Prevention of dementia using mobile phone applications (PRODEMOS): a multinational, randomised, controlled effectiveness-implementation trial.

BACKGROUND: The expected increase of dementia prevalence in the coming decades will mainly be in low-income and middle-income countries and in people with low socioeconomic status in high-income countries. This study aims to reduce dementia risk factors in underserved populations at high-risk using a coach-supported mobile health (mHealth) intervention. METHODS: This open-label, blinded endpoint, hybrid effectiveness-implementation randomised controlled trial (RCT) investigated whether a coach-supported mHealth intervention can reduce dementia risk in people aged 55-75 years of low socioeconomic status in the UK or from the general population in China with at least two dementia risk factors. The primary effectiveness outcome was change in cardiovascular risk factors, ageing, and incidence of dementia (CAIDE) risk score from baseline to after 12-18 months of intervention. Implementation outcomes were coverage, adoption, sustainability, appropriateness, acceptability, fidelity, feasibility, and costs assessed using a mixed-methods approach. All participants with complete data on the primary outcome, without imputation of missing outcomes were included in the analysis (intention-to-treat principle). This trial is registered with ISRCTN, ISRCTN15986016, and is completed. FINDINGS: Between Jan 15, 2021, and April 18, 2023, 1488 people (601 male and 887 female) were randomly assigned (734 to intervention and 754 to control), with 1229 (83%) of 1488 available for analysis of the primary effectiveness outcome. After a mean follow-up of 16 months (SD 2·5), the mean CAIDE score improved 0·16 points in the intervention group versus 0·01 in the control group (mean difference -0·16, 95% CI -0·29 to -0·03). 1533 (10%) invited individuals responded; of the intervention participants, 593 (81%) of 734 adopted the intervention and 367 (50%) of 734 continued active participation throughout the study. Perceived appropriateness (85%), acceptability (81%), and fidelity (79%) were good, with fair overall feasibility (53% of intervention participants and 58% of coaches), at low cost. No differences in adverse events between study arms were found. INTERPRETATION: A coach-supported mHealth intervention is modestly effective in reducing dementia risk factors in those with low socioeconomic status in the UK and any socioeconomic status in China. Implementation is challenging in these populations, but those reached actively participated. Whether this intervention will result in less cognitive decline and dementia requires a larger RCT with long follow-up. FUNDING: EU Horizon 2020 Research and Innovation Programme and the National Key R&D Programmes of China. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Prevention of dementia using mobile phone applications (PRODEMOS): protocol for an international randomised controlled trial.

INTRODUCTION: Profiles of high risk for future dementia are well understood and are likely to concern mostly those in low-income and middle-income countries and people at greater disadvantage in high-income countries. Approximately 30%-40% of dementia cases have been estimated to be attributed to modifiable risk factors, including hypertension, smoking and sedentary lifestyle. Tailored interventions targeting these risk factors can potentially prevent or delay the onset of dementia. Mobile health (mHealth) improves accessibility of such prevention strategies in hard-to-reach populations while at the same time tailoring such approaches. In the current study, we will investigate the effectiveness and implementation of a coach-supported mHealth intervention, targeting dementia risk factors, to reduce dementia risk. METHODS AND ANALYSIS: The prevention of dementia using mobile phone applications (PRODEMOS) randomised controlled trial will follow an effectiveness-implementation hybrid design, taking place in the UK and China. People are eligible if they are 55-75 years old, of low socioeconomic status (UK) or from the general population (China); have ≥2 dementia risk factors; and own a smartphone. 2400 participants will be randomised to either a coach-supported, interactive mHealth platform, facilitating self-management of dementia risk factors, or a static control platform. The intervention and follow-up period will be 18 months. The primary effectiveness outcome is change in the previously validated Cardiovascular Risk Factors, Ageing and Incidence of Dementia dementia risk score. The main secondary outcomes include improvement of individual risk factors and cost-effectiveness. Implementation outcomes include acceptability, adoption, feasibility and sustainability of the intervention. ETHICS AND DISSEMINATION: The PRODEMOS trial is sponsored in the UK by the University of Cambridge and is granted ethical approval by the London-Brighton and Sussex Research Ethics Committee (reference: 20/LO/01440). In China, the trial is approved by the medical ethics committees of Capital Medical University, Beijing Tiantan Hospital, Beijing Geriatric Hospital, Chinese People's Liberation Army General Hospital, Taishan Medical University and Xuanwu Hospital. Results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN15986016.

Design and Development of a Mobile Health (mHealth) Platform for Dementia Prevention in the Prevention of Dementia by Mobile Phone Applications (PRODEMOS) Project.

Background: Mobile health (mHealth) has the potential to bring preventive healthcare within reach of populations with limited access to preventive services, by delivering personalized support at low cost. Although numerous mHealth interventions are available, very few have been developed following an evidence-based rationale or have been tested for efficacy. This article describes the systematic development of a coach-supported mHealth application to improve healthy lifestyles for the prevention of dementia and cardiovascular disease in the United Kingdom (UK) and China. Methods: Development of the Prevention of Dementia by Mobile Phone applications (PRODEMOS) platform built upon the experiences with the Healthy Aging Through Internet Counseling in the Elderly (HATICE) eHealth platform. In the conceptualization phase, experiences from the HATICE trial and needs and wishes of the PRODEMOS target population were assessed through semi-structured interviews and focus group sessions. Initial technical development of the platform was based on these findings and took place in consecutive sprint sessions. Finally, during the evaluation and adaptation phase, functionality and usability of the platform were evaluated during pilot studies in UK and China. Results: The PRODEMOS mHealth platform facilitates self-management of a healthy lifestyle by goal setting, progress monitoring, and educational materials on healthy lifestyles. Participants receive remote coaching through a chat functionality. Based on lessons learned from the HATICE study and end-users, we made the intervention easy-to-use and included features to personalize the intervention. Following the pilot studies, in which in total 77 people used the mobile application for 6 weeks, the application was made more intuitive, and we improved its functionalities. Conclusion: Early involvement of end-users in the development process and during evaluation phases improved acceptability of the mHealth intervention. The actual use and usability of the PRODEMOS intervention will be assessed during the ongoing PRODEMOS randomized controlled trial, taking a dual focus on effectiveness and implementation outcomes.

Dementia Research Fit for the Planet: Reflections on Population Studies of Dementia for Researchers and Policy Makers Alike.

In recent years, a rapidly increasing collection of investigative methods in addition to changes in diagnostic criteria for dementia have followed "high-tech" trends in medicine, with the aim to better define the dementia syndrome and its biological substrates, mainly in order to predict risk prior to clinical expression. These approaches are not without challenge. A set of guidelines have been developed by a group of European experts in population-based cohort research through a series of workshops, funded by the Joint Program for Neurodegenerative Disorders (JPND). The aims of the guidelines are to assist policy makers and researchers to understand (1) What population studies for ageing populations should encompass and (2) How to interpret the findings from population studies. Such studies are essential to provide evidence relevant to the understanding of healthy and frail brain ageing, including the dementia syndrome for contemporary and future societies by drawing on the past.

Immune reconstitution in children following chemotherapy for acute leukemia.

Although survival rates for pediatric acute lymphoblastic leukemia are now excellent, this is at the expense of prolonged chemotherapy regimens. We report the long-term immune effects in children treated according to the UK Medical Research Council UKALL 2003 protocol. Peripheral blood lymphocyte subsets and immunoglobulin levels were studied in 116 participants, at six time points, during and for 18-month following treatment, with 30-39 patients analyzed at each time point. Total lymphocytes were reduced during maintenance chemotherapy and remained low 18 months following treatment completion. CD4 T cells remained significantly reduced 18 months after treatment, but CD8 cells and natural killer cells recovered to normal values. The fall in naïve B-cell numbers during maintenance was most marked, but numbers recovered rapidly after cessation of treatment. Memory B cells, particularly nonclass-switched memory B cells, remained below normal levels 18 months following treatment. All immunoglobulin subclasses were reduced during treatment compared to normal values, with IgM levels most affected. This study demonstrates that immune reconstitution differs between lymphocyte compartments. Although total B-cell numbers recover rapidly, disruption of memory/naïve balance persists and T-cell compartment persist at 18 months. This highlights the impact of modern chemotherapy regimens on immunity, and thus, infectious susceptibility and response to immunization.

Daily muscle stretching enhances blood flow, endothelial function, capillarity, vascular volume and connectivity in aged skeletal muscle.

KEY POINTS: In aged rats, daily muscle stretching increases blood flow to skeletal muscle during exercise. Daily muscle stretching enhanced endothelium-dependent vasodilatation of skeletal muscle resistance arterioles of aged rats. Angiogenic markers and capillarity increased in response to daily stretching in muscles of aged rats. Muscle stretching performed with a splint could provide a feasible means of improving muscle blood flow and function in elderly patients who cannot perform regular aerobic exercise. ABSTRACT: Mechanical stretch stimuli alter the morphology and function of cultured endothelial cells; however, little is known about the effects of daily muscle stretching on adaptations of endothelial function and muscle blood flow. The present study aimed to determine the effects of daily muscle stretching on endothelium-dependent vasodilatation and muscle blood flow in aged rats. The lower hindlimb muscles of aged Fischer rats were passively stretched by placing an ankle dorsiflexion splint for 30 min day-1 , 5 days week-1 , for 4 weeks. Blood flow to the stretched limb and the non-stretched contralateral limb was determined at rest and during treadmill exercise. Endothelium-dependent/independent vasodilatation was evaluated in soleus muscle arterioles. Levels of hypoxia-induced factor-1α, vascular endothelial growth factor A and neuronal nitric oxide synthase were determined in soleus muscle fibres. Levels of endothelial nitric oxide synthase and superoxide dismutase were determined in soleus muscle arterioles, and microvascular volume and capillarity were evaluated by microcomputed tomography and lectin staining, respectively. During exercise, blood flow to plantar flexor muscles was significantly higher in the stretched limb. Endothelium-dependent vasodilatation was enhanced in arterioles from the soleus muscle from the stretched limb. Microvascular volume, number of capillaries per muscle fibre, and levels of hypoxia-induced factor-1α, vascular endothelial growth factor and endothelial nitric oxide synthase were significantly higher in the stretched limb. These results indicate that daily passive stretching of muscle enhances endothelium-dependent vasodilatation and induces angiogenesis. These microvascular adaptations may contribute to increased muscle blood flow during exercise in muscles that have undergone daily passive stretch.

Hypercalcaemia secondary to ectopic parathyroid hormone expression in an adolescent with metastatic alveolar rhabdomyosarcoma.

We report the case of a 14-year-old male with metastatic alveolar rhabdomyosarcoma, presenting with hypercalcaemia (3.89 mmol/l) and elevated parathyroid hormone (PTH) level (10.2 pmol/l). Imaging demonstrated extensive bony lytic damage, with "floating teeth" in the mandible. Normalisation of calcium levels and bony reformation of the mandible occurred following chemotherapy; PTH levels decreased initially but remained above normal levels. Imaging did not demonstrate any evidence of parathyroid abnormality. Tumour ectopic PTH secretion is a very rare cause of hypercalcaemia of malignancy in children. Hypercalcaemia with an elevated PTH, in the absence of parathyroid-related cause, should prompt investigation for underlying malignancy.

Greenhouse Gas Emissions from Septic Systems in New York State.

Onsite septic systems use microbial processes to eliminate organic wastes and nutrients such as nitrogen; these processes can contribute to air pollution through the release of greenhouse gases (GHGs). Current USEPA estimates for septic system GHG emissions are based on one study conducted in north-central California and are limited to methane; therefore, the contribution of these systems to the overall GHG emission budget is unclear. This study quantified and compared septic system GHG emissions from the soil over leach fields and the roof vent, which are the most likely locations for gas emissions during normal septic system operation. At each of eight septic systems, we measured fluxes of CH, CO, and NO using a static chamber method. The roof vent released the majority of septic system gas emissions. In addition, the leach field was a significant source of NO fluxes. Comparisons between leach field and vent emissions suggest that biological processes in the leach field soil may influence the type and quantity of gas released. Overall, our results suggest that (i) revisions are needed in USEPA guidance (e.g., septic systems are not currently listed as a source of NO emissions) and (ii) similar studies representing a wider range of climatic and geographic settings are needed. The total vent, sand filter, and leach field GHG emissions were 0.17, 0.045, and 0.050 t CO-equivalents capita yr, respectively. In total, this represents about 1.5% of the annual carbon footprint of an individual living in the United States.