Distinct Reproductive Phenotypes Segregate With Differences in Body Weight in Adolescent Polycystic Ovary Syndrome.

Introduction: Polycystic ovary syndrome (PCOS) is a heterogenous clinical syndrome defined by hyperandrogenism and irregular menses. In adult women with PCOS, discrete metabolic and reproductive subgroups have been identified. We hypothesize that distinct phenotypes can be distinguished between adolescent girls who are lean (LN-G) and girls with obesity (OB-G) at the time of PCOS diagnosis. Methods: Data were extracted from the CALICO multisite PCOS database. Clinical data collected at the time of diagnosis were available in 354 patients (81% with obesity) from 7 academic centers. Patients with body mass index (BMI) < 85th percentile for age and sex were characterized as lean (LN-G) and those with BMI percentile ≥ 95th percentile as obese (OB-G). We compared metabolic and reproductive phenotypes in LN-G and OB-G. Results: Reproductive phenotypes differed between the groups, with LN-G having higher total testosterone, androstenedione, and LH levels, while OB-G had lower sex hormone binding globulin (SHBG) and higher free testosterone. Metabolic profiles differed as expected, with OB-G having higher hemoglobin A1c, alanine aminotransferase, and serum triglycerides and more severe acanthosis nigricans. Conclusion: LN-G with PCOS had a distinct reproductive phenotype characterized by increased LH, total testosterone, and androstenedione levels, suggesting neuroendocrine-mediated ovarian androgen production. In contrast, phenotypes in OB-G suggest hyperandrogenemia is primarily driven by insulin resistance with low SHBG levels. These observations support the existence of distinct metabolic and reproductive subtypes in adolescent PCOS characterized by unique mechanisms for hyperandrogenemia.

Multisite Quality Improvement Program Within the Project ECHO Diabetes Remote Network.

BACKGROUND: The telementoring Project ECHO (Extension for Community Healthcare Outcomes) model has been shown to improve disease management in diabetes in many underserved communities. The authors aim to evaluate if ECHO could also be an effective tool for quality improvement (QI) of diabetes care in these communities. METHODS: Thirteen clinics in underserved communities in California and Florida participating in Project ECHO Diabetes were recruited for a 12-month QI program. The program provided weekly tele-education sessions, including a didactic presentation and case-based discussion. In addition, clinics chose their own set of quality measures to improve and met remotely to discuss their efforts, successes, and setbacks every quarter with mentorship from QI experts. RESULTS: Of the 31 QI initiatives attempted by different clinics, all had either made improvements (25 initiatives, 80.6%) or were in the process of making improvements (6 initiatives, 19.4%) in structural, process, and outcome measures. Examples of these measures include whether clinics have protocols to identify high-risk patients (structure), numbers of continuous glucose monitor prescriptions submitted by the clinics (process), and percentage of patients with diabetes whose most recent HbA1c are > 9% (outcome). For one measure, 40.0% of the clinics had achieved a higher percentage of cumulative HbA1c measurement in the third quarter of the year, compared to the fourth quarter in the previous year. The cost of QI implementation varied widely due to different number of personnel involved across sites. CONCLUSION: A QI program delivered via Project ECHO Diabetes can facilitate quality improvements in underserved communities.

Adolescent Bariatric Surgery: The Need for Tailored Educational Materials.

Rates of class III, or greater, obesity have risen among adolescents in the United States. Metabolic and bariatric surgery (MBS) is a safe and effective treatment option for severe obesity among teenagers that results in improvements in cardiometabolic and psychosocial health. Despite its effectiveness, MBS remains largely underutilized and misconceptions exist among providers, parents/guardians, and adolescents. In addition, adolescents who have undergone MBS procedures report there are some topics they wish they had known more about before surgery and express concern that their unique needs are not understood. One potential solution to address these concerns includes preoperative educational materials tailored for adolescents. Currently, there are no standardized recommendations for preoperative educational materials. This editorial suggests the use of community-engaged research, and qualitative methodology, to consult with the primary stakeholder groups of preoperative adolescents, postoperative adolescents, parents/guardians, and clinicians to develop tailored materials that address the unique needs of adolescents undergoing surgical treatment for obesity.

The Promising Success of Project Extension for Community Healthcare Outcomes (ECHO) Diabetes: Case Series.

BACKGROUND: In the United States, there are over 37 million people with diabetes but only 8000 endocrinologists. Therefore, many people with diabetes receive care exclusively from primary care providers (PCPs). To democratize knowledge regarding insulin-requiring diabetes through tele-education, Stanford University and the University of Florida developed Project Extension for Community Healthcare Outcomes (ECHO) Diabetes. OBJECTIVE: ECHO Diabetes uses a Hub and Spoke model connecting specialists (the "Hub") with PCPs (the "Spokes"). One-hour, weekly sessions include Hub diabetes didactic presentations and Spoke deidentified case presentations. Lessons learned during these sessions target provider knowledge and confidence surrounding diabetes management and patient care. METHODS: Spokes were asked to provide short descriptions of people with diabetes whose diabetes management improved directly or indirectly from their providers' participation or their involvement with a Diabetes Support Coach (DSC). We provide a case series to describe individuals and outcomes. Because this study was not a randomized controlled trial and was a prospective observation of patients with the intervention delivered to providers, the trial is not registered in a public trials registry. RESULTS: A case series of 11 people with diabetes was compiled from 10 PCPs and 1 DSC from California and Florida between 2021 and 2022. The principal impact of ECHO Diabetes is the education amplified from PCPs and DSCs to people with diabetes. In all cases, people with diabetes reported increased engagement and improved diabetes management. Several cases reflected increased access to diabetes technology, improvement in glycemic outcomes, and positive trends in mental health measures. CONCLUSIONS: This case series elucidates the potential value of the ECHO Diabetes program to people with diabetes who receive their diabetes care from PCPs. Those matched with a DSC saw clinically significant improvements in hemoglobin A1c and mental health outcomes.

Telehealth Use in a National Pediatric Weight Management Sample During the COVID-19 Pandemic.

Background: This study aimed to assess the implementation and access to telehealth-delivered pediatric weight management (PWM) during the initial phase of the COVID-19 pandemic at six US PWM programs (PWMP) using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. Methods: The COVID-19 period (COVID) was defined in this retrospective, multisite study as the time when each site closed in-person care during 2020. The Pre-COVID period (Pre-COVID) was an equivalent time frame in 2019. Patients were stratified by visit completion status. Patient characteristics for COVID and Pre-COVID were compared to examine potential changes/disparities in access to care. Results: There were 3297 unique patients included across the six sites. On average, telehealth was initiated 4 days after in-person clinic closure. Compared with Pre-COVID, COVID (mean duration: 9 weeks) yielded fewer total completed visits (1300 vs. 2157) and decreased revenue (mean proportion of nonreimbursed visits 33.30% vs. 16.67%). Among the completed visits, COVID included a lower proportion of new visits and fewer patients who were male, non-English speaking, Hispanic, or Asian and more patients who were Black or lived ≥20 miles from the program site (p < 0.05 for all). Among no-show/canceled visits, COVID included more patients who had private insurance, older age, or a longer time since the last follow-up. Conclusion: Rapid implementation of telehealth during COVID facilitated continuity of PWM care. Clinic volume and reimbursement were lower during COVID and differences in the patient population reached by telehealth emerged. Further characterization of barriers to telehealth for PWM is needed.

Home Visitation Program Staff Attitudes and Intentions Towards Using Digital Technology to Educate Families About Preventing Early Childhood Obesity: A Qualitative Study.

INTRODUCTION: Home visitation programs that reach families of young children offer a unique opportunity for large-scale early childhood obesity prevention efforts. The objective of this qualitative research was to determine stakeholder attitudes, subjective norms, perceived ease of use and usefulness, behavioral control, and behavioral intentions towards utilizing technology in a home visitation program targeting early childhood obesity prevention. METHODS: Staff from the Florida Maternal, Infant, and Early Childhood Home Visiting Program (n = 27) were interviewed individually by a trained research assistant using a semi-structured script based on constructs from the Technology Acceptance Model and Theory of Planned Behavior. Demographic and technology use information were collected. Interviews were recorded and transcribed verbatim, with data extracted and coded by two trained researchers using a theoretical thematic analysis approach. RESULTS: Most of the home visiting staff (78%) were white and non-Hispanic and employed for an average of 5 years with the program. Most staff (85%) indicated they were currently using videoconferencing for home visits. Themes and subthemes emerged, including positive attitudes towards technology as a flexible and time-efficient program alternative for childhood obesity prevention with recommendations to keep content short, at a low literacy level, and available in more than one language for ease of use. Participants recommended developing training tutorials to improve program implementation. Internet access and potential social disconnect were cited as concerns for using technology. DISCUSSION: Overall, home visitation staff had positive attitudes and intentions for using technology in home visiting programs with families for early childhood obesity prevention.

Non-Nutritive Sweetened Beverages Impair Therapeutic Benefits of Metformin in Prediabetic Diet-Induced Obese Mice.

Metformin, a frontline therapy for type 2 diabetes and related metabolic diseases, results in variable outcomes. This study aimed to investigate whether sweetened beverages (caloric or non-caloric) affect the therapeutic benefits of metformin on glucose, food intake, and weight loss in diet-induced obesity. Mice were given a high-fat diet and sweetened water for 8 weeks to induce obesity and glucose intolerance. Then, mice were randomized to receive metformin in either water, high-fructose corn syrup (HFCS), or the non-nutritive sweetener saccharin for 6 weeks. After 6 weeks of metformin treatment, all groups had improved glucose tolerance compared to pretreatment. However, saccharin resulted in worse glucose tolerance and weight gain outcomes than the water or HFCS groups and correlated with lower plasma growth differentiation factor 15 levels. In conclusion, reducing non-nutritive sweetener consumption during metformin therapy is recommended to avoid impairing the therapeutic effects of metformin on body weight and glucose homeostasis.

Short-Term Impact of Exercise Fitness Testing in a Pediatric Metabolic and Obesity Clinic: Initiative to Improve Health Care Quality.

This 2-phase pilot initiative determined whether (1) fitness testing could feasibly be implemented in pediatric practice, and (2) short-term changes in fitness and body mass index occur with Specific, Measurable, Attainable, Relevant, and Time-based (SMART) goals. Phase 1 (N = 580), clinic feasibility: evidence-based prognostic tests were successfully performed to measure cardiorespiratory fitness (CRF; 3-minute bench step), strength (handgrip dynamometry), and flexibility (sit-and-reach distance). Mean CRF percentile was 58.1 (worst >95 percentile, best <5 percentile), strength percentile was 73.5, and flexibility was 42.3 (worst <5 percentile, best >95 percentile). Phase 2, goal setting and follow-up: SMART fitness goals were developed. In phase 2, patients demonstrated 11.9% and 12.4% improvements in CRF and strength percentiles (P < .05) respectively. All patients who were assigned a strength goal improved handgrip strength. Body mass index percentile changes were not different by SMART goal target. Fitness testing was feasible and successfully improved CRF and strength in children at high risk of metabolic complications and future disability.

Type 1 diabetes knowledge assessment: The KAT-1 validation study.

OBJECTIVE: This study sought to examine the reliability and validity of a novel pediatric type 1 diabetes knowledge assessment (KAT-1) designed for children, adolescents, young adults and their parents/guardians. The instrument was designed to be integrated into the clinic workflow to obtain objective data electronically. RESEARCH DESIGN AND METHODS: KAT-1 was developed by a multidisciplinary team and includes 11 independent topical subscales. Forty children/caregivers participated in a pilot study; their feedback was used to improve item clarity and readability. Subsequently, a validation study was performed in 200 participants (100 children/adolescents/young adults with type 1 diabetes ages 11-21 years and 100 parents/guardians of children with type 1 diabetes ages 1-15 years) to examine correlations between the KAT-1 scores and Revised Diabetes Knowledge Test (DKT2) scores and HbA1c. An item analysis was conducted to determine internal consistency and reliability; topical subscales were evaluated using Cronbach's alpha. RESULTS: Total KAT-1 scores were positively correlated with DKT2 scores r = 0.674, p < 0.001, and negatively correlated with HbA1c, r = -0.3, p < 0.001. All KAT-1 subscales were positively and significantly correlated with one another and with total KAT-1 score. Internal consistency of total KAT-1 score was strong (Cronbach's α = 0.938, mean score 84.6, SD = 16.1) and 9 of 11 independent topical subscales demonstrated strong internal consistency. Completion time for subscales was <5 min. CONCLUSIONS: KAT-1 is a valid instrument to assess type 1 diabetes knowledge. The instrument's short topical subscales can be used to objectively assess specific knowledge and individualize diabetes education. KAT-1 has been integrated into our electronic health record (EPIC) and is available online at no cost.

Using Peer Power to Reduce Health Disparities: Implementation of a Diabetes Support Coach Program in Federally Qualified Health Centers.

Community health workers (CHWs) provide vital support to underserved communities in the promotion of health equity by addressing barriers related to the social determinants of health that often prevent people living with diabetes from achieving optimal health outcomes. Peer support programs in diabetes can also offer people living with diabetes invaluable support through a shared understanding of the disease and by offsetting diabetes-related stigma. As part of a Project Extension for Community Healthcare Outcomes (ECHO) Diabetes program, participating federally qualified healthcare centers were provided diabetes support coaches (DSCs) to facilitate patient engagement. DSCs hold invaluable expert knowledge, as they live with diabetes themselves and reside in areas they serve, thus combining the CHW role with peer support models. The use of DSCs and CHWs during the coronavirus disease 2019 pandemic and beyond is highly effective at reaching underserved communities with diabetes and promoting health equity.

Democratizing type 1 diabetes specialty care in the primary care setting to reduce health disparities: project extension for community healthcare outcomes (ECHO) T1D.

INTRODUCTION: Project ECHO (Extension for Community Healthcare Outcomes) is a tele-education outreach model that seeks to democratize specialty knowledge to reduce disparities and improve health outcomes. Limited utilization of endocrinologists forces many primary care providers (PCPs) to care for patients with type 1 diabetes (T1D) without specialty support. Accordingly, an ECHO T1D program was developed and piloted in Florida and California. Our goal was to demonstrate the feasibility of an ECHO program focused on T1D and improve PCPs' abilities to manage patients with T1D. RESEARCH DESIGN AND METHODS: Health centers (ie, spokes) were recruited into the ECHO T1D pilot through an innovative approach, focusing on Federally Qualified Health Centers and through identification of high-need catchment areas using the Neighborhood Deprivation Index and provider geocoding. Participating spokes received weekly tele-education provided by the University of Florida and Stanford University hub specialty team through virtual ECHO clinics, real-time support with complex T1D medical decision-making, access to a diabetes support coach, and access to an online repository of diabetes care resources. Participating PCPs completed pre/post-tests assessing diabetes knowledge and confidence and an exit survey gleaning feedback about overall ECHO T1D program experiences. RESULTS: In Florida, 12 spoke sites enrolled with 67 clinics serving >1000 patients with T1D. In California, 11 spoke sites enrolled with 37 clinics serving >900 patients with T1D. During the 6-month intervention, 27 tele-education clinics were offered and n=70 PCPs (22 from Florida, 48 from California) from participating spoke sites completed pre/post-test surveys assessing diabetes care knowledge and confidence in diabetes care. There was statistically significant improvement in diabetes knowledge (p≤0.01) as well as in diabetes confidence (p≤0.01). CONCLUSIONS: The ECHO T1D pilot demonstrated proof of concept for a T1D-specific ECHO program and represents a viable model to reach medically underserved communities which do not use specialists.

Feasibility/acceptability of an acceptance-based therapy intervention for diverse adolescent girls with overweight/obesity.

BACKGROUND: Behavioral obesity interventions using an acceptance-based therapy (ABT) approach have demonstrated efficacy for adults, yet feasibility and acceptability of tailoring an ABT intervention for adolescents remains unknown. OBJECTIVE: This study assessed the feasibility and acceptability of an ABT healthy lifestyle intervention among diverse adolescent cisgender girls with overweight/obesity (OW/OB). METHODS: Adolescent cisgender girls aged 14-19 with a BMI of ≥85th percentile-for-sex-and-age were recruited for participation in a single-arm feasibility study. The primary outcomes were recruitment and retention while the secondary outcome was change in BMI Z-score over the 6-month intervention. Exploratory outcomes included obesity-related factors, health-related behaviors, and psychological factors. RESULTS: Recruitment goals were achieved; 13 adolescents (>60% racial/ethnic minorities) participated in the intervention, and 11 completed the intervention (85% retention). In completers (n = 11), a mean decrease in BMI Z-score of -0.15 (SD = 0.34, Cohen's d = -0.44) was observed. Improvements were also noted for change in percentage of 95th percentile (d = -0.35), percent body fat (d = -0.35), quality of life (d = 0.71), psychological flexibility (d = -0.86), and depression (d = -0.86). CONCLUSIONS: These preliminary findings suggest an ABT healthy lifestyle intervention tailored for adolescent cisgender girls with OW/OB may be an acceptable treatment that could lead to improvements in BMI Z-score, obesity-related measures, and psychological outcomes.

Absence of relationship between serum cortisol and critical illness in premature infants.

BACKGROUND: Inadequate cortisol production in response to critical illness in extremely preterm infants may exacerbate poor outcomes. Despite commonly measuring cortisol concentration and administering hydrocortisone for presumed adrenal insufficiency, the relationship between serum cortisol concentration and illness severity remains unclear in this unique population. OBJECTIVE: To determine the relationship between cortisol concentrations and illness severity as measured by the Score for Neonatal Acute Physiology II, neonatal Sequential Organ Failure Assessment and Vasoactive-Inotropic Score in premature infants. DESIGN/METHODS: This retrospective, single-center cohort study included preterm infants born <30 weeks gestational age admitted to a level IV neonatal intensive care unit (NICU) between June 2011 and July 2018, who had a serum cortisol obtained for clinical indications before 36 weeks PMA. Demographic data were collected on infants and mothers. Nine clinical variables were identified a priori that could potentially modify cortisol concentration including critical illness. Univariate and multivariable analyses determined the relationship between cortisol concentration and each of these variables. RESULTS: A total of 224 preterm infants with pretreatment serum cortisol concentration met criteria for inclusion. The median (IQR) gestational age at birth was 25 weeks (24, 26) and at cortisol measurement was 26 weeks (25, 28). The median cortisol was 13.3 ug/dL. Non-survivors had the highest values. Cortisol concentration did not correlate with any of the selected illness severity scores. CONCLUSIONS: Cortisol concentrations in extremely preterm infants did not correlate with illness severity regardless of gestational age. Further studies are needed to identify clinically useful mediators of adrenal dysfunction and to guide clinical management.

Perceived barriers/facilitators to a healthy lifestyle among diverse adolescents with overweight/obesity: A qualitative study.

Objective: Effectiveness of behavioural obesity treatments in adolescents is modest. Thus, incorporating participant feedback may lead to improvement of intervention acceptability. This qualitative study's objective was to assess perceived barriers/facilitators to weight loss and healthy lifestyles among diverse adolescents with overweight/obesity (OW/OB). Methods: Adolescents ages 14-19 with BMI ≥ 85th percentile participated in focus groups and identified perceived barriers/facilitators to weight loss and healthy lifestyles. Results: Ten sex-stratified focus groups (n = 41; n = 13 males, n = 28 females) were conducted in 2018 and 2019. Females reported experiencing weight struggles, whereas males often stated no struggles with weight, despite all participants meeting criterion for OW/OB. Barriers included eating behaviours, family members and internal motivation, with additional barriers of physical activity, friends, time and support cited in females. Facilitators included parental, familial and peer support of healthy eating and exercise, modelling behaviours, internal motivation and organized sports. Two additional findings regarding adolescents' perceived barriers/facilitators include substantial overlap and sex differences of perceived barriers/facilitators. Conclusions: Adolescent males and females with OW/OB experience weight status differently, affecting their perceived barriers/facilitators to weight loss and healthy lifestyles. Tailoring weight management interventions to the unique needs of adolescent females versus adolescent males has the potential to improve intervention quality and effectiveness.

Simple tests of cardiorespiratory fitness in a pediatric population.

A progressive, treadmill-based VO2max is the gold standard of cardiorespiratory fitness determination but is rarely used in pediatric clinics due to time requirements and cost. Simpler and shorter fitness tests such as the Squat Test or Step Test may be feasible and clinically useful alternatives. However, performance comparisons of these tests to treadmill VO2max tests are lacking. The primary aim of this cross-sectional study was to assess the correlation between Squat and Step Test scores and VO2max in a pediatric population. As secondary outcomes, we calculated correlations between Rated Perceived Exertion Scale (RPE) scores, NIH PROMIS Physical Activity scores, and BMI z-score with VO2max, and we also evaluated the ability of each fitness test to discriminate low and high-risk patients based on the FITNESSGram. Forty children aged 10-17 completed these simple cardiorespiratory fitness tests. Statistically significant correlations were observed between VO2max and the Step Test (r = -0.549) and Squat Test (r = -0.429) scores, as well as participant BMI z-score (r = -0.458). RPE and PROMIS scores were not observed to be correlated with VO2max. Area Under the Receiver Operator Curve was relatively high for BMI z-scores and the Step Test (AUC = 0.813, 0.713 respectively), and lower for the Squat Test (AUC = 0.610) in discriminating risk according to FITNESSGram Scores. In this sample, the Step Test performed best overall. These tests were safe, feasible, and may add great value in assessing cardiorespiratory fitness in a clinical setting.

IL-27: An endogenous constitutive repressor of human monocytes.

Interleukin (IL)-27 is a pleiotropic cytokine that initially was described as being pro-inflammatory and an inducer of T helper (Th)1 cells. In contrast, it has also been described as an anti-inflammatory cytokine in that it suppresses pro-inflammatory Th17 cells and induces anti-inflammatory IL-10 producing T regulatory (Tr)1 cells. While the majority of studies have been focused on the effects of IL-27 on T cells, human antigen-presenting cells express high levels of the IL-27 receptor ex vivo, in addition to being the major producer of IL-27. We report here that human monocytes are repressed by endogenous IL-27, in that the addition of an anti-IL-27 neutralizing antibody increases the production of pro-inflammatory cytokines ex vivo. We observed that neutralizing monocyte-derived IL-27 leads to increased IL-17A production by CD4+ T cells and a down-regulation of the IL-17 modulating ectonucleotidase CD39 on monocytes. The locus that contains the IL27 gene has been linked to susceptibility for type 1 diabetes (T1D). Interestingly, ex vivo monocytes from subjects with T1D produce more IL-27 suggesting this upregulation of IL-27 acts as a negative feedback loop to attempt to counterbalance the pro-inflammatory immune response in the disease state. In summary, we provide evidence that IL-27 is an endogenous regulator of human monocytes and has consequences on CD4+ T cell phenotype, particularly Th17 cells.