Mapping multimorbidity progression among 190 diseases.

BACKGROUND: Current clustering of multimorbidity based on the frequency of common disease combinations is inadequate. We estimated the causal relationships among prevalent diseases and mapped out the clusters of multimorbidity progression among them. METHODS: In this cohort study, we examined the progression of multimorbidity among 190 diseases among over 500,000 UK Biobank participants over 12.7 years of follow-up. Using a machine learning method for causal inference, we analyzed patterns of how diseases influenced and were influenced by others in females and males. We used clustering analysis and visualization algorithms to identify multimorbidity progress constellations. RESULTS: We show the top influential and influenced diseases largely overlap between sexes in chronic diseases, with sex-specific ones tending to be acute diseases. Patterns of diseases that influence and are influenced by other diseases also emerged (clustering significance Pau > 0.87), with the top influential diseases affecting many clusters and the top influenced diseases concentrating on a few, suggesting that complex mechanisms are at play for the diseases that increase the development of other diseases while share underlying causes exist among the diseases whose development are increased by others. Bi-directional multimorbidity progress presents substantial clustering tendencies both within and across International Classification Disease chapters, compared to uni-directional ones, which can inform future studies for developing cross-specialty strategies for multimorbidity. Finally, we identify 10 multimorbidity progress constellations for females and 9 for males (clustering stability, adjusted Rand index >0.75), showing interesting differences between sexes. CONCLUSION: Our findings could inform the future development of targeted interventions and provide an essential foundation for future studies seeking to improve the prevention and management of multimorbidity.

Mapping out clusters of diseases is crucial to addressing the rising challenge of co-occurrence of multiple diseases, known as multimorbidity. However, the current way of grouping diseases based on their associations isn't enough to understand how they develop over time. We've come up with a new approach to map out how groups of diseases progress together based on the strength of their causal relationships. By looking at how each disease affects the development of others, we can get a better understanding of how they form clusters. Our research goes beyond just showing which diseases occur together, and it's a step toward improving how we prevent and manage multiple health conditions in the future.

Involving different stakeholders in prioritising outcomes to assess healthcare systems response for type 1 diabetes management: Using co-creation approaches in Peru.

BACKGROUND: Engaging diverse stakeholders in developing core outcome sets (COSs) can produce more meaningful metrics as well as research responsive to patient needs. The most common COS prioritisation method, Delphi surveys, has limitations related to selection bias and participant understanding, while qualitative methods like group discussions are less frequently used. This study aims to test a co-creation approach to COS development for type 1 diabetes (T1DM) in Peru. METHODS: Using a co-creation approach, we aimed to prioritise outcomes for T1DM management in Peru, incorporating perspectives from people with T1DM, caregivers, healthcare professionals, and decision-makers. A set of outcomes were previously identified through a systematic review and qualitative evidence synthesis. Through qualitative descriptive methods, including in-person workshops, each group of stakeholders contributed to the ranking of outcomes. Decision-makers also discussed the feasibility of measuring these outcomes within the Peruvian healthcare system. RESULTS: While priorities varied among participant groups, all underscored the significance of monitoring healthcare system functionality over mortality. Participants recognized the interconnected nature of healthcare system performance, clinical outcomes, self-management, and quality of life. When combining the rankings from all the groups, metrics related to economic impact on the individual and structural support, policies promoting health, and protecting those living with T1DM were deemed more important in comparison to measuring clinical outcomes. CONCLUSION: We present the first COS for T1DM focused on low-and-middle-income countries and show aspects of care that are relevant in this setting. Diverse prioritisation among participant groups underscores the need of inclusive decision-making processes. By incorporating varied perspectives, healthcare systems can better address patient needs and enhance overall care quality.

Research Translation to Promote Urban Health in Latin America: The SALURBAL Experience.

In highly urbanized and unequal Latin America, urban health and health equity research are essential to effective policymaking. To ensure the application of relevant and context-specific evidence to efforts to reduce urban health inequities, urban health research in Latin America must incorporate strategic research translation efforts. Beginning in 2017, the Urban Health in Latin America (SALURBAL) project implemented policy-relevant research and engaged policymakers and the public to support the translation of research findings. Over 6 years, more than 200 researchers across eight countries contributed to SALURBAL's interdisciplinary network. This network allowed SALURBAL to adapt research and engagement activities to local contexts and priorities, thereby maximizing the policy relevance of research findings and their application to promote policy action, inform urban interventions, and drive societal change. SALURBAL achieved significant visibility and credibility among academic and nonacademic urban health stakeholders, resulting in the development of evidence and tools to support urban policymakers, planners, and policy development processes across the region. These efforts and their outcomes reveal important lessons regarding maintaining flexibility and accounting for local context in research, ensuring that resources are dedicated to policy engagement and dissemination activities, and recognizing that assessing policy impact requires a nuanced understanding of complex policymaking processes. These reflections are relevant for promoting urban health and health equity research translation across the global south and worldwide. This paper presents SALURBAL's strategy for dissemination and policy translation, highlights innovative initiatives and their outcomes, discusses lessons learned, and shares recommendations for future efforts to promote effective translation of research findings.

Allostasis, health, and development in Latin America.

The lifespan is influenced by adverse childhood experiences that create predispositions to poor health outcomes. Here we propose an allostatic framework of childhood experiences and their impact on health across the lifespan, focusing on Latin American and Caribbean countries. This region is marked by significant social and health inequalities nested in environmental and social stressors, such as exposure to pollution, violence, and nutritional deficiencies, which critically influence current and later-life health outcomes. We review several manifestations across cognition, behavior, and the body, observed at the psychological (e.g., cognitive, socioemotional, and behavioral dysfunctions), brain (e.g., alteration of the development, structure, and function of the brain), and physiological levels (e.g., dysregulation of the body systems and damage to organs). To address the complexity of the interactions between environmental and health-related factors, we present an allostatic framework regarding the cumulative burden of environmental stressors on physiological systems (e.g., cardiovascular, metabolic, immune, and neuroendocrine) related to health across the life course. Lastly, we explore the relevance of this allostatic integrative approach in informing regional interventions and public policy recommendations. We also propose a research agenda, potentially providing detailed profiling and personalized care by assessing the social and environmental conditions. This framework could facilitate the delivery of evidence-based interventions and informed childhood-centered policy-making.

Core outcome sets for trials of interventions to prevent and to treat multimorbidity in low- and middle-income countries: the COSMOS study.

Introduction: The burden of multimorbidity is recognised increasingly in low- and middle-income countries (LMICs), creating a strong emphasis on the need for effective evidence-based interventions. A core outcome set (COS) appropriate for the study of multimorbidity in LMIC contexts does not presently exist. This is required to standardise reporting and contribute to a consistent and cohesive evidence-base to inform policy and practice. We describe the development of two COS for intervention trials aimed at the prevention and treatment of multimorbidity in LMICs. Methods: To generate a comprehensive list of relevant prevention and treatment outcomes, we conducted a systematic review and qualitative interviews with people with multimorbidity and their caregivers living in LMICs. We then used a modified two-round Delphi process to identify outcomes most important to four stakeholder groups with representation from 33 countries (people with multimorbidity/caregivers, multimorbidity researchers, healthcare professionals, and policy makers). Consensus meetings were used to reach agreement on the two final COS. Registration: https://www.comet-initiative.org/Studies/Details/1580. Results: The systematic review and qualitative interviews identified 24 outcomes for prevention and 49 for treatment of multimorbidity. An additional 12 prevention, and six treatment outcomes were added from Delphi round one. Delphi round two surveys were completed by 95 of 132 round one participants (72.0%) for prevention and 95 of 133 (71.4%) participants for treatment outcomes. Consensus meetings agreed four outcomes for the prevention COS: (1) Adverse events, (2) Development of new comorbidity, (3) Health risk behaviour, and (4) Quality of life; and four for the treatment COS: (1) Adherence to treatment, (2) Adverse events, (3) Out-of-pocket expenditure, and (4) Quality of life. Conclusion: Following established guidelines, we developed two COS for trials of interventions for multimorbidity prevention and treatment, specific to LMIC contexts. We recommend their inclusion in future trials to meaningfully advance the field of multimorbidity research in LMICs.

Outcomes measured in studies assessing health systems interventions for type 1 diabetes management: A scoping review.

AIMS: Describe the outcomes reported in research on health systems interventions for type 1 diabetes management in comparison to the outcomes proposed by a core outcome set (COS) for this condition, an essential list of outcomes that studies should measure. METHODS: Systematic search of studies published between 2010 and 2021 reporting health systems interventions directed to improve the management of type 1 diabetes using PubMed, EMBASE and CENTRAL. Information on the outcomes was extracted and classified according to a COS: self-management, level of clinical engagement, perceived control over diabetes, diabetes-related quality of life, diabetes burden, diabetes ketoacidosis, severe hypoglycemia, and glycated hemoglobin (HbA1C). RESULTS: 187 studies were included. Most of the studies included either children (n = 82/187) or adults (n = 82/187) living with type 1 diabetes. The most common outcome measured was HbA1C (n = 149/187), followed by self-management (n = 105/187). While the least measured ones were diabetes ketoacidosis (n = 15/187), and clinical engagement (n = 0/187). None of the studies measured all the outcomes recommended in the COS. Additionally, different tools were found to be used in measuring the same outcome. CONCLUSIONS: This study provides a description of what researchers are measuring when assessing health systems interventions to improve type 1 diabetes management. In contrast to a COS, it was found that there is a predominance of clinical-based outcomes over patient-reported outcome measures.

Assessing pandemic preparedness, response, and lessons learned from the COVID-19 pandemic in four south American countries: agenda for the future.

Introduction: The COVID-19 pandemic emerged in a context that lacked adequate prevention, preparedness, and response (PPR) activities, and global, regional, and national leadership. South American countries were among world's hardest hit by the pandemic, accounting for 10.1% of total cases and 20.1% of global deaths. Methods: This study explores how pandemic PPR were affected by political, socioeconomic, and health system contexts as well as how PPR may have shaped pandemic outcomes in Argentina, Brazil, Colombia, and Peru. We then identify lessons learned and advance an agenda for improving PPR capacity at regional and national levels. We do this through a mixed-methods sequential explanatory study in four South American countries based on structured interviews and focus groups with elite policy makers. Results: The results of our study demonstrate that structural and contextual barriers limited PPR activities at political, social, and economic levels in each country, as well as through the structure of the health care system. Respondents believe that top-level government officials had insufficient political will for prioritizing pandemic PPR and post-COVID-19 recovery programs within their countries' health agendas. Discussion: We recommend a regional COVID-19 task force, post-pandemic recovery, social and economic protection for vulnerable groups, improved primary health care and surveillance systems, risk communication strategies, and community engagement to place pandemic PPR on Argentina, Brazil, Colombia, and Peru and other South American countries' national public health agendas.

Ambient nitrogen dioxide in 47 187 neighbourhoods across 326 cities in eight Latin American countries: population exposures and associations with urban features.

BACKGROUND: Health research on ambient nitrogen dioxide (NO2) is sparse in Latin America, despite the high prevalence of NO2-associated respiratory diseases in the region. This study describes within-city distributions of ambient NO2 concentrations at high spatial resolution and urban characteristics associated with neighbourhood ambient NO2 in 326 Latin American cities. METHODS: We aggregated estimates of annual surface NO2 at 1 km2 spatial resolution for 2019, population counts, and urban characteristics compiled by the SALURBAL project to the neighbourhood level (ie, census tracts). We described the percentage of the urban population living with ambient NO2 concentrations exceeding WHO air quality guidelines. We used multilevel models to describe associations of neighbourhood ambient NO2 concentrations with population and urban characteristics at the neighbourhood and city levels. FINDINGS: We examined 47 187 neighbourhoods in 326 cities from eight Latin American countries. Of the roughly 236 million urban residents observed, 85% lived in neighbourhoods with ambient annual NO2 above WHO guidelines. In adjusted models, higher neighbourhood-level educational attainment, closer proximity to the city centre, and lower neighbourhood-level greenness were associated with higher ambient NO2. At the city level, higher vehicle congestion, population size, and population density were associated with higher ambient NO2. INTERPRETATION: Almost nine out of every ten residents of Latin American cities live with ambient NO2 concentrations above WHO guidelines. Increasing neighbourhood greenness and reducing reliance on fossil fuel-powered vehicles warrant further attention as potential actionable urban environmental interventions to reduce population exposure to ambient NO2. FUNDING: Wellcome Trust, National Institutes of Health, Cotswold Foundation.

Prioritising and planning scale-up research projects targeting non-communicable diseases: a mixed-method study by the Global Alliance for Chronic Diseases upscaling working group.

INTRODUCTION: Governments must scale-up evidence-based interventions to reduce the burden of non-communicable diseases (NCDs). Implementation research can help develop contextually appropriate strategies and optimise interventions for scale-up. We aimed to determine the priorities of the Global Alliance for Chronic Diseases (GACD) 2019 funding round for scale-up research targeting NCD interventions. The research questions were: (a) What was the purpose of the call and what were the specific issues considered by funders when supporting the selected projects? (b) How did the selected research projects align with the objectives of GACD scale-up call? METHODS: We undertook a mixed-methods study to examine the projects funded by the GACD in 2019. We completed semistructured interviews with representatives from 5 out of 8 funding agencies and complemented this by reviewing project documents from 21 (78%) of the 27 funded studies. A literature review of scale-up frameworks informed the interview guide and data extraction template. The transcripts were open-coded using thematic analysis to identify critical issues for funders. Data were extracted to identify the common elements considered when planning, implementing and evaluating interventions for scale-up. RESULTS: Interviews with the funders revealed three enabling themes related to scale-up: local research priorities (contextualisation through engagement), capacity building (developing knowledge base) and connections (networking opportunities). We further identified that timelines (more flexibility) and equity (funding low-income and middle-income researchers) could be considered for future funding investments. Multidisciplinary international research teams led the development of diverse studies to address funder's priorities. The detailed plans included a range of implementation frameworks to help develop contextual scale-up strategies. CONCLUSIONS: Fundamental to NCD scale-up research are (1) funding opportunities that reflect the complexity and time necessary to enable contextualisation; (2) investment in building multidisciplinary research capacity and leadership and (3) better networking to encourage cohesive action and align NCD-related scale-up research activities globally.

"I want to be there for my children": fatherhood, diabetes and temporality among Peruvian men.

Introduction: Living with a chronic condition is a challenging experience, as it can disrupt your capacity to function and fulfill social roles such as being a father. Fatherhood constitutes an important component of masculinity that has not received significant attention in studies aimed at understanding the role of gender norms in health-related behaviors. Fatherhood refers to the set of social expectations placed on men to provide, protect, and care for those considered his children. Our paper aims to show the importance of understanding men's perspectives around fatherhood and its relevance for staying healthy. Methods: In-depth semi-structured interviews with men living with Type 2 diabetes in Peru to explore their experiences with diabetes management. Results: Eighteen Peruvian men, diagnosed with Type 2 diabetes for at least one year and with ages between 27 and 59 years old were interviewed. They had an average of three children each and were all insured under the national insurance plan aimed at low-income groups in Peru. Their accounts described their concern of not being able to fulfill their roles as fathers as a result of their condition. They mentioned the importance of being physically and emotionally present in the lives of their children, taking care of them, and being an example. These concerns varied depending on the age of their children: those with younger children were more preoccupied with ensuring they stayed healthy. Temporality provides a relevant analytical approach to understand the interplay of fatherhood and motivation for diabetes management. Discussion: Our study advances the research around the intersection between health and gender norms and argues that a more nuanced understanding of the construction of masculinity and the relevance of fatherhood in the lives of men could be useful to design and identify better health promotion strategies tailored to men with diabetes.

Chronic Obstructive Pulmonary Disease Self-Management in Three Low- and Middle-Income Countries: A Pilot Randomized Trial.

Objectives: Chronic obstructive pulmonary disease (COPD) disproportionately affects low- and middle-income countries. Health systems are ill prepared to manage the increase in COPD cases. Methods: We performed a pilot effectiveness-implementation randomized field trial of a community health worker (CHW)-supported, 1-year self-management intervention in individuals with COPD grades B-D. The study took place in low-resource settings of Nepal, Peru, and Uganda. The primary outcome was the St. George's Respiratory Questionnaire (SGRQ) score at 1 year. We evaluated differences in moderate to severe exacerbations, all-cause hospitalizations, and the EuroQol score (EQ-5D-3 L) at 12 months. Measurements and Main Results: We randomly assigned 239 participants (119 control arm, 120 intervention arm) with grades B-D COPD to a multicomponent, CHW-supported intervention or standard of care and COPD education. Twenty-five participants (21%) died or were lost to follow-up in the control arm compared with 11 (9%) in the intervention arm. At 12 months, there was no difference in mean total SGRQ score between the intervention and control arms (34.7 vs. 34.0 points; adjusted mean difference, 1.0; 95% confidence interval, -4.2, 6.1; P = 0.71). The intervention arm had a higher proportion of hospitalizations than the control arm (10% vs. 5.2%; adjusted odds ratio, 2.2; 95% confidence interval, 0.8, 7.5; P = 0.15) at 12 months. Conclusions: A CHW-based intervention to support self-management of acute exacerbations of COPD in three resource-poor settings did not result in differences in SGRQ scores at 1 year. Fidelity was high, and intervention engagement was moderate. Although these results cannot differentiate between a failed intervention or implementation, they nonetheless suggest that we need to revisit our strategy. Clinical trial registered with www.clinicaltrials.gov (NCT03359915).

In Utero Exposure to Metals and Birth Outcomes in an Artisanal and Small-Scale Gold Mining Birth Cohort in Madre de Dios, Peru.

BACKGROUND: Few birth cohorts in South America evaluate the joint effect of minerals and toxic metals on neonatal health. In Madre de Dios, Peru, mercury exposure is prevalent owing to artisanal gold mining, yet its effect on neonatal health is unknown. OBJECTIVES: We aimed to determine whether toxic metals are associated with lower birth weight and shorter gestational age independently of antenatal care and other maternal well-being factors. METHODS: Data are from the COhorte de NAcimiento de MAdre de Dios (CONAMAD) birth cohort, which enrolled pregnant women in Madre de Dios prior to their third trimester and obtained maternal and cord blood samples at birth. We use structural equation models (SEMs) to construct latent variables for the maternal metals environment (ME) and the fetal environment (FE) using concentrations of calcium, iron, selenium, zinc, magnesium, mercury, lead, and arsenic measured in maternal and cord blood, respectively. We then assessed the relationship between the latent variables ME and FE, toxic metals, prenatal visits, hypertension, and their effect on gestational age and birth weight. RESULTS: Among 198 mothers successfully enrolled and followed at birth, 29% had blood mercury levels that exceeded the U.S. Centers for Disease Control and Prevention threshold of 5.8µg/L and 2 mothers surpassed the former 5-µg/dL threshold for blood lead. The current threshold value is 3.5µg/dL. Minerals and toxic metals loaded onto ME and FE latent variables. ME was associated with FE (ß=0.24; 95% CI: 0.05, 0.45). FE was associated with longer gestational age (ß=2.31; 95% CI: -0.3, 4.51) and heavier birth weight. Mercury exposure was not directly associated with health outcomes. A 1% increase in maternal blood lead shortened gestational age by 0.05 d (ß=-0.75; 95% CI: -1.51, -0.13), which at the 5-µg/dL threshold resulted in a loss of 3.6 gestational days and 76.5g in birth weight for newborns. Prenatal care visits were associated with improved birth outcomes, with a doubling of visits from 6 to 12 associated with 5.5 more gestational days (95% CI: 1.6, 9.4) and 319g of birth weight (95% CI: 287.6, 350.7). DISCUSSION: Maternal lead, even at low exposures, was associated with shorter gestation and lower birth weight. Studies that focus only on harmful exposures or nutrition may mischaracterize the dynamic maternal ME and FE. SEMs provide a framework to evaluate these complex relationships during pregnancy and reduce overcontrolling that can occur with linear regression. https://doi.org/10.1289/EHP10557.

How Could Taxes on Sugary Drinks and Foods Help Reduce the Burden Of Type 2 Diabetes?

PURPOSE OF REVIEW: Taxes on sugary drinks and foods have emerged as a key strategy to counteract the alarming levels of diabetes worldwide. Added sugar consumption from industrialized foods and beverages has been strongly linked to type 2 diabetes. This review provides a synthesis of evidence on how taxes on sugary products can influence the onset of type 2 diabetes, describing the importance of the different mechanisms through which the consumption of these products is reduced, leading to changes in weight and potentially a decrease in the incidence of type 2 diabetes. RECENT FINDINGS: Observational studies have shown significant reductions in purchases, energy intake, and body weight after the implementation of taxes on sugary drinks or foods. Simulation studies based on the association between energy intake and type 2 diabetes estimated the potential long-term health and economic effects, particularly in low- and middle-income countries, suggesting that the implementation of sugary food and beverage taxes may have a meaningful impact on reducing type 2 diabetes and complications. Public health response to diabetes requires multi-faceted approaches from health and non-health actors to drive healthier societies. Population-wide strategies, such as added sugar taxes, highlight the potential benefits of financial incentives to address behaviors and protective factors to significantly change an individual's health trajectory and reduce the onset of type 2 diabetes worldwide, both in terms of economy and public health.