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.

Innovative blood transfusion strategies to address global blood deserts: a consensus statement from the Blood Delivery via Emerging Strategies for Emergency Remote Transfusion (Blood DESERT) Coalition.

In rural settings worldwide, many people live in effective blood deserts without access to any blood transfusion. The traditional system of blood banking is logistically complex and expensive for many resource-restricted settings and demands innovative and multidisciplinary solutions. 17 international experts in medicine, industry, and policy participated in an exploratory process with a 2-day hybrid seminar centred on three promising innovative strategies for blood transfusions in blood deserts: civilian walking blood banks, intraoperative autotransfusion, and drone-based blood delivery. Participant working groups conducted literature reviews and interviews to develop three white papers focused on the current state and knowledge gaps of each innovation. Seminar discussion focused on defining blood deserts and developing innovation-specific implementation agendas with key research and policy priorities for future work. Moving forward, advocates should prioritise the identification of blood deserts and address the context-specific challenges for these innovations to alleviate the ongoing crisis in blood deserts.

Protocol: identifying policy, system, and environment change interventions to enhance availability of blood for transfusion in Kenya, a mixed-methods study.

BACKGROUND: Safe blood is essential for the care of patients with life-threatening anemia and hemorrhage. Low blood donation rates, inefficient testing procedures, and other supply chain disruptions in blood administration affect patients in low-resource settings across Sub-Saharan countries, including Kenya. Most efforts to improve access to transfusion have been unidimensional, usually focusing on only point along the blood system continuum, and have excluded community stakeholders from early stages of intervention development. Context-appropriate interventions to improve the availability of safe blood at the point of use in low-resource settings are of paramount importance. Thus, this protocol proposes a multifaceted approach to characterize the Kenyan blood supply chain through quantitative and qualitative analyses as well as an industrial engineering approach. METHODS: This study will use a mixed-methods approach in addition to engineering process mapping, modeling and simulation of blood availability in Kenya. It will be guided by a multidimensional three-by-three-by-three matrix: three socioeconomic settings, three components of the blood system continuum, and three levels of urgency of blood transfusion. Qualitative data collection includes one-on-one interviews and focus group discussions with stakeholders across the continuum to characterize ground-level deficits and potential policy, systems, and environment (PSE) interventions. Prospectively-collected quantitative data will be used to estimate blood collection and transfusion of blood. We will create a process map of the blood system continuum to model the response to PSE changes proposed by stakeholders. Lastly, we will identify those PSE changes that may have the greatest impact on blood transfusion availability, accounting for differences across socioeconomic settings and levels of urgency. DISCUSSION: Identifying and prioritizing community-driven interventions to improve blood supply in low-resource settings are of utmost importance. Varied constraints in blood collection, processing, delivery, and use make each socioeconomic setting unique. Using a multifaceted approach to understand the Kenyan blood supply and model the response to stakeholder-proposed PSE changes may lead to identification of contextually appropriate intervention targets to meet the transfusion needs of the population.

The Cell and Gene Therapy Consortium's Perspective on Harmonizing Data Collection for Patient Enrollment, Therapy Ordering and Scheduling, and Cell Collection.

Established in October 2021, the Cell and Gene Therapy (CGT) Consortium convened with the goal to bring together key CGT stakeholders - manufacturers, treatment centers, regulators, services providers, and ecosystem partners - to gain alignment on process definitions, terminology, challenges, and opportunities for process and data standardization from CGT program start-up and patient enrollment to therapy administration. With the recognition that the number of investigational and commercial cell and gene therapies will scale over the next several years, so will the number of manufacturer-specific processes and solutions (e.g., portals). As a result, this will increase the burden on academic medical centers, community hospitals, standalone clinics, collection facilities, and labs. Healthcare professionals (HCPs) and other industry stakeholders agree that a multiplicity of manufacturer portals with varying data requirements and nomenclature is unsustainable and adds unnecessary complexity - risk, cost, and time - in coordinating patient treatment. Following extensive discussions and multiple stakeholder meetings and interviews, we have developed a manuscript reporting on our activities and conclusions. Through the course of the manuscript, we delineate a framework for defining common principles, terminology, and user experiences for enrolling patients, ordering therapies, and collecting starting material in a standardized way. We also provide substantial background information on opportunities to streamline communications between manufacturing and healthcare organizations from the HCP end-user's perspective.

Characterizing Therapeutic Pluralism Policies in Latin America: A Qualitative Content Analysis.

Introduction: The 1978 Alma Ata Declaration initiated international recognition of non-biomedical healing systems and their relevance for primary health. World Health Assembly (WHA) resolutions have called for the study and inclusion of traditional and complementary medicine (T&CM) into national health systems through policy development. The increased public, political, and scholarly attention given to T&CM has focused on clinical efficacy, cost-effectiveness, mechanisms of action, consumer demand, and supply-side regulation. Although >50% of WHO member states have T&CM policies, scant research has focused on these policies and their public health implications. This paper defines a novel term "therapeutic pluralism," and it aims at characterizing related policies in Latin America. Methods: A qualitative content analysis of Latin American therapeutic pluralism policies was performed. Policies' characteristics and the reported social, political, and economic forces that have made possible their development were assessed. Pre-defined policy features were categorized on an MS-Excel; in-depth text analyses were conducted in NVivo. Analyses followed the steps described by Bengtsson: decontextualization, recontextualization, categorization, and compilation. Results: Seventy-four (74) policy documents from 16 of the 20 sovereign Latin American countries were included. Mechanisms for policy enactment included: Constitution, National Law, National Policy, National Healthcare Model, National Program Guideline, Specific Regulatory Norms, and Supporting Legislation, Policies, and Norms. We propose a four-category typology of policy approaches in Latin America: Health Services-centered, Model of Care-based, Participatory, and Indigenous People-focused. Common themes countries used when justifying developing these policies included: benefits to the health system, legal and political mandates, supply and demand, and culture and identity. Social forces these policies referenced as influencing their development included: pluralism, self-determination and autonomy, anticapitalism and decolonization, safeguarding cultural identity, bridging cultural barriers, and sustainability. Conclusion: Policy approaches to therapeutic pluralism in Latin America go beyond integrating non-biomedical interventions into health services; they offer perspectives for transforming health systems. Characterizing these approaches has implications for policy development, implementation, evaluation, international collaboration, the development of technical cooperation tools and frameworks, and research.

Transfusion medicine research in Africa: Insights from investigators in the field.

BACKGROUND AND OBJECTIVES: Research in low-resource settings is inherently challenging. We sought to assess the factors that have impeded or facilitated transfusion medicine (TM) research in various African settings. MATERIALS AND METHODS: A qualitative case study was conducted of selected investigators in Africa; selection was based on productivity-spanning publication, leadership and research in TM. We designed a questionnaire to explore the factors impeding or facilitating TM research to understand the impact on the investigators' careers. Written responses were independently coded and double-checked for precision. Qualitative analysis was conducted, whereby responses were grouped thematically and clustered by relationship. The initial findings were discussed with respondents to validate and refine the interpretations. The recorded transcript was analysed and incorporated into the final analysis. RESULTS: Six investigators participated in the study. Their responses yielded 471 coded comments: 389 from the questionnaires and 82 from the ensuing discussion. The most frequently cited factors described included knowledge and intellectual abilities (n = 104), personal effectiveness (n = 99), research and governance structure (n = 97), and engagement, influence and impact (n = 75). Four relationship clusters emerged from the facilitators (n = 42), barriers (n = 28), and common approaches (n = 26) to research, informing summary themes of adaptation, collaboration, perseverance, and resiliency. CONCLUSION: Individual attributes were found to be central to a successful TM research career in African settings. However, given other public health priorities and constraints, interpersonal relationships, organizational structures and the broader research context were important to TM researchers. Overcoming complexities demands adaptation, collaboration, perseverance and resiliency.

Impact of COVID-19 policies on perceptions of loneliness in people aged 75 years and over in the cognitive function and aging study (CFAS II).

BACKGROUND: The COVID-19 pandemic and associated social distancing measures have profoundly impacted society and social contact patterns, with older people disproportionately affected. Concerns have been raised about a resulting pandemic of loneliness in older people, although the current evidence is mixed. This study provides a unique perspective on the prevalence of loneliness in a population cohort of older people before the pandemic, followed up after the introduction of social restrictions. METHODS: Data analysis was conducted using Wave 3 of the longitudinal Cognitive Function and Aging Study II (2018-2019) and a sub-study focusing on experiences during the COVID-19 pandemic (2020). The sample comprised 379 adults aged over 75 living in Cambridge, Newcastle, and Nottingham. Multivariable binary logistic regression was conducted to identify correlates of prevalent loneliness, adjusted for confounding covariates, during the pandemic. The prevalence of loneliness during the pandemic was compared to loneliness in 2018-2019. RESULTS: Prevalence of loneliness in this sample during the pandemic was 25.1% (95% CI 20.9%-29.7%) compared to 17.2% (95% CI 13.7%-21.3%) in 2018-2019 (χ2  = 14.1, p < 0.01). Variables associated with increased odds of prevalent loneliness included: prior loneliness, living alone, female gender, living in an area of higher deprivation, frequent pre-pandemic social contact at community groups, and separation from family during the pandemic, adjusted for age and sex. Weekly technology-mediated contact using telephone or video calls was associated with lower odds of loneliness. CONCLUSIONS: COVID-19 recovery plans should address loneliness in older people. Target groups should include those who have previously been lonely, people who live alone, those living in deprived areas, and those who had previously been socially active through community groups.

The BLOODSAFE program: Building the future of access to safe blood in Sub-Saharan Africa.

BACKGROUND: The supply of blood in many low- and middle-income nations in Sub-Saharan Africa (SSA) does not meet the patient care needs. Lack and delay of blood transfusion cause harm to patients and slow the rate of progress in other parts of the health system. Recognizing the power of implementation science, the BLOODSAFE Program was initiated which supports three SSA research study teams and one data coordinating center (DCC) with the goal to improve access to safe blood transfusion in SSA. STUDY DESIGN AND METHODS: The study team in Ghana is focusing on studying and decreasing iron deficiency in blood donors and evaluating social engagement of blood donors through different approaches. The study team in Kenya is building a "vein to vein" workflow model to elucidate and devise strategies to overcome barriers to blood donation and improve infrastructural components of blood product production and use. The Malawi team is studying the infectious disease ramifications of blood donation as well as blood donor retention strategies aimed at blood donors who commence their donation career in secondary schools. RESULTS AND DISCUSSION: Together the project teams and the DCC work as a consortium to support each other through a shared study protocol that will study donor motivations, outcomes, and adverse events across all three countries. The BLOODSAFE Program has the potential to lead to generalizable improvement approaches for increasing access to safe blood in SSA as well as mentoring and building the research capacity and careers of many investigators.

Delirium and Delirium Severity Predict the Trajectory of the Hierarchical Assessment of Balance and Mobility in Hospitalized Older People: Findings From the DECIDE Study.

BACKGROUND: Delirium is common, distressing, and associated with poor outcomes. Despite this, delirium remains poorly recognized, resulting in worse outcomes. There is an urgent need for methods to objectively assess for delirium. Physical function has been proposed as a potential surrogate marker, but few studies have monitored physical function in the context of delirium. We examined if trajectories of physical function are affected by the presence and severity of delirium in a representative sample of hospitalized participants older than 65 years. METHOD: During hospital admissions in 2016, we assessed participants from the Delirium and Cognitive Impact in Dementia study daily for delirium and physical function, using the Hierarchical Assessment of Balance and Mobility (HABAM). We used linear mixed models to assess the effect of delirium and delirium severity during admission on HABAM trajectory. RESULTS: Of 178 participants, 58 experienced delirium during admission. Median HABAM scores in those with delirium were significantly higher (indicating worse mobility) than those without delirium. Modeling HABAM trajectories, HABAM scores at first assessment were worse in those with delirium than those without, by 0.76 (95% CI: 0.49-1.04) points. Participants with severe delirium experienced a much greater perturbance in their physical function, with an even lower value at first assessment and slower subsequent improvement. CONCLUSIONS: Physical function was worse in those with delirium compared to without. This supports the assertion that motor disturbances are a core feature of delirium and monitoring physical function, using a tool such as the HABAM, may have clinical utility as a surrogate marker for delirium and its resolution.

Status of hospital-based blood transfusion services in low-income and middle-income countries: a cross-sectional international survey.

OBJECTIVES: Blood transfusion is life-saving for patients experiencing acute blood loss and severe anaemia. In low-income and middle-income countries (LMICs), low blood donation rates and unavailability of whole blood and blood components (blood products) impairs timely blood transfusion. To fulfil patient-specific blood orders, a hospital blood transfusion service (HBTS) receives orders from a prescriber for blood transfusion, tests and prepares blood products for the patient. This study sought to describe the current state of LMIC HBTS. DESIGN: A cross-sectional survey explored LMIC HBTS access to blood products, testing methods, policies and structure. Surveys were administered in English, Spanish, French and Russian, followed by a mixed-methods analysis. SETTING: HBTS within LMICs. PARTICIPANTS: From among 124 public and private facilities invited to participate, we received 71 (57%) responses. Of these responses, 50 HBTS from 27 LMICs performed on-site blood transfusions. RESULTS: Most LMIC HBTS perform blood collection to generate blood products for their patients (36/47, 77%); few relied exclusively on an external supply of blood products (11/47, 23%). The primary reason for blood transfusion was adult anaemia for non-malignant conditions (17/112, 15%). Testing methods varied by gross national income per capita. Blood transfusion delays to patients were common (17/30, 57%) attributed to inadequate blood inventories (13/29, 45%). Other barriers included lack of regular clinician education about transfusion (8/29, 28%) and sustainable financial models for the HBTS (4/29, 14%). CONCLUSION: This survey describes the status of HBTS in diverse LMICs, illustrating that the availability of blood products remains a principal problem, requiring HBTS to generate its own facility's blood supply. Currently, blood shortages are not reported as a patient-specific adverse event making systematic tracking of delays in transfusion difficult. These findings highlight areas for further exploration related to the lack of available blood inventories for transfusions at HBTS in LMICs.

COVID-19 and the impact on blood availability and transfusion practices in low- and middle-income countries.

BACKGROUND/CASE STUDIES: The coronavirus disease 2019 (COVID-19) pandemic disrupted the global blood supply. Low- and middle-income countries (LMICs) already experienced blood supply deficits that preceded the pandemic. We sought to characterize the challenges experienced during the pandemic, and adaptations, such as COVID-19 convalescent plasma (CCP). STUDY DESIGN/METHODS: A cross-sectional survey explored blood availability, challenges, and adaptations. The survey contained 31 questions, e-mailed in English, French, or Spanish, to selected LMIC blood transfusion practitioners. Data acquisition occurred between October 28 and December 28, 2020. A mixed methods analysis followed. RESULTS/FINDINGS: A total of 31 responses from 111 invitations represented 26 LMIC countries. Languages included English (22, 71%), Spanish (7, 22.6%), and French (2, 6.4%). Most respondents (29/31, 93.5%) collected blood; 58% also transfused blood (18/31). The supply of blood came from hospital-based blood donations (61%, 11/18); blood suppliers (17%, 3/18); and both sources (22%, 4/18). Collectively, 77.4% (24/31) of respondents experienced a decline in blood availability, ranging from 10% to 50%. Contributing factors included public fear of COVID-19 (21/24); stay-at-home measures (18/24); logistics (14/24); and canceled blood drives (16/24). Adaptations included increased collaboration within and between institutions (17/27), donor eligibility changes (21/31); social media or phone promotion (22/39); and replacement donation (3/27). Fifteen of 31 responses reported CCP donation (48.4%); CCP transfusion occurred in 6 (19.4%). The primary barrier was engaging recovered patients for donation (7/15). CONCLUSION: Our survey describes challenges experienced by LMIC blood systems during the COVID-19 pandemic. While the decline in blood supplies was severe, adaptive measures included collaboration, outreach, and CCP programs.

Evaluation of Bedside Tests of Attention and Arousal Assessing Delirium in Parkinson's Disease, Dementia, and Older Adults.

BACKGROUND: Delirium is a serious acute neuropsychiatric condition associated with altered attention and arousal. OBJECTIVE: To evaluate simple bedside tests for attention and arousal to detect delirium in those with and without Parkinson's disease (PD) and dementia. METHODS: Participants from two prospective delirium studies were pooled comprising 30 with PD without cognitive impairment, 24 with Lewy body cognitive impairment (PD dementia or dementia with Lewy bodies), 16 with another dementia and 179 PD and dementia-free older adults. Participants completed standardised delirium assessments including tests of attention: digit span, Memorial Delirium Assessment Scale (MDAS) attention and months of the year backwards; and arousal: Glasgow Coma Scale (GSC), Observational Scale of Level of Arousal (OSLA), Modified Richmond Agitation Scale and MDAS consciousness. Delirium was diagnosed using the DSM-5 criteria. RESULTS: On their first admission, 21.7%participants had prevalent delirium. Arousal measures accurately detected delirium in all participants (p < 0.01 for all), but only selected attention measures detected delirium in PD and dementia. In PD and dementia-free older adults, impaired digit span and OSLA were the optimal tests to detect delirium (area under the curve [AUC] = 0.838, p < 0.001) while in PD and dementia the optimal tests were MDAS attention and GCS (AUC=0.90 and 0.84, respectively, p < 0.001 for both). CONCLUSION: Simple bedside tests of attention and arousal at a single visit could accurately detect delirium in PD, dementia and PD and dementia-free older adults; however, the optimal tests differed between groups. Combined attention and arousal scores increased accuracy, which could have clinical utility to aid the identification of delirium neurodegenerative disorders.

Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis.

Importance: In clinical guidelines, overt and subclinical thyroid dysfunction are mentioned as causal and treatable factors for cognitive decline. However, the scientific literature on these associations shows inconsistent findings. Objective: To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia. Design, Setting, and Participants: This multicohort individual participant data analysis assessed 114 267 person-years (median, 1.7-11.3 years) of follow-up for cognitive function and 525 222 person-years (median, 3.8-15.3 years) for dementia between 1989 and 2017. Analyses on cognitive function included 21 cohorts comprising 38 144 participants. Analyses on dementia included eight cohorts with a total of 2033 cases with dementia and 44 573 controls. Data analysis was performed from December 2016 to January 2021. Exposures: Thyroid function was classified as overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism based on uniform thyrotropin cutoff values and study-specific free thyroxine values. Main Outcomes and Measures: The primary outcome was global cognitive function, mostly measured using the Mini-Mental State Examination. Executive function, memory, and dementia were secondary outcomes. Analyses were first performed at study level using multivariable linear regression and multivariable Cox regression, respectively. The studies were combined with restricted maximum likelihood meta-analysis. To overcome the use of different scales, results were transformed to standardized mean differences. For incident dementia, hazard ratios were calculated. Results: Among 74 565 total participants, 66 567 (89.3%) participants had normal thyroid function, 577 (0.8%) had overt hyperthyroidism, 2557 (3.4%) had subclinical hyperthyroidism, 4167 (5.6%) had subclinical hypothyroidism, and 697 (0.9%) had overt hypothyroidism. The study-specific median age at baseline varied from 57 to 93 years; 42 847 (57.5%) participants were women. Thyroid dysfunction was not associated with global cognitive function; the largest differences were observed between overt hypothyroidism and euthyroidism-cross-sectionally (-0.06 standardized mean difference in score; 95% CI, -0.20 to 0.08; P = .40) and longitudinally (0.11 standardized mean difference higher decline per year; 95% CI, -0.01 to 0.23; P = .09). No consistent associations were observed between thyroid dysfunction and executive function, memory, or risk of dementia. Conclusions and Relevance: In this individual participant data analysis of more than 74 000 adults, subclinical hypothyroidism and hyperthyroidism were not associated with cognitive function, cognitive decline, or incident dementia. No rigorous conclusions can be drawn regarding the role of overt thyroid dysfunction in risk of dementia. These findings do not support the practice of screening for subclinical thyroid dysfunction in the context of cognitive decline in older adults as recommended in current guidelines.

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.

A phase 2 trial of inhaled nitrous oxide for treatment-resistant major depression.

Nitrous oxide at 50% inhaled concentration has been shown to improve depressive symptoms in patients with treatment-resistant major depression (TRMD). Whether a lower concentration of 25% nitrous oxide provides similar efficacy and persistence of antidepressant effects while reducing the risk of adverse side effects is unknown. In this phase 2 clinical trial (NCT03283670), 24 patients with severe TRMD were randomly assigned in a crossover fashion to three treatments consisting of a single 1-hour inhalation with (i) 50% nitrous oxide, (ii) 25% nitrous oxide, or (iii) placebo (air/oxygen). The primary outcome was the change on the Hamilton Depression Rating Scale (HDRS-21). Whereas nitrous oxide significantly improved depressive symptoms versus placebo (P = 0.01), there was no difference between 25 and 50% nitrous oxide (P = 0.58). The estimated differences between 25% and placebo were -0.75 points on the HDRS-21 at 2 hours (P = 0.73), -1.41 points at 24 hours (P = 0.52), -4.35 points at week 1 (P = 0.05), and -5.19 points at week 2 (P = 0.02), and the estimated differences between 50% and placebo were -0.87 points at 2 hours (P = 0.69), -1.93 points at 24 hours (P = 0.37), -2.44 points at week 1 (P = 0.25), and -7.00 points at week 2 (P = 0.001). Adverse events declined substantially with dose (P < 0.001). These results suggest that 25% nitrous oxide has comparable efficacy to 50% nitrous oxide in improving TRMD but with a markedly lower rate of adverse effects.

Hospitalisation without delirium is not associated with cognitive decline in a population-based sample of older people-results from a nested, longitudinal cohort study.

BACKGROUND: Acute hospitalisation and delirium have individually been shown to adversely affect trajectories of cognitive decline but have not previously been considered together. This work aimed to explore the impact on cognition of hospital admission with and without delirium, compared to a control group with no hospital admissions. METHODS: The Delirium and Cognitive Impact in Dementia (DECIDE) study was nested within the Cognitive Function and Ageing Study II (CFAS II)-Newcastle cohort. CFAS II participants completed two baseline interviews, including the Mini-Mental State Examination (MMSE). During 2016, surviving participants from CFAS II-Newcastle were recruited to DECIDE on admission to hospital. Participants were reviewed daily to determine delirium status.During 2017, all DECIDE participants and age, sex and years of education matched controls without hospital admissions during 2016 were invited to repeat the CFAS II interview. Delirium was excluded in the control group using the Informant Assessment of Geriatric Delirium Scale (i-AGeD). Linear mixed effects modelling determined predictors of cognitive decline. RESULTS: During 2016, 82 of 205 (40%) DECIDE participants had at least one episode of delirium. At 1 year, 135 of 205 hospitalised participants completed an interview along with 100 controls. No controls experienced delirium (i-AGeD>4). Delirium was associated with a faster rate of cognitive decline compared to those without delirium (ß = -2.2, P < 0.001), but number of hospital admissions was not (P = 0.447). CONCLUSIONS: These results suggest that delirium during hospitalisation rather than hospitalisation per se is a risk factor for future cognitive decline, emphasising the need for dementia prevention studies that focus on delirium intervention.

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.

Recurrent delirium over 12 months predicts dementia: results of the Delirium and Cognitive Impact in Dementia (DECIDE) study.

BACKGROUND: Delirium is common, distressing and associated with poor outcomes. Previous studies investigating the impact of delirium on cognitive outcomes have been limited by incomplete ascertainment of baseline cognition or lack of prospective delirium assessments. This study quantified the association between delirium and cognitive function over time by prospectively ascertaining delirium in a cohort aged ≥ 65 years in whom baseline cognition had previously been established. METHODS: For 12 months, we assessed participants from the Cognitive Function and Ageing Study II-Newcastle for delirium daily during hospital admissions. At 1-year, we assessed cognitive decline and dementia in those with and without delirium. We evaluated the effect of delirium (including its duration and number of episodes) on cognitive function over time, independently of baseline cognition and illness severity. RESULTS: Eighty two of 205 participants recruited developed delirium in hospital (40%). One-year outcome data were available for 173 participants: 18 had a new dementia diagnosis, 38 had died. Delirium was associated with cognitive decline (-1.8 Mini-Mental State Examination points [95% CI -3.5 to -0.2]) and an increased risk of new dementia diagnosis at follow up (OR 8.8 [95% CI 1.9-41.4]). More than one episode and more days with delirium (>5 days) were associated with worse cognitive outcomes. CONCLUSIONS: Delirium increases risk of future cognitive decline and dementia, independent of illness severity and baseline cognition, with more episodes associated with worse cognitive outcomes. Given that delirium has been shown to be preventable in some cases, we propose that delirium is a potentially modifiable risk factor for dementia.

Asian Immigrant Parents' Role Enactment While Accessing and Using Services for Their Child With Developmental Disabilities in the United States: A Meta-Synthesis Study.

We conducted a meta-synthesis to explore how Asian immigrant parents in the United States enact their perceived parental role while using health and educational services for their child with developmental disabilities. We identified 11 qualitative studies for analysis, and examined these studies using a constant comparative approach and thematic analysis informed by role theory and acculturation theory. Based on our analysis, five themes related to parents' role enactment emerged: (a) parents perceive a multifaceted parental role; (b) parents' individual factors influence their role enactment; (c) system factors influence parents' role enactment; (d) parents use coping strategies to address role dissatisfaction; and (e) parental role enactment is a continuously evolving process influenced by acculturation, which spirals them toward their ultimate goal of helping their child thrive. Findings can inform practitioners' and researchers' understanding of how to create a culturally safe environment to support Asian immigrant parents in realizing their parental role.

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.