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Polygenic prediction of body mass index and obesity through the life course and across ancestries.
Get PDFPolygenic scores (PGSs) for body mass index (BMI) may guide early prevention and targeted treatment of obesity. Using genetic data from up to 5.1 million people (4.6% African ancestry, 14.4% American ancestry, 8.4% East Asian ancestry, 71.1% European ancestry and 1.5% South Asian ancestry) from the GIANT consortium and 23andMe, Inc., we developed ancestry-specific and multi-ancestry PGSs. The multi-ancestry score explained 17.6% of BMI variation among UK Biobank participants of European ancestry. For other populations, this ranged from 16% in East Asian-Americans to 2.2% in rural Ugandans. In the ALSPAC study, children with higher PGSs showed accelerated BMI gain from age 2.5 years to adolescence, with earlier adiposity rebound. Adding the PGS to predictors available at birth nearly doubled explained variance for BMI from age 5 onward (for example, from 11% to 21% at age 8). Up to age 5, adding the PGS to early-life BMI improved prediction of BMI at age 18 (for example, from 22% to 35% at age 5). Higher PGSs were associated with greater adult weight gain. In intensive lifestyle intervention trials, individuals with higher PGSs lost modestly more weight in the first year (0.55 kg per s.d.) but were more likely to regain it. Overall, these data show that PGSs have the potential to improve obesity prediction, particularly when implemented early in life
Brazil's Bolsa Família conditional cash transfer and child malnutrition: a nationwide birth cohort study.
Get PDFINTRODUCTION: Poverty amplifies the risk of malnutrition, which is particularly harmful to children as it can perpetuate a cycle of poverty and poor health. This study aims to assess the association of a conditional cash transfer programme (Bolsa Família Program (BFP)) with child nutrition nationwide in Brazil. METHODS: We used the Centre for Data and Knowledge Integration for Health Birth Cohort (baseline data from the National Registry for Social Programmes (CadÚnico) linked with live births and nutrition registries) to conduct a longitudinal population-based study between 2008 and 2015. This cohort study followed children from birth until 5 years old between 1 January 2008 and 31 December 2015. Children exposed were those who received the BFP benefit at any time during follow-up and were compared with those who never received it. Malnutrition outcomes were assessed using height-for-age, weight-for-height and body mass index-for-age z-scores classified according to WHO cut-offs. Binary and multinomial logistic regressions and kernel-based matching were performed. Subgroup analyses considered maternal education and urban/rural areas of residence. RESULTS: Our cohort included 3 116 138 children born in Brazil between 2008 and 2015. BFP participation was associated with a 17% lower chance of stunting (OR 0.83; 95% CI 0.81 to 0.85). Additionally, BFP was associated with a 19% higher chance of wasting (OR 1.19; 95% CI 1.16 to 1.22). The protective association with stunting was more pronounced in children from less-educated mothers (OR 0.75; 95% CI 0.70 to 0.81) and those living in rural areas (OR 0.77; 95% CI 0.73 to 0.81). BFP participation was associated with higher overweight/obesity among children from mothers with 8 or more years of education and living in urban areas, while those with 3 or fewer years of education and living in rural areas experienced protective effects. CONCLUSION: Our findings suggest a complex relationship between BFP participation and child malnutrition outcomes. The study underscores BFP participation's benefits in child nutritional outcomes, emphasising the programme's potential to reduce stunting in all children and to reduce overweight/obesity in the most vulnerable ones. However, BFP was also associated with an increased risk of overweight/obesity, which may be a consequence of overlapping stages of Brazil's rapid nutrition transition, a scenario that contributes to the double burden of malnutrition. Further research is needed to understand this finding better
"My Little Son, My Everything": Comparative Caregiving and Emotional Bonds in Dog and Child Parenting.
Get PDFDogs are often viewed as family members, and many owners describe them as "fur babies." However, little is known about how women with and without children perceive and practice caregiving toward their dogs, and how these experiences relate to parenting. This qualitative study explored the meanings of dog and child caregiving among 28 dog-owning women (13 mothers and 15 childless) through semi-structured interviews. All participants had lived with their dog for at least one year. Thematic analysis identified five main themes: (1) emotional meanings and motivations of caregiving, (2) practical caregiving and daily routines, (3) responsibility and dependency, (4) social relationships and support, and (5) life course perspectives. Both mothers and non-mothers described their dogs as sources of joy, companionship, and unconditional love. Women without children often saw their dogs as child substitutes, while mothers stressed the greater responsibility and permanence of raising children. Dog ownership and parenting influenced social life and work differently: dogs often increased social interaction and offered flexibility, whereas children introduced stricter routines and reduced spontaneity. Overall, dogs fulfilled important emotional and caregiving needs, particularly among women without children, but did not replace the unique social and moral responsibilities of parenting
Effect of smoking on drug-resistant tuberculosis treatment outcomes and potential mechanistic pathways: a multicountry cohort study.
No full textBACKGROUND: People who smoke are at increased risk of unfavourable tuberculosis treatment outcomes compared with those who do not, but the pathways that explain this disparity are unclear. OBJECTIVE: To estimate the difference in a successful end-of-treatment outcome by smoking status among people with multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) and to examine if this difference changes if people who smoked had the same retention in treatment as those who did not smoke. DESIGN AND METHODS: Using data from the prospective endTB Observational Study, we estimated the difference in treatment success by cigarette smoking status, adjusting for baseline confounders including demographics, social history and comorbidities. To examine how this difference changed if everyone was retained in treatment, we censored participants who were lost to follow-up and applied inverse probability of censoring weights to simulate this scenario. RESULTS: Among 1786 participants in 12 countries, 539 (30.2%) reported smoking at least one cigarette daily. People who smoked were more frequently found in post-Soviet countries and had a complex social history (eg, incarceration and substance use) and infectious comorbidities (eg, hepatitis C). At the end of treatment, 73.5% of people who smoked and 80.3% of people who did not smoke had treatment success (risk difference in percentage points: -6.8, 95% CI -11.1 to -2.6). After adjusting for baseline confounders, the risk difference was similar (-5.2 percentage points), but the 95% CI was less precise (-14.1 to 3.2). When simulating a scenario in which everyone was retained in treatment, the risk difference was attenuated (-1.9 percentage points; 95% CI -11.1 to 4.7). CONCLUSION: People who smoked had a lower frequency of MDR/RR-TB treatment success than those who did not smoke. Eliminating loss to follow-up reduced this difference by smoking status, suggesting that pathways related to retention in treatment were a major driver of this disparity
Disability-Inclusive Poverty Graduation (DIG) Evidence Brief
Get PDFThe need: There are 1.3 billion people with disabilities
globally, making up 16% of the world’s population [1].
People with disabilities are much more likely to
experience poverty, economic deprivation, limited
access to resources, and barriers to social inclusion
[2-4]. In low- and middle-income countries, these
challenges are compounded by a lack of
interventions tailored to their needs. Consequently, a
focus on disability-inclusive poverty reduction is
needed to achieve the Sustainable Development
Goal (SDG) to “end poverty in all its forms
everywhere”.
The Disability-Inclusive Poverty Graduation (DIG)
programme was adapted from a proven Ultra-Poor
Graduation model, which has improved the
livelihoods of people living in poverty in over 50
countries. DIG uses a multi-pronged approach to
poverty alleviation for ultra-poor households,
focusing on individuals with disabilities and women.
This brief summarises the findings from the trial of
effectiveness of DIG, conducted in Uganda
The Estimand Framework and Causal Inference: Complementary Not Competing Paradigms.
Get PDFThe creation of the ICH E9 (R1) estimands framework has led to more precise specification of the treatment effects of interest in the design and statistical analysis of clinical trials. However, it is unclear how the new framework relates to causal inference, as both approaches appear to define what is being estimated and have a quantity labeled an estimand. Using illustrative examples, we show that both approaches can be used to define a population-based summary of an effect on an outcome for a specified population and highlight the similarities and differences between these approaches. We demonstrate that the ICH E9 (R1) estimand framework offers a descriptive, structured approach that is more accessible to non-mathematicians, facilitating clearer communication of trial objectives and results. We then contrast this with the causal inference framework, which provides a mathematically precise definition of an estimand and allows the explicit articulation of assumptions through tools such as causal graphs. Despite these differences, the two paradigms should be viewed as complementary rather than competing. The combined use of both approaches enhances the ability to communicate what is being estimated. We encourage those familiar with one framework to appreciate the concepts of the other to strengthen the robustness and clarity of clinical trial design, analysis, and interpretation
School Meals Case Study: Sweden
Get PDFThis school meals case study forms part of a collection led by the Research Consortium for School Health and Nutrition’s "Good Examples" Community of Practice. The School Meals Case Study of Sweden serves to document how the national school meals programme is organized, funded, and monitored throughout the country. The objectives of this case study include presenting an introduction to the country profile, outlining the design and implementation of school feeding programmes, describing their monitoring and evaluation processes, and highlighting lessons learned, best practices, and challenges. This case study is written as a working paper, and can be updated to reflect evolving circumstances. The ‘Good Examples’ Community of Practice supports the evidence generation of the Research Consortium for School Health and Nutrition, the evidence-generating arm of the School Meals Coalition. The Research Consortium’s objective is to carry out independent research across diverse sectors and generate solid, compelling, and actionable evidence regarding the benefits of school food programs to inform evidence-based decision-making on school health and nutrition policies and practices
Impact of Cerebral Embolic Protection on Cognitive Function After Transcatheter Aortic Valve Implantation: Data From the BHF PROTECT-TAVI Randomized Trial.
No full textBACKGROUND: In addition to the risk of stroke, patients undergoing transcatheter aortic valve implantation (TAVI) are susceptible to a decline of neurocognitive function. This may occur because of embolization of material (eg, valve or calcium) to the brain. Cerebral embolic protection (CEP) devices are engineered to capture this debris, potentially mitigating its incidence. METHODS: This is a secondary analysis of the BHF PROTECT-TAVI trial (British Heart Foundation Randomized Trial of Routine Cerebral Embolic Protection in Transcatheter Aortic Valve Implantation), in which participants with aortic stenosis from across 33 centers in the United Kingdom were randomly assigned at a 1:1 ratio to undergo TAVI with a CEP device (SENTINEL, Boston Scientific; SENTINEL CEP group) or TAVI without a CEP device (control group). This analysis is restricted to those who underwent cognitive assessment. The primary outcome was the mean change in the telephone version of the Montreal Cognitive Assessment (t-MoCA) between baseline and 6 to 8 weeks after TAVI. The secondary outcome was a ≥3-point drop in total t-MoCA score between baseline and 6 to 8 weeks after TAVI. RESULTS: A total of 3535 participants, 1763 in the SENTINEL CEP group and 1772 in the control group (mean age 81.0 years, 37.7% women) randomized in BHF PROTECT-TAVI were included in the modified intention-to-treat population for this analysis. The median t-MoCA at presentation was 18 (interquartile range, 16-20). The median t-MoCA at 6 to 8 weeks was 20 (interquartile range, 17-21). The mean change in total t-MoCA score between baseline and 6 to 8 weeks adjusted for the baseline score was 0.83 (95% CI, 0.70-0.96) in the SENTINEL CEP group and 0.91 (95% CI, 0.79-1.04) in the control group. There was no difference in means between the treatment groups (-0.07 [95% CI, -0.22 to 0.09], P=0.42). The incidence of a ≥3-point drop in the total t-MoCA score was 154 of 1763 (8.7%) in the SENTINEL CEP group and 142 of 1772 (8.0%) in the control group. The corresponding risk difference was 0.72% (95% CI, -1.10 to 2.55; P=0.44). These findings were robust to sensitivity analyses. There was no evidence of an interaction between treatment assignment and any of the subgroups assessed. CONCLUSIONS: In the BHF PROTECT-TAVI trial, the use of CEP did not impact cognition after TAVI. REGISTRATION: URL: https://www.isrctn.com; Unique identifier: ISRCTN16665769
Systematic review of barriers to and enablers of tuberculosis diagnosis, notification, and intervention for designing customised intervention package to minimise 'missing millions' in tribal communities of India.
No full textBACKGROUND: Tribal communities in India experience a very high burden of tuberculosis (TB), estimated at 7030 per million. The diagnosis and notification gaps are substantial, partly due to the geographical remoteness of these populations. Within an overarching study to design an intervention for finding the 'missing millions' among tribal communities, we conducted a systematic review to identify the barriers and enablers of tuberculosis diagnosis and notification, with the aim of developing a contextually relevant intervention. METHODS: We searched PubMed, Embase and Web of Science using terms related to TB, diagnosis, notification, barriers, enablers, and interventions. Studies from lower- and lower-middle-income countries (LICs and LMICs) published between 2000-2023 were included. Qualitative and quantitative studies were assessed using the Critical Appraisal Skills Programme tool and Newcastle Ottawa scale, respectively. Narrative and thematic analyses were performed, applying the socio-ecological model (SEM) to categorise barriers and enablers of diagnosis and notification, and the consolidated framework for implementation research (CFIR) to assess intervention implementation. RESULTS: Thirty-four eligible studies from 15 LICs and LMICs were included in the review. At community level, limited knowledge, illiteracy, stigma, geographical inaccessibility, and financial constraints were key barriers of diagnosis. At health system level, active case finding was the major intervention; however, inadequate diagnostic facilities, shortage of trained staff, insufficient incentives, weak counselling, and inadequate budget were the major barriers. Reported enablers were: increasing awareness about TB in the community to reduce stigma, encouragement from family members and TB survivors, mobilising human resources, regular capacity-building and monetary incentives to health workers. CONCLUSIONS: This systematic review identified barriers and enablers at multiple levels of the SEM and CFIR frameworks. To addressed the interconnected challenges, multifaceted and context-specific strategies are essential. Approaches that combine community engagement along with health system strengthening are essential for reducing the diagnosis and notification gaps among tribal populations. REGISTRATION: PROSPERO: CRD42023439841
Accelerated forgetting in presymptomatic Alzheimer’s: mediation by prefrontal cortical degeneration
Get PDFIn Alzheimer’s disease (AD), accelerated long-term forgetting (ALF), where information is retained normally over 10–30 min but lost at an accelerated rate over subsequent days to weeks, develops several years before symptom onset. However, the neuroanatomical changes underpinning ALF remain undetermined. Eighteen presymptomatic autosomal dominant AD mutation carriers and 12 non-carriers underwent ALF assessment with a list, a story, and visual figure, testing 30-min and 7-day recall of each, separately. T1 and diffusion-weighted MRI were acquired. Cortical thickness was estimated for 13 pre-defined grey matter regions, with streamline tractography assessing associated structural connectivity. In mutation carriers, lower verbal ALF performance (list and story) was strongly associated with thinner prefrontal cortex (PFC) across four contiguous regions bilaterally. This association was absent in non-carriers. No associations were found between ALF and the thickness/volume of medial temporal lobe (MTL) structures. The association between ALF and PFC connectivity was weaker than for cortical thickness. Our results suggest that early subtle pathological change in PFC underpins ALF development, highlighting the central role of PFC dysfunction in very early AD-related cognitive decline. ALF may represent a qualitatively different (non-MTL driven) form of forgetting compared with the short interval forgetting that develops at later disease stages