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.

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.

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.

Increasing the reach of evidence-based interventions for weight management and diabetes prevention among Medicaid patients: study protocol for a pilot Sequential Multiple Assignment Randomised Trial.

INTRODUCTION: Over 40% of US adults meet criteria for obesity, a major risk factor for chronic disease. Obesity disproportionately impacts populations that have been historically marginalised (eg, low socioeconomic status, rural, some racial/ethnic minority groups). Evidence-based interventions (EBIs) for weight management exist but reach less than 3% of eligible individuals. The aims of this pilot randomised controlled trial are to evaluate feasibility and acceptability of dissemination strategies designed to increase reach of EBIs for weight management. METHODS AND ANALYSIS: This study is a two-phase, Sequential Multiple Assignment Randomized Trial, conducted with 200 Medicaid patients. In phase 1, patients will be individually randomised to single text message (TM1) or multiple text messages (TM+). Phase 2 is based on treatment response. Patients who enrol in the EBI within 12 weeks of exposure to phase 1 (ie, responders) receive no further interventions. Patients in TM1 who do not enrol in the EBI within 12 weeks of exposure (ie, TM1 non-responders) will be randomised to either TM1-Continued (ie, no further TM) or TM1 & MAPS (ie, no further TM, up to 2 Motivation And Problem Solving (MAPS) navigation calls) over the next 12 weeks. Patients in TM+ who do not enrol in the EBI (ie, TM+ non-responders) will be randomised to either TM+Continued (ie, monthly text messages) or TM+ & MAPS (ie, monthly text messages, plus up to 2 MAPS calls) over the next 12 weeks. Descriptive statistics will be used to characterise feasibility (eg, proportion of patients eligible, contacted and enrolled in the trial) and acceptability (eg, participant opt-out, participant engagement with dissemination strategies, EBI reach (ie, the proportion of participants who enrol in EBI), adherence, effectiveness). ETHICS AND DISSEMINATION: Study protocol was approved by the University of Utah Institutional Review Board (#00139694). Results will be disseminated through study partners and peer-reviewed publications. TRIAL REGISTRATION NUMBER: clinicaltrials.gov; NCT05666323.

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 I effectiveness-implementation pragmatic clinical trial investigating telehealth strategies to provide nonpharmacologic care from physical therapists to persons with chronic back pain receiving care in Community 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 5-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 (https://clinicaltrials.gov/study/NCT04923334.

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.

Rapid-cycle designs to adapt interventions for COVID-19 in safety-net healthcare systems.

Racial/ethnic minority, low socioeconomic status, and rural populations are disproportionately affected by COVID-19. Developing and evaluating interventions to address COVID-19 testing and vaccination among these populations are crucial to improving health inequities. The purpose of this paper is to describe the application of a rapid-cycle design and adaptation process from an ongoing trial to address COVID-19 among safety-net healthcare system patients. The rapid-cycle design and adaptation process included: (a) assessing context and determining relevant models/frameworks; (b) determining core and modifiable components of interventions; and (c) conducting iterative adaptations using Plan-Do-Study-Act (PDSA) cycles. PDSA cycles included: Plan. Gather information from potential adopters/implementers (e.g., Community Health Center [CHC] staff/patients) and design initial interventions; Do. Implement interventions in single CHC or patient cohort; Study. Examine process, outcome, and context data (e.g., infection rates); and, Act. If necessary, refine interventions based on process and outcome data, then disseminate interventions to other CHCs and patient cohorts. Seven CHC systems with 26 clinics participated in the trial. Rapid-cycle, PDSA-based adaptations were made to adapt to evolving COVID-19-related needs. Near real-time data used for adaptation included data on infection hot spots, CHC capacity, stakeholder priorities, local/national policies, and testing/vaccine availability. Adaptations included those to study design, intervention content, and intervention cohorts. Decision-making included multiple stakeholders (e.g., State Department of Health, Primary Care Association, CHCs, patients, researchers). Rapid-cycle designs may improve the relevance and timeliness of interventions for CHCs and other settings that provide care to populations experiencing health inequities, and for rapidly evolving healthcare challenges such as COVID-19.

Racial/ethnic minority, low socioeconomic status, and rural populations experience a disproportionate burden of COVID-19. Finding ways to address COVID-19 among these populations is crucial to improving health inequities. The purpose of this paper is to describe the rapid-cycle design process for a research project to address COVID-19 testing and vaccination among safety-net healthcare system patients. The project used real-time information on changes in COVID-19 policy (e.g., vaccination authorization), local case rates, and the capacity of safety-net healthcare systems to iteratively change interventions to ensure interventions were relevant and timely for patients. Key changes that were made to interventions included a change to the study design to include vaccination as a focus of the interventions after the vaccine was authorized; change in intervention content according to the capacity of local Community Health Centers to provide testing to patients; and changes to intervention cohorts such that priority groups of patients were selected for intervention based on characteristics including age, residency in an infection "hot spot," or race/ethnicity. Iteratively improving interventions based on real-time data collection may increase intervention relevance and timeliness, and rapid-cycle adaptions can be successfully implemented in resource constrained settings like safety-net healthcare systems.

BeatPain Utah: study protocol for a pragmatic randomised trial examining telehealth strategies to provide non-pharmacologic pain care for persons with chronic low back pain receiving care in federally qualified health centers.

INTRODUCTION: Although evidence-based guidelines recommend non-pharmacologic treatments as first-line care for chronic low back pain (LBP), uptake has been limited, particularly in rural, low-income and ethnically diverse communities. The BeatPain study will evaluate the implementation and compare the effectiveness of two strategies to provide non-pharmacologic treatment for chronic LBP. The study will use telehealth to overcome access barriers for persons receiving care in federally qualified health centres (FQHCs) in the state of Utah. METHODS AND ANALYSIS: BeatPain Utah is a pragmatic randomised clinical trial with a hybrid type I design investigating different strategies to provide non-pharmacologic care for adults with chronic LBP seen in Utah FQHCs. The intervention strategies include a brief pain consult (BPC) and telehealth physical therapy (PT) component provided using either an adaptive or sequenced delivery strategy across two 12-week treatment phases. Interventions are provided via telehealth by centrally located physical therapists. The sequenced delivery strategy provides the BPC, followed by telehealth PT in the first 12 weeks for all patients. The adaptive strategy uses a stepped care approach and provides the BPC in the first 12 weeks and telehealth PT to patients who are non-responders to the BPC component. We will recruit 500 English-speaking or Spanish-speaking participants who will be individually randomised with 1:1 allocation. The primary outcome is the Pain, Enjoyment and General Activity measure of pain impact with secondary outcomes including the additional pain assessment domains specified by the National Institutes (NIH) of Health Helping to End Addiction Long Initiative and implementation measures. Analyses of primary and secondary measures of effectiveness will be performed under longitudinal mixed effect models across assessments at baseline, and at 12, 26 and 52 weeks follow-ups. ETHICS AND DISSEMINATION: Ethics approval for the study was obtained from the University of Utah Institutional Review Board. On completion, study data will be made available in compliance with NIH data sharing policies. TRIAL REGISTRATION NUMBER: NCT04923334.

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.

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.

Mobile Virtual Reality Versus Mobile 360° Video to Promote Enrollment in the Diabetes Prevention Program Among Hispanic Adults: Pilot Study.

BACKGROUND: Hispanic adults are at increased risk of developing type 2 diabetes. The Diabetes Prevention Program (DPP) reduces the risk of developing type 2 diabetes; however, the rate of enrollment is very low. OBJECTIVE: The goal of this pilot project was to determine whether presenting brief motivational mobile videos in virtual reality vs 360° video has differential effects on risk perceptions and enrollment in the DPP. METHODS: Adults with prediabetes were recruited at a clinic serving a low-income Hispanic community. After consenting, the participants completed a baseline survey that collected information about demographics and risk perceptions. All participants then viewed 2 videos. Per random assignment, the videos were presented either using the participant's smartphone alone (360° video) or were viewed with their smartphone in a virtual reality (VR) cardboard headset. Two weeks later, a follow-up survey collected measures of enrollment in the DPP, risk perceptions, health literacy, the importance of contextual factors related to the decision of whether to enroll in the DPP (eg, distance to the class), and qualitative feedback on the interventions. We used logistic regression to determine whether enrollment in the DPP differed by intervention mode, while accounting for health literacy and contextual factors related to the DPP. We used unpaired t tests to examine differences in change in risk perceptions between groups. Paired t tests were used to examine within-subject changes in risk perceptions. RESULTS: A total of 116 participants provided complete data. Most participants were middle-aged (mean age 44.6 years; SD 11.9) Hispanic (114/116), female (79/116), with low health literacy (mean score 12.3/20; SD 3.4). Enrollment in the DPP was 44/116 (37.9%) overall but did not differ by group (odds ratio for enrolling in VR group 1.78, 95% CI 0.75-4.3; P=.19). Individuals who rated the distance needed to travel to attend the DPP as more important were less likely to enroll in the DPP (odds ratio 0.56, 95% CI 0.33-0.92; P=.03). Risk perceptions did not differ by group (mean change in 360° video group -0.07, mean change in VR group 0.03, t=0.6, P=.54) and did not change within subjects (mean 0.02, t=0.21, P=.83). Participant feedback suggested that the videos are emotionally engaging and educational. CONCLUSIONS: The videos presented in 360° video and mobile VR had equal efficacy in promoting enrollment in the DPP. Future work to rigorously evaluate this intervention, its mechanism of action, and potential moderators of the efficacy are discussed.

Patient Perceptions of Hospital Experiences: Implications for Innovations in Patient Safety.

OBJECTIVE: The purpose of this study was to qualitatively examine safety experiences of hospitalized patients and families. METHODS: We conducted 5 focus groups at 2 sites with patients and family members of patients who had been hospitalized at least once within the preceding 2 years. Using a semistructured focus group script, participants were asked to describe hospital experiences, including any safety risks or problems, and to discuss trust in the hospital care team or members of the care team. All focus groups were audiorecorded and transcribed, and transcriptions were qualitatively analyzed using thematic analysis by experienced qualitative analysts and experts in patient safety. RESULTS: We collected rich descriptions of safety problems in the hospital. We identified 4 main themes from our focus group data. (1) Experiences with safety problems were not unusual among participants, (2) patients and families develop a structured "care story" about their hospital experiences, (3) there is a spectrum of trust between patients and the hospital care team members that can be diminished or enhanced by experiences, and (4) patients believed having someone who could advocate for them during their hospitalization was important. CONCLUSIONS: Our results suggest that acknowledgment of safety problems, clear communication, building trust, and a role for advocacy are impactful pathways health care providers and health care systems can improve patient experiences. Information technology such as patient- and clinician-facing displays can support each of these actions.

Engaging Patients in the Use of Real-Time Electronic Clinical Data to Improve the Safety and Reliability of Their Own Care.

OBJECTIVES: There is considerable evidence that providing patients with access to their health information is beneficial, but there is limited evidence regarding the effect of providing real-time patient safety-related information on health outcomes. The aim of this study was to evaluate the association between use of an electronic patient safety dashboard (Safety Advisor) and health outcomes. METHODS: The Safety Advisor was implemented in 6 adult medicine units at one hospital in the United States. Study participants were asked to use the Safety Advisor, which provides real-time patient safety-related information through a Web-based portal. The primary outcome was the association between the application usage and health outcomes (readmission rate and mortality rate) per 3 different usage groups, and the secondary outcome was the association of Patient Activation Measure (PAM) scores with use. RESULTS: One hundred eighty-one participants were included for the data analysis. Approximately 90% of users accessed the application during the first 4 days of enrollment: 51.6% of users only accessed it on 1 day, whereas 5.8% used it more than 3 days. Patients who used the application more had lower 30-day readmission rates (P = 0.01) compared with the lower-usage group. The PAM scores for users of Safety Advisor (71.8) were higher than the nonpatient portal users (60.8, P < 0.0001). CONCLUSIONS: We found an association between the use of Safety Advisor and health outcomes. Differences in PAM scores between groups were statistically significant. A larger-scale randomized control trial is warranted to evaluate the impact on patient outcomes among a high-risk patient population.

Successful Multi-Level HPV Vaccination Intervention at a Rural Healthcare Center in the Era of COVID-19.

Objectives: To develop and test a human papillomavirus (HPV) vaccination intervention that includes healthcare team training activities and patient reminders to reduce missed opportunities and improves the rate of appointment scheduling for HPV vaccination in a rural medical clinic in the United States. Methods: The multi-level and multi-component intervention included healthcare team training activities and the distribution of patient education materials along with technology-based patient HPV vaccination reminders for parents/caregivers and young adult patients. Missed vaccination opportunities were assessed pre- and post-intervention (n = 402 and n = 99, respectively) by retrospective chart review and compared using Pearson χ2. The patient parent/caregiver and young adult patient population (n = 80) was surveyed following the reminder messages and penalized logistic regression quantified unadjusted odds of scheduling a visit. Results: Missed opportunities for HPV vaccination declined significantly from the pre-intervention to the post-intervention period (21.6 vs. 8.1%, respectively, p = 0.002). Participants who recalled receipt of a vaccination reminder had 7.0 (95% CI 2.4-22.8) times higher unadjusted odds of scheduling a visit compared with those who did not recall receiving a reminder. The unadjusted odds of confirming that they had scheduled or were intending to schedule a follow-up appointment to receive the HPV vaccine was 4.9 (95% CI 1.51-20.59) times greater among those who had not received the vaccine for themselves or for their child. Conclusions: Results from this intervention are promising and suggest that vaccination interventions consisting of provider and support staff education and parent/caregiver and patient education materials, and reminders can reduce missed opportunities for vaccinations in rural settings.

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.

Workflow analysis for design of an electronic health record-based tobacco cessation intervention in community health centers.

OBJECTIVE: Tobacco use is the leading cause of preventable morbidity and mortality in the United States. Quitlines are effective telephone-based tobacco cessation services but are underutilized. The goal of this project was to describe current clinical workflows for Quitline referral and design an optimal electronic health record (EHR)-based workflow for Ask-Advice-Connect (AAC), an evidence-based intervention to increase Quitline referrals. MATERIALS AND METHODS: Ten Community Health Center systems (CHC), which use three different EHRs, participated in this study. Methods included: 9 group discussions with CHC leaders; 33 observations/interviews of clinical teams' workflow; surveys with 57 clinical staff; and assessment of the EHR ecosystem in each CHC. Data across these methods were integrated and coded according to the Fit between Individual, Task, Technology and Environment (FITTE) framework. The current and optimal workflow were notated using Business Process Modelling Notation. We compared the requirements of the optimal workflow with EHR capabilities. RESULTS: Current workflows are inefficient in data collection, variable in who, how, and when tobacco cessation advice and referral are enacted, and lack communication between referring clinics and the Quitline. In the optimal workflow, medical assistants deliver a standardized AAC intervention during the visit intake. Referrals are submitted electronically, and there is bidirectional communication between the clinic and Quitline. We implemented AAC within all three EHRs; however, deviations from the optimal workflow were necessary. CONCLUSION: Current workflows for Quitline referral are inefficient and ineffective. We propose an optimal workflow and discuss improvements in EHR capabilities that would improve the implementation of AAC.

Motivation and Problem Solving Versus Mobile 360° Videos to Promote Enrollment in the National Diabetes Prevention Program's Lifestyle Change Program Among People With Prediabetes: Protocol for a Randomized Trial.

BACKGROUND: More than 88 million Americans are at risk of developing type 2 diabetes mellitus (T2DM). The National Diabetes Prevention Program's Lifestyle Change Program (DPP LCP) has been shown to be effective in reducing the risk of progressing from prediabetes to T2DM. However, most individuals who could benefit from the program do not enroll. OBJECTIVE: The aim of this trial is to test the real-world efficacy of 3 mobile phone-based approaches to increasing enrollment in the DPP LCP including a best-practice condition and 2 novel approaches. METHODS: We will conduct a 3-armed randomized clinical trial comparing enrollment and 1-month engagement in the DPP LCP among adults with prediabetes from 2 health care settings. Participants in the best-practice condition will receive SMS-based notifications that they have prediabetes and a link to a website that explains prediabetes, T2DM, and the DPP LCP. This will be followed by a single question survey, "Would you like the DPP LCP to call you to enroll?" Participants in the 2 intervention arms will receive the same best-practice intervention plus either 2 mobile 360° videos or up to 5 brief phone calls from a health coach trained in a motivational coaching approach known as Motivation and Problem Solving (MAPS). We will collect measures of diabetes-related knowledge, beliefs in the controllability of risk for T2DM, risk perceptions for T2DM, and self-efficacy for lifestyle change pre-intervention and 4 weeks later. The primary outcomes of the study are enrollment in the DPP LCP and 4-week engagement in the DPP LCP. In addition, data on the person-hours needed to deliver the interventions as well as participant feedback about the interventions and their acceptability will be collected. Our primary hypotheses are that the 2 novel interventions will lead to higher enrollment and engagement in the DPP LCP than the best-practice intervention. Secondary hypotheses concern the mechanisms of action of the 2 intervention arms: (1) whether changes in risk perception are associated with program enrollment among participants in the mobile 360° video group and (2) whether changes in self-efficacy for lifestyle change are associated with program enrollment among participants in the MAPS coaching group. Finally, exploratory analyses will examine the cost effectiveness and acceptability of the interventions. RESULTS: The project was funded in September 2020; enrollment began in February 2021 and is expected to continue through July 2022. CONCLUSIONS: We are conducting a test of 2 novel, scalable, mobile phone-based interventions to increase enrollment in the DPP LCP. If effective, they have tremendous potential to be scaled up to help prevent T2DM nationwide. TRIAL REGISTRATION: ClinicalTrials.gov NCT04746781; https://clinicaltrials.gov/ct2/show/NCT04746781. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28884.

Inhibition of CRISPR-Cas12a DNA targeting by nucleosomes and chromatin.

Genome engineering nucleases must access chromatinized DNA. Here, we investigate how AsCas12a cleaves DNA within human nucleosomes and phase-condensed nucleosome arrays. Using quantitative kinetics approaches, we show that dynamic nucleosome unwrapping regulates target accessibility to Cas12a and determines the extent to which both steps of binding-PAM recognition and R-loop formation-are inhibited by the nucleosome. Relaxing DNA wrapping within the nucleosome by reducing DNA bendability, adding histone modifications, or introducing target-proximal dCas9 enhances DNA cleavage rates over 10-fold. Unexpectedly, Cas12a readily cleaves internucleosomal linker DNA within chromatin-like, phase-separated nucleosome arrays. DNA targeting is reduced only ~5-fold due to neighboring nucleosomes and chromatin compaction. This work explains the observation that on-target cleavage within nucleosomes occurs less often than off-target cleavage within nucleosome-depleted genomic regions in cells. We conclude that nucleosome unwrapping regulates accessibility to CRISPR-Cas nucleases and propose that increasing nucleosome breathing dynamics will improve DNA targeting in eukaryotic cells.

Identification of PARP-7 substrates reveals a role for MARylation in microtubule control in ovarian cancer cells.

PARP-7 (TiPARP) is a mono(ADP-ribosyl) transferase whose protein substrates and biological activities are poorly understood. We observed that PARP7 mRNA levels are lower in ovarian cancer patient samples compared to non-cancerous tissue, but PARP-7 protein nonetheless contributes to several cancer-related biological endpoints in ovarian cancer cells (e.g. growth, migration). Global gene expression analyses in ovarian cancer cells subjected to PARP-7 depletion indicate biological roles for PARP-7 in cell-cell adhesion and gene regulation. To identify the MARylated substrates of PARP-7 in ovarian cancer cells, we developed an NAD+ analog-sensitive approach, which we coupled with mass spectrometry to identify the PARP-7 ADP-ribosylated proteome in ovarian cancer cells, including cell-cell adhesion and cytoskeletal proteins. Specifically, we found that PARP-7 MARylates α-tubulin to promote microtubule instability, which may regulate ovarian cancer cell growth and motility. In sum, we identified an extensive PARP-7 ADP-ribosylated proteome with important roles in cancer-related cellular phenotypes.

Cancer is a complex illness where changes inside healthy cells causes them to grow and reproduce rapidly. Specialized proteins called enzymes ­ which regulate chemical reactions in the cell ­ often help cancer develop and spread through the body. One such enzyme called PARP-7 labels other proteins by attaching a chemical group which changes their behavior. However, it was unknown which proteins PARP-7 modifies and how this tag alters the actions of these proteins. To investigate this, Parsons, Challa, Gibson et al. developed a method to find and identify the proteins labelled by PARP-7 in ovarian cancer cells taken from patients and cultured in the laboratory. This revealed that PARP-7 labels hundreds of different proteins, including adhesion proteins which affect the connections between cells and cytoskeletal proteins which regulate a cell's shape and how it moves. One of the cytoskeletal proteins modified by PARP-7 is α-tubulin, which joins together with other tubulins to form long, tube-like structures known as microtubules. Parsons et al. found that when α-tubulin is labelled by PARP-7, it creates unstable microtubules that alter how the cancer cells grow and move. They discovered that depleting PARP-7 or mutating the sites where it modifies α-tubulin increased the stability of microtubules and slowed the growth of ovarian cancer cells. Ovarian cancer is the fifth leading cause of cancer-related deaths among women in the United States. A new drug which suppresses the activity of PARP-7 has recently been developed, and this drug could potentially be used to treat ovarian cancer patients with high levels of PARP-7. Clinical trials are ongoing to see how this drug affects the behavior of cancer cells in patients.