An intervention to promote self-management, independence and self-efficacy in people with early-stage dementia: the Journeying through Dementia RCT.

BACKGROUND: There are few effective interventions for dementia. AIM: To determine the clinical effectiveness and cost-effectiveness of an intervention to promote self-management, independence and self-efficacy in people with early-stage dementia. OBJECTIVES: To undertake a randomised controlled trial of the Journeying through Dementia intervention compared with usual care, conduct an internal pilot testing feasibility, assess intervention delivery fidelity and undertake a qualitative exploration of participants' experiences. DESIGN: A pragmatic two-arm individually randomised trial analysed by intention to treat. PARTICIPANTS: A total of 480 people diagnosed with mild dementia, with capacity to make informed decisions, living in the community and not participating in other studies, and 350 supporters whom they identified, from 13 locations in England, took part. INTERVENTION: Those randomised to the Journeying through Dementia intervention (n = 241) were invited to take part in 12 weekly facilitated groups and four one-to-one sessions delivered in the community by secondary care staff, in addition to their usual care. The control group (n = 239) received usual care. Usual care included drug treatment, needs assessment and referral to appropriate services. Usual care at each site was recorded. MAIN OUTCOME MEASURES: The primary outcome was Dementia-Related Quality of Life score at 8 months post randomisation, with higher scores representing higher quality of life. Secondary outcomes included resource use, psychological well-being, self-management, instrumental activities of daily living and health-related quality of life. RANDOMISATION AND BLINDING: Participants were randomised in a 1 : 1 ratio. Staff conducting outcome assessments were blinded. DATA SOURCES: Outcome measures were administered in participants' homes at baseline and at 8 and 12 months post randomisation. Interviews were conducted with participants, participating carers and interventionalists. RESULTS: The mean Dementia-Related Quality of Life score at 8 months was 93.3 (standard deviation 13.0) in the intervention arm (n = 191) and 91.9 (standard deviation 14.6) in the control arm (n = 197), with a difference in means of 0.9 (95% confidence interval -1.2 to 3.0; p = 0.380) after adjustment for covariates. This effect size (0.9) was less than the 4 points defined as clinically meaningful. For other outcomes, a difference was found only for Diener's Flourishing Scale (adjusted mean difference 1.2, 95% confidence interval 0.1 to 2.3), in favour of the intervention (i.e. in a positive direction). The Journeying through Dementia intervention cost £608 more than usual care (95% confidence interval £105 to £1179) and had negligible difference in quality-adjusted life-years (-0.003, 95% confidence interval -0.044 to 0.038). Therefore, the Journeying through Dementia intervention had a mean incremental cost per quality-adjusted life-year of -£202,857 (95% confidence interval -£534,733 to £483,739); however, there is considerable uncertainty around this. Assessed fidelity was good. Interviewed participants described receiving some benefit and a minority benefited greatly. However, negative aspects were also raised by a minority. Seventeen per cent of participants in the intervention arm and 15% of participants in the control arm experienced at least one serious adverse event. None of the serious adverse events were classified as related to the intervention. LIMITATIONS: Study limitations include recruitment of an active population, delivery challenges and limitations of existing outcome measures. CONCLUSIONS: The Journeying through Dementia programme is not clinically effective, is unlikely to be cost-effective and cannot be recommended in its existing format. FUTURE WORK: Research should focus on the creation of new outcome measures to assess well-being in dementia and on using elements of the intervention, such as enabling enactment in the community. TRIAL REGISTRATION: This trial is registered as ISRCTN17993825. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 24. See the NIHR Journals Library website for further project information.

There are few services proven effective for people with mild dementia. We therefore explored the potential benefit of a programme called Journeying through Dementia. The content, devised in partnership with people living with dementia, aims to help affected individuals to live well and participate in life. The programme involves meeting in groups of about eight every week for 12 weeks. Each person also has four face-to-face meetings with a staff member. Carers are invited to 3 of the 12 group meetings to all individual meetings if the participant wanted this involvement. A total of 480 people with dementia and 350 carers from 13 locations in England took part. Just over half of the participants were randomly allocated to the new programme, whereas the others were not. This allowed us to compare the groups. We were interested in whether or not attending the Journeying through Dementia programme improved participants' quality of life. The results showed that it did not. We also measured participants' mood, self-management skills, positive attitudes and ability with daily living skills. Only one measure of positive psychology suggested even a small benefit. There was no difference between groups in the remaining measures. Although some individual participants described being more confident, enjoying social contact, trying new activities, feeling valued and having increased independence, overall, the programme is unlikely to be worth implementing. Certain aspects of the programme are worth implementing.

Major surgery induces acute changes in measured DNA methylation associated with immune response pathways.

Surgery is an invasive procedure evoking acute inflammatory and immune responses that can influence risk for postoperative complications including cognitive dysfunction and delirium. Although the specific mechanisms driving these responses have not been well-characterized, they are hypothesized to involve the epigenetic regulation of gene expression. We quantified genome-wide levels of DNA methylation in peripheral blood mononuclear cells (PBMCs) longitudinally collected from a cohort of elderly patients undergoing major surgery, comparing samples collected at baseline to those collected immediately post-operatively and at discharge from hospital. We identified acute changes in measured DNA methylation at sites annotated to immune system genes, paralleling changes in serum-levels of markers including C-reactive protein (CRP) and Interleukin 6 (IL-6) measured in the same individuals. Many of the observed changes in measured DNA methylation were consistent across different types of major surgery, although there was notable heterogeneity between surgery types at certain loci. The acute changes in measured DNA methylation induced by surgery are relatively stable in the post-operative period, generally persisting until discharge from hospital. Our results highlight the dramatic alterations in gene regulation induced by invasive surgery, primarily reflecting upregulation of the immune system in response to trauma, wound healing and anaesthesia.

DNA methylation and inflammation marker profiles associated with a history of depression.

Depression is a common and disabling disorder, representing a major social and economic health issue. Moreover, depression is associated with the progression of diseases with an inflammatory etiology including many inflammatory-related disorders. At the molecular level, the mechanisms by which depression might promote the onset of these diseases and associated immune-dysfunction are not well understood. In this study we assessed genome-wide patterns of DNA methylation in whole blood-derived DNA obtained from individuals with a self-reported history of depression (n = 100) and individuals without a history of depression (n = 100) using the Illumina 450K microarray. Our analysis identified six significant (Sidák corrected P < 0.05) depression-associated differentially methylated regions (DMRs); the top-ranked DMR was located in exon 1 of the LTB4R2 gene (Sidák corrected P = 1.27 × 10-14). Polygenic risk scores (PRS) for depression were generated and known biological markers of inflammation, telomere length (TL) and IL-6, were measured in DNA and serum samples, respectively. Next, we employed a systems-level approach to identify networks of co-methylated loci associated with a history of depression, in addition to depression PRS, TL and IL-6 levels. Our analysis identified one depression-associated co-methylation module (P = 0.04). Interestingly, the depression-associated module was highly enriched for pathways related to immune function and was also associated with TL and IL-6 cytokine levels. In summary, our genome-wide DNA methylation analysis of individuals with and without a self-reported history of depression identified several candidate DMRs of potential relevance to the pathogenesis of depression and its associated immune-dysfunction phenotype.

Cervical vertebral bone mineral density changes in adolescents during orthodontic treatment.

INTRODUCTION: The cervical vertebral maturation (CVM) stages have been used to estimate facial growth status. In this study, we examined whether cone-beam computed tomography images can be used to detect changes of CVM-related parameters and bone mineral density distribution in adolescents during orthodontic treatment. METHODS: Eighty-two cone-beam computed tomography images were obtained from 41 patients before (14.47 ± 1.42 years) and after (16.15 ± 1.38 years) orthodontic treatment. Two cervical vertebral bodies (C2 and C3) were digitally isolated from each image, and their volumes, means, and standard deviations of gray-level histograms were measured. The CVM stages and mandibular lengths were also estimated after converting the cone-beam computed tomography images. RESULTS: Significant changes for the examined variables were detected during the observation period (P ≤0.018) except for C3 vertebral body volume (P = 0.210). The changes of CVM stage had significant positive correlations with those of vertebral body volume (P ≤0.021). The change of the standard deviation of bone mineral density (variability) showed significant correlations with those of vertebral body volume and mandibular length for C2 (P ≤0.029). CONCLUSIONS: The means and variability of the gray levels account for bone mineral density and active remodeling, respectively. Our results indicate that bone mineral density distribution and the volume of the cervical vertebral body changed because of active bone remodeling during maturation.

Effect of passive smoke exposure on general anesthesia for pediatric dental patients.

The purpose of this study was to test the null hypothesis that children with environmental tobacco smoke (ETS) exposure (also known as passive smoke exposure) do not demonstrate an increased likelihood of adverse respiratory events during or while recovering from general anesthesia administered for treatment of early childhood caries. Parents of children (ages 19 months-12 years) preparing to receive general anesthesia for the purpose of dental restorative procedures were interviewed regarding the child's risk for ETS. Children were observed during and after the procedure by a standardized dentist anesthesiologist and postanesthesia care unit nurse who independently recorded severity of 6 types of adverse respiratory events-coughing, laryngospasm, bronchospasm, breath holding, hypersecretion, and airway obstruction. Data from 99 children were analyzed. The children for whom ETS was reported were significantly older than their ETS-free counterparts (P = .03). If the primary caregiver smoked, there was a significantly higher incidence of smoking by other members of the family (P < .0001) as well as smoking in the house (P < .0005). There were no significant differences between the adverse respiratory outcomes of the ETS (+) and ETS (-) groups. The ETS (+) children did have significantly longer recovery times (P < .0001) despite not having significantly more dental caries (P = .38) or longer procedure times. ETS is a poor indicator of post-general anesthesia respiratory morbidity in children being treated for early childhood caries.