Shannon Rhodes

Evidence for Improving Palliative Care at the End of Life: A Systematic Review

Americans struggling with symptoms and disability often die of chronic illness, and improving care during this period is important (1, 2). About 30% of Medicares expenditures arise in patients last year of life, and outlays will increase as the population ages (3). Hospices serve most Americans dying of cancer and 10% of all others (3). More than 25% of hospitals had palliative care services in 2003 (4). Even with growing specialization in palliative medicine and geriatrics, generalist physicians will provide most services. People tend to follow characteristic patterns of clinical and functional decline as they approach the end of life. The clinical course exemplified by cancer often ends with obvious decline in the last weeks or months (5). In contrast, organ system failure tends to cause long-term lack of reserve and intermittent serious exacerbations, making the timing of death unpredictable (6, 7). A third group marked by frailty and often dementia usually declines slowly (68, 8) (Appendix Figure). Organizing our report around these 3 common trajectories, we systematically reviewed the literature to address the following questions posed by the American College of Physicians Clinical Efficacy Assessment Subcommittee: Appendix Figure. Trajectories of late-life illness. What are the critical elements for clinicians to address when caring for persons coming to the end of life? What do definitions of the end of life suggest about identifying patients who could benefit from palliative approaches? What treatment strategies work well for pain, dyspnea, and depression? What elements are important in advance care planning for patients coming to the end of life? What elements of collaboration and consultation are effective in promoting improved end of life care? What elements of assessment and support are effective for serving caregivers, including family, when patients are coming to the end of life? Methods Objectives We reviewed evidence for the National Institutes of Health (NIH) State-of-the-Science Conference on Improving End-of-Life Care in December 2004 and updated it through November 2005 to support guideline development by the American College of Physicians. In addressing the 6 questions posed by this report, we focused on the clinical problems and literature related to pain, dyspnea, and depression; advance care planning; continuity; and caregiver concerns because they are especially important to patients and families (9). We focused on cancer, chronic heart failure, and dementia to illustrate differences in patient and caregiver experiences in the 3 characteristic trajectories of clinical and functional decline (58). Literature Search National Library of Medicine librarians searched MEDLINE for English-language publications (January 1990 to April 2004), and 1 reviewer used the Database of Abstracts of Reviews of Effects to search for reviews on cancer, congestive heart failure (CHF), and dementia. We added citations identified by the National Consensus Project for Quality Palliative Care (10). An advisory panel and peer reviewers suggested additional references until September 2004. We updated the original search strategy through November 2005 and further updated the literature to January 2007 by using the American Academy of Hospice and Palliative Medicine literature surveillance (for example, Fast Article Critical Summaries for Clinicians in Palliative Care) and the Annual Update (available at www.aahpm.org/membership/pcfacs.html). We did not search gray literature because it did not contribute to a recent review of the effectiveness of palliative care teams (11). Literature Selection and Abstraction Eight reviewers familiar with palliative care formed topic-oriented, 2-person teams. We accepted English-language publications from the United States, Canada, Western Europe, Australia, and New Zealand. We included studies about the definition of end-of-life care. Advance care planning reports had to address process or outcomes for patients and families (not just clinicians). Continuity publications had to address relationships with providers over time (12). Informal caregiving articles excluded bereavement. We described spiritual care outcomes when reported with emotional well-being. We rejected studies that addressed only surgery, chemotherapy, radiotherapy, stents, lasers, and similar technical interventions or if they reported only physiologic, laboratory, or radiologic outcomes. We characterized articles by research design quality, study population, settings, intervention, and outcomes. Studies addressing several topics are included in each topics section. Several methods reduced bias and enhanced accuracy, and 1 reviewer screened each citation. Two experts in systematic reviews conducted a structured, implicit evaluation of the quality of reviews. For intervention studies, each reviewer completed a training set, and 1 principal investigator reviewed a random subset from each reviewers citations and double-reviewed outlier sets. Reviewers discussed uncertain decisions, and we abstracted full articles in teams, coming to consensus after independent review. Two principal investigators reviewed abstractions from articles, and we used piloted, standard forms throughout. Data Analysis The variety of outcome measures and study designs required qualitative synthesis of the evidence. We evaluated the strength of evidence related to each of the 6 questions for each of the 3 clinical and functional trajectories (for example, cancer, CHF, and dementia) (58). We discuss specific interventions only for reports not previously covered in high-quality reviews. We rated the study design, quality, consistency, and directness in each domain according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system, yielding ratings of the strength of evidence of high, moderate, low, or very low (13). In each area, we rated the overall evidence based on unique studies within each domain, qualitatively taking into account studies addressed by several reviews. Role of the Funding Source The Agency for Healthcare Research and Quality (AHRQ) and the National Institute of Nursing Research funded our initial systematic review. An advisory group from the National Institute of Nursing Research shaped our initial aims and review priorities. We complied with the methodological standards of the AHRQ and the National Institutes of Health Office of Medical Applications of Research (available at www.ahrq.gov/clinic/epcsums/eolsum.htm) (14). The funding sources played no role in the analysis of the data or decision to submit this material for publication. We produced this updated report under contract to the American College of Physicians Clinical Efficacy Assessment Subcommittee. This research did not involve human participants. Results Literature Flow The April 2004 search identified 24423 titles, from which we identified 6381 potentially relevant abstracts and then 1274 potentially relevant articles. Accepted articles included 95 systematic reviews and 109 reports of interventions. The November 2005 update identified an additional 944 titles, including 8 systematic reviews and 19 reports of interventions. After November 2005, expert sources added an additional 3 systematic reviews and 3 interventions. This report includes 33 high-quality systematic reviews and 89 intervention reports (Figure). Appendix Tables 1, 2, 3, 4, and 5 provide details about the literature cited. Appendix Table 1. Systematic Reviews and Meta-analyses of Symptoms, Advance Care Planning, Continuity, and Caregiving Appendix Table 2. Interventions Appendix Table 3. Caregiving Appendix Table 4. Continuity Appendix Table 5. Symptoms Figure. Study flow diagram. *From the American Academy of Hospice and Palliative Medicine Fast Article Critical Summaries for Clinicians in Palliative Care and Annual Updates, November 2006 to January 2007. Some reviews and interventions were relevant to more than 1 domain. What Are the Critical Issues for Clinicians to Address when Caring for Persons Nearing the End of Life? Expert opinion and qualitative research have characterized priority concerns for patients in late life (1519). One national survey defined whether patients, caregivers, and providers have similar concerns (15), and an after-death survey evaluated whether health care achieves these ends (20). Important topics include preventing and treating pain and other symptoms, supporting families and caregivers, ensuring continuity, making informed decisions, attending to emotional well-being (including spiritual concerns), sustaining function, and surviving longer. The studies addressed various illnesses and settings, showing that dying patients and their families generally share these concerns. What Do Definitions of End of Life Suggest about Identifying Patients Who Could Benefit from Palliative Approaches? The literature used various approaches to identify patients at the end of life. Some used clinician assessment of active dying or patient readiness, but no precise definitions or performance characteristics of these terms have been published. Many studies used specified clinical characteristics, survival prediction rules, or physician judgment (21). Although prognostic tools usefully characterize subpopulations (for example, heart failure), many patients with fatal conditions have substantial probabilities for 2- or 6-month survival, even in their last week of life (6, 7). Patients with metastatic cancer, who have an estimated 10% or greater chance of dying within 6 months, are more likely to prefer to avoid resuscitation, even when survival was much less likely than they acknowledged (22). Thus, clinicians might define the end of life as having a fatal condition, risking death with the next exacerbation, or beginning to acknowledge the seriousness of the situation (23). Asking clinicians Would it be a surprise if this patient were to die withi

Efficacy of Angiotensin-Converting Enzyme Inhibitors and Beta-Blockers in the Management of Left Ventricular Systolic Dysfunction According to Race, Gender, and Diabetic Status A Meta-Analysis of Major Clinical Trials

OBJECTIVESnThis study sought to assess the effect of angiotensin-converting enzyme (ACE) inhibitors and beta-blockers on all-cause mortality in patients with left ventricular (LV) systolic dysfunction according to gender, race, and the presence of diabetes.nnnBACKGROUNDnMajor randomized clinical trials have established that ACE inhibitors and beta-blockers have life-saving benefits in patients with LV systolic dysfunction. Most patients enrolled in these trials were Caucasian men. Whether an equal effect is achieved in women, non-Caucasians, and patients with major comorbidities has not been established.nnnMETHODSnThe authors performed a meta-analysis of published and individual patient data from the 12 largest randomized clinical trials of ACE inhibitors and beta-blockers to produce random effects estimates of mortality for subgroups.nnnRESULTSnData support beneficial reductions in all-cause mortality for the use of beta-blockers in men and women, the use of ACE inhibitors and some beta-blockers in black and white patients, and the use of ACE inhibitors and beta-blockers in patients with or without diabetes. Women with symptomatic LV systolic dysfunction probably benefit from ACE inhibitors, but women with asymptomatic LV systolic dysfunction may not have reduced mortality when treated with ACE inhibitors (pooled relative risk = 0.96; 95% confidence interval: 0.75 to 1.22). The pooled estimate of three beta-blocker studies supports a beneficial effect in black patients with heart failure, but one study assessing bucindolol reported a nonsignificant increase in mortality.nnnCONCLUSIONSnAngiotensin-converting enzyme inhibitors and beta-blockers provide life-saving benefits in most of the subpopulations assessed. Women with asymptomatic LV systolic dysfunction may not achieve a mortality benefit when treated with ACE inhibitors.

Systematic review of the effects of n−3 fatty acids in inflammatory bowel disease

BACKGROUNDnn-3 Fatty acids are purported to have health effects in patients with inflammatory bowel disease (IBD), but studies have reported mixed results.nnnOBJECTIVEnWe aimed to synthesize published and unpublished evidence to determine estimates of the effect of n-3 fatty acids on clinical outcomes in IBD and whether n-3 fatty acids modify the effects of or need for treatment with other agents.nnnDESIGNnComputerized databases were searched for studies of n-3 fatty acids in immune-mediated diseases from 1966 to 2003. We also contacted experts in the nutraceutical industry to identify unpublished studies; however, none were identified.nnnRESULTSnReviewers identified 13 controlled trials that assessed the effects of n-3 fatty acids on clinical, sigmoidoscopic, or histologic scores; rates of induced remission or relapse; or requirements for steroids and other immunosuppressive agents in Crohn disease or ulcerative colitis. Most clinical trials were of good quality. Fewer than 6 were identified that assessed the effects of n-3 fatty acids on any single outcome of clinical, endoscopic, or histologic scores or remission or relapse rates. Consistent across 3 studies was the finding that n-3 fatty acids reduce corticosteroid requirements, although statistical significance was shown in only 1 of these studies.nnnCONCLUSIONnThe available data are insufficient to draw conclusions about the effects of n-3 fatty acids on clinical, endoscopic, or histologic scores or remission or relapse rates.