Background Assistive technology and telecare have been promoted to manage the risks associated with independent living for people with dementia, but there is limited evidence of their effectiveness. Objectives This trial aimed to establish whether or not assistive technology and telecare assessments and interventions extend the time that people with dementia can continue to live independently at home and whether or not they are cost-effective. Caregiver burden, the quality of life of caregivers and of people with dementia and whether or not assistive technology and telecare reduce safety risks were also investigated. Design This was a pragmatic, randomised controlled trial. Blinding was not undertaken as it was not feasible to do so. All consenting participants were included in an intention-to-treat analysis. Setting This trial was set in 12 councils in England with adult social services responsibilities. Participants Participants were people with dementia living in the community who had an identified need that might benefit from assistive technology and telecare. Interventions Participants were randomly assigned to receive either assistive technology and telecare recommended by a health or social care professional to meet their assessed needs (a full assistive technology and telecare package) or a pendant alarm, non-monitored smoke and carbon monoxide detectors and a key safe (a basic assistive technology and telecare package). Main outcome measures The primary outcomes were time to admission to care and cost-effectiveness. Secondary outcomes assessed caregivers using the 10-item Center for Epidemiological Studies Depression Scale, the State–Trait Anxiety Inventory 6-item scale and the Zarit Burden Interview. Results Of 495 participants, 248 were randomised to receive full assistive technology and telecare and 247 received the limited control. Comparing the assistive technology and telecare group with the control group, the hazard ratio for institutionalisation was 0.76 (95% confidence interval 0.58 to 1.01; p = 0.054). After adjusting for an imbalance in the baseline activities of daily living score between trial arms, the hazard ratio was 0.84 (95% confidence interval 0.63 to 1.12; p = 0.20). At 104 weeks, there were no significant differences between groups in health and social care resource use costs (intervention group – control group difference: mean –£909, 95% confidence interval –£5336 to £3345) or in societal costs (intervention group – control group difference: mean –£3545; 95% confidence interval –£13,914 to £6581). At 104 weeks, based on quality-adjusted life-years derived from the participant-rated EuroQol-5 Dimensions questionnaire, the intervention group had 0.105 (95% confidence interval –0.204 to –0.007) fewer quality-adjusted life-years than the control group. The number of quality-adjusted life-years derived from the proxy-rated EuroQol-5 Dimensions questionnaire did not differ between groups. Caregiver outcomes did not differ between groups over 24 weeks. Limitations Compliance with the assigned trial arm was variable, as was the quality of assistive technology and telecare needs assessments. Attrition from assessments led to data loss additional to that attributable to care home admission and censoring events. Conclusions A full package of assistive technology and telecare did not increase the length of time that participants with dementia remained in the community, and nor did it decrease caregiver burden, depression or anxiety, relative to a basic package of assistive technology and telecare. Use of the full assistive technology and telecare package did not increase participants’ health and social care or societal costs. Quality-adjusted life-years based on participants’ EuroQol-5 Dimensions questionnaire responses were reduced in the intervention group compared with the control group; groups did not differ in the number of quality-adjusted life-years based on the proxy-rated EuroQol-5 Dimensions questionnaire. Future work Future work could examine whether or not improved assessment that is more personalised to an individual is beneficial. Trial registration Current Controlled Trials ISRCTN86537017. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 25, No. 19. See the NIHR Journals Library website for further project information.
Abstract Background: Ganetespib is a fully synthetic and selective inhibitor of heat shock protein 90 (HSP90), a molecular chaperone recognized as a key facilitator of breast cancer initiation, progression and metastasis. Methods: Preclinical activity of ganetespib across the four major breast cancer subtypes and inflammatory breast cancer was assessed in vitro and in vivo. Modulation of cell proliferation and viability was determined both in monolayer and three-dimensional cultures. HSP90 client protein expression and activity was monitored by Western blot and protein array. To recapitulate clinical dosing, kinetics of client protein destabilization were measured following short exposures to drug in vitro. Anticancer activity of ganetespib was further investigated in vivo using breast cancer xenografts. Results: Ganetespib displayed potent, low nanomolar activity in luminal (A and B), basal (A and B) and inflammatory breast cancer cell lines grown as monolayers in vitro. BT-474 (HER2 amplified) luminal cells grown as mammospheres in 3D were equally as sensitive to ganetespib as those grown in monolayer. In luminal cells, ganetespib simultaneously disrupted multiple signaling components including the estrogen and progesterone receptor, several receptor and non-receptor tyrosine kinases, as well as the MAPK pathway. Further, ganetespib effectively inhibited AKT, PDK1 and SGK3 activity in PIK3CA mutant cells suggesting that HSP90 is essential for both AKT-dependent and AKT-independent signaling. Clinically relevant exposure times to ganetespib in vitro resulted in potent, long term destabilization of HER2. In the basal-like breast cancer cell line MDA-MB-231, enriched in CD44+CD24- stem like cells that commonly display chemotherapeutic resistance and activated JAK2/STAT3 signaling, ganetespib (50 nM) induced significant degradation of JAK2 concordant with loss of both tyrosine and serine phosphorylation of STAT3, followed by cell death. The potent anticancer activity in vitro translated in vivo, where ganetespib was effective in modulating breast cancer xenograft growth as a single agent in both luminal and basal-like breast cancer models. Finally, ganetespib has demonstrated encouraging signs of clinical activity in breast cancer patients, including confirmed partial responses in both a triple negative breast cancer patient and a HER2 positive breast cancer patient. Conclusions: Ganetespib is a highly potent HSP90 inhibitor that displays preclinical activity in breast cancer due to its ability to simultaneously perturb multiple oncogenic signaling pathways. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-17-05.
Very late (aged ≥60 years) onset schizophrenia-like psychosis occurs frequently but no placebo-controlled, randomised trials have assessed the efficacy and risks of antipsychotic treatment. We investigated whether low-dose amisulpride (100 mg daily) is superior to placebo in reducing psychosis symptoms over 12 weeks and whether any benefit is maintained by continuing treatment after 12 weeks.The ATLAS double-blind controlled trial enrolled participants from 25 old age psychiatry services in the UK. Eligible participants (ie, those with a diagnosis of very late-onset schizophrenia-like psychosis and a Brief Psychiatric Rating Scale [BPRS] score of ≥30, without cognitive impairment) were randomly assigned (1:1:1) to one of three groups in a two-stage trial: amisulpride in stage 1 and 2 (group A), amisulpride then placebo (group B), or placebo then amisulpride (group C). Treatment (100 mg oral amisulpride daily vs placebo) was given for 12 weeks in stage 1 and, initially, 24 weeks then reduced to 12 weeks in stage 2. Participants, investigators, and outcome assessors were masked to treatment allocation. Primary outcomes were psychosis symptoms assessed by the BPRS at 4, 12, and 24, or 36 weeks, and trial treatment discontinuation for non-efficacy. The primary, secondary, and safety endpoints were all analysed in participants given at least one dose of study treatment in modified intention-to-treat analyses. This study is registered with EudraCT, number 2010-022184-35, and ISRCTN, number ISRCTN45593573.Between Sept 27, 2012, and June 28, 2016, we recruited 101 participants. 92 (91%) of 101 participants took trial medication, of whom 59 (64%) completed stage 1 and 34 (58%) of these 59 participants completed stage 2 treatment. Despite suboptimal compliance, improvements in BPRS scores at 12 weeks were 7·7 points (95% CI 3·8-11·5, p=0·0002) greater with amisulpride (mean 11·9 points [SE 1·3]) than with placebo (4·2 points [1·0]). In stage 2, BPRS scores improved by a mean of 1·1 points (1·6) from 12 weeks to the final assessment in those who continued amisulpride but deteriorated by 5·2 points (2·0) in those who switched from amisulpride to placebo (difference 6·3 points [95% CI 0·9-11·7], p=0·024). Fewer participants who were allocated amisulpride than placebo stopped treatment because of non-efficacy in stage 1 (p=0·010) and stage 2 (p=0·031). Serious adverse events were reported more frequently in the amisulpride group than in the placebo group in stage 1 (p=0·057) and stage 2 (p=0·19). The most common serious adverse events were infection (five patients in the amisulpride group, three in the placebo group) and extrapyramidal side-effects (three patients in the amisulpride group, none in the placebo group). Five patients died during the study, one from a gastric ulcer bleed before treatment started (group B), two while taking stage 2 treatment (one in group A and one in group C), and two who stopped trial treatment in stage 1 and died many weeks later (one in group B and one in group C). No deaths were related to treatment.Low-dose amisulpride is effective and well tolerated as a treatment for very late-onset schizophrenia-like psychosis, with benefits maintained by prolonging treatment.UK National Institute for Health Research.
The objective of this study was to define current assistive technology and telecare (ATT) practice for people with dementia living at home.This is a randomized controlled trial (N = 495) of ATT assessment and ATT installation intervention, compared with control (restricted ATT package). ATT assessment and installation data were collected. Qualitative work identified value networks delivering ATT, established an ATT assessment standard.ATT was delivered by public and not-for-profit telecare networks. ATT assessments showed 52% fidelity to the ATT assessment standard. Areas of assessment most frequently leading to identifying ATT need were daily activities (93%), memory (89%), and problem-solving (83%). ATT needs and recommendations were weakly correlated (τ = 0.242; P < .000), with ATT recommendations and installations moderately correlated (τ = -0.470; P < .000). Half (53%) of recommended technology was not installed. Safety concerns motivated 38% of installations.Assessment recommendations were routinely disregarded at the point of installation. ATT was commonly recommended for safety and seldom for supporting leisure.
Abstract Background Studies have indicated that addressing lifestyle risk factors in people with mild cognitive impairment (MCI), may slow symptom progression or even reduce their risk of progressing to dementia. However, this important window for dementia risk reduction and brain health promotion is often missed in existing UK clinical pathways. This work aims to develop and pilot a brain health navigation pathway for individuals receiving an MCI diagnosis from a UK memory assessment service in Greater Manchester. Methods To date we have worked closely with people living with MCI to develop this pathway and all associated resources and materials. In January 2023 we developed and embedded a new role, which we refer to as a brain health navigator, within an existing memory assessment service team in one commissioning region of Greater Manchester. Starting in April 2023, patients identified in memory assessments as having MCI, will receive a referral to the brain health navigation service. With support from our navigator, all those who accept the referral will receive: • A personalised brain health plan. • Brain health and prevention information and signposting to local community and professional resources. • A follow‐up appointment to assess the impact of this intervention on their wellbeing, skills, knowledge, and confidence in managing their own health. Results We will use a mixed methods approach to evaluate this work. We will collect Quantitative data describing the number of patients between April and June 2023 accepting a referral into the program, the number accessing community services; and wellbeing scores (using the Warwick‐Edinburgh Mental Wellbeing scale) pre‐and post‐intervention. Qualitative feedback will also be discussed including patient and clinical reflections of the service. Conclusions Our poster will discuss the feasibility and effectiveness of this model of patient support and how this approach may be expanded across the UK and beyond.
Background Minocycline is an anti-inflammatory drug and protects against the toxic effects of β-amyloid in vitro and in animal models of Alzheimer’s disease. To the best of our knowledge, no randomised placebo-controlled clinical trials in patients with Alzheimer’s disease looking at the efficacy and tolerability of minocycline have been carried out. Objectives The trial investigated whether or not minocycline was superior to placebo in slowing down the rate of decline in cognitive and functional ability over 2 years. The safety and tolerability of minocycline were also assessed. Design A Phase II, three-arm, randomised, double-blind, multicentre trial with a semifactorial design. Participants continued on trial treatment for up to 24 months. Setting Patients were identified from memory services, both within the 32 participating NHS trusts and within the network of memory services supported by the Dementias and Neurodegenerative Diseases Research Network (also known as DeNDRoN). Participants Patients with standardised Mini Mental State Examination scores of > 23 points and with Alzheimer’s disease assessed by the National Institute on Aging–Alzheimer’s Association’s criteria were identified from memory services. Intervention Patients with mild Alzheimer’s disease were randomly allocated 1 : 1 : 1 to receive one of three treatments: arm 1 – 400 mg per day of minocycline; arm 2 – 200 mg per day of minocycline; or arm 3 – placebo. Patients continued treatment for 24 months. Participants, investigators and outcome assessors were blind to treatment allocation. Main outcome measures Primary outcome measures were decline in standardised Mini Mental State Examination and Bristol Activities of Daily Living Scale scores of combined minocycline treatment arms versus placebo, as analysed by intention-to-treat repeated measures regression. Results Between 23 May 2014 and 14 April 2016, 554 participants were randomised. Of the 544 eligible participants, the mean age was 74.3 years and the average standardised Mini Mental State Examination score was 26.4 points. A total of 252 serious adverse events were reported, with the most common categories being neuropsychiatric and cardiocirculatory. Significantly fewer participants completed treatment with 400 mg of minocycline [29% (53/184)] than 200 mg [62% (112/181)] or placebo [64% (114/179)] ( p < 0.0001), mainly because of gastrointestinal symptoms ( p = 0.0008), dermatological side effects ( p = 0.02) and dizziness ( p = 0.01). Assessment rates were also lower in the 400-mg treatment arm: 68% (119 of 174 expected) for standardised Mini Mental State Examination scores at 24 months, compared with 82% (144/176) for the 200-mg treatment arm and 84% (140/167) for the placebo arm. Decline in standardised Mini Mental State Examination scores over the 24-month study period in the combined minocycline arms was similar to that in the placebo arm (4.1- vs. 4.3-point reduction; p = 0.9), as was the decline in the 400- and 200-mg treatment arms (3.3 vs. 4.7 points; p = 0.08). Likewise, worsening of Bristol Activities of Daily Living Scale scores over 24 months was similar in all trial arms (5.7, 6.6 and 6.2 points in the 400-mg treatment arm, 200-mg treatment arm and placebo arm, respectively; a p -value of 0.57 for minocycline vs. placebo and a p -value of 0.77 for 400 vs. 200 mg of minocycline). Results were similar in different patient subgroups and in sensitivity analyses adjusting for missing data. Limitations Potential limitations of the study include that biomarkers were not used to confirm the diagnosis of Alzheimer’s disease, as these and apolipoprotein E ( APOE ) genotyping are not routinely available within the NHS. Compliance was also worse than expected and differential follow-up rates were observed, with fewer assessments obtained for the 400-mg treatment arm than for the 200-mg treatment and placebo arms. Conclusions Minocycline does not delay the progress of cognitive or functional impairment in people with mild Alzheimer’s disease over a 2-year period. Minocycline at a dose of 400 mg is poorly tolerated in this population. Future work The Minocycline in mild Alzheimer’s DiseasE (MADE) study provides a framework for a streamlined trial design that can be usefully applied to test other disease-modifying therapies. Trial registration Current Controlled Trials ISRCTN16105064 and EudraCT 2013-000397-30. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership, and will be published in full in Efficacy and Mechanism Evaluation ; Vol. 7, No. 2. See the NIHR Journals Library website for further project information.
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