Favorable Antiviral Effect of Metformin on Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load in a Randomized, Placebo-Controlled Clinical Trial of Coronavirus Disease 2019.

BACKGROUND: Metformin has antiviral activity against RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The mechanism appears to be suppression of protein translation via targeting the host mechanistic target of rapamycin pathway. In the COVID-OUT randomized trial for outpatient coronavirus disease 2019 (COVID-19), metformin reduced the odds of hospitalizations/death through 28 days by 58%, of emergency department visits/hospitalizations/death through 14 days by 42%, and of long COVID through 10 months by 42%. METHODS: COVID-OUT was a 2 × 3 randomized, placebo-controlled, double-blind trial that assessed metformin, fluvoxamine, and ivermectin; 999 participants self-collected anterior nasal swabs on day 1 (n = 945), day 5 (n = 871), and day 10 (n = 775). Viral load was quantified using reverse-transcription quantitative polymerase chain reaction. RESULTS: The mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo (-0.56 log10 copies/mL; 95% confidence interval [CI], -1.05 to -.06; P = .027). Those who received metformin were less likely to have a detectable viral load than placebo at day 5 or day 10 (odds ratio [OR], 0.72; 95% CI, .55 to .94). Viral rebound, defined as a higher viral load at day 10 than day 5, was less frequent with metformin (3.28%) than placebo (5.95%; OR, 0.68; 95% CI, .36 to 1.29). The metformin effect was consistent across subgroups and increased over time. Neither ivermectin nor fluvoxamine showed effect over placebo. CONCLUSIONS: In this randomized, placebo-controlled trial of outpatient treatment of SARS-CoV-2, metformin significantly reduced SARS-CoV-2 viral load, which may explain the clinical benefits in this trial. Metformin is pleiotropic with other actions that are relevant to COVID-19 pathophysiology. CLINICAL TRIALS REGISTRATION: NCT04510194.

Cumulative environmental stress and emerging cardiometabolic risk during childhood.

OBJECTIVE: To prospectively evaluate the relationship between cumulative environmental stress and cardiometabolic risk in middle childhood, and to examine whether hair cortisol, a measure of hypothalamic pituitary adrenal-axis activity, mediates this relationship. METHODS: In a cohort of children from low-income households (n = 320; 59% Hispanic, 23% Black, body mass index (BMI) percentile >50th at enrollment), environmental stressors including family and neighbourhood factors representing disadvantage/deprivation, and cortisol concentrations from hair samples, were measured over five timepoints beginning when children were 2-4 years old. Cardiometabolic risk factors (i.e., BMI, blood pressure, lipids, blood sugar, C-reactive protein) were measured at the final timepoint when children were 7-11 years of age. RESULTS: In adjusted logistic regression models, greater cumulative environmental stress was associated with a higher likelihood of elevated cardiometabolic risk in middle childhood (p = 0.01). Children from minoritized racial/ethnic groups had a higher prevalence of both stressors and cardiometabolic risk factors. Cumulative environmental stress was associated with higher hair cortisol concentrations (p < 0.01). However, hair cortisol was not directly associated with cardiometabolic risk factors and did not explain the association between environmental stress and cardiometabolic risk in causal mediation analysis. CONCLUSIONS: The influence of cumulative stress on cardiometabolic health can be observed in middle childhood and may contribute to cardiometabolic health disparities, highlighting the importance of public health interventions to mitigate disadvantage.

SMART use of medications for the treatment of adolescent severe obesity: A sequential multiple assignment randomized trial protocol.

BACKGROUND: Severe obesity is a complex, chronic disease affecting nearly 9% of adolescents in the U.S. Although the current mainstay of treatment is lifestyle therapy, pediatric clinical practice guidelines recommend the addition of adjunct anti-obesity medication (AOM), such as phentermine and topiramate. However, guidance regarding when adjunct AOM should be started and how AOM should be used is unclear. Furthermore, an inherent limitation of current treatment guidelines is their "one-size-fits-all" approach, which does not account for the heterogeneous nature of obesity and high degree of patient variability in response to all interventions. METHODS: This paper describes the study design and methods of a sequential multiple assignment randomized trial (SMART), "SMART Use of Medications for the Treatment of Adolescent Severe Obesity." The trial will examine 1) when to start AOM (specifically phentermine) in adolescents who are not responding to lifestyle therapy and 2) how to modify AOM when there is a sub-optimal response to the initial pharmacological intervention (specifically, for phentermine non-responders, is it better to add topiramate to phentermine or switch to topiramate monotherapy). Critically, participant characteristics that may differentially affect response to treatment will be assessed and evaluated as potential moderators of intervention efficacy. CONCLUSION: Data from this study will be used to inform the development of an adaptive intervention for the treatment of adolescent severe obesity that includes empirically-derived decision rules regarding when and how to use AOM. Future research will test this adaptive intervention against standard "one-size-fits-all" treatments.

The Relationship between Household SNAP Participation, Parent Feeding Styles, and Child Eating Behaviors.

This cross-sectional analysis of the Minnesota Now Everybody Together for Amazing Healthful Kids (NET-Works) study evaluated whether SNAP participation was associated with specific parental feeding styles and child eating behaviors. Associations between parent-reported feeding styles and child eating behaviors and SNAP participation were examined using multiple linear regression analyses and responses from 534 parent/child dyads (49.1% female children, 91.7% female parents). SNAP participation was not associated with specific feeding styles or child eating behaviors when adjusting for food insecurity, timing in SNAP cycle, and other covariates in this large, ethnically and racially diverse sample of predominantly mothers and preschool-aged children. Other factors, such as food insecurity, not SNAP participation, may influence parental feeding and child eating behaviors, and screening by health care providers is recommended.

Adolescent sources of stress, stress levels, and associations between stress and changes in weight outcomes at the time of COVID-19 related school closure in March 2020.

Objective: Stress is associated with weight changes, yet how level and sources of stress relate to this association is poorly understood. This mixed methods study examined associations between adolescent stress at the COVID-19 pandemic onset and standardized BMI (BMIz) over a three-month period. Methods: Participants (N = 197, mean age 13.66 ± 1.43 years, 85% Hispanic, 56% female) were recruited from a charter school in Texas to participate in a healthy lifestyle intervention during physical education class. We calculated BMIz using height and weight measurements taken December 2019 and the week of COVID-19 school closures in March 2020. We measured stress in March 2020 with the 4-item Perceived Stress Scale. We ran a multiple linear regression model controlling for baseline BMIz (December 2019), age, sex, intervention condition, and assessed the interaction between baseline BMIz and PSS-4 score on BMIz change. Results: Overall, our sample had an average PSS-4 score of seven and mean BMIz decrease of 0.04 over the three-month period. We observed a significant interaction between PSS-4 score and baseline BMIz. At lower baseline BMIz scores, higher PSS-4 scores were associated with decreases in BMIz over time. There was no significant association at higher baseline BMIz scores. COVID-19 pandemic-related concerns and school performance were the two primary stressors reported. Conclusions: The relation between stress and weight changes differed based on starting weight status. Future interventions should consider the influence of external stressors on intervention adherence and outcomes.

Body Mass Index Trajectories and Biomarkers of Cardiometabolic Risk in Children from Low-Income and Racially and Ethnically Diverse Households.

Background: This study examined the associations between BMI trajectories and emerging cardiometabolic risk (CMR) in children living in low-income and racially and ethnically diverse households in the United States. Methods: Data were drawn from NET-Works randomized intervention trial and NET-Works 2 prospective follow-up study (N = 338). BMI was measured across 6 follow-up visits and biomarkers of cardiometabolic risk (CMR) at the sixth visit. Group-based trajectory modeling identified child BMI trajectories. Adjusted multivariable linear regressions evaluated the associations between BMI trajectories and CMR. Results: We identified two BMI trajectories: 25% followed a trajectory of steep BMI increase, and 75% followed a moderate decreasing BMI trajectory over time. Relative to children in the moderate decreasing trajectory, children in the increasing trajectory had higher adjusted mean levels of C-reactive protein [CRP; 3.3; 95% confidence interval (CI): 1.6 to 5.0], leptin (63.1; 95% CI: 44.3 to 81.8), triglycerides (35.4; 95% CI: 22.1 to 48.6), triglyceride/high-density lipoprotein (HDL) ratio (1.2; 95% CI: 0.8 to 1.6), hemoglobin A1c (HbA1C; 0.1; 95% CI: 0.03 to 0.2), fasting glucose (1.8; 0.1 to 3.5) and insulin (8.8; 95% CI: 6.5 to 11.0), overall CMR score (0.7; 95% CI: 0.5 to 0.9), and lower adiponectin (-1.3; 95% CI: -2.5 to -0.1) and HDL (-10.8; 95% CI: -14.3 to -7.4). Conclusions: Children with high BMIs early in childhood were more likely to maintain an accelerated BMI trajectory throughout childhood, which was associated with adverse CMR in pre-adolescence. To advance health equity and support children's healthy weight and cardiovascular health trajectories, public health efforts are needed to address persistent disparities in childhood obesity and CMR.

Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial.

BACKGROUND: Post-COVID-19 condition (also known as long COVID) is an emerging chronic illness potentially affecting millions of people. We aimed to evaluate whether outpatient COVID-19 treatment with metformin, ivermectin, or fluvoxamine soon after SARS-CoV-2 infection could reduce the risk of long COVID. METHODS: We conducted a decentralised, randomised, quadruple-blind, parallel-group, phase 3 trial (COVID-OUT) at six sites in the USA. We included adults aged 30-85 years with overweight or obesity who had COVID-19 symptoms for fewer than 7 days and a documented SARS-CoV-2 positive PCR or antigen test within 3 days before enrolment. Participants were randomly assigned via 2 × 3 parallel factorial randomisation (1:1:1:1:1:1) to receive metformin plus ivermectin, metformin plus fluvoxamine, metformin plus placebo, ivermectin plus placebo, fluvoxamine plus placebo, or placebo plus placebo. Participants, investigators, care providers, and outcomes assessors were masked to study group assignment. The primary outcome was severe COVID-19 by day 14, and those data have been published previously. Because the trial was delivered remotely nationwide, the a priori primary sample was a modified intention-to-treat sample, meaning that participants who did not receive any dose of study treatment were excluded. Long COVID diagnosis by a medical provider was a prespecified, long-term secondary outcome. This trial is complete and is registered with ClinicalTrials.gov, NCT04510194. FINDINGS: Between Dec 30, 2020, and Jan 28, 2022, 6602 people were assessed for eligibility and 1431 were enrolled and randomly assigned. Of 1323 participants who received a dose of study treatment and were included in the modified intention-to-treat population, 1126 consented for long-term follow-up and completed at least one survey after the assessment for long COVID at day 180 (564 received metformin and 562 received matched placebo; a subset of participants in the metformin vs placebo trial were also randomly assigned to receive ivermectin or fluvoxamine). 1074 (95%) of 1126 participants completed at least 9 months of follow-up. 632 (56·1%) of 1126 participants were female and 494 (43·9%) were male; 44 (7·0%) of 632 women were pregnant. The median age was 45 years (IQR 37-54) and median BMI was 29·8 kg/m2 (IQR 27·0-34·2). Overall, 93 (8·3%) of 1126 participants reported receipt of a long COVID diagnosis by day 300. The cumulative incidence of long COVID by day 300 was 6·3% (95% CI 4·2-8·2) in participants who received metformin and 10·4% (7·8-12·9) in those who received identical metformin placebo (hazard ratio [HR] 0·59, 95% CI 0·39-0·89; p=0·012). The metformin beneficial effect was consistent across prespecified subgroups. When metformin was started within 3 days of symptom onset, the HR was 0·37 (95% CI 0·15-0·95). There was no effect on cumulative incidence of long COVID with ivermectin (HR 0·99, 95% CI 0·59-1·64) or fluvoxamine (1·36, 0·78-2·34) compared with placebo. INTERPRETATION: Outpatient treatment with metformin reduced long COVID incidence by about 41%, with an absolute reduction of 4·1%, compared with placebo. Metformin has clinical benefits when used as outpatient treatment for COVID-19 and is globally available, low-cost, and safe. FUNDING: Parsemus Foundation; Rainwater Charitable Foundation; Fast Grants; UnitedHealth Group Foundation; National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health; and National Center for Advancing Translational Sciences.

NET-Works paediatric obesity prevention trial: 66 month outcomes.

BACKGROUND AND OBJECTIVES: The NET-Works trial (2012-2018) randomized 534 children ages 2-4 years at baseline and their caregivers to either a 3-year multicomponent obesity prevention intervention or a control group. This research examined treatment effects on body mass index and other outcomes at 66 months. METHODS: Parent-child dyads (n = 338) who agreed to participate in a 66 month measurement visit were measured for child BMI, physical activity, diet, and cardiometabolic risk factor variables. RESULTS: At 66 months, no significant treatment effects were observed on BMI (Effect = -0.38; 95% CI = -1.13, 0.37). Subgroup results were consistent with the NET-Works 36 month results. Children with overweight at baseline in the intervention group gained significantly less BMI versus children with overweight in the control group (Effect = -1.28; 95% CI = -2.48, -0.07). Among Hispanic children, those in the intervention gained significantly less BMI than those in the control group (Effect = -1.04; 95% CI = -1.97, -0.11). CONCLUSIONS: Evidence suggests that early intervention with children at highest risk for obesity, using community-based, multicomponent, multisetting interventions, may be effective in reducing excess weight gain and obesity among certain subgroups of children. The intervention appeared to be effective in slowing BMI gain 66 months after randomization among children who were already overweight at ages 2-4 years and among children of Hispanic ethnicity.

Is economic hardship associated with young children's cortisol levels?

Economic hardship during childhood has been linked to poor physical and mental health. This study examines cross-sectional and longitudinal associations of a summed economic hardship score of poverty, food insecurity, and financial hardship with hair cortisol in young children. Data from 24-month (Time 1, mean age 5 years) and 36-month (Time 2, mean age 6 years) follow-up from the NET-Works obesity prevention trial (NET-Works, NCT0166891) were used. Hair cortisol measures obtained at each time point were log-transformed and regressed on economic hardship at Time 1 and a cumulative economic hardship from Time 1 to Time 2, using generalized linear regressions. All models were adjusted for child age, sex, race/ethnicity, and intervention (prevention vs. control) arm. The final analytic sample sizes ranged from 248 to 287. Longitudinal analyses indicated that for every 1-unit higher economic hardship score at Time 1, hair cortisol at Time 2 follow-up was on average 0.07 log-picograms per milligram (pg/mg) higher (95% confidence interval [CI]: 0.01, 0.13). For every 1-unit increase in the cumulative economic hardship score between Time 1 and 2, there was a 0.04 log-pg/mg (95% CI: 0.00, 0.07) average higher level of hair cortisol at Time 2 follow-up. Results show suggestive but limited evidence for an association between economic hardship and cortisol in young children.

Household Income, Cortisol, and Obesity During Early Childhood: A Prospective Longitudinal Study.

OBJECTIVE: To prospectively evaluate the relationship between household income, children's cortisol, and body mass index (BMI) trajectories over a 3-year period in early childhood. STUDY DESIGN: Household income, child hair cortisol levels, and BMI were measured at baseline, 12-, 24-, and 36-month follow-up visits in the Now Everybody Together for Amazing and Healthful Kids (NET-Works) Study (n = 534, children ages 2-4 years, and household income <$65 000/year at baseline). Relationships were examined between very low household income (<$25 000/year) at baseline, income status over time (remained <$25 000/year or had increasing income), cortisol accumulation from hair samples, and BMI percent of the 95th percentile (BMIp95) trajectories using adjusted linear growth curve modeling. Households with baseline income between $25 000 and $65 000/year were the reference group for all analyses. RESULTS: Children from very low-income households at baseline had annual changes in BMIp95 that were higher (P < .001) than children from reference group households (0.40 vs -0.62 percentage units/year). Annual increases in BMIp95 were also greater among children from households that remained very low income (P < .01, .34 percentage units/year) and among those with increasing income (P = .01, .51 percentage units/year) compared with the reference group (-0.61 percentage units/year). Children from households that remained very low income had higher hair cortisol accumulations (0.22 pg/mg, P = .02) than reference group children, whereas hair cortisol concentrations of children from households with increasing income (0.03 pg/mg) did not differ significantly from the reference group. Cortisol was not related to BMIp95. CONCLUSIONS: The economic circumstances of families may impact children's BMI trajectories and their developing stress systems, but these processes may be independent of one another.

Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccination and Booster on Coronavirus Disease 2019 (COVID-19) Symptom Severity Over Time in the COVID-OUT Trial.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has decreasing protection from acquiring any infection with emergence of new variants; however, vaccination continues to protect against progression to severe coronavirus disease 2019 (COVID-19). The impact of vaccination status on symptoms over time is less clear. METHODS: Within a randomized trial on early outpatient COVID-19 therapy testing metformin, ivermectin, and/or fluvoxamine, participants recorded symptoms daily for 14 days. Participants were given a paper symptom diary allowing them to circle the severity of 14 symptoms as none (0), mild (1), moderate (2), or severe (3). This is a secondary analysis of clinical trial data on symptom severity over time using generalized estimating equations comparing those unvaccinated, SARS-CoV-2 vaccinated with primary vaccine series only, or vaccine-boosted. RESULTS: The parent clinical trial prospectively enrolled 1323 participants, of whom 1062 (80%) prospectively recorded some daily symptom data. Of these, 480 (45%) were unvaccinated, 530 (50%) were vaccinated with primary series only, and 52 (5%) vaccine-boosted. Overall symptom severity was least for the vaccine-boosted group and most severe for unvaccinated at baseline and over the 14 days (P < .001). Individual symptoms were least severe in the vaccine-boosted group including cough, chills, fever, nausea, fatigue, myalgia, headache, and diarrhea, as well as smell and taste abnormalities. Results were consistent over Delta and Omicron variant time periods. CONCLUSIONS: SARS-CoV-2 vaccine-boosted participants had the least severe symptoms during COVID-19, which abated the quickest over time. Clinical Trial Registration. NCT04510194.

Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19.

BACKGROUND: Early treatment to prevent severe coronavirus disease 2019 (Covid-19) is an important component of the comprehensive response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. METHODS: In this phase 3, double-blind, randomized, placebo-controlled trial, we used a 2-by-3 factorial design to test the effectiveness of three repurposed drugs - metformin, ivermectin, and fluvoxamine - in preventing serious SARS-CoV-2 infection in nonhospitalized adults who had been enrolled within 3 days after a confirmed diagnosis of infection and less than 7 days after the onset of symptoms. The patients were between the ages of 30 and 85 years, and all had either overweight or obesity. The primary composite end point was hypoxemia (≤93% oxygen saturation on home oximetry), emergency department visit, hospitalization, or death. All analyses used controls who had undergone concurrent randomization and were adjusted for SARS-CoV-2 vaccination and receipt of other trial medications. RESULTS: A total of 1431 patients underwent randomization; of these patients, 1323 were included in the primary analysis. The median age of the patients was 46 years; 56% were female (6% of whom were pregnant), and 52% had been vaccinated. The adjusted odds ratio for a primary event was 0.84 (95% confidence interval [CI], 0.66 to 1.09; P = 0.19) with metformin, 1.05 (95% CI, 0.76 to 1.45; P = 0.78) with ivermectin, and 0.94 (95% CI, 0.66 to 1.36; P = 0.75) with fluvoxamine. In prespecified secondary analyses, the adjusted odds ratio for emergency department visit, hospitalization, or death was 0.58 (95% CI, 0.35 to 0.94) with metformin, 1.39 (95% CI, 0.72 to 2.69) with ivermectin, and 1.17 (95% CI, 0.57 to 2.40) with fluvoxamine. The adjusted odds ratio for hospitalization or death was 0.47 (95% CI, 0.20 to 1.11) with metformin, 0.73 (95% CI, 0.19 to 2.77) with ivermectin, and 1.11 (95% CI, 0.33 to 3.76) with fluvoxamine. CONCLUSIONS: None of the three medications that were evaluated prevented the occurrence of hypoxemia, an emergency department visit, hospitalization, or death associated with Covid-19. (Funded by the Parsemus Foundation and others; COVID-OUT ClinicalTrials.gov number, NCT04510194.).

Race/ethnicity and age associations with hair cortisol concentrations among children studied longitudinally from early through middle childhood.

A total of 513 children were included in this secondary analysis of data from the NET-Works trial of low income children at risk for obesity. The purpose of the analysis was to examine HCC longitudinally over 5 assessments from early through middle childhood with the goal of i) determining if there were racial/ethnic differences in HCC, and if so, how early in childhood these differences could be observed; and (ii) whether racial/ethnic differences in HCC reflected structural and family-level indicators of disadvantage. The sample consisted of children from diverse racial/ethnic backgrounds: Black, including Hispanic Black (N = 156), non-Hispanic White (N = 67) and Non-Black Hispanic (N = 290) children. As the largest group, the last group was used as the reference group in analyses. Structural and family-level indicators of disadvantage, including the neighborhood child opportunity index (COI), family income, and parent perceived neighborhood safety, were collected at each assessment. The results showed higher HCC among Black children beginning as early as 2-4 years of age than non-Black Hispanic children who did not differ from non-Hispanic White children. Although family income and COI were lower for children from minoritized racial-ethnic backgrounds, entering these measures as covariates did not reduce the difference in HCC between Black children and the other two groups. The results also showed that HCC initially decreased with age and then plateaued, with no evidence that this pattern differed by race/ethnicity. Because of the potential health risks of chronically elevated cortisol concentrations, these data argue for increased attention to the myriad of factors (oppressive structures, systems, and interpersonal experiences) that likely contribute to elevated cortisol levels among Black children.

Household food insecurity and obesity risk in preschool-aged children: A three-year prospective study.

BACKGROUND: Household food insecurity (FI) is a pressing social, economic and public health issue. However, little is known regarding the effect of FI exposure during the first few years of life, the most active postnatal time for neurobiological and physiological development, on patterns of weight gain during early childhood. It is also unknown whether dietary quality would serve as a pathway through which FI affects children's weight development. METHOD: This was a secondary data analysis from a three-year randomized clinical trial with five hundred and thirty-four parent/child dyads. Household FI in the past year was reported by parents at baseline when children were 2-4 years of age using the USDA Household Food Security Survey Module-Six Item Short Form. Children's dietary quality at baseline was measured by the US Department of Agriculture Healthy Eating Index (HEI). Child body mass index (BMI) was measured following standardized protocols at baseline and 12-, 24-, and 36-month follow-up. A latent growth curve model was used to examine 1) the association between baseline FI and sex-and-age-adjusted BMI z-scores in children and 2) the HEI pathway between the FI- BMI association. RESULTS: FI early in life was associated with higher baseline BMI z-scores. Children who had higher BMI at baseline maintained their higher BMI status over the next three years. Children's dietary intake quality did not explain the association between baseline FI and BMI z-scores. CONCLUSION: Early exposure to FI was associated with higher BMI in children as early as two years of age, setting them up for an increased likelihood of persistently high BMI-for-age in later childhood. These data suggest that the first few years may be a critical time for developing obesity risk, calling for policy and practices designed for early intervention of food insecurity.

What Brings Young Adults to the Yoga Mat? Cross-Sectional Associations Between Motivational Profiles and Physical and Psychological Health Among Participants in the Project EAT-IV Survey.

Objectives: This study examines motivations for yoga and identifies unique motivational profiles among a sample of young adult yoga practitioners. This study further determines how young adult yoga practitioners' motivational profiles associate with physical health behaviors and psychological factors. Subjects/Setting: Survey data were drawn from the fourth wave of a large, population-based study (Project EAT-IV; Eating and Activity in Teens and Young Adults). Design: Latent class analysis (LCA) was used to identify motivational profiles among Project EAT-IV participants practicing yoga (n = 297; mean age: 30.8-1.7 years; 79.7 % female). Cross-sectional associations between latent motivational profiles, physical health behaviors, and psychological factors were determined with unadjusted and adjusted (gender, race/ethnicity, and body mass index) general linear models. Results: Across motivational profiles, most young adult yoga practitioners were motivated by enhanced fitness and stress reduction/relaxation. Additional motivations for yoga clustered by appearance (desire to change body appearance or weight) or mindfulness (desire to increase present moment awareness) underpinnings. The LCA characterized motivational profiles as "Low Appearance, Low Mindfulness" (Class 1; n = 77), "Low Appearance, High Mindfulness" (Class 2; n = 48), "High Appearance, Low Mindfulness" (Class 3; n = 79), and "High Appearance, High Mindfulness" (Class 4; n = 93). Having a profile with high mindfulness and low appearance motivations (Class 2) was associated with higher body satisfaction in comparison to the other classes (p < 0.001). Relative to Class 2, those with low mindfulness motivations (Class 1; Class 3) reported less total physical activity (p = 0.002) and those with high appearance motivations (Class 3; Class 4) reported higher compulsive exercise scores (p = 0.002). Conclusions: In this sample, high mindfulness and low appearance motivations for yoga appeared optimal for physical and psychological health. Cross-sectional findings suggest that young adult yoga practitioners' mind-body health may be supported by motivational underpinnings that emphasize yoga's internal (mindfulness) rather than external (appearance) benefits.

Vaccination Against SARS-CoV-2 Is Associated With a Lower Viral Load and Likelihood of Systemic Symptoms.

Background: Data conflict on whether vaccination decreases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load. The objective of this analysis was to compare baseline viral load and symptoms between vaccinated and unvaccinated adults enrolled in a randomized trial of outpatient coronavirus disease 2019 (COVID-19) treatment. Methods: Baseline data from the first 433 sequential participants enrolling into the COVID-OUT trial were analyzed. Adults aged 30-85 with a body mass index (BMI) ≥25 kg/m2 were eligible within 3 days of a positive SARS-CoV-2 test and <7 days of symptoms. Log10 polymerase chain reaction viral loads were normalized to human RNase P by vaccination status, by time from vaccination, and by symptoms. Results: Two hundred seventy-four participants with known vaccination status contributed optional nasal swabs for viral load measurement: median age, 46 years; median (interquartile range) BMI 31.2 (27.4-36.4) kg/m2. Overall, 159 (58%) were women, and 217 (80%) were White. The mean relative log10 viral load for those vaccinated <6 months from the date of enrollment was 0.11 (95% CI, -0.48 to 0.71), which was significantly lower than the unvaccinated group (P = .01). Those vaccinated ≥6 months before enrollment did not differ from the unvaccinated with respect to viral load (mean, 0.99; 95% CI, -0.41 to 2.40; P = .85). The vaccinated group had fewer moderate/severe symptoms of subjective fever, chills, myalgias, nausea, and diarrhea (all P < .05). Conclusions: These data suggest that vaccination within 6 months of infection is associated with a lower viral load, and vaccination was associated with a lower likelihood of having systemic symptoms.

BMI metrics and their association with adiposity, cardiometabolic risk factors, and biomarkers in children and adolescents.

BACKGROUND: There are limited data comparing the relative associations of various BMI metrics with adiposity and cardiometabolic risk factors in youth. OBJECTIVE: Examine correlations of 7 different BMI metrics with adiposity, cardiometabolic risk factors, and biomarkers (i.e. blood pressure, waist circumference, cholesterol, leptin, insulin, high molecular weight adiponectin, high-sensitivity c-reactive protein (hsCRP)). METHODS: This was a cross-sectional analysis of youth in all BMI categories. BMI metrics: BMI z-score (BMIz), extended BMIz (ext.BMIz), BMI percentile (BMIp), percent of the BMI 95th percentile (%BMIp95), percent of the BMI median (%BMIp50), triponderal mass index (TMI), and BMI (BMI). Correlations between these BMI metrics and adiposity, visceral adiposity, cardiometabolic risk factors and biomarkers were summarized using Pearson's correlations. RESULTS: Data from 371 children and adolescents ages 8-21 years old were included in our analysis: 52% were female; 20.2% with Class I obesity, 20.5% with Class II, and 14.3% with Class III obesity. BMIp consistently demonstrated lower correlations with adiposity, risk factors, and biomarkers (r = 0.190-0.768) than other BMI metrics. The %BMIp95 and %BMIp50 were marginally more strongly correlated with measures of adiposity as compared to other BMI metrics. The ext.BMIz did not meaningfully outperform BMIz. CONCLUSION: Out of all the BMI metrics evaluated, %BMIp95 and %BMIp50 were the most strongly correlated with measures of adiposity. %BMIp95 has the benefit of being used currently to define obesity and severe obesity in both clinical and research settings. BMIp consistently had the lowest correlations. Future research should evaluate the longitudinal stability of various BMI metrics and their relative associations with medium to long-term changes in adiposity and cardiometabolic outcomes in the context of intervention trials.

BestFIT Sequential Multiple Assignment Randomized Trial Results: A SMART Approach to Developing Individualized Weight Loss Treatment Sequences.

BACKGROUND: State-of-the-art behavioral weight loss treatment (SBT) can lead to clinically meaningful weight loss, but only 30-60% achieve this goal. Developing adaptive interventions that change based on individual progress could increase the number of people who benefit. PURPOSE: Conduct a Sequential Multiple Assignment Randomized Trial (SMART) to determine the optimal time to identify SBT suboptimal responders and whether it is better to switch to portion-controlled meals (PCM) or acceptance-based treatment (ABT). METHOD: The BestFIT trial enrolled 468 adults with obesity who started SBT and were randomized to treatment response assessment at Session 3 (Early TRA) or 7 (Late TRA). Suboptimal responders were re-randomized to PCM or ABT. Responders continued SBT. Primary outcomes were weight change at 6 and 18 months. RESULTS: PCM participants lost more weight at 6 months (-18.4 lbs, 95% CI -20.5, -16.2) than ABT participants (-15.7 lbs, 95% CI: -18.0, -13.4), but this difference was not statistically significant (-2.7 lbs, 95% CI: -5.8, 0.5, p = .09). PCM and ABT participant 18 month weight loss did not differ. Early and Late TRA participants had similar weight losses (p = .96), however, Early TRA PCM participants lost more weight than Late TRA PCM participants (p = .03). CONCLUSIONS: Results suggest adaptive intervention sequences that warrant further research (e.g., identify suboptimal responders at Session 3, use PCMs as second-stage treatment). Utilizing the SMART methodology to develop an adaptive weight loss intervention that would outperform gold standard SBT in a randomized controlled trial is an important next step, but may require additional optimization work. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov identifier; NCT02368002.

Association of childhood abuse with behavioral weight-loss outcomes: Examining the mediating effect of binge eating severity.

OBJECTIVE: The study aims were to (1) document the relationship between a history of childhood abuse and weight change during behavioral obesity treatment and (2) estimate the indirect effect of childhood abuse on weight change through binge eating severity. METHODS: Participants (n = 431) were enrolled in a behavioral weight-loss intervention. Childhood physical and emotional abuse history and current binge eating severity were self-reported. Percent weight loss at 6 months was calculated using measured weight. Adjusted mediation models examined whether there was an indirect effect of childhood physical and emotional abuse on 6-month percent weight loss that operated through binge eating severity. RESULTS: After covariate adjustment, childhood physical abuse, but not emotional abuse, predicted a lower percent weight loss (B = -1.78%; 95% CI: -3.10% to -0.47%). Although childhood physical and emotional abuse were positively related to baseline binge eating severity, binge eating severity did not mediate the associations between either childhood abuse type and percent weight loss. CONCLUSIONS: Individuals with a childhood physical abuse history had a lower percent weight loss than those without such histories during behavioral obesity treatment. This effect was not explained by binge eating severity. Individuals with a history of childhood abuse may benefit from trauma-informed obesity care.

Characterizing Self-Monitoring Behavior and Its Association With Physical Activity and Weight Loss Maintenance.

Introduction: Reviewing gaps in self-monitoring during weight loss interventions may help identify individuals demonstrating signs of disengagement in behaviors, including moderate to vigorous physical activity (MVPA), associated with weight loss maintenance. This study examined the associations of different aspects of self-monitoring during a weight loss intervention with 24-month MVPA and weight. Methods: Secondary data analysis from the Tracking Study, a trial comparing weight-tracking frequency during a lifestyle weight loss program, was conducted. Self-monitoring logs from n =339 participants were used to define 4 characteristics and 4 specific gap lengths: short (1-4 weeks), medium (5-8 weeks), long (9-12 weeks), and extra long (>12 weeks). Self-reported MVPA and staff-measured weight were measured at baseline, 6, 12, 18, and 24 months. Generalized estimating equation modeling examined the association between self-monitoring characteristics and reported MVPA and weight. Results: Participants with gaps in self-monitoring as early as the second week of the intervention reported less MVPA and weighed more at 24 months. Furthermore, consistent tracking of MVPA was associated with higher reported MVPA and lower weight. Conclusions: Behavior tracking provides important information about behavioral disengagement early in the intervention process. Future work should test intervention augmentations to improve behavior change when disengagement is detected.