Janet K. Williams

National Institutes of Health State-of-the-Science Conference Statement: Family History and Improving Health

The role of obtaining family history information in the primary care setting, the validity of such information, and whether the information affects health outcomes must be clarified. Accordingly, t...

Outcomes of family involvement in care intervention for caregivers of individuals with dementia

Health concerns and management strategies among families of young and middle-age adults with Huntington’s disease (HD) are unknown. This study developed and tested psychometric properties of the Huntington Disease Family Concerns and Strategies Survey (HDFCSS). Focus group data from 91 adult family members were used to develop content. Content analysis yielded four domains that were transferred into Personal, Person With HD, Community Health Care Services, and Strategies scales. Focus group data, expert validation, and cognitive interviews demonstrated survey content validity. Cronbach’s alpha internal consistency coefficients for the scales were 0.83 or above. The measure can be used to generate reliable and valid data to identify adult family members’ health-related concerns and management strategies for themselves and persons with HD.

Prediction of manifest Huntington's disease with clinical and imaging measures: a prospective observational study

BACKGROUND Although the association between cytosine-adenine-guanine (CAG) repeat length and age at onset of Huntingtons disease is well known, improved prediction of onset would be advantageous for clinical trial design and prognostic counselling. We compared various measures for tracking progression and predicting conversion to manifest Huntingtons disease. METHODS In this prospective observational study, we assessed the ability of 40 measures in five domains (motor, cognitive, psychiatric, functional, and imaging) to predict time to motor diagnosis of Huntingtons disease, accounting for CAG repeat length, age, and the interaction of CAG repeat length and age. Eligible participants were individuals from the PREDICT-HD study (from 33 centres in six countries [USA, Canada, Germany, Australia, Spain, UK]) with the gene mutation for Huntingtons disease but without a motor diagnosis (a rating below 4 on the diagnostic confidence level from the 15-item motor assessment of the Unified Huntingtons Disease Rating Scale). Participants were followed up between September, 2002, and July, 2014. We used joint modelling of longitudinal and survival data to examine the extent to which baseline and change of measures analysed separately was predictive of CAG-adjusted age at motor diagnosis. FINDINGS 1078 individuals with a CAG expansion were included in this analysis. Participants were followed up for a mean of 5·1 years (SD 3·3, range 0·0-12·0). 225 (21%) of these participants received a motor diagnosis of Huntingtons disease during the study. 37 of 40 cross-sectional and longitudinal clinical and imaging measures were significant predictors of motor diagnosis beyond CAG repeat length and age. The strongest predictors were in the motor, imaging, and cognitive domains: an increase of one SD in total motor score (motor domain) increased the risk of a motor diagnosis by 3·07 times (95% CI 2·26-4·16), a reduction of one SD in putamen volume (imaging domain) increased risk by 3·32 times (2·37-4·65), and a reduction of one SD in Stroop word score (cognitive domain) increased risk by 2·32 times (1·88-2·87). INTERPRETATION Prediction of diagnosis of Huntingtons disease can be improved beyond that obtained by CAG repeat length and age alone. Such knowledge about potential predictors of manifest Huntingtons disease should inform discussions about guidelines for diagnosis, prognosis, and counselling, and might be useful in guiding the selection of participants and outcome measures for clinical trials. FUNDING US National Institutes of Health, US National Institute of Neurological Disorders and Stroke, and CHDI Foundation.

Cognitive domains that predict time to diagnosis in prodromal Huntington disease

Background Prodromal Huntingtons disease (prHD) is associated with a myriad of cognitive changes but the domains that best predict time to clinical diagnosis have not been studied. This is a notable gap because some domains may be more sensitive to cognitive decline, which would inform clinical trials. Objectives The present study sought to characterise cognitive domains underlying a large test battery and for the first time, evaluate their ability to predict time to diagnosis. Methods Participants included gene negative and gene positive prHD participants who were enrolled in the PREDICT-HD study. The CAG–age product (CAP) score was the measure of an individuals genetic signature. A factor analysis of 18 tests was performed to identify sets of measures or latent factors that elucidated core constructs of tests. Factor scores were then fit to a survival model to evaluate their ability to predict time to diagnosis. Results Six factors were identified: (1) speed/inhibition, (2) verbal working memory, (3) motor planning/speed, (4) attention–information integration, (5) sensory–perceptual processing and (6) verbal learning/memory. Factor scores were sensitive to worsening of cognitive functioning in prHD, typically more so than performances on individual tests comprising the factors. Only the motor planning/speed and sensory–perceptual processing factors predicted time to diagnosis, after controlling for CAP scores and motor symptoms. Conclusions The results suggest that motor planning/speed and sensory–perceptual processing are important markers of disease prognosis. The findings also have implications for using composite indices of cognition in preventive Huntingtons disease trials where they may be more sensitive than individual tests.

‘Information is information’: a public perspective on incidental findings in clinical and research genome-based testing

The potential for genomic incidental findings is increasing with the use of genome‐based testing. At the same time approaches to clinical decision making are shifting to shared decision‐making models involving both the healthcare community and the public. The publics voice has been nearly absent in discussions on managing incidental findings. We conducted nine focus groups and nine interviews (n = 63) with a broad cross‐section of lay public groups to elucidate public viewpoints on incidental findings that could occur as a result of genome‐based testing in clinical and research situations. Data were analyzed using qualitative content analysis. Participants wanted incidental findings disclosed to them whether or not these were clinical or research findings. Participants used different terms to define and describe incidental findings; they wanted to know that incidental findings are possible and be given a choice to learn about them. Personal utility was an important reason for disclosure, and participants believed that managing information is a shared responsibility between professionals and themselves. Broad public input is needed in order to understand and incorporate the publics perspective on management of incidental findings as disclosure guidelines, and policies are developed in clinical and research settings.

Challenges assessing clinical endpoints in early Huntington disease

The basic aim of this study was to evaluate the current accepted standard clinical endpoint for the earliest‐studied HD participants likely to be recruited into clinical trials. As the advent of genetic testing for HD, it is possible to identify gene carriers before the diagnosis of disease, which opens up the possibility of clinical trials of disease‐modifying treatments in clinically asymptomatic persons. Current accepted standard clinical endpoints were examined as part of a multinational, 32‐site, longitudinal, observational study of 786 research participants currently in the HD prodrome (gene‐positive but not clinically diagnosed). Clinical signs and symptoms were used to prospectively predict functional loss as assessed by current accepted standard endpoints over 8 years of follow‐up. Functional capacity measures were not sensitive for HD in the prodrome; over 88% scored at ceiling. Prospective evaluation revealed that the first functional loss was in their accustomed work. In a survival analysis, motor, cognitive, and psychiatric measures were all predictors of job change. To our knowledge, this is the first prospective study ever conducted on the emergence of functional loss secondary to brain disease. We conclude that future clinical trials designed for very early disease will require the development of new and more sensitive measures of real‐life function.

Implications for Educating the Next Generation of Nurses on Genetics and Genomics in the 21st Century

PURPOSE To provide nurse educators with an updated overview of advances in genetics and genomics in the context of the holistic perspective of nursing. ORGANIZING FRAMEWORK Recent advances in genetic and genomic research, testing, therapies, and resources are presented, and the continuing importance of the family history is discussed. METHODS Genomic nurse experts reviewed recent literature and consumer resources to elucidate updates in technology through the lens of the genetically vulnerable patient and family. FINDINGS Genetic and genomic technologies are becoming routinely used in health care, and nurse educators will be challenged to incorporate these technologies and implications for patients and families into educational programs. CONCLUSIONS New technology and its applications are perennial challenges to nurse educators, but the common focus for nursing, historically and geographically, is health promotion, symptom management, and disease prevention. Education for the next generation of nurses can lay a foundation in genetics and genomics that will enable interpretation and responsible integration of new technologies in a context of individual and family value systems, personal experiences, risk perception, decision consequences, and available resources. CLINICAL RELEVANCE Nurses are ideally situated to inform patients about new options in healthcare, and nurse educators are challenged to prepare their students to interpret and responsibly integrate new genetic-genomic information into practice.

The emotional experiences of family carers in Huntington disease

AIM This paper is a report of a study conducted to examine the emotional experience of caregiving by family carers of people with Huntington disease and to describe strategies they used to deal with that experience. BACKGROUND Huntington disease, commonly diagnosed in young to middle adulthood, is an inherited single gene disorder involving loss of cognitive, motor and neuropsychiatric function. Many family members become caregivers as well as continuing as parents and wage earners. The emotional aspects of caregiving contribute to mental health risks for family members. METHODS Focus groups were conducted with 42 adult carers of people with Huntington disease in four United States and two Canadian Huntington disease centers between 2001 and 2005. Data were analyzed through descriptive coding and thematic analysis. FINDINGS All participants reported multiple aspects of emotional distress. Being a carer was described as experiencing disintegration of ones life. Carers attempted to cope by seeking comfort from selected family members, anticipating the time when the care recipient had died and/or using prescription medications. Spousal carers were distressed by the loss of their relationship with their spouse and dealt with this by no longer regarding the person as an intimate partner. Carers were concerned about the disease risk for children in their families and hoped for a cure. CONCLUSION Emotional distress can compromise the well-being of family carers, who attempt to maintain multiple roles. Nurses should monitor carer mental health, identify sources of emotional distress and support effective strategies used by carers to mediate distress.

Perceptions of discrimination among persons who have undergone predictive testing for Huntington's disease†

Potential discrimination from genetic testing may undermine technological advances for health care. Researching long‐term consequences of testing for genetic conditions that may lead to discrimination is a public health priority. The consequences of genetic discrimination generate social, health, and economic burdens for society by diminishing opportunities for at‐risk individuals in a range of contexts. The current study objective was to investigate perceptions of genetic stigmatization and discrimination among persons who completed predictive testing for Huntingtons disease (HD). Using semi‐structured interviews and computerized qualitative analysis, the perceptions of 15 presymptomatic persons with a positive gene test predicting HD were examined with regard to differential treatment following testing. The sample comprised 11 women and 4 men, mostly married (73%), aged between 22 and 62 years, with an average education of 14.6 years (SD ± 2.57) and residing in urban, rural and suburban settings of eight U.S. States. Participants reported perceptions of consequences following disclosure of genetic test results in three areas: employment, insurance, and social relationships. Although most employed participants (90%) revealed their test results to their employers, nearly all reported they would not disclose this information to future employers. Most (87%) participants disclosed test results to their physician, but a similar majority (83%) did not tell their genetic status to insurers. Most participants (87%) disclosed test results to family and peers; patterns of disclosure varied widely. Discrimination concerns remain high in this sample and point to the need for more information to determine the extent and scope of the problem.

Benefits and burdens of genetic carrier identification

This qualitative study examined experiences of adults requesting genetic-carrier testingforfour autosomal-recessive and X-linked-recessive disorders. The sample consisted of 34 adults with a positive family history or membership in an ethnic group at risk for the inherited disorder A semistructured interview guide was used to collect data during an interview I month after receipt of test results. Noncarriers experienced benefits of emotional relief andfreedom to move ahead with reproductive planning. Carriers experienced burdens of sadness and loss of reproductive expectations. Some subjects in both groups experienced difficulty disclosing results to selected family members and expressed concerns regarding disclosure of testing to insurance providers.