiegel K, Lockhart SH, Pasternak GW. Separation of opioid analgesia from respiratory depression: evidence for different receptor mechanisms. J Pharmacol Exp Ther 1985;232:149-155.4.Wieskopf JS, Pan YX, Marcovitz J, et al. Broad-spectrum analgesic efficacy of IBNtxA is mediated by exon 11-associated splice variants of the mu-opioid receptor gene. Pain 2014;155:2063-2070. Severe psychomotor impairment (SPMI) may affect caregiver health and quality of life (QOL).1 How does sleep disturbance in children affect parental sleep and QOL? This was a multisite, questionnaire-based, cross-sectional survey of parents of children with SPMI. Eligible families were recruited from three inpatient institutions and one outpatient facility in Germany. Eligibility criteria included an SPMI diagnosis, presence at a stable phase of the condition, and patient age ≤ 25 years. The three most common diagnoses were cerebral palsy, metabolic/neurodegenerative disorder, and global developmental delay. Parents completed the validated questionnaires HOST,2 Pittsburgh Sleep Quality Index (PSQI),3 SF-36,4 Epworth Sleepiness Scale (ESS),5 and SNAKE6 to assess parental sleep quality and the impact of sleep disturbance–related burden on QOL. Patient participants (n = 214) were 53% male and mean age 10 years; 25% had cerebral palsy/neuromuscular disorder, 16% had global developmental delay, and 87% were inpatients. Mean parental age was 41 years (SD, 8; mothers) and 44 years (SD, 7; fathers). Parents of children with SPMI reported a greater number of sleep problems and more daytime sleeping compared with a normal population, as indicated by PSQI and ESS surveys (P < 0.001). Parents also scored significantly lower on the vitality, cognitive health, and general health scales of the SF-36 health survey (P < 0.001). Parental sleep disturbance by the HOST scale was highly correlated with the child's sleep disturbance as measured by all four scales of the SNAKE (r = 0.36-0.7; P < 0.01). An average of 52 minutes per night was spent caring for the child (median, 30 min; range, 0-300 min). This paper addresses QOL among parents of severely disabled children. Many of these children sleep in their parents' bedrooms more than three nights per week. Why parents awoke to provide care is unclear, as is whether their ministrations increased the children's well-being. False alarms were common. Measures used correlated well, including the SF-36, but practical outcomes (e.g., job and income loss, irritability and marital strife, use of psychotropics and general health services) were not assessed. Documented social isolation and increased use of psychological services could result from caregiving generally rather than sleep deprivation, thus the study raises many questions. It is irrefutable that parents' well-being is impaired by their child's severe illness and associated caregiving needs. Parents of children with SPMI have compromised QOL, which should be assessed and managed by their child's care team; practical guidance (e.g., encourage that the child sleep in another room) and technical innovation (e.g., improved alarm reliability) may help. Marcia Levetown, MD, FAAP, FAAHPM, HealthCare Communication Associates, Houston, TX. Tietze AL, Zernikow B, Michel E, Blankenburg M. Sleep disturbances in children, adolescents, and young adults with severe psychomotor impairment: impact on parental quality of life and sleep. Dev Med Child Neurol 2014;56(12):1187-1193. 1.Raina P, O'Donnell M, Rosenbaum P, et al. The health and well-being of caregivers of children with cerebral palsy. Pediatrics 2005;115:e626-e636.2.Tietze A-L, Zernikow B, Hirschfeld G, et al. Development and psychometric assessment of a questionnaire to assess sleep and daily troubles in parents of children and young adults with severe psychomotor impairment. Sleep Med 2014;15:219-227.3.Buysse DJ, Reynolds CF III, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989;28:193-213.4.Bullinger M, Kirchberger I, Ware J. Der deutsche SF-36 Health Survey. J Publ Health 1995;3:21-36.5.Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991;14:540-545.6.Blankenburg M, Tietze A-L, Hechler T, et al. SNAKE: the development and validation of a questionnaire on sleep disturbances in children with severe psychomotor impairments. Sleep Med 2013;14:339-351. Psychological distress is common in patients with cancer, but prevalence rates are often based on self-report.1,2 What is the incidence of mental disorders in this population when assessed by a standardized diagnostic system? This was a multicenter, epidemiologic cross-sectional study of the four-week incidence of mental disorders in adult patients with cancer. Eligible patients were recruited from acute care hospitals, outpatient cancer care facilities, and cancer rehabilitation clinics in Germany. Eligibility criteria included confirmed malignant tumor diagnosis and age of 18 to 75 years. Each cancer diagnosis stratum was represented in the sample in the same proportion in which it occurs in the German population. Patients (N = 4020) were screened by the Patient Health Questionnaire (PHQ-9) depression module.3 Those scoring ≥9, along with a random sample of the remaining participants, were administered the Composite International Diagnostic Interview for Oncology (CIDI-O).4 Interviewed participants (n = 2141) were 42% PHQ-9 score ≥9, 52% female, 63% married, mean age 58 years (SD, 11), and mean 14 months since diagnosis. Thirty-two percent (95% CI, 30%-34%) of patient participants were diagnosed with at least one mental disorder. Anxiety disorders (11%; 95 % CI, 10%-13%) and adjustment disorders (11%; 95% CI, 10%-12%) were the most prevalent axis I mental disorders. Six percent of patients were diagnosed with two disorders (95% CI, 5%-7%). Patients with breast cancer had the highest four-week prevalence of any mental disorder (42%; 95% CI, 37%-46%), followed by head and neck cancer (41%; 95% CI, 29%-53%) and malignant melanoma (39%; 95% CI, 22%-56%). There is a high level of psychological distress among various cancer populations, often manifesting as anxiety and depression that closely interact with pain and other physical symptoms. While a relatively large study, only 69% of eligible patients actually participated in screening. The prevalence of 32% for “any mental disorder” is in agreement with previous studies but could be off by a significant fraction if the unscreened portion had a preponderance (or absence) of mental pathology. Not controlled for, the wide variation in prevalence by tumor type could be explained by differences in staging or socioeconomic factors. It is also possible that patients underreported symptoms, which is suggested by the surprisingly low rates of alcohol use/abuse identified in this survey (0.3% compared with 3% in the population at large). The sample was biased toward younger age, which also could influence outcomes. Although there is little question that this study confirms a need for cancer-specific psychological interventions, studies with more rigorous controls are needed to determine whether certain tumor types need focused treatment. Steven J. Baumrucker, MD, FAAFP, FAAHPM, Wellmont Health System and East Tennessee State University, Kingsport, TN. Mehnert A, Brahler E, Faller H, et al. Four-week prevalence of mental disorders in patients with cancer across major tumor entities. J Clin Oncol 2014;32:3540-3546. 1.Zabora J, BrintzenhofeSzoc K, Curbow B, et al. The prevalence of psychological distress by cancer site. Psychooncology 2001;10:19-28.2.Linden W, Vodermaier A, Mackenzie R, et al. Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age. J Affect Disorders 2012;141:343-351.3.Lowe B, Kroenke K, Herzog W, et al. Measuring depression outcome with a brief self-report instrument: sensitivity to change of the patient health questionnaire (PHQ-9). J Affect Disorders 2004;81:61-66.4.Hund B, Reuter K, Jacobi F, et al. Adaptation of the composite international diagnostic interview (CIDI) for the assessment of comorbid mental disorders in oncology patients: the CIDI-O. Psychother Psychosom Med Psychol 2014;64:101-107. Corticosteroids are often used to manage cancer-related pain, but the literature may not support their use as an analgesic.1 Is the efficacy of corticosteroid therapy greater than that of a placebo? This was a randomized, placebo-controlled, double-blind, parallel group, multicenter trial of corticosteroid pain management in patients with cancer. Eligible patients were older than 18 years, had average pain of at least 4 of 10, had greater than four weeks expected survival, and were receiving an opioid for moderate or severe cancer pain. Patients were randomly allocated to one of two groups receiving either placebo or 16 mg/day methylprednisolone twice daily for seven days. Primary outcome was average pain intensity (NRS 0-10) by the Brief Pain Inventory on days 0 and 7. Secondary outcomes included fatigue and appetite by the EORTC-QLQ-C30 questionnaire (0-100) and satisfaction by NRS (0-10). Patient participants (N = 49) were 50% female, mean age 64 years, and mean Karnofsky score 66. No difference in average pain intensity was reported between placebo and treatment groups (mean difference, -0.08; 95% CI, -0.97 to 1.13; corticosteroid arm, 3.6; 95% CI, 2.8 to 4.4; placebo arm, 3.7; 95% CI, 3.0 to 4.4; P = 0.88). No difference in opioid consumption was present. Fatigue and appetite improved in the treatment group by 17 and 24 points, respectively, and deteriorated in the placebo group (P < 0.005). Satisfaction was higher with corticosteroid treatment (5.4; 95% CI, 4.1 to 6.7 vs. 2.0; 95% CI, 0.7 to 3.3 for placebo; P =0.001). Previous studies evaluating the use of steroids in the treatment of cancer pain have yielded mixed results. The design and patient population are worth noting for this study. The baseline oral morphine equivalents (OME) were 269.9 mg in the intervention group, and approximate mean ECOG score was 2. Previous positive studies looked at patients on OMEs closer to 35 mg, and a mean ECOG score was 3.5. Subgroup analysis was not possible in this study due to the small size. Finally the exclusion criteria are numerous and disallowed enrollment if pain scores were <4 or >7 on a numeric scale. With these factors in mind, along with the collateral benefits from steroids and their tolerability, it would be premature to remove this drug class from the cancer pain treatment quiver. While steroids may help some cancer-related symptoms, the jury debating their impact on pain is still out. Stephen J. Bekanich, MD, Seton Palliative Care, Austin, TX. Paulsen O, Klepstad P, Rosand JH, et al. Efficacy of methylprednisolone on pain, fatigue, and appetite loss in patients with advanced cancer using opioids: a randomized, placebo-controlled, double-blind trial. J Clin Oncol 2014;32:3221-3228. 1.Paulsen O, Aass N, Kaasa S, et al. Do corticosteroids provide analgesic effects in cancer patients? A systematic literature review. J Pain Symptom Manage 2013;46:96-105. End-of-life (EOL) care transitions are common in patients with advanced dementia.1 What are the frequency and associated characteristics of burdensome transitions (BTs) in this population? This was a retrospective, nationwide study of patients with dementia in Finland. Eligible patients were in residence during the final months of life and died at 70 years or older. Data were drawn from nationwide registry data of health and social service use in care facilities in the last two years of life. BTs were defined as care facility transition during the last three days of life, lack of continuity in long-term-care facilities (LTCF) during the last 90 days of life, and multiple hospitalizations during the last 90 days of life.2 Group (N = 18,912) demographics were 76% women, three diagnoses, and mean age at death 87 years. The mean time spent in care was 172 days. Frequency of BTs was 9.5% (n = 1798); 0.7% (n = 129) experienced two different types of transitions. Multiple hospitalizations in the last 90 days of life (5.5%) followed by transitions in the last three days before death (4.4%) were most common. BTs were more likely in men younger than 90 years compared with women and those who died after age 90 years. The likelihood of at least one BT was higher among people in sheltered housing (odds ratio, 3.14; 95% CI, 2.8-3.5) than for those in nursing homes. Only 0.3% of dementia patients experienced a change in LTCF after a transition. At first glance, 9.5% BTs among dementia patients might be dismissed as immaterial. In a US study, Gozalo and colleagues found 11.6% transitions in the last three days of life, and 8.1% with multiple hospitalizations in the last 90 days of life.2 with tremendous variability by state; rates in Finland were similar to the Northern Plains and Pacific Northwest. A key finding is the high transition rate in “sheltered housing” compared with nursing homes. This is apropos to practices in states where dementia care is provided in “board and care” or “adult care homes” as alternatives to nursing homes. BTs for dementia patients are common enough that it should be addressed early with surrogates as part of advance care planning. When transitions occur, care plans must be portable and hospice care offered as an alternative. Burdensome dementia care transitions are common before death; sheltered housing alternatives have higher transition rates than traditional nursing homes. Paul Tatum, MD, MSPH, AGSF, CMD, FAAHPM, University of Missouri, Columbia, MO. Aaltonen M, Raitanen J, Forma L, et al. Burdensome transitions at the end of life among long-term care residents with dementia. J Am Med Dir Assoc 2014;15: 643-648. 1.Lamberg J, Person C, Kiely D, Mitchell S. Decisions to hospitalize nursing home residents dying with advanced dementia. J Am Geriatr Soc 2005;53:1396-1401.2.Gozalo P, Teno JM, Mitchell SL, et al. End-of-life transitions among nursing home residents with cognitive issues. N Engl J Med 2011;365:1212-1221. 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 Moses Sandrof and 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, MB, BCh, BAO, CCFP(C), 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. 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