Margo B. Holm

Primary Outcomes for Resuscitation Science Studies A Consensus Statement From the American Heart Association

Background and Purpose— The guidelines presented in this consensus statement are intended to serve researchers, clinicians, reviewers, and regulators in the selection of the most appropriate primary outcome for a clinical trial of cardiac arrest therapies. The American Heart Association guidelines for the treatment of cardiac arrest depend on high-quality clinical trials, which depend on the selection of a meaningful primary outcome. Because this selection process has been the subject of much controversy, a consensus conference was convened with national and international experts, the National Institutes of Health, and the US Food and Drug Administration. Methods— The Research Working Group of the American Heart Association Emergency Cardiovascular Care Committee nominated subject leaders, conference attendees, and writing group members on the basis of their expertise in clinical trials and a diverse perspective of cardiovascular and neurological outcomes (see the online-only Data Supplement). Approval was obtained from the Emergency Cardiovascular Care Committee and the American Heart Association Manuscript Oversight Committee. Preconference position papers were circulated for review; the conference was held; and postconference consensus documents were circulated for review and comments were invited from experts, conference attendees, and writing group members. Discussions focused on (1) when after cardiac arrest the measurement time point should occur; (2) what cardiovascular, neurological, and other physiology should be assessed; and (3) the costs associated with various end points. The final document underwent extensive revision and peer review by the Emergency Cardiovascular Care Committee, the American Heart Association Science Advisory and Coordinating Committee, and oversight committees. Results— There was consensus that no single primary outcome is appropriate for all studies of cardiac arrest. The best outcome measure is the pairing of a time point and physiological condition that will best answer the question under study. Conference participants were asked to assign an outcome to each of 4 hypothetical cases; however, there was not complete agreement on an ideal outcome measure even after extensive discussion and debate. There was general consensus that it is appropriate for earlier studies to enroll fewer patients and to use earlier time points such as return of spontaneous circulation, simple “alive versus dead,” hospital mortality, or a hemodynamic parameter. For larger studies, a longer time point after arrest should be considered because neurological assessments fluctuate for at least 90 days after arrest. For large trials designed to have a major impact on public health policy, longer-term end points such as 90 days coupled with neurocognitive and quality-of-life assessments should be considered, as should the additional costs of this approach. For studies that will require regulatory oversight, early discussions with regulatory agencies are strongly advised. For neurological assessment of post–cardiac arrest patients, researchers may wish to use the Cerebral Performance Categories or modified Rankin Scale for global outcomes. Conclusions— Although there is no single recommended outcome measure for trials of cardiac arrest care, the simple Cerebral Performance Categories or modified Rankin Scale after 90 days provides a reasonable outcome parameter for many trials. The lack of an easy-to-administer neurological functional outcome measure that is well validated in post–cardiac arrest patients is a major limitation to the field and should be a high priority for future development.

Improving Morning Care Routines of Nursing Home Residents with Dementia

OBJECTIVES: This study examined the effectiveness of a behavioral rehabilitation intervention for improving the performance of morning care activities of daily living (ADL) of nursing home residents with dementia.

An early, novel illness severity score to predict outcome after cardiac arrest

BACKGROUND Illness severity scores are commonly employed in critically ill patients to predict outcome. To date, prior scores for post-cardiac arrest patients rely on some event-related data. We developed an early, novel post-arrest illness severity score to predict survival, good outcome and development of multiple organ failure (MOF) after cardiac arrest. METHODS Retrospective review of data from adults treated after in-hospital or out-of-hospital cardiac arrest in a single tertiary care facility between 1/1/2005 and 12/31/2009. In addition to clinical data, initial illness severity was measured using serial organ function assessment (SOFA) scores and full outline of unresponsiveness (FOUR) scores at hospital or intensive care unit arrival. Outcomes were hospital mortality, good outcome (discharge to home or rehabilitation) and development of multiple organ failure (MOF). Single-variable logistic regression followed by Chi-squared automatic interaction detector (CHAID) was used to determine predictors of outcome. Stepwise multivariate logistic regression was used to determine the independent association between predictors and each outcome. The Hosmer-Lemeshow test was used to evaluate goodness of fit. The n-fold method was used to cross-validate each CHAID analysis and the difference between the misclassification risk estimates was used to determine model fit. RESULTS Complete data from 457/495 (92%) subjects identified distinct categories of illness severity using combined FOUR motor and brainstem subscales, and combined SOFA cardiovascular and respiratory subscales: I. Awake; II. Moderate coma without cardiorespiratory failure; III. Moderate coma with cardiorespiratory failure; and IV. Severe coma. Survival was independently associated with category (I: OR 58.65; 95% CI 27.78, 123.82; II: OR 14.60; 95% CI 7.34, 29.02; III: OR 10.58; 95% CI 4.86, 23.00). Category was also similarly associated with good outcome and development of MOF. The proportion of subjects in each category changed over time. CONCLUSIONS Initial illness severity explains much of the variation in cardiac arrest outcome. This model provides prognostic information at hospital arrival and may be used to stratify patients in future studies.

Maintenance Treatment of Depression in Old Age: A Randomized, Double-blind, Placebo-Controlled Evaluation of the Efficacy and Safety of Donepezil Combined With Antidepressant Pharmacotherapy

CONTEXT Cognitive impairment in late-life depression is a core feature of the illness. OBJECTIVE To test whether donepezil hydrochloride and antidepressant therapy is superior to placebo and antidepressant therapy in improving cognitive performance and instrumental activities of daily living and in reducing recurrences of depression over 2 years of maintenance treatment. DESIGN Randomized, double-blind, placebo-controlled maintenance trial. SETTING University clinic. PARTICIPANTS One hundred thirty older adults aged 65 years and older with recently remitted major depression. INTERVENTIONS Random assignment to maintenance antidepressant pharmacotherapy and donepezil or to maintenance antidepressant pharmacotherapy and placebo. MAIN OUTCOME MEASURES Global neuropsychological performance, cognitive instrumental activities of daily living, and recurrent depression. RESULTS Donepezil and antidepressant therapy temporarily improved global cognition (treatment × time interaction, F₂,₂₁₆ = 3.78; P = .03), but effect sizes were small (Cohen d = 0.27, group difference at 1 year). A marginal benefit to cognitive instrumental activities of daily living was also observed (treatment × time interaction, F₂,₁₃₇ = 2.94; P = .06). The donepezil group was more likely than the placebo group to experience recurrent major depression (35% [95% confidence interval {CI}, 24%-46%] vs 19% [95% CI, 9%-29%], respectively; log-rank χ² = 3.97; P = .05; hazard ratio = 2.09 [95% CI, 1.00-4.41]). Post hoc subgroup analyses showed that of 57 participants with mild cognitive impairment, 3 of 30 participants (10% [95% CI, 0%-21%]) receiving donepezil and 9 of 27 participants (33% [95% CI, 16%-51%]) receiving placebo had a conversion to dementia over 2 years (Fisher exact test, P = .05). The mild cognitive impairment subgroup had recurrence rates of major depression of 44% with donepezil vs 12% with placebo (likelihood ratio = 4.91; P = .03). The subgroup with normal cognition (n = 73) showed no benefit with donepezil and no increase in recurrence of major depression. CONCLUSIONS Whether a cholinesterase inhibitor should be used as augmentation in the maintenance treatment of late-life depression depends on a careful weighing of risks and benefits in those with mild cognitive impairment. In cognitively intact patients, donepezil appears to have no clear benefit for preventing progression to mild cognitive impairment or dementia or for preventing recurrence of depression. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00177671.

Cognitive and affective predictors of rehabilitation participation after stroke.

OBJECTIVE To examine associations between cognitive and affective impairments and rehabilitation participation during stroke rehabilitation. DESIGN Secondary analyses of stroke patients who received acetylcholinesterase inhibitors during inpatient rehabilitation. SETTING University-affiliated inpatient rehabilitation facilities. PARTICIPANTS Patients (N=44) admitted to inpatient stroke rehabilitation with impairment in attention, memory, or executive functions. INTERVENTIONS Secondary analysis of patients receiving inpatient stroke rehabilitation care plus random assignment to one of two acetylcholinesterase inhibitors or no drug at rehabilitation admission. MAIN OUTCOME MEASURES Correlations between measures of cognitive (Digit Span, Hopkins Verbal Learning Test, Executive Interview) and affective impairments (Hamilton Rating Scale for Depression, Apathy Evaluation Scale) and participation (Pittsburgh Rehabilitation and Participation Scale) were examined. Significant correlates of participation were examined in a linear multiple regression model. RESULTS Executive functions and depressive symptoms were significant correlates of participation. After controlling for baseline disability, executive functions predicted participation, but depressive symptoms did not (F(4,32)=9.35; R(2)=.54, P<.001). CONCLUSIONS These findings are an important first step toward understanding potentially modifiable clinical factors that contribute to rehabilitation participation and overall functional status after rehabilitation. A better understanding of cognitive impairment and rehabilitation participation may be used to develop strategies for improving functional outcomes after stroke.

A randomized clinical trial on preventing pressure ulcers with wheelchair seat cushions.

OBJECTIVES: To determine the efficacy of skin protection wheelchair seat cushions in preventing pressure ulcers in the elderly nursing home population.

Excess Disability During Morning Care in Nursing Home Residents With Dementia

Excess disability was examined in 17 nursing home residents with dementia by comparing their performance of morning care tasks under two activities of daily living (ADL) caregiving approaches-a dependence-supportive one under usual care and an independence-supportive one under functional rehabilitation. The results suggest that excess disability in severely cognitively impaired and functionally disabled residents can be reduced by increasing opportunities for independent activity, and substituting nondirective and directive verbal assists for physical assists. Further, the findings indicate that increased independence in ADL can be achieved without increasing disruptive behaviors and can foster appropriate requests for task-related help during caregiving. Functional rehabilitation, however, requires more time than usual care.

Cognition in older adults with bipolar disorder versus major depressive disorder.

Gildengers AG, Butters MA, Chisholm D, Anderson SJ, Begley A, Holm M, Rogers JC, Reynolds CF III, Mulsant BH. Cognition in older adults with bipolar disorder versus major depressive disorder. Bipolar Disord 2012: 14: 198–205.

The feasibility of meta-cognitive strategy training in acute inpatient stroke rehabilitation: Case report

Meta-cognitive strategy training may be used to augment inpatient rehabilitation to promote active engagement and subsequent benefit for individuals with cognitive impairments after stroke. We examined the feasibility of administering a form of meta-cognitive strategy training, Cognitive Orientation to daily Occupational Performance (CO-OP), during inpatient rehabilitation. We trained an individual with cognitive impairments after right hemisphere stroke to identify performance problems, set self-selected goals, develop plans to address goals, and evaluate performance improvements. To assess feasibility, we examined the number of meta-cognitive training sessions attended, the number of self-selected goals, and changes in goal-related performance. We also examined changes in rehabilitation engagement and disability. The participant used the meta-cognitive strategy to set eight goals addressing physically oriented, instrumental, and work-related activities. Mean improvement in Canadian Occupational Performance Measure Performance Scale scores was 6.1. Pittsburgh Rehabilitation Participation Scale scores (measuring rehabilitation engagement) improved from 3.2 at admission to 4.9 at discharge. Functional Independence Measure scores (measuring disability) improved from 68 at admission, to 97 at discharge. Performance Assessment of Self-Care Skills scores improved from 1.1 at admission to 2.9 at discharge. The results indicate that meta-cognitive strategy training was feasible during inpatient rehabilitation and warrants further evaluation to determine its effectiveness.

Development of a consumer-driven Wheelchair Seating Discomfort Assessment Tool (WcS-DAT)

This study examined the concept of seating discomfort in a population of full-time wheelchair users with intact sensation. The goal was to construct a tool that would quantify seating discomfort experienced by wheelchair users. Ten participants were interviewed using ethnographic interview techniques. Data were analyzed using a cross-classifying matrix to examine commonalities among the 10 participants’ responses. There were 16 discomfort and 13 comfort descriptors used by the participants. Of these, eight discomfort and five comfort descriptors were selected to include in the Wheelchair Seating Discomfort Assessment Tool (WcS-DAT). The discomfort descriptors selected were: aches and pains, need to move, pressure points, feeling poorly positioned, unable to concentrate, instability, not comfortable, and feeling too hot, cold or damp. The comfort descriptors selected were: absence of discomfort, feeling good, having no pain, able to concentrate, and feeling stable. The WcS-DAT also includes general information, such as the amount of time spent sitting and whether the individual was transferred into the chair properly—factors thought to affect discomfort—and ratings of discomfort intensity—in general and differentiated by body area. The WcS-DAT is a comprehensive tool for quantification of wheelchair seat discomfort for this population.