Patient Expectations of Benefit from Phase I Clinical Trials: Linguistic Considerations in Diagnosing a Therapeutic Misconception

The ethical treatment of cancer patientsparticipating in clinical trials requiresthat patients are well-informed about thepotential benefits and risks associated withparticipation. When patients enrolled in phaseI clinical trials report that their chance ofbenefit is very high, this is often taken as evidence of a failure of the informed consent process. We argue, however, that some simple themes from the philosophy of language may make such a conclusion less certain. First, the patient may receive conflicting statements from multiple speakers about the expected outcome of the trial. Patients may be reporting the message they like best. Second, there is a potential problem of multivocality. Expressions of uncertainty of the frequency type(e.g., ``On average, 5 out of every 100 patientswill benefit') can be confused with expressionsof uncertainty of the belief type (e.g.,``The chance that I will benefit is about80%'). Patients may be informed using frequency-type statements and respond using belief-type statements. Third, each speech episode involving the investigator and the patient regarding outcomes may subservemultiple speech acts, some of which may beindirect. For example, a patient reporting ahigh expected benefit may be reporting a beliefabout the future, reassuring family members,and/or attempting to improve his or her outcome by apublic assertion of optimism. These sources oflinguistic confusion should be considered injudging whether the patient's reported expectation isgrounds for a bioethical concern that there hasbeen a failure in the informed consent process.     

Evaluating the neuropsychological dissociation evidence for multiple memory systems

This article presents a critical evaluation of the logic and nature of the neuropsychological dissociation evidence that has provided one of the essential lines of support for claims of multiple memory systems--specifically, suggesting that amnesia selectively compromises, and an intact hippocampal system selectively supports, a particular form of memory. An analysis of the existing neuropsychological dissociation evidence is offered in which different classes of evidence--different dissociation approaches-are identified and characterized. The logic of these neuropsychological dissociation approaches is evaluated critically in terms of their ability to distinguish among alternative theoretical views. We conclude that although they support a multiple memory systems account, the findings from these types of neuropsychological dissociation, taken individually and without support from other converging lines of cognitive neuroscience evidence, cannot definitively rule out alternative formulations. A more powerful neuropsychological dissociation approach is then outlined, involving dissociation within condition, that, by more effectively limiting the critical domains of difference between the dissociated performances, can successfully rule out alternative accounts. Its application in Ryan, Althoff, Whitlow, and Cohen (2000) is described, providing strong support for the power of the dissociation within condition approach.     

Changes in functional status among older adults in Japan: successful and usual aging

This research aimed to chart the trajectories of functional status in old age in Japan and to assess how self-rated health and cognitive functioning differentiate these trajectories and account for interpersonal differences. Data came from a 5-wave panel study of a national sample of 2,200 Japanese older adults between 1987 and 1999. The sample as a whole showed an accelerated increase in functional limitations with age. approximated by a quadratic function. More important, 3 major trajectories of functional change were identified: (a) minimal functional decrement, (b) early onset of functional impairment. and (c) late onset of functional impairment. These findings may serve as useful benchmarks for observations derived from other developed nations.     

Medication treatment for depression in children and adolescents

Depression in children and adolescents is relatively common and associated with significant morbidity and mortality-thus, it is strongly deserving of treatment. To date, there have been a number of randomized, controlled trials of both tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) in the acute treatment of depression in youths. Surprisingly, the available data do not demonstrate TCA superiority over placebo for this disorder in this age group. There is, however, evidence of SSRI superiority to placebo, and longer-term treatment with SSRIs may help prevent recurrence. There is almost no data on other pharmacologic approaches. Effective use of the efficacious treatments also depends on effective case-finding and providing treatment, which families and youths will take in adequate quantity and duration. The right approaches to these aspects of effective treatment are greatly understudied.     

Depression as measured by the Beck Depression Inventory-II among injecting drug users

This study conducts a confirmatory factor analysis of the Beck Depression Inventory-II (BDI-II) with a sample of 598 individuals who reported recent injecting drug use. Findings indicate that out of four models tested, the best model for this sample is a three-factor solution (somatic, affective, and cognitive) previously reported by Buckley, Parker, and Heggie. The findings that nearly 50% of participants provided BDI-II scores indicating significant depressive symptomatology reveals that these individuals are in need of treatment for their psychiatric symptoms as well as substance use. Somatic symptoms are endorsed more strongly than affective or cognitive symptoms of depression, suggesting a possible, but yet poorly defined, relationship between depressive symptomatology and drug use that centers on shared somatic symptomatology.     

Training Community Members to Serve as Paraprofessionals in an Evidence-Based,Prevention Program for Parents of Preschoolers

Widespread dissemination of evidence-based programs for underserved populations may require non-traditional means of service provision. Collaboration with paraprofessionals from communities that are targeted for intervention holds promise as a delivery strategy that may make programs more accessible and acceptable, especially to parents living in low-income, urban neighborhoods. We describe a paraprofessional training program for individuals living in a community targeted for preventive intervention based on high levels of poverty and community violence. The design and implementation of the training program are described in the context of issues related to the use of paraprofessionals in community-based, preventive interventions with parents of young children. We also provide insight into lessons learned from a feasibility study as well as general guidelines for the development of paraprofessional training programs for delivery of evidence-based programs.     

Altered Emotional Processing in Pediatric Anxiety,Depression, and Comorbid Anxiety-Depression

The goal of this study was to examine some of the mechanisms underlying emotion regulation in childhood affective disorders by examining the impact of distracting emotional information during performance on a working memory task (Emotional n-back or E-n-back). The sample included 75 children (38 girls and 37 boys) between 8 and 16 years of age meeting criteria for: Anxiety disorder (ANX, n = 17), Major depressive disorder (MDD, n = 16), Comorbid anxiety and depression (CAD, n = 24), or Low-risk normal control (LRNC, n = 18). Results showed that the MDD and CAD groups had significantly longer reaction times on negative emotional backgrounds compared to neutral backgrounds, whereas the LRNC group had significantly longer reaction times on positive backgrounds. These results suggest altered processing of emotional information particularly associated with depression. Because the E-n-back task engages higher-order cognitive processes, these results suggest that these alterations in processing emotional information also interfere with the cognitive processes that govern how attentional resources are allocated. Further, research is needed to replicate this study and delineate underlying neural mechanisms.     

The role of secondary covariates when estimating latent trait population distributions

The U.S. National Assessment of Educational Progress (NAEP), the Third International Mathematics and Science Study (TIMSS), and the U.S. Adult Literacy Survey collect probability samples of students (or adults) who are administered brief examinations in subject areas such as mathematics and reading (cognitive variables), along with background demographic (primary) and educational environment (secondary) questions. The demographic questions are used in the primary reporting, while the numerous explanatory secondary variables, or covariates, are only directly utilized in subsequent secondary analyses. The covariates are also used indirectly to create the plausible values (multiple imputations) that are an integral part of analyses because of the use of sparse matrix sampling of cognitive items. The improvement in the precision of the primary reporting due to the inclusion of the covariates is assessed here and contrasted with the precision of reporting using plausible values created using only the primary demographic variables.The results demonstrate that the improvement in precision depends on the matrix sampling designs for the cognitive assessments. The improvements range from essentially none for the most common designs, to moderate for some less common designs. Consequently, two potential changes in the reporting procedures that could improve the statistical and operational efficiency of primary reporting are (a) eliminate or reduce the collection of covariates and increase the number of cognitive items, (b) to avoid delays, eliminate the covariates from the creation of plausible values used for the primary reports, but include them later when creating public-use files for secondary analyses. The potential improvements in statistical and operational efficiency must be weighed against the intrinsic interest in the covariates, and the potential for small discrepancies in the primary and secondary reporting.Thanks to Donald Rubin, Robert Mislevy, and John Barnard for their helpful comments and computing assistance. This work was supported by NCES Grant 84.902B980011.     

Attentional control in the aging brain: insights from an fMRI study of the stroop task

Several recent studies of aging and cognition have attributed decreases in the efficiency of working memory processes to possible declines in attentional control, the mechanism(s) by which the brain attempts to limit its processing to that of task-relevant information. Here we used fMRI measures of neural activity during performance of the color-word Stroop task to compare the neural substrates of attentional control in younger (ages: 21-27 years old) and older participants (ages: 60-75 years old) during conditions of both increased competition (incongruent and congruent neutral) and increased conflict (incongruent and congruent neutral). We found evidence of age-related decreases in the responsiveness of structures thought to support attentional control (e.g., dorsolateral prefrontal and parietal cortices), suggesting possible impairments in the implementation of attentional control in older participants. Consistent with this notion, older participants exhibited more extensive activation of ventral visual processing regions (i.e., temporal cortex) and anterior inferior prefrontal cortices, reflecting a decreased ability to inhibit the processing of task-irrelevant information. Also, the anterior cingulate cortex, a region involved in evaluatory processes at the level of response (e.g., detecting potential for error), showed age-related increases in its sensitivity to the presence of competing color information. These findings are discussed in terms of newly emerging models of attentional control in the human brain.