Deliberative assessment of surrogate consent in dementia research

BackgroundResearch involving incapacitated persons with dementia entails complex scientific, legal, and ethical issues, making traditional surveys of layperson views on the ethics of such research challenging. We therefore assessed the impact of democratic deliberation (DD), involving balanced, detailed education and peer deliberation, on the views of those responsible for persons with dementia.MethodsOne hundred and seventy-eight community-recruited caregivers or primary decision-makers for persons with dementia were randomly assigned to either an all-day DD session group or a control group. Educational materials used for the DD session were vetted for balance and accuracy by an interdisciplinary advisory panel. We assessed the acceptability of family-surrogate consent for dementia research (“surrogate-based research”) from a societal policy perspective as well as from the more personal perspectives of deciding for a loved one or for oneself (surrogate and self-perspectives), assessed at baseline, immediately post-DD session, and 1 month after DD date, for four research scenarios of varying risk-benefit profiles.ResultsAt baseline, a majority in both the DD and control groups supported a policy of family consent for dementia research in all research scenarios. The support for a policy of family consent for surrogate-based research increased in the DD group, but not in the control group. The change in the DD group was maintained 1 month later. In the DD group, there were transient changes in attitudes from surrogate or self-perspectives. In the control group, there were no changes from baseline in attitude toward surrogate consent from any perspective.ConclusionsIntensive, balanced, and accurate education, along with peer deliberation provided by democratic deliberation, led to a sustained increase in support for a societal policy of family consent in dementia research among those responsible for dementia patients.     

Disorders of awareness in neuropsychiatric syndromes: An update

Impaired awareness has been reported in a number of neuropsychiatric disorders. The purpose of this review is to provide an update on the current understanding of impaired awareness in neuropsychiatric syndromes, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), traumatic brain injury (TBI), schizophrenia, mood disorders, and obsessive-compulsive disorder (OCD). Unawareness of illness or deficits can have important diagnostic, treatment, and functional implications, and further understanding of its clinical and neural correlates will be extremely helpful in mediating its impact. Nevertheless, the area of unawareness has received relatively little attention as compared with other manifestations of neuropsychiatric illness. Evidence supporting a role for the involvement of frontal and parietal lobes across disorders is presented. Although most research has used neuropsychologic measures to assess brain functioning, more recent, limited literature in AD and schizophrenia has begun to examine neural correlates of unawareness using structural and functional imaging.     

Innovations: geriatric psychiatry: diagnosis and treatment of neuropsychiatric symptoms in Alzheimer's disease

The authors review research on the treatment of behavioral disturbances and psychiatric symptoms of patients with dementia, including pharmacological treatment with antipsychotics, antidepressants, cholinesterase inhibitors, and other psychotropic drugs. They conclude that although these medications have some beneficial effects, no intervention is currently able to eradicate behavioral disturbances and psychiatric symptoms of demented patients. Research suggests that multiple interventions for an individual patient are likely to replace the use of a single treatment. Such interventions include caregiver training and support, antipsychotics, antidepressants, and cholinesterase inhibitors, along with other drugs developed for the treatment of Alzheimer's disease.     

Cerebrospinal fluid puncture,consent inform,and ethics in research: the Brazilian Academy of Neurology recommendations

The Cerebrospinal Fluid (CSF) Scientific Department of the Brazilian Academy of Neurology (SD-BAN) suggests the use of consent inform for patients submitted to lumbar puncture. It should be explained to the patients the possible complications related to CSF puncture. The laws related to the research in human beings have also been discussed by the CSF SD-BAN.     

Munchausen Syndrome by Proxy: two case reports and an update of the literature

OBJECTIVES AND METHODS: Munchausen Syndrome by Proxy (MSP) may significantly hamper the normal development of children. Our aim was to describe the first two Israeli children who fit this diagnosis. RESULTS: Case #1 was diagnosed at the age of seven months with failure to thrive, severe recurrent vomiting, and recurrent unexplained fever. Medical tests performed were normal. No improvement was noted following prolonged treatment, which included several surgical interventions. Case #2 was hospitalized at the age of four years because of recurrent convulsive episodes. Medical examinations performed were normal, and there was no improvement in the reported seizure disorder despite continuous treatment. In both cases, MSP was suspected because of a persistent illness that could not be explained by adequate medical basis, and because the symptoms and signs occurred only in the mother's presence. A confrontation was made, leading to rapid deterioration of the hitherto devoted relationship of the mother of case #1 with her child, and of the previous cooperative relationship of both mothers with the medical staff. Removal of both children from their families ensued, with considerable improvement within a brief period, which continued in a one- to two-year follow-up period. CONCLUSIONS: The study reviews the required diagnostic criteria for MSP and possible treatment options.     

Research consent for cognitively impaired adults: recommendations for institutional review boards and investigators

Adults with cognitive impairment are considered a vulnerable population. The conditions associated with cognitive impairment, such as dementia and delirium, cause great suffering to affected patients and their families. Improving clinical care for these conditions depends on research involving cognitively impaired participants. Cognitive impairment is at times associated with partial or full impairment of the capacity to consent to research. This both limits the ability of the individual to consent personally to research participation, and also increases pressure upon Institutional Review Boards (IRBs) and investigators to place additional safeguards for the appropriate participation of cognitively impaired individuals in research. While the ethical and legal principles permitting and safeguarding the participation of cognitively impaired persons in research are generally agreed upon, there are no specific methods that operationalize these principles in a language that can be used by IRBs and researchers to guide their day-to-day work in this area. This document contains recommendations that IRBs and investigators can use to operationalize the informed consent process for individuals with cognitive impairment. In situations in which IRBs might not have specific policies in this area, this guideline may also serve as the foundation for such policies. The recommendations discuss when to consider that cognitively impaired participants might be involved in a research project, the use of screening for cognitive impairment, the conduct of assessments evaluating capacity to consent to research, situations in which proxies might consent for research participation in the place of cognitively impaired participants, how to go about identifying appropriate proxies, and how to deal with the loss of consent capacity in the course of a research project.     

Informed consent in medication-free schizophrenia research

OBJECTIVE: The authors' goal was to determine whether people with schizophrenia experience changes in decisional capacity when their antipsychotic regimens are discontinued for research purposes. METHOD: Capacity for informed consent for research, neuropsychological performance, and psychiatric symptoms were assessed before and after discontinuation of antipsychotic medication in 10 individuals with schizophrenia. RESULTS: Overall, participants showed minimal change on most measures during the medication-free interval, although their reasoning ability declined significantly. All participants who demonstrated adequate understanding of study procedures at enrollment retained this capacity throughout the study. CONCLUSIONS: Participants in medication-free schizophrenia research do not show a major decline in decisional capacity. However, the apparent decline in reasoning ability found in this study is of concern and underscores the need for both additional research on this topic and the development of remediational interventions aimed at enhancing this aspect of decisional capacity.     

Childhood-onset schizophrenia: research update.

This review is a research update of recent literature related to childhood-onset schizophrenia (onset of psychotic symptoms by age 12 years). This subgroup of patients has attracted considerable research interest because patients with a childhood onset may represent a more homogeneous patient population in which to search for risk or etiologic factors. We examine data indicating that childhood-onset schizophrenia (COS) shares the same clinical and neurobiologic features as later-onset forms of the disorder. Compared with adults with schizophrenia, however, this subgroup of patients appears to have more severe premorbid neuro-developmental abnormalities, more cytogenetic anomalies, and potentially greater family histories of schizophrenia and associated spectrum disorders. While preliminary, these data indicate that a greater genetic vulnerability may be one of the underpinnings of COS. Future studies of this subgroup may provide important clues as to the genetic basis for schizophrenia and how gene products influence certain features of the disease, such as age of onset and mode of inheritance.     

Neuronal ceroid lipofuscinoses: research update

This study describes the phenotype/genotype analysis of 159 probands with neuronal ceroid lipofuscinosis (37 CLN1, 72 classic CLN2, 10 variant LINCL, and 40 CLN3) collected at the New York State Institute for Basic Research in Developmental Disabilities (IBR). Phenotype/genotype comparison showed that mutations in the CLN1 gene were associated with different phenotypes: infantile, late infantile, and juvenile. Two common mutations (223A → C and 451C → T) were found in 26 of 37 CLN1 subjects (64% of alleles examined). A nonsense point mutation, 451C → T, was the most common in CLN1 subjects with infantile onset at 0–2 years, accounting for 50% of alleles studied. A missense point mutation, 223A → C, was the most common among CLN1 subjects with juvenile onset older than 4 years, accounting for 45% of alleles examined. Twenty-one other CLN1 mutations were identified in 4 of 37 subjects with infantile onset, 6 of 37 with late-infantile onset, and 6 of 37 with juvenile onset. All CLN1 probands were palmitoyl-protein thioesterase (PPT)-deficient and showed granular osmiophilic deposits (GROD) at the electron microscopic (EM) level. In the group of classic CLN2 (72 probands), two common mutations were found; an intronic 3556G → C transversion in the invariant AG of 3’ splice junction in 55% of probands, and a nonsense mutation 3670C → T in 30% of probands. Classic late-infantile onset (2–4 years) was found in 68 of 72 (95%) cases. All probands had deficiency of tripeptidyl-peptidase I (TPP1) activity and, at the EM level, curvilinear profiles. Ten probands with late-infantil onset did not show mutations in the CLN2 gene, had normal TPP1 activity, and at the EM level had mixed profiles. Further studies are in progress to identify genetic defect(s) in these subjects. The CLN3 group (40 probands) was divided into two categories: classic or typical presentation, and delayed classic or atypical presentation. All CLN3 patients had onset of symptoms after 4 years of age. In 40 probands, the 1.02-kb common deletion was found in one or two alleles of the CLN3 gene. Homozygotes for the common CLN3 deletion showed the classic phenotype. The phenotype in compound heterozygotes was either the classic or the delayed classic or atypical form. Thus, our study indicates that some mutations in the CLN1 and CLN2 genes may be associated with juvenile onset of the disease process and a more benign clinical course. Interfamilial and intrafamilial variations also were found, especially in the speed of becoming blind and neurologically disabled.     

Coercion and informed consent in research involving prisoners

Prison-based research has been limited due to concern that prisoners may represent a vulnerable population secondary to possible coercion and limited capacity for voluntary informed consent. This study was designed to assess decisional capacity and susceptibility to coercion in prison research subjects. Subjects were 30 mentally ill prisoners and 30 healthy controls. The groups were compared on ability to provide informed consent to a hypothetical drug trial, susceptibility to possible coercion, neuropsychological functioning, and psychiatric symptoms. Results indicated that all controls and all but one of the prisoners demonstrated adequate capacity to consent to the hypothetical drug trial. However, when decisional capacity was measured quantitatively, prisoners performed significantly worse regarding two aspects of this ability. Regarding possible coercion, prisoners' main reasons for participating in research included avoiding boredom, meeting someone new, appearing cooperative in hopes of being treated better, and helping society. Neuropsychological functioning was strongly positively correlated with decisional capacity and negatively correlated with susceptibility to possible coercion, whereas psychiatric symptoms were only weakly correlated with these variables. In conclusion, a very high percentage of particularly vulnerable, mentally ill prisoners demonstrated adequate capacity to consent to research. Lower scores on a quantitative measure of decisional capacity suggest that extra care should be taken during the consent process when working with these subjects. The reasons prisoners gave for participating in our research indicated that the prison setting may have influenced their decision to participate, but that they were not actually coerced into doing so. Despite serious past incidents, ethicists will need to consider the possibility that prisoners have become an overprotected population.     

Evolution of research in geriatric psychiatry

During the past 30 years the knowledge base of geriatric psychiatry has grown exponentially to replace the folklore and myths which for many years pervaded the as yet undefined field of geriatric psychiatry. The advances in geriatric psychiatry, as with many areas of medicine, have been fostered by the appearance of sophisticated technologies including analytic chemistry techniques, functional and structural brain-imaging studies and molecular biology. However, many of these advances could not have been achieved without the supported initiatives in education and research in geriatric psychiatry by major agencies such as the National Institute of Mental Health Center for Studies of Mental Health of the Aging and the National Institute for Aging. For example, the number of geriatric specialty training programs in the United States increased to more than 30 between 1978 and 1989 as compared to the existence of only one prior to 1978 in the setting of a medical school (Cohen, 1989). These clinical and research training programs continue to the present day and are not only the source of the future researchers in geriatric psychiatry but also the ‘centres’ of research activity in areas such as the mood disorders, dementias, late onset schizophrenia, anxiety, and other psychiatric disorders of the elderly which are reviewed in this issue of the Journal.     

Comparing clinical practice with guideline recommendations for the treatment of depression in geriatric patients: findings from the APA practice research network.

OBJECTIVE: The authors describe treatments provided for depressed geriatric patients (age 65+) treated by psychiatrists in the American Psychiatric Association's (APA) Practice Research Network (PRN) and compare treatments with recommended guidelines for treating late-life depression. METHODS: Detailed demographics, diagnoses, service utilization, and treatment information were collected on relevant patients treated by psychiatrists participating in the APA's PRN during 1997, sample-weighted to produce nationally representative estimates. Treatment data were qualitatively compared with existing depression treatment guidelines from the APA and the Expert Consensus Guideline Series on pharmacotherapy of depressive disorders in older patients. RESULTS: Of patients treated by psychiatrists in the PRN (N=152), just over 41% had a diagnosable depressive disorder, and, of those with depression, nearly 84% had major depression. Over 90% received a psychotropic medication, and over 75% received an antidepressant. Treatment intensity, as measured by visit frequency and duration of treatment, were more intense than typically found in primary care. Most patients received a combination of medication management and psychotherapy. Selective serotonin reuptake inhibitors were the most frequently prescribed antidepressant, although they were less frequently prescribed than in primary care and other national surveys. Just over 11% received a tertiary amine antidepressant, and nearly 43% received benzodiazepines, this frequency being inconsistent with existing guidelines. CONCLUSION: Depressed geriatric patients treated by psychiatrists in APA's PRN receive active treatments largely consistent with existing guidelines, which generally resulted in favorable patient outcomes.     

Deliberate self-harm in children and adolescents: a research update

PURPOSE OF REVIEW: We outline research developments in 2004 and early 2005 published in English language journals on deliberate self-harm among children and adolescents up to the age of 18 years. RECENT FINDINGS: The main issue of concern in recent times has been the risk/benefit profile of using antidepressants, especially selective serotonin reuptake inhibitors, in depressed children and adolescents. Other important topics include treatment approaches, particularly cognitive behaviour therapy, dialectical behaviour therapy and multisystemic therapy, barriers to help seeking, the Internet and prevention. SUMMARY: Rates of deliberate self-harm appear to be rising among young people. Risk factors associated with deliberate self-harm are becoming clearer and the evaluation of treatments is progressing. However, the recent conflicting evidence and guidelines regarding selective serotonin reuptake inhibitors and suicidality are presenting major difficulties for clinicians. The role of the Internet and initiatives to prevent suicidal behaviour in adolescents require further research.     

Informed consent,dementia and clinical research

The problem of informed consent in clinical research involving demented patients is more and more vexed. Together with an historical review of the most authoritative international statements taken since Nuremberg till today, the document on this topic recently published in the Italian Journal of Neurological Sciences and prepared by members of the Bioethics and Neurology Working Group of the Italian Society of Neurology (including the author) is further commented.The critique on distinction between therapeutic and non-therapeutic research and the recommendations of the Group in relation to the different phases of pharmacological research are among the subjects dealt with.