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A woman has recognized rights under the Constitution to obtain an abortion, but she also has a right to personal autonomy. To preserve this right, the state must regulate the disclosures regarding an abortion procedure to ensure the patient is getting the information needed to make an informed decision about what happens to her body during an abortion. As history shows, courts have dealt with abortions with care by honoring the woman's autonomy. As the right to choose to get an abortion is fundamental, the right of the woman to be apprised of all of the facts and all of the risks associated with the procedure is equally as fundamental when looking at our nation's history. One of the ways to advocate for the woman's right to an abortion and to consent to what happens to her body is to uphold the constitutionality of the display and describe requirements and grant the power to compel disclosures in this context to the state. There is a circuit split between the Fourth, Eighth, Fifth, and Sixth Circuits over the constitutionality of the display and describe requirements of their respective states. The Fourth Circuit has held that the display and describe requirement violates the physician's First Amendment rights by compelling the physician to disclose an ideological message. Whereas the Eighth, Fifth, and Sixth Circuits have upheld the requirements on the basis that they are medically necessary and thereby do not infringe on the constitutional rights of the physicians. The Supreme Court has denied review and subsequently, the answer is not clear. Abortion is a prevalent topic and upholding the display and describe statutes on constitutional grounds is vital to ensuring the continuing evolution of abortion litigation and legislation toward a more cohesive and unified approach. The Supreme Court has held that a woman has the right to obtain an abortion and the state may not enact regulations that place an undue burden on that right. However, the state has the authority to reasonably regulate physician speech because the state has an interest in human life and maintaining the standards in the medical industry. The state may not compel a speaker to disclose an ideological message, but the state can compel the physician to apprise the patient of the risks and the alternatives, if any, of a medical procedure in order to obtain informed consent from the patient. The Fourth, Eighth, Fifth, and Sixth circuits disagree on the constitutionality of the display and describe requirements that North Carolina, South Dakota, Texas, and Kentucky, respectively, have enacted. This Article is the first to advocate for the woman's right to be informed and to consent to the surgical procedure, and it urges the Supreme Court to resolve the circuit split and hold the display and describe requirements of the states' abortion statutes as not violating the physician's First Amendment right to free speech. All physicians are required to reveal information in order for the patient to give informed consent. Resultantly, displaying the ultrasound and explaining what the ultrasound depicts is medically necessary to obtain the woman's informed consent. Therefore, this does not violate the physician's constitutional rights. This speech is commercial speech because it is speech involved in a commercial transaction and is subject to reasonable regulations. Individuals can differ on their beliefs regarding abortion and still agree that the woman has a right to know and consent to what happens to her body. This Article is not divisive; it protects to the woman's right to an abortion, her right of access to information, and her right of personal autonomy. [ABSTRACT FROM AUTHOR]

Abstract Background There are currently no reliable markers of acute domoic acid toxicosis (DAT) for California sea lions. We investigated whether patterns of serum peptides could diagnose acute DAT. Serum peptides were analyzed by MALDI-TOF mass spectrometry from 107 sea lions (acute DAT n = 34; non-DAT n = 73). Artificial neural networks (ANN) were trained using MALDI-TOF data. Individual peaks and neural networks were qualified using an independent test set (n = 20). Results No single peak was a good classifier of acute DAT, and ANN models were the best predictors of acute DAT. Performance measures for a single median ANN were: sensitivity, 100%; specificity, 60%; positive predictive value, 71%; negative predictive value, 100%. When 101 ANNs were combined and allowed to vote for the outcome, the performance measures were: sensitivity, 30%; specificity, 100%; positive predictive value, 100%; negative predictive value, 59%. Conclusions These results suggest that MALDI-TOF peptide profiling and neural networks can perform either as a highly sensitive (100% negative predictive value) or a highly specific (100% positive predictive value) diagnostic tool for acute DAT. This also suggests that machine learning directed by populations of predictive models offer the ability to modulate the predictive effort into a specific type of error.

Rationale and Objectives: Adoption of the Prostate Imaging Reporting & Data System (PI-RADS) has been shown to increase detection of clinically significant prostate cancer on prostate mpMRI. We propose that a rule-based algorithm based on Regular Expression (RegEx) matching can be used to automatically categorize prostate mpMRI reports into categories as a means by which to assess for opportunities for quality improvement., Materials and Methods: All prostate mpMRIs performed in the Duke University Health System from January 2, 2015, to January 29, 2021, were analyzed. Exclusion criteria were applied, for a total of 5343 male patients and 6264 prostate mpMRI reports. These reports were then analyzed by our RegEx algorithm to be categorized as PI-RADS 1 through PI-RADS 5, Recurrent Disease, or "No Information Available." A stratified, random sample of 502 mpMRI reports was reviewed by a blinded clinical team to assess performance of the RegEx algorithm., Results: Compared to manual review, the RegEx algorithm achieved overall accuracy of 92.6%, average precision of 88.8%, average recall of 85.6%, and F1 score of 0.871. The clinical team also reviewed 344 cases that were classified as "No Information Available," and found that in 150 instances, no numerical PI-RADS score for any lesion was included in the impression section of the mpMRI report., Conclusion: Rule-based processing is an accurate method for the large-scale, automated extraction of PI-RADS scores from the text of radiology reports. These natural language processing approaches can be used for future initiatives in quality improvement in prostate mpMRI reporting with PI-RADS., (Copyright © 2022 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: The Expert Recommendations for Implementing Change (ERIC) compilation includes 73 defined implementation strategies clustered into nine content areas. This taxonomy has been used to track implementation strategies over time using surveys. This study aimed to improve the ERIC survey using cognitive interviews with non-implementation scientist clinicians., Methods: Starting in 2015, we developed and fielded annual ERIC surveys to evaluate liver care in the Veterans Health Administration (VA). We invited providers who had completed at least three surveys to participate in cognitive interviews (October 2020 to October 2021). Before the interviews, participants reviewed the complete 73-item ERIC survey and marked which strategies were unclear due to wording, conceptual confusion, or overlap with other strategies. They then engaged in semi-structured cognitive interviews to describe the experience of completing the survey and elaborate on which strategies required further clarification., Results: Twelve VA providers completed surveys followed by cognitive interviews. The "Engage Consumer" and "Support Clinicians" clusters were rated most highly in terms of conceptual and wording clarity. In contrast, the "Financial" cluster had the most wording and conceptual confusion. The "Adapt and Tailor to Context" cluster strategies were considered to have the most redundancy. Providers outlined ways in which the strategies could be clearer in terms of wording (32%), conceptual clarity (51%), and clarifying the distinction between strategies (51%)., Conclusions: Cognitive interviews with ERIC survey participants allowed us to identify and address issues with strategy wording, combine conceptually indistinct strategies, and disaggregate multi-barreled strategies. Improvements made to the ERIC survey based on these findings will ultimately assist VA and other institutions in designing, evaluating, and replicating quality improvement efforts., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Implementation strategies supporting the translation of evidence into practice need to be tailored and adapted for maximum effectiveness, yet the field of adapting implementation strategies remains nascent. We aimed to adapt "Getting To Outcomes" ® (GTO), a 10-step implementation playbook designed to help community-based organizations plan and evaluate behavioral health programs, into "Getting To Implementation" (GTI) to support the selection, tailoring, and use of implementation strategies in health care settings., Methods: Our embedded evaluation team partnered with operations, external facilitators, and site implementers to employ participatory methods to co-design and adapt GTO for Veterans Health Administration (VA) outpatient cirrhosis care improvement. The Framework for Reporting Adaptations and Modifications to Evidenced-based Implementation Strategies (FRAME-IS) guided documentation and analysis of changes made pre- and post-implementation of GTI at 12 VA medical centers. Data from multiple sources (interviews, observation, content analysis, and fidelity tracking) were triangulated and analyzed using rapid techniques over a 3-year period., Results: Adaptations during pre-implementation were planned, proactive, and focused on context and content to improve acceptability, appropriateness, and feasibility of the GTI playbook. Modifications during and after implementation were unplanned and reactive, concentrating on adoption, fidelity, and sustainability. All changes were collaboratively developed, fidelity consistent at the level of the facilitator and/or implementer., Conclusion: GTO was initially adapted to GTI to support health care teams' selection and use of implementation strategies for improving guideline-concordant medical care. GTI required ongoing modification, particularly in steps regarding team building, context assessment, strategy selection, and sustainability due to difficulties with step clarity and progression. This work also highlights the challenges in pragmatic approaches to collecting and synthesizing implementation, fidelity, and adaptation data., Trial Registration: This study was registered on ClinicalTrials.gov (Identifier: NCT04178096)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yakovchenko, Rogal, Goodrich, Lamorte, Neely, Merante, Gibson, Scott, McCurdy, Nobbe, Morgan and Chinman.)

Many patients with chronic lymphocytic leukemia (CLL) experience physical dysfunction and low overall fitness. It remains unknown what factors drive CLL physical dysfunction. We assessed physical function and metabolic lipoprotein panels in 106 patients with CLL. In univariate analyses of clinical factors, a longer time since diagnosis was associated with a higher likelihood of dysfunctional aerobic fitness (OR = 3.56, 95% CI: 1.37-9.22; p = 0.002) and physical performance (SPPB: OR = 2.03, 95% CI: 1.20-3.44; p = 0.004). Having received treatment was associated with a higher likelihood of dysfunctional aerobic fitness (OR = 1.57, 95% CI: 1.02-2.40; p = 0.036), SPPB (OR = 1.85, 95% CI: 1.13-3.03; p = 0.011) and grip strength (OR = 1.67, 95% CI: 1.10-2.55; p = 0.015). We found that several small HDL particle parameters, higher levels of citrate (OR = 2.01, 95% CI: 1.22-3.31; p = 0.030), and lower levels of hemoglobin (OR = 0.50, 95% CI: 0.31-0.82; p = 0.030) were associated with a higher likelihood of dysfunctional aerobic fitness. Multivariable least absolute shrinkage and selection operator (LASSO)-penalized regression analyses using variable importance measures (VIM) showed that 7.8-nm HDL particles (VIM = 1.000) and total HDL particle levels (VIM = 1.000) were more informative than clinical measures for the odds of dysfunctional aerobic fitness and 6-min walk functional fitness, respectively, while 10.3-nm HDL particles (VIM = 0.383) were more informative for grip strength. Time since diagnosis (VIM = 0.680) and having received treatment (VIM = 0.490) were more informative than lipoprotein measures for the odds of having dysfunctional SPPB. Taken together, we establish significant relationships between clinical and metabolic factors and physical characteristics that might prompt early use of ancillary support services., Competing Interests: EG and MC are employees of Labcorp. DB has been a consultant, scientific advisory board member, and site clinical trial Principal Investigator (PI) (grant paid to institution) for AbbVie, Genentech, and Verastem; scientific advisory board member and site clinical trial PI (grant paid to institution) for ArQule and TG Therapeutics; site clinical trial PI (grant paid to institution) for Ascentage, BeiGene, DTRM, Juno/Celgene/BMS, MEI Pharma, and Tolero; consultant and site clinical trial PI (grant paid to institution) for AstraZeneca and Pharmacyclics; consultant and scientific advisory board member for Pfizer; consultant for Teva; National Comprehensive Cancer Network panel member; and has participated in the informCLL registry steering committee (AbbVie), REAL registry steering committee (Verastem), and Biosimilars outcomes research panel (Pfizer). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sitlinger, Deal, Garcia, Connelly, Thompson, Stewart, Macdonald, Hanson, Neely, Neely, Artese, Weinberg, Brander and Bartlett.)

Background: As treatments for cancer have improved, more people are surviving cancer. However, compared to people without a history of cancer, cancer survivors are more likely to die of cardiovascular disease (CVD). Increased risk for CVD-related mortality among cancer survivors is partially due to lack of medication adherence and problems that exist in care coordination between cancer specialists, primary care physicians, and cardiologists., Methods/design: The Onco-primary care networking to support TEAM-based care (ONE TEAM) study is an 18-month cluster-randomized controlled trial with clustering at the primary care clinic level. ONE TEAM compares the provision of the iGuide intervention to patients and primary care providers versus an education-only control. For phase 1, at the patient level, the intervention includes video vignettes and a live webinar; provider-level interventions include electronic health records-based communication and case-based webinars. Participants will be enrolled from across North Carolina one of their first visits with a cancer specialist (e.g., surgeon, radiation or medical oncologist). We use a sequential multiple assignment randomized trial (SMART) design. Outcomes (measured at the patient level) will include Healthcare Effectiveness Data and Information Set (HEDIS) quality measures of management of three CVD comorbidities using laboratory testing (glycated hemoglobin [A1c], lipid profile) and blood pressure measurements; (2) medication adherence assessed pharmacy refill data using Proportion of Days Covered (PDC); and (3) patient-provider communication (Patient-Centered Communication in Cancer Care, PCC-Ca-36). Primary care clinics in the intervention arm will be considered non-responders if 90% or more of their participating patients do not meet the modified HEDIS quality metrics at the 6-month measurement, assessed once the first enrollee from each practice reaches the 12-month mark. Non-responders will be re-randomized to either continue to receive the iGuide 1 intervention, or to receive the iGuide 2 intervention, which includes tailored videos for participants and specialist consults with primary care providers., Discussion: As the population of cancer survivors grows, ONE TEAM will contribute to closing the CVD outcomes gap among cancer survivors by optimizing and integrating cancer care and primary care teams. ONE TEAM is designed so that it will be possible for others to emulate and implement at scale., Trial Registration: This study (NCT04258813) was registered in clinicaltrals.gov on February 6, 2020., (© 2021. The Author(s).)

Background: Immunofluorescent confocal microscopy uses labeled antibodies as probes against specific macromolecules to discriminate between multiple cell types. For images of the developmental mouse lung, these cells are themselves organized into densely packed higher-level anatomical structures. These types of images can be challenging to segment automatically for several reasons, including the relevance of biomedical context, dependence on the specific set of probes used, prohibitive cost of generating labeled training data, as well as the complexity and dense packing of anatomical structures in the image. The use of an application ontology helps surmount these challenges by combining image data with its metadata to provide a meaningful biological context, modeled after how a human expert would make use of contextual information to identify histological structures, that constrains and simplifies the process of segmentation and object identification., Results: We propose an innovative approach for the semi-supervised analysis of complex and densely packed anatomical structures from immunofluorescent images that utilizes an application ontology to provide a simplified context for image segmentation and object identification. We describe how the logical organization of biological facts in the form of an ontology can provide useful constraints that facilitate automatic processing of complex images. We demonstrate the results of ontology-guided segmentation and object identification in mouse developmental lung images from the Bioinformatics REsource ATlas for the Healthy lung database of the Molecular Atlas of Lung Development (LungMAP1) program CONCLUSION: We describe a novel ontology-guided approach to segmentation and classification of complex immunofluorescence images of the developing mouse lung. The ontology is used to automatically generate constraints for each image based on its biomedical context, which facilitates image segmentation and classification.

Cone snails produce venom that contains diverse groups of peptides (conopeptides/conotoxins) and display a wide mass range, high rate of posttranslational modifications, and many potential pharmacological targets. Here we employ a proteogenomic approach to maximize conopeptide identification from the injected venom of Conus purpurascens. mRNA sequences from C. purpurascens venom ducts were assembled into a search database and complemented with known sequences and de novo approaches. We used a top-down peptidomic approach and tandem mass spectrometry identification to compare injected venom samples of 27 specimens. This intraspecific analysis yielded 543 unique conopeptide identifications, which included 33 base conopeptides and their toxiforms, 21 of which are novel. The results reveal two distinct venom profiles with different synergistic interactions to effectively target neural pathways aimed to immobilize prey. These venom expression patterns will aid target prediction, a significant step toward developing conotoxins into valuable drugs or neural probes., Competing Interests: Conflict of interest The authors declare no competing interests., (Published by Elsevier Inc.)

Background: Cirrhosis is a rapidly increasing cause of global mortality. To improve cirrhosis care, the Veterans Health Administration (VHA) developed the Hepatic Innovation Team (HIT) Collaborative to support VA Medical Centers (VAMCs) to deliver evidence-based cirrhosis care. This randomized HIT program evaluation aims to develop and assess a novel approach for choosing and applying implementation strategies to improve the quality of cirrhosis care., Methods: Evaluation aims are to (1) empirically determine which combinations of implementation strategies are associated with successful implementation of evidence-based practices (EBPs) for Veterans with cirrhosis, (2) manualize these "data-driven" implementation strategies, and (3) assess the effectiveness of data-driven implementation strategies in increasing cirrhosis EBP uptake. Aim 1 will include an online survey of all VAMCs' use of 73 implementations strategies to improve cirrhosis care, as defined by the Expert Recommendations for Implementing Change taxonomy. Traditional statistical as well as configurational comparative methods will both be employed to determine which combinations of implementation strategies are associated with site-level adherence to EBPs for cirrhosis. In aim 2, semi-structured interviews with high-performing VAMCs will be conducted to operationalize successful implementation strategies for cirrhosis care. These data will be used to inform the creation of a step-by-step guide to tailoring and applying the implementation strategies identified in aim 1. In aim 3, this manualized implementation intervention will be assessed using a hybrid type III stepped-wedge cluster randomized design. This evaluation will be conducted in 12 VAMCs, with four VAMCs crossing from control to intervention every 6 months, in order to assess the effectiveness of using data-driven implementation strategies to improve guideline-concordant cirrhosis care., Discussion: Successful completion of this innovative evaluation will establish the feasibility of using early evaluation data to inform a manualized, user-friendly implementation intervention for VAMCs with opportunities to improve care. This evaluation will provide implementation support tools that can be applied to enhance the implementation of other evidence-based practices., Trial Registration: This project was registered at ClinicalTrials.Gov ( NCT04178096 ) on 4/29/20.

Managers are increasingly being asked to integrate climate change adaptation into public land management. The literature discusses a range of adaptation approaches, including managing for resistance, resilience, and transformation; but many strategies have not yet been widely tested. This study employed in-depth interviews and scenario-based focus groups in the Upper Gunnison Basin in Colorado to learn how public land managers envision future ecosystem change, and how they plan to utilize different management approaches in the context of climate adaptation. While many managers evoked the past in thinking about projected climate impacts and potential responses, most managers in this study acknowledged and even embraced (if reluctantly) that many ecosystems will experience regime shifts in the face of climate change. However, accepting that future ecosystems will be different from past ecosystems led managers in different directions regarding how to respond and the appropriate role of management intervention. Some felt management actions should assist and even guide ecosystems toward future conditions. Others were less confident in projections and argued against transformation. Finally, some suggested that resilience could provide a middle path, allowing managers to help ecosystems adapt to change without predicting future ecosystem states. Scalar challenges and institutional constraints also influenced how managers thought about adaptation. Lack of institutional capacity was believed to constrain adaptation at larger scales. Resistance, in particular, was considered impractical at almost any scale due to institutional constraints. Managers negotiated scalar challenges and institutional constraints by nesting different approaches both spatially and temporally.

Introduction: Understanding the symptom profiles of seriously ill patients who receive palliative care, especially noncancer diagnoses where the data are sparse and are critical to better targeting our resources to the needs of patients., Methods: We performed a retrospective, multicohort study of patients evaluated during their first consultative palliative care visit in a community-based palliative care registry. We placed into one of seven major disease categories based on clinician-reported primary diagnosis for consultation. Our primary aim of this analysis was to determine the univariate association between several patient-specific characteristics (e.g., demographics, care of setting, initial screening score) and the primary diagnosis., Results: We evaluated the first visit consultation records of 1615 patients. Most prevalent diagnosis was Neurologic (564; 35%), followed by Cardiovascular (266; 16%), Pulmonary (229; 14%), and Cancer (208; 13%). Patients in the study with the highest symptom burden were those diagnosed with cancer or pulmonary disease, with 45% and 37% of cancer and pulmonary patients, respectively, having two or more moderate-to-severe symptoms; 26% of cardiovascular disease patients reported two or more moderate-to-severe symptoms, whereas 11% reported three or more. Patients with a neurologic or infectious diagnosis had less symptom burden, but a large percentage of neurologic patients were unable to respond., Discussion: This study is one of the first to describe symptom burden and functional scores by diagnostic categories and care settings across a community-based interdisciplinary specialty palliative care program. Results demonstrated statistically significant and clinically relevant differences among settings of care, functional status, and symptom profiles between patients with various serious illnesses., (Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Within the last decade, use of Electronic Health Record (EHR) systems has become intimately integrated into healthcare practice in the United States. However, large gaps remain in the study of clinical usability and require rigorous and innovative approaches for testing usability principles. In this study, validated tools from the core functions that EHRs serve-software, medicine and human factors-were combined to holistically understand and objectively measure usability of medication data displays. The first phase of this study included 132 medical trainee participants who were randomized to one of two simulated EHR environments with either a medication list or a medication timeline visualization. Within these environments human-computer interaction metrics, clinical reasoning and situation awareness tests, and usability surveys captured their multi-faceted interactions. Results showed no statistically significant differences in the two displays from software and situation awareness perspectives, though there were higher statistically significant usability scores of the medication timeline (intervention) as compared to the medication list (control). This first phase of a novel design in triangulating methodologies revealed several limitations from which future experiments will be adjusted with hopes of yielding further insight and a generalizable testing platform for evolving EHR interfaces.

Objective: We assessed the sensitivity and specificity of 8 electronic health record (EHR)-based phenotypes for diabetes mellitus against gold-standard American Diabetes Association (ADA) diagnostic criteria via chart review by clinical experts., Materials and Methods: We identified EHR-based diabetes phenotype definitions that were developed for various purposes by a variety of users, including academic medical centers, Medicare, the New York City Health Department, and pharmacy benefit managers. We applied these definitions to a sample of 173 503 patients with records in the Duke Health System Enterprise Data Warehouse and at least 1 visit over a 5-year period (2007-2011). Of these patients, 22 679 (13%) met the criteria of 1 or more of the selected diabetes phenotype definitions. A statistically balanced sample of these patients was selected for chart review by clinical experts to determine the presence or absence of type 2 diabetes in the sample., Results: The sensitivity (62-94%) and specificity (95-99%) of EHR-based type 2 diabetes phenotypes (compared with the gold standard ADA criteria via chart review) varied depending on the component criteria and timing of observations and measurements., Discussion and Conclusions: Researchers using EHR-based phenotype definitions should clearly specify the characteristics that comprise the definition, variations of ADA criteria, and how different phenotype definitions and components impact the patient populations retrieved and the intended application. Careful attention to phenotype definitions is critical if the promise of leveraging EHR data to improve individual and population health is to be fulfilled., (© The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Background: The relationship between "on-treatment" low platelet reactivity and longitudinal risks of major bleeding dual antiplatelet therapy following acute coronary syndromes remains uncertain, especially for patients who do not undergo percutaneous coronary intervention., Methods and Results: We analyzed 2428 medically managed acute coronary syndromes patients from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial who had serial platelet reactivity measurements (P2Y 12 reaction units; PRUs) and were randomized to aspirin+prasugrel versus aspirin+clopidogrel for up to 30 months. Contal's method was used to determine whether a cut point for steady-state PRU values could distinguish high versus low bleeding risk using 2-level composites: Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) severe/life-threatening or moderate bleeding unrelated to coronary artery bypass grafting (CABG) and non-CABG Thrombolysis In Myocardial Infarction (TIMI) major or minor bleeding. Exploratory analyses used 3-level composites that incorporated mild and minimal GUSTO and TIMI events. Continuous measures of PRUs (per 10-unit decrease) were not independently associated with the 2-level GUSTO (adjusted hazard ratio [HR], 1.01; 95% CI, 0.96-1.06) or TIMI composites (1.02; 0.98-1.07). Furthermore, no PRU cut point could significantly distinguish bleeding risk using the 2-level composites. However, the PRU cut point of 75 differentiated bleeding risk with the 3-level composites of GUSTO (26.5% vs 12.6%; adjusted HR, 2.28; 95% CI, 1.77-2.94; P<0.001) and TIMI bleeding events (25.9% vs 12.2%; adjusted HR, 2.30; 95% CI, 1.78-2.97; P<0.001)., Conclusions: Among medically managed non-ST-segment elevation acute coronary syndromes patients receiving prolonged dual antiplatelet therapy, PRU values were not significantly associated with the long-term risk of major bleeding events, suggesting that low on-treatment platelet reactivity does not independently predict serious bleeding risk., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00699998., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background and Purpose: The role of more intense, sustained platelet inhibition in preventing stroke after acute coronary syndrome (ACS) is unclear. We observed a signal for reduced stroke risk in the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial after 12 months of treatment with prasugrel versus clopidogrel in medically managed patients with ACS., Methods: We examined 7243 patients with ACS, aged <75 years and without prior stroke, analyzing differences in baseline characteristics between patients with and without a stroke event through 30 months with a Cox proportional hazards model. We also assessed the effect of prasugrel versus clopidogrel (plus aspirin) on risk of all stroke events and ischemic stroke over time with an extended Cox proportional hazards model., Results: Stroke events were infrequent through 30 months (ischemic stroke=62; hemorrhagic stroke=15). Patients with stroke were older, had more comorbidities, and had a higher Global Registry of Acute Coronary Events (GRACE) risk score. There was a trend for a lower unadjusted frequency of all stroke events through 30 months for prasugrel versus clopidogrel: 31 (1.5%) versus 46 (2.2%); P=0.08. There was a significant treatment-by-time interaction for those with ischemic stroke (P=0.03), consistent with the 12-month landmarked Kaplan-Meier log-rank test showing a reduced hazard of ischemic stroke after 12 months with prasugrel (P=0.04). No significant interactions between treatment effect of prasugrel versus clopidogrel and time were observed for all stroke events., Conclusions: We observed a potential late treatment effect for prasugrel versus clopidogrel for a reduced risk of ischemic stroke in medically managed patients with ACS aged <75 years. These hypothesis-generating findings suggest that longer duration and more potent platelet inhibition with prasugrel may be associated with lower risk of ischemic stroke after 12 months., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00699998., (© 2016 American Heart Association, Inc.)

Background: Patients with acute coronary syndrome (ACS), especially those receiving medical management without revascularization, are at high risk for spontaneous myocardial infarction (MI), but its frequency and predictors are unknown., Objectives: This study sought to characterize spontaneous MI events in a randomized population during 30 months of follow-up and develop a prediction model for spontaneous MI to assign risk of spontaneous MI events in ACS populations., Methods: We analyzed data from the randomized TRILOGY ACS (TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medically manage Acute Coronary Syndromes) trial of aspirin plus prasugrel or clopidogrel following ACS. The trial included 9,326 patients with non-ST-segment elevation myocardial infarction (NSTEMI)/unstable angina (UA) who were managed medically without planned revascularization. Our study population included 9,294 patients. A multivariable Cox proportional hazards model was developed to determine predictors of time to first spontaneous MI event through 30 months. After model validation, we developed a calculator for model implementation., Results: Among 9,294 patients, 695 spontaneous MI events occurred over a median of 17 months, representing 94% of adjudicated MI events (n = 737). The Kaplan-Meier event rate of spontaneous MI through 30 months was 10.7%. The strongest predictors of spontaneous MI were older age, NSTEMI versus UA as index event, diabetes mellitus, no pre-randomization angiography, and higher baseline creatinine values. The model exhibited good predictive capabilities (c-index = 0.732) and had good calibration, especially for patients with low-to-moderate risk of spontaneous MI., Conclusions: Spontaneous MI following a medically managed UA/NSTEMI event is common. Baseline characteristics can be used to predict subsequent risk of spontaneous MI in this population. These findings provide insight into the long-term natural history of medically managed UA/NSTEMI patients and could be used to optimize risk stratification and treatment of these patients. (A Comparison of Prasugrel and Clopidogrel in Acute Coronary Syndrome Subjects [TRILOGY ACS]; NCT00699998)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Many young adults with moderate hyperlipidemia do not meet statin treatment criteria under the new American Heart Association/American College of Cardiology cholesterol guidelines because they focus on 10-year cardiovascular risk. We evaluated the association between years of exposure to hypercholesterolemia in early adulthood and future coronary heart disease (CHD) risk., Methods and Results: We examined Framingham Offspring Cohort data to identify adults without incident cardiovascular disease to 55 years of age (n=1478), and explored the association between duration of moderate hyperlipidemia (non-high-density lipoprotein cholesterol ≥ 160 mg/dL) in early adulthood and subsequent CHD. At median 15-year follow-up, CHD rates were significantly elevated among adults with prolonged hyperlipidemia exposure by 55 years of age: 4.4% for those with no exposure, 8.1% for those with 1 to 10 years of exposure, and 16.5% for those with 11 to 20 years of exposure (P<0.001); this association persisted after adjustment for other cardiac risk factors including non-high-density lipoprotein cholesterol at 55 years of age (hazard ratio, 1.39; 95% confidence interval, 1.05-1.85 per decade of hyperlipidemia). Overall, 85% of young adults with prolonged hyperlipidemia would not have been recommended for statin therapy at 40 years of age under current national guidelines. However, among those not considered statin therapy candidates at 55 years of age, there remained a significant association between cumulative exposure to hyperlipidemia in young adulthood and subsequent CHD risk (adjusted hazard ratio, 1.67; 95% confidence interval, 1.06-2.64)., Conclusions: Cumulative exposure to hyperlipidemia in young adulthood increases the subsequent risk of CHD in a dose-dependent fashion. Adults with prolonged exposure to even moderate elevations in non-high-density lipoprotein cholesterol have elevated risk for future CHD and may benefit from more aggressive primary prevention., (© 2015 American Heart Association, Inc.)

Objectives: The aim of this study was to determine whether biomarkers of myocardial stress and fibrosis improve prediction of the mode of death in patients with chronic heart failure., Background: The 2 most common modes of death in patients with chronic heart failure are pump failure and sudden cardiac death. Prediction of the mode of death may facilitate treatment decisions. The relationship between amino-terminal pro-brain natriuretic peptide (NT-proBNP), galectin-3, and ST2, biomarkers that reflect different pathogenic pathways in heart failure (myocardial stress and fibrosis), and mode of death is unknown., Methods: HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized controlled trial of exercise training versus usual care in patients with chronic heart failure due to left ventricular systolic dysfunction (left ventricular ejection fraction ≤35%). An independent clinical events committee prospectively adjudicated mode of death. NT-proBNP, galectin-3, and ST2 levels were assessed at baseline in 813 subjects. Associations between biomarkers and mode of death were assessed using cause-specific Cox proportional hazards modeling, and interaction testing was used to measure differential associations between biomarkers and pump failure versus sudden cardiac death. Discrimination and risk reclassification metrics were used to assess the added value of galectin-3 and ST2 in predicting mode of death risk beyond a clinical model that included NT-proBNP., Results: After a median follow-up period of 2.5 years, there were 155 deaths: 49 from pump failure, 42 from sudden cardiac death, and 64 from other causes. Elevations in all biomarkers were associated with increased risk for both pump failure and sudden cardiac death in both adjusted and unadjusted analyses. In each case, increases in the biomarker had a stronger association with pump failure than sudden cardiac death, but this relationship was attenuated after adjustment for clinical risk factors. Clinical variables along with NT-proBNP levels were stronger predictors of pump failure (C statistic: 0.87) than sudden cardiac death (C statistic: 0.73). Addition of ST2 and galectin-3 led to improved net risk classification of 11% for sudden cardiac death, but not pump failure., Conclusions: Clinical predictors along with NT-proBNP levels were strong predictors of pump failure risk, with insignificant incremental contributions of ST2 and galectin-3. Predictability of sudden cardiac death risk was less robust and enhanced by information provided by novel biomarkers., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: This study describes and evaluates a teaching model for training family medicine residents to perform cesarean deliveries and determines whether family medicine residents can achieve adequate quality care in the procedure., Methods: The teaching model for cesarean deliveries involved direct instruction and supervision by an obstetrician. We conducted a review of all cesarean deliveries performed over a 3-year period by family medicine residents. The review analyzed associated medical conditions, cesarean section indications, cesarean rate, blood loss, postoperative complications, and fetal outcome. We compared these data to published outcomes in obstetrical literature and local obstetricians' data., Results: Maternal outcomes of all 277 cases performed under the teaching model were similar to other published results. The family medicine residency's cesarean section rate (19.1%) was less than the national cesarean section rate (27.6%) and the local obstetricians' rate (22.6%)., Conclusions: The teaching model outlined provides family medicine residents with the knowledge and skill to perform cesarean deliveries with high-quality standards.

Objective: To determine if the developmental potential of embryos resulting from in vivo- and in vitro-matured monkey oocytes could be increased through the use of a coculture system., Design: Randomized prospective comparison of embryos resulting from either in vitro- or in vivo-matured oocytes cocultured with Vero cells or cultured in medium alone (control)., Setting: Basic research laboratory., Main Outcome Measures: In vitro embryo development to the blastocyst stage and blastocyst hatching., Results: No significant difference in development was noted between coculture and control groups with embryos resulting from in vivo-matured oocytes. However, coculture was found to improve significantly the development of monkey embryos resulting from in vitro-matured oocytes., Conclusions: These results demonstrate that primate embryos resulting from in vitro-matured and in vitro-fertilized oocytes differ in their culture requirement when compared with embryos resulting from in vivo-matured oocytes.

The response of the atrioventricular (AV) junction to brief intense adrenergic stimulation applied during episodes of second degree heart block achieved by acetylcholinesterase paralysis in the AV junction was examined in six dogs. Despite profound depression of AV conduction due to enhanced cholinergic activity, strong local adrenergic stimulation still readily elicited AV junctional tachycardia. Increase in cholinomimetic influences in the AV junction did not prolong transatrial or His bundle-ventricular conduction times. During AV junctional rhythm and retrograde atrial capture (n = 4), neither the sequence of retrograde atrial activation nor the atrial electrogram configurations were altered. In the two remaining dogs the AV junctional tachycardia was associated with AV dissociation. These findings suggest that the acetylcholine-induced depression of AV conduction is located in the AV node region exclusively. More important, however, is the demonstration that retrograde atrial activation originating from a pacemaker located in the AV node or immediate vicinity could actually precede the inscription of the H spike by a considerable amount of time, further suggesting that anterograde conduction from the pacemaker site to the bundle of His is far more depressed by acetylcholine than is the concomitant retrograde conduction from the pacemaker site to the atrium. Thus, inference of the origin of a subsidiary pacemaker from the P wave configuration or the relation of the A wave to the His bundle electrogram, or both, may lead to erroneous conclusions.