Applying a Bayesian Spatiotemporal Model to Examine Excess County-Level Cardiovascular Disease Death Rates During the COVID-19 Pandemic.

Amid the COVID-19 pandemic, national cardiovascular disease (CVD) death rates increased, especially among younger adults. County-level variation has not been documented. Using county-level CVD deaths (ICD-10 codes: I00-I99) from the US National Vital Statistics System, we developed a Bayesian multivariate spatiotemporal model to estimate excess CVD death rates in 2020 based on trends from 2010-2019 for adults aged 35-64 and ≥65 years. Among adults aged 35-64 years, 64.7% of counties experienced significant excess CVD death rates. The median county-level CVD death rate in 2020 was 150 per 100,000 persons, which exceeded the predicted rate for 2020 (median excess death rate: 11 per 100,000; median excess rate ratio: 1.08). Among adults aged ≥65 years, 15.2% of counties experienced significant excess CVD death rates. The median county-level CVD death rate was 1,546 per 100,000 in 2020, which exceeded the predicted rate in 2020 (median excess death rate: 48 per 100,000, median excess rate ratio: 1.03). Counties with significant excess death rates in 2020 were geographically dispersed. In 2020, disruptions of county-level CVD death rates were widespread, especially among younger adults, suggesting the continued importance of CVD prevention and treatment in younger adults in communities across the country.

Utilizing risk factors to guide treatment decisions in chronic lymphocytic leukemia.

INTRODUCTION: In the era of chemo-immunotherapy, high-risk factors unequivocally predicted inferior outcomes for patients with CLL. The widespread adoption of BTK inhibitors has challenged the practical implications of such testing, as many patients have improved outcomes despite the presence of high-risk features. The impact of adverse prognostic factors, such as unmutated IGHV, on survival has been ameliorated by continuous treatment with BTK inhibitors, but not by finite-duration therapy with venetoclax-based combinations. Furthermore, TP53 abnormalities continue to be associated with worse outcomes in the era of novel agents. New treatment modalities, such as pirtobrutinib, lisocabtagene maraleucel, and ongoing studies combining BTK inhibitors with venetoclax, raise new questions on the significance of prognostic factors of survival for patients with CLL. AREAS COVERED: Herein, we summarized the available literature on patients with CLL harboring high-risk biomarkers, with a focus on data from key clinical trials. EXPERT OPINION: Testing for prognostic biomarkers will remain relevant to identify patients who may have increased benefit from novel therapeutic strategies, such as combination therapies and novel agents. Patients with high-risk disease should be encouraged to participate in clinical trials.

Time domain characterization of nonstationary low-Mach number aeroacoustic sources using principal component analysis.

This paper presents the use of principal component analysis (PCA) for time domain microphone array denoising to characterize an impulsive aeroacoustic source, which is illustrated with the aeroacoustic emission caused by a vortex ring/edge interaction. Prior studies have used signal processing approaches that required assumptions about the source directivity or user intervention at low signal-to-noise ratio (SNR) conditions. In this context, PCA, a matrix decomposition tool which identifies the most common features across an ensemble of observations, provides a data-driven (hands-off) approach to signal processing. For microphone array time series, particular attention is paid to the temporal alignment of the signals to facilitate PCA. A time domain approach is necessary when sources are impulsive and nonstationary. Two such signal arrangements are discussed in this work. Results from this method are in good agreement with theory, validated by prior results using an ensemble averaging approach requiring user support. Furthermore, the results of this method are improved when compared to the ensemble averaging approach without user intervention. A SNR limit is identified where PCA becomes less effective for the vortex/edge interaction problem. This SNR limit is intended to aid in the design of similar future experiments.

Development and psychometric evaluation of the Violation Appraisal Measure (VAM).

Mental contamination refers to feelings of dirtiness and/or urges to wash that arise without direct contact with a contaminant. Cognitive models propose that this results from "serious, negative misappraisals of perceived violations". However, the specific violation misappraisals most relevant to mental contamination have yet to be established empirically, in part due to the lack of a comprehensive validated inventory of violation appraisals. Therefore, this study's aim was to develop and validate such a measure. Items for the new Violation Appraisal Measure (VAM) were developed from qualitative interviews, theoretical models, and previous empirical work. An Exploratory Factor Analysis was conducted in a sample of (n = 300) undergraduate participants, which revealed a four-factor structure: Responsibility/Self-Blame, Permanence, Mistrust, and Self-Worth. The VAM showed excellent internal consistency (α = 0.90), good convergent (r = .50 to .64) and adequate divergent (r = -.01 to .46) validity and was predictive of mental contamination symptoms over and above existing related appraisal measures, ΔF(1,289) = 29.35, p < .001, ΔR2 = 0.06. A Confirmatory Factor Analysis in a second sample of (n = 300) undergraduate students confirmed strong model fit for the four-factor structure of the VAM. The development of the VAM is an important contribution to the search for empirically based cognitive mechanisms in mental contamination and other violation-related sequelae.

Capillary mediated vitrification is a novel technique that enables storage of antibody critical reagents at ambient temperature: Impact on binding, structure, and laboratory sustainability.

Antibodies and antibody conjugates are essential components of life science research, but their inherent instability necessitates cold storage or lyophilization, posing logistical and sustainability challenges. Capillary-mediated vitrification has shown promise as a tool for improving biomolecule stability. In this study, we assess the feasibility of shipping and storing CMV-stabilized antibody reagents at ambient temperature using a purified rabbit polyclonal as a model system. The conditions tested included a simulated temperature excursion, ambient shipping, and storage for approximately two months at room-temperature. Antibody function was measured by both ELISA and Octet bio-layer interferometry kinetic measurements. Yield, aggregation, and thermal stability were assessed by UV/VIS, Size Exclusion Chromatography (SEC), thermal melting, and thermal aggregation studies. Results indicate >97 % protein yield and no impact on the binding activity. No evidence of aggregation or oligomer formation was detected. Addition of the vitrification buffer to the sample matrix resulted in an increase in the aggregation on-set temperature, indicating enhanced thermostability. A slight shift in both the SEC retention time for the main peak and a difference in aggregation behavior at high temperatures were noted post-vitrification. We hypothesize that these differences are related to the interaction of the protein with the saccharide component of the vitrification matrix and the stabilization mechanism of sugars. The cumulative data supports the use of Capillary Mediated Vitrification as a viable alternative to frozen reagent storage, with the potential to significantly impact reagent stability, assay performance, laboratory operations, and sustainability initiatives.

The genetic landscape of neuro-related proteins in human plasma.

Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioural traits and the disease aetiology of neuropsychiatric disorders. Here the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,000 individuals for 184 neuro-related proteins in human plasma. The analysis identified 125 cis-regulatory protein quantitative trait loci (cis-pQTL) and 164 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. At the cis-pQTL, multiple proteins shared a genetic basis with human behavioural traits such as alcohol and food intake, smoking and educational attainment, as well as neurological conditions and psychiatric disorders such as pain, neuroticism and schizophrenia. Integrating with established drug information, the causal inference analysis validated 52 out of 66 matched combinations of protein targets and diseases or side effects with available drugs while suggesting hundreds of repurposing and new therapeutic targets.

Epidemiology of injuries in united states high school track and field jumping events from 2008 - 2019.

OBJECTIVES: Reports of injury characteristics of high school track and field athletes participating in jumping events in the United States are limited. In this descriptive epidemiological study, we report injury rates and patterns in these athletes. METHODS: Injuries and athletic exposures (AE) from the National High School Sports Related Injury Surveillance System, and High School Reporting Information Online (RIO) from 2008-2019 were analyzed. Jumping events included high jump, long jump, triple jump, and pole vault. Injury rate ratios (IRR) and injury proportion ratios (IPR) were examined by sex. RESULTS: A total of 727 injuries related to jumping events during 5,486,279 AEs occurred with the highest frequency at the thigh (20.3%) followed by the ankle (18.2%), knee (16.1%), and lower leg (11.0%). The most common types of injuries were muscle strain (29.0%) and ligament sprain (21.2%). Most athletes returned to sport within 1 week (43.1%, n = 312) or 3 weeks (34.7%, n = 243). Few jumping-related injuries resulted in surgery (4.9%, n = 35) or medical disqualification (4.4%, n = 31). The jumping-related injury rate was 1.33 injuries/10,000 AEs from 2008 to 2019. The rate of jumping-related injuries was higher in competition than in practice (IRR = 2.63, 95% confidence interval [CI]: 2.25-3.06). Injury rates were significantly higher in practice for female athletes than for males (IRR = 1.51, 95% CI: 1.23-1.86). Compared to male athletes, female athletes sustained a higher proportion of ankle injuries (IPR = 1.63, 95% CI: 1.15-2.32) and ligament sprains (IPR = 1.55, 95% CI: 1.16-2.09). CONCLUSIONS: This study describes injury characteristics of high school track and field jumping athletes from 2008 to 2019. We found an overall injury rate of 1.33 injuries per 10,000 AEs. Higher overall rates of jumping-related injuries occurred during competitions than in practice, and female athletes displayed a significantly higher rate of injuries during practices compared to male athletes.

Cluster effect for SNP-SNP interaction pairs for predicting complex traits.

Single nucleotide polymorphism (SNP) interactions are the key to improving polygenic risk scores. Previous studies reported several significant SNP-SNP interaction pairs that shared a common SNP to form a cluster, but some identified pairs might be false positives. This study aims to identify factors associated with the cluster effect of false positivity and develop strategies to enhance the accuracy of SNP-SNP interactions. The results showed the cluster effect is a major cause of false-positive findings of SNP-SNP interactions. This cluster effect is due to high correlations between a causal pair and null pairs in a cluster. The clusters with a hub SNP with a significant main effect and a large minor allele frequency (MAF) tended to have a higher false-positive rate. In addition, peripheral null SNPs in a cluster with a small MAF tended to enhance false positivity. We also demonstrated that using the modified significance criterion based on the 3 p-value rules and the bootstrap approach (3pRule + bootstrap) can reduce false positivity and maintain high true positivity. In addition, our results also showed that a pair without a significant main effect tends to have weak or no interaction. This study identified the cluster effect and suggested using the 3pRule + bootstrap approach to enhance SNP-SNP interaction detection accuracy.

Neurological Complications After Transcatheter Aortic Valve Replacement: A Review.

Transcatheter aortic valve replacement (TAVR) has become the dominant procedural modality for aortic valve replacement in the United States. The reported rates of neurological complications in patients undergoing TAVR have changed over time and are dependent on diagnostic definitions and modalities. Most strokes after TAVR are likely embolic in origin, and the incidence of stroke has decreased over time. Studies have yielded conflicting results when comparing stroke rates between TAVR and surgical aortic valve replacement (SAVR), especially due to differences in diagnostic criteria and neurocognitive testing. In this narrative review, we summarize the available data on the incidence of stroke, delirium, and cognitive decline after TAVR and highlight potential areas in need of future research. We also discuss silent cerebral ischemic lesions (SCILs) and their association with a decline in postoperative neurocognitive status after TAVR. Finally, we describe that the risk of delirium and postoperative decline is increased when nonfemoral access routes are used, and we highlight the need for standardized imaging and valid, repeatable methodologies to assess cognitive changes after TAVR.

Prevalence of unruptured intracranial aneurysms (UIAs) examined in the trauma population.

BACKGROUND: Previous data on the prevalence of unruptured intracranial aneurysms (UIAs) vary widely, and studies based on these data are plagued with unintentional bias. Accurate prevalence data are paramount for any physician who counsels patients with intracranial aneurysms on rupture risk and treatment. We therefore sought to determine a more accurate number for the true prevalence of UIAs. METHODS: A retrospective chart review was conducted at a level 1 trauma center and tertiary care hospital in an urban setting between 2019 and 2020. Inclusion criteria included patients admitted with blunt trauma. Exclusion criteria included not having a head and neck CTA performed and read by an attending radiologist. All head and neck CTA radiology reads were reviewed for incidentally discovered UIAs. Subgroup analysis was performed by age group, race, and gender. RESULTS: A total of 5978 out of 8999 patients met the inclusion criteria, and 54 patients with 58 total aneurysms were identified giving an overall prevalence of 0.9%. Subgroup analysis was performed for all age groups, genders, and racial groups. CONCLUSION: The overall aneurysm prevalence was found to be 0.9% in this sample. This rate is lower than rates previously cited in the literature and those quoted in local practice. This finding has significant implications when attempting to understand average rupture risk. Further studies are needed to power more subgroup analyses to use a more personalized approach to understanding an individual's risk of rupture.

Parent decisional regret regarding neonatal circumcision in an American outpatient pediatric urology clinic.

INTRODUCTION/BACKGROUND: Requests for circumcision revision are common in our American pediatric urology clinic. As parents are the surrogate decision maker for their child, there are several influences that can impact a parent's decision for or against circumcision. OBJECTIVE: We sought to assess parents' regret regarding their child's circumcision status and to correlate regret to factors that might have affected the original decision. STUDY DESIGN: From March 2023 to January 2024, we surveyed parents who brought their male child to our office for any reason, independent of circumcision status. The questionnaire was two-fold: a validated Decisional Regret Scale (DRS) (0-100 where higher scores = higher regret) and our questions regarding their decision-making process and outcome. Regret scores served as a function of each of the independent decision making and outcome variables. RESULTS: Overall, decisional regret scores from both uncircumcised and circumcised parent groups were positively skewed with a median 0, mean 22, and ranged from 0 to 75. For those circumcised (n = 91), the median regret score was 0 (IQR 0-25). For those uncircumcised (n = 28), median regret score was 0 (IQR 0-24). Overall, 55% of both groups reported no regret (DRS = 0), 24% had low-mild regret (DRS 5-25), and 21% yielded moderate-strong regret (DRS 30-100). Parents who felt they made an informed decision or were counseled by any physician had lower regret scores. Parents who presented for issues related to their child's uncircumcised or circumcised penis (DRS score 37.5 and 25 respectively) had higher regret scores. DISCUSSION: We found that a large portion of parents expressed no regret regarding their decision to have or not have their child circumcised (55%). There also was no difference in median regret scores between parent groups. However, a significant portion of parents did express moderate-strong regret (21%) and several influential factors were correlated with regret scores. These factors included informed decision making, physician counseling, appearance satisfaction, and problems related to their child's circumcised or uncircumcised penis. These factors are supported by other literature using the DRS and population studies. The limitations of our study included the limited recruitment of participants and potential time dependent bias of responses. CONCLUSION: One in five parents of both circumcised and uncircumcised boys expressed moderate to strong regret regarding their decision about neonatal circumcision in our pediatric urology clinic. Our data suggests that ensuring parents have sufficient counseling prior to a decision regarding neonatal circumcision is important.

Atrial fibrillation burden and clinical outcomes following BTK inhibitor initiation.

Bruton's tyrosine kinase inhibitors (BTKi) have dramatic efficacy against B-cell malignancies, but link with cardiotoxicity, including atrial fibrillation (AF). Burden, severity, and implications of BTKi-related AF are unknown. Leveraging a large-cohort of consecutive B-cell malignancy patients initiated on BTKi from 2009-2020, we identified patients with extended ambulatory rhythm monitoring. The primary outcome was AF burden after BTKi-initiation. Secondary outcomes included ventricular arrhythmia burden and other arrhythmias. Observed incident-AF rates and burden with next-generation BTKi's were compared to ibrutinib. Multivariable regression defined association between rhythm measures and major adverse cardiac events (MACE), and mortality. There were 98 BTKi-treated patients [38.8% next-generation BTKi's, 14.3% prior-AF], with 28,224 h of monitoring. Median duration BTKi-use was 34 months. Over mean duration 12 days monitoring, 72.4% developed arrhythmias (16.3% incident-AF, 31.6% other SVTs, 14.3% ventricular tachycardia). 14.3% had high AF-burden. AF-burden was similar between ibrutinib and next-generation BTKi's. No single antiarrhythmic-therapy prevented BTKi-related AF. However, antiarrhythmic initiation associated with reduction in arrhythmic burden (P = 0.009). In a multivariable model accounting for traditional cardiovascular risk factors, prior-AF associated with increased post-BTKi AF-burden. In follow-up, high AF burden associated with MACE (HR 3.12, P = 0.005) and mortality (HR 2.97, P = 0.007). Among BTKi-treated patients, high AF burden prognosticates future MACE and mortality risk.

Bone stress injuries in athletics (track and field) championships: findings from a prospective injury surveillance conducted across 24 international championships with 29,147 registered athletes.

BACKGROUND: Athletics (track and field) athletes are prone to develop bone stress injuries (BSIs) but epidemiological data on BSIs from top-level sports events are scarce. OBJECTIVE: To describe the incidence and characteristics of BSIs during 24 international athletics championships held from 2007 to 2023. METHODS: BSI-related data were prospectively collected during 24 international athletics championships, including the Olympic Games (n = 3), World Outdoor Championships (n = 4), European Outdoor Championships (n = 6), World Indoor Championships (n = 3) and European Indoor Championships (n = 8). Descriptive and comparative statistics were used to assess the epidemiological characteristics of BSIs. RESULTS: BSIs accounted for 1.5% of all reported injuries (n = 36; 1.2 per 1000 registered athletes (95%CI 0.8 to 1.6)). No significant difference of BSI incidence was detected between female (2.0 per 1000 athletes (95%CI: 0.9 to 2.3)) and male athletes (0.9 per 1000 athletes (95%CI: 0.4 to 1.4)) (relative risk (RR) = 1.73, 95%CI: 0.88 to 3.40). BSI incidence was significantly higher during outdoor championships (1.6 per 1000 registered athletes (95%CI: 1.0 to 2.1)) as compared to indoor championships (0.2 per 1000 registered athletes (95%CI: 0.0 to 0.5)) (RR = 10.4, 95%CI: 1.43 to 76.0). Most BSIs were sustained in the foot (n = 50%) or leg (n = 33%). BSIs were reported in athletes participating in endurance disciplines (52.8%) or in explosive disciplines (47.2%). CONCLUSIONS: BSIs represent a small portion of injuries sustained during international athletics championships. Collective results suggest that injury rates are higher in outdoor competitions as compared to indoor competitions. The most common injury locations comprise the foot and leg. CLINICAL TRIAL NUMBER: Not applicable.

Severe Polypharmacy Increases Risk of Hospitalization Among Older Adults with IBD.

BACKGROUND: As the inflammatory bowel disease (IBD) patient population is aging, the prevalence of polypharmacy is rising. However, data exploring the prevalence, risk factors, and clinical outcomes associated with polypharmacy among older adults with IBD are limited. AIMS: To determine (i) prevalence of polypharmacy (≥5 medications) and potentially inappropriate medication (PIM) utilization in older adults with IBD, (ii) changes in medications over time (iii) predictors of polypharmacy, and (iv) the impact of polypharmacy/PIMs on one-year hospitalization rates. METHODS: We conducted a retrospective single-center study of older adults with IBD from September 1st 2011 to December 31st 2022. Wilcoxon-signed rank and McNemar's tests were used to assess changes in polypharmacy between visits, with ordinal logistic regression and Cox proportional hazards models used to determine risk factors for polypharmacy and time to hospitalization, respectively. RESULTS: Among 512 older adults with IBD, 74.0% experienced polypharmacy at initial visit, with 42.6% receiving at least one PIM. Additionally, severe polypharmacy (≥10 medications) was present among 28.6% individuals at index visit and increased to 38.6% by last visit (p<0.01). Multivariable analysis revealed that age ≥70 years, BMI ≥30.0 kg/m2, prior IBD-related surgery, and the presence of comorbidities were associated with polypharmacy. Moreover, severe polypharmacy (adjHR 1.95, 95%CI 1.29-2.92), as well as PIM use (adjHR 2.16, 95%CI 1.37-3.43) among those with polypharmacy, were significantly associated with all-cause hospitalization within a year of index visit. DISCUSSION: Severe polypharmacy was initially present in more than 25% of older adults with IBD and increased to 34% within 4 years of index visit. Severe polypharmacy, as well as PIM utilization among those with polypharmacy, were also associated with an increased risk of hospitalization at one-year, highlighting the need for deprescribing efforts in this population.

Sarcopenia Is a Risk Factor for Postoperative Complications Among Older Adults With Inflammatory Bowel Disease.

BACKGROUND: Sarcopenia has been associated with adverse postoperative outcomes in older age cohorts, but has not been assessed in older adults with inflammatory bowel disease (IBD). Further, current assessments of sarcopenia among all aged individuals with IBD have used various measures of muscle mass as well as cutoffs to define its presence, leading to heterogeneous findings. METHODS: In this single-institution, multihospital retrospective study, we identified all patients aged 60 years and older with IBD who underwent disease-related intestinal resection between 2012 and 2022. Skeletal Muscle Index (SMI) and Total Psoas Index (TPI) were measured at the superior L3 endplate on preoperative computed tomography scans and compared through receiver operating characteristic curve. We then performed multivariable logistic regression to assess risk factors associated with an adverse 30-day postoperative outcome. Our primary outcome included a 30-day composite of postoperative mortality and complications, including infection, bleeding, cardiac event, cerebrovascular accident, acute kidney injury, venous thromboembolism, reoperation, all-cause rehospitalization, and need for intensive care unit-level care. RESULTS: A total of 120 individuals were included. Overall, 52% were female, 40% had ulcerative colitis, 60% had Crohn's disease, and median age at time of surgery was 70 years (interquartile range: 65-75). Forty percent of older adults had an adverse 30-day postoperative outcome, including infection (23%), readmission (17%), acute kidney injury (13%), bleeding (13%), intensive care unit admission (10%), cardiac event (8%), venous thromboembolism (7%), reoperation (6%), mortality (5%), and cerebrovascular accident (2%). When evaluating the predictive performance of SMI vs TPI for an adverse 30-day postoperative event, SMI had a significantly higher area under the curve of 0.66 (95% CI, 0.56-0.76) as compared to 0.58 (95% CI, 0.48-0.69) for TPI (P = .02). On multivariable logistic regression, prior IBD-related surgery (adjusted odds ratio [adjOR] 6.46, 95% CI, 1.85-22.51) and preoperative sepsis (adjOR 5.74, 95% CI, 1.36-24.17) significantly increased the odds of adverse postoperative outcomes, whereas increasing SMI was associated with a decreased risk of an adverse postoperative outcome (adjOR 0.88, 95% CI, 0.82-0.94). CONCLUSIONS: Sarcopenia, as measured by SMI, is associated with an increased risk of postoperative complications among older adults with IBD. Measurement of SMI from preoperative imaging can help risk stratify older adults with IBD undergoing intestinal resection.

Sarcopenia has been associated with adverse postoperative outcomes in older adult populations but data among older adults with inflammatory bowel disease are limited. In our study, sarcopenia was significantly associated with adverse postoperative outcomes in older adults undergoing disease-related intestinal resection.

Exploring Hospital Overcrowding with an Explainable Time-to-Event Machine Learning Approach.

Emergency department (ED) overcrowding is a complex problem that is intricately linked with the operations of other hospital departments. Leveraging ED real-world production data provides a unique opportunity to comprehend this multifaceted problem holistically. This paper introduces a novel approach to analyse healthcare production data, treating the length of stay of patients, and the follow up decision regarding discharge or admission to the hospital as a time-to-event analysis problem. Our methodology employs traditional survival estimators and machine learning models, and Shapley additive explanations values to interpret the model outcomes. The most relevant features influencing length of stay were whether the patient received a scan at the ED, emergency room urgent visit, age, triage level, and the medical alarm unit category. The clinical insights derived from the explanation of the models holds promise for increase understanding of the overcrowding from the data. Our work demonstrates that a time-to-event approach to the over- crowding serves as a valuable initial to uncover crucial insights for further investigation and policy design.

Review of Key Elements in Developing a Common Data Model for Rare Diseases: Identifying Common Success Factors.

This paper explores key success factors for the development and implementation of a Common Data Model (CDM) for Rare Diseases (RDs) focusing on the European context. Several challenges hinder RD care and research in diagnosis, treatment, and research, including data fragmentation, lack of standardisation, and Interoperability (IOP) issues within healthcare information systems. We identify key issues and recommendations for an RD-CDM, drawing on international guidelines and existing infrastructure, to address organisational, consensus, interoperability, usage, and secondary use challenges. Based on these, we analyse the importance of balancing the scope and IOP of a CDM to cater to the unique requirements of RDs while ensuring effective data exchange and usage across systems. In conclusion, a well-designed RD-CDM can bridge gaps in RD care and research, enhance patient care and facilitate international collaborations.

Markers of imminent myocardial infarction.

Myocardial infarction is a leading cause of death globally but is notoriously difficult to predict. We aimed to identify biomarkers of an imminent first myocardial infarction and design relevant prediction models. Here, we constructed a new case-cohort consortium of 2,018 persons without prior cardiovascular disease from six European cohorts, among whom 420 developed a first myocardial infarction within 6 months after the baseline blood draw. We analyzed 817 proteins and 1,025 metabolites in biobanked blood and 16 clinical variables. Forty-eight proteins, 43 metabolites, age, sex and systolic blood pressure were associated with the risk of an imminent first myocardial infarction. Brain natriuretic peptide was most consistently associated with the risk of imminent myocardial infarction. Using clinically readily available variables, we devised a prediction model for an imminent first myocardial infarction for clinical use in the general population, with good discriminatory performance and potential for motivating primary prevention efforts.

Predicting Recovery After Concussion in Pediatric Patients: A Meta-Analysis.

CONTEXT: Prognostic prediction models (PPMs) can help clinicians predict outcomes. OBJECTIVE: To critically examine peer-reviewed PPMs predicting delayed recovery among pediatric patients with concussion. DATA SOURCES: Ovid Medline, Embase, Ovid PsycInfo, Web of Science Core Collection, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Google Scholar. STUDY SELECTION: The study had to report a PPM for pediatric patients to be used within 28 days of injury to estimate risk of delayed recovery at 28 days to 1 year postinjury. Studies had to have at least 30 participants. DATA EXTRACTION: The Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies checklist was completed. RESULTS: Six studies of 13 PPMs were included. These studies primarily reflected male patients in late childhood or early adolescence presenting to an emergency department meeting the Concussion in Sport Group concussion criteria. No study authors used the same outcome definition nor evaluated the clinical utility of a model. All studies demonstrated high risk of bias. Quality of evidence was best for the Predicting and Preventing Postconcussive Problems in Pediatrics (5P) clinical risk score. LIMITATIONS: No formal PPM Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) process exists. CONCLUSIONS: The 5P clinical risk score may be considered for clinical use. Rigorous external validations, particularly in other settings, are needed. The remaining PPMs require external validation. Lack of consensus regarding delayed recovery criteria limits these PPMs.

Functional Connectivity Favors Aberrant Visual Network c-Fos Expression Accompanied by Cortical Synapse Loss in a Mouse Model of Alzheimer's Disease.

Background: While Alzheimer's disease (AD) has been extensively studied with a focus on cognitive networks, visual network dysfunction has received less attention despite compelling evidence of its significance in AD patients and mouse models. We recently reported c-Fos and synaptic dysregulation in the primary visual cortex of a pre-amyloid plaque AD-model. Objective: We test whether c-Fos expression and presynaptic density/dynamics differ in cortical and subcortical visual areas in an AD-model. We also examine whether aberrant c-Fos expression is inherited through functional connectivity and shaped by light experience. Methods: c-Fos+ cell density, functional connectivity, and their experience-dependent modulation were assessed for visual and whole-brain networks in both sexes of 4-6-month-old J20 (AD-model) and wildtype (WT) mice. Cortical and subcortical differences in presynaptic vulnerability in the AD-model were compared using ex vivo and in vivo imaging. Results: Visual cortical, but not subcortical, networks show aberrant c-Fos expression and impaired experience-dependent modulation. The average functional connectivity of a brain region in WT mice significantly predicts aberrant c-Fos expression, which correlates with impaired experience-dependent modulation in the AD-model. We observed a subtle yet selective weakening of excitatory visual cortical synapses. The size distribution of cortical boutons in the AD-model is downscaled relative to those in WT mice, suggesting a synaptic scaling-like adaptation of bouton size. Conclusions: Visual network structural and functional disruptions are biased toward cortical regions in pre-plaque J20 mice, and the cellular and synaptic dysregulation in the AD-model represents a maladaptive modification of the baseline physiology seen in WT conditions.