Upstream open reading frames control PLK4 translation and centriole duplication in primordial germ cells.

Centrosomes are microtubule-organizing centers comprised of a pair of centrioles and the surrounding pericentriolar material. Abnormalities in centriole number are associated with cell division errors and can contribute to diseases such as cancer. Centriole duplication is limited to once per cell cycle and is controlled by the dosage-sensitive Polo-like kinase 4 (PLK4). Here, we show that PLK4 abundance is translationally controlled through conserved upstream open reading frames (uORFs) in the 5' UTR of the mRNA. Plk4 uORFs suppress Plk4 translation and prevent excess protein synthesis. Mice with homozygous knockout of Plk4 uORFs (Plk4 Δu/Δu ) are viable but display dramatically reduced fertility because of a significant depletion of primordial germ cells (PGCs). The remaining PGCs in Plk4 Δu/Δu mice contain extra centrioles and display evidence of increased mitotic errors. PGCs undergo hypertranscription and have substantially more Plk4 mRNA than somatic cells. Reducing Plk4 mRNA levels in mice lacking Plk4 uORFs restored PGC numbers and fully rescued fertility. Together, our data uncover a specific requirement for uORF-dependent control of PLK4 translation in counterbalancing the increased Plk4 transcription in PGCs. Thus, uORF-mediated translational suppression of PLK4 has a critical role in preventing centriole amplification and preserving the genomic integrity of future gametes.

Time is of the essence: the molecular mechanisms of primary microcephaly.

Primary microcephaly is a brain growth disorder characterized by a severe reduction of brain size and thinning of the cerebral cortex. Many primary microcephaly mutations occur in genes that encode centrosome proteins, highlighting an important role for centrosomes in cortical development. Centrosomes are microtubule organizing centers that participate in several processes, including controlling polarity, catalyzing spindle assembly in mitosis, and building primary cilia. Understanding which of these processes are altered and how these disruptions contribute to microcephaly pathogenesis is a central unresolved question. In this review, we revisit the different models that have been proposed to explain how centrosome dysfunction impairs cortical development. We review the evidence supporting a unified model in which centrosome defects reduce cell proliferation in the developing cortex by prolonging mitosis and activating a mitotic surveillance pathway. Finally, we also extend our discussion to centrosome-independent microcephaly mutations, such as those involved in DNA replication and repair.

Targeting TRIM37-driven centrosome dysfunction in 17q23-amplified breast cancer.

Genomic instability is a hallmark of cancer, and has a central role in the initiation and development of breast cancer1,2. The success of poly-ADP ribose polymerase inhibitors in the treatment of breast cancers that are deficient in homologous recombination exemplifies the utility of synthetically lethal genetic interactions in the treatment of breast cancers that are driven by genomic instability3. Given that defects in homologous recombination are present in only a subset of breast cancers, there is a need to identify additional driver mechanisms for genomic instability and targeted strategies to exploit these defects in the treatment of cancer. Here we show that centrosome depletion induces synthetic lethality in cancer cells that contain the 17q23 amplicon, a recurrent copy number aberration that defines about 9% of all primary breast cancer tumours and is associated with high levels of genomic instability4-6. Specifically, inhibition of polo-like kinase 4 (PLK4) using small molecules leads to centrosome depletion, which triggers mitotic catastrophe in cells that exhibit amplicon-directed overexpression of TRIM37. To explain this effect, we identify TRIM37 as a negative regulator of centrosomal pericentriolar material. In 17q23-amplified cells that lack centrosomes, increased levels of TRIM37 block the formation of foci that comprise pericentriolar material-these foci are structures with a microtubule-nucleating capacity that are required for successful cell division in the absence of centrosomes. Finally, we find that the overexpression of TRIM37 causes genomic instability by delaying centrosome maturation and separation at mitotic entry, and thereby increases the frequency of mitotic errors. Collectively, these findings highlight TRIM37-dependent genomic instability as a putative driver event in 17q23-amplified breast cancer and provide a rationale for the use of centrosome-targeting therapeutic agents in treating these cancers.

Centrosome defects cause microcephaly by activating the 53BP1-USP28-TP53 mitotic surveillance pathway.

Mutations in centrosome genes deplete neural progenitor cells (NPCs) during brain development, causing microcephaly. While NPC attrition is linked to TP53-mediated cell death in several microcephaly models, how TP53 is activated remains unclear. In cultured cells, mitotic delays resulting from centrosome loss prevent the growth of unfit daughter cells by activating a pathway involving 53BP1, USP28, and TP53, termed the mitotic surveillance pathway. Whether this pathway is active in the developing brain is unknown. Here, we show that the depletion of centrosome proteins in NPCs prolongs mitosis and increases TP53-mediated apoptosis. Cell death after a delayed mitosis was rescued by inactivation of the mitotic surveillance pathway. Moreover, 53BP1 or USP28 deletion restored NPC proliferation and brain size without correcting the upstream centrosome defects or extended mitosis. By contrast, microcephaly caused by the loss of the non-centrosomal protein SMC5 is also TP53-dependent but is not rescued by loss of 53BP1 or USP28. Thus, we propose that mutations in centrosome genes cause microcephaly by delaying mitosis and pathologically activating the mitotic surveillance pathway in the developing brain.

The Psychosocial Impact of the COVID-19 Pandemic on Families of Youth of Color: A Prospective Cohort Study.

OBJECTIVE: Prospectively examine racial and ethnic disparities in exposure to COVID-19-related stressors and their impact on families. METHODS: A racially, ethnically, and socioeconomically diverse cohort of caregivers of youth (n = 1,581) representative of the population served by a pediatric healthcare system completed the COVID-19 Exposure and Family Impact Scales in Oct/Nov 2020 and March/April 2021. Linear mixed-effects models were used to examine exposure to COVID-19-related events (Exposure), impact of the pandemic on family functioning and well-being (Impact), and child and parent distress (Distress) across time and as a function of race and ethnicity, adjusting for other sociodemographic variables. RESULTS: Exposure and Distress increased over time for all participants. After adjusting for sociodemographic factors, caregivers of Black and Hispanic youth reported greater Exposure than caregivers of White youth and caregivers of Black youth had a greater increase in Exposure over time than caregivers of White youth. Caregivers of White youth reported greater Impact than caregivers of Black and Other race youth. CONCLUSIONS: Exposure to and impact of the COVID-19 pandemic on family psychosocial functioning varied by race and ethnicity. Although exposure to COVID-19-related events was greater among Hispanic and non-Hispanic Black families, those of marginalized races reported less family impact than non-Hispanic White families, suggesting resiliency to the pandemic. Research should examine such responses to public health crises in communities of color, with a focus on understanding protective factors. These findings suggest the importance of culturally tailored interventions and policies that support universal psychosocial screenings during times of public health crises.

Tracheal reconstruction surgery for congenital tracheal stenosis.

PURPOSE: Congenital tracheal stenosis is a rare but dangerous disease. Reconstructive tracheal surgery is a life-saving treatment but also a challenging procedure. This study aims to evaluate the outcomes of tracheal reconstruction surgery. METHODS: A prospective cohort study was conducted with all the records of congenital tracheal stenosis which had been managed by tracheal reconstruction surgery at Children's Hospital 2 Ho Chi Minh City from August 2013 to August 2022. RESULTS: Sixty-seven cases, who underwent slide tracheoplasty, were included in our study. Mean age was 7.6 months (25 days - 8 years). Common congenital-associated lesion was left pulmonary artery sling, accounting for 65.7% of cases. Bronchial stenosis was found in 22.4% patients. Emergency surgery was performed in eight cases. The survival rate in this review was 86.6%. Nine patients died in which four of nine cases (44.4%) were emergency surgery. The recurrent stenosis rate was 8.9%, only two cases needed reoperation in which one died and one recovered uneventfully. The outcomes of surgery were good in 53 cases (79.1%). CONCLUSION: Tracheal reconstruction surgery with slide tracheoplasty technique is safe and versatile technique which is feasible in every case of congenital tracheal stenosis. Mortality was associated with severe cases which required emergency surgery.

ELN missense variant in patient with mid-aortic syndrome case report.

BACKGROUND: Mid-aortic syndrome (MAS) is characterized by the congenital coarctation of the abdominal aorta, abdominal and limb claudication, and hypertension. The etiology of this disorder is very diverse and often manifests in conjunction with Takayasu's arteritis, Williams-Beurens syndrome, and neurofibromatosis. The isolated mid-aortic syndrome is very rare with only a few cases reported in the literature. CASE PRESENTATION: A 45 years old man was admitted to the Emergency Department with sudden muscle weakness and facial paralysis on the left side. Imaging studies reveal right middle cerebral artery infarction at the M1 section. Incidental findings include multiple moderate to severe stenoses in the right internal carotid artery, and total abdominal aorta occlusion. A variant at the ELN gene (Elastin, OMIM*130,160): c.1768G > A/wt (p.Ala590Thr) was identified. CONCLUSION: This is the first reported case of ELN related mid-aortic syndrome in Vietnam which was diagnosed through careful clinical and genetic workup. The finding of mid-aortic syndrome, in this case, was incidental and the decision to reverse the occlusion was postponed as there was no immediate risk of renal failure or reduced blood flow to the lower limb.

Validation of the COVID-19 Exposure and Family Impact Scales.

OBJECTIVE: The COVID-19 Exposure and Family Impact Scales (CEFIS) were developed in Spring 2020 to assess effects of the COVID-19 pandemic on families and caregivers. Initial psychometric properties were promising. The current study examined the factor structure and evaluated convergent and criterion validity of the CEFIS in a new sample. METHODS: In October and November 2020, caregivers (N = 2,531) of youth (0-21 years) scheduled for an ambulatory care visit at Nemours Children's Hospital, Delaware completed the CEFIS and measures of convergent (PROMIS Global Mental Health Scale, Family Assessment Device) and criterion validity (PTSD Checklist-Civilian). Confirmatory factor analysis was used to examine the factor structure of the CEFIS. Bivariate correlations and logistic regression were used to examine convergent and criterion validity. RESULTS: Factor analysis supported the original six- and three-factor structures for the Exposure and Impact scales, respectively. Second-order factor analyses supported the use of Exposure, Impact, and Distress total scores. Higher scores on the CEFIS Exposure, Impact, and Distress scales were associated with increased mental health concerns and poorer family functioning. Higher scores on all CEFIS scales were also associated with greater odds of having clinically significant posttraumatic stress symptoms. CONCLUSIONS: The CEFIS is a psychometrically sound measure of the impact of the COVID-19 pandemic on family and caregiver functioning and may also be useful in identifying families who would benefit from psychological supports.

COVID-19 Exposure and Family Impact Scales for Adolescents and Young Adults.

OBJECTIVE: To understand the impact of the coronavirus disease 2019 (COVID-19) pandemic on adolescents and young adults (AYAs), we adapted the COVID-19 Exposure and Family Impact Scales (CEFIS; Kazak et al., 2021) for AYAs. Here, we report on the development, structure, and psychometric properties of the CEFIS-AYA. METHODS: The CEFIS-AYA was developed by a multidisciplinary, multi-institutional team using a rapid iterative process. Data from 3,912 AYAs from 21 programs at 16 institutions across the United States were collected from May 2020 to April 2021. We examined the underlying structure of the CEFIS-AYA using principal component analysis (PCA), calculated internal consistencies, and explored differences in scores by gender and age. RESULTS: Participants reported exposure to a range of COVID-19-related events (M = 9.08 events, of 28). On the bidirectional 4-point Impact scale, mean item scores were mostly above the midpoint, indicating a slightly negative impact. Kuder-Richardson 20/Cronbach's Alpha was good for Exposure (α = .76) and excellent for Impact (α = .93). PCA identified seven factors for Exposure (Severe COVID-19, Loss of Income, Limited Access to Essentials, COVID-19 Exposure, Disruptions to Activities, Disruptions to Living Conditions, and Designation as an Essential Worker) and five for Impact (Self and Family Relationships, Physical Well-Being, Emotional Well-Being, Social Well-Being, and Distress). Gender and age differences in CEFIS-AYA scores were identified. DISCUSSION: Initial reliability data are strong and support use of the CEFIS-AYA for measuring the effect of the COVID-19 pandemic on AYAs in research and clinical care.

Atropopeptides are a Novel Family of Ribosomally Synthesized and Posttranslationally Modified Peptides with a Complex Molecular Shape.

Biomacromolecules are known to feature complex three-dimensional shapes that are essential for their function. Among natural products, ambiguous molecular shapes are a rare phenomenon. The hexapeptide tryptorubin A can adopt one of two unusual atropisomeric configurations. Initially hypothesized to be a non-ribosomal peptide, we show that tryptorubin A is the first characterized member of a new family of ribosomally synthesized and posttranslationally modified peptides (RiPPs) that we named atropopeptides. The sole modifying enzyme encoded in the gene cluster, a cytochrome P450 monooxygenase, is responsible for the atropospecific formation of one carbon-carbon and two carbon-nitrogen bonds. The characterization of two additional atropopeptide biosynthetic pathways revealed a two-step maturation process. Atropopeptides promote pro-angiogenic cell functions as indicated by an increase in endothelial cell proliferation and undirected migration. Our study expands the biochemical space of RiPP-modifying enzymes and paves the way towards the chemoenzymatic utilization of atropopeptide-modifying P450s.

A Longitudinal Comparison of Alternatives to Body Mass Index Z-Scores for Children with Very High Body Mass Indexes.

OBJECTIVE: The current Centers for Disease Control and Prevention (CDC) body mass index (BMI) z-scores are inaccurate for BMIs of ≥97th percentile. We, therefore, considered 5 alternatives that can be used across the entire BMI distribution: modified BMI-for-age z-score (BMIz), BMI expressed as a percentage of the 95th percentile (%CDC95th percentile), extended BMIz, BMI expressed as a percentage of the median (%median), and %median adjusted for the dispersion of BMIs. STUDY DESIGN: We illustrate the behavior of the metrics among children of different ages and BMIs. We then compared the longitudinal tracking of the BMI metrics in electronic health record data from 1.17 million children in PEDSnet using the intraclass correlation coefficient to determine if 1 metric was superior. RESULTS: Our examples show that using CDC BMIz for high BMIs can result in nonsensical results. All alternative metrics showed higher tracking than CDC BMIz among children with obesity. Of the alternatives, modified BMIz performed poorly among children with severe obesity, and %median performed poorly among children who did not have obesity at their first visit. The highest intraclass correlation coefficients were generally seen for extended BMIz, adjusted %median, and %CDC95th percentile. CONCLUSIONS: Based on the examples of differences in the BMI metrics, the longitudinal tracking results and current familiarity BMI z-scores and percentiles. Both extended BMIz and extended BMI percentiles may be suitable replacements for the current z-scores and percentiles. These metrics are identical to those in the CDC growth charts for BMIs of <95th percentile and are superior for very high BMIs. Researchers' familiarity with the current CDC z-scores and clinicians with the CDC percentiles may ease the transition to the extended BMI scale.

COVID-19 Exposure and Family Impact Scales: Factor Structure and Initial Psychometrics.

OBJECTIVE: In response to the rapidly unfolding coronavirus disease 2019 (COVID-19) pandemic in spring 2020, we developed a caregiver-report measure to understand the extent to which children and families were exposed to events related to COVID-19 and their perceptions of its impact. This article reports on the factor structure and psychometric properties of this measure. METHODS: The COVID-19 Exposure and Family Impact Scales (CEFIS) were developed by a multidisciplinary, multi-institutional team using a rapid iterative process. Data from 1805 caregivers recruited from 28 programs at 15 institutions across the United States were collected from May-September 2020. We examined the underlying structure of the CEFIS using exploratory factor analyses and its internal consistency (Cronbach's alpha). RESULTS: Participants reported a range of COVID-19-related events (M = 8.71 events of 25). On the bidirectional 4-point impact scale, mean scores were mostly above the midpoint, indicating a slightly negative impact. Cronbach's alpha was excellent for Exposure (α = .80) and Impact (α = .92). Factor analysis identified six factors for Exposure (COVID-19 experiences, Access to essentials, Disruptions to living conditions, Loss of income, Family caregiving and activities, and Designation as an essential worker). There were three factors for Impact (Personal well-being, Family interactions, and Distress). DISCUSSION: The CEFIS has strong factors assessing Exposure to events related to COVID-19, and the Impact of these events on families of children in pediatric healthcare. These initial validation data support use of the CEFIS for measuring the effect of the pandemic.

Impact of Psychosocial Risk on Outcomes among Families Seeking Treatment for Obesity.

OBJECTIVES: To test the hypothesis that children with elevated psychosocial risk would have increased attrition and worse weight outcomes in weight management treatment. STUDY DESIGN: This was a prospective cohort study of 100 new patients, aged 4-12 years, in a weight management clinic. Parents completed the Psychosocial Assessment Tool. Logistic regression analyses were conducted to calculate the odds of attrition from the clinic and a nonmeaningful change in body mass index (BMI) z-score (ie, <0.1 unit decrease in BMI z-score) over a 6-month period based on psychosocial risk category, adjusting for child demographics and baseline weight category. RESULTS: The majority of patients were male (59%), black (36%) or white (43%), and had severe obesity (55%), and 59% of families were categorized as having moderate or high psychosocial risk. Over the 6-month period, 53% of families were lost to follow-up, and 67% did not have a clinically meaningful decrease in BMI z-score. Compared with children of families with low psychosocial risk, children of families with moderate or high psychosocial risk were 3.1 times (95% CI, 1.3-7.2 times) more likely to be lost to follow-up and 2.9 times (95% CI, 1.1-7.9 times) more likely to have a non-clinically meaningful change in BMI z-score. CONCLUSIONS: Children presenting with increased psychosocial risk have higher attrition and poorer weight outcomes, supporting the need for psychosocial screening as a standard component of pediatric weight management treatment.

Current and future economic burden of diabetes among working-age adults in Asia: conservative estimates for Singapore from 2010-2050.

BACKGROUND: Diabetes not only imposes a huge health burden but also a large economic burden worldwide. In the working-age population, cost of lost productivity can far exceed diabetes-related medical cost. In this study, we aimed to estimate the current and future indirect and excess direct costs of diagnosed type 2 diabetes among the working-age population in Singapore. METHODS: A previously-published epidemiological model of diabetes was adapted to forecast prevalence among working-age patients with diagnosed type 2 diabetes in the absence of interventions. The current methodology of the American Diabetes Association was adopted to estimate the costs of diabetes for this population. Diabetes-related excess direct medical costs were obtained from a local cost study while indirect costs were calculated using the human capital approach applied to local labor force statistics. These cost were estimated conservatively from a societal perspective on a per patient basis and projected to the overall Singapore population from 2010 to 2050. RESULTS: In 2010, total economic costs per working-age patient were estimated to be US$5,646 (US$4,432-US$10,612), of which 42% were excess direct medical costs and 58% indirect productivity-related losses. Total cost is projected to rise to US$7,791 (US$5,741-US$12,756) in 2050, with the share of indirect costs rising to 65%. Simultaneous increases in prevalence imply that the total economic costs of diabetes for the entire working-age population will increase by 2.4 fold from US$787 million in 2010 to US$1,867 million in 2050. CONCLUSIONS: By current projections, diabetes in Singapore represents a growing economic burden. Among the working-age population, the impact of productivity loss will become increasingly significant. Prevention efforts to reduce overall prevalence should also engage stakeholders outside the health sector who ultimately bear the indirect burden of disease.

Reliable prediction of childhood obesity using only routinely collected EHRs may be possible.

Background: Early identification of children at high risk of obesity can provide clinicians with the information needed to provide targeted lifestyle counseling to high-risk children at a critical time to change the disease course. Objectives: This study aimed to develop predictive models of childhood obesity, applying advanced machine learning methods to a large unaugmented electronic health record (EHR) dataset. This work improves on other studies that have (i) relied on data not routinely available in EHRs (like prenatal data), (ii) focused on single-age predictions, or (iii) not been rigorously validated. Methods: A customized sequential deep-learning model to predict the development of obesity was built, using EHR data from 36,191 diverse children aged 0-10 years. The model was evaluated using extensive discrimination, calibration, and utility analysis; and was validated temporally, geographically, and across various subgroups. Results: Our results are mostly better or comparable to similar studies. Specifically, the model achieved an AUROC above 0.8 in all cases (with most cases around 0.9) for predicting obesity within the next 3 years for children 2-7 years of age. Validation results show the model's robustness and top predictors match important risk factors of obesity. Conclusions: Our model can predict the risk of obesity for young children at multiple time points using only routinely collected EHR data, greatly facilitating its integration into clinical care. Our model can be used as an objective screening tool to provide clinicians with insights into a patient's risk for developing obesity so that early lifestyle counseling can be provided to prevent future obesity in young children.

Associations of Longitudinal BMI-Percentile Classification Patterns in Early Childhood with Neighborhood-Level Social Determinants of Health.

Background: Understanding social determinants of health (SDOH) that may be risk factors for childhood obesity is important to developing targeted interventions to prevent obesity. Prior studies have examined these risk factors, mostly examining obesity as a static outcome variable. Methods: We extracted electronic health record data from 2012 to 2019 for a children's health system that includes two hospitals and wide network of outpatient clinics spanning five East Coast states in the United States. Using data-driven and algorithmic clustering, we have identified distinct BMI-percentile classification groups in children from 0 to 7 years of age. We used two separate algorithmic clustering methods to confirm the robustness of the identified clusters. We used multinomial logistic regression to examine the associations between clusters and 27 neighborhood SDOHs and compared positive and negative SDOH characteristics separately. Results: From the cohort of 36,910 children, five BMI-percentile classification groups emerged: always having obesity (n = 429; 1.16%), overweight most of the time (n = 15,006; 40.65%), increasing BMI percentile (n = 9,060; 24.54%), decreasing BMI percentile (n = 5,058; 13.70%), and always normal weight (n = 7,357; 19.89%). Compared to children in the decreasing BMI percentile and always normal weight groups, children in the other three groups were more likely to live in neighborhoods with higher poverty, unemployment, crowded households, single-parent households, and lower preschool enrollment. Conclusions: Neighborhood-level SDOH factors have significant associations with children's BMI-percentile classification and changes in classification. This highlights the need to develop tailored obesity interventions for different groups to address the barriers faced by communities that can impact the weight and health of children living within them.

Rural Family Satisfaction With Telehealth Delivery of an Intervention for Pediatric Obesity and Associated Family Characteristics.

Objective: To describe satisfaction with the telehealth aspect of a pediatric obesity intervention among families from multiple rural communities and assess differences in satisfaction based on sociodemographic factors. Methods: This is a secondary analysis of data from a pilot randomized controlled trial of a 6-month intensive lifestyle intervention (iAmHealthy) delivered through telehealth to children 6-11 years old with BMI ≥85th%ile and their parents from rural communities. Parents completed a sociodemographic survey and a validated survey to assess satisfaction with the telehealth intervention across four domains (technical functioning, comfort of patient and provider with technology and perceived privacy, timely and geographic access to care, and global satisfaction) on a 5-point Likert scale. Kruskal-Wallis nonparametric rank test were used to compare mean satisfaction scores based on parent sociodemographics. Results: Forty-two out of 52 parents (67% White, 29% Black, 5% multiracial, and 50% with household income <$40,000) completed the survey. Mean satisfaction scores ranged from 4.16 to 4.54 (standard deviation 0.44-0.61). Parents without a college degree reported higher satisfaction across all domains compared with parents with a college degree, including global satisfaction (mean 4.64 vs. 4.31, p = 0.03). Parents reporting a household income <$40,000 (mean 4.70) reported higher scores in the comfort with technology and perceived privacy domain compared with parents with higher incomes (mean 4.30-4.45, p = 0.04). Discussion: Parents from rural communities, especially those from lower socioeconomic backgrounds, were highly satisfied with the iAmHealthy telehealth intervention. These findings can be used to inform future telehealth interventions among larger more diverse populations. ClinicalTrials.gov Identifier: NCT04142034.

Community Partnership to Co-Develop an Intervention to Promote Equitable Uptake of the COVID-19 Vaccine Among Pediatric Populations.

Objective: To describe the process of engaging community, caregiver, and youth partners in codeveloping an intervention to promote equitable uptake of the COVID-19 vaccine in non-Hispanic Black (Black) and Hispanic youth who experience higher rates of COVID-19 transmission, morbidity, and mortality but were less likely to receive the COVID-19 vaccine. Methods: A team of 11 Black and Hispanic community partners was assembled to codevelop intervention strategies with our interdisciplinary research team. We used a mixed-methods crowdsourcing approach with Black and Hispanic youth (n=15) and caregivers of Black and Hispanic youth (n=20) who had not yet been vaccinated against COVID-19, recruited from primary care clinics, to elicit perspectives on the acceptability of these intervention strategies. Results: We codeveloped five strategies: (1) community-tailored handouts and posters, (2) videos featuring local youth, (3) family-centered language to offer vaccines in the primary care clinic, (4) communication-skills training for primary care providers, and (5) use of community health workers to counsel families about the vaccine. The majority (56-96.9%) of youth and caregivers rated each of these strategies as acceptable, especially because they addressed common concerns and facilitated shared decision-making. Conclusions: Engaging community and family partners led to the co-development of culturally- and locally-tailored strategies to promote dialogue and shared decision-making about the COVID-19 vaccine. This process can be used to codevelop interventions to address other forms of public health disparities. Policy Implications: Intervention strategies that promote dialogues with trusted healthcare providers and support shared decision-making are acceptable strategies to promote COVID-19 vaccine uptake among youth from historically underserved communities. Stakeholder-engaged methods may also help in the development of interventions to address other forms of health disparities.

Patient-Reported Outcomes to Describe Global Health and Family Relationships in Pediatric Weight Management.

Background: Patient-reported outcomes (PROs) can assess chronic health. The study aims were to pilot a survey through the PEDSnet Healthy Weight Network (HWN), collecting PROs in tertiary care pediatric weight management programs (PWMP) in the United States, and demonstrate that a 50% enrollment rate was feasible; describe PROs in this population; and explore the relationship between child/family characteristics and PROs. Methods: Participants included 12- to 18-year-old patients and parents of 5- to 18-year-olds receiving care at PWMP in eight HWN sites. Patient-Reported Outcomes Measurement Information System (PROMIS®) measures assessed global health (GH), fatigue, stress, and family relationships (FR). T-score cut points defined poor GH or FR or severe fatigue or stress. Generalized estimating equations explored relationships between patient/family characteristics and PROMIS measures. Results: Overall, 63% of eligible parents and 52% of eligible children enrolled. Seven sites achieved the goal enrollment for parents and four for children. Participants included 1447 children. By self-report, 44.6% reported poor GH, 8.6% poor FR, 9.3% severe fatigue, and 7.6% severe stress. Multiple-parent household was associated with lower odds of poor GH by parent proxy report [adjusted odds ratio (aOR) 0.69, 95% confidence interval (CI) 0.55-0.88] and poor FR by self-report (aOR 0.36, 95% CI 0.17-0.74). Parents were significantly more likely to report that the child had poor GH and poor FR when a child had multiple households. Conclusions: PROs were feasibly assessed across the HWN, although implementation varied by site. Nearly half of the children seeking care in PWMP reported poor GH, and family context may play a role. Future work may build on this pilot to show how PROs can inform clinical care in PWMP.