Organization of Chromatin by Intrinsic and Regulated Phase Separation.

Eukaryotic chromatin is highly condensed but dynamically accessible to regulation and organized into subdomains. We demonstrate that reconstituted chromatin undergoes histone tail-driven liquid-liquid phase separation (LLPS) in physiologic salt and when microinjected into cell nuclei, producing dense and dynamic droplets. Linker histone H1 and internucleosome linker lengths shared across eukaryotes promote phase separation of chromatin, tune droplet properties, and coordinate to form condensates of consistent density in manners that parallel chromatin behavior in cells. Histone acetylation by p300 antagonizes chromatin phase separation, dissolving droplets in vitro and decreasing droplet formation in nuclei. In the presence of multi-bromodomain proteins, such as BRD4, highly acetylated chromatin forms a new phase-separated state with droplets of distinct physical properties, which can be immiscible with unmodified chromatin droplets, mimicking nuclear chromatin subdomains. Our data suggest a framework, based on intrinsic phase separation of the chromatin polymer, for understanding the organization and regulation of eukaryotic genomes.

A mitotic chromatin phase transition prevents perforation by microtubules.

Dividing eukaryotic cells package extremely long chromosomal DNA molecules into discrete bodies to enable microtubule-mediated transport of one genome copy to each of the newly forming daughter cells1-3. Assembly of mitotic chromosomes involves DNA looping by condensin4-8 and chromatin compaction by global histone deacetylation9-13. Although condensin confers mechanical resistance to spindle pulling forces14-16, it is not known how histone deacetylation affects material properties and, as a consequence, segregation mechanics of mitotic chromosomes. Here we show how global histone deacetylation at the onset of mitosis induces a chromatin-intrinsic phase transition that endows chromosomes with the physical characteristics necessary for their precise movement during cell division. Deacetylation-mediated compaction of chromatin forms a structure dense in negative charge and allows mitotic chromosomes to resist perforation by microtubules as they are pushed to the metaphase plate. By contrast, hyperacetylated mitotic chromosomes lack a defined surface boundary, are frequently perforated by microtubules and are prone to missegregation. Our study highlights the different contributions of DNA loop formation and chromatin phase separation to genome segregation in dividing cells.

In diverse conditions, intrinsic chromatin condensates have liquid-like material properties.

Nuclear DNA in eukaryotes is wrapped around histone proteins to form nucleosomes on a chromatin fiber. Dynamic folding of the chromatin fiber into loops and variations in the degree of chromatin compaction regulate essential processes such as transcription, recombination, and mitotic chromosome segregation. Our understanding of the physical properties that allow chromatin to be dynamically remodeled even in highly compacted states is limited. Previously, we reported that chromatin has an intrinsic capacity to phase separate and form dynamic liquid-like condensates, which can be regulated by cellular factors [B. A. Gibson et al., Cell 179, 470-484.e421 (2019)]. Recent contradictory reports claim that a specific set of solution conditions is required for fluidity in condensates that would otherwise be solid [J. C. Hansen, K. Maeshima, M. J. Hendzel, Epigenetics Chromatin 14, 50 (2021); H. Strickfaden et al., Cell 183, 1772-1784.e1713 (2020)]. We sought to resolve these discrepancies, as our ability to translate with confidence these biophysical observations to cells requires their precise characterization. Moreover, whether chromatin assemblies are dynamic or static affects how processes such as transcription, loop extrusion, and remodeling will engage them inside cells. Here, we show in diverse conditions and without specific buffering components that chromatin fragments form phase separated fluids in vitro. We also explore how sample preparation and imaging affect the experimental observation of chromatin condensate dynamics. Last, we describe how liquid-like in vitro behaviors can translate to the locally dynamic but globally constrained chromatin movement observed in cells.

PARP-1 Controls the Adipogenic Transcriptional Program by PARylating C/EBPß and Modulating Its Transcriptional Activity.

Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification of proteins mediated by PARP family members, such as PARP-1. Although PARylation has been studied extensively, few examples of definitive biological roles for site-specific PARylation have been reported. Here we show that C/EBPß, a key pro-adipogenic transcription factor, is PARylated by PARP-1 on three amino acids in a conserved regulatory domain. PARylation at these sites inhibits C/EBPß's DNA binding and transcriptional activities and attenuates adipogenesis in various genetic and cell-based models. Interestingly, PARP-1 catalytic activity drops precipitously during the first 48 hr of differentiation, corresponding to a release of C/EBPß from PARylation-mediated inhibition. This promotes the binding of C/EBPß at enhancers controlling the expression of adipogenic target genes and continued differentiation. Depletion or chemical inhibition of PARP-1, or mutation of the PARylation sites on C/EBPß, enhances these early adipogenic events. Collectively, our results provide a clear example of how site-specific PARylation drives biological outcomes.

New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs.

Poly(ADP-ribose) polymerases (PARPs) are enzymes that transfer ADP-ribose groups to target proteins and thereby affect various nuclear and cytoplasmic processes. The activity of PARP family members, such as PARP1 and PARP2, is tied to cellular signalling pathways, and through poly(ADP-ribosyl)ation (PARylation) they ultimately promote changes in gene expression, RNA and protein abundance, and the location and activity of proteins that mediate signalling responses. PARPs act in a complex response network that is driven by the cellular, molecular and chemical biology of poly(ADP-ribose) (PAR). This PAR-dependent response network is crucial for a broad array of physiological and pathological responses and thus is a good target for chemical therapeutics for several diseases.

Expanding a Behavioral View on Digital Health Access: Drivers and Strategies to Promote Equity.

The potential and threat of digital tools to achieve health equity has been highlighted for over a decade, but the success of achieving equitable access to health technologies remains challenging. Our paper addresses renewed concerns regarding equity in digital health access that were deepened during the COVID-19 pandemic. Our viewpoint is that (1) digital health tools have the potential to improve health equity if equitable access is achieved, and (2) improving access and equity in digital health can be strengthened by considering behavioral science-based strategies embedded in all phases of tool development. Using behavioral, equity, and access frameworks allowed for a unique and comprehensive exploration of current drivers of digital health inequities. This paper aims to present a compilation of strategies that can potentially have an actionable impact on digital health equity. Multilevel factors drive unequal access, so strategies require action from tool developers, individual delivery agents, organizations, and systems to effect change. Strategies were shaped with a behavioral medicine focus as the field has a unique role in improving digital health access; arguably, all digital tools require the user (individual, provider, and health system) to change behavior by engaging with the technology to generate impact. This paper presents a model that emphasizes using multilevel strategies across design, delivery, dissemination, and sustainment stages to advance digital health access and foster health equity.

Clinician documentation of patient centered care in the electronic health record.

BACKGROUND: In this study we sought to explore the possibility of using patient centered care (PCC) documentation as a measure of the delivery of PCC in a health system. METHODS: We first selected 6 VA medical centers based on their scores for a measure of support for self-management subscale from a national patient satisfaction survey (the Survey for Healthcare Experience-Patients). We accessed clinical notes related to either smoking cessation or weight management consults. We then annotated this dataset of notes for documentation of PCC concepts including: patient goals, provider support for goal progress, social context, shared decision making, mention of caregivers, and use of the patient's voice. We examined the association of documentation of PCC with patients' perception of support for self-management with regression analyses. RESULTS: Two health centers had < 50 notes related to either tobacco cessation or weight management consults and were removed from further analysis. The resulting dataset includes 477 notes related to 311 patients total from 4 medical centers. For a majority of patients (201 out of 311; 64.8%) at least one PCC concept was present in their clinical notes. The most common PCC concepts documented were patient goals (patients n = 126; 63% clinical notes n = 302; 63%), patient voice (patients n = 165, 82%; clinical notes n = 323, 68%), social context (patients n = 105, 52%; clinical notes n = 181, 38%), and provider support for goal progress (patients n = 124, 62%; clinical notes n = 191, 40%). Documentation of goals for weight loss notes was greater at health centers with higher satisfaction scores compared to low. No such relationship was found for notes related to tobacco cessation. CONCLUSION: Providers document PCC concepts in their clinical notes. In this pilot study we explored the feasibility of using this data as a means to measure the degree to which care in a health center is patient centered. PRACTICE IMPLICATIONS: clinical EHR notes are a rich source of information about PCC that could potentially be used to assess PCC over time and across systems with scalable technologies such as natural language processing.

A Multisite Preregistered Paradigmatic Test of the Ego-Depletion Effect.

We conducted a preregistered multilaboratory project (k = 36; N = 3,531) to assess the size and robustness of ego-depletion effects using a novel replication method, termed the paradigmatic replication approach. Each laboratory implemented one of two procedures that was intended to manipulate self-control and tested performance on a subsequent measure of self-control. Confirmatory tests found a nonsignificant result (d = 0.06). Confirmatory Bayesian meta-analyses using an informed-prior hypothesis (δ = 0.30, SD = 0.15) found that the data were 4 times more likely under the null than the alternative hypothesis. Hence, preregistered analyses did not find evidence for a depletion effect. Exploratory analyses on the full sample (i.e., ignoring exclusion criteria) found a statistically significant effect (d = 0.08); Bayesian analyses showed that the data were about equally likely under the null and informed-prior hypotheses. Exploratory moderator tests suggested that the depletion effect was larger for participants who reported more fatigue but was not moderated by trait self-control, willpower beliefs, or action orientation.

Understanding cancer survivors' information needs and information-seeking behaviors for complementary and alternative medicine from short- to long-term survival: a mixed-methods study.

OBJECTIVE: The research examined complementary and alternative medicine (CAM) information-seeking behaviors and preferences from short- to long-term cancer survival, including goals, motivations, and information sources. METHODS: A mixed-methods approach was used with cancer survivors from the "Assessment of Patients' Experience with Cancer Care" 2004 cohort. Data collection included a mail survey and phone interviews using the critical incident technique (CIT). RESULTS: Seventy survivors from the 2004 study responded to the survey, and eight participated in the CIT interviews. Quantitative results showed that CAM usage did not change significantly between 2004 and 2015. The following themes emerged from the CIT: families' and friends' provision of the initial introduction to a CAM, use of CAM to manage the emotional and psychological impact of cancer, utilization of trained CAM practitioners, and online resources as a prominent source for CAM information. The majority of participants expressed an interest in an online information-sharing portal for CAM. CONCLUSION: Patients continue to use CAM well into long-term cancer survivorship. Finding trustworthy sources for information on CAM presents many challenges such as reliability of source, conflicting information on efficacy, and unknown interactions with conventional medications. Study participants expressed interest in an online portal to meet these needs through patient testimonials and linkage of claims to the scientific literature. Such a portal could also aid medical librarians and clinicians in locating and evaluating CAM information on behalf of patients.

Generation and Characterization of Recombinant Antibody-like ADP-Ribose Binding Proteins.

ADP-ribosylation is an enzyme-catalyzed post-translational modification of proteins in which the ADP-ribose (ADPR) moiety of NAD+ is transferred to a specific amino acid in a substrate protein. The biological functions of ADP-ribosylation are numerous and diverse, ranging from normal physiology to pathological conditions. Biochemical and cellular studies of the diverse forms and functions of ADPR require immunological reagents that can be used for detection and enrichment. The lack of a complete set of tools that recognize all forms of ADPR [i.e., mono-, oligo-, and poly(ADP-ribose)] has hampered progress. Herein, we describe the generation and characterization of a set of recombinant antibody-like ADP-ribose binding proteins, in which naturally occurring ADPR binding domains, including macrodomains and WWE domains, have been functionalized by fusion to the Fc region of rabbit immunoglobulin. These reagents, which collectively recognize all forms of ADPR with different specificities, are useful in a broad array of antibody-based assays, such as immunoblotting, immunofluorescent staining of cells, and immunoprecipitation. Observations from these assays suggest that the biology of ADPR is more diverse, rich, and complex than previously thought. The ARBD-Fc fusion proteins described herein will be useful tools for future exploration of the chemistry, biochemistry, and biology of ADP-ribose.

Veterans Like Me: Formative evaluation of a patient decision aid design.

Patient decision aids are tools intended to facilitate shared decision-making. Currently development of a patient decision aid is resource intensive: it requires a decision-specific review of the scientific literature by experts to ascertain the potential outcomes under different treatments. The goal of this project was to conduct a formative evaluation of a generalizable, scalable decision aid component we call Veterans Like Me (VLme). VLme mines EHR data to present the outcomes of individuals "like you" on different treatments to the user. These outcome are presented through a combination of an icon array and simulated narratives. Twenty-six patients participated in semi-structured interviews intended to elicit feedback on the tool's functional and interface design. The interview focused on the filters users desired with which to make cases similar to them, the kinds of outcomes they wanted presented, and their envisioned use of the tool. The interview also elicited participants information needs and salient factors related to the therapeutic decision. The interview transcripts were analyzed using an iteratively refined coding schema and content analysis. . Participants generally expressed enthusiasm for the tool's design and functionality. Our analysis identified desired filters for users to view patients like themselves, outcome types that should be included in future iterations of the tool (e.g. patient reported outcomes), and information needs that need to be addressed for patients to effectively participate in shared decision making. Implications for the integration of our findings into the design of patient decision aids are discussed.

Behavior change interventions: the potential of ontologies for advancing science and practice.

A central goal of behavioral medicine is the creation of evidence-based interventions for promoting behavior change. Scientific knowledge about behavior change could be more effectively accumulated using "ontologies." In information science, an ontology is a systematic method for articulating a "controlled vocabulary" of agreed-upon terms and their inter-relationships. It involves three core elements: (1) a controlled vocabulary specifying and defining existing classes; (2) specification of the inter-relationships between classes; and (3) codification in a computer-readable format to enable knowledge generation, organization, reuse, integration, and analysis. This paper introduces ontologies, provides a review of current efforts to create ontologies related to behavior change interventions and suggests future work. This paper was written by behavioral medicine and information science experts and was developed in partnership between the Society of Behavioral Medicine's Technology Special Interest Group (SIG) and the Theories and Techniques of Behavior Change Interventions SIG. In recent years significant progress has been made in the foundational work needed to develop ontologies of behavior change. Ontologies of behavior change could facilitate a transformation of behavioral science from a field in which data from different experiments are siloed into one in which data across experiments could be compared and/or integrated. This could facilitate new approaches to hypothesis generation and knowledge discovery in behavioral science.

Baseline Ability Makes a Larger Contribution to Race Performance in High-School Sprinters Than Race Experience or Training Exposure.

PURPOSE: There has long been a debate regarding the importance of talent versus training in athletic performance. In this study we sought to quantify their relative contributions to the race performance of high-school sprinters. METHODS: Using race results from the athletic.net website, we identified high-school athletes who participated in at least one race in both 9th and 12th grade in the 100 m, 200 m or 400 m. Athletes with a record of racing before high school were excluded from the analyses. Using separate linear regression models for each event and gender, we analyzed the effect of baseline ability, race experience and training exposure on race time in the 12th grade. RESULTS: 35,909 athletes, running a total of 1,627,652 races, contributed to the final analyses. The proportion of variance (R2) in 12th grade race times accounted for by baseline ability ranged from 40% to 51% depending on the event, and was consistently higher for females than males. Race experience explained 3.6-4.4% of the variance and training exposure explained 0.8-1.7%. CONCLUSION: Although race experience and training exposure impact high-school sprinters' performance, baseline ability is the dominant influence.

Regular expression-based learning to extract bodyweight values from clinical notes.

BACKGROUND: Bodyweight related measures (weight, height, BMI, abdominal circumference) are extremely important for clinical care, research and quality improvement. These and other vitals signs data are frequently missing from structured tables of electronic health records. However they are often recorded as text within clinical notes. In this project we sought to develop and validate a learning algorithm that would extract bodyweight related measures from clinical notes in the Veterans Administration (VA) Electronic Health Record to complement the structured data used in clinical research. METHODS: We developed the Regular Expression Discovery Extractor (REDEx), a supervised learning algorithm that generates regular expressions from a training set. The regular expressions generated by REDEx were then used to extract the numerical values of interest. To train the algorithm we created a corpus of 268 outpatient primary care notes that were annotated by two annotators. This annotation served to develop the annotation process and identify terms associated with bodyweight related measures for training the supervised learning algorithm. Snippets from an additional 300 outpatient primary care notes were subsequently annotated independently by two reviewers to complete the training set. Inter-annotator agreement was calculated. REDEx was applied to a separate test set of 3561 notes to generate a dataset of weights extracted from text. We estimated the number of unique individuals who would otherwise not have bodyweight related measures recorded in the CDW and the number of additional bodyweight related measures that would be additionally captured. RESULTS: REDEx's performance was: accuracy=98.3%, precision=98.8%, recall=98.3%, F=98.5%. In the dataset of weights from 3561 notes, 7.7% of notes contained bodyweight related measures that were not available as structured data. In addition 2 additional bodyweight related measures were identified per individual per year. CONCLUSION: Bodyweight related measures are frequently stored as text in clinical notes. A supervised learning algorithm can be used to extract this data. Implications for clinical care, epidemiology, and quality improvement efforts are discussed.

A qualitative evaluation of the crucial attributes of contextual information necessary in EHR design to support patient-centered medical home care.

BACKGROUND: Effective implementation of a Primary Care Medical Home model of care (PCMH) requires integration of patients' contextual information (physical, mental, social and financial status) into an easily retrievable information source for the healthcare team and clinical decision-making. This project explored clinicians' perceptions about important attributes of contextual information for clinical decision-making, how contextual information is expressed in CPRS clinical documentation as well as how clinicians in a highly computerized environment manage information flow related to these areas. METHODS: A qualitative design using Cognitive Task Analyses and a modified Critical Incident Technique were used. The study was conducted in a large VA with a fully implemented EHR located in the western United States. Seventeen providers working in a PCMH model of care in Primary Care, Home Based Care and Geriatrics reported on a recent difficult transition requiring contextual information for decision-making. The transcribed interviews were qualitatively analyzed for thematic development related to contextual information using an iterative process and multiple reviewers with ATLAS@ti software. RESULTS: Six overarching themes emerged as attributes of contextual information: Informativeness, goal language, temporality, source attribution, retrieval effort, and information quality. CONCLUSIONS: These results indicate that specific attributes are needed to in order for contextual information to fully support clinical decision-making in a Medical Home care delivery environment. Improved EHR designs are needed for ease of contextual information access, displaying linkages across time and settings, and explicit linkages to both clinician and patient goals. Implications relevant to providers' information needs, team functioning and EHR design are discussed.

Tailoring of Health-Promotion Video Messaging for Reproductive-Aged Women at Risk for Developing Cardiometabolic Disease: Qualitative Focus-Groups Study.

BACKGROUND: Targeting reproductive-aged women at high risk for type 2 diabetes (T2D) provides an opportunity for prevention earlier in the life course. A woman's experiences during her reproductive years may have a large impact on her future risk of T2D. Her risk is 7 to 10 times higher if she has had gestational diabetes (GDM). Despite these risks, T2D is preventable. Evidence-based programs, such as the National Diabetes Prevention Program (DPP), can reduce the risk of developing T2D by nearly 60%. However, only 0.4% of adults with prediabetes have participated in the DPP to date and reproductive-aged women are 50% less likely to participate than older women. In prior work, our team developed a mobile 360° video to address diabetes risk awareness and promote DPP enrollment among at-risk adults; this video was not designed, however, for reproductive-aged women. OBJECTIVE: This study aims to obtain feedback from reproductive-aged women with cardiometabolic disease risk about a 360° video designed to promote enrollment in the DPP, and to gather suggestions about tailoring video messages to reproductive-aged women. METHODS: Focus groups and a qualitative descriptive approach were used. Women with at least 1 previous pregnancy, aged 18 to 40 years, participated in one of three focus groups stratified by the following health risks: (1) a history of GDM or a hypertensive disorder of pregnancy, (2) a diagnosis of prediabetes, or (3) a BMI classified as obese. Focus-group questions addressed several topics; this report shared findings regarding video feedback. The 3 focus-group discussions were conducted via Zoom and were recorded and transcribed for analysis. Deductive codes were used to identify concepts related to the research question and inductive codes were created for novel insights shared by participants. The codes were then organized into categories and themes. RESULTS: The main themes identified were positive feedback, negative feedback, centering motherhood, and the importance of storytelling. While some participants said the video produced a sense of urgency for health-behavior change, all participants agreed that design changes could improve the video's motivating effect on health-behavior change in reproductive-aged women. Participants felt a tailored video should recognize the complexities of being a mother and how these dynamics contribute to women's difficulty engaging in healthy behaviors without stirring feelings of guilt. Women desired a video with a positive, problem-solving perspective, and recommended live links as clickable resources for practical solutions promoting health behavior change. Women suggested using storytelling, both to describe how complications experienced during pregnancy impact long-term health and to motivate health behavior change. CONCLUSIONS: Reproductive-aged women require tailored lifestyle-change messaging that addresses barriers commonly encountered by this population (eg, parenting or work responsibilities). Moreover, messaging should prioritize a positive tone that harnesses storytelling and human connection while offering realistic solutions.

Use of implementation mapping in the planning of a hybrid type 1 pragmatic clinical trial: the BeatPain Utah study.

BACKGROUND: Considerable disparities in chronic pain management have been identified. Persons in rural, lower income, and minoritized communities are less likely to receive evidence-based, nonpharmacologic care. Telehealth delivery of nonpharmacologic, evidence-based interventions for persons with chronic pain is a promising strategy to lessen disparities, but implementation comes with many challenges. The BeatPain Utah study is a hybrid type 1 effectiveness-implementation pragmatic clinical trial investigating telehealth strategies to provide nonpharmacologic care from physical therapists to persons with chronic back pain receiving care in ommunity health centers (CHCs). CHCs provide primary care to all persons regardless of ability to pay. This paper outlines the use of implementation mapping to develop a multifaceted implementation plan for the BeatPain study. METHODS: During a planning year for the BeatPain trial, we developed a comprehensive logic model including the five-step implementation mapping process informed by additional frameworks and theories. The five iterative implementation mapping steps were addressed in the planning year: (1) conduct needs assessments for involved groups; (2) identify implementation outcomes, performance objectives, and determinants; (3) select implementation strategies; (4) produce implementation protocols and materials; and (5) evaluate implementation outcomes. RESULTS: CHC leadership/providers, patients, and physical therapists were identified as involved groups. Barriers and assets were identified across groups which informed identification of performance objectives necessary to implement two key processes: (1) electronic referral of patients with back pain in CHC clinics to the BeatPain team and (2) connecting patients with physical therapists providing telehealth. Determinants of the performance objectives for each group informed our choice of implementation strategies which focused on training, education, clinician support, and tailoring physical therapy interventions for telehealth delivery and cultural competency. We selected implementation outcomes for the BeatPain trial to evaluate the success of our implementation strategies. CONCLUSIONS: Implementation mapping provided a comprehensive and systematic approach to develop an implementation plan during the planning phase for our ongoing hybrid effectiveness-implementation trial. We will be able to evaluate the implementation strategies used in the BeatPain Utah study to inform future efforts to implement telehealth delivery of evidence-based pain care in CHCs and other settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04923334 . Registered June 11, 2021.

SCALE-UP II: protocol for a pragmatic randomised trial examining population health management interventions to increase the uptake of at-home COVID-19 testing in community health centres.

INTRODUCTION: SCALE-UP II aims to investigate the effectiveness of population health management interventions using text messaging (TM), chatbots and patient navigation (PN) in increasing the uptake of at-home COVID-19 testing among patients in historically marginalised communities, specifically, those receiving care at community health centres (CHCs). METHODS AND ANALYSIS: The trial is a multisite, randomised pragmatic clinical trial. Eligible patients are >18 years old with a primary care visit in the last 3 years at one of the participating CHCs. Demographic data will be obtained from CHC electronic health records. Patients will be randomised to one of two factorial designs based on smartphone ownership. Patients who self-report replying to a text message that they have a smartphone will be randomised in a 2×2×2 factorial fashion to receive (1) chatbot or TM; (2) PN (yes or no); and (3) repeated offers to interact with the interventions every 10 or 30 days. Participants who do not self-report as having a smartphone will be randomised in a 2×2 factorial fashion to receive (1) TM with or without PN; and (2) repeated offers every 10 or 30 days. The interventions will be sent in English or Spanish, with an option to request at-home COVID-19 test kits. The primary outcome is the proportion of participants using at-home COVID-19 tests during a 90-day follow-up. The study will evaluate the main effects and interactions among interventions, implementation outcomes and predictors and moderators of study outcomes. Statistical analyses will include logistic regression, stratified subgroup analyses and adjustment for stratification factors. ETHICS AND DISSEMINATION: The protocol was approved by the University of Utah Institutional Review Board. On completion, study data will be made available in compliance with National Institutes of Health data sharing policies. Results will be disseminated through study partners and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT05533918 and NCT05533359.

Perceptions about future health trajectories among women at risk for developing cardiometabolic disease: A qualitative study.

Background: The reproductive years provide a window into future risk for Type 2 Diabetes (T2DM); women's risk is seven to 10 times higher after gestational diabetes (GDM) and two to four times higher after a hypertensive disorder of pregnancy (HDP). Targeting reproductive-aged women at high risk for T2DM could reduce future T2DM incidence. However, little is known about such women's diabetes risk perceptions, or their knowledge or barriers/motivators of lifestyle change-information essential to understanding how to engage these at-risk women in tailored prevention programs promoting long-term health. This study's aims include: among reproductive-aged women at high risk for T2DM, what is/are 1) personal health-risk awareness, 2) lifestyle-change interest, and 3) barriers/motivators of participation in lifestyle-change programs? Methods: Women aged 18 to 48 were eligible if they had one of the following health risks: 1) GDM or HDP during pregnancy, 2) prediabetes diagnosis, or 3) BMI classified as obese. Three Zoom focus groups, organized by risk group, were conducted with a total of 20 participants. Qualitative content and thematic analysis were used for the focus group transcriptions. Results: Women's personal health-risk awareness was limited and generalized (e.g., being overweight might lead to other risks) and rarely reflected awareness connected to their personal health history (e.g., GDM increases their lifetime risk of T2DM). Participants reported that healthcare providers did not adequately follow or address their health risks. All women expressed interest in making healthy lifestyle changes, including engagement in formal programs, but they shared multiple barriers to healthy behavior change related to being "busy moms." Women emphasized the need for social support and realistic solutions that accounted for the dynamics of motherhood and family life. Common motivators included the desire to maintain health for their families and to set a good example for their children. Conclusions: Participants lacked knowledge and were eager for information. Healthcare improvement opportunities include better coordination of care between primary and specialty-care providers, and more frequent communication and education on diabetes-related health risks and long-term health. Formal lifestyle programs should tailor content by providing multiple formats and flexibility of scheduling while leveraging peer support for sustained engagement.