Margaret Maglione

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.

Efficacy and Comparative Effectiveness of Atypical Antipsychotic Medications for Off-Label Uses in Adults: A Systematic Review and Meta-analysis

CONTEXTnAtypical antipsychotic medications are commonly used for off-label conditions such as agitation in dementia, anxiety, and obsessive-compulsive disorder.nnnOBJECTIVEnTo perform a systematic review on the efficacy and safety of atypical antipsychotic medications for use in conditions lacking approval for labeling and marketing by the US Food and Drug Administration.nnnDATA SOURCES AND STUDY SELECTIONnRelevant studies published in the English language were identified by searches of 6 databases (PubMed, EMBASE, CINAHL, PsycInfo, Cochrane DARE, and CENTRAL) from inception through May 2011. Controlled trials comparing an atypical antipsychotic medication (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, asenapine, iloperidone, or paliperidone) with placebo, another atypical antipsychotic medication, or other pharmacotherapy for adult off-label conditions were included. Observational studies with sample sizes of greater than 1000 patients were included to assess adverse events.nnnDATA EXTRACTIONnIndependent article review and study quality assessment by 2 investigators.nnnDATA SYNTHESISnOf 12 228 citations identified, 162 contributed data to the efficacy review. Among 14 placebo-controlled trials of elderly patients with dementia reporting a total global outcome score that includes symptoms such as psychosis, mood alterations, and aggression, small but statistically significant effects sizes ranging from 0.12 and 0.20 were observed for aripiprazole, olanzapine, and risperidone. For generalized anxiety disorder, a pooled analysis of 3 trials showed that quetiapine was associated with a 26% greater likelihood of a favorable response (defined as at least 50% improvement on the Hamilton Anxiety Scale) compared with placebo. For obsessive-compulsive disorder, risperidone was associated with a 3.9-fold greater likelihood of a favorable response (defined as a 25% improvement on the Yale-Brown Obsessive Compulsive Scale) compared with placebo. In elderly patients, adverse events included an increased risk of death (number needed to harm [NNH] = 87), stroke (NNH = 53 for risperidone), extrapyramidal symptoms (NNH = 10 for olanzapine; NNH = 20 for risperidone), and urinary tract symptoms (NNH range = 16-36). In nonelderly adults, adverse events included weight gain (particularly with olanzapine), fatigue, sedation, akathisia (for aripiprazole), and extrapyramidal symptoms.nnnCONCLUSIONSnBenefits and harms vary among atypical antipsychotic medications for off-label use. For global behavioral symptom scores associated with dementia in elderly patients, small but statistically significant benefits were observed for aripiprazole, olanzapine, and risperidone. Quetiapine was associated with benefits in the treatment of generalized anxiety disorder, and risperidone was associated with benefits in the treatment of obsessive-compulsive disorder; however, adverse events were common.

Depression and Medication Adherence in the Treatment of Chronic Diseases in the United States: A Meta-Analysis

ObjectiveTo conduct a meta-analysis of the association between depression and medication adherence among patients with chronic diseases. Poor medication adherence may result in worse outcomes and higher costs than if patients fully adhere to their medication regimens.Data SourcesWe searched the PubMed and PsycINFO databases, conducted forward searches for articles that cited major review articles, and examined the reference lists of relevant articles.Study Eligibility Criteria, Participants, and InterventionsWe included studies on adults in the United States that reported bivariate relationships between depression and medication adherence. We excluded studies on special populations (e.g., substance abusers) that were not representative of the general adult population with chronic diseases, studies on certain diseases (e.g., HIV) that required special adherence protocols, and studies on interventions for medication adherence.Study Appraisal and Synthesis MethodsData abstracted included the study population, the protocol, measures of depression and adherence, and the quantitative association between depression and medication adherence. Synthesis of the data followed established statistical procedures for meta-analysis.ResultsThe estimated odds of a depressed patient being non-adherent are 1.76 times the odds of a non-depressed patient, across 31 studies and 18,245 participants. The association was similar across disease types but was not as strong among studies that used pharmacy records compared to self-report and electronic cap measures.LimitationsThe meta-analysis results are correlations limiting causal inferences, and there is some heterogeneity among the studies in participant characteristics, diseases studied, and methods used.ConclusionsThis analysis provides evidence that depression is associated with poor adherence to medication across a range of chronic diseases, and we find a new potential effect of adherence measurement type on this relationship. Although this study cannot assess causality, it supports the importance that must be placed on depression in studies that assess adherence and attempt to improve it.

Development quality criteria to evaluate nontherapeutic studies of incidence, prevalence, or risk factors of chronic diseases: Pilot study of new checklists

OBJECTIVEnTo develop two checklists for the quality of observational studies of incidence or risk factors of diseases.nnnSTUDY DESIGN AND SETTINGnInitial development of the checklists was based on a systematic literature review. The checklists were refined after pilot trials of validity and reliability were conducted by seven experts, who tested the checklists on 10 articles.nnnRESULTSnThe checklist for studies of incidence or prevalence of chronic disease had six criteria for external validity and five for internal validity. The checklist for risk factor studies had six criteria for external validity, 13 criteria for internal validity, and two aspects of causality. A Microsoft Access database produced automated standardized reports about external and internal validities. Pilot testing demonstrated face and content validities and discrimination of reporting vs. methodological qualities. Interrater agreement was poor. The experts suggested future reliability testing of the checklists in systematic reviews with preplanned protocols, a priori consensus about research-specific quality criteria, and training of the reviewers.nnnCONCLUSIONnWe propose transparent and standardized quality assessment criteria of observational studies using the developed checklists. Future testing of the checklists in systematic reviews is necessary to develop reliable tools that can be used with confidence.

Mindfulness Meditation for Chronic Pain: Systematic Review and Meta-analysis

BackgroundChronic pain patients increasingly seek treatment through mindfulness meditation.PurposeThis study aims to synthesize evidence on efficacy and safety of mindfulness meditation interventions for the treatment of chronic pain in adults.MethodWe conducted a systematic review on randomized controlled trials (RCTs) with meta-analyses using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. Quality of evidence was assessed using the GRADE approach. Outcomes included pain, depression, quality of life, and analgesic use.ResultsThirty-eight RCTs met inclusion criteria; seven reported on safety. We found low-quality evidence that mindfulness meditation is associated with a small decrease in pain compared with all types of controls in 30 RCTs. Statistically significant effects were also found for depression symptoms and quality of life.ConclusionsWhile mindfulness meditation improves pain and depression symptoms and quality of life, additional well-designed, rigorous, and large-scale RCTs are needed to decisively provide estimates of the efficacy of mindfulness meditation for chronic pain.

Residential Treatment of Methamphetamine Users: Correlates of Drop-Out from the California Alcohol and Drug Data System (Cadds), 1994–1997

This paper explores correlates of retention among 2,570 methamphetamine users entering public residential treatment programs in California from January 1,1994 through September 30, 1997. A secondary analysis of the California Alcohol and Drug Data System (CADDS) was performed and predictors of drop-out before treatment completion (as measured by a retention of 90 days or more) were determined using logistic regression. Overall, 31.1% of methamphetamine users completed at least 90 days of treatment: very close to that for users of all other drugs (32.0%). As expected, methamphetamine users with more severe drug use (used daily or injected) were less likely to complete treatment. Those under coerced treatment were significantly more likely to complete treatment than other methamphetamine users. Clients who reported prior treatment experience were less likely to drop out. Surprisingly, men were significantly more likely than women to drop out of treatment before 90 days. Until studies currently collecting primary data on methamphetamine treatment are completed, the present secondary analysis provides a useful foundation upon which future research and intervention strategies may be based.

A cost-effectiveness analysis of a proposed national falls prevention program.

Falls are a major health concern for elderly people and cause substantial health care costs. The authors used meta-analytic findings on the effectiveness of fall prevention interventions to determine cost-effectiveness of a proposed Medicare fall prevention program for people who experience a recent fall. Using published clinical trial data, the authors constructed a population-based economic model and estimated that, in the base case, the program could prevent a half million people from falling again within a year. From the model, under most circumstances the cost-effectiveness ratio is less than

The effectiveness of covering smoking cessation services for medicare beneficiaries.

1500 per person prevented from experiencing a recurrent fall. Paying for a fall prevention program to increase the use of evidence-based interventions would be a cost-effective use of Medicare dollars.

Updating comparative effectiveness reviews: Current efforts in AHRQ's Effective Health Care Program

OBJECTIVEnTo examine whether reimbursement for Provider Counseling, Pharmacotherapies, and a telephone Quitline increase smoking cessation relative to Usual Care.nnnSTUDY DESIGNnRandomized comparison trial testing the effectiveness of four smoking cessation benefits.nnnSETTINGnSeven states that best represented the national population in terms of the proportion of those > or = 65 years of age and smoking rate.nnnPARTICIPANTSnThere were 7,354 seniors voluntarily enrolled in the Medicare Stop Smoking Program and they were followed-up for 12 months.nnnINTERVENTION(S)n(1) Usual Care, (2) reimbursement for Provider Counseling, (3) reimbursement for Provider Counseling with Pharmacotherapy, and (4) telephone counseling Quitline with nicotine patch.nnnMAIN OUTCOME MEASUREnSeven-day self-reported cessation at 6- and 12-month follow-ups.nnnPRINCIPAL FINDINGSnUnadjusted quit rates assuming missing data=smoking were 10.2 percent (9.0-11.5), 14.1 percent (11.7-16.5), 15.8 percent (14.4-17.2), and 19.3 percent (17.4-21.2) at 12 months for the Usual Care, Provider Counseling, Provider Counseling + Pharmacotherapy, and Quitline arms, respectively. Results were robust to sociodemographics, smoking history, motivation, health status, and survey nonresponse. The additional cost per quitter (relative to Usual Care) ranged from several hundred dollars to