Search

Introduction: Pregnancy-associated mortality involving opioids represents a significant public health issue. Limited social support is a known factor, contributing to a more complex recovery and a greater risk for relapse and overdose. Community-based doulas have been used in other marginalized populations yet are under-studied among pregnant and parenting persons with Opioid Use Disorder (OUD). Therefore, we aimed to investigate the perspectives of Opioid Treatment Program (OTP) clinical staff and community doulas about doula support for persons with perinatal OUD to 1) describe the perceived utility of doula support and 2) identify structural considerations for integrating doula support at an OTP., Methods: This study conducted focus groups and utilized domains of the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. Purposive sampling recruited 10 participants (5 doulas, 5 OTP staff: 1 clinical director, two counselors, one nurse, and one Community Health Worker) from an OTP program and a Philadelphia Department of Public Health Community Doula Support Program (CDSP). One focus group was held for doula staff, and two focus groups were held for OTP clinical staff. Thematic analytic procedures were used to analyze data using NVivo and an interdisciplinary coding team., Results: Five key themes were identified from the focus group data: 1) Role of advocacy in the court system, 2) Need for collaborative care, 3) Use of doulas to de-stigmatize healthcare experiences, 4) Impact of doula support on recovery, 5) Considerations to integrating doula referrals into OTPs., Conclusion: Perinatal doula support among persons with OUD is perceived as beneficial by critical stakeholders to advocate in healthcare and legal systems, de-stigmatize healthcare experiences, and promote recovery engagement. The implementation recommendations outlined may guide other OTPs looking to integrate doula support to improve maternal outcomes associated with opioid use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In light of the new nomenclature of steatotic liver disease (SLD), we aimed to enhance the existing knowledge on the epidemiology and clinical outcomes of metabolic and alcohol related/associated liver disease (MetALD)., Methods: A systematic review and meta-analysis were performed in Medline/PubMed, Embase, Scopus and Cochrane databases to evaluate the prevalence and outcomes of MetALD within the SLD population and to compare the characteristics between MetALD patients and those with metabolic dysfunction associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD). Nineteen studies from nine countries that evaluated 4,543,341 adult participants with SLD were included., Results: The pooled overall prevalence of MetALD among the SLD population was 10 % (95%CI:7-13 %) without significant difference between Asian and non-Asian populations. However, MetALD was more frequent in men than women (86 % vs 14 %, p < 0.01), while Asian MetALD patients, were more frequent men (92 % vs 66 %, p < 0.01) compared to non-Asians. Additionally, in terms of metabolic characteristics there were no significant differences between MetALD, MASLD and ALD patients. Regarding outcomes, patients with MetALD, compared to non-SLD, were at increased risk of all-cause [HR 1.44 (95%CI:1.24-1.66)], cardiovascular disease (CVD) [HR 1.17 (95%CI:1.12-1.21)] and cancer-related mortality [HR 2.07 (95%CI:1.32-3.25)]. Finally, patients with MetALD, had increased incidence of CVD and liver decompensating events, compared to non-SLD participants [HR 1.49 (95%CI:1.03-2.15); HR 10.55 (95%CI:3.46-32.16) respectively]., Conclusions: Based on the existing literature, patients with MetALD consist a significant part of the SLD population, with high all-cause, CVD and cancer-related mortality and increased risk for CVD and hepatic decompensation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Amidst an ongoing surge of opioid use disorder (OUD) incidence, clinicians and policymakers are seeking partnerships with faith communities - including with faith-affiliated treatment centers (FATCs) - to expand access to evidence-based OUD treatment. However, little is known whether FATCs differentially offer such evidence-based treatment services, particularly medications for opioid use disorder (MOUD) and co-occurring mental health care., Methods: We use the 2021 National Substance Use and Mental Health Services Survey (N-SUMHSS) to examine differences in provision of several OUD services, including MOUD, psychological treatments, mental health services, medical services, recovery support services, and services related to treatment accessibility, between self-identified FATCs and non-FATCs. We also explored differences in characteristics related to insurance, licensure, and accreditation., Results: FATCs were less likely than non-FATCs to offer almost all measure of MOUD and more likely to refuse to accept clients who use MOUD. They were also less likely to report using telemedicine. However, they were more likely to offer residential treatment, Twelve Step facilitation, and transitional housing. We find little evidence that FATCs offer co-occurring mental health treatments at different rates than non-FATCs., Conclusion: More research is needed to examine the factors that drive these differences, especially in MOUD and transitional housing. When partnering with FATCs, clinicians and policymakers should seek common ground with FATCs and recognize the philosophies, values, and concerns that may potentially be driving these differences., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Cannabis use and misuse have mental health implications, particularly affecting mood and anxiety symptoms. Vortioxetine, a potent serotonin partial agonist/antagonist reuptake inhibitor antidepressant, has well-established effects in treating depressive and anxiety disorders and may serve as a potential treatment for individuals with cannabis use disorder and comorbid mood symptoms. In the current study, we aimed to investigate the efficacy of vortioxetine for cannabis users with anxiety and depressive symptoms alongside their cannabis dependence., Methods: This 6-month prospective, randomized controlled interventional pilot study investigated if vortioxetine could improve cannabis dependence, comorbid anxiety and/or depressive symptoms, and cognitive and functional outcomes in individuals using cannabis. Participants were randomized to receive either vortioxetine (N = 11) or standard treatment (N = 19)., Results: Participants taking vortioxetine (mean dose 10 mg/day) showed significant improvement on clinician-observed overall mood states over time (p < .05) but not on their self-reported anxiety or depressive symptoms. Cannabis users receiving standard treatment did not exhibit similar improvement. No significant differences were found on cannabis dependence, cognition and functional outcomes between the two groups otherwise., Conclusions: The results suggest that the multimodal antidepressant vortioxetine may benefit cannabis users with depressive and anxiety symptoms in ameliorating their overall mood state., Competing Interests: Declaration of competing interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Post-traumatic stress disorder and substance use disorders commonly co-occur and are associated with worse health outcomes. Currently, only psychosocial therapies are specifically recommended for use in the co-occurring population, but these come with numerous barriers to access and engagement. This study aims to identify potential pharmacological treatments to enhance treatment options and outcomes for this population., Methods: This systematic review identified studies on pharmacological treatment of co-occurring PTSD and SUD in humans, using validated outcome measurements, with study design of RCT, observational study, case control study or cohort study., Results: 29 studies were identified for inclusion, looking at a range of 16 pharmacotherapies. A majority concentrated on alcohol use disorders and males, with many focused on the veteran population., Conclusions: This is an area for further research, inclusive of more SUDs, genders and civilians. Future studies utilizing consistent dosing, populations and measurement outcomes will allow for future meta-analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Evidence is limited regarding the association of circulating metabolites with decline of kidney function, letting alone their value in prediction of development of chronic kidney disease (CKD)., Methods: This study included 3802 participants aged 64.1 ± 7.4 years from the Dongfeng-Tongji cohort, among whom 3327 were CKD-free at baseline (estimated glomerular filtration rate [eGFR] > 60 ml/min per 1.73 m 2 ). We measured baseline levels of 211 metabolites with liquid chromatography coupled with mass spectrometry, including 25 amino acids, 12 acyl-carnitines, 161 lipids, and 13 other metabolites., Results: The mean (SD) absolute annual change in eGFR was -0.14 ± 4.11 ml/min per 1.73 m 2 per year, and a total of 472 participants who were free of CKD at baseline developed incident CKD during follow-up of 4.6 ± 0.2 years (14.2 %). We identified a total of 22 metabolites associated with annual eGFR change and survived Bonferroni correction for multiple testing, including seven metabolites associated with eGFR increase (six being docosahexaenoic acid [DHA]-containing lipids) and 15 associated with eGFR decline (nine being phosphatidylcholines [PCs]). Among them, eight metabolites obtained non-zero coefficients in least absolute shrinkage and selection operator (LASSO) regression on incident CKD, indicating predictive potential, including one amino acid (arginine), one acyl-carnitine (C2), one lysophosphatidylcholine (LPC 22:6), two PCs (32:1 and 34:3), one triacylglycerol (TAG 56:8 [22:6]) and two other metabolites (inosine, niacinamide), and the composite score of these eight metabolites showed an odds ratio (OR) of 8.79 (95 % confidence interval [CI]: 7.49, 10.32; P < 0.001) per SD increase in association with incident CKD. The addition of the metabolite score increased the c-statistic of the reference model of traditional risk factors (including baseline eGFR) by 0.065 (95 % CI: 0.046 to 0.084; P = 3.39 × 10 -11 ) to 0.765 (0.742 to 0.788) in 1000 repetitions of 10-fold cross-validation, while the application of two advanced machine learning algorithms, random forest (RF), and extreme gradient boosting (XGBoost) models produced similar c-statistics, to 0.753 (0.729 to 0.777) and 0.778 (0.733 to 0.824) with increases of 0.074 (0.055 to 0.093; P = 4.11 × 10 -14 ) and 0.073 (0.032 to 0.114; P = 4.00 × 10 -4 ), respectively., Conclusions: In this study, we identified 22 metabolites associated with longitudinal eGFR change, nine of which were PCs and six were DHA-containing lipids. We screened out a panel of eight metabolites which improved prediction for the development of CKD by 9 % beyond traditional risk factors including baseline eGFR. Our findings highlighted involvement of lipid metabolism in kidney function impairment, and provided novel predictors for CKD risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The dorsomedial hypothalamus (DMH) receives inputs from the preoptic area (POA), where ambient temperature mediates physiological adaptations of energy expenditure and food intake. Warm-activated POA neurons suppress energy expenditure via brown adipose tissue (BAT) projecting neurons in the dorsomedial hypothalamus/dorsal hypothalamic area (dDMH/DHA). Our earlier work identified leptin receptor (Lepr)-expressing, BAT-projecting dDMH/DHA neurons that mediate metabolic leptin effects. Yet, the neurotransmitter (glutamate or GABA) used by dDMH/DHA Lepr neurons remains unexplored and was investigated in this study using mice. We report that dDMH/DHA Lepr neurons represent equally glutamatergic and GABAergic neurons. Surprisingly, chemogenetic activation of glutamatergic and/or GABAergic dDMH/DHA neurons were capable to increase energy expenditure and locomotion, but neither reproduced the beneficial metabolic effects observed after chemogenetic activation of dDMH/DHA Lepr neurons. We clarify that BAT-projecting dDMH/DHA neurons that innervate the raphe pallidus (RPa) are exclusively glutamatergic Lepr neurons. In contrast, projections of GABAergic or dDMH/DHA Lepr neurons overlapped in the ventromedial arcuate nucleus (vmARC), suggesting distinct energy expenditure pathways. Brain slice patch clamp recordings further demonstrate a considerable proportion of leptin-inhibited dDMH/DHA Lepr neurons, while removal of pre-synaptic (indirect) effects with synaptic blocker increased the proportion of leptin-activated dDMH/DHA Lepr neurons, suggesting that pre-synaptic Lepr neurons inhibit dDMH/DHA Lepr neurons. We conclude that stimulation of BAT-related, GABA- and glutamatergic dDMH/DHA Lepr neurons in combination mediate the beneficial metabolic effects. Our data support the idea that dDMH/DHA Lepr neurons integrate upstream Lepr neurons (e.g., originating from POA and ARC). We speculate that these neurons manage dynamic adaptations to a variety of environmental changes including ambient temperature and energy state. SIGNIFICANCE STATEMENT: Our earlier work identified leptin receptor expressing neurons in the dDMH/DHA as an important thermoregulatory site. Dorsomedial hypothalamus (DMH) Lepr neurons participate in processing and integration of environmental exteroceptive signals like ambient temperature and circadian rhythm, as well as interoceptive signals including leptin and the gut hormone glucagon-like-peptide-1 (GLP1). The present work further characterizes dDMH/DHA Lepr neurons as a mixed glutamatergic and GABAergic population, but with distinct axonal projection sites. Surprisingly, select activation of glutamatergic and/or GABAergic populations are all able to increase energy expenditure, but are unable to replicate the beneficial metabolic effects observed by Lepr activation. These findings highlighting dDMH/DHA Lepr neurons as a distinct subgroup of glutamatergic and GABAergic neurons that are under indirect and direct influence of the interoceptive hormone leptin and if stimulated are uniquely capable to mediate beneficial metabolic effects. Our work significantly expands our knowledge of thermoregulatory circuits and puts a spotlight onto DMH-Lepr neurons for the integration into whole body energy and body weight homeostasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Obesity is a growing global health epidemic with limited orally administered therapeutics. Serotonin (5-HT) is one neurotransmitter which remains an excellent target for new weight-loss therapies, but a gap remains in understanding the mechanisms involved in 5-HT produced in the dorsal Raphe nucleus (DRN) and its involvement in meal initiation. Using an optogenetic feeding paradigm, we showed that the 5-HT DRN ➔arcuate nucleus (ARH) circuit plays a role in meal initiation. Incorporating electrophysiology and ChannelRhodopsin-2-Assisted Circuit Mapping, we demonstrated that 5-HT DRN neurons receive inhibitory input partially from GABAergic neurons in the DRN, and the 5-HT response can be enhanced by hunger. Additionally, deletion of the GABA A receptor subunit in 5-HT neurons inhibits meal initiation with no effect on the satiation process. Finally, we identified the role of dopaminergic inputs via dopamine receptor D2 in enhancing the response to GABA-induced feeding. Thus, our results indicate that 5-HT DRN neurons are inhibited by synergistic inhibitory actions of GABA and dopamine, for the initiation of a meal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The association between Life's Essential 8 (LE8) score and all-cause mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) remains unknown., Methods: This population-based prospective cohort study analyzed data of participants aged 20-79 years in the National Health and Nutrition Examination Survey from 2005 to 2018, with linked mortality information until 2019. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association between different cardiovascular health (CVH) scores and all-cause mortality in participants with MASLD., Results: Among 11,988 participants, 4109 (34.3 %) were diagnosed with MASLD. During the median 7.8 years of follow-up, 912 deaths were recorded. Unexpectedly, the total LE8 CVH score was not associated with all-cause mortality in patients with MASLD (all P > .05). However, individuals with MASLD with moderate and poor LE8 health behaviors scores exhibited an increased risk of all-cause mortality (moderate: HR, 1.51; 95 % CI, 1.05-2.17; poor: HR, 2.32; 95 % CI, 1.64-3.30), particularly among patients with advanced fibrosis (moderate: HR, 1.77; 95 % CI, 1.07-2.92; poor: HR, 2.43; 95 % CI, 1.23-4.78). Population-attributable fraction estimates suggest that 35.0 % of all-cause mortality attributed to poor or moderate health behaviors scores could be avoided if ideal CVH metrics were achieved in all patients with MASLD., Conclusion: These findings demonstrate a significant association between the LE8 health behaviors score and all-cause mortality in patients with MASLD, highlighting the usefulness of this score in optimizing risk management strategies for MASLD in future clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: Atherosclerotic cardiovascular diseases are the leading cause of death. Apolipoprotein A-I (apoA-I) mediates cholesterol efflux to lower the risks of atherosclerosis. Elevating circulating apoA-I is an effective strategy for atheroprotection. However, the regulatory mechanisms of apoA-I have been elusive., Methods: Protein-protein interactions were examined by co-immunoprecipitations. Chemical biology tools were used to determine the binding of 5PP-InsP 5 to its target proteins and its roles in mediating protein-protein interactions. The mouse atherosclerotic model was generated by injecting AAV-PCSK9 and feeding a Western diet. Atherosclerotic plaques were determined by Oil Red O and H&E staining., Results: We show that blocking IP6K1 activity increases apoA-I production in hepatocytes. IP6K1 binds to apoA-I and via its product 5PP-InsP 5 to induce apoA-I degradation, which requires ubiquitination factor E4A (UBE4A). Depleting 5PP-InsP 5 by deleting IP6K1 or blocking IP6K1 activity disrupts the interaction between UBE4A and apoA-I, preventing apoA-I degradation, leading to increased production of apoA-I. Hepatocyte-specific deletion of IP6K1 elevates circulating apoA-I levels, which augments cholesterol efflux and lowers the burden of atherosclerosis. Mice with both apoA-I KO and hepatocyte-specific IP6K1 KO were generated to validate that IP6K1 deletion-induced atheroprotection requires apoA-I., Conclusions: Our findings reveal a mechanism by which blocking IP6K1 boosts apoA-I production. Blocking IP6K1 represents a potential treatment strategy to elevate circulating apoA-I for atheroprotection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Rural populations have higher rates of tobacco use but are less likely to use evidence-based smoking cessation treatments than urban residents. There is limited evidence on the use of smoking cessation treatments and the factors associated with their use in rural populations. This study explored quit attempts, use of smoking cessation treatments, quitting intention and associated factors among rural residents seeking smoking cessation treatment., Methods: Participants were adult rural or remote residents of New South Wales, Australia who enrolled in a randomized trial of smoking cessation treatment (n = 1244). Participants completed an online baseline survey assessing quit attempts, quitting intention, and prior use of smoking cessation treatments. Multivariable logistic regressions that adjusted for other variables examined associations and derived odds ratios., Results: Almost half (48.3 %) of participants made a quit attempt in the last 12 months, and 44.6 % intended to quit in the next 30 days. Women (OR = 0.74, 95 % CI 0.56-0.99), Australian-born participants (OR = 0.67, 95 % CI 0.45-0.99) and those with moderate (OR = 0.53, 95 % CI 0.40-0.71) or high (OR = 0.42, 95 % CI 0.28-0.63) nicotine dependence had significantly lower odds of making a quit attempt in the last 12 months. Among participants who had ever made a quit attempt, most had used pharmacotherapies (82.2 %) or behavioral interventions (68.3 %) during any quit attempt. Participants with moderate (OR = 1.96, 95 % CI 1.37-2.79) or high (OR = 3.27, 95 % CI 1.66-6.45) nicotine dependence and chronic conditions (OR = 1.45, 95 % CI 1.00-2.11) had significantly greater odds of pharmacotherapy use while those who drank alcohol daily or almost daily (OR = 0.46, 95 % CI 0.26-0.81) had significantly lower odds of pharmacotherapy use. Those with moderate (OR = 1.38, 95 % CI 1.02-1.87) or high (OR = 3.31, 95 % CI 1.94-5.66) nicotine dependence, university education (OR = 1.47, 95 % CI 1.04-2.07), moderate (OR = 1.63, 95 % CI 1.19-2.22) or high (OR = 1.73, 95 % CI 1.12-2.68) financial stress, and anxiety (OR = 1.61, 95 % CI 1.16-2.22) had significantly greater odds of using behavioral treatments whereas those with depression (OR = 0.66, 95 % CI 0.47-0.92) had significantly lower odds., Conclusions: Some sub-groups had lower odds of using smoking cessation treatments. Understanding if particular barriers hinder use of smoking cessation treatments among certain sub-groups of rural residents is needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Ray has received research support to his institution Imperial College London from Amgen, Sanofi, Regeneron, MSD, Pfizer, Daiichi Sankyo, Ultragenix and reports personal fees for Consultancy from Amgen, Sanofi, Regeneron, Pfizer, Viatris, Abbott, AstraZeneca, Lilly, Kowa Pharmaceutics, Novo Nordisk, Boehringer Ingelheim, Esperion, Cargene Therapeutics, Resverlogix, Novartis, Silence Therapeutics, NewAmsterdam Pharma, Scribe Therapeutics, CRISPR Therapeutics, VAXXINITY, Amarin, CSL Behring, Bayer, Cleerly Health, Emendobio and holds stock options from PEMI31, SCRIBE and New Amsterdam Pharma. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Introduction: Hispanic/Latinx (hereafter Hispanic) individuals who smoke have challenges in quitting and a disproportionate risk of smoking-related health problems when compared to the general population. The smoking inequalities among the Hispanic population are influenced by limited treatment access and chronic stress exposure (e.g., racial/ethnic discrimination). The present study sought to culturally adapt and initially test a novel, Spanish-language mobile intervention entitled Impacto. Impacto helps address aversive psychosomatic stress (e.g., bodily symptoms, negative affect states) that can maintain smoking by targeting individual differences in anxiety sensitivity during the cessation process., Methods: The current study utilized a single-arm open-label pilot trial of an integrated, anxiety sensitivity and smoking cessation Spanish language mobile health application for the Android platform, Impacto. Participants were 30 adults who engaged in daily combustible cigarette use (females n = 15, M age  = 40.2 years, SD = 11.1). The study evaluated effects of Impacto on 7-day point-prevalence smoking abstinence, cigarettes smoked per day, and anxiety sensitivity and examined feasibility, acceptability, and engagement., Results: Results indicated that Impacto had a positive impact on smoking abstinence with over half of the sample (65.4 %) reporting smoking abstinence 4-weeks post-quit. Moreover, rates of cigarettes smoked per day and anxiety sensitivity levels significantly decreased from baseline through 4-weeks post-quit. High rates of feasibility, acceptability, and engagement were also observed., Conclusions: Impacto represents a promising new smoking cessation intervention for Hispanic individuals with elevated psychosomatic symptoms who smoke., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Introduction: Buprenorphine and other medications for opioid use disorder (MOUD) are highly effective but substantially under prescribed in the rural United States. Among the most cited barriers to buprenorphine prescribing is stigma, yet little progress has been made in developing successful strategies to reduce stigma and increase access to life-saving medication. One of the key challenges to developing successful implementation strategies is understanding the different types of stigma that limit implementation., Methods: This study draws from qualitative interviews with 23 primary care professionals (PCPs) in rural Ohio. We conducted semi-structured interviews focused on prior experiences with buprenorphine, willingness to prescribe it, prior buprenorphine training, and barriers to prescribing. Thematic analysis resulted in 3 forms of stigma that must be addressed to improve implementation., Results: PCPs discussed 3 key forms of stigma that limit buprenorphine prescribing in rural areas: 1) stigma towards patients-PCPs feared being harmed by patients with opioid use disorder (OUD) if they began prescribing buprenorphine; 2) stigma towards providers-PCPs believed their clinics would be stigmatized if they began treating addiction; and 3) stigma towards buprenorphine-PCPs worried they might unintentionally harm patients through prescribing a partial opioid agonist., Conclusions: Stigma remains a critical barrier to buprenorphine prescribing among rural PCPs but is not limited to negative attitudes towards people with OUD. Buprenorphine is also stigmatized and PCPs fear becoming stigmatized if they prescribe the medication. Implementation research is urgently needed to test whether multicomponent stigma-reduction strategies increase access to buprenorphine in rural communities., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Berkeley Franz reports financial support was provided by National Institute on Drug Abuse. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

The nonenergy-producing or biomass-accumulating functions of metabolism are attracting increasing attention, as metabolic changes are gaining importance as discrete signaling pathways in modulating enzyme activity and gene expression. Substantial evidence suggests that myocardial metabolic remodeling occurring during diabetic cardiomyopathy, heart failure, and cardiac pathological stress (e.g., myocardial ischemia, pressure overload) contributes to the progression of pathology. Within the rewired metabolic network, metabolic intermediates and end-products can directly alter protein function and/or regulate epigenetic modifications by providing acyl groups for posttranslational modifications, thereby affecting the overall cardiac stress response and providing a direct link between cellular metabolism and cardiac pathology. This review provides a comprehensive overview of the functional diversity and mechanistic roles of several types of metabolite-mediated histone and nonhistone acylation, namely O-GlcNAcylation, lactylation, crotonylation, β-hydroxybutyrylation, and succinylation, as well as fatty acid-mediated modifications, in regulating physiological processes and contributing to the progression of heart disease. Furthermore, it explores the potential of these modifications as therapeutic targets for disease intervention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Introduction: Buprenorphine is a highly effective medication for opioid use disorder (MOUD; OUD), which can be prescribed alongside naloxone in the primary care setting as part of a harm reduction approach to OUD. Despite this potential, implementation challenges have limited adoption of MOUD. To address barriers at the organizational level, we need better tools to measure perceived organizational support for the treatment of OUD and use of MOUD in the primary care setting. In this study, we developed an OUDSUPPORT measure to assess the relationship between organizational culture and critical treatment attitudes and behaviors in primary care., Methods: We conducted a statewide survey of 404 primary care-aligned health professionals (PCPs) in Ohio. We analyzed the survey data using descriptive and bivariate statistics. Additionally, three stepwise multivariable regression models assess the relationship between organizational support and three primary outcomes: willingness to treat OUD; receipt of the X-waiver, which was previously required to prescribe buprenorphine; and naloxone prescribing, independent of individual and county-level predictors., Results: The OUDSUPPORT measure demonstrated satisfactory psychometric properties, and was associated with meaningful treatment outcomes. PCPs perceived the strongest organizational support for a shared mission of providing care to people with OUD. The least commonly endorsed form of organizational support was for prescribing buprenorphine. Perceived organizational support was associated with increased willingness to treat OUD (b = 0.26; 95 % CI: 0.17, 0.35); higher odds of having received the X-waiver (OR = 1.63; 95 % CI: 1.26, 2.12); and higher odds of naloxone prescribing (OR = 1.71; 95 % CI: 1.30, 2.25)., Conclusions: OUDSUPPORT is a multidimensional measure of perceived organizational support for the treatment of OUD, which was associated with treatment willingness, receipt of buprenorphine prescribing training, and naloxone prescribing among PCPs. Implementation strategies to increase buprenorphine prescribing in the primary care setting must include efforts to decrease stigma, and address hesitance related to MOUD and harm reduction at the administrative level, in addition to addressing well known barriers at the individual prescriber level., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Berkeley Franz reports financial support was provided by National Institute on Drug Abuse. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Identifying novel, high-yield drug targets is challenging and often results in a high failure rate. However, recent data indicates that leveraging human genetic evidence to identify and validate these targets significantly increases the likelihood of success in drug development. Two recent papers from Open Targets claimed that around half of FDA-approved drugs had targets with direct human genetic evidence. By expanding target identification to include protein network partners-molecules in physical contact-the proportion of drug targets with genetic evidence support increased to two-thirds. However, the efficacy of using these network partners for target identification was not formally tested. To address this, we tested the approach on a list of robust positive control genes. We used the IntAct database to find physically interacting proteins of genes identified by exome-wide association studies (ExWAS), genome-wide association studies (GWAS) combined with a locus-to-gene mapping algorithm called the Effector Index and Genetic Priority Score (GPS) which integrated eight genetic features with drug indications from the Open Targets and SIDER databases. We assessed how accurately including interacting genes with the ExWAS, Effector Index and Genetic Priority Scores selected genes identified positive controls, focusing on precision, sensitivity, and specificity. Our results indicated that although molecular interactions led to higher sensitivity in identifying positive control genes, their practical application is limited by low precision. Expanding genetically identified targets to include network partners using IntAct did not increase the likelihood of identifying drug targets across the 412 tested traits, suggesting that such results should be interpreted with caution., (Copyright © 2025. Published by Elsevier Inc.)

Competing Interests: Funding support and author disclosures Dr Pellikka receives research support from Ultromics, with money paid to her institution; is supported as the Betty Knight Scripps- George M. Gura, Jr. MD, Professor of Cardiovascular Diseases Clinical Research, Mayo Clinic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Despite having high prevalence of short sleep duration, poor sleep quality, and sleep disorders in adult Hispanics living in the US, there is limited understanding of the underlying barriers to sleep and effective interventions in these groups. This study aimed to increase understanding of sleep duration and attitudes toward sleep interventions among Hispanic adults., Methods: We conducted 5 online focus group discussions with male and female participants aged 18-65 recruited from the Hispanic community who reported sleeping <7 hours per night. Interviewers utilized a semistructured interview guide to assess attitudes and beliefs about sleep and sleep interventions. Focus groups were conducted in Spanish, recorded, transcribed, and coded to elicit common themes., Results: Focus groups included 31 participants (19=women) from 12 Hispanic nationalities. Coders identified three main topics: (1) Sleep perceptions, (2) External and internal factors that affect sleep, and (3) Feedback about sleep interventions. Participants discussed the importance of sleep and factors related to stress, family, environment, and acculturation. Sleep interventions were viewed as desirable, and the group discussed a variety of topics of interest. The use of consumer sleep technology was considered a favorable intervention despite few participants having experience with consumer sleep-tracking devices., Conclusion: Results demonstrated that participants were aware of the importance of sleep and sleep duration recommendations. The discussion identified unique issues affecting sleep health in Hispanics as well as enthusiasm for sleep interventions, including interventions using consumer sleep trackers., Competing Interests: Declaration of conflicts of interest There are no conflicts of interest for this paper. The study was funded by a google health equity award, but the company was not involved in the conduct of this study, analyses or preparation of results., (Copyright © 2025 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The 2022 Curriculum Outcomes and Entrustable Professional Activities (COEPA) include an updated set of entrustable professional activities (EPAs) for PharmD graduates. To assist pharmacy educators with the integration and assessment of EPAs, the objective of this work was to review and synthesize 1) approaches to integrate EPAs in health professions curricula 2) strategies for EPA-related assessments and entrustment in health professions curricula and 3) challenges and research needs for integrating EPAs in assessment frameworks in PharmD curricula FINDINGS: A literature review resulted in 114 articles identified as having relevance with 33 articles specific to pharmacy education. There are multiple components of an effective EPA integration and assessment plan, including administrative leadership, determination of programmatic EPAs with comprehensive descriptions, selection of an entrustment-supervision scale, identification of EPA-based assessments, EPA mapping, data management, and training and development., Summary: Strategies with applicability for integrating and assessing EPAs in pharmacy education were analyzed and synthesized. Evidence-informed and expert recommendations for EPA integration and assessment are discussed. Programs can apply these recommendations to implement and assess EPAs in alignment with their own institutional and curricular contexts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 American Association of Colleges of Pharmacy. Published by Elsevier Inc. All rights reserved.)

Background: Patients with severe tricuspid regurgitation (TR) typically present with heterogeneity in the extent of cardiac dysfunction and extra-cardiac comorbidities, which play a decisive role for survival after transcatheter tricuspid valve intervention (TTVI)., Objectives: This aim of this study was to create a survival tree-based model to determine the cardiac and extra-cardiac features associated with 2-year survival after TTVI., Methods: The study included 918 patients (derivation set, n = 631; validation set, n = 287) undergoing TTVI for severe TR. Supervised machine learning-derived survival tree-based modelling was applied to preprocedural clinical, laboratory, echocardiographic, and hemodynamic data., Results: Following univariate regression analysis to pre-select candidate variables for 2-year mortality prediction, a survival tree-based model was constructed using 4 key parameters. Three distinct cluster-related risk categories were identified, which differed significantly in survival after TTVI. Patients from the low-risk category (n = 261) were defined by mean pulmonary artery pressure ≤28 mm Hg and N-terminal pro-B-type natriuretic peptide ≤2,728 pg/mL, and they exhibited a 2-year survival rate of 85.5%. Patients from the high-risk category (n = 190) were defined by mean pulmonary artery pressure >28 mm Hg, right atrial area >32.5 cm 2 , and estimated glomerular filtration rate ≤51 mL/min, and they showed a significantly worse 2-year survival of only 52.6% (HR for 2-year mortality: 4.3, P < 0.001). Net re-classification improvement analysis demonstrated that this model was comparable to the TRI-Score and outperformed the EuroScore II in identifying high-risk patients. The prognostic value of risk phenotypes was confirmed by external validation., Conclusions: This simple survival tree-based model effectively stratifies patients with severe TR into distinct risk categories, demonstrating significant differences in 2-year survival after TTVI., Competing Interests: Funding Support and Author Disclosures Dr Fortmeier has received funding from the Ruhr University Bochum (Female Clinician Scientist Grant). Dr Lachmann has received funding from the Technical University of Munich (Clinician Scientist Grant), from the German Center for Cardiovascular Research (DZHK; Postdoc Start-up Grant on Advancing Digital Aspects), and from the German Heart Foundation. Amelie Hesse received funding from the German Cardiac Society (DGK; Otto Hess Doctoral Scholarship). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Liver synthetic dysfunction predicts outcomes in cardiac intensive care unit (CICU) patients., Objectives: The purpose of this study was to evaluate the associations between the severity and extent of admission liver function test (LFT) abnormalities and mortality in a mixed CICU population., Methods: This historical cohort study included unique CICU patients from 2007 to 2018 with available data for admission LFT values. We categorized each LFT from grade 0 to grade 4 based on multiples of the upper limit of normal. We evaluated in-hospital mortality using logistic regression and 1-year mortality using Cox proportional hazards regression., Results: We included 7,284 patients, and 3,477 (47.7%) had at least 1 LFT with grade 1 or greater. In-hospital mortality was higher for patients with 1 or more abnormal LFTs (17.9% vs 6.4%; adjusted OR: 1.54 [95% CI: 1.27-1.86]; P  < 0.001). A stepwise increase in in-hospital mortality was observed with increasing LFT grade, both overall (adjusted OR: 1.25 [95% CI: 1.16-1.34] per each higher grade; P  < 0.001) and for each individual LFT. Each additional abnormal LFT was associated with higher in-hospital mortality (adjusted OR: 1.19 [95% CI: 1.10-1.29] per each; P  < 0.001). One-year mortality was significantly higher in patients with abnormal LFT values (unadjusted HR: 1.70 [95% CI: 1.56-1.86]; P  < 0.001) and increased incrementally as a function of the severity and extent of LFT abnormality., Conclusions: The severity and extent of LFT abnormalities are positively associated with in-hospital and 1-year mortality in CICU patients. Cardiohepatic syndrome is an important predictor of prognosis in CICU patients, and inclusion of LFTs in future risk-prediction tools could enhance prognostication., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Aim: Disease misdiagnosis is more likely if standardised diagnostic criteria are not used. This study systematically examined the effect on diagnosing dry eye disease (DED), when tests for evaluating tear film homeostasis were included/excluded from a multi-test protocol., Method: For 1427 participants across five sites, data for the full suite of diagnostic tests defined in the Tear Film and Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II) Diagnostic Methodology report algorithm were evaluated; diagnostic sensitivity was calculated when individual signs were removed, and when different combinations of signs were required., Results: Evaluating just one of the three TFOS DEWS II homeostatic signs resulted in between 12.3% and 36.2% of patients who met the DED diagnostic criteria not being assigned this diagnosis. While comprehensive ocular surface staining evaluation, including corneal, conjunctival and lid margin staining, in combination with symptoms had the highest sensitivity (87.7%) of the three markers, the sensitivity dropped to 44.6% if only corneal staining was evaluated. Omitting either non-invasive tear breakup time or osmolarity each dropped the sensitivity by <5%. The prevalence of DED was substantially reduced if a diagnosis required symptoms and two of the three signs to be present (by 43.7% to 61.2%) and by 65.9% if all three signs indicating a loss of tear film homeostasis were required. The analysis did not change significantly across differing severities of DED symptoms., Conclusions: The TFOS DEWS II diagnostic algorithm of symptoms plus assessing for a tear film or ocular surface sign can be considered a robust and appropriate approach for DED diagnosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: James Wolffsohn and Jennifer Craig reports a relationship with Tear Film and Ocular Surface Society that includes: board membership and travel reimbursement. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Background: Biomarkers are used for long-term risk prediction of cardiovascular (CV) events in patients presenting with suspected acute coronary syndromes., Objectives: This study investigated whether there are sex differences in the long-term prognostic value of biomarkers in patients presenting with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS)., Methods: High-sensitivity cardiac troponin (hs-cTn), hs-cTnI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15, and C-reactive protein (CRP) concentrations were measured in 1,476 patients admitted with suspected NSTE-ACS. Patients were followed up for a median of 1,547 (IQR: 873-1,842) days until a primary composite endpoint of all-cause mortality, incident myocardial infarction, or heart failure hospitalization. A secondary endpoint of CV death was also registered., Results: For the primary endpoint, a log2 increase of hs-cTn and hs-cTnI concentration was associated with a higher adjusted hazard ratio in women (hs-cTn: 1.3, 95% CI: 1.2-1.5; hs-cTnI: 1.2, 95% CI: 1.1-1.2) than in men (hs-cTn: 1.1, 95% CI: 1.0-1.2; hs-cTnI: 1.0, 95% CI: 1.0-1.1); P value for interaction with sex: 0.009 (hs-cTn) and 0.005 (hs-cTnI). A similar interaction was shown for NT-proBNP (P for interaction: 0.043). GDF-15 and CRP were independent predictors of the primary endpoint, but the interaction by sex was nonsignificant., Conclusions: In contrast to CRP and GDF-15, increasing concentrations of hs-cTn, hs-cTnI, and NT-proBNP are associated with higher risk of death and CV events in female than in male patients presenting with suspected NSTE-ACS. Sex-adjustment of hs-cTn and NT-proBNP may increase the accuracy of long-term CV prognostication in women and men., Competing Interests: Funding Support and Author Disclosures This study was financed by a grant from the Western Norway Regional Health Authority (grant number: 912265). Dr G.M.S. Myrmel has had a part time research grant from Trond Mohn Foundation and currently is receiving a Ph.D. grant from the Western Norway Regional Health Authority (grant number: F-12589). The reagent costs for GDF-15 were covered by Roche Diagnostics. The sponsor had no influence on the analyzing or interpretation of the data, nor on the writing of the manuscript. Dr Aakre has served on the advisory board of Roche Diagnostics, Siemens Healthineers, and SpinChip; consultant honoraria from CardiNor; lecturing honorarium from Siemens Healthineers, Roche Diagnostics, Mindray, and Snibe Diagnostics; and research grants from Siemens Healthineers and Roche Diagnostics. She is an Associate Editor of Clinical Biochemistry and Chair of the IFCC Committee of Clinical Application of Cardiac Bio-markers. Dr Omland has received speaker and/or consultancy honoraria from Abbott Diagnostics, Bayer, CardiNor, Roche Diagnostics, and Siemens Healthineers and has received research support from Abbott Diagnostics, Novartis, Roche Diagnostics, via Akershus University Hospital. Dr Skadberg has received lecture fees from Abbott Diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Previous research on the interaction of physical activity and sleep on depressive symptoms was mostly cross-sectional or conducted with children or young adults. This study examines the main and interactive associations of physical activity and sleep duration with depressive symptoms over a 3-year period among middle-aged and older Chinese adults., Methods: Data from 4269 Chinese adults aged 45 or older from the China Health and Retirement Longitudinal Study (CHARLS) were used. Physical activity was categorized as inadequate (<600 MET), adequate (600-8000 MET), and extremely high (>8000 MET). Sleep was classified as inadequate (<6 hours), adequate (6-9 hours), and excessive (>9 hours). The Center for Epidemiologic Studies Depression Scale (CES-D) was used to measure depressive symptoms., Results: Inadequate sleep was linked to greater increases in depressive symptoms over 3years. A significant interaction between baseline physical activity and sleep duration in predicting depressive symptoms at the 3-year follow-up showed that inadequate sleep, when combined with either inadequate or extremely high physical activity, was associated with higher depressive symptoms at the 3-year follow-up. In middle-aged subgroups, for people with either inadequate physical activity or an extremely high level of physical activity, inadequate sleep was associated with higher CES-D score compared to adequate sleep; for older adults, only inadequate sleep was associated with a higher follow-up CES-D score., Conclusion: Physical activity and sleep interactively impacted depressive symptoms, suggesting future personalized interventions that simultaneously target physical activity and sleep. Adequate sleep was associated with lower levels of future depressive symptoms in people with inadequate or extremely high physical activity., Competing Interests: Declaration of conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Background: Psoriasis in pregnancy is associated with adverse maternal outcomes. However, there are limited data on this subject., Objectives: The purpose of our study was to investigate the association between psoriasis and related cardiovascular complications during delivery., Methods: The National Inpatient Sample was used to identify hospitalizations for delivery from 2011 to 2020. Propensity score matching was performed to study the association of psoriasis with the primary outcomes of in-hospital medical and obstetric complications., Results: A total of 37,482,206 weighted delivery hospitalizations in women ≥18 years were identified; of which, 23,588 patients had psoriasis. Pregnant patients with psoriasis had a higher incidence of complications during delivery, including preeclampsia/eclampsia, acute kidney injury, pulmonary edema, cardiac arrhythmias, and venous thromboembolism compared to those without psoriasis. In propensity-matched analysis, psoriasis was significantly associated with a higher risk of preeclampsia/eclampsia (OR: 1.25, 95% CI: 1.08 to 1.43, P = 0.002) and cardiac arrhythmias (OR: 1.44, 95% CI: 1.08-1.93, P = 0.012), compared to patients without psoriasis., Conclusions: Delivery hospitalizations in patients with psoriasis are associated with a higher risk of preeclampsia/eclampsia and cardiac arrhythmias., Competing Interests: Funding support and author disclosures Dr Michos reports Advisory Board participation for Amgen, Arrowhead, AstraZeneca, Boehringer Ingelheim, Edwards Life Science, Esperion, Ionis, Lilly, Medtronic, Merck, New Amsterdam, Novartis, Novo Nordisk, and Pfizer. Dr Weber has received scientific advisory board/consulting fees from Novo Nordisk, Kiniksa Pharmaceuticals, BMS, Agepha, and Horizon Therapeutic (now owned by Amgen). Dr Michos is supported by the Amato Fund for Women's Cardiovascular Health research at Johns Hopkins University, as well as an American Heart Association grant 946222. Dr Weber has grants from NHLBIK23 HL159276-01, AHA21CDA851511. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: HIV induced endothelial dysfunction (ED) contributes to cardiovascular disease (CVD) in women with HIV (WWH). Although psychosocial stress has been implicated in the development of CVD in HIV, its impact on ED in WWH remains unknown., Objectives: The authors hypothesized that posttraumatic stress disorder (PTSD) and HIV interact to contribute to ED in WWH., Methods: We enrolled 87 women from the Women's Interagency HIV Study in Atlanta, Georgia, who reported previous trauma and completed the PTSD Checklist: Civilian Version (PCL-C), which assesses PTSD symptom severity (PCL-C score) and PTSD status (PCL-C >44). Brachial artery flow-mediated dilation (FMD) was measured to assess endothelial function. The impact of PTSD, HIV, and their interaction on endothelial function was evaluated using linear regression models adjusted for demographics, CVD risk factors, depressive symptoms, and statin use., Results: Overall, 55 (63.2%) had HIV, 24 (27.5%) had PTSD, and 13 (14.9%) had both. Those with PTSD were more likely to smoke (18 [75%] vs 28 [44.4%], P = 0.02) and have depressive symptoms (14 [58.3%] vs 18 [28.6%], P = 0.02) than those without PTSD. In adjusted models, the HIV-PTSD (severity and status) interaction effect on FMD was significant (P = 0.01). Both PTSD severity (β per 10-point increase: -0.72% [95% CI: -1.22 to -0.21], P = 0.01) and PTSD status (β: -2.51% [95% CI: -4.21 to -0.77], P = 0.01) were independently associated with lower FMD in WWH but not in those without HIV., Conclusions: PTSD is independently associated with ED in WWH. Whether treatment for PTSD improves ED and CVD in WWH needs further study., Competing Interests: Funding support and author disclosures Supported by the National Institutes of Health (NIH, nih.gov) under Award Numbers U54AG062334. Dr Vatsa has been supported by Abraham J. & Phyllis Katz Foundation (Atlanta, GA), NIH - NHLBI grant 1R01HL157311, and T32 HL130025. Dr Moran has been supported by NIH grant K23HL152903. Dr Quyyumi has been supported by NIH grants P01HL154996-01A1, R33HL138657-05, P30DK111024-07S2, R61HL154116-01, R01HL109413-07, R01HL166004-01, 15SFCRN23910003, 5P01HL086773-09, 5P01HL101398-05, and 1P20HL113451-04. Dr Vaccarino is supported by NIH grants R01 HL109413 and R01 HL163998. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Limited data exist on the long-term impact of beta-blocker therapy after percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD) and preserved left ventricular ejection fraction (LVEF)., Objectives: The aim of the study was to evaluate the effects of early beta-blocker initiation vs no initiation following PCI in patients with stable CAD and preserved LVEF., Methods: This retrospective cohort study employed target trial emulation and incident user design, utilizing the TriNetx database (2009-2024). Early beta-blocker initiation (within days 1 and 7) was compared with no initiation using 1:1 greedy propensity score matching. The outcomes included all-cause mortality, hospitalization for myocardial infarction, heart failure, atrial fibrillation/flutter, stroke, and safety endpoints. Hospitalization for bone fracture and acute appendicitis served as falsification endpoints. In the intention-to-treat analysis, outcomes were analyzed over 5 years using Cox-proportional hazards., Results: Out of 11,681 matched patients per group, beta-blocker therapy was associated with increased all-cause mortality (HR: 1.11 [95% CI: 1.09-1.18]). No significant differences were found in hospitalization for myocardial infarction (HR: 1.03 [95% CI: 0.97-1.09]), stroke (HR: 0.98 [95% CI: 0.91-1.05]), heart failure (HR: 0.99 [95% CI: 0.95-1.03]), and atrial fibrillation/flutter (HR: 0.97 [95% CI: 0.93-1.01]). Hospitalization for hypotension was higher with beta-blockers (HR: 1.10 [95% CI: 1.06-1.14]). Hospitalization for bone fracture (HR: 1.02 [95% CI: 0.85-1.22]) and acute appendicitis (HR: 1.17 [95% CI: 0.95-1.45]) showed no significant associations. Several sensitivity analyses showed consistent results., Conclusions: Early beta-blocker initiation after PCI for stable CAD with preserved LVEF was associated with higher mortality, with no impact on cardiovascular events., Competing Interests: Funding support and author disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with Fontan circulation are frail and experience multisystem dysfunction including impaired exercise capacity, low resting and exercise-augmented cardiac output, and progressive liver fibrosis. However, common underlying biochemical abnormalities or disease-specific biomarkers have not been well-described., Objectives: We wish to investigate Fontan and their matched healthy subjects using a nontargeted, followed by targeted metabolomic analysis., Methods: Patients with Fontan circulation were compared to age- and sex-matched healthy controls with regard to body composition, markers of frailty, cardiopulmonary exercise testing, and resting and exercise-augmented hemodynamics. Subsequently, the study participants underwent a nontargeted metabolomics assessment, followed by targeted plasma bile acid (BA) analysis., Results: Twenty Fontan patients (28.8 ± 9.8 years of age; 35% women) and 20 healthy controls (29.7 ± 6.0 years of age; 30% women) were enrolled. Fontan patients had significantly lower skeletal muscle mass, took longer to complete the 5 times sit-to-stand test; achieved lower %VO 2 max, and had lower resting and postexercise hemodynamic parameters. Nontargeted metabolomics assessment demonstrated elevated BAs, oxylipins, and leucine metabolites in Fontan patients. Total BA as well as 17 BA components were markedly elevated in the Fontan patients. Selective BAs were negatively associated with age, degree of frailty, cardiopulmonary function, and hemodynamic parameters., Conclusions: Elevated BAs are associated with worsening Fontan physiology. These findings warrant further exploration., Competing Interests: Funding support and author disclosures This work was supported by Establishment grant—Department of Internal Medicine, University of Manitoba, Winnipeg, Canada. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Biomarker-based prognostic staging systems, including the National Amyloidosis Centre (NAC) and the Mayo staging systems, are widely-used but have only been validated for treatment-naive patients with cardiac transthyretin amyloidosis (ATTR-CA)., Objectives: The purpose of this study was to assess the accuracy of the NAC and Mayo staging systems in patients with ATTR-CA treated with tafamidis., Methods: A retrospective observational study following patients with ATTR-CA from initiation of tafamidis (baseline) to time of all-cause death was conducted. Patients were stratified according to the NAC and an adapted Mayo staging system incorporating high-sensitivity cardiac troponin T. Agreement was assessed using weighted Cohen's kappa. The staging systems' ability to identify subgroups with distinct overall survival was assessed using Kaplan-Meier analyses and pairwise log-rank tests., Results: A total of 251 patients with wild-type ATTR-CA treated with tafamidis were followed for a median of 521 (IQR: 262-842) days. There was substantial agreement (weighted kappa = 0.661; P < 0.001) between the NAC and the adapted Mayo staging system. Significant differences in estimated overall survival were observed across all disease stages of the adapted Mayo staging system (I vs II: P = 0.032; I vs III: P < 0.001; II vs III: P = 0.036). Accordingly, estimated overall survival was significantly lower in NAC III compared to NAC I (P < 0.001) and NAC II (P = 0.015). However, there was no significant difference between NAC I and NAC II (P = 0.340)., Conclusions: Both staging systems identified a distinct group of patients with ATTR-CA at the highest risk of death but only the adapted Mayo staging system could accurately distinguish between low- and intermediate-risk patients in the setting of disease-modifying treatment with tafamidis., Competing Interests: Funding support and author disclosures The Amyloidosis Center Charité Berlin (ACCB) has received financial support from Alnylam Pharmaceuticals, Inc (Cambridge, Massachusetts, United States) for the management of the databank that was used for the identification of enrolled patients. Alnylam Pharmaceuticals, Inc (Cambridge, Massachusetts, United States) had no influence on the collection, management, statistical analysis, or interpretation of data and did not partake in the preparation, review, approval, or submission of the manuscript. Drs Messroghli and Heidecker have received speaker fees and research funding from Pfizer Pharmaceuticals unrelated to this project. Dr Mattig has received research grants from Pfizer Pharmaceuticals and Sanofi; and has received lecture fee and financial reimbursement for advisory board activities from Sanofi, Takeda, Pfizer, BridgeBio, and Chiesi Farmaceutici S.p.A outside the submitted work. Dr Hahn has received financial reimbursement for consulting, advisory board activities, speaker fees, and/or contributions to congresses; has received travel support to attend scientific meetings by Akcea Therapeuticals Inc, Alnylam Pharmaceuticals Inc, Amicus, AstraZeneca, GSK, Hormosan, Takeda Pharmaceutical Inc, Pfizer Pharmaceuticals Inc, Swedish Orphan Biovitrum Inc, and ViiV Healthcare GmbH; and further received research funding by the foundation Charite (BIH clinical fellow), Alnylam Pharmaceuticals Inc, and Pfizer Pharmaceuticals. Prof Landmesser has received research grants from Abbott, Bayer, and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

A total of 9 million veterans receive care in a unique healthcare system, the Veterans Healthcare Administration (VHA), with nearly 50% reporting at least one cardiovascular disease. Despite evidence for high quality of health care in the VHA, more veteran care is being moved to the non-VHA community. An assumption of this shift in care is that the quality of non-VHA care is at least comparable to VHA care. This paper reviews the quality of cardiovascular care delivered by the VHA in comparison to community care, which is care delivered in non-VHA facilities by non-VHA providers and is authorized and paid for by VHA, examining quality metrics and highlighting novel national care programs. The critical examination of this data is valuable for deriving health care policy, sharing novel and effective quality initiatives throughout the healthcare sector, and will help veterans and their providers make important healthcare decisions., Competing Interests: Funding Support and Author Disclosures Dr Waldo has received unrelated investigator-initiated support from Abiomed, Cardiovascular Systems Incorporated, Janssen Pharmaceuticals, the National Institutes of Health, and VA Health Services Research & Development. Dr Shah has received funding from Abbott Vascular and the United States Food and Drug Administration. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025. Published by Elsevier Inc.)

Objective: To compare the impact of examination feedback versus access to historical examination questions on information retention., Methods: First-year student-pharmacists completed a baseline knowledge assessment composed of 30 examination questions divided into three conditions of 10 questions each. In the CHEAT condition, students were provided with 10 questions and their correct answers ahead of time. These 10 questions appeared on the baseline assessment. In the FEEDBACK condition, students answered 10 previously unseen questions but received feedback at the end of the baseline assessment, including the correct answers and explanations. The CONTROL condition included 10 previously unseen questions, and no information on correctness or feedback was provided. Three days after the baseline assessment, students took a surprise retention quiz with 30 similar questions, including all three conditions. The primary outcome measure was student performance on this retention quiz., Results: On measures of retention, the FEEDBACK condition resulted in the highest performance compared to the CHEAT condition (50% vs 44%) and the CONTROL condition (50% vs 23%). Students were 30% more likely to answer questions correctly when they received feedback in advance through explanations than only correct answers through access to the historical examination., Conclusion: Providing students with feedback on examinations improves future performance. Despite concerns about returning completed examinations and the subsequent potential for future students to access these materials, the advantages of feedback in enhancing learning and retention outweigh the associated risks., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Objective: The study aimed to evaluate student knowledge and perceptions regarding career options and knowledge of the pharmaceutical industry based on pre-post module quizzes, reflections and team presentations in a hybrid medical affairs elective certificate course., Methods: A qualitative research design was utilized to analyze reflections from 19 students enrolled in the Accreditation Council for Medical Affairs (ACMA) Pharmaceutical Industry Training Certificate elective at Marshall University during Spring 2023. The course utilized seven modules from the Medical Affairs Competency Certificate (MACC) offered by ACMA. Students completed pre- and post-module quizzes, engaged in discussions with industry professionals, and submitted written reflections on the five most significant concepts learned. The reflections were qualitatively analyzed while paired sample t-test was used to analyze quantitative data from pre-post scores on module quizzes. A post course survey was administered to evaluate changes in students' career preferences in the pharmacy field., Results: The qualitative analysis identified 17 key concepts including breadth of career opportunities in the pharmaceutical industry, role of Medical Science Liaisons (MSLs), ethical communication practices, and the importance of diversity in clinical trials. A significant improvement in knowledge was observed across all modules on medical affairs, with the highest increase in the compliance module. Twenty percent of respondents (n=3/15) reported changing their career choice to pursue a path in pharmaceutical industry., Conclusion: The course broadened students' knowledge of industry practices and career opportunities. The structured approach and professional engagement offered valuable insights, enabling student exploration, and influencing career choices., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 American Association of Colleges of Pharmacy. Published by Elsevier Inc. All rights reserved.)

Background: Literature on the prevalence and management of atrial arrhythmias in patients with myotonic muscular dystrophy type 1 (MMD1) or myotonic muscular dystrophy type 2 (MMD2) is limited., Objectives: This study sought to describe incidence, prevalence, and predictors of atrial fibrillation (AF) and atrial flutter (AFL) in a contemporary cohort of patients with myotonic muscular dystrophy (MMD)., Methods: Associations between patient factors and incident AF/AFL were analyzed in patients with MMD referred for routine electrophysiology evaluation between January 2013 and September 2023., Results: We identified 120 patients (96 MMD1, 24 MMD2) seen for new electrophysiology clinic visits for MMD cardiac evaluation. Median age at MMD diagnosis was 34.6 years (Q1-Q3: 21.8-51.0 years), with a younger age at diagnosis for MMD1 patients (P < 0.001). AF or AFL was diagnosed in 31% of patients (31 of 96 MMD1 patients vs 6 of 24 MMD2 patients; P = 0.656) during the study period. AF occurred in 34 (28%) patients, AFL in 9 (8%), and 6 of 37 had both AF and AFL. Anticoagulation (AC) was prescribed at initial AF/AFL diagnosis in 41% (n = 15 of 37) of patients. The CHA 2 DS 2 -VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65-74 years, sex category) score was higher in patients who received AC (P < 0.001). Twelve (32%) patients underwent catheter ablation. One stroke occurred in the AF/AFL group (no AC, CHA 2 DS 2 -VASc score 0). Female MMD1 patients were less likely to develop AF/AFL (HR: 0.08). Diagnosis of MMD1 at a younger age (HR: 0.95 per year) and greater CTG nucleotide repeats (HR: 1.09 per 50 repeats) were associated with incident AF/AFL., Conclusions: There was a high prevalence of AF/AFL in this single-institution MMD cohort. The CHA 2 DS 2 -VASc score may not be an effective tool in this population., Competing Interests: Funding Support and Author Disclosures Dr Nazarian is principal investigator for the National Institute of Health grant R01HL142893. Dr Nazarian has served as a consultant for Dyne Pharmaceuticals, ImriCor, and Biosense Webster; and principal investigator for research funding from Biosense Webster, ADAS software, and the U.S. National Institutes of Health. The University of Pennsylvania Conflict of Interest Committee manages all commercial arrangements. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures Dr Burri has received speaker fees and institutional research and fellowship support from Abbott Laboratories, Biotronik, Boston Scientific, Medtronic, and MicroPort. Mr Paamand, Ms Clua i Sánchez, Mr Leonard, and Mr Firth are employees of CathVision. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Earlier studies have documented the risk for sinoatrial node injury and phrenic nerve paralysis as complications following radiofrequency catheter ablation for electrical isolation of the superior vena cava (SVCI)., Objectives: The aim of this study was to assess the safety and feasibility of SVCI in patients with atrial fibrillation undergoing pulsed field ablation (PFA) METHODS: Six hundred sixteen consecutive patients undergoing PFA for pulmonary vein isolation plus SVCI were included in this multicenter analysis. Superior vena cava (SVC) ablation was performed under the continuous guidance of intracardiac echocardiography. The PFA catheter was placed at the junction between the SVC and the right atrium at the level of the lower border of the pulmonary artery. A total of 4 applications were given to achieve complete electrical isolation of the SVC. Sinus node injury and phrenic nerve stunning were checked during the procedure, before discharge, and at 2-month follow-up., Results: A total of 616 patients receiving SVCI were included in the analysis. Acute SVCI was achieved in all 616 patients (100%). In the flower configuration used in the first 10 patients, 2 transient sinus node injuries and 2 episodes of phrenic nerve stunning were observed, which resolved spontaneously during the procedure. In the remaining patients, the basket configuration was used; only 1 episode of phrenic nerve stunning was registered, which regressed before the end of the procedure. No permanent damages were registered at discharge and at 2-month follow-up., Conclusions: Intracardiac echocardiography-guided PFA can effectively isolate the SVC with a good safety profile., Competing Interests: Funding Support and Author Disclosures Dr Natale is a consultant for Abbott Laboratories, Biosense Webster, Biotronik, Boston Scientific, Medtronic, and iRhythm Technologies. Dr Tondo is an advisory board member of Boston Scientific and Medtronic; and has received lecture, proctoring, and travel fees from Boston Scientific, Abbott Laboratories, AtriCure, and Medtronic. Dr Dello Russo is a consultant for Abbott Laboratories. Dr Burkhardt is a consultant for Biosense Webster and Stereotaxis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Accurate electroanatomic mapping is critical for identifying scar and the long-term success of ventricular tachycardia ablation., Objectives: This study sought to determine the accuracy of multielectrode mapping (MEM) catheters to identify scar on cardiac magnetic resonance (CMR) and histopathology., Methods: In an ovine model of myocardial infarction, we examined the effect of electrode size, spacing, and mapping rhythm on scar identification compared to CMR and histopathology using 5 multielectrode mapping catheters. We co-registered electroanatomic mapping, CMR, and histopathology for comparison. Catheter-specific voltage thresholds were identified based on underlying amounts of normal myocardium on transmural histology biopsies., Results: Ten animals were included: 6 with anteroseptal myocardial infarction and 4 control animals. A total of 419,597 points were manually reviewed across the catheters, with 315,487 points used in the analysis. There were minimal differences in bipolar and unipolar voltages, scar areas, and abnormal electrograms between catheters and between rhythms. Catheter-specific bipolar and unipolar voltage thresholds for normal myocardium were High-Density Grid >2.78 mV and >6.19 mV, DuoDecapolar >2.22 mV and >6.05 mV, PentaRay >1.66 mV and >5.35 mV, Decanav >1.36 mV and >4.75 mV, Orion >1.21 mV and >6.05 mV, respectively. Catheter-specific bipolar thresholds improved the accuracy for detecting endo-mid myocardial scar on CMR by 1.8%-15.6% and catheter-specific unipolar thresholds improved the accuracy in the mid-epicardial layers by 25.3%-81.1%., Conclusions: Minimal differences were observed in scar detection and electrogram markers between commercially available multielectrode mapping catheters and differing wave fronts. Compared to traditional voltage criteria for bipolar and unipolar scar, catheter-specific thresholds markedly improved accuracy for delineating scar on CMR., Competing Interests: Funding Support and Author Disclosures Dr Campbell has received speaker fees from Biosense Webster. Dr Kumar has received research grants from Abbott Medical and Biotronik; and speaker fees from Biosense Webster, Abbott Medical, Biotronik, Medtronic and Sanofi Aventis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Crown Copyright © 2025. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures Dr Arbelo has received speaker and consulting honoraria from Biosense Webster and Bayer. Dr Guichard has received consulting honoraria from Microport CRM; lecturing honoraria from Microport CRM and Abbott; and an unrestricted grant support for a fellowship from Abbott. Drs Porta-Sánchez and Roca-Luque have received speaker and consulting honoraria from Biosense Webster, Abbott, and Boston Scientific. Dr Brugada is a shareholder of Galgo Medical. Prof Lluís Mont has received honoraria as a lecturer and consultant; has received research grants from Abbott Medical, Biosense Webster, Boston Scientific and Medtronic; and is a shareholder of Corify Care and Galgo Medical. Dr Althoff has received research grants for investigator-initiated trials from Biosense Webster; and honoraria as a lecturer and consultant for Abbott Medical Devices and Corify Care. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Lipoprotein(a) [Lp(a)] has been independently associated with increased cardiovascular risk., Objectives: The authors examined the effect of monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) on plasma Lp(a) levels across multiple trials., Methods: Studies were retrieved comparing the effect of PCSK9i vs placebo on Lp(a) levels. The primary outcome was percent change in Lp(a) levels. Factors associated with the treatment effect were determined by meta-regression analysis. Subgroup analyses were done to explore potential treatment effect differences., Results: PCSK9i reduced Lp(a) levels on average of -27% (95% CI: -29.8% to -24.1%, P  < 0.001). Factors associated with the treatment effect included mean percent change in low-density lipoprotein cholesterol ( P  = 0.003, beta coefficient 0.34, 95% CI: 0.11-0.57, tau 2  = 94.8, R 2  = 11.82) and apolipoprotein B ( P  < 0.002, beta coefficient 0.4, 95% CI: 0.14-0.64, tau 2  = 93.68, R 2  = 11.86). Subgroup analyses revealed consistent treatment effect amongst comparators vs placebo: -27.69% (95% CI: -30.85% to -24.54%, P  < 0.001), vs ezetimibe: -24.0% (95% CI: -29.95% to -18.01%, P  < 0.001), type of PCSK9i, evolocumab: -29.35% (95% CI: -33.56% to -25.14%, P  < 0.001) vs alirocumab: -24.50% (95% CI: -27.96% to -21.04%, P  < 0.001), and presence of familial hypercholesterolemia: -25.63% (95% CI: -31.96% to -19.30%, P  < 0.001 vs no familial hypercholesterolemia: -27.22%; 95% CI: -30.34% to -24.09%, P  < 0.001). Varying treatment effects were noted in the duration of treatment (12 weeks or shorter: -32.43% [95% CI: -36.63% to -28.23% vs >12 weeks: -22.31%] [95% CI: -25.13% to -19.49%, P  < 0.001]), P interaction < 0.01., Conclusions: PCSK9is reduce Lp(a) levels by an average of 27%. Mean percent change in low-density lipoprotein cholesterol and apolipoprotein B were associated with treatment effect., Competing Interests: Dr Gulati has received consultant fees/honoraria from Esperion, Novartis, and Boehringer Ingelheim; and has received research/research grants from Congressionally Directed Medical Research Program-Department of Defense (WARRIOR study). Dr Pagidipati has received consulting fees/honoraria from Bayer, Boehringer Ingelheim, CRISPR Therapeutics, Eli Lilly, Esperion, AstraZeneca, Merck, Novartis, and Novo Nordisk; grants to institution from 10.13039/100006400Alnylam, 10.13039/100002429Amgen, 10.13039/100001003Boehringer Ingelheim, Eggland’s Best, Eli Lilly, 10.13039/100004336Novartis, and 10.13039/501100004191Novo Nordisk; and DSMB for trials sponsored by J + J and 10.13039/100004336Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2025 The Authors.)

Objective: Primary care offers an entry point into the health care system for adolescents experiencing mental illnesses. This study explored the perceptions of adolescents with an anxiety or mood disorder accessing primary care for mental health services., Methods: Qualitative interpretive descriptive design was employed. Participants ages 15-18 years (n = 10) were recruited from a mid-sized city in Canada utilizing flyers and social media advertisements. Data were collected between August and December 2019. Data generation methods included photo-elicitation, demographic survey, and semi-structured interviews. Analysis was guided by a health care access framework and ecological model., Results: Adolescents perceived the process of accessing primary care for mental health services as complex and beginning prior to entering the primary care environment; a novel conceptual framework was developed to depict the process. Adolescents described three stages in this process: feeling uncertain about their concerns and requiring help; seeking informal support from parents and friends to initiate help-seeking; and receiving mental health services through primary care., Discussion: A novel conceptual framework to depict the process of access for adolescents is proposed. Primary care practitioners require awareness of the access process adolescents conceptualize prior to deciding to seek help in primary care, as well as the need to foster their emerging adulthood in care. Targeted interventions to enable early intervention include providing information about mental health services available during routine interactions., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lisa De Panfilis reports financial support was provided by Registered Nurses Association of Ontario. Lisa De Panfilis reports financial support was provided by Canadian Nurses Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025 The Authors.)

Background: Atrial fibrillation (AF) and heart failure (HF) often coexist and impact morbidity and mortality. There is limited knowledge on the association of AF subtypes with HF according to sex., Objectives: The purpose of this study was to explore sex-specific associations between AF subtypes and subsequent HF, identifying HF risk factors in participants with AF, and exploring the combined impact on mortality., Methods: 14,790 women and 13,181 men from the Tromsø Study were enrolled between 1994 and 2008 and followed for incident AF and HF through 2016. Cox regression was conducted to provide HRs and 95% CIs., Results: Those with AF had higher risk of subsequent HF in both sexes compared to those without AF. Women with permanent AF had higher relative risk of HF than men (HR: 10.52; 95% CI: 8.72-12.70, and HR: 7.65; 95% CI: 6.40-9.15, respectively). Risk factors for HF in participants with AF included smoking in all, higher diastolic blood pressure and hypertension in women, underweight, obesity, and low alcohol consumption in men. All-cause mortality was higher in women with both subtypes (paroxysmal/persistent: HR: 2.10; 95% CI: 1.78-2.48, permanent: HR: 1.40, 95% CI: 1.14-1.72) and in men with paroxysmal/persistent AF (HR: 1.66; 95% CI: 1.40-1.96). Subsequent HF increased risk of mortality in both sexes., Conclusions: All AF subtypes were associated with increased risk of HF. Smoking was a shared risk factor, while diastolic blood pressure and hypertension were specific to women, and underweight, obesity, and low alcohol intake were specific to men. Subsequent HF increased mortality risk in all., Competing Interests: This study has been supported by internal fundings from UiT The Arctic University of Norway. Dr Schnabel has received funding from the 10.13039/501100000781European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme under the grant agreement No 648131, from the European Union’s Horizon 2020 research and innovation programme under the grant agreement No 847770 (AFFECT-EU), from the European Union’s Horizon Europe research and innovation programme under the grant agreement ID: 101095480 and German Center for Cardiovascular Research (DZHK e.V.) (81Z1710103 and 81Z0710114); German Ministry of Research and Education (BMBF 01ZX1408A) and ERACoSysMed3 (031L0239). Wolfgang Seefried project funding 10.13039/501100005971German Heart Foundation. Dr Schnabel has received lectures fees and advisory board fees from BMS/Pfizer and Bayer outside this work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2025 The Authors.)

Naxos disease is a rare autosomal recessive condition combining arrhythmogenic right ventricular cardiomyopathy, woolly hair, and palmoplantar keratoderma. The first identified causative variant was in the gene encoding the desmosomal protein plakoglobin. Naxos disease exhibits fibro-fatty myocardial replacement with immunohistological abnormalities in cardiac protein and signaling pathways, highlighting the role of inflammation and potential anti-inflammatory treatments. Childhood cutaneous signs precede cardiac features, which are diagnosed by familial and genetic evaluation, electrocardiography and cardiac imaging. Disease progression necessitates holistic care with risk management and lifestyle adjustments, often needing treatment for arrhythmia and heart failure. Similar phenotypes have been linked to desmoplakin and rarely desmocollin2 gene variants, highlighting the importance of familial and genetic evaluation. This document summarizes current knowledge on Naxos disease and related cardiocutaneous syndromes and initiates an international endeavor to collect and study all global cases, aiming to improve understanding, treatment, and patient care through shared data and research., Competing Interests: Dr Protonotarios holds consulting agreements with Tenaya Therapeutics and Avidity Biosciences. Dr Crisci has received a research grant by the CardioPath program from Federico II University of Naples, Italy. Dr Abrams is a consultant/scientific advisory board for Thryv Therapeutics, Rockets Pharmaceuticals, Solid Biosciences. Dr Anastasakis is on the advisory board of Pfizer, Genesis, Takeda, Sanofi, and BMS. Dr Mestroni has received grant support from Tenaya Therapeutics, Pfizer, AstraZeneca, Owkin, Greenstone Bioscience, and Bristol Myers Squibb; and is a member of the scientific advisory board of Tenaya Therapeutics. Dr Saffitz is consultant for Implicit Bioscience and Rocket Pharmaceuticals. Dr McKenna is a scientific advisor to Health in Code and to Tenaya Therapeutics. Dr Elliott holds consultancies in Biomarin, Pfizer, BMS, and the Patent: US Pat No 62/903,103: GENE THERAPY COMPOSITIONS AND TREATMENT OF RIGHT VENTRICULAR ARRYTHMOGENIC CARDIOMYOPATHY. Dr Kaski has consultancy/advisory board activities with Tenaya Therapeutics, Cytokinetics, Lexeo, Avidity Biosciences, and Accord Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2025 The Authors.)

Background: Assessing individuals' risk of developing incident atrial fibrillation (AF) is important for making preventive and screening strategies., Objectives: The performance of the mC 2 HEST score for predicting incident AF has scarcely been evaluated, especially in a multi-ethnic population., Methods: Participants from the MESA (Multi-Ethnic Study of Atherosclerosis were enrolled in the present study, which involved population of different ethnicities (Caucasian, African-American, Chinese-American, and Hispanic) aged between 45 and 84 from 6 communities in the United States. The discriminative and calibration performance of the mC 2 HEST score was compared with other risk models., Results: A total of 4,524 subjects (mean age 60.2 ± 9.5 years; 53.0% female) were included; 565 (mean age 67.0 ± 7.9 years; 46.5% female) developed AF during 13.6 ± 2.5 years of follow-up, with an incidence of 0.93%/year. The mC 2 HEST score had good prediction at 10 years (C-index, 0.72; 95% CI: 0.701 to 0.753), and 15 years (0.773, 95% CI: 0.749 to 0.798). The risk of incident AF increased with higher mC 2 HEST score points and risk groups (log-rank P  < 0.001). The mC 2 HEST score showed positive net reclassification indexes (0.057, 0.090, 0.128, and 0.143) and integrated discriminative improvement (3.2%, 3.9%, 5.7%, and 4.9%) compared with C 2 HEST, HAVOC, HATCH, and CHA 2 DS 2 -VASc scores, respectively. Optimal calibration was seen in the mC 2 HEST score ( P  = 0.41)., Conclusions: The mC 2 HEST score is a practical model for predicting individuals' risk of incident AF that may be used for guiding AF surveillance, resource allocation, and screening strategies., Competing Interests: This work was supported by the 10.13039/100014717National Natural Science Foundation of China (No. 82300349). Dr Lip is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, and Anthos. No fees were received personally; and he is a 10.13039/501100000272National Institute for Health and Care Research (NIHR) Senior Investigator and co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 899871. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2025 The Authors.)

Background: There continue to be significant gender disparities with women being underrepresented in medical professional society leadership roles, despite more women entering medical school., Objectives: This study aimed to elucidate the pattern of representation of women in medical society presidential positions in the United States and Europe over the past 50 years. It further examines gender-related trends in the field of cardiology and among medical trainees., Methods: Using publicly available data from major medical societies, we calculated the number of male and female presidents in major medical societies across most specialties in the United States and Europe over the past 50 years. We also examined cardiology societies specifically. These numbers and percentages were observed alongside those of medical students, internal medicine residents, cardiology fellows, and attending cardiologists., Results: Women constituted 4% and 0% of medical professional society presidents from 1974 to 2023 in the United States and Europe, respectively; this increased to a respective 32% and 40% in the past decade. For cardiology societies, the United States trended from 7% to 22% female presidents in the past 50 years, and Europe trended from 0% to 10%. Doctor of medicine and doctor of osteopathic medicine students have shown steady increases in women to now greater than 50%. Medicine residents, cardiology fellows, and cardiology attendings all have smaller percentages of women, though the number is increasing with time., Conclusions: While women remain underrepresented in medical professional society leadership in the United States and Europe, there is a trend toward more representation of women, which mirrors growth in this realm among medical trainees., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2025 The Authors.)

Tonne-Kalscheuer syndrome (TOKAS; MIM: 300978) is an X-linked recessive disorder with devastating consequences for patients, such as intellectual disability, developmental delay, and multiple congenital abnormalities. TOKAS is associated with hemizygous variants in the RLIM gene, which encodes a RING-type E3 ubiquitin ligase. The current sustained increase in reported RLIM variants of uncertain significance creates an urgent need to develop assays that can screen these variants and experimentally determine their pathogenicity and disease association. Here, we engineered flow cytometry-based RLIM-specific reporters to measure RLIM activity in TOKAS. This paper describes the design and use of RLIM-specific reporters to determine the pathogenicity of a TOKAS RLIM gene variant. Our data demonstrate that RLIM-specific flow cytometry reporters based on either the full length or a degron region of the substrate REX1 measure RLIM activity in cells. Further, we describe the TOKAS variant RLIM p.Asn581Lys and, using reporter assays, determine that it disrupts RLIM catalytic activity. These data reveal how the p.Asn581Lys variant impairs RLIM function and suggests pathogenic mechanisms. The use of RLIM-specific reporters will greatly accelerate the resolution of variants of uncertain significance and disease association in TOKAS., Competing Interests: Declaration of interests H.C. is an employee of GeneDx, LLC., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)