Stabilization of ß-Catenin Directs HEB to Limit Thymic Selection.

Activation of ß-catenin in CD4+CD8+ double-positive (DP) thymocytes halts development before the thymic selection stage and predisposes to transformation. Leukemogenesis, but not the developmental block, depends on TCF-1, ß-catenin's DNA-binding partner. In this study, we show that ß-catenin activation directs the DNA-binding protein HEB to block DP thymocyte development. Conditional loss of HEB in DP thymocytes with stabilized ß-catenin restores the frequencies of postselection TCRßhi/CCR7+ and TCRßhi/CD69+ DPs and their cell-cycle profile. This recovery is associated with significant reversal of ß-catenin-induced expression changes, particularly those related to the CD69+ DP cell signature and to cell-cycle pathways. Stabilizing ß-catenin in DP thymocytes directs HEB binding to ≈11,000 novel DNA sites throughout the genome. Novel HEB sites mark most CD69+ DP cell signature genes that change expression upon activation of ß-catenin and then revert after loss of HEB. Moreover, many of the novel HEB sites occupy promoter regions of genes enriched in mitotic cell cycle pathways. HEB binding to those regions correlates with downregulation of the associated genes, and HEB inactivation restores expression to physiologic levels. These findings highlight a molecular interplay between HEB and ß-catenin that can impair thymic development.

Associations between maternal periconceptional alcohol consumption and risk of omphalocele among offspring, National Birth Defects Prevention Study, 1997-2011.

OBJECTIVE: Previous studies of alcohol consumption during pregnancy and omphalocele have produced mixed results. We updated an earlier analysis of National Birth Defects Prevention Study (NBDPS) data, adding six years of participants, to examine associations between maternal alcohol consumption and omphalocele. METHODS: NBDPS was a multi-site, population-based case-control study in the United States. Cases were identified from birth defect surveillance programs in 10 states; controls were liveborn infants without a birth defect randomly selected from the same catchment areas. Mothers self-reported alcohol consumption during the periconceptional period (one month before through the third gestational month) via telephone interview. Our study included mothers of 410 omphalocele cases and 11,219 controls with estimated dates of delivery (EDDs) during 1997-2011. We used logistic regression to estimate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for periconceptional alcohol consumption and omphalocele. We performed a probabilistic bias analysis to evaluate the impact of alcohol exposure misclassification on our results. RESULTS: Overall, 44% of case and 38% of control mothers reported periconceptional alcohol consumption; 22% and 17%, respectively, reported binge drinking. Any maternal periconceptional alcohol consumption was associated with modestly increased odds of omphalocele (AOR 1.35, 95% CI 1.09, 1.68), as was binge drinking (AOR 1.47, 95% CI 1.08, 2.01). Our bias analysis yielded estimates further from the null. CONCLUSIONS: We observed modest associations between maternal periconceptional alcohol consumption and omphalocele. Based on our bias analysis, studies of alcohol and birth defects not accounting for exposure misclassification may underestimate associations.

Maternal exposure to zolpidem and risk of specific birth defects.

Zolpidem is a non-benzodiazepine agent indicated for treatment of insomnia. While zolpidem crosses the placenta, little is known about its safety in pregnancy. We assessed associations between self-reported zolpidem use 1 month before pregnancy through to the end of the third month ("early pregnancy") and specific birth defects using data from two multi-site case-control studies: National Birth Defects Prevention Study and Slone Epidemiology Center Birth Defects Study. Analysis included 39,711 birth defect cases and 23,035 controls without a birth defect. For defects with ≥ 5 exposed cases, we used logistic regression with Firth's penalised likelihood to estimate adjusted odds ratios and 95% confidence intervals, considering age at delivery, race/ethnicity, education, body mass index, parity, early-pregnancy antipsychotic, anxiolytic, antidepressant use, early-pregnancy opioid use, early-pregnancy smoking, and study as potential covariates. For defects with three-four exposed cases, we estimated crude odds ratios and 95% confidence intervals. Additionally, we explored differences in odds ratios using propensity score-adjustment and conducted a probabilistic bias analysis of exposure misclassification. Overall, 84 (0.2%) cases and 46 (0.2%) controls reported early-pregnancy zolpidem use. Seven defects had sufficient sample size to calculate adjusted odds ratios, which ranged from 0.76 for cleft lip to 2.18 for gastroschisis. Four defects had odds ratios > 1.8. All confidence intervals included the null. Zolpidem use was rare. We could not calculate adjusted odds ratios for most defects and estimates are imprecise. Results do not support a large increase in risk, but smaller increases in risk for certain defects cannot be ruled out.

A Systematic Review of Systems Science Approaches to Understand and Address Domestic and Gender-Based Violence.

Purpose: We aimed to synthesize insights from systems science approaches applied to domestic and gender-based violence. Methods: We conducted a systematic review of systems science studies (systems thinking, group model-building, agent-based modeling [ABM], system dynamics [SD] modeling, social network analysis [SNA], and network analysis [NA]) applied to domestic or gender-based violence, including victimization, perpetration, prevention, and community responses. We used blinded review to identify papers meeting our inclusion criteria (i.e., peer-reviewed journal article or published book chapter that described a systems science approach to domestic or gender-based violence, broadly defined) and assessed the quality and transparency of each study. Results: Our search yielded 1,841 studies, and 74 studies met our inclusion criteria (45 SNA, 12 NA, 8 ABM, and 3 SD). Although research aims varied across study types, the included studies highlighted social network influences on risks for domestic violence, clustering of risk factors and violence experiences, and potential targets for intervention. We assessed the quality of the included studies as moderate, though only a minority adhered to best practices in model development and dissemination, including stakeholder engagement and sharing of model code. Conclusions: Systems science approaches for the study of domestic and gender-based violence have shed light on the complex processes that characterize domestic violence and its broader context. Future research in this area should include greater dialogue between different types of systems science approaches, consideration of peer and family influences in the same models, and expanded use of best practices, including continued engagement of community stakeholders. Supplementary Information: The online version contains supplementary material available at 10.1007/s10896-023-00578-8.

Agreement between maternal report and medical records on use of medications during early pregnancy in New York.

BACKGROUND: Studies evaluating associations between medication use in pregnancy and birth outcomes rely on various sources of exposure information. We sought to assess agreement between self-reported use of medications during early pregnancy and medication information in prenatal medical records to understand the reliability of each of these information sources. METHODS: We compared self-reported prescription medication use in early pregnancy to medical records from 184 New York women with deliveries in 2018 who participated in the Birth Defects Study To Evaluate Pregnancy exposureS. We assessed medications used chronically and episodically, and medications within 12 therapeutic groups. We calculated agreement using kappa (κ) coefficients, sensitivity, and specificity. We assessed differences by case/control status, maternal age, education, time to interview, and interview language. RESULTS: Medications used chronically showed substantial agreement between self-report and medical records (κ = 0.75, 0.61-0.88), with agreement for therapeutic groups used chronically ranging from κ = 0.61 for antidiabetics to κ = 1.00 for antihypertensives. Prescription medications used episodically showed worse agreement (κ = 0.40, 0.25-0.54), with the lowest agreement for opioid analgesics (κ = 0.20) and anti-infectives (κ = 0.33). Agreement did not differ by the characteristics examined, although we observed potential differences by interview language. CONCLUSIONS: Among our sample, we observed good agreement between self-report and medical records for medications used chronically and substantially less agreement for medications used episodically. Differences by source may be due to poor recall in self-reports, non-adherence with prescribed medications and lack of complete prescription information within medical records. Limitations should be considered when assessing prescription medication exposures during early pregnancy in epidemiologic studies.

Applications of agent-based modeling in trauma research.

OBJECTIVE: Trauma, violence, and their consequences for population health are shaped by complex, intersecting forces across the life span. We aimed to illustrate the strengths of agent-based modeling (ABM), a computational approach in which population-level patterns emerge from the behaviors and interactions of simulated individuals, for advancing trauma research; Method: We provide an overview of agent-based modeling for trauma research, including a discussion of the model development process, ABM as a complement to other causal inference and complex systems approaches in trauma research, and past ABM applications in the trauma literature; Results: We use existing ABM applications to illustrate the strengths of ABM for trauma research, including incorporating interactions between individuals, simulating processes across multiple scales, examining life-course effects, testing alternate theories, comparing intervention strategies in a virtual laboratory, and guiding decision making. We also discuss the challenges of applying ABM to trauma research and offer specific suggestions for incorporating ABM into future studies of trauma and violence; Conclusion: Agent-based modeling is a useful complement to other methodological advances in trauma research. We recommend a more widespread adoption of ABM, particularly for research into patterns and consequences of individual traumatic experiences across the life course and understanding the effects of interventions that may be influenced by social norms and social network structures. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Sex-based disparities and in-hospital outcomes of patients hospitalized with atrial fibrillation with and without dementia.

Study objective: We sought to evaluate the sex-based disparities and comparative in-hospital outcomes of principal AF hospitalizations in patients with and without dementia, which have not been well-studied. Design: This is a non-interventional retrospective cohort study. Setting and participants: We identified principal hospitalizations of AF in the National Inpatient Sample in adults (≥18 years old) between January 2016 and December 2019. Main outcome measure: In-hospital mortality. Results: Of 378,230 hospitalized patients with AF, 49.2 % (n = 186,039) were females and 6.1 % (n = 22,904) had dementia. The mean age (SD) was 71 (13) years. Patients with dementia had higher odds of in-hospital mortality {adjusted odds ratio (aOR): 1.48, 95 % confidence interval (CI): 1.34, 1.64, p < 0.001} and nontraumatic intracerebral hemorrhage (aOR: 1.60, 95 % CI: 1.04, 2.47, p = 0.032), but they had lower odds of catheter ablation (0.39, 95 % CI: 0.35, 0.43, p < 0.001) and electrical cardioversion (aOR: 0.33, 95 % CI: 0.31, 0.35, p < 0.001). In patients with AF and dementia, compared to males, females had similar in-hospital mortality (aOR: 1.00, 95 % CI: 0.93, 1.07, p = 0.960), fewer gastrointestinal bleeds (aOR: 0.92, 95 % CI: 0.85, 0.99, p = 0.033), lower odds of getting catheter ablation (aOR: 0.79, 95 % CI: 0.76, 0.81, p < 0.001), and less likelihood of getting electrical cardioversion (aOR: 0.78, 95 % CI: 0.76, 0.79, p < 0.001). Conclusions: Patients with AF and dementia have higher mortality and a lower likelihood of getting catheter ablation and electrical cardioversion.

Childhood violence exposure and externalizing behaviors: A systematic review of the role of physiological biomarkers.

Childhood exposure to violence has been consistently linked to externalizing behaviors like delinquency and aggression. Growing evidence indicates that physiological biomarkers from the parasympathetic and sympathetic nervous systems (PNS and SNS) and hypothalamic-pituitary-adrenal (HPA) axis may moderate or mediate the relation between childhood violence exposure and externalizing behaviors. We conducted a systematic review to synthesize recent findings on physiological biomarkers as mediators and/or moderators of this association across the life course, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our search yielded 3878 articles, of which 44 met inclusion criteria (describing a total of 46 independent studies). We found consistent evidence for blunted HPA-axis reactivity as a mediator of the relation between childhood violence exposure and subsequent externalizing behaviors, and for non-reciprocal PNS/SNS activation as moderators exacerbating this relation. However, the results of the majority of included studies that demonstrated significant moderating effects of physiological biomarkers varied by participant sex, type of childhood violence exposure, and type of stimuli used to induce physiological reactivity. The observed mixed findings are consistent with some theories that emphasize that both high and low stress reactivity can be adaptive depending on one's early environment. These findings highlight the need for systematic explorations of heterogeneity, theory-driven research questions, and longitudinal studies that span multiple developmental periods and multiple biological systems. Clinical implications include the need to assess physiological biomarkers in treatment and intervention studies and the potential to target interventions based on both autonomic functioning and environmental contexts.

Tcf-1 promotes genomic instability and T cell transformation in response to aberrant ß-catenin activation.

Understanding the mechanisms promoting chromosomal translocations of the rearranging receptor loci in leukemia and lymphoma remains incomplete. Here we show that leukemias induced by aberrant activation of ß-catenin in thymocytes, which bear recurrent Tcra/Myc-Pvt1 translocations, depend on Tcf-1. The DNA double strand breaks (DSBs) in the Tcra site of the translocation are Rag-generated, whereas the Myc-Pvt1 DSBs are not. Aberrantly activated ß-catenin redirects Tcf-1 binding to novel DNA sites to alter chromatin accessibility and down-regulate genome-stability pathways. Impaired homologous recombination (HR) DNA repair and replication checkpoints lead to retention of DSBs that promote translocations and transformation of double-positive (DP) thymocytes. The resulting lymphomas, which resemble human T cell acute lymphoblastic leukemia (T-ALL), are sensitive to PARP inhibitors (PARPis). Our findings indicate that aberrant ß-catenin signaling contributes to translocations in thymocytes by guiding Tcf-1 to promote the generation and retention of replication-induced DSBs allowing their coexistence with Rag-generated DSBs. Thus, PARPis could offer therapeutic options in hematologic malignancies with active Wnt/ß-catenin signaling.

Identifying joint impacts of sun radiation, temperature, humidity, and rain duration on triggering mental disorders using a high-resolution weather monitoring system.

BACKGROUND: Mental disorders (MDs) are behavioral or mental patterns that cause significant distress or impairment of personal functioning. Previously, temperature has been linked to MDs, but most studies suffered from exposure misclassification due to limited monitoring sites. We aimed to assess whether multiple meteorological factors could jointly trigger MD-related emergency department (ED) visits in warm season, using a highly dense weather monitoring system. METHODS: We conducted a time-stratified, case-crossover study. MDs-related ED visits (primary diagnosis) from May-October 2017-2018 were obtained from New York State (NYS) discharge database. We obtained solar radiation (SR), relative humidity (RH), temperature, heat index (HI), and rainfall from Mesonet, a real-time monitoring system spaced about 17 miles (126 stations) across NYS. We used conditional logistic regression to assess the weather-MD associations. RESULTS: For each interquartile range (IQR) increase, both SR (excess risk (ER): 4.9%, 95% CI: 3.2-6.7%) and RH (ER: 4.0%, 95% CI: 2.6-5.4%) showed the largest risk for MD-related ED visits at lag 0-9 days. While temperature presented a short-term risk (highest ER at lag 0-2 days: 3.7%, 95% CI: 2.5-4.9%), HI increased risk over a two-week period (ER range: 3.7-4.5%), and rainfall hours showed an inverse association with MDs (ER: -0.5%, 95% CI: 0.9-(-0.1)%). Additionally, we observed stronger association of SR, RH, temperature, and HI in September and October. Combination of high SR, RH, and temperature displayed the largest increase in MDs (ER: 7.49%, 95% CI: 3.95-11.15%). The weather-MD association was stronger for psychoactive substance usage, mood disorders, adult behavior disorders, males, Hispanics, African Americans, individuals aged 46-65, or Medicare patients. CONCLUSIONS: Hot and humid weather, especially the joint effect of high sun radiation, temperature and relative humidity showed the highest risk of MD diseases. We found stronger weather-MD associations in summer transitional months, males, and minority groups. These findings also need further confirmation.

Would restricting firearm purchases due to alcohol- and drug-related misdemeanor offenses reduce firearm homicide and suicide? An agent-based simulation.

BACKGROUND: Substance-related interactions with the criminal justice system are a potential touchpoint to identify people at risk for firearm violence. We used an agent-based model to simulate the change in firearm violence after disqualifying people from owning a firearm given prior alcohol- and drug-related misdemeanors. METHODS: We created a population of 800,000 agents reflecting a 15% sample of the adult New York City population. RESULTS: Disqualification from purchasing firearms for 5 years after an alcohol-related misdemeanor conviction reduced population-level rates of firearm homicide by 1.0% [95% CI 0.4-1.6%] and suicide by 3.0% [95% CI 1.9-4.0%]. Disqualification based on a drug-related misdemeanor conviction reduced homicide by 1.6% [95% CI 1.1-2.2%] and suicide by 4.6% [95% CI 3.4-5.8%]. Reductions were generally 2 to 8 times larger for agents meeting the disqualification criteria. CONCLUSIONS: Denying firearm access based on a history of drug and alcohol misdemeanors may reduce firearm violence among the high-risk group. Enactment of substance use-related firearms denial criteria needs to be balanced against concerns about introducing new sources of disenfranchisement among already vulnerable populations.

Simulating the bounds of plausibility: Estimating the impact of high-risk versus population-based approaches to prevent firearm injury.

BACKGROUND: Firearm violence remains a persistent public health threat. Comparing the impact of targeted high-risk versus population-based approaches to prevention may point to efficient and efficacious interventions. We used agent-based modeling to conduct a hypothetical experiment contrasting the impact of high-risk (disqualification) and population-based (price increase) approaches on firearm homicide in New York City (NYC). METHODS: We simulated 800,000 agents reflecting a 15% sample of the adult population of NYC. Three groups were considered and disqualified from all firearm ownership for five years, grouped based on prevalence: low prevalence (psychiatric hospitalization, alcohol-related misdemeanor and felony convictions, 0.23%); moderate prevalence (drug misdemeanor convictions, domestic violence restraining orders, 1.03%); and high prevalence (all other felony/misdemeanor convictions, 2.30%). Population-level firearm ownership was impacted by increasing the price of firearms, assuming 1% price elasticity. RESULTS: In this hypothetical scenario, to reduce firearm homicide by 5% in NYC, 25% of the moderate prevalence group, or 12% of the high prevalence group needed to be effectively disqualified; even when all of the low prevalence group was disqualified, homicide did not decrease by 5%. An 18% increase in price similarly reduced firearm homicide by 5.37% (95% CI 4.43-6.31%). Firearm homicide declined monotonically as the proportion of disqualified individuals increased and/or price increased. A combined intervention that both increased price and effectively disqualified "high-risk" groups achieved approximately double the reduction in homicide as any one intervention alone. Increasing illegal firearm ownership by 20%, a hypothetical response to price increases, did not meaningfully change results. CONCLUSION: A key takeaway of our study is that adopting high-risk versus population-based approaches should not be an "either-or" question. When individual risk is variable and diffuse in the population, "high-risk approaches" to firearm violence need to focus on relatively prevalent groups and be highly efficacious in disarming people at elevated risk to achieve meaningful reductions in firearm homicide, though countering issues of social justice and stigma should be carefully considered. Similar reductions can be achieved with population-based approaches, such as price increases, albeit with fewer such countering issues.

In-hospital mortality and length of stay among patients with infective endocarditis and solid organ transplant: A study from National Inpatient Sample 2016-2019.

Infective endocarditis (IE) is a rare but serious complication following a Solid Organ Transplant (SOT). Due to the lack of sufficient studies, we aimed to compare in-hospital mortality and length of stay (LOS) of patients primarily admitted for IE (index or principal hospitalization) with history of SOT, including the subgroup of heart or lung transplant (HLT), to those without a history of SOT (non-SOT) or HLT (non-HLT). We used the 2016-2019 National Inpatient Sample, the largest all-payer inpatient hospital data from Healthcare Cost and Utilization Project (HCUP), including patients 18 years or older with IE, as a principal diagnosis for hospitalization. From 2016 to 2019, there were 56,330 principal or index hospitalizations for IE. Among them, 0.6 % (n = 327) were SOT recipients, 0.1% (n = 68) were HLT recipients, and 41.4% were females. The mean age was 51.9 ± 19.2 years. Compared to non-SOT controls, SOT recipients were older (mean age 59.3 vs. 51.8 years; P = 0.002) and had higher Charlson-comorbidity-index (CCI) of 3 or more (87.7% vs. 33.2%; p < 0.001). SOT status was not statistically significant for a higher or lower odds of in-hospital mortality (adjusted odds ratio (aOR) 0.7; 95% confidence interval (CI): 0.2, 2.4; p = 0.60) or increased or decreased LOS (coefficient: -0.1, 95% CI: -0.4, 0.1; p = 0.23) among index IE hospitalizations after controlling for age, sex, race, hospital-region, hospital-teaching status, income, insurance status, and CCI. HLT status was also not associated with higher or lower odds of in-hospital mortality (aOR 1.4; 95% CI: 0.2, 13.1; p = 0.77) or increased or decreased LOS (coefficient: -0.1, 95% CI: -0.3, 0.5; p = 0.59). From 2016 to 2019, the rate of index IE hospitalization trends from 37.8 to 41.4 per 100,000 overall hospitalizations (p = 0.001). We found the rate of index IE hospitalizations increasing with time. Among index IE hospitalizations, SOT, including a subgroup of HLT recipients, have similar in-hospital mortality and LOS compared to non-SOT or non-HLT groups. We need a larger sample size to comment on outcomes of IE hospitalizations with the HLT subgroup.

Applications of Complex Systems Models to Improve Retail Food Environments for Population Health: A Scoping Review.

Retail food environments (RFEs) are complex systems with important implications for population health. Studying the complexity within RFEs comes with challenges. Complex systems models are computational tools that can help. We performed a systematic scoping review of studies that used complex systems models to study RFEs for population health. We examined the purpose for using the model, RFE features represented, extent to which the complex systems approach was maximized, and quality and transparency of methods employed. The PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) guidelines were followed. Studies using agent-based modeling, system dynamics, discrete event simulations, networks, hybrid, or microsimulation models were identified from 7 multidisciplinary databases. Fifty-six studies met the inclusion criteria, including 23 microsimulation, 13 agent-based, 10 hybrid, 4 system dynamics, 4 network, and 2 discrete event simulation models. Most studies (n = 45) used models for experimental purposes and evaluated effects of simulated RFE policies and interventions. RFE characteristics simulated in models were diverse, and included the features (e.g., prices) customers encounter when shopping (n = 55), the settings (e.g., restaurants, supermarkets) where customers purchase food and beverages (n = 30), and the actors (e.g., store managers, suppliers) who make decisions that influence RFEs (n = 25). All models incorporated characteristics of complexity (e.g., feedbacks, conceptual representation of multiple levels), but these were captured to varying degrees across model types. The quality of methods was adequate overall; however, few studies engaged stakeholders (n = 10) or provided sufficient transparency to verify the model (n = 12). Complex systems models are increasingly utilized to study RFEs and their contributions to public health. Opportunities to advance the use of these approaches remain, and areas to improve future research are discussed. This comprehensive review provides the first marker of the utility of leveraging these approaches to address RFEs for population health.

Childhood Adversity Trajectories and Violent Behaviors in Adolescence and Early Adulthood.

Violence and other antisocial behaviors, including fighting and weapon carrying, are highly prevalent among adolescents but usually decrease in young adulthood. Childhood adversities, including exposure to abuse, intimate partner violence, and household substance use and mental health problems, have been linked to violent behaviors in adolescence and adulthood. However, few studies of childhood adversity as determinants of persistent violent behavior among community-based samples have been conducted. Furthermore, the effects of adversity timing and duration on subsequent violent behaviors are unclear. We examined the association between five childhood adversity trajectories (representing stable-low, stable-mild, decreasing, increasing, and stable-high adversity from birth through age 11.5 years) and physical fighting and weapon carrying at ages 13-20 years among a sample of young adults followed continuously since birth from the Avon Longitudinal Study of Parents and Children (n = 9,665). The prevalence of violent behaviors declined sharply as participants aged (e.g., whereas 42.8% reported engaging in physical fighting in the past year at ages 13-15 years, this dropped to 10.4% at ages 17-20 years). Childhood adversity trajectories exhibited a strong dose-response relation with physical fighting and weapon carrying, with particularly pronounced relations for violent behaviors persisting across both adolescence and early adulthood (e.g., for physical fighting at both ages 13-15 years and 17-20 years compared to no fighting at either period, adjusted odds ratio [aOR] = 1.62, 95% confidence interval [CI] = 1.31-2.00 for stable-mild; aOR = 2.33, 95% CI = 1.64-3.33 for decreasing; aOR = 3.18, 95% CI = 2.20-4.60 for increasing; and aOR = 3.73, 95% CI = 2.13-6.52 for stable-high adversity, compared to stable-low adversity). This work highlights the substantial implications of exposure to childhood adversity for youth violence prevention.

G-Computation and Agent-Based Modeling for Social Epidemiology: Can Population Interventions Prevent Posttraumatic Stress Disorder?

Agent-based modeling and g-computation can both be used to estimate impacts of intervening on complex systems. We explored each modeling approach within an applied example: interventions to reduce posttraumatic stress disorder (PTSD). We used data from a cohort of 2,282 adults representative of the adult population of the New York City metropolitan area from 2002-2006, of whom 16.3% developed PTSD over their lifetimes. We built 4 models: g-computation, an agent-based model (ABM) with no between-agent interactions, an ABM with violent-interaction dynamics, and an ABM with neighborhood dynamics. Three interventions were tested: 1) reducing violent victimization by 37.2% (real-world reduction); 2) reducing violent victimization by100%; and 3) supplementing the income of 20% of lower-income participants. The g-computation model estimated population-level PTSD risk reductions of 0.12% (95% confidence interval (CI): -0.16, 0.29), 0.28% (95% CI: -0.30, 0.70), and 1.55% (95% CI: 0.40, 2.12), respectively. The ABM with no interactions replicated the findings from g-computation. Introduction of interaction dynamics modestly decreased estimated intervention effects (income-supplement risk reduction dropped to 1.47%), whereas introduction of neighborhood dynamics modestly increased effectiveness (income-supplement risk reduction increased to 1.58%). Compared with g-computation, agent-based modeling permitted deeper exploration of complex systems dynamics at the cost of further assumptions.

Oral anticoagulants and relative risk of acute kidney injury in patients with atrial fibrillation: A systematic review and network meta-analysis.

Study objective: Oral anticoagulants (direct oral anticoagulants [DOACs] or warfarin) prevent stroke in patients with atrial fibrillation (AF), but their use may be associated with acute kidney injury (AKI). We aimed to compare AKI risk across individual oral anticoagulants in patients with AF. Design: Systematic review and network meta-analysis. Setting: Randomized trials and population-based studies. Participants: Patients with AF. Interventions: Oral anticoagulants. Main outcome measures: AKI. Results: A systematic literature search in Medline and Embase databases performed on December 17, 2021 identified ten randomized trials and eight population-based longitudinal studies based on prespecified inclusion criteria for systematic review. Clinical trials had short follow-ups and reported only low event rates of serious AKI. Retrospective longitudinal studies were assessed to be at higher risk for bias from confounding and outcome ascertainment, but follow-up was longer (1.5 to 8 years), with AKI incidence ranging from 2 to 29/100 person-years. Eight longitudinal studies that met transitivity assumption were included in a random-effects network meta-analysis within a Bayesian framework. All DOACs were associated with significantly lower risk of AKI compared to warfarin. Dabigatran was associated with lower risk of AKI compared to apixaban (hazard ratio [HR] = 0.82; 95% confidence interval [CI]: 0.68-0.99), rivaroxaban (HR = 0.84; 95%CI: 0.72-0.98), and warfarin (HR = 0.68; 95%CI: 0.59-0.77). Effect size estimates varied by chronic kidney disease status and study geographic locations. Conclusion: Apixaban, rivaroxaban, and dabigatran were associated with lower long-term risk of AKI compared to warfarin among patients with AF, with dabigatran potentially associated with the lowest risk.

Cardiac rehabilitation - The answer for the second chance.

In the United States and worldwide, the leading cause of death in females is cardiovascular disease (CVD). However, compared to males, females have overall higher mortality rates, especially within the first few years of having an acute myocardial infarction (AMI). Despite the increased awareness of CVD in females and established benefits of cardiac rehabilitation (CR) programs, there is still delayed initiation of care, under-recognition of atypical presentations of angina in females, under referral of females to CR, and under-representation of females in CVD trials. In this paper, we will investigate the barriers to female participation in CR, explore the fundamental differences in physiology between males and females, and current limitations in CVD trials where females are under-represented. Finally, we aim to provide potential methods to increase enrollment of females in CR and CR related trials.

Managing Ischemic Heart Disease in Women: Role of a Women's Heart Center.

PURPOSE OF REVIEW: Heart centers for women (HCW) were developed due to the rising cardiovascular morbidity and mortality in women in the United States in the early 1990s. Our review encompasses the epidemiology, risk factors, diagnostic strategies, treatments, and the role of HCW in managing women with ischemic heart disease (IHD). RECENT FINDINGS: HCW use a multidisciplinary team to manage women with IHD. Due to the paucity of randomized controlled trials investigating various manifestations of IHD, some treatments are not evidence-based such as those for coronary microvascular dysfunction and spontaneous coronary artery dissection. Sex-specific risk factors have been identified and multimodality cardiac imaging is improving in diagnosing IHD in women. Treatments are being studied to help improve symptoms and outcomes in women with IHD. There has been progress in the care of women with IHD. HCW can be instrumental in treating women with IHD, doing research, and being a source of research study participants.