The PhenX Toolkit: Recommended Measurement Protocols for Social Determinants of Health Research.

Health disparities are driven by unequal conditions in the environments in which people are born, live, learn, work, play, worship, and age, commonly termed the Social Determinants of Health (SDoH). The availability of recommended measurement protocols for SDoH will enable investigators to consistently collect data for SDoH constructs. The PhenX (consensus measures for Phenotypes and eXposures) Toolkit is a web-based catalog of recommended measurement protocols for use in research studies with human participants. Using standard protocols from the PhenX Toolkit makes it easier to compare and combine studies, potentially increasing the impact of individual studies, and aids in comparability across literature. In 2018, the National Institute on Minority Health and Health Disparities provided support for an initial expert Working Group to identify and recommend established SDoH protocols for inclusion in the PhenX Toolkit. In 2022, a second expert Working Group was convened to build on the work of the first SDoH Working Group and address gaps in the SDoH Toolkit Collections. The SDoH Collections consist of a Core Collection and Individual and Structural Specialty Collections. This article describes a Basic Protocol for using the PhenX Toolkit to select and implement SDoH measurement protocols for use in research studies. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA. Basic Protocol: Using the PhenX Toolkit to select and implement SDoH protocols.

Meaning from movement and stillness: Signatures of coordination dynamics reveal infant agency.

How do human beings make sense of their relation to the world and realize their ability to effect change? Applying modern concepts and methods of coordination dynamics, we demonstrate that patterns of movement and coordination in 3 to 4-mo-olds may be used to identify states and behavioral phenotypes of emergent agency. By means of a complete coordinative analysis of baby and mobile motion and their interaction, we show that the emergence of agency can take the form of a punctuated self-organizing process, with meaning found both in movement and stillness.

2D Capsule Networks Detect Perceived Changes in Infant∼Environment Relationship Reflected in 3D Movement Dynamics.

Can infant exploration and causal discovery be detected using Artificial Intelligence (AI)? A recent experiment probed how purposeful action emerges in early life by manipulating infants' functional connection to an object in the environment (i.e., tethering one foot to a colorful mobile). Vicon motion capture data from multiple infant joints were used here to create Histograms of Joint Displacements (HJDs) to generate pose-based descriptors for 3D infant spatial trajectories. Using HJDs as inputs, machine and deep learning systems were tasked with classifying the experimental state from which snippets of movement data were sampled. The architectures tested included k-Nearest Neighbour (kNN), Linear Discriminant Analysis (LDA), Fully connected network (FCNet), 1D-Convolutional Neural Network (1D-Conv), 1D-Capsule Network (1D-CapsNet), 2D-Conv and 2D-CapsNet. Sliding window scenarios were used for temporal analysis to search for topological changes in infant movement related to functional context. kNN and LDA achieved higher classification accuracy with single joint features, while deep learning approaches, particularly 2D-CapsNet, achieved higher accuracy on full-body features. For each AI architecture tested, measures of foot activity displayed the most distinct and coherent pattern alterations across different experimental stages (reflected in the highest classification accuracy rate), indicating that interaction with the world impacts the infant behaviour most at the site of organism∼world connection. Pairing theory-driven experimentation with AI tools thus opens a path to developing functionally-relevant assessments of infant behaviour that are likely to be useful in clinical settings.

The PhenX Toolkit: Measurement Protocols for Assessment of Social Determinants of Health.

INTRODUCTION: Social determinants are structures and conditions in the biological, physical, built, and social environments that affect health, social and physical functioning, health risk, quality of life, and health outcomes. The adoption of recommended, standard measurement protocols for social determinants of health will advance the science of minority health and health disparities research and provide standard social determinants of health protocols for inclusion in all studies with human participants. METHODS: A PhenX (consensus measures for Phenotypes and eXposures) Working Group of social determinants of health experts was convened from October 2018 to May 2020 and followed a well-established consensus process to identify and recommend social determinants of health measurement protocols. The PhenX Toolkit contains data collection protocols suitable for inclusion in a wide range of research studies. The recommended social determinants of health protocols were shared with the broader scientific community to invite review and feedback before being added to the Toolkit. RESULTS: Nineteen social determinants of health protocols were released in the PhenX Toolkit (https://www.phenxtoolkit.org) in May 2020 to provide measures at the individual and structural levels for built and natural environments, structural racism, economic resources, employment status, occupational health and safety, education, environmental exposures, food environment, health and health care, and sociocultural community context. CONCLUSIONS: Promoting the adoption of well-established social determinants of health protocols can enable consistent data collection and facilitate comparing and combining studies, with the potential to increase their scientific impact.

Mindfulness-Training in Preadolescents in School: The Role of Emotionality, EEG in Theta/Beta Bands, Creativity and Attention.

Mindfulness meditation is a means of increasing awareness of the present moment. Mindfulness Mediation Interventions (MMI) positively impact psychological functioning, yet the neurocognitive mechanisms that mediate these effects have been less well-defined. Here, the primary aim was to evaluate whether the effects of a 10-week MMI were mediated by changes in attention and creativity performance, as well as resting-state theta/beta (TB) ratio and alpha power. We also sought to determine whether any of these measures at baseline were predictive of mindfulness success, as rated by the 7-11-year-old participants and their teachers. Reductions in depression from pre-to-post were mediated by reductions in TB ratio and increases in alpha power; however, they were not mediated by attention/creativity changes. Higher baseline attention and creativity scores predicted enhanced mindfulness success post-intervention but notably, follow-up analyses revealed that those scoring lower on these measures were more likely to have reduced depression from pre-to-post.

Development of trofinetide for the treatment of Rett syndrome: from bench to bedside.

Rett syndrome (RTT) is rare neurodevelopmental disorder caused by mutations in the MECP2 gene that encodes methyl-CpG-binding protein 2 (MeCP2), a DNA-binding protein with roles in epigenetic regulation of gene expression. Functional loss of MeCP2 results in abnormal neuronal maturation and plasticity, characterized by loss of verbal communication and loss of fine and gross motor function, among others. Trofinetide, a synthetic analog of glycine-proline-glutamate, was approved by the US Food and Drug Administration for the treatment of RTT in adult and pediatric patients aged 2 years and older. Here, we present the development of trofinetide from bench research to clinical studies and emphasize how the collaboration between academia, the pharmaceutical industry, and patient advocacy led to the recent approval. The bench-to-bedside development of trofinetide underscores the value of collaboration between these groups in the development and approval of treatments for rare diseases.

Differential Contributions of Parental Warmth and Mindfulness to Child Executive Function and Pediatric Type 1 Diabetes Management.

OBJECTIVE: Positive parenting (e.g., parental warmth, mindful parenting) has been posited to promote effective pediatric type 1 diabetes mellitus (T1DM) management. This promotive effect may partly be conferred by fostering child self-regulatory development, such as executive function (EF). However, no research has examined whether better child EF serves as a mechanism underlying associations between positive parenting and child blood glucose levels (HbA1c). Moreover, it is unclear whether mindful parenting offers a unique benefit beyond that of parental warmth-a key pillar of effective parental involvement in T1DM management. METHODS: Primary caregivers of children with T1DM (N = 101; Mage = 12.02) reported on parenting behaviors and child EF. Children's medical information was obtained through chart review. Path analysis was used to examine direct and indirect relations in the cross-sectional data. RESULTS: The path analysis indicated that only parental warmth, not mindful parenting, was significantly associated with lower HbA1c. Both parental warmth and mindful parenting were significantly related to better child EF, but child EF did not mediate the associations between parenting and HbA1c. CONCLUSION: Parental warmth may constitute a key parenting behavior promoting effective pediatric T1DM management. Enhancing parental warmth may be an important target of interventions aiming to improve HbA1c. Although child EF was unrelated to HbA1c in this sample, given positive associations between parental warmth and mindfulness and child EF, longitudinal research is warranted to examine whether these positive parenting behaviors may confer long-term benefits for T1DM self-management through improved EF.

Youth Temperament Moderates Associations Between Parental Involvement and Pediatric Type 1 Diabetes Treatment Outcome.

OBJECTIVE: Both youth self-regulation and quality of parental involvement have been associated with blood glucose levels (HbA1c) of youth with type 1 diabetes mellitus (T1DM). However, it is unclear whether and how youth and parental factors interact in their relation to youth HbA1c. The differential susceptibility hypothesis proposes that youth with high negative affectivity (NA) and low effortful control (EC) may be more susceptible to the deleterious impact of lower quality parenting behaviors but also reap greater benefit from higher quality parenting behaviors. This study investigated whether youth temperament would moderate the link between diabetes-specific parental assistance (e.g., checking blood sugar) or support (e.g., encouraging, praising) and HbA1c among youth with T1DM. METHODS: Primary caregivers of youth with T1DM (N = 101; M age = 12.02, SD = 2.43) completed surveys on diabetes-specific parental involvement and youth temperament. Medical information (i.e., HbA1c) was obtained from chart review. RESULTS: Multiple regression analyses indicated that youth NA and EC significantly interacted with parental assistance, but not support. Specifically, higher parental assistance was associated with higher HbA1c among youth with high NA or high EC. High assistance was only linked to lower HbA1c for youth with low NA. CONCLUSIONS: Results suggest that optimal levels of parental involvement related to better T1DM outcomes depend on youth's NA or EC. Consistent with the goodness-of-fit framework, when parenting approaches match youth's temperament, youth with T1DM may be better able to maintain lower HbA1c. Family interventions for pediatric T1DM management may take into consideration youth temperament.

Design and outcome measures of LAVENDER, a phase 3 study of trofinetide for Rett syndrome.

INTRODUCTION: Rett syndrome (RTT) is a debilitating neurodevelopmental disorder with no approved treatments. Trofinetide is a synthetic analog of glycine-proline-glutamate, the N-terminal tripeptide of insulin-like growth factor 1. In a phase 2, placebo-controlled trial in 82 females with RTT aged 5-15 years, a significant (p ≤ 0.042) improvement over placebo was observed with the highest trofinetide dose (200 mg/kg twice daily [BID]) on three measures: Rett Syndrome Behaviour Questionnaire (RSBQ), Clinical Global Impression-Improvement (CGI-I), and RTT-Clinician Domain Specific Concerns-Visual Analog Scale (RTT-DSC-VAS). Trofinetide was well tolerated at all doses (50, 100, and 200 mg/kg BID). A phase 3 trial utilizing disease-specific and novel scales was designed to investigate the efficacy and safety of trofinetide in girls and women with RTT. METHODS: This 12-week, double-blind, randomized, placebo-controlled study (LAVENDER; NCT04181723) will evaluate trofinetide in 187 females, aged 5-20 years, with RTT. Co-primary endpoints are the RSBQ and CGI-I scales. Clinical domains of the CGI-I include communication, ambulation, hand use, seizures, attentiveness, and social (eye contact) and autonomic (breathing) aspects. Secondary endpoints will leverage four novel RTT-specific clinician ratings (derived from the RTT-DSC-VAS) of hand function, ambulation, ability to communicate, and verbal communication, and existing scales, to evaluate other core symptoms of RTT, quality of life and caregiver burden. A 40-week, open-label extension study will follow. DISCUSSION: This study was designed using disease-specific scales optimized to demonstrate changes in core symptoms of RTT and may provide the first phase 3 data demonstrating drug efficacy in individuals with RTT. TRIAL REGISTRATION: Clinicaltrials.govNCT04181723.

Computerized inhibitory control training reduces anxiety in preadolescent students.

The study examined the relationship between anxiety, inhibitory control (IC), and resting-state electroencephalography (EEG) in a critical age-range for social and emotional development (8-12-year-olds). The participants were assigned to 4 weeks of either an emotional IC training program, a neutral IC training program, or a waitlisted control, and were tested using cognitive, emotional, and EEG measures. The training was computerized and completed remotely. At baseline, IC accuracy scores were negatively related to both anxiety and depression levels (N = 42). Additionally, increased right lateral frontal alpha asymmetry was predictive of increased anxiety/depression scores. A series of multivariate analyses of covariance and post-hoc tests were conducted to compare effects in the participants that completed the full 16 sessions of training (N = 32). Overall the emotional and neutral training conditions showed similar improvements in IC accuracy, as well as reductions in anxiety compared to the waitlist condition. Minimal neurophysiological changes occurred from pre-to-post; however, lateral frontal asymmetry shifted leftward in the emotional training group. These findings highlight the potential of computerized IC training for mitigating negative emotional functioning in preadolescents. Future research is necessary to determine the long-term effects of IC training and whether longer training intervals facilitate persisting impacts.

Affectionate Touch in the Context of Breastfeeding and Maternal Depression Influences Infant Neurodevelopmental and Temperamental Substrates.

BACKGROUND: While numerous studies have demonstrated maternal depression's influence on infant brain development, few studies have examined the changes that occur as a consequence of co-occurring experiential factors that affect quality of mother and infant affectionate touch as well as infant temperament and neurophysiological systems. The aim of the study was to examine the interactive effects of maternal depression and breastfeeding on mother and infant affectionate touch and infant temperament and cortical maturation patterns across early development. METHODS: 113 mothers and their infants participated when infants were 1 and 3 months of age. Questionnaires to assess maternal depressive symptoms, feeding, and temperament were completed. Tonic EEG patterns (asymmetry and left and right activity) were collected and the dyads were video-recorded during feeding to assess mother and infant affectionate touch patterns. RESULTS: Data analysis showed that EEG activity and mother-infant affectionate touch differed as a function of mood and feeding method. Notably, only infants of depressed mothers that bottle-fed showed right frontal EEG asymmetry and attenuated change in the left frontal region across 3 months. Breastfeeding positively impacted affectionate touch behaviors and was associated with increased left and decreased right frontal EEG activation even for depressed groups. Furthermore, a model incorporating physiology, maternal depression, touch, temperament, and feeding indicated significant prediction for infant affectionate touch (with breastfeeding and affectively positive temperament demonstrating the strongest prediction). Con-clusion: The findings suggest that breastfeeding and the infant's positive temperament influence mother-infant affectionate touch patterns and result in neuroprotective outcomes for infants, even those exposed to maternal depression within early development.

A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Fragile X Syndrome.

BACKGROUND: We analyze the safety and tolerability of trofinetide and provide a preliminary evaluation of its efficacy in adolescent and adult males with fragile X syndrome. METHODS: This study was an exploratory, phase 2, multicenter, double-blind, placebo-controlled, parallel group study of the safety and tolerability of orally administered trofinetide in 72 adolescent and adult males with fragile X syndrome. Subjects were randomly assigned in a 1:1:1 ratio to 35 or 70 mg/kg twice daily trofinetide or placebo for 28 days. Safety assessments included adverse events, clinical laboratory tests, vital signs, electrocardiograms, physical examinations, and concomitant medications. Efficacy measurements were categorized into four efficacy domains, which related to clinically relevant phenotypic dimensions of impairment associated with fragile X syndrome. RESULTS: Both 35 and 70 mg/kg dose levels of trofinetide were well tolerated and appeared to be generally safe. Trofinetide at the 70 mg/kg dose level demonstrated efficacy compared with placebo based on prespecified criteria. On the basis of a permutation test, the probability of a false-positive outcome for the achieved prespecified success was 0.045. In the group analysis, improvement from treatment baseline was demonstrated on three fragile X syndrome-specific outcome measures. CONCLUSIONS: Trofinetide was well tolerated in adolescent and adult males with fragile X syndrome. Despite the relatively short duration of the study, a consistent signal of efficacy at the higher dose was observed in both caregiver and clinician assessments, based on a novel analytical model incorporating evaluation of multiple key symptom areas of fragile X syndrome. This finding suggests a potential for trofinetide treatment to provide clinically meaningful improvement in core fragile X syndrome symptoms.

Perceptions of Breastfeeding for Women with Perinatal Depression: A Descriptive Phenomenological Study.

Women with perinatal depression have an increased risk for breastfeeding cessation, yet few studies have explored their lived experience. In this qualitative study, semistructured interviews were conducted with a purposeful sample of women (N = 10) who self-reported perinatal depression. Using Giorgi's descriptive phenomenological method of data analysis, five components were found to embody their lived experience of breastfeeding: (a) choosing selflessness, (b) harboring inadequacy, (c) deliberate persevering, (d) discerning meaning, and (e) cherishing intimacy. Findings contribute to understanding the experience of breastfeeding for this population and could provide guidance to improve lactation management and perinatal mental health education for nurses.

A workshop report on the causes and consequences of sleep health disparities.

Sleep deficiencies, which include insufficient or long sleep duration, poor sleep quality, and irregular timing of sleep, are disproportionately distributed among populations that experience health disparities in the United States. Sleep deficiencies are associated with a wide range of suboptimal health outcomes, high-risk health behaviors, and poorer overall functioning and well-being. This report focuses on sleep health disparities (SHDs), which is a term defined as differences in one or more dimensions of sleep health on a consistent basis that adversely affect designated disadvantaged populations. SHDs appear to share many of the same determinants and causal pathways observed for health outcomes with well-known disparities. There also appears to be common behavioral and biological mechanisms that connect sleep with poorer health outcomes, suggesting a link between SHDs and other health disparities observed within these designated populations. In 2018, the National Institute on Minority Health and Health Disparities, the National Heart, Lung, and Blood Institute, and the Office of Behavioral and Social Sciences Research convened a workshop with experts in sleep, circadian rhythms, and health disparities to identify research gaps, challenges, and opportunities to better understand and advance research to address SHDs. The major strategy to address SHDs is to promote integration between health disparity causal pathways and sleep and circadian-related mechanisms in research approaches and study designs. Additional strategies include developing a comprehensive, integrative conceptual model, building transdisciplinary training and research infrastructure, and designing as well as testing multilevel, multifactorial interventions to address SHDs.

Parent-Training with Kangaroo Care Impacts Infant Neurophysiological Development & Mother-Infant Neuroendocrine Activity.

A randomized control trial was conducted to investigate the effects of skin-to-skin, chest-to-chest contact (kangaroo care, KC) in mother-infant dyads on patterns of infant brain activity and associated mother-infant neurohormone releases. 33 mother-infant dyads participated during pregnancy (29-38 weeks gestation), at neonatal and 3-month periods. Overall, analyses indicated that: 1) infants in the KC group showed left frontal brain activation patterns (asymmetry and coherence) associated with KC training; 2) KC produced moderate to large increases in oxytocin levels; and 3) KC yielded moderate decreases in cortisol reactivity. Findings suggest KC may garner favorable neuro-maturational and neurobiological outcomes for dyads.

Evaluation of Direct Oral Anticoagulant Dosing and Monitoring in Two Geriatric Outpatient Clinics.

OBJECTIVE: This study was conducted to evaluate direct oral anticoagulants (DOACs) prescribed to elderly patients in an outpatient setting, specifically evaluating if Food and Drug Administration (FDA) -approved dosing recommendations are followed.
DESIGN: This study was a retrospective quality improvement project.
SETTING: This study was conducted at geriatric hospital-based primary care clinics at the University of Pittsburgh Medical Center (UPMC), UPMC Senior Care Institute and UPMC Benedum Geriatric Center.
PATIENTS: Subjects included were 65 years of age or older; had an office visit at UPMC Senior Care Institute or UPMC Benedum Geriatric Center from September 1, 2015, to August 31, 2017; and had a DOAC on their home medications.
INTERVENTIONS: Data were obtained through retrospective chart review.
MAIN OUTCOME MEASURE: The primary objective of the study was to evaluate the appropriateness of dosing of DOACs based on FDA-labeled recommendations.
RESULTS: Of 232 patients included in analysis, 42.7% were found to have dosing inconsistent with FDAlabeled recommendations (47.3% apixaban, 35.8% rivaroxaban, and 31.6% dabigatran). No patients were prescribed edoxaban. The majority (72.7%) were dosed lower than FDA-recommended doses. Of all patients, the most frequent parameter (54.5%) for inappropriate dosing was patients meeting only 1 of 3 dose-reduction criteria when prescribed reduced-dose apixaban. Geriatrician and nongeriatrician prescribers had similar rates of prescribing DOACs with doses inconsistent with FDA-labeled recommendations (44.0% vs. 40.8%; P = 0.62).
CONCLUSION: Results suggest that DOACs used in outpatient geriatric patients are frequently dosed inconsistent with FDA-approved dosing recommendations. Further research is needed regarding clinical outcomes in older patients receiving DOACs and in those with dose adjustments inconsistent with FDA-labeled recommendations.
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Double-blind, randomized, placebo-controlled study of trofinetide in pediatric Rett syndrome.

OBJECTIVE: To determine safety, tolerability, and pharmacokinetics of trofinetide and evaluate its efficacy in female children/adolescents with Rett syndrome (RTT), a debilitating neurodevelopmental condition for which no pharmacotherapies directed at core features are available. METHODS: This was a phase 2, multicenter, double-blind, placebo-controlled, parallel-group study, in which safety/tolerability, pharmacokinetics, and clinical response to trofinetide were characterized in 82 children/adolescents with RTT, aged 5 to 15 years. Sixty-two participants were randomized 1:1:1:1 to receive placebo twice a day (bid) for 14 days, followed by placebo, 50, 100, or 200 mg/kg bid of trofinetide for 42 days. Following blinded safety data review, 20 additional participants were randomized 1:1 to the 200 mg/kg or placebo bid groups. Safety assessments included adverse events, clinical laboratory tests, physical examinations, and concomitant medications. Clinician- and caregiver-based efficacy measurements assessed clinically relevant, phenotypic dimensions of impairment of RTT. RESULTS: All dose levels were well tolerated and generally safe. Trofinetide at 200 mg/kg bid showed statistically significant and clinically relevant improvements relative to placebo on the Rett Syndrome Behaviour Questionnaire, RTT-Clinician Domain Specific Concerns-Visual Analog Scale, and Clinical Global Impression Scale-Improvement. Exploratory analyses suggested that observed changes correlated with trofinetide exposure. CONCLUSION: These results, together with those from a previous adolescent/adult trial, indicate trofinetide's potential for treating core RTT symptoms and support further trials. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for children/adolescents with RTT, trofinetide was safe, well-tolerated, and demonstrated improvement over placebo at 200 mg/kg bid in functionally important dimensions of RTT.

The Nature of Facial Emotion Recognition Impairments in Children on the Autism Spectrum.

This study examined socio-emotional skills, utilizing a facial emotion recognition (FER) task featuring unfamiliar and familiar faces, in children with autism spectrum disorders (ASD) compared to typically developing (TD) children. Results showed that the TD children were more proficient on the FER overall whereas ASD children recognized familiar expressions more precisely than unfamiliar ones. Further, ASD children did not differ from TD children in recognizing happy expressions but ASD children were less skilled with recognizing negative expressions. Findings suggest that ASD children possess more adept FER abilities than previously thought especially for important social others. Ultimately, a task featuring an array of positive and negative familiar and unfamiliar expressions may provide a more comprehensive assessment of socio-emotional abilities in ASD children.

Life Course Approaches to the Causes of Health Disparities.

Reducing health disparities requires an understanding of the mechanisms that generate disparities. Life course approaches to health disparities leverage theories that explain how socially patterned physical, environmental, and socioeconomic exposures at different stages of human development shape health within and across generations and can therefore offer substantial insight into the etiology of health disparities. Life course approaches are informed by developmental and structural perspectives. Developmental perspectives emphasize how socially patterned exposures to risk factors during sensitive life stages shift health trajectories, whereas structural perspectives emphasize how social identity and position within socially patterned environments disproportionately allocate risk factors and resources, resulting in altered health trajectories. We conclude that the science of health disparities will be advanced by integrating life course approaches into etiologic and intervention research on health disparities. The following 4 strategies are offered to guide in this process: (1) advance the understanding of multiple exposures and their interactions, (2) integrate life course approaches into the understanding of biological mechanisms, (3) explore transgenerational transmission of health disparities, and (4) integrate life course approaches into health disparities interventions.