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Standard Cardiovascular Risk Prediction Scores Underestimate Risk in Immune-Mediated Thrombotic Thrombocytopenic Purpura Survivors
Get PDFBackground: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare hematologic disorder with improved survival due to advancements in treatment. However, long-term cardiovascular morbidity and mortality remain significant. Established cardiovascular risk calculators, such as the 2008 Framingham Heart Study (FHS) global cardiovascular disease (CVD) and the American College of Cardiology/American Heart Association (ACC/AHA) atherosclerotic CVD (ASCVD) risk estimators, may not adequately account for the elevated and unique cardiovascular risks in iTTP survivors.
Objectives: To evaluate the discrimination and calibration of the ACC/AHA ASCVD and FHS global CVD models in predicting major adverse cardiovascular events (MACEs) among iTTP survivors.
Methods: This retrospective study analyzed 135 iTTP survivors from Johns Hopkins University (1994-2024). Presence of MACEs, including myocardial infarction, stroke, and cardiac revascularization, was the primary outcome and was assessed during clinical remission. Discriminatory ability of the model was assessed using c-statistics, while calibration was evaluated with Hosmer-Lemeshow tests and calibration plots. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were also calculated.
Results: MACEs occurred in 37.8% of the cohort over a median follow-up of 3.8 years. The ASCVD and FHS models demonstrated poor discrimination (c-statistics, 0.54 and 0.52, respectively) and poor calibration, with observed MACE rates exceeding predicted probabilities (Hosmer-Lemeshow P \u3c .05). The ASCVD model showed sensitivity of 56.5%, specificity of 49.4%, PPV of 36.6%, and NPV of 64.9%, while the FHS model showed sensitivity of 69.6%, specificity of 39.3%, PPV of 37.2%, and NPV of 67.9%.
Conclusion: Standard cardiovascular risk models inadequately predict MACE risk in iTTP survivors, underscoring the need for tailored tools that incorporate iTTP-specific factors to improve cardiovascular risk stratification and management
County-Level Association Between Modifiable Health Behaviors and Premature Mortality in the United States
No full textObjective: Unhealthy lifestyle habits are associated with increased morbidity and mortality. This study aims to examine the county-level association of physical inactivity, insufficient sleep, and current smoking, three elements of the American Heart Association\u27s Life\u27s Essential 8, with premature mortality.
Methods: Premature country-level age-adjusted death rate (AADR) in 2018-2020 were obtained from National Center for Health Statistics Mortality Files. County-level data were included from County Health Rankings data set for 2022. Counties were divided into deciles based on the percentage of adults with physical inactivity, insufficient sleep, and current smoking (separate decile for each metric) from Behavioral Risk Factor Surveillance System in 2019. Multivariable linear regression were used to evaluate the association of premature AADR with physical inactivity, insufficient sleep, and current smoking (lowest deciles as reference), controlling for median county income as a social determinant of health.
Results: A total of 3082 counties were included in the analysis. Mean physical inactivity, current smoking, and insufficient sleep ranged from 20.7 % to 41 %, 13.4 % to 28.2 %, and 30.3 % to 43.7 % from 1st to 10th decile, respectively. There was a stepwise increase in premature mortality in each progressive decile with an increase in county-level physical inactivity, insufficient sleep, and current smoking, which remained significant in the adjusted analyses.
Conclusion: We demonstrate an independent association of county-level physical inactivity, insufficient sleep, and current smoking with premature mortality. Further research and public health efforts are needed to understand and mitigate these risk factors at the county level to improve health outcomes
Baroreflex Function in Cardiovascular Disease
No full textThe baroreflex system is involved in modulating several physiological functions of the cardiovascular system and can modulate cardiac output, blood pressure, and cardiac electrophysiology directly and indirectly. In addition, it is involved in regulating neurohormonal pathways involved in the cardiovascular function, such as the renin-angiotensin-aldosterone system and vasopressin release. Baroreflex dysfunction is characterized by sympathetic overactivation and parasympathetic withdrawal and is associated with several cardiovascular diseases, such as hypertension, heart failure, and coronary artery disease. Targeting the baroreflex system via invasive (eg, baroreflex activation therapy and endovascular baroreceptor amplification) and noninvasive approaches (eg, slow breathing exercises and exercise training) has emerged as a novel pathway to manage cardiovascular diseases. Studies examining the long-term safety and efficacy of such interventions in various cardiovascular diseases are needed
Plain Language Summary About Glp-1 Treatments in People With Metabolic Dysfunction-Associated Steatotic Liver Disease
Get PDFGovernance of Polygenic Embryo Screening: A Qualitative Study on the Perspectives of Clinicians and Patients
Get PDFObjective: To investigate the perspectives of stakeholders on their attitudes toward potential regulation of polygenic embryo screening (PES), a new form of preimplantation genetic testing that is used to screen embryos for the genetic chances of developing medical conditions and nonmedical traits involving hundreds or thousands of genes.
Design: We conducted individual, semistructured interviews and analyzed transcripts using thematic analysis.
Subjects: Twenty-seven US-based reproductive endocrinology and infertility specialists and 26 patients who were currently undergoing in vitro fertilization or had within the past five years.
Main outcome measures: Repeating ideas and patterned responses were organized into themes and subthemes.
Results: Although most clinicians advocate for some form of regulation to ensure patient well-being, patients largely oppose restrictive measures, prioritizing procreative autonomy.
Conclusion: Our results highlight a tension between the welfarist approach favored by clinicians and the libertarian approach favored by patients, underscoring the complexity of developing governance frameworks for PES that satisfies multiple stakeholder groups. Ultimately, our findings call attention to the need for ongoing dialogue among stakeholders to address the ethical and practical implications of PES and any potential regulation of it
De Novo Variants in Rybp Are Associated With a Severe Neurodevelopmental Disorder and Congenital Anomalies
Get PDFPurpose: Polycomb group proteins are key epigenetic transcriptional regulators. Multiple neurodevelopmental disorders are associated with pathogenic variants of the genes encoding Polycomb group proteins. RYBP is a core component of the noncanonical Polycomb Repressor Complex 1; however, its role in disease is unclear.
Methods: Functional consequences of RYBP variants were assessed using in vitro cellular and in vivo Drosophila melanogaster studies.
Results: We described 7 individuals with heterozygous de novo variants of RYBP and their clinical findings, including severe developmental delay, dysmorphisms, and multiple congenital anomalies. We showed that all single-nucleotide variants in RYBP localize to the N-terminal domain of the gene, which encodes the zinc-finger domain and ubiquitin-binding moiety. In vitro studies have demonstrated that the RYBP c.132C\u3eG p.(Cys44Trp) variant causes reduced protein expression but does not affect the binding of YY1, RING1B, or ubiquitin. In vivo overexpression studies in Drosophila melanogaster showed a dramatic functional difference between human RYBP and its variant forms, affecting the C44 amino acid residue. DNA methylation studies suggested a possible episignature associated with RYBP-related disorder.
Conclusion: Heterozygous de novo variants in RYBP are associated with an identifiable syndromic neurodevelopmental disorder with multiple congenital anomalies
Home-Based Transcranial Direct Current Stimulation for Major Depressive Disorder: 6-Month Follow-Up From Randomised Sham-Controlled Trial and Open-Label Treatment Phases
Get PDFTranscranial direct current stimulation (tDCS) is a potential home-based treatment for major depressive disorder (MDD). In our double-blind randomised controlled trial (RCT) (n = 174; UK and USA), a 10-week course of home-based tDCS demonstrated clinical efficacy (clinical response: 58.3 % active treatment arm and 37.8 % sham (p = 0.017). tDCS was delivered in a bifrontal montage, with anode over left dorsolateral prefrontal cortex (DLPFC) and cathode over right DLPFC. Each session was 30 min, with active stimulation at 2 mA and sham at 0 mA, incorporating brief ramp-up and ramp-down phased. Following the 10-week RCT, all participants were offered active tDCS in a 10-week open-label treatment phase, with 111 participants completing this phase. UK cohort (n = 77 MDD) were invited for additional 3-month and 6-month follow-ups, extending the total study period to 11 months post-randomisation. Participants were able to continue using the tDCS device during follow-up. At least one follow-up visit was attended by 42 MDD participants (27 women). Device usage rates were 59 % at 3-month follow-up and 55 % at 6-month follow-up. Clinical response rate was 64 % at 3-month follow-up and 76 % at 6-month follow-up. Among participants who had shown a clinical response after the open-label phase, 90 % maintained their response at the 6-month follow-up. In summary, long-term follow-up showed high and sustained clinical response rates regardless of continued tDCS device use
Evaluation of Quantum Contouring Algorithms for Treatment Planning on MR Abdominal Images
No full textIntroduction: Quantum computing is increasingly being investigated for integration into medical radiology and healthcare applications worldwide. Given its potential to enhance clinical care and medical research, there is growing interest in evaluating its practical applications in clinical workflows.
Methods: We developed an evaluation of quantum computing-based auto-contouring methods to introduce medical physicists to this emerging technology. We implemented existing quantum algorithms as prototypes tailored for specific quantum hardware, focusing on their application to auto-contouring in medical imaging. The evaluation was performed using a medical resonance imaging (MRI) abdominal dataset, comprising 102 patient scans.
Results: The quantum algorithms were applied to the dataset and assessed for their potential in auto-contouring tasks. One of the quantum-based auto contouring methods demonstrated conceptual feasibility, practical performance is still limited by current available quantum hardware and scalability constraints.
Discussion: Our findings suggest that while quantum computing for auto-contouring shows promise, it remains in its early stages. At present, artificial intelligence-based algorithms continue to be the preferred choice for auto-contouring in treatment planning due to their greater efficiency and accuracy. As quantum hardware and algorithms mature, their integration into clinical workflows may become more viable
Potential Intermediate-Term Survival Differences Among Heart Transplant Recipients From Circulatory Death vs Brain Death Donors
No full textBackground: This study builds upon previous analyses by examining heart transplant survival from donation after circulatory death (DCD) vs donation after brain death (DBD) using the United Network for Organ Sharing (UNOS) database, with follow-up extended to 3 years post-transplant.
Methods: We conducted a retrospective cohort study of 1,453 DCD and 16,561 DBD adult heart transplants from January 2019 to June 2024 using the UNOS database. Propensity scores were generated based on clinically relevant covariates, and 1-to-1 propensity-score matching was performed. Survival analysis was conducted using Cox proportional hazards regression and Kaplan-Meier curves, with the log-rank test comparing overall survival and the Wald test examining yearly survival rates between DCD and DBD groups.
Results: Mortality was not significantly different between DCD and DBD total cohorts (hazard ratio [HR] = 1.1, 95% confidence interval [CI] 0.9-1.3, p = 0.493). After propensity-score matching, balanced cohorts of 1,423 DCD and 1,423 DBD transplants were created with standardized mean difference among covariates well below 6%. In the matched cohort, DCD transplant mortality was 1.2 times higher than that of DBD transplants (HR 1.2, 95% CI 0.9-1.5). Kaplan-Meier curves revealed nonsignificantly lower overall survival for DCD recipients (log-rank p = 0.096). Survival rates were comparable in year 1: 91.6% vs 91.5%, p = 0.96, but significant differences emerged in subsequent years: 84.7% vs 89.4%, p = 0.007 in year 2; 80.3% vs 85.6%, p = 0.025 in year 3.
Conclusions: Intermediate-term survival following DCD heart transplantation may be lower compared to DBD transplantation. Further investigation is warranted to identify the underlying factors contributing to this potential disparity
Healthcare Utilization Unchanged in the Control Arm of a Randomized Clinical Trial
No full textincluding among control groups. Increased access to care and heightened health awareness during trial enrollment could lead to altered behaviors, a phenomenon known as the Hawthorne effect, which may obscure true intervention impacts; however, this effect remains poorly studied in low-income environments.
Aim: To conduct a secondary exploratory analysis of healthcare utilization among control participants of a randomized clinical trial (RCT).
Methods: We retrospectively analyzed electronic medical records from the control arm (n = 26) of an RCT involving low-income Hispanic adults with type 2 diabetes receiving care at a community clinic. Before randomization to a 12-month diabetes education intervention or usual care (control), participants underwent on-site measurements of HbA1c, blood pressure, and weight. Healthcare utilization among control participants was compared during the year before and throughout the study, including all types of exposures: provider visits and other services (eg, orders).
Results: Total healthcare utilization was similar between the pre-period (11.9 exposures/year) and the study-period (11.4 exposures/year; P = .93), with no significant changes across visit types. There were no significant differences in fitted mean monthly visits between the pre- and study-periods (P = .93), nor over time (P = .89).
Conclusions: This exploratory study found no evidence of a Hawthorne effect on healthcare utilization among control participants. While this may suggest consistent healthcare behaviors, it may also highlight an important public health concern: individuals in low-income settings may lack the resources to translate increased awareness into health-related action. Larger studies are needed to further elucidate behavioral patterns in low-income populations