Anthropometric, biochemical, dietary, morbidity and well-being assessments in women and children in Indonesia, India and Senegal: a UKRI GCRF Action Against Stunting Hub protocol paper.

INTRODUCTION: Child stunting has a complex aetiology, especially in the first 1000 days of life. Nutrition interventions alone have not produced expected impacts in reducing/preventing child stunting, indicating the importance of understanding the complex interplay between environmental, physiological and psychological factors influencing child nutritional status. This study will investigate maternal and child nutrition, health and well-being status and associated factors through the assessment of: (1) anthropometry, (2) biomarkers of nutrition and health status, (3) dietary intakes, (4) fetal growth and development, (5) infant morbidity, (6) infant and young child feeding (IYCF) and (7) perinatal maternal stress, depression and social support. METHODS: This study will be conducted in a prospective pregnancy cohort in India, Indonesia and Senegal. Pregnant women will be recruited in the second (Indonesia, Senegal) and third (India) trimester of pregnancy, and the mother and infant dyads followed until the infant is 24 months of age. During pregnancy, anthropometric measures will be taken, venous blood samples will be collected for biochemical assessment of nutrition and health status, dietary intakes will be assessed using a 4-pass-24-hour dietary recall method (MP24HR), fetal ultrasound for assessment of fetal growth. After birth, anthropometry measurements will be taken, venous blood samples will be collected, MP24HR will be conducted, infant morbidity and IYCF practices will be assessed and a sample of breastmilk will be collected for nutrient composition analyses. Perinatal maternal stress, depression, social support and hair cortisol levels (stress) will be measured. The results from this study will be integrated in an interdisciplinary analysis to examine factors influencing infant growth and inform global efforts in reducing child stunting. ETHICS AND DISSEMINATION: Ethical approval was granted by the Ethics Committee of the London School of Hygiene and Tropical Medicine (17915/RR/17513); National Institute of Nutrition (ICMR)-Ministry of Health and Family Welfare, Government of India (CR/04/I/2021); Health Research Ethics Committee, University of Indonesia and Cipto Mangunkusumo Hospital (KET-887/UN2.F1/ETIK/PPM.00.02/2019); and the Comité National d'Ethique pour la Recherche en Santé, Senegal (Protocole SEN19/78); the Royal Veterinary College (URN SR2020-0197) and the International Livestock Research Institute Institutional Research Ethics Committee (ILRI-IREC2020-33). Results will be published in peer-reviewed journals and disseminated to policy-makers and participating communities.

Eggs for Improving Nutrition, cognitive development and reducing linear growth retardation among Infants and young Children (ENRICH): protocol of an egg supplementation trial among children aged 9-18 months in Hyderabad, India.

INTRODUCTION: Evidence on the impact of nutrient-rich animal source foods such as eggs for improving child growth and cognition is inconsistent. This study aims to examine the impact of an egg intervention in children, along with behaviour change communication (BCC) to the mother, on linear growth and cognition, and nutritional status in children aged 9-18 months. METHODS AND ANALYSIS: A 9-month open-labelled randomised controlled trial will be conducted in three urban slums in Hyderabad, India, as a substudy of an observational cohort study (n=350) following pregnant women and their children until 18 months of age in a population at risk of stunting. The children born to women enrolled during the third trimester of pregnancy will be block randomised in a 1:4 ratio into the intervention (n=70) and control (n=280) groups. Children in the intervention group will be supplemented with one egg per day starting from 9 months until 18 months of age. BCC designed to enhance adherence to the intervention will be used. The control group will be a part of the observational cohort and will not receive any intervention from the study team. The primary outcome will be length-for-age z-scores, and the secondary outcomes will include cognition, blood biomarkers of nutritional status including fatty acid profile and epigenetic signatures linked with linear growth and cognition. Multivariate intention-to-treat analyses will be conducted to assess the effect of the intervention. ETHICS AND DISSEMINATION: The study is approved by the Institutional ethics committees of ICMR-National Institute of Nutrition, Hyderabad, India and London School of Hygiene and Tropical Medicine, UK. The results will be published in peer-reviewed journals and disseminated to policy-makers. Findings will also be shared with study participants and community leaders. TRIAL REGISTRATION NUMBER: CTRI/2021/11/038208.

Impact of SARS-CoV-2 infection and mitigation strategy during pregnancy on prenatal outcome, growth and development in early childhood in India: a UKRI GCRF Action Against Stunting Hub protocol paper.

INTRODUCTION: The COVID-19 pandemic has offset some of the gains achieved in global health, particularly in relation to maternal, child health and nutrition. As pregnancy is a period of plasticity where insults acting on maternal environment have far-reaching consequences, the pandemic has had a significant impact on prenatal outcomes, intrauterine and postnatal development of infants. This research will investigate both the direct and indirect impacts of the COVID-19 pandemic during pregnancy on prenatal outcomes, growth and development in early childhood. METHODS AND ANALYSIS: Community and hospital data in Hyderabad and Gujarat, India will be used to recruit women who were pregnant during the COVID-19 pandemic and contracted SARS-CoV-2 infection. In comparison with women who were pregnant around the same time and did not contract the virus, the study will investigate the impact of the pandemic on access to healthcare, diet, nutrition, mental health and prenatal outcomes in 712 women (356 per study arm). Children born to the women will be followed prospectively for an 18-month period to investigate the impact of the pandemic on nutrition, health, growth and neurocognition in early childhood. ETHICS AND DISSEMINATION: Ethics approval was granted from the institutional ethics committees of the Indian Institute of Public Health Gandhinagar (SHSRC/2021/2185), Indian Council of Medical Research-National Institute of Nutrition (EC/NEW/INST/2021/1206), and London School of Hygiene and Tropical Medicine (72848). The findings of the study will be disseminated to policy and research communities through engagements, scientific conferences, seminars, and open-access, peer-reviewed publication.

Investigating market-based opportunities for the provision of nutritious and safe diets to prevent childhood stunting: a UKRI-GCRF action against stunting hub protocol paper.

BACKGROUND: Inadequate access to affordable, safe, desirable and convenient nutrient-dense food is one of the underlying causes of child stunting. While targeted nutrition-sensitive interventions (eg, backyard 'nutri-gardens') may increase dietary diversity within farming households, such interventions have limited scalability across the wider food system where markets remain underdeveloped. This research aims to develop and assess market-based interventions for key nutrient-dense foods to help improve the diets of women and children in the first 1000 days of life. METHODS: Data collection uses four parallel approaches in each of the three study countries (India, Indonesia and Senegal). (1) A novel food environment tool will be developed to characterise the accessibility and affordability of nutrient-dense foods in the study countries. The tool will be validated through pretesting using cognitive interviewing and piloting in purposively sampled households, 10 (cognitive interviewing) and 30 (piloting) households in each country; (2) stakeholder interviews (eg, with producers, intermediaries and retailers) will be conducted to map out nutrition-sensitive entry points of key value chains (eg, animal-sourced foods), before hotspots of potential food safety hazards will be identified from food samples collected along the chains; (3) the Optifood and Agrifood tools will be used to identify foods that can address food system nutrient gaps and engage key stakeholders to prioritise market interventions to improve nutrition outcomes. Optifood and Agrifood parameters will be informed by publicly available data, plus interviews and focus groups with value chain stakeholders; (4) informed by the previous three approaches and a campaign of participatory 'group model building', a novel system dynamics model will evaluate the impact of alternative market-based solutions on the availability and affordability of nutrient-dense foods over time. ETHICS AND DISSEMINATION: The study has received ethical approval in the United Kingdom, Senegal, Indonesia and India. Dissemination comprises peer-reviewed journals, international disciplinary conferences and multistakeholder dissemination workshops.

The role of loneliness on hearing ability and dementia: A novel mediation approach.

BACKGROUND: To determine the potential mediating role of loneliness in the relationship between hearing ability and dementia. METHODS: Design: Longitudinal observational study. SETTING: English Longitudinal Study of Ageing (ELSA). PARTICIPANTS: Individuals aged 50 and older (N = 4232). MEASUREMENTS: Self-reported hearing ability and loneliness were assessed from Wave 2 (2004-2005) to Wave 7 (2014-2015) of ELSA. Dementia cases were ascertained via self- or carer-report or dementia medication at these waves. The medeff command in Stata version 17 was used to do cross-section mediation analysis between hearing ability, loneliness, and dementia (Waves 3-7). Path-specific effects proportional (cause-specific) hazard models were then used to investigate longitudinal mediation (Waves 2-7). RESULTS: In cross-sectional analyses in Wave 7 alone, loneliness only mediated 5.4% of the total effects of limited hearing on dementia (indirect effects = increased risk of 0.06%; 95% CI: 0.002%-0.15%) under limited hearing and 0.04% (95% CI: 0.001%-0.11%) under normal hearing). In longitudinal analyses, there was no statistical evidence of a mediating role for loneliness in explaining the relationship between hearing ability and time-to-dementia (indirect effect estimate hazard ratio = 1.01 (95% CI: 0.99-1.05). CONCLUSION: In this community-dwelling sample of English adults, there is a lack of evidence that loneliness mediates the relationship between hearing ability and dementia in both cross-sectional and longitudinal analyses. However, as the number of dementia cases in this cohort was low, replication in other cohorts with larger sample sizes is required to confirm the absence of a mediated effect via loneliness.

Longitudinal mediation analysis of time-to-event endpoints in the presence of competing risks.

This proposal is motivated by an analysis of the English Longitudinal Study of Ageing (ELSA), which aims to investigate the role of loneliness in explaining the negative impact of hearing loss on dementia. The methodological challenges that complicate this mediation analysis include the use of a time-to-event endpoint subject to competing risks, as well as the presence of feedback relationships between the mediator and confounders that are both repeatedly measured over time. To account for these challenges, we introduce path-specific effect proportional (cause-specific) hazard models. These extend marginal structural proportional (cause-specific) hazard models to enable effect decomposition on either the cause-specific hazard ratio scale or the cumulative incidence function scale. We show that under certain ignorability assumptions, the path-specific direct and indirect effects indexing this model are identifiable from the observed data. We next propose an inverse probability weighting approach to estimate these effects. On the ELSA data, this approach reveals little evidence that the total effect of hearing loss on dementia is mediated through the feeling of loneliness, with a non-statistically significant indirect effect equal to 1.01 (hazard ratio (HR) scale; 95% confidence interval (CI) 0.99 to 1.05).

Vision Impairment and Risk of Dementia: Findings from the English Longitudinal Study of Ageing.

OBJECTIVES: To determine whether vision impairment is independently associated cross-sectionally and longitudinally with dementia. DESIGN: Retrospective cohort study. SETTING: English Longitudinal Study of Ageing. PARTICIPANTS: Individuals aged 50 and older MEASUREMENTS: Cross-sectional association between self-rated vision (poor or blind, moderate, normal) and dementia was analyzed, adjusting for potential confounders (sex, wealth, education, cardiovascular risk factors) using multivariable logistic regression. We also modelled the adjusted longitudinal association between vision impairment and dementia over an average of 11 years of follow-up using Cox proportional hazards regression for individuals aged 50 to 69 and those aged 70 and older. RESULTS: After adjustment for confounders, participants who rated their vision as moderate were 2.0 (95% confidence interval (CI)=1.4-3.1) times as likely as those with normal vision to have dementia, and those who rated their vision as poor were 4.0 (95% CI=2.6-6.1) times as likely. Longitudinally, individuals aged 50 to 69 who rated their vision as moderate (1.8, 95% CI=1.0-3.0) or poor (3.6, 95% CI=1.1-11.8) were at greater risk of developing dementia than those who rated their vision as normal. There was no significant difference in risk in those aged 70 and older. CONCLUSION: Our study confirms and extends findings from other countries, demonstrating cross-sectional associations between moderate and poor self-rated vision and dementia in England in all participants aged 50 and older and longitudinally over an 11-year period in those aged 50 to 69. These results help establish vision loss as a risk factor for dementia, although it is unclear why. Research is needed to determine whether screening and treatment for vision loss may slow cognitive decline.

Walking Speed, Cognitive Function, and Dementia Risk in the English Longitudinal Study of Ageing.

OBJECTIVES: To determine the relationships between walking speed, cognitive function, and the interaction between changes in these measures and dementia risk. DESIGN: Longitudinal observational study. SETTING: English Longitudinal Study of Ageing. PARTICIPANTS: Individuals aged 60 and older (N=3,932). MEASUREMENTS: Walking speed and cognition were assessed at Waves 1 (2002-03) and 2 (2004-05) of the English Longitudinal Study of Ageing. New dementia cases were assessed from Wave 3 (2006-07) to Wave 7 (2014-15). The associations were modelled using Cox proportional hazards regression. RESULTS: Participants with faster baseline walking speeds were at lower risk of developing dementia (hazard ratio (HR)=0.36, 95% confidence interval (CI)=0.22-0.60). Those with a greater decline in walking speed from Wave 1 to 2 were at greater risk of developing dementia (HR=1.23, 95% CI=1.03-1.47). Participants with better baseline cognition (HR=0.42, 95% CI=0.34-0.54) were at lower risk of developing dementia. Those with a greater decline in cognition from Wave 1 to 2 were at greater risk of developing dementia (HR=1.78, 95% CI=1.53-2.06). Change in walking speed and change in cognition did not have an interactive effect on dementia risk (HR=1.01, 95% CI=0.88-1.17). CONCLUSION: In this community-dwelling sample of English adults, those with slower walking speeds and a greater decline in speed over time were at greater risk of developing dementia independent of changes in cognition. Further research is required to understand the mechanisms that may drive these associations.

Factors influencing recording of drug misuse in primary care: a qualitative study of GPs in England.

BACKGROUND: Drug misuse is a serious public health problem. Evidence from previous epidemiological studies show that GPs are recording drug misuse in electronic patient records (EPR). However, although the recording trends are similar to national surveys, recording rates are much lower. AIM: To explore the factors that influence GPs to record drug misuse in the EPR, and to gain a clearer understanding of the gap between the amount of drug misuse recorded in primary care and that in national surveys and other studies. DESIGN AND SETTING: A semi-structured qualitative interview study of GPs working in general practices across England. METHOD: Purposive sampling was employed to recruit 12 GPs, both with and without a special interest in drug misuse, from across England. Semi-structured face-to-face interviews were conducted to consider whether and why GPs record drug misuse, which methods GPs use for recording, GPs' actions if a patient asks for the information not to be recorded, and GPs' actions if they think a patient misuses drugs but does not disclose the information. Resulting data were analysed using a combination of inductive and deductive thematic analysis. RESULTS: The complexity of asking about drug misuse preceded GPs' decision to record. They described how the context of the general practice protocols, interaction between GP and patient, and the questioning process affected whether, how, and in which circumstances they asked about drug use. This led to GPs making a clinical decision on whether, who, and how to record in the EPR. CONCLUSION: When making decisions about whether or not to record drug misuse, GPs face complex choices. Aside from their own views, they reported feelings of pressure from the general practice environment in which they worked and their clinical commissioning group, as well as government policies.