Abstract
Cummings JL, Lyketsos CG, Peskind ER, et al.: Effects of dextromethorphan-quinidine on agitation in patients with Alzheimer disease dementia. A randomized trial. JAMA 2015;314:1242–1254.
The objective of this phase 2 randomized, multicenter, double-blind, placebo-controlled trial was to assess the efficacy, safety, and tolerability of dextromethorphan hydrobromide–quinidine sulfate for Alzheimer disease–related agitation. The study used a sequential parallel comparison design with two consecutive five-week treatment stages conducted August 2012 to August 2014. Patients with probable Alzheimer disease, clinically significant agitation (Clinical Global Impressions–Severity agitation score ≥4), and a Mini-Mental State Examination score of 8–28 participated at 42 U.S. study sites. Stable dosages of antidepressants, antipsychotics, hypnotics, and antidementia medications were allowed. In stage 1, 220 patients were randomized in a 3:4 ratio to receive dextromethorphan-quinidine (n = 93) or placebo (n = 127). In stage 2, patients receiving dextromethorphan-quinidine continued; those receiving placebo were stratified by response and rerandomized in a 1:1 ratio to dextromethorphan-quinidine (n = 59) or placebo (n = 60). The primary endpoint was change from baseline on the Neuropsychiatric Inventory (NPI) agitation/aggression domain (scale range, 0 [absence of symptoms] to 12 [symptoms occur daily and with marked severity]).
Results demonstrated that a total of 194 patients (88.2%) completed the study. With the sequential parallel comparison design, 152 patients received dextromethorphan-quinidine and 127 received placebo during the study. Analysis combining stages 1 (all patients) and 2 (rerandomized placebo nonresponders) showed significantly reduced NPI agitation/aggression scores for dextromethorphan-quinidine versus placebo (P < 0.001). In stage 1, mean NPI agitation/aggression scores were reduced from 7.1 to 3.8 with dextromethorphan-quinidine and from 7.0 to 5.3 with placebo. Between-group treatment differences were significant in stage 1 (P < 0.001). In stage 2, NPI agitation/aggression scores were reduced from 5.8 to 3.8 with dextromethorphan-quinidine and from 6.7 to 5.8 with placebo. Between-group treatment differences were also significant in stage 2 (P = 0.02). Adverse events included falls (8.6% for dextromethorphan-quinidine versus 3.9% for placebo); diarrhea (5.9% versus 3.1%, respectively); and urinary tract infection (5.3% versus 3.9%, respectively). Serious adverse events occurred in 7.9% with dextromethorphan-quinidine versus 4.7% with placebo. Dextromethorphan-quinidine was not associated with cognitive impairment, sedation, or clinically significant QTc prolongation. The authors conclude that in this preliminary 10-week phase 2 randomized clinical trial of patients with probable Alzheimer disease, combination dextromethorphan-quinidine demonstrated clinically relevant efficacy for agitation and was generally well tolerated.
Branigan M: Desire for hastened death: Exploring the emotions and the ethics. Curr Opin Support Palliat Care 2015;9:64–71.
As we approach the end of our lives, many of us will have a desire for hastened death (DHD). Fortunately, our ability to respond to suffering at the end of life is improving. At the same time, in many jurisdictions, changes are underway to legislate physician-assisted death. This compels us as clinicians to explore DHD in a compassionate way—to reduce suffering and reduce premature death. This challenge is becoming more compelling as a large cohort of individuals, who value autonomy and control, age and experience illness. Studies confirm that DHD is not always a request to die. Clarifying the intention behind the desire and exploring the individual factors and underlying reasons behind the wish have been described. Another theme questions our basic assumptions about these statements—a normal part of a human experience or an indicator of disease. This tension is also manifested in the appropriate balance between patient autonomy and preventing harm. In summary, the author suggests that we have a professional responsibility to mindfully explore with the patient the suffering that can be relieved and the suffering that remains.
Kirkpatrick JN, Wieselthaler G, Strueber M, et al.: Ventricular assist devices for treatment of acute heart failure and chronic heart failure. Heart 2015;101:1091–1096.
Despite therapeutic advances that improve longevity and quality of life, heart failure (HF) remains a relentless disease. At the end stage of HF, patients may become eligible for mechanical circulatory support (MCS) for the indications of stabilizing acute cardiogenic shock or for chronic HF management. MCS use is growing rapidly in the United States and some countries of the European Union, especially in transplant-ineligible patients. In others, it remains largely a tool to stabilize patients until heart transplant. MCS comprises a heterogeneous group of temporary and durable devices which augment or replace the pumping function of one or both ventricles, with post-implant two-year survival rivaling that of transplant in selected, lower-risk patients. In transplant-eligible and nontransplant-eligible patients, improvement in end-organ perfusion, functional capacity, and quality of life have been noted. Even for optimal candidates, however, there are a host of potential complications that require constant vigilance of a coordinated care team. Recently there has been official recognition of the importance of palliative care expertise in advance care planning pre-implant and management of patients with ventricular assist devices at the end of their lives. In fact, the Centers for Medicare & Medicaid Services (CMS) now requires a palliative care representative on the MCS team.
Bajwah S, Ross JR, Wells AU, et al.: Palliative care for patients with advanced fibrotic lung disease. A randomised controlled phase II and feasibility trial of a community case conference intervention. Thorax 2015;70:830–839.
Those affected by advanced fibrotic interstitial lung diseases (ILDs) have considerable unmet symptom and psychological needs. Case conferencing has been proposed to address these issues, but their impact requires evaluation. The aim of this study was to obtain preliminary information on the impact of a case conference intervention delivered in the home (Hospital2Home) in addressing palliative care concerns of patients and their caregivers, and to evaluate conference feasibility and acceptability. Hospital2Home was trialed at a specialist center using a phase 2 fast-track randomized controlled trial with qualitative interviews. The primary outcome for effect was mean change from baseline in the Palliative Care Outcome Scale (POS), a measure of symptoms and concerns, at four weeks. Secondary outcomes included symptom control, quality of life, consent and recruitment rates, and percentage of patients in the fast-track group receiving case conferences within 14 days. Results demonstrated that with 53 patients recruited (26 fast-track, 27 controls) there was a greater reduction in mean (SD) POS scores at four weeks in the fast track: −5.7 versus −0.4 control (mean change difference between the two arms was −5.3). The secondary outcomes of quality of life, anxiety, and depression were better in the fast-track arm, and none were worse. Qualitative findings corroborated these data. The authors conclude that community case conferences improve palliative symptoms and quality of life after four weeks. Hospital2Home case conferences for the most part are both feasible and acceptable; this approach requires further testing in multicenter trials. For more information on the POS, go to pos-pal.org/.
Bushor L, Rowser M: Symptom management of chronic illness in the adult outpatient setting. J Hosp Palliat Nurs 2015;17:285–290.
Veterans experience high rates of recidivism, with 75% of those older than 65 years having symptomatic chronic illness. Five diagnoses—congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, dementia, and cancer—account for 25% of health care visits associated with high rates of recidivism. A convenience sample of 37 veterans with advanced chronic illness from one rural home-based primary care clinic was evaluated. All subjects had at least one of the five listed diagnoses. One-way repeated-measures analysis of variance was used to evaluate retrospective and prospective data at 30, 60, and 90 days before/after implementation of palliative care modalities. Congestive heart failure and chronic obstructive pulmonary disease accounted for 53% of diagnoses. Sixty-five percent had two or more diagnoses. By day 90 after palliative management there were 122 fewer emergency department/hospital days (P < 0.01), with an estimated cost avoidance of $220,000. The authors conclude that initiating palliative care early in the trajectory of symptomatic illness reduces recidivism and overall costs of care through management of symptoms and focusing on patient/caregiver-directed goals for improving life.
Pattison N, O'Gara G, Wigmore T: Negotiating transitions: Involvement of critical care outreach teams in end-of-life decision making. Am J Crit Care 2015;24:232–240.
Little research has examined the involvement of critical care outreach teams in end-of-life decision making. Consequently, the authors attempted to establish how much time critical care outreach teams spend with patients who are subsequently subject to limitation of medical treatment and end-of-life decisions and how much influence the teams have on those decisions. This was a single-center retrospective review, with qualitative analysis, in a large cancer center. Data were retrieved from all patients referred emergently for critical care outreach from October 2010 to October 2011 who later had limitation of medical treatment or end-of-life care. Findings were analyzed by using SPSS 19.0 (IBM, Armonk, NY) and qualitative free-text analysis.
Results demonstrated that of 890 patients referred for critical care outreach from October 2010 to October 2011, 377 were referred as an emergency; 108 of those had limitation of medical treatment and were included in the review. Thirty-five patients (32.4%) died while hospitalized. As a result of outreach intervention and a decision to limit medical treatment, 56 (51.9%) of the 108 patients received a formal end-of-life care plan (including care pathways, referral to palliative care team, hospice).
About a fifth (21.5%) of clinical contact time is being spent on patients who subsequently are subject to limitation of medical treatment. Qualitative document analysis showed five emerging themes: difficulty of discussions about not attempting cardiopulmonary resuscitation, complexities in coordinating multiple teams, delays in referral and decision making, decision reversals and opaque decision making, and technical versus ethical imperatives. The authors conclude that a considerable amount of time is being spent on these emergency referrals, and decisions to limit medical treatment are common. The appropriateness of escalation of levels of care is often not questioned until patients become critically or acutely unwell and outreach teams subsequently intervene.