Stakeholder perceptions on scaling-up community-led interventions for prevention and control of non-communicable diseases in Bangladesh: a qualitative study.

BACKGROUND: Engaging communities is an important component of multisectoral action to address the growing burden of non-communicable diseases (NCDs) in low- and middle-income countries. We conducted research with non-communicable disease stakeholders in Bangladesh to understand how a community-led intervention which was shown to reduce the incidence of type 2 diabetes in rural Bangladesh could be scaled-up. METHODS: We purposively sampled any actor who could have an interest in the intervention, or that could affect or be affected by the intervention. We interviewed central level stakeholders from donor agencies, national health policy levels, public, non-governmental, and research sectors to identify scale-up mechanisms. We interviewed community health workers, policy makers, and non-governmental stakeholders, to explore the feasibility and acceptability of implementing the suggested mechanisms. We discussed scale-up options in focus groups with community members who had attended a community-led intervention. We iteratively developed our data collection tools based on our analysis and re-interviewed some participants. We analysed the data deductively using a stakeholder analysis framework, and inductively from codes identified in the data. RESULTS: Despite interest in addressing NCDs, there was a lack of a clear community engagement strategy at the government level, and most interventions have been implemented by non-governmental organisations. Many felt the Ministry of Health and Family Welfare should lead on community engagement, and NCD screening and referral has been added to the responsibilities of community health workers and health volunteers. Yet there remains a focus on reproductive health and NCD diagnosis and referral instead of prevention at the community level. There is potential to engage health volunteers in community-led interventions, but their present focus on engaging women for reproductive health does not fit with community needs for NCD prevention. CONCLUSIONS: Research highlighted the need for a preventative community engagement strategy to address NCDs, and the potential to utilise existing cadres to scale-up community-led interventions. It will be important to work with key stakeholders to address gender issues and ensure flexibility and responsiveness to community concerns. We indicate areas for further implementation research to develop scaled-up models of community-led interventions to address NCDs.

Intermediate hyperglycaemia, diabetes and blood pressure in rural Bangladesh: five-year post-randomisation follow-up of the DMagic cluster-randomised controlled trial.

Background: The DMagic trial showed that participatory learning and action (PLA) community mobilisation delivered through facilitated community groups, and mHealth voice messaging interventions improved diabetes knowledge in Bangladesh and the PLA intervention reduced diabetes occurrence. We assess intervention effects three years after intervention activities stopped. Methods: Five years post-randomisation, we conducted a cross-sectional survey among a random sample of adults aged ≥30-years living in the 96 DMagic villages, and a cohort of individuals identified with intermediate hyperglycaemia at the start of the DMagic trial in 2016. Primary outcomes were: 1) the combined prevalence of intermediate hyperglycaemia and diabetes; 2) five-year cumulative incidence of diabetes among the 2016 cohort of individuals with intermediate hyperglycaemia. Secondary outcomes were: weight, BMI, waist and hip circumferences, blood pressure, knowledge and behaviours. Primary analysis compared outcomes at the cluster level between intervention arms relative to control. Findings: Data were gathered from 1623 (82%) of the randomly selected adults and 1817 (87%) of the intermediate hyperglycaemia cohort. 2018 improvements in diabetes knowledge in mHealth clusters were no longer observable in 2021. Knowledge remains significantly higher in PLA clusters relative to control but no difference in primary outcomes of intermediate hyperglycaemia and diabetes prevalence (OR (95%CI) 1.23 (0.89, 1.70)) or five-year incidence of diabetes were observed (1.04 (0.78, 1.40)). Hypertension (0.73 (0.54, 0.97)) and hypertension control (2.77 (1.34, 5.75)) were improved in PLA clusters relative to control. Interpretation: PLA intervention effect on intermediate hyperglycaemia and diabetes was not sustained at 3 years after intervention end, but benefits in terms of blood pressure reduction were observed. Funding: Medical Research Council UK: MR/M016501/1 (DMagic trial); MR/T023562/1 (DClare study), under the Global Alliance for Chronic Diseases (GACD) Diabetes and Scale-up Programmes, respectively.

Community participatory learning and action cycle groups to reduce type 2 diabetes in Bangladesh (D:Clare): an updated study protocol for a parallel arm cluster randomised controlled trial.

The "Diabetes: Community-led Awareness, Response and Evaluation" (D:Clare) trial aims to scale up and replicate an evidence-based participatory learning and action cycle intervention in Bangladesh, to inform policy on population-level T2DM prevention and control.The trial was originally designed as a stepped-wedge cluster randomised controlled trial, with the interventions running from March 2020 to September 2022. Twelve clusters were randomly allocated (1:1) to implement the intervention at months 1 or 12 in two steps, and evaluated through three cross-sectional surveys at months 1, 12 and 24. However, due to the COVID-19 pandemic, we suspended project activities on the 20th of March 2020. As a result of the changed risk landscape and the delays introduced by the COVID-19 pandemic, we changed from the stepped-wedge design to a wait-list parallel arm cluster RCT (cRCT) with baseline data. We had four key reasons for eventually agreeing to change designs: equipoise, temporal bias in exposure and outcomes, loss of power and time and funding considerations.Trial registration ISRCTN42219712 . Registered on 31 October 2019.

Magnetic activation of TREK1 triggers stress signalling and regulates neuronal branching in SH-SY5Y cells.

TWIK-related K+ 1 (TREK1) is a potassium channel expressed in the nervous system with multiple functions including neurotransmission and is a prime pharmacological target for neurological disorders. TREK1 gating is controlled by a wide range of external stimuli including mechanical forces. Previous work has demonstrated that TREK1 can be mechano-activated using magnetic nanoparticles (MNP) functionalised with antibodies targeted to TREK1 channels. Once the MNP are bound, external dynamic magnetic fields are used to generate forces on the TREK channel. This approach has been shown to drive cell differentiation in cells from multiple tissues. In this work we investigated the effect of MNP-mediated TREK1 mechano-activation on early stress response pathways along with the differentiation and connectivity of neuronal cells using the model neuronal cell line SH-SY5Y. Results showed that TREK1 is well expressed in SH-SY5Y and that TREK1-MNP initiate c-Myc/NF-κB stress response pathways as well as Nitrite production after magnetic stimulation, indicative of the cellular response to mechanical cues. Results also showed that TREK1 mechano-activation had no overall effect on neuronal morphology or expression of the neuronal marker ßIII-Tubulin in Retinoic Acid (RA)/Brain-derived Neurotrophic factor (BDNF) differentiated SH-SY5Y but did increase neurite number. These results suggest that TREK1 is involved in cellular stress response signalling in neuronal cells, which leads to increased neurite production, but is not involved in regulating RA/BDNF mediated neuronal differentiation.

Equity impact of participatory learning and action community mobilisation and mHealth interventions to prevent and control type 2 diabetes and intermediate hyperglycaemia in rural Bangladesh: analysis of a cluster randomised controlled trial.

BACKGROUND: A cluster randomised trial of mHealth and participatory learning and action (PLA) community mobilisation interventions showed that PLA significantly reduced the prevalence of intermediate hyperglycaemia and type 2 diabetes mellitus (T2DM) and the incidence of T2DM among adults in rural Bangladesh; mHealth improved knowledge but showed no effect on glycaemic outcomes. We explore the equity of intervention reach and impact. METHODS: Intervention reach and primary outcomes of intermediate hyperglycaemia and T2DM were assessed through interview surveys and blood fasting glucose and 2-hour oral glucose tolerance tests among population-based samples of adults aged ≥30 years. Age-stratified, gender-stratified and wealth-stratified intervention effects were estimated using random effects logistic regression. RESULTS: PLA participants were similar to non-participants, though female participants were younger and more likely to be married than female non-participants. Differences including age, education, wealth and marital status were observed between individuals exposed and those not exposed to the mHealth intervention.PLA reduced the prevalence of T2DM and intermediate hyperglycaemia in all age, gender and wealth strata. Reductions in 2-year incidence of T2DM of at least 51% (0.49, 95% CI 0.26 to 0.92) were observed in all strata except among the oldest and least poor groups. mHealth impact on glycaemic outcomes was observed only among the youngest group, where a 47% reduction in the 2-year incidence of T2DM was observed (0.53, 95% CI 0.28 to 1.00). CONCLUSION: Large impacts of PLA across all strata indicate a highly effective and equitable intervention. mHealth may be more suitable for targeting higher risk, younger populations. TRIAL REGISTRATION NUMBER: ISRCTN41083256.

Learning from a diabetes mHealth intervention in rural Bangladesh: what worked, what did not and what next?

There is an urgent need for population-based interventions to slow the growth of the diabetes epidemic in low-and middle-income countries. We tested the effectiveness of a population-based mHealth voice messaging intervention for T2DM prevention and control in rural Bangladesh through a cluster randomised controlled trial. mHealth improved knowledge and awareness about T2DM but there was no detectable effect on T2DM occurrence. We conducted mixed-methods research to understand this result. Exposure to messages was limited by technological faults, high frequency of mobile phone number changes, message fatigue and (mis)perceptions that messages were only for those who had T2DM. Persistent social norms, habits and desires made behaviour change challenging, and participants felt they would be more motivated by group discussions than mHealth messaging alone. Engagement with mHealth messages for T2DM prevention and control can be increased by (1) sending identifiable messages from a trusted source (2) using participatory design of mHealth messages to inform modelling of behaviours and increase relevance to the general population (3) enabling interactive messaging. mHealth messaging is likely to be most successful if implemented as part of a multi-sectoral, multi-component approach to address T2DM and non-communicable disease risk factors.

Changes in non-communicable diseases, diet and exercise in a rural Bangladesh setting before and after the first wave of COVID-19.

Prevalence of non-communicable diseases (NCDs) is high in rural Bangladesh. Given the complex multi-directional relationships between NCDs, COVID-19 infections and control measures, exploring pandemic impacts in this context is important. We conducted two cross-sectional surveys of adults ≥30-years in rural Faridpur district, Bangladesh, in February to March 2020 (survey 1, pre-COVID-19), and January to March 2021 (survey 2, post-lockdown). A new random sample of participants was taken at each survey. Anthropometric measures included: blood pressure, weight, height, hip and waist circumference and fasting and 2-hour post-glucose load blood glucose. An interviewer-administered questionnaire included: socio-demographics; lifestyle and behavioural risk factors; care seeking; self-rated health, depression and anxiety assessments. Differences in NCDs, diet and exercise were compared between surveys using chi2 tests, logistic and linear regression; sub-group analyses by gender, age and socio-economic tertiles were conducted. We recruited 950 (72.0%) participants in survey 1 and 1392 (87.9%) in survey 2. The percentage of the population with hypertension increased significantly from 34.5% (95% CI: 30.7, 38.5) to 41.5% (95% CI: 38.2, 45.0; p-value = 0.011); the increase was more pronounced in men. Across all measures of self-reported health and mental health, there was a significant improvement between survey 1 and 2. For self-rated health, we observed a 10-point increase (71.3 vs 81.2, p-value = 0.005). Depression reduced from 15.3% (95% CI: 8.4, 26.1) to 6.0% (95% CI: 2.7, 12.6; p-value = 0.044) and generalised anxiety from 17.9% (95% CI: 11.3, 27.3) to 4.0% (95% CI: 2.0, 7.6; p-value<0.001). No changes in fasting blood glucose, diabetes status, BMI or abdominal obesity were observed. Our findings suggest both positive and negative health outcomes following COVID-19 lockdown in a rural Bangladeshi setting, with a concerning increase in hypertension. These findings need to be further contextualised, with prospective assessments of indirect effects on physical and mental health and care-seeking.

Care-seeking and managing diabetes in rural Bangladesh: a mixed methods study.

BACKGROUND: Type 2 diabetes mellitus poses a major health challenge worldwide and in low-income countries such as Bangladesh, however little is known about the care-seeking of people with diabetes. We sought to understand the factors that affect care-seeking and diabetes management in rural Bangladesh in order to make recommendations as to how care could be better delivered. METHODS: Survey data from a community-based random sample of 12,047 adults aged 30 years and above identified 292 individuals with a self-reported prior diagnosis of diabetes. Data on health seeking practices regarding testing, medical advice, medication and use of non-allopathic medicine were gathered from these 292 individuals. Qualitative semi-structured interviews and focus group discussions with people with diabetes and semi-structured interviews with health workers explored care-seeking behaviour, management of diabetes and perceptions on quality of care. We explore quality of care using the WHO model with the following domains: safe, effective, patient-centred, timely, equitable and efficient. RESULTS: People with diabetes who are aware of their diabetic status do seek care but access, particularly to specialist diabetes services, is hindered by costs, time, crowded conditions and distance. Locally available services, while more accessible, lack infrastructure and expertise. Women are less likely to be diagnosed with diabetes and attend specialist services. Furthermore costs of care and dissatisfaction with health care providers affect medication adherence. CONCLUSION: People with diabetes often make a trade-off between seeking locally available accessible care and specialised care which is more difficult to access. It is vital that health services respond to the needs of patients by building the capacity of local health providers and consider practical ways of supporting diabetes care. TRIAL REGISTRATION: ISRCTN41083256 . Registered on 30/03/2016.

Community participatory learning and action cycle groups to reduce type 2 diabetes in Bangladesh (D:Clare trial): study protocol for a stepped-wedge cluster randomised controlled trial.

BACKGROUND: An estimated 463 million people globally have diabetes, with the prevalence growing in low-and middle-income settings, such as Bangladesh. Given the need for context-appropriate interventions to prevent type 2 diabetes mellitus (T2DM), the 'Diabetes: Community-led Awareness, Response and Evaluation' (D:Clare) trial will rigorously evaluate the replication and scale-up of a participatory learning and action (PLA) cycle intervention in Bangladesh, to inform policy on population-level T2DM prevention and control. METHODS: This is a stepped-wedge cluster randomised controlled trial, with integrated process and economic evaluations, conducted from March 2020 to September 2022. The trial will evaluate a community-based four-phase PLA cycle intervention focused on prevention and control of T2DM implemented over 18 months, against a control of usual care. Twelve clusters will be randomly allocated (1:1) to implement the intervention at project month 1 or 12. The intervention will be evaluated through three cross-sectional surveys at months 1, 12 and 24. The trial will be conducted in Alfadanga Upazila, Faridpur district, with an estimated population of 120,000. Clusters are defined as administrative geographical areas, with approximately equal populations. Each of the six unions in Alfadanga will be divided into two clusters, forming 12 clusters in total. Given the risk of inter-cluster contamination, evaluation surveys will exclude villages in border areas. Participants will be randomly sampled, independently for each survey, from a population census conducted in January 2020. The primary outcome is the combined prevalence of intermediate hyperglycaemia and T2DM, measured through fasting and 2-h post-glucose load blood tests. A total of 4680 participants provide 84% power to detect a 30% reduction in the primary outcome, assuming a baseline of 30% and an ICC of 0.07. The analysis will be by intention-to-treat, comparing intervention and control periods across all clusters, adjusting for geographical clustering. DISCUSSION: This study will provide further evidence of effectiveness for community-based PLA to prevent T2DM at scale in a rural Bangladesh setting. However, we encountered several challenges in applying the stepped-wedge design to our research context, with particular consideration given to balancing seasonality, timing and number of steps and estimation of partial versus full effect. TRIAL REGISTRATION: ISRCTN: ISRCTN42219712 . Registered on 31 October 2019.

Parallelized Manipulation of Adherent Living Cells by Magnetic Nanoparticles-Mediated Forces.

The remote actuation of cellular processes such as migration or neuronal outgrowth is a challenge for future therapeutic applications in regenerative medicine. Among the different methods that have been proposed, the use of magnetic nanoparticles appears to be promising, since magnetic fields can act at a distance without interactions with the surrounding biological system. To control biological processes at a subcellular spatial resolution, magnetic nanoparticles can be used either to induce biochemical reactions locally or to apply forces on different elements of the cell. Here, we show that cell migration and neurite outgrowth can be directed by the forces produced by a switchable parallelized array of micro-magnetic pillars, following the passive uptake of nanoparticles. Using live cell imaging, we first demonstrate that adherent cell migration can be biased toward magnetic pillars and that cells can be reversibly trapped onto these pillars. Second, using differentiated neuronal cells we were able to induce events of neurite outgrowth in the direction of the pillars without impending cell viability. Our results show that the range of forces applied needs to be adapted precisely to the cellular process under consideration. We propose that cellular actuation is the result of the force on the plasma membrane caused by magnetically filled endo-compartments, which exert a pulling force on the cell periphery.

Participatory learning and action to address type 2 diabetes in rural Bangladesh: a qualitative process evaluation.

BACKGROUND: Diabetes is 7th largest cause of death worldwide, and prevalence is increasing rapidly in low-and middle-income countries. There is an urgent need to develop and test interventions to prevent and control diabetes and develop the theory about how such interventions can be effective. We conducted a participatory learning and action (PLA) intervention with community groups in rural Bangladesh which was evaluated through a cluster randomised controlled trial. There was a large reduction in the combined prevalence of type 2 diabetes and intermediate hyperglycaemia in the PLA group compared with the control group. We present findings from qualitative process evaluation research to explore how this intervention was effective. METHODS: We conducted group interviews and focus group discussions using photovoice with purposively sampled group attenders and non-attenders, and intervention implementers. Data were collected before the trial analysis. We used inductive content analysis to generate theory from the data. RESULTS: The intervention increased the health literacy of individuals and communities - developing their knowledge, capacity and self-confidence to enact healthy behaviours. Community, household and individual capacity increased through social support and social networks, which then created an enabling community context, further strengthening agency and enabling community action. This increased opportunities for healthy behaviour. Community actions addressed lack of awareness about diabetes, gendered barriers to physical activity and lack of access to blood glucose testing. The interaction between the individual, household, and community contexts amplified change, and yet there was limited engagement with macro level, or 'state', barriers to healthy behaviour. CONCLUSIONS: The participatory approach enabled groups to analyse how context affected their ability to have healthy behaviours and participants engaged with issues as a community in the ways that they felt comfortable. We suggest measuring health literacy and social networks in future interventions and recommend specific capacity strengthening to develop public accountability mechanisms and health systems strengthening to complement community-based interventions. TRIAL REGISTRATION: Registered at ISRCTN on 30th March 2016 (Retrospectively Registered) Registration number: ISRCTN41083256 .

Gendered perceptions of physical activity and diabetes in rural Bangladesh: a qualitative study to inform mHealth and community mobilization interventions.

Background Diabetes prevalence is increasing rapidly in Bangladesh, and there is an urgent need to promote preventive behaviours for type 2 diabetes, such as maintaining a healthy body weight, eating healthily, avoiding tobacco and being active for 150 minutes per week. Methods We used a qualitative methodology informed by the capability, opportunity, motivation theory of behaviour change to explore the factors affecting physical activity among men and women in rural Bangladesh. We conducted semi-structured interviews and focus group discussions with 64 purposively sampled participants with and without diabetes, and five health workers. From the results of descriptive content analysis, we identified key capabilities, opportunities and motivations to engage with in our mHealth and community mobilization interventions. Results Men and women without diabetes lacked awareness about the need to remain physically active to prevent diabetes, and most felt that their activity levels were sufficient. Housework was not commonly perceived as physical activity among all respondents. These knowledge and capability gaps could be addressed through mHealth messaging and community mobilization providing information on sufficiency and types of physical activity to prevent and control diabetes. Men were physically active while working outside the home, whereas women felt unsafe and conspicuous, and were constrained by family commitments and social expectations of appropriate behaviour. Women engaged in strategies to protect their own and their family's reputations. These opportunity factors affecting physical activity indicated the need for strategies developed through participatory processes to challenge unhealthy gender norms and increase women's safety. Conclusion Formative research data can enable the development of contextually relevant interventions. Data show that mHealth interventions should consider gendered barriers to physical activity, tailoring information to meet men's and women's needs, and that community mobilization interventions should enable unhealthy, gendered community norms to be challenged. Participatory interventions can enable communities to push the boundaries of socially acceptable behaviours to increase physical activity, helping to prevent and control diabetes.

Implementation and fidelity of a participatory learning and action cycle intervention to prevent and control type 2 diabetes in rural Bangladesh.

INTRODUCTION: There is an urgent need to address the growing type 2 diabetes disease burden. 20-30% of adults in rural areas of Bangladesh have intermediate hyperglycaemia and about 10% have diabetes. We report on the implementation and fidelity of a Participatory Learning and Action (PLA) intervention, evaluated through a three-arm cluster randomised controlled trial which reduced the incidence of diabetes and intermediate hyperglycaemia in rural Bangladesh. PLA interventions have been effective in addressing population level health problems in low income country contexts, and therefore we sought to use this approach to engage communities to identify and address community barriers to prevention and control of type 2 diabetes. METHODS: We used a mixed methods approach collecting quantitative data through field reports and qualitative data through observations and focus group discussions. Through descriptive analysis, we considered fidelity to the participatory approach and implementation plans. RESULTS: One hundred twenty-two groups per month were convened by 16 facilitators and supervised by two coordinators. Groups worked through a four phase PLA cycle of problem identification, planning together, implementation and evaluation to address the risk factors for diabetes - diet, physical activity, smoking and stress. Groups reported a lack of awareness about diabetes prevention and control, the prohibitive cost of care and healthy eating, and gender barriers to exercise for women. Groups set targets to encourage physical activity, kitchen-gardening, cooking with less oil, and reduced tobacco consumption. Anti-tobacco committees operated in 90 groups. One hundred twenty-two groups arranged blood glucose testing and 74 groups organized testing twice. Forty-one women's groups established funds, and 61 communities committed not to ridicule women exercising. Experienced and committed supervisors enabled fidelity to a participatory methodology. A longer intervention period and capacity building could enable engagement with systems barriers to behaviour change. CONCLUSION: Our complex intervention was implemented as planned and is likely to be valid in similar contexts given the flexibility of the participatory approach to contextually specific barriers to prevention and control of type 2 diabetes. Fidelity to the participatory approach is key to implementing the intervention and effectively addressing type 2 diabetes in a low-income country.

Developing a theory-driven contextually relevant mHealth intervention.

Background: mHealth interventions have huge potential to reach large numbers of people in resource poor settings but have been criticised for lacking theory-driven design and rigorous evaluation. This paper shares the process we developed when developing an awareness raising and behaviour change focused mHealth intervention, through applying behavioural theory to in-depth qualitative research. It addresses an important gap in research regarding the use of theory and formative research to develop an mHealth intervention. Objectives: To develop a theory-driven contextually relevant mHealth intervention aimed at preventing and managing diabetes among the general population in rural Bangladesh. Methods: In-depth formative qualitative research (interviews and focus group discussions) were conducted in rural Faridpur. The data were analysed thematically and enablers and barriers to behaviour change related to lifestyle and the prevention of and management of diabetes were identified. In addition to the COM-B (Capability, Opportunity, Motivation-Behaviour) model of behaviour change we selected the Transtheoretical Domains Framework (TDF) to be applied to the formative research in order to guide the development of the intervention. Results: A six step-process was developed to outline the content of voice messages drawing on in-depth qualitative research and COM-B and TDF models. A table to inform voice messages was developed and acted as a guide to scriptwriters in the production of the messages. Conclusions: In order to respond to the local needs of a community in Bangladesh, a process of formative research, drawing on behavioural theory helped in the development of awareness-raising and behaviour change mHealth messages through helping us to conceptualise and understand behaviour (for example by categorising behaviour into specific domains) and subsequently identify specific behavioural strategies to target the behaviour.

Community groups or mobile phone messaging to prevent and control type 2 diabetes and intermediate hyperglycaemia in Bangladesh (DMagic): a cluster-randomised controlled trial.

BACKGROUND: Strategies are needed to prevent and control type 2 diabetes and intermediate hyperglycaemia, which together affect roughly a third of adults in Bangladesh. We aimed to assess the effects of mHealth and community mobilisation on the prevalence of intermediate hyperglycaemia and diabetes among the general adult population in rural Bangladesh, and to assess the effect of these interventions on the incidence of type 2 diabetes among people with intermediate hyperglycaemia within the study population. METHODS: DMagic was a three-arm, cluster-randomised trial of participatory community mobilisation, mHealth mobile phone messaging, and usual care (control) in 96 villages (population roughly 125 000) in Bangladesh. Community mobilisation involved 18 monthly group meetings, led by lay facilitators, applying a participatory learning and action (PLA) cycle focused on diabetes prevention and control. mHealth involved twice-weekly voice messages over 14 months promoting behaviour change to reduce diabetes risk. The primary outcomes were the combined prevalence of type 2 diabetes and intermediate hyperglycaemia in the overall population at the end of the intervention implementation period, and 2-year cumulative incidence of type 2 diabetes in a cohort with intermediate hyperglycaemia at baseline. Primary outcomes were assessed through fasting blood glucose concentrations and 2-h oral glucose tolerance tests among a cross-section of adults aged 30 years and older and a cohort of individuals identified with intermediate hyperglycaemia. Prevalence findings are based on a cross-sectional survey at the end of the study; incidence findings are based on 2-year follow-up survey of a cohort of individuals identified with intermediate hyperglycaemia through a cross-sectional survey at baseline. We also assessed the cost-effectiveness of the interventions. This trial is registered with the ISRCTN registry, number ISRCTN41083256, and is completed. FINDINGS: The study took place between June 27, 2015, and June 28, 2018, with the PLA intervention running in 32 villages from June, 2016, to December, 2017, and the mHealth intervention running in 32 villages from Oct 21, 2016, to Dec 24, 2017. End-of study prevalence was assessed in 11 454 individuals and incidence in 2100 individuals. There was a large reduction in the combined prevalence of type 2 diabetes and intermediate hyperglycaemia in the PLA group compared with the control group at the end of the study (adjusted [for stratification, clustering, and wealth] odds ratio [aOR] 0·36 [0·27-0·48]), with an absolute reduction of 20·7% (95% CI 14·6-26·7). Among 2470 adults with intermediate hyperglycaemia at baseline, 2100 (85%) were followed-up at 2 years. The 2-year cumulative incidence of diabetes in this cohort was significantly lower in the PLA group compared with control (aOR 0·39, 0·24-0·65), representing an absolute incidence reduction of 8·7% (3·5-14·0). There was no evidence of effect of mHealth on combined prevalence of intermediate hyperglycaemia and diabetes (aOR 0·93, 0·74-1·16) or the incidence of diabetes (1·02, 0·73-1·43). The incremental cost-effectiveness ratios for PLA were INT$316 per case of intermediate hyperglycaemia or type 2 diabetes prevented and $6518 per case of type 2 diabetes prevented among individuals with intermediate hyperglycaemia. INTERPRETATION: Our data provide strong evidence to support the use of community mobilisation based on PLA to prevent type 2 diabetes in this rural Bangladeshi population. Despite raising knowledge and awareness of diabetes, the mHealth intervention did not change disease outcomes in our population. Replication studies in other populations should be a priority. FUNDING: UK Medical Research Council.

Magnetic Mechanoactivation of Wnt Signaling Augments Dopaminergic Differentiation of Neuronal Cells.

Wnt signaling is a key developmental pathway that regulates dopaminergic progenitor cell proliferation and differentiation during neuronal development. This makes Wnt signaling an important therapeutic target for neurodegenerative conditions such as Parkinson's disease. Wnt signaling can be modulated using peptides such as UM206, which bind to the Wnt receptor Frizzled. Previous work has demonstrated remote activation of the Wnt pathway through Frizzled using peptide-functionalized magnetic nanoparticles (MNPs) with magnetic field stimulation. Using this technology, Wnt signaling is remotely activated in the neuronal cell line SH-SY5Y, and the phenotypic response to stimulation is assessed. Results indicate ß-catenin translocalization and activation of TCF/LEF responsive transcription in response to MNP and magnetic fields, which result in dopaminergic marker expression when synergistically combined with differentiation factors retinoic acid and the phorbol ester phorbol 12-myristate 13-acetate. This approach is translated into ex vivo postnatal rat brain slices modeling the developing nigrostriatal pathway. Dopaminergic marker expression is maintained in MNP-labeled SH-SY5Y cells after injection and magnetic stimulation. These results demonstrate the translational value of remote control of signal transduction for controlling neuronal precursor cell behavior and highlight the potential applications for controlled cell differentiation as part of cell therapies for neurodegenerative disease.

Distribution of diabetes, hypertension and non-communicable disease risk factors among adults in rural Bangladesh: a cross-sectional survey.

BACKGROUND: Non-communicable diseases (NCDs) are increasing in low-income settings. We conducted a survey of risk factors, blood pressure and blood glucose in rural Bangladesh and assessed variations by age, sex and wealth. METHODS: We surveyed a random sample of 12 280 adults aged >30 years in 96 villages in rural Bangladesh. Fieldworkers measured blood glucose and conducted an insulin tolerance test with a repeat blood test 120 min post glucose ingestion. Blood pressure, anthropometric, socioeconomic, lifestyle and behavioural risk factors data were also collected. Data were analysed to describe the prevalence of diabetes, intermediate hyperglycaemia, hypertension and NCD risk factors by age, sex and wealth. RESULTS: Women had higher levels of overweight or obesity and lower levels of physical activity and fruit and vegetable consumption than men; 63% of men used tobacco compared with 41.3% of women. Overweight or obesity and abdominal obesity (waist to hip ratio) increased with socioeconomic status (least poor vs most poor: OR (95% CI) 3.21 (2.51 to 4.11) for men and 2.83 (2.28 to 3.52) for women). Tobacco use, passive smoke exposure and salt consumption fell with increasing socioeconomic status in both sexes. Clustering of risk factors showed more than 70% of men and women reported at least three risk factors. Women in the least poor group were 33% more likely to have three or more risk factors compared with women in the most poor group (1.33 (95% CI 1.17 to 1.58)). The combined prevalence of impaired fasting glucose, impaired glucose tolerance and diabetes was 26.1% among men and 34.9% among women, and increased with age. The prevalence of prehypertension and hypertension was 30.7% and 15.9% among men and 27.2% and 22.5% among women, with similar rising prevalence with age. CONCLUSION: NCD risk factors, hyperglycaemia and raised blood pressure are an immediate health threat in rural Bangladesh. Initiatives to improve detection, treatment and prevention strategies are needed.

Protocol of economic evaluation and equity impact analysis of mHealth and community groups for prevention and control of diabetes in rural Bangladesh in a three-arm cluster randomised controlled trial.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is one of the leading causes of death and disability worldwide, generating substantial economic burden for people with diabetes and their families, and to health systems and national economies. Bangladesh has one of the largest numbers of adults with diabetes in the South Asian region. This paper describes the planned economic evaluation of a three-arm cluster randomised control trial of mHealth and community mobilisation interventions to prevent and control T2DM and non-communicable diseases' risk factors in rural Bangladesh (D-Magic trial). METHODS AND ANALYSIS: The economic evaluation will be conducted as a within-trial analysis to evaluate the incremental costs and health outcomes of mHealth and community mobilisation interventions compared with the status quo. The analyses will be conducted from a societal perspective, assessing the economic impact for all parties affected by the interventions, including implementing agencies (programme costs), healthcare providers, and participants and their households. Incremental cost-effectiveness ratios (ICERs) will be calculated in terms of cost per case of intermediate hyperglycaemia and T2DM prevented and cost per case of diabetes prevented among individuals with intermediate hyperglycaemia at baseline and cost per mm Hg reduction in systolic blood pressure. In addition to ICERs, the economic evaluation will be presented as a cost-consequence analysis where the incremental costs and all statistically significant outcomes will be listed separately. Robustness of the results will be assessed through sensitivity analyses. In addition, an analysis of equity impact of the interventions will be conducted. ETHICS AND DISSEMINATION: The approval to conduct the study was obtained by the University College London Research Ethics Committee (4766/002) and by the Ethical Review Committee of the Diabetic Association of Bangladesh (BADAS-ERC/EC/t5100246). The findings of this study will be disseminated through different means within academia and the wider policy sphere. TRIAL REGISTRATION NUMBER: ISRCTN41083256; Pre-results.

Diabetes knowledge and care practices among adults in rural Bangladesh: a cross-sectional survey.

BACKGROUND: Population knowledge of how to prevent, detect and control diabetes is critical to public health initiatives to tackle the disease. We undertook a cross-sectional survey of adults in rural Bangladesh to estimate knowledge and practices related to diabetes. METHODS: In 96 villages in Faridpur district, trained fieldworkers surveyed 12 140 randomly selected men and women aged ≥30. They collected data on sociodemographic status, knowledge of diabetes and history of blood and urine glucose testing. Fasting and 2-hour post-glucose load capillary blood tests ascertained the diabetic status of respondents. Levels of knowledge and practices were analysed by sociodemographic characteristics and diabetic status. RESULTS: The population showed low levels of diabetes knowledge overall, with only one in three adults able to report any valid causes of the disease. Knowledge of diabetes causes, symptoms, complications, prevention and control was significantly associated with age, education, wealth and employment. Only 14% of respondents reported ever having had a blood glucose test and strong associations with wealth were observed (least poor relative to most poor 2.91 (2.32-3.66)). 78.4% of known diabetics (ie, with a prior diagnosis) reported that they did not monitor their blood glucose levels on at least a monthly basis. However, they had better knowledge of the causes (odds relative to normoglycaemic individuals 1.62 (1.23-2.09)), symptoms (5.17 (3.41-7.82)), complications (5.18 (3.75-7.14)), prevention (4.18 (3.04-5.74)) and control (8.43 (4.83-14.71)). CONCLUSION: Knowledge of diabetes among rural adults in Faridpur is extremely poor. Levels of diabetes testing are low and monitoring of blood glucose among known diabetics infrequent. Diabetes prevention and control efforts in this population must include large-scale awareness initiatives which focus not only on high-risk individuals but the whole population. TRIAL REGISTRATION NUMBER: ISRCTN41083256; Pre-results.

Growth and body composition of children aged 2-4 years after exposure to community mobilisation women's groups in Bangladesh.

BACKGROUND: Women's groups interventions in Bangladesh reduced neonatal deaths by 38% and improved hygienic delivery, newborn care practices and breast feeding. We explore the longer-term impact of exposure to women's groups during pregnancy on child growth at 2-4 years. METHODS: We performed a cross-sectional survey of child anthropometric measures (analysed as z-scores) among children born to women who had participated in the women's groups interventions while pregnant, compared with an age-matched and sex-matched sample of children born to control mothers. Results were stratified by maternal body mass index (BMI) and adjusted for possible confounding effects of maternal education, household asset ownership and, in a separate model, mother-child height difference, a proxy for improved survival of small babies in intervention groups. RESULTS: Data were obtained from 2587 mother-child pairs (91% response). After adjustment for asset ownership, maternal education and potential survival effects, children whose mothers were exposed to the women's group intervention had higher head (0.16 (0.04 to 0.28)), mid-upper arm (0.11 (0.04 to 0.19)), abdominal (0.13 (0.00 to 0.26)) and chest (0.18 (0.08 to 0.29)) circumferences than their control counterparts. No significant differences in subcutaneous fat (subscapular and triceps skinfold thickness) were observed. When stratified by maternal BMI, intervention children had higher weight, BMI and circumferences, and these effects decreased with increasing maternal BMI category. CONCLUSIONS: Women's groups appear to have had a lasting, positive impact on child anthropometric outcomes, with most significant results clustering in children of underweight mothers. Observed differences are likely to be of public health significance in terms of the nutritional and metabolic development of children.