Results From La Vida Buena (The Good Life): A Quasi-Experimental Intervention of a Community Health Worker-Led Family-Based Childhood Obesity Program for Latino Children 5-8 Years of Age on the U.S.-Mexico Border.

OBJECTIVE: To evaluate the effectiveness of the 8-week, community health worker (CHW)-led La Vida Buena childhood obesity program among Latino children 5 to 8 years old in a rural county along the U.S.-Mexico border. METHODS: This quasi-experimental study used a community-based participatory research approach to compare the effectiveness of the La Vida Buena (The Good Life) curriculum as compared with a single educational session. We took anthropomorphic measures and administered parent-reported nutrition and physical activity surveys at baseline, 3 months, and 6 months. The study took place between 2017 and 2020 in Santa Cruz County, Arizona. RESULTS: Change in body mass index (BMI) z-score was negligible for both groups. The parent-reported behavior indicated a shift toward healthier family behaviors and environment in the intervention group. IMPLICATIONS FOR PRACTICE: This study adds to the growing literature of CHW-led childhood obesity interventions. The engagement of the CHWs in all aspects of the intervention helped to facilitate important behavior changes. Future interventions should emphasize health and wellness rather than BMI z-score and include community, socioeconomic, and systems-level interventions to promote healthy environments.

Risk controlled decision trees and random forests for precision Medicine.

Statistical methods generating individualized treatment rules (ITRs) often focus on maximizing expected benefit, but these rules may expose patients to excess risk. For instance, aggressive treatment of type 2 diabetes (T2D) with insulin therapies may result in an ITR which controls blood glucose levels but increases rates of hypoglycemia, diminishing the appeal of the ITR. This work proposes two methods to identify risk-controlled ITRs (rcITR), a class of ITR which maximizes a benefit while controlling risk at a prespecified threshold. A novel penalized recursive partitioning algorithm is developed which optimizes an unconstrained, penalized value function. The final rule is a risk-controlled decision tree (rcDT) that is easily interpretable. A natural extension of the rcDT model, risk controlled random forests (rcRF), is also proposed. Simulation studies demonstrate the robustness of rcRF modeling. Three variable importance measures are proposed to further guide clinical decision-making. Both rcDT and rcRF procedures can be applied to data from randomized controlled trials or observational studies. An extensive simulation study interrogates the performance of the proposed methods. A data analysis of the DURABLE diabetes trial in which two therapeutics were compared is additionally presented. An R package implements the proposed methods ( https://github.com/kdoub5ha/rcITR).

A Community Health Worker-Led Community-Clinical Linkage Model to Address Emotional Well-Being Outcomes Among Latino/a People on the US-Mexico Border.

INTRODUCTION: Compared with their non-Hispanic White counterparts, Latino/a people have limited access to health resources that might improve their emotional well-being. Interventions that prioritize the Latino/a population, address social determinants of health, and decrease health disparities are needed. The objective of this study was to describe a community-clinical linkage intervention led by community health workers (CHWs) in 3 Latino/a populations along the US-Mexico border. METHODS: Researchers at the Arizona Prevention Research Center conducted the Linking Individual Needs to Community and Clinical Services (LINKS) study during 2017-2018. Clinic-based CHWs referred participants to community-based CHWs who met with participants monthly for 6 months to assess participant needs, provide support for emotional well-being, and link them to resources. Two community-based CHWs collaborated to maximize participant care; they also administered an emotional well-being questionnaire at baseline and at 3-month and 6-month follow-up. We estimated changes in emotional well-being outcomes. RESULTS: Scores for social support, perceived hopefulness, and quality-of-life measures among 189 LINKS participants increased significantly during the study period, especially among men and participants with low baseline scores. For each of the 3 outcomes, the standardized change was approximately 0.28 per 3 months of intervention, a decrease of more than half an SD (0.56) during 6 months of follow-up. CONCLUSION: A CHW-led community-clinical linkage intervention can result in positive emotional well-being outcomes. We encourage policy makers, funders, and public health practitioners to further investigate such interventions as a solution to reduce disparities in emotional well-being.

An integrated mixed methods approach to clarifying delivery, receipt and potential benefits of CHW-facilitated social support in a health promotion intervention.

BACKGROUND: Social support plays a critical role in physical and emotional health, making it an important component of community health worker (CHW) health promotion interventions. Different types of support operate in different ways, however, and the relationship between the nature of CHW support and the subsequent health benefit for their clients is not well understood. METHODS: This paper describes an integrated mixed methods study of the emotional, informational, appraisal and tangible support CHWs provided to Latinx community members residing in three US-Mexico border communities. Using a cohort (n = 159) from a CHW community-based intervention, we identify and describe four clusters of social support in which participants are characterized by life situations that informed the types of social support provided by the CHW. We examine the association between each cluster and client perceptions of social support over the 6-month intervention. RESULTS: CHWs provided emotional, appraisal, informational and tangible support depending on the needs of participants. Participants who received higher levels of emotional support from the CHW experienced the greatest post intervention increase in perceived social support. CONCLUSIONS: Study findings suggest that CHWs may be adept at providing non-directive social support based on their interaction with a client rather than a health outcome objective. Health promotion interventions should allow CHWs the flexibility to tailor provision of social support based on their assessment of client needs.

Metformin: Experimental and Clinical Evidence for a Potential Role in Emphysema Treatment.

Rationale: Cigarette smoke (CS) inhalation triggers oxidative stress and inflammation, leading to accelerated lung aging, apoptosis, and emphysema, as well as systemic pathologies. Metformin is beneficial for protecting against aging-related diseases. Objectives: We sought to investigate whether metformin may ameliorate CS-induced pathologies of emphysematous chronic obstructive pulmonary disease (COPD). Methods: Mice were exposed chronically to CS and fed metformin-enriched chow for the second half of exposure. Lung, kidney, and muscle pathologies, lung proteostasis, endoplasmic reticulum (ER) stress, mitochondrial function, and mediators of metformin effects in vivo and/or in vitro were studied. We evaluated the association of metformin use with indices of emphysema progression over 5 years of follow-up among the COPDGene (Genetic Epidemiology of COPD) study participants. The association of metformin use with the percentage of emphysema and adjusted lung density was estimated by using a linear mixed model. Measurements and Main Results: Metformin protected against CS-induced pulmonary inflammation and airspace enlargement; small airway remodeling, glomerular shrinkage, oxidative stress, apoptosis, telomere damage, aging, dysmetabolism in vivo and in vitro; and ER stress. The AMPK (AMP-activated protein kinase) pathway was central to metformin's protective action. Within COPDGene, participants receiving metformin compared with those not receiving it had a slower progression of emphysema (-0.92%; 95% confidence interval [CI], -1.7% to -0.14%; P = 0.02) and a slower adjusted lung density decrease (2.2 g/L; 95% CI, 0.43 to 4.0 g/L; P = 0.01). Conclusions: Metformin protected against CS-induced lung, renal, and muscle injury; mitochondrial dysfunction; and unfolded protein responses and ER stress in mice. In humans, metformin use was associated with lesser emphysema progression over time. Our results provide a rationale for clinical trials testing the efficacy of metformin in limiting emphysema progression and its systemic consequences.

Predictors of Treatment Response for Preschool Children With Developmental Language Disorder.

Purpose Enhanced Conversational Recast treatment is an effective intervention for remediating expressive grammatical deficits in preschool-age children with developmental language disorder, but not all children respond equally well. In this study, we sought to identify which child-level variables predict response to treatment of morphological deficits. Method Predictor variables of interest, including pre-intervention test scores and target morpheme production, age, and mother's level of education (proxy for socio-economic status) were included in analyses. The sample included 105 children (M = 5;1 [years;months]) with developmental language disorder who participated in 5 weeks of daily Enhanced Conversational Recast treatment. Classification and regression tree analysis was used to identify covariates that predicted children's generalization of their trained grammatical morpheme, as measured by treatment effect size d. Results Our analysis indicates that the Structured Photographic Expressive Language Test-Preschool 2 (SPELT-P 2) scores and the Peabody Picture Vocabulary Test-Fourth Edition scores significantly predicted the degree of benefit a child derived from Enhanced Conversational Recast treatment. Specifically, a SPELT-P 2 score above 75 (but still in the impaired range, < 87) combined with a high Peabody Picture Vocabulary Test-Fourth Edition score (> 100) yielded the largest treatment effect size, whereas a SPELT-P 2 score below 75 predicted the smallest treatment effect size. Other variables included in the model did not significantly predict treatment outcomes. Conclusions Understanding individual differences in response to treatment will allow service providers to make evidence-based decisions regarding how likely a child is to benefit from Enhanced Conversational Recast treatment and the expected magnitude of the response based on the child's background characteristics.

Lower oxygen consumption and Complex I activity in mitochondria isolated from skeletal muscle of fetal sheep with intrauterine growth restriction.

Fetal sheep with placental insufficiency-induced intrauterine growth restriction (IUGR) have lower hindlimb oxygen consumption rates (OCRs), indicating depressed mitochondrial oxidative phosphorylation capacity in their skeletal muscle. We hypothesized that OCRs are lower in skeletal muscle mitochondria from IUGR fetuses, due to reduced electron transport chain (ETC) activity and lower abundances of tricarboxylic acid (TCA) cycle enzymes. IUGR sheep fetuses (n = 12) were created with mid-gestation maternal hyperthermia and compared with control fetuses (n = 12). At 132 ± 1 days of gestation, biceps femoris muscles were collected, and the mitochondria were isolated. Mitochondria from IUGR muscle have 47% lower State 3 (Complex I-dependent) OCRs than controls, whereas State 4 (proton leak) OCRs were not different between groups. Furthermore, Complex I, but not Complex II or IV, enzymatic activity was lower in IUGR fetuses compared with controls. Proteomic analysis (n = 6/group) identified 160 differentially expressed proteins between groups, with 107 upregulated and 53 downregulated mitochondria proteins in IUGR fetuses compared with controls. Although no differences were identified in ETC subunit protein abundances, abundances of key TCA cycle enzymes [isocitrate dehydrogenase (NAD+) 3 noncatalytic subunit ß (IDH3B), succinate-CoA ligase ADP-forming subunit-ß (SUCLA2), and oxoglutarate dehydrogenase (OGDH)] were lower in IUGR mitochondria. IUGR mitochondria had a greater abundance of a hypoxia-inducible protein, NADH dehydrogenase 1α subcomplex 4-like 2, which is known to incorporate into Complex I and lower Complex I-mediated NADH oxidation. Our findings show that mitochondria from IUGR skeletal muscle adapt to hypoxemia and hypoglycemia by lowering Complex I activity and TCA cycle enzyme concentrations, which together, act to lower OCR and NADH production/oxidation in IUGR skeletal muscle.

La Vida Buena (The Good Life) evaluation: a quasi experimental intervention of a community health worker-led family-based childhood obesity program for Latino children 5-8 years of age on the US-Mexico border.

BACKGROUND: Due to multiple and interacting factors, Latino children are disproportionately at risk for overweight and obesity in the United States. Childhood obesity increases the risk for adverse physical and psychosocial outcomes throughout the lifespan. Intensive behavioral interventions recommended in primary care settings may not conform to current practices, and the most vulnerable populations are often unable to access these services. Community Health Workers (CHWs) offer a promising approach to bridging the gap between vulnerable communities and culturally competent services. La Vida Buena (The Good Life) is an 8-week family-focused intervention for Latino children 5-8 years old and their parents or caregivers who are patients at a Federally-Qualified Community Health Center (FQHC). It is a culturally and linguistically appropriate curriculum, facilitated by CHWs, that targets family behaviors to foster a healthy lifestyle in order to prevent and mitigate childhood overweight and obesity. METHODS: The primary objective is to test the effectiveness of the La Vida Buena (LVB) childhood obesity program among Latino children 5-8 years old and their families as compared with a single educational session. This study uses a parallel two-arm quasi-experimental design. The intervention group receives the 8-week La Vida Buena intervention and the comparison group receives a single educational session. The primary outcome is the change in the child's BMI z-score from baseline to 6 months. DISCUSSION: The implementation and evaluation of La Vida Buena may inform research and practice for linking Latino patients in FQHCs to culturally responsive community-based childhood obesity interventions. It will also contribute to the literature about CHWs as facilitators of behavior change for families underserved by health services and preventive programs. La Vida Buena can serve as a culturally and linguistically appropriate early intervention curriculum that will foster a healthy home environment for childhood obesity mitigation and prevention. TRIAL REGISTRATION: The trial was retrospectively registered on December 18, 2018. The ClinicalTrials.gov Identifier is NCT03781856.

Protocol for LINKS (linking individual needs to community and clinical services): a prospective matched observational study of a community health worker community clinical linkage intervention on the U.S.-Mexico border.

BACKGROUND: Latinos are currently the largest and fastest growing racial/ethnic group in the United States and have the lowest rates nationally of regular sources of primary care. The changing demographics of Latino populations have significant implications for the future health of the nation, particularly with respect to chronic disease. Community-based agencies and clinics alike have a long history of engaging community health workers (CHWs) to provide a broad range of tangible and emotional support strategies for Latinos with chronic diseases. In this paper, we present the protocol for a community intervention designed to evaluate the impact of CHWs in a Community-Clinical Linkage model to address chronic disease through innovative utilization of electronic health records (EHRs) and application of mixed methodologies. Linking Individual Needs to Community and Clinical Services (LINKS) is a 3-year, prospective matched observational study designed to examine the feasibility and impact of CHW-led Community-Clinical Linkages in reducing chronic disease risk and promoting emotional well-being among Latinos living in three U.S.-Mexico border communities. METHODS: The primary aim of LINKS is to create Community-Clinical Linkages between three community health centers and their respective county health departments in southern Arizona. Our primary analysis is to examine the impact of the intervention 6 to 12-months post program entry. We will assess chronic disease risk factors documented in the EHRs of participants versus matched non-participants. By using a prospective matched observational study design with EHRs, we have access to numerous potential comparators to evaluate the intervention effects. Secondary analyses include modeling within-group changes of extended research-collected measures. This approach enhances the overall evaluation with rich data on physical and emotional well-being and health behaviors of study participants that EHR systems do not collect in routine clinical practice. DISCUSSION: The LINKS intervention has practical implications for the development of Community-Clinical Linkage models. The collaborative and participatory approach in LINKS illustrates an innovative evaluation framework utilizing EHRs and mixed methods research-generated data collection. TRIAL REGISTRATION: This study protocol was retrospectively registered, approved, and made available on Clinicaltrials.gov by NCT03787485 as of December 20, 2018.

An Algorithm for Generating Individualized Treatment Decision Trees and Random Forests.

With new treatments and novel technology available, precision medicine has become a key topic in the new era of healthcare. Traditional statistical methods for precision medicine focus on subgroup discovery through identifying interactions between a few markers and treatment regimes. However, given the large scale and high dimensionality of modern data sets, it is difficult to detect the interactions between treatment and high dimensional covariates. Recently, novel approaches have emerged that seek to directly estimate individualized treatment rules (ITR) via maximizing the expected clinical reward by using, for example, support vector machines (SVM) or decision trees. The latter enjoys great popularity in clinical practice due to its interpretability. In this paper, we propose a new reward function and a novel decision tree algorithm to directly maximize rewards. We further improve a single tree decision rule by an ensemble decision tree algorithm, ITR random forests. Our final decision rule is an average over single decision trees and it is a soft probability rather than a hard choice. Depending on how strong the treatment recommendation is, physicians can make decisions based on our model along with their own judgment and experience. Performance of ITR forest and tree methods is assessed through simulations along with applications to a randomized controlled trial (RCT) of 1385 patients with diabetes and an EMR cohort of 5177 patients with diabetes. ITR forest and tree methods are implemented using statistical software R (https://github.com/kdoub5ha/ITR.Forest).

Community Health Worker Impact on Chronic Disease Outcomes Within Primary Care Examined Using Electronic Health Records.

OBJECTIVES: To investigate community health worker (CHW) effects on chronic disease outcomes using electronic health records (EHRs). METHODS: We examined EHRs of 32 147 patients at risk for chronic disease during 2012 to 2015. Variables included contact with clinic-based CHWs, vitals, and laboratory tests. We estimated a mixed model for all outcomes. RESULTS: Within-group findings showed statistically significant improvements in chronic disease indicators after exposure to CHWs. In health center 1, HbA1c (glycated hemoglobin) decreased 0.15 millimoles per mole (95% confidence interval [CI] = -0.24, -0.06), body mass index decreased 0.29 kilograms per meter squared (CI = -0.39, -0.20), and total cholesterol decreased 11.9 milligrams per deciliter (CI = -13.5, -10.2). In health center 2, HbA1c decreased 0.43 millimoles per mole (CI = -0.7, -0.17), body mass index decreased by 0.08 kilograms per meter squared (CI = -0.14, -0.02), and triglycerides decreased by 22.50 milligrams per deciliter (CI = -39.0, -6.0). Total cholesterol of 3.62 milligrams per deciliter (CI = -6.6, -0.6) in health center 1 was the only improvement tied to CHW contact. CONCLUSIONS: Although patients' chronic disease indicators consistently improved, between-group models provided no additional evidence of impact. EHRs' evolution may elucidate CHW contributions moving forward.

Applying an Integrative Framework of Executive Function to Preschoolers With Specific Language Impairment.

Purpose: The first goal of this research was to compare verbal and nonverbal executive function abilities between preschoolers with and without specific language impairment (SLI). The second goal was to assess the group differences on 4 executive function components in order to determine if the components may be hierarchically related as suggested within a developmental integrative framework of executive function. Method: This study included 26 4- and 5-year-olds diagnosed with SLI and 26 typically developing age- and sex-matched peers. Participants were tested on verbal and nonverbal measures of sustained selective attention, working memory, inhibition, and shifting. Results: The SLI group performed worse compared with typically developing children on both verbal and nonverbal measures of sustained selective attention and working memory, the verbal inhibition task, and the nonverbal shifting task. Comparisons of standardized group differences between executive function measures revealed a linear increase with the following order: working memory, inhibition, shifting, and sustained selective attention. Conclusion: The pattern of results suggests that preschoolers with SLI have deficits in executive functioning compared with typical peers, and deficits are not limited to verbal tasks. A significant linear relationship between group differences across executive function components supports the possibility of a hierarchical relationship between executive function skills.