User Experience of Access to Sexual Assault Nurse Examiner and Emergency Contraception in Emergency Departments in the United States: A National Survey.

Background: Despite the prevalence of sexual assault presentations to emergency departments (ED) in the United States, current access to sexual assault nurse examiners (SANE) and emergency contraception (EC) in EDs is unknown. Methods: In this study we employed a "secret shopper," cross-sectional telephonic survey. A team attempted phone contact with a representative sample of EDs and asked respondents about the availability of SANEs and EC in their ED. Reported availability was correlated with variables including region, urban/rural status, hospital size, faith affiliation, academic affiliation, and existence of legislative requirements to offer EC. Results: Over a two-month period in 2019, 1,046 calls to hospitals were attempted and 960 were completed (91.7% response rate). Of the 4,360 eligible hospitals listed in a federal database, 960 (22.0%) were contacted. Access to SANEs and EC were reported to be available in 48.9% (95% confidence interval [CI] 45.5-52.0) and 42.5% (95% CI 39.4-45.7) of hospitals, respectively. Access to EC was positively correlated with SANE availability. The EDs reporting SANE and EC availability were more likely to be large, rural, and affiliated with an academic institution. Those reporting access to EC were more likely to be in the Northeast and in states with legislative requirements to offer EC. Conclusion: Our results suggest that perceived access to sexual assault services and emergency contraception in EDs in the United States remains poor with regional and legislative disparities. Results suggest disparities in perceived access to EC and SANE in the ED, which have implications for improving ED practices regarding care of sexual assault victims.

Impact of Fontan fenestration on adverse cardiovascular outcomes: a multicenter study.

BACKGROUND: Fenestrating a Fontan baffle has been associated with improved peri-operative outcomes in patients with univentricular hearts. However, longer-term potential adverse effects remain debated. We sought to assess the impact of a fenestrated Fontan baffle on adverse cardiovascular events including all-cause mortality, cardiac transplantation, atrial arrhythmias, and thromboemboli. METHODS: A multicenter North American retrospective cohort study was conducted on patients with a total cavopulmonary connection Fontan baffle, with and without fenestration. All components of the composite outcome were independently adjudicated. Potential static and time-varying confounders were taken into consideration, along with competing risks. RESULTS: A total of 407 patients were followed for 10.4 (7.1-14.4) years, 70.0% of whom had fenestration of their Fontan baffle. The fenestration spontaneously closed or was deliberately sealed in 79.9% of patients a median of 2.0 years after Fontan completion. In multivariable analysis in which a persistent fenestration was modelled as a time-dependent variable, an open fenestration did not confer a higher risk of the composite outcome [hazard ratio 1.18, 95% confidence interval (0.71 to 1.97), P=0.521]. In secondary analyses, an open fenestration was not significantly associated with components of the primary outcome, i.e., mortality or transplantation, atrial arrhythmias, or thromboemboli. However, sensitivity analyses to assess the possible range of error resulting from imprecise dates for spontaneous fenestration closures could not rule-out significant associations between an open fenestration and atrial arrhythmias or thromboemboli. CONCLUSION: In this multicenter study, no significant association was identified between an open fenestration in the Fontan baffle and major adverse cardiovascular events.

The vascular complications of diabetes: a review of their management, pathogenesis, and prevention.

INTRODUCTION: This review highlights the pathogenesis of both microvascular and macrovascular complications of diabetes and how these mechanisms influence both the management and preventative strategies of these complications. The cumulative data shown in this review suggest hyperglycemic and blood pressure control remain central to this intricate process. AREAS COVERED: We reviewed the literature including retrospective, prospective trials as well as meta-analysis, and post hoc analysis of randomized trials on microvascular andmacrovascular complications. EXPERT OPINION: Further research is needed to explore the ideal intervention targets and preventative strategies needed to prevent macrovascular complications. Furthermore, as the data for trials looking at microvascular complications lengthen more long-term data will further elucidate the role that the duration of diabetes has on these complications. Additionally, trials looking to maximize hyperglycemic control with multiple agents in diabetes, such as metformin, SGL2isand GLP-1 receptor agonists are currently in process, which will have implications for rates of microvascular as well as macrovascular complications.

Quantifying Health Outcome Disparity in Invasive Methicillin-Resistant Staphylococcus aureus Infection using Fairness Algorithms on Real-World Data.

This study quantifies health outcome disparities in invasive Methicillin-Resistant Staphylococcus aureus (MRSA) infections by leveraging a novel artificial intelligence (AI) fairness algorithm, the Fairness-Aware Causal paThs (FACTS) decomposition, and applying it to real-world electronic health record (EHR) data. We spatiotemporally linked 9 years of EHRs from a large healthcare provider in Florida, USA, with contextual social determinants of health (SDoH). We first created a causal structure graph connecting SDoH with individual clinical measurements before/upon diagnosis of invasive MRSA infection, treatments, side effects, and outcomes; then, we applied FACTS to quantify outcome potential disparities of different causal pathways including SDoH, clinical and demographic variables. We found moderate disparity with respect to demographics and SDoH, and all the top ranked pathways that led to outcome disparities in age, gender, race, and income, included comorbidity. Prior kidney impairment, vancomycin use, and timing were associated with racial disparity, while income, rurality, and available healthcare facilities contributed to gender disparity. From an intervention standpoint, our results highlight the necessity of devising policies that consider both clinical factors and SDoH. In conclusion, this work demonstrates a practical utility of fairness AI methods in public health settings.

Optimizing Dynamic Antibiotic Treatment Strategies against Invasive Methicillin-Resistant Staphylococcus Aureus Infections using Causal Survival Forests and G-Formula on Statewide Electronic Health Record Data.

Developing models for individualized, time-varying treatment optimization from observational data with large variable spaces, e.g., electronic health records (EHR), is problematic because of inherent, complex bias that can change over time. Traditional methods such as the g-formula are robust, but must identify critical subsets of variables due to combinatorial issues. Machine learning approaches such as causal survival forests have fewer constraints and can provide fine-tuned, individualized counterfactual predictions. In this study, we aimed to optimize time-varying antibiotic treatment -identifying treatment heterogeneity and conditional treatment effects- against invasive methicillin-resistant Staphylococcus Aureus (MRSA) infections, using statewide EHR data collected in Florida, USA. While many previous studies focused on measuring the effects of the first empiric treatment (i.e., usually vancomycin), our study focuses on dynamic sequential treatment changes, comparing possible vancomycin switches with other antibiotics at clinically relevant time points, e.g., after obtaining a bacterial culture and susceptibility testing. Our study population included adult individuals admitted to the hospital with invasive MRSA. We collected demographic, clinical, medication, and laboratory information from the EHR for these patients. Then, we followed three sequential antibiotic choices (i.e., their empiric treatment, subsequent directed treatment, and final sustaining treatment), evaluating 30-day mortality as the outcome. We applied both causal survival forests and g-formula using different clinical intervention policies. We found that switching from vancomycin to another antibiotic improved survival probability, yet there was a benefit from initiating vancomycin compared to not using it at any time point. These findings show consistency with the empiric choice of vancomycin before confirmation of MRSA and shed light on how to manage switches on course. In conclusion, this application of causal machine learning on EHR demonstrates utility in modeling dynamic, heterogeneous treatment effects that cannot be evaluated precisely using randomized clinical trials.

The Use of Virtual Reality Learning on Transition Education in Adolescents with Congenital Heart Disease.

Improvement in congenital heart disease (CHD) outcomes has created a growing population of adolescents and young adults with unique health needs that require thoughtful transition planning and eventual transfer of care to an adult provider. Often, poor health literacy and limited resources can lead to interrupted care, which places them at risk for adverse health-related consequences. In 2019, the Wisconsin Adult Congenital Heart Disease transition program partnered with Stanford Virtual Heart (SVH), a virtual reality (VR) platform, to allow young adult patients to learn about their CHD in a clinic-based setting. We completed a single-center pilot study to evaluate these patients' experience and perceptions to using VR during their transition education. At an initial transition visit, we used an immediate post-VR experience survey, scored using Likert scales of 1-5 (1 = strongly disagree, 5 = strongly agree). Twenty-two patients (13 males) between the ages of 16 and 19 participated. Lesions included pulmonary stenosis, Tetralogy of Fallot, atrial and ventricular septal defect, coarctation, aortic stenosis, hypoplastic left heart syndrome, and patent ductus arteriosus. Likert averages were 4.7 for finding VR helped with understanding their heart lesion, 4.6 for finding VR helped with understanding their heart surgery, 4.7 for enjoying the VR heart simulation, and 4.6 for finding that it was a good use of time. This study demonstrates that adolescents enjoyed using SVH and found it helpful. Clinical implementation shows promise as a plausible adjunct tool for transition education.

Design and Harmonization Approach for the Multi-Institutional Neurocognitive Discovery Study (MINDS) of Adult Congenital Heart Disease (ACHD) Neuroimaging Ancillary Study: A Technical Note.

Dramatic advances in the management of congenital heart disease (CHD) have improved survival to adulthood from less than 10% in the 1960s to over 90% in the current era, such that adult CHD (ACHD) patients now outnumber their pediatric counterparts. ACHD patients demonstrate domain-specific neurocognitive deficits associated with reduced quality of life that include deficits in educational attainment and social interaction. Our hypothesis is that ACHD patients exhibit vascular brain injury and structural/physiological brain alterations that are predictive of specific neurocognitive deficits modified by behavioral and environmental enrichment proxies of cognitive reserve (e.g., level of education and lifestyle/social habits). This technical note describes an ancillary study to the National Heart, Lung, and Blood Institute (NHLBI)-funded Pediatric Heart Network (PHN) "Multi-Institutional Neurocognitive Discovery Study (MINDS) in Adult Congenital Heart Disease (ACHD)". Leveraging clinical, neuropsychological, and biospecimen data from the parent study, our study will provide structural-physiological correlates of neurocognitive outcomes, representing the first multi-center neuroimaging initiative to be performed in ACHD patients. Limitations of the study include recruitment challenges inherent to an ancillary study, implantable cardiac devices, and harmonization of neuroimaging biomarkers. Results from this research will help shape the care of ACHD patients and further our understanding of the interplay between brain injury and cognitive reserve.

Endothelial dysfunction in autoimmune, pulmonary, and kidney systems, and exercise tolerance following SARS-CoV-2 infection.

Long COVID is characterized by persistent symptoms beyond 3-months of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection that last for at least 2 months and cannot be explained by an alternative diagnosis. Autonomic, immunologic, endothelial, and hypercoagulation are implicated as possible mechanisms of long COVID symptoms. Despite recognition of the public health challenges posed by long COVID, the current understanding of the pathophysiological underpinnings is still evolving. In this narrative review, we explore the long-term effects of SARS-CoV-2 infection on T cell activation such as autoimmune disorders and endothelial cell dysfunction involving vascular impairments within pulmonary and renal architecture. We have described how endothelial dysfunction and vascular abnormalities may underscore findings of exercise intolerance by way of impaired peripheral oxygen extraction in individuals with long COVID.

TCAB1 prevents nucleolar accumulation of the telomerase RNA to facilitate telomerase assembly.

Localization of a variety of RNAs to non-membrane-bound cellular compartments such as nucleoli and Cajal bodies is critical for their stability and function. The molecular mechanisms that underly the recruitment and exclusion of RNAs from these phase-separated organelles is incompletely understood. Telomerase is a ribonucleoprotein composed of the reverse transcriptase protein telomerase reverse transcriptase (TERT), the telomerase RNA (TR), and several auxiliary proteins, including TCAB1. Here we show that in the absence of TCAB1, a large fraction of TR is tightly bound to the nucleolus, while TERT is largely excluded from the nucleolus, reducing telomerase assembly. This suggests that nuclear compartmentalization by the non-membrane-bound nucleolus counteracts telomerase assembly, and TCAB1 is required to retain TR in the nucleoplasm. Our work provides insight into the mechanism and functional consequences of RNA recruitment to organelles formed by phase separation and demonstrates that TCAB1 plays an important role in telomerase assembly.

Design of a multi-institutional neurocognitive discovery study in adult congenital heart disease (MINDS-ACHD).

BACKGROUND: Neurocognitive dysfunction (NCD) is a common comorbidity among children with congenital heart disease (CHD). However, it is unclear how underlying CHD and its sequelae combine with genetics and acquired cardiovascular and neurological disease to impact NCD and outcomes across the lifespan in adults with CHD. METHODS: The Multi-Institutional Neurocognitive Discovery Study in Adults with Congenital Heart Disease (MINDS-ACHD) is a partnership between the Pediatric Heart Network (PHN) and the Adult Alliance for Research in Congenital Cardiology (AARCC) that examines objective and subjective neurocognitive function and genetics in young ACHD. This multicenter cross-sectional pilot study is enrolling 500 young adults between 18 and 30 years with moderate or severe complexity CHD at 14 centers in North America. Enrollment includes 4 groups (125 participants each): (1) d-looped Transposition of the Great Arteries (d-TGA); (2) Tetralogy of Fallot (TOF); (3) single ventricle (SV) physiology; and (4) "other moderately or severely complex CHD." Participants complete the standardized tests from the NIH Toolbox Cognitive Battery, the NeuroQoL, the Hospital Anxiety and Depression Scale, and the PROMIS Global QoL measure. Clinical and demographic variables are collected by interview and medical record review, and an optional biospecimen is collected for genetic analysis. Due to the COVID-19 pandemic, participation may be done remotely. Tests are reviewed by a Neurocognitive Core Laboratory. CONCLUSIONS: MINDS-ACHD is the largest study to date characterizing NCD in young adults with moderate or severely complex CHD in North America. Its results will provide valuable data to inform screening and management strategies for NCD in ACHD and improve lifelong care.

Point-of-Care Ultrasound Use in Nephrology: A Survey of Nephrology Program Directors, Fellows, and Fellowship Graduates.

Rationale & Objective: Adoption of point-of-care ultrasound (POCUS) into nephrology practice has been relatively slow. We surveyed US nephrology program directors, their fellows, and graduates from a single training program regarding current/planned POCUS training, clinical use, and barriers to training and use. Study Design: Anonymous, online survey. Setting & Participants: All US nephrology program directors (n=151), their fellows (academic year 2021-2022), and 89/90 graduates (1980-2021) of the Walter Reed Nephrology Program. Analytical Approach: Descriptive. Results: 46% (69/151) of program directors and 33% (118/361) of their fellows responded. Response rate was 62% (55/89) for Walter Reed graduates. 51% of program directors offered POCUS training, most commonly bedside training in non-POCUS oriented rotations (71%), didactic lectures (68%), and simulation (43%). 46% of fellows reported receiving POCUS training, but of these, many reported not being sufficiently trained/not confident in kidney (56%), bladder (50%), and inferior vena cava assessment (46%). Common barriers to training reported by program directors were not enough trained faculty (78%), themselves not being sufficiently trained (55%), and equipment expense (51%). 64% of program directors and 55% of fellows reported <10% of faculty were able to perform POCUS. 64% of fellows reported having too little POCUS training. 72% of program directors and 77% of graduates felt POCUS should be incorporated into the fellowship curriculum. 59% of fellows and 61% of graduates desired hands-on POCUS training rather than didactic lectures or simulation. Limitations: Loss of respondents as program directors and fellows progressed through the survey. Conclusions: Nephrology program directors, fellows, and graduates surveyed want POCUS training incorporated into the fellowship curriculum. No group felt sufficiently trained to confidently perform POCUS, and the major barrier to training was lack of sufficiently trained faculty. This highlights the need to "train the trainers" before POCUS can be fully integrated into fellowship training and regularly used in nephrology practice.

The Supported vs Unsupported Ross in Pediatric Patients: Neoaortic Root and Ventricular Function.

BACKGROUND: The supported Ross is used to mitigate the neoaortic root dilation that has been described with the unsupported Ross. There is limited literature assessing the efficacy of the supported Ross in young patients. In this study, the fate of the neoaortic root was compared in the supported and unsupported Ross procedure in adolescent patients. METHODS: A retrospective review was performed of patients who underwent the Ross procedure between 1996 and 2019. An analysis was conducted of patients aged 10 to 18 years who underwent the supported and unsupported Ross operation, without a Konno enlargement, to assess for longitudinal echocardiographic changes. Given differences in follow-up time, both regression analysis and Mann-Whitney nonparametric tests were used to correct for time from discharge to most recent follow-up. RESULTS: The median follow-up time for supported and unsupported Ross patients without a Konno enlargement was 2.90 years (0.21-13.03 years) and 12.13 years (2.63-19.47 years), respectively. Unsupported Ross patients experienced a higher rate of change per year in the aortic annulus (P = .003 and P = .014) and aortic sinus (P = .002 and P = .002) diameters, respectively. There was no significant difference in the rate of change of end-diastolic left ventricular internal diameter (P = .703 and P = .92) and aortic insufficiency (P = .687 and P = .215) between the supported and unsupported Ross patients. CONCLUSIONS: Progressive dilation of the neoaortic root in unsupported Ross patients is significantly mitigated with the supported Ross with excellent stability. The supported Ross is safe and effective and may play an increasing role in the management of children with aortic disease.

Semantic Layout Manipulation With High-Resolution Sparse Attention.

We tackle the problem of semantic image layout manipulation, which aims to manipulate an input image by editing its semantic label map. A core problem of this task is how to transfer visual details from the input images to the new semantic layout while making the resulting image visually realistic. Recent work on learning cross-domain correspondence has shown promising results for global layout transfer with dense attention-based warping. However, this method tends to lose texture details due to the resolution limitation and the lack of smoothness constraint on correspondence. To adapt this paradigm for the layout manipulation task, we propose a high-resolution sparse attention module that effectively transfers visual details to new layouts at a resolution up to 512x512. To further improve visual quality, we introduce a novel generator architecture consisting of a semantic encoder and a two-stage decoder for coarse-to-fine synthesis. Experiments on the ADE20k and Places365 datasets demonstrate that our proposed approach achieves substantial improvements over the existing inpainting and layout manipulation methods.

Targeting telomerase reverse transcriptase with the covalent inhibitor NU-1 confers immunogenic radiation sensitization.

Beyond synthesizing telomere repeats, the telomerase reverse transcriptase (TERT) also serves multiple other roles supporting cancer growth. Blocking telomerase to drive telomere erosion appears impractical, but TERT's non-canonical activities have yet to be fully explored as cancer targets. Here, we used an irreversible TERT inhibitor, NU-1, to examine impacts on resistance to conventional cancer therapies. In vitro, inhibiting TERT sensitized cells to chemotherapy and radiation. NU-1 delayed repair of double-strand breaks, resulting in persistent DNA damage signaling and cellular senescence. Although NU-1 alone did not impact growth of syngeneic CT26 tumors in BALB/c mice, it dramatically enhanced the effects of radiation, leading to immune-dependent tumor elimination. Tumors displayed persistent DNA damage, suppressed proliferation, and increased activated immune infiltrate. Our studies confirm TERT's role in limiting genotoxic effects of conventional therapy but also implicate TERT as a determinant of immune evasion and therapy resistance.

Time in Therapeutic Range With Vitamin K Antagonists in Congenital Heart Disease: A Multicentre Study.

BACKGROUND: Vitamin K antagonists (VKAs) are frequently prescribed to patients with congenital heart disease (CHD) for atrial arrhythmias or Fontan palliation, but there is a paucity of data regarding time spent in the therapeutic range (TTR). We sought to determine the TTR in patients with CHD and atrial arrhythmias or Fontan palliation prescribed VKAs and explore associations with thromboembolic and bleeding events. METHODS: A multicentre North American cohort study was conducted on patients with CHD who received VKAs for sustained atrial arrhythmia or Fontan palliation. TTR was calculated using the Rosendaal linear interpolation method. Generalized estimating equations were used to explore factors associated with time outside the therapeutic range. RESULTS: A total of 567 patients, aged 33 ± 17 years, 56% female, received VKAs for 11.5 ± 8.4 years for atrial arrhythmias (63.0%) or Fontan palliation (58.0%). CHD was simple, moderate, and complex in 10.8%, 20.3%, and 69.0%, respectively. Site investigators perceived good control over international normalized ratio (INR) levels in most patients (75.3%), with no or minor compliance or adherence issues (85.6%). The mean TTR was 41.9% (95% confidence interval [CI], 39.0%-44.8%). Forty-seven (8.3%) and 34 (6.0%) patients had thromboembolic and bleeding events, respectively. Thromboembolic events were associated with a higher proportion of time below the therapeutic range (31.3% vs 19.1%, P = 0.003) and bleeding complications with a higher proportion of time above the therapeutic range (32.5% vs 19.5%, P = 0.006). CONCLUSIONS: Patients with CHD who receive VKAs spend < 42% of their time with INR levels in the therapeutic range, with repercussions regarding thromboembolic and bleeding complications.