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OBJECTIVE: To validate AnthropoAge, a new metric of biological age (BA), for prediction of all-cause mortality and age-related outcomes and characterize population-specific aging patterns using multinational longitudinal cohorts. METHODS: We analyzed harmonized multinational data from the Gateway to Global Aging, including studies from the US, England, Mexico, Costa Rica, and China. We used body mass index and waist-to-height ratio to estimate AnthropoAge and AnthropoAgeAccel in participants aged 50-90 years old as proxies of BA and age acceleration, respectively. We compared the predictive capacity for all-cause mortality of AnthropoAge and chronological age (CA) using Cox models, described aging trends in all countries and explored the utility of longitudinal assessments of AnthropoAgeAccel to predict new-onset functional decline and age-related diseases using generalized estimating equations (GEE). FINDINGS: Using data from 55,628 participants, we found AnthropoAge (c-statistic 0.772) outperformed CA (0.76) for prediction of mortality independently of comorbidities, sex, race/ethnicity, education, and lifestyle; this result was replicated in most countries individually except for Mexico. Individuals with accelerated aging had a ~39% higher risk of death, and AnthropoAge also identified trends of faster biological aging per year. In longitudinal analyses, higher AnthropoAgeAccel values were independently predictive of self-reported health deterioration and new-onset deficits in basic/instrumental activities of daily living (ADL/IADL), diabetes, hypertension, cancer, chronic lung disease, myocardial infarction, and stroke. CONCLUSIONS: AnthropoAge is a robust and reproducible BA metric associated with age-related outcomes. Its implementation could facilitate modeling trends of biological aging acceleration in different populations, although recalibration may enhance its utility in underrepresented populations such as individuals from Latin America.

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CONTEXT: Thyroid-stimulating hormone (TSH) trajectory classification represents a novel approach to defining the adequacy of levothyroxine (LT4) treatment for hypothyroidism over time. OBJECTIVE: This is a proof of principle study that uses longitudinal clinical data, including thyroid hormone levels from a large prospective study to define classes of TSH trajectories and examine changes in cardiovascular (CV) health markers over the study period. METHODS: Growth mixture modeling (GMM), including latent class growth analysis (LCGA), was used to classify LT4-treated individuals participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) based on serial TSH levels. Repeated measure analyses were then utilized to assess within-class changes in blood pressure, lipid levels, hemoglobin A1c, and CV-related medication utilization. RESULTS: From the 621 LT4-treated study participants, the best-fit GMM approach identified 4 TSH trajectory classes, as defined by their relationship to the normal TSH range: (1) high-high normal TSH, (2) normal TSH, (3) normal to low TSH, and (4) low to normal TSH. Notably, the average baseline LT4 dose was lowest in the high-high normal TSH group (77.7 µg, P < .001). There were no significant differences in CV health markers between the classes at baseline. At least 1 significant difference in CV markers occurred in all classes, highlighted by the low to normal class, in which total and high-density lipoprotein cholesterol, triglycerides, and A1c all increased significantly (P = .049, P < .001, P < .001, and P = .001, respectively). Utilization of antihypertensive, antihyperlipidemic, and antidiabetes medications increased in all classes. CONCLUSION: GMM/LCGA represents a viable approach to define and examine LT4 treatment by TSH trajectory. More comprehensive datasets should allow for more complex trajectory modeling and analysis of clinical outcome differences between trajectory classes.

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BACKGROUND AND AIMS: Longitudinal studies have revealed that substance use treatment use is often recurrent among patients; the longitudinal patterns and characteristics of those treatment trajectories have received less attention, particularly in the global south. This study aimed to disentangle heterogeneity in treatment use among adult patients in Chile by identifying distinct treatment trajectory groups and factors associated with them. DESIGN: National-level registry-based retrospective cohort. SETTING AND PARTICIPANTS: Adults admitted to publicly funded substance use disorder treatment programs in Chile from November 2009 to November 2010 and followed for 9 years (n = 6266). MEASUREMENTS: Monthly treatment use; type of treatment; ownership of the treatment center; discharge status; primary substance used; sociodemographic. FINDINGS: A seven-class treatment trajectory solution was chosen using latent class growth analysis. We identified three trajectory groups that did not recur and had different treatment lengths: Early discontinuation (32%), Less than a year in treatment (19.7%) and Year-long episode, without recurrence (12.3%). We also identified a mixed trajectory group that had a long first treatment or two treatment episodes with a brief time between treatments: Long first treatment, or immediate recurrence (6.3%), and three recurrent treatment trajectory groups: Recurrent and decreasing (14.2%), Early discontinuation with recurrence (9.9%) and Recurrent after long between treatments period (5.7%). Inpatient or outpatient high intensity (vs. outpatient low intensity) at first entry increased the odds of being in the longer one-episode groups compared with the Early discontinuation group. Women had increased odds of belonging to all the recurrent groups. Using cocaine paste (vs. alcohol) as a primary substance decreased the odds of belonging to long one-episode groups. CONCLUSIONS: In Chile, people in publicly funded treatment for substance use disorder show seven distinct care trajectories: three groups with different treatment lengths and no recurring episodes, a mixed group with a long first treatment or two treatment episodes with a short between-treatment-episodes period and three recurrent treatment groups.

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OBJECTIVE: To investigate the longitudinal association between breastfeeding duration and cardiometabolic health, using repeated measures study design among children and adolescents. STUDY DESIGN: This study included 634 offsprings aged 10 to 21 years (52% female) from the Early Life Exposure in Mexico to Environmental Toxicants birth cohort followed up to four time points during adolescence. Breastfeeding duration was prospectively quantified using questionnaires during early childhood. Cardiometabolic risk factors, body composition, and weight-related biomarkers were assessed as outcomes during adolescent follow-up visits. Sex-stratified linear mixed-effects models were used to model the association between quartiles of breastfeeding duration and outcomes, adjusting for age and additional covariates. RESULTS: Median breastfeeding duration was 7 months (minimum = 0, maximum = 36). Boys in the second quartile (median breastfeeding = 5 months) had lower total fat mass % (ß (SE) -3.2 (1.5) P = .037), and higher lean mass % (3.1 (1.6) P = .049) and skeletal muscle mass % (1.8 (0.8) P = .031) compared with the reference group (median breastfeeding = 2 months). A positive linear trend between breastfeeding duration and trunk lean mass % (0.1 (0.04) P = .035) was found among girls. No association was found with other cardiometabolic indicators. CONCLUSION: Despite sex-specific associations of breastfeeding duration with body composition, there was a lack of substantial evidence for the protective effects of breastfeeding against impaired cardiometabolic health during adolescence among Mexican youth. Further longitudinal studies with a robust assessment of breastfeeding are recommended.

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BACKGROUND AND OBJECTIVES: To examine the role of probable dementia on changes in living arrangements and mortality among very old Mexicans and Mexican Americans in 2 different nations. RESEARCH DESIGN AND METHODS: We employ the Hispanic Established Population for the Epidemiologic Study of the Elderly and the Mexican Health and Aging Study, 2 comparable longitudinal data sets, to identify predictors of changes in living arrangements using multinomial logistic regression, controlling for cognitive status, demographic characteristics, and resources. RESULTS: In Mexico, women with dementia who lived alone at baseline were more likely to become part of an extended family household than men with similar levels of cognitive impairment. A similar pattern emerges for the oldest Mexican-American women. Spousal loss increases the likelihood of living alone for women in the United States regardless of dementia. Although dementia elevates the risk of mortality for men living alone in the United States, in both countries, women in their 90s who lived alone with dementia had a lower risk of mortality relative to men. DISCUSSION AND IMPLICATIONS: Longer life spans increase the risk of living alone with dementia in both countries, especially for women. Older individuals in both countries face financial hardships. Mexicans have limited formal options in dementia care. Mexican Americans with dementia continue to live alone despite low income although, unlike the Mexicans, they have access to Medicaid long-term care. For Mexico and the United States, the growing number of older individuals with dementia represents a growing public health concern.

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OBJECTIVE: To assess the relationship between childhood immunization and mortality risks for nonvaccine-preventable diseases (competing mortality risks, or CMR) in Kenya. STUDY DESIGN: A combination of the Global Burden of Disease and Demographic Health Survey data was used to measure basic vaccination status, CMR, and control variables for each child in the Demographic Health Survey data. A longitudinal analysis was performed. This uses within-mother variation between children to compare the vaccine decisions for different children, who are exposed to different mortality risks. The analysis also distinguishes between overall and disease-specific risks. RESULTS: The study included 15 881 children born between 2009 and 2013, who were at least 12 months old at the time of interview and not part of a twin birth. Mean basic vaccination rates ranged from 27.1% to 90.2% and mean CMR from 13.00 to 738.32 deaths per 100 000 across different counties. A one-unit increase in mortality risk from diarrhea, the most prevalent disease among children in Kenya, is associated with a 1.1 percentage point decline in basic vaccination status. In contrast, mortality risks for other diseases and HIV increase the likelihood of vaccination. The effect of CMR was found to be stronger for children with higher birth orders. CONCLUSIONS: A significant negative correlation between severe CMR and vaccination status was found, which has important implications for immunization policies, particularly in Kenya. Interventions aimed at reducing the most severe CMR, such as diarrhea, and targeted toward multiparous mothers may improve childhood immunization coverage.

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BACKGROUND: intrinsic capacity (IC) is a construct encompassing people's physical and mental abilities. There is an implicit link amongst IC domains: cognition, locomotion, nutrition, sensory and psychological. However, little is known about the integration of the domains. OBJECTIVES: to investigate patterns in the presentation and evolution of IC domain impairments in low-and-middle-income countries and if such patterns were associated with adverse outcomes. METHODS: secondary analyses of the first two waves of the 10/66 study (population-based surveys conducted in eight urban and four rural catchment areas in Cuba, Dominican Republic, Puerto Rico, Venezuela, Peru, Mexico and China). We applied latent transition analysis on IC to find latent statuses (latent clusters) of IC domain impairments. We evaluated the longitudinal association of the latent statuses with the risk of frailty, disability and mortality, and tested concurrent and predictive validity. RESULTS: amongst 14,923 participants included, the four latent statuses were: high IC (43%), low deterioration with impaired locomotion (17%), high deterioration without cognitive impairment (22%), and high deterioration with cognitive impairment (18%). A total of 61% of the participants worsened over time, 35% were stable, and 3% improved to a healthier status.Participants with deteriorated IC had a significantly higher risk of frailty, disability and dementia than people with high IC. There was strong concurrent and predictive validity. (Mortality Hazard Ratio = 4.60, 95%CI 4.16; 5.09; Harrel's C = 0.73 (95%CI 0.72;0.74)). CONCLUSIONS: half of the study population had high IC at baseline, and most participants followed a worsening trend. Four qualitatively different IC statuses or statuses were characterised by low and high levels of deterioration associated with their risk of disability and frailty. Locomotion and cognition impairments showed other trends than psychological and nutrition domains across the latent statuses.

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BACKGROUND AND HYPOTHESIS: Despite accounting for significant disease morbidity in schizophrenia, the neuropathological basis of negative symptoms remains poorly understood and options for treatment limited. Our recent study identified robust associations between diminished auditory cortex (AC) dynamic range and social functioning impairments and negative symptoms in first episode psychosis (FESz). The current investigation examined the progression of these relationships 4-8 months from baseline testing. STUDY DESIGN: Twenty-six FESz and 38 healthy controls (HC) were tested at baseline and follow-up. Magnetoencephalography (MEG) was recorded during binaural presentation of tones (75, 80, and 85 dB). Assessments included the MATRICS cognitive consensus battery (MCCB) and Global Functioning: Role and Social scales (GFR/GFS) and the Positive and Negative Syndrome Scale. STUDY RESULTS: Overall, FESz exhibited a blunted response to increasing tone intensity relative to HC. While this deficit did not change over time at the group level, recovery of right hemisphere AC dynamic range (85-75 dB response) among FESz individuals was associated with reductions in negative symptoms (ρ = -0.50). Diminished dynamic range was also associated with impaired GFS (ρ = 0.65), GFR (ρ = 0.51), and MCCB (ρ = 0.49) at baseline and increased negative symptoms at baseline (ρ = -0.53) and follow-up (ρ = -0.51). CONCLUSION: Despite persistent dynamic range impairment in FESz as a group, individual recovery of this AC response property was associated with significant reduction in negative symptoms. Identification of a functional neural deficit that tracts progression of negative symptoms during a critical period for disease modification is essential to the management of these devastating and historically treatment refractory symptoms.

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BACKGROUND: Labels are a key element of the marketing strategies of infant formula companies, and often include text or images that idealize their use, undermining efforts to promote breastfeeding. RESEARCH AIMS: To evaluate the prevalence of marketing cues that idealize infant formula on labels of products commercialized in Uruguay and to assess changes after a periodic monitoring of compliance with the International Code of Marketing of Breast-Milk Substitutes (IC). METHOD: This study is a descriptive, observational, and longitudinal assessment of the information included on infant formula labels. The first data collection was in 2019, as part of a periodic assessment to monitor the marketing of human-milk substitutes. In 2021, the same products were purchased to evaluate changes in their labels. Thirty-eight products were identified in 2019, of which 33 were still available in 2021. All information available on the labels was analyzed through content analysis. RESULTS: Most products included at least one textual or visual marketing cue idealizing infant formula in both 2019 (n = 30, 91%) and 2021 (n = 29, 88%). This represents a violation of both the IC and national regulations. References to nutritional composition were the most frequent marketing cue, followed by references to child growth and development. No relevant changes were observed after the periodic assessment conducted by the Uruguayan government. CONCLUSIONS: Monitoring compliance with the IC per se cannot be expected to trigger changes in the marketing strategies of infant formula companies. More explicit regulations and strong enforcement mechanisms are needed to end the inappropriate marketing practices on infant formula labels.

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Ageing has been related to the onset of disability and dependency in older adults. There is a need to better understand the disability and dependency trajectories of older adults and their relationship with socio-demographic characteristics and institutional or cultural context. This study analyses the role of age, sex, education and self-perceived health in disability, dependency and death transitions, addressing the heterogeneity across European countries and inconsistencies when using different measures of disability. Multi-state models were adjusted to evaluate the role of risk and protective factors in the transitions to disability, dependency and death. Difficulties in performing activities of daily living (ADLs) assess disability and dependency states. Data were from the Survey of Health, Ageing and Retirement in Europe conducted in 2004-2013, considering individuals aged 65 and older at baseline from Austria, Belgium, Denmark, France, Germany, Italy, the Netherlands, Spain, Sweden and Switzerland. The results showed that transitions to disability and dependency varied with age, sex, education and self-perceived health. The probability of transition to disability and dependency states increases until the age of 70 for all countries. However, there was heterogeneity in the disability and dependency trajectories with ageing between men and women. In most countries, women live with difficulties and may need help for longer than men. Care policies should consider sex differences to decrease the burden of care of informal caregivers, particularly in countries where care systems are absent or partially developed and a high level of family obligations to care needs exist.