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BACKGROUND: People with behavioural variant frontotemporal dementia, Lewy body dementia, posterior cortical atrophy and young onset Alzheimer's disease may experience language and communication difficulties. However, the role of speech and language interventions for people with these non-language led dementias has received little attention. AIMS: This study aimed to explore the experiences and perspectives of people living with these conditions, and their families, regarding their language and communication difficulties and how speech and language therapy could address these needs. METHODS: This study employed a qualitative design to explore the experiences of people living with or caring for somebody with behavioural variant frontotemporal dementia, Lewy body dementia, posterior cortical atrophy or young onset Alzheimer's disease, and to understand their opinions about speech and language therapy. Participants were recruited from a support service connected to a dementia clinic to attend one of five focus group meetings. Videorecorded focus groups and interviews were transcribed, and reflexive thematic analysis was used to analyse data from people affected by each type of dementia. RESULTS: A total of 25 participants were recruited to the study, with representation across the different forms of non-language led dementias. The four main themes identified were: (1) communication difficulties as a key difficulty, (2) loss and loneliness, (3) speech and language therapy, and (4) the role of the caregiver. Sixteen subthemes were also identified which highlighted individual issues across disease types. DISCUSSION: Although all the forms of dementia studied here are not considered to be language-led, people with these conditions and/or their care partners identified speech, language and communication as common challenges. These communication difficulties were reported to have a negative impact on their social participation and mental health and participants felt speech and language interventions could help. There is a need for research exploring speech and language interventions developed for and with people with non-language led dementias and their care partners, to ensure they meet the needs of the people they are designed for. WHAT THIS PAPER ADDS: What is already known on the subject People with primary progressive aphasia present with speech, language and communication difficulties, and several speech and language interventions have been developed to meet the needs of this population. However, people with non-language led dementias may also experience speech, language and communication difficulties, and little is known about interventions that may address these difficulties. What this paper adds to existing knowledge People living with or caring for somebody with behavioural variant frontotemporal dementia, Lewy body dementia, posterior cortical atrophy and young onset Alzheimer's disease report experiencing speech, language and communication difficulties that impact on the person with dementia's social participation and mood. Participants in this study also shared their opinions about how speech and language interventions could help, from the earliest stages of the disease. What are the potential or actual clinical implications of this work? Speech and language therapists need to address the individual speech, language and communication needs of people with dementias, even those that are not thought to be language-led. Current speech and language therapy service provision does not meet the needs of people with non-language led dementias and further research is required to develop interventions and services to meet these needs.
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Patients lacking functional adenosine deaminase activity have severe combined immunodeficiency (ADA SCID), which can be treated with ADA enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (HSCT), or autologous HSCT with gene-corrected cells (gene therapy [GT]). A cohort of 10 ADA SCID patients, aged 3 months to 15 years, underwent GT in a phase 2 clinical trial between 2009 and 2012. Autologous bone marrow CD34+ cells were transduced ex vivo with the MND (myeloproliferative sarcoma virus, negative control region deleted, dl587rev primer binding site)-ADA gammaretroviral vector (gRV) and infused following busulfan reduced-intensity conditioning. These patients were monitored in a long-term follow-up protocol over 8 to 11 years. Nine of 10 patients have sufficient immune reconstitution to protect against serious infections and have not needed to resume ERT or proceed to secondary allogeneic HSCT. ERT was restarted 6 months after GT in the oldest patient who had no evidence of benefit from GT. Four of 9 evaluable patients with the highest gene marking and B-cell numbers remain off immunoglobulin replacement therapy and responded to vaccines. There were broad ranges of responses in normalization of ADA enzyme activity and adenine metabolites in blood cells and levels of cellular and humoral immune reconstitution. Outcomes were generally better in younger patients and those receiving higher doses of gene-marked CD34+ cells. No patient experienced a leukoproliferative event after GT, despite persisting prominent clones with vector integrations adjacent to proto-oncogenes. These long-term findings demonstrate enduring efficacy of GT for ADA SCID but also highlight risks of genotoxicity with gRVs. This trial was registered at www.clinicaltrials.gov as #NCT00794508.