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Purpose: Little is known about the long-term efficacy of virtual leadership training for physicians. This study compares two highly similar groups of Obstetricians-Gynecologists' (OB-GYN) 6-month post-program changes in competency and skills after experiencing equity-centered leadership training in a virtual or in-person format., Participants and Methods: Using a retrospective pre- and post-test method, we collected 6-month post-program data on 14 competencies for knowledge gains and skills use, comparing the virtual cohort (2021, n = 22) to the in-person cohort (2022, n = 33) in 55 total participants. Qualitative data from open-ended feedback questions informed on skills relevancy and professional impact since program participation., Results: Data indicate strong, statistically significant knowledge and skills retention in both cohorts, with 63% of the virtual and 85% of the in-person participants responding. Data indicate participants report the course having a positive impact on their healthcare provision and nearly all report they made changes to their communication and leadership approaches in the 6-months after the program. 59% of the virtual and 55% of the in-person cohorts report new leadership opportunities since their participation and that the course helped prepare them for those roles. Qualitative data support the need for the training, specific elements of the training these physicians found particularly helpful, and that the learning was "sticky", in that it stayed with them in the months post-program. There was a clear stated preference for in-person experiences., Conclusion: Either virtual or in-person leadership training can result in long-term (6-month) significant retention and application of knowledge and skills in physicians. While limited in size, this study suggests that in-person experiences seem to foster more effective bonds and also greater willingness to participate in post-program follow-up. Physicians find equity-centered leadership training to impact their subsequent communication and leadership practices and they report career benefits even in 6-month follow-up., Competing Interests: Dr Claudia SP Fernandez reports that Mr. Ruben Fernandez, JD, is the co-author of It-FACTOR Leadership, a text used in the ACOG-Cefalo Leadership Institute and is related to the corresponding author. Mr. Fernandez also serves as an executive coach and faculty in the program. Dr. and Mr. Fernandez are related by marriage. The authors report no other conflicts of interest in this work., (© 2024 Fernandez et al.)

Objective: To investigate the feasibility, acceptability, and clinical outcome measures of a transitional care intervention for patients with traumatic brain injury (TBI) and their family caregivers., Setting: Inpatient and outpatient rehabilitation at a level I trauma center in the Southeastern United States., Participants: Patients (ages 18-75) diagnosed with moderate to severe TBI, receiving rehabilitation, and their family caregivers., Design: Quasi-experimental, single-arm, single-center feasibility study with pre- and post-test design. Participants completed a 4-month transitional care program involving monthly education and social support., Main Measures: Feasibility of enrollment, data collection, intervention completion rates, and intervention acceptability. Clinical outcome measures included patient quality of life (QOL) (12-Item Short Form Health Survey (SF-12), primary outcome) and patient and caregiver self-efficacy (Self-Efficacy for Management of Chronic Conditions Scale)., Results: Eleven dyads and 1 monad enrolled (N = 23, 12 patients, 11 caregivers). All completed baseline data; 91.3% (n = 21, 11 patients, 10 caregivers) completed 2-month (intervention midpoint) data; and 86% (n = 20, 11 patients, 9 caregivers) completed 4-month (intervention endpoint) data. The intervention completion rate was 91.67%. Participants engaged in a mean of 2.17 (SD = 1.34) monthly educational webinars and 2.42 (SD = 1.51) social support groups during the intervention period. Approximately 70% of participants (n = 16, 9 patients, 7 caregivers) completed acceptability data, indicating positive intervention experiences (patients: mean 9.44/10 [SD = 1.01]; caregivers: mean 9.57/10 [SD = 0.79]). Patient QOL scores did not statistically improve over time; however, patient self-efficacy scores did statistically significantly improve from baseline (mean = 7.03, SD = 1.53; P = .0197) to intervention end point (4 months) (mean = 8.35, SD = 1.71)., Conclusion: Brain Injury Support To Optimize Recovering Minds (BrainSTORM) is a promising new TBI transitional care intervention that has potential to enhance care standards for patients with TBI and their family caregivers. Further research is needed to determine its efficacy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Despite the shortage of physicians in the United States, there is no consensus among medical educators as to how to address the nation's unmet needs. A growing but unfulfilled argument is to revisit the configuration of medical education and the time required to complete medical training. Pilot programs, such as shortened programs or advancement-in-place structures to accelerate the practice capability of trainees, have been attempted. This manuscript addresses underlying economic and human considerations that medical educators must reconcile, drawing on lessons from international educational structures, as we advance toward a system that supports the needs of the communities that our graduates will serve., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Surgical endarterectomy is currently considered the front-line therapy for the treatment of calcified lesions in the common femoral artery (CFA). Endovascular interventions have evolved, and their use is increasing in frequency. Intravascular lithotripsy (IVL) has shown promising safety and effectiveness in calcified CFA lesions in a small pilot study, but "real-world" evidence from a larger cohort is lacking., Methods: The Disrupt PAD III Observational Study (NCT02923193) was a prospective, multicenter registry designed to assess the acute safety and effectiveness of IVL treatment for calcified peripheral arterial disease. Any concomitant treatment with other calcium-modifying technologies as well as definitive treatment strategies was at the discretion of the operators. Patients with CFA lesions were evaluated for acute angiographic safety and effectiveness outcomes following IVL treatment as determined by an independent angiographic core lab., Results: Common femoral artery treatment was indicated in 177 patients (n=163 could be analyzed based on core-laboratory data) enrolled at 23 sites. Characteristics for 164 treated lesions included moderate-severe calcification 95.1%, diameter stenosis 74.8±17.7%, and lesion length 53.6±53.1 mm. Concomitant calcium-modifying therapy was used in 32.3% of lesions. Final therapy included drug-coated balloons in 68.9% and stenting in 16.5% of lesions. Post-IVL and final residual stenoses were 29.2±16.5%and 23.6±11.5%, respectively. No vascular complications (flow-limiting dissections, perforations, embolization, slow or no reflow, or abrupt closure) were present at the end of the procedure by core-laboratory assessment, with 1 (0.8%) flow-limiting dissection initially occurring immediately following IVL treatment., Conclusion: This study represents the largest real-world experience of IVL treatment in heavily calcified CFA lesions. Intravascular lithotripsy treatment showed significant stenosis reduction and favorable periprocedural safety in this challenging patient population., Clinical Impact: In this study we show that calcified common femoral artery disease can be safely and effectively treated with shockwave balloon angioplasty with high procedural success and low complication rates and in clinical practice can now be offered as an alternative to surgical treatment in those patients reluctant to or high risk for vascular surgery. This opens another option for clinicians to treat calcified common femoral artery disease without the risk of dissection, perforation or distal embolization that are associated with atherectomy. This study shows that shockwave lithoplasty offers an innovative plaque modification technology to tackle calcified disease in the common femoral artery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr N.W.S. receives educational and research grants from Angiodynamics, Boston Scientific, Bard/BD, and Abbott and is an investigator on several Shockwave Medical studies. He is a consultant to Cardiovascular Systems, Inc, Abbott, Angiodynamics, and Bard. Dr S.M. is a consultant for Shockwave Medical, Philips, Cardiovascular Systems Inc, and Medtronic. Dr A.M. is a consultant and trainer for Abbott, Phillips, and a speaker for Janssen. Dr GA is a consultant and has education responsibilities for Shockwave Medicalm Abbott Vascular, Phillips, and is CMO of Cordis. Dr B.B. is a consultant and trainer for Medtronic Vascular and a speaker for Shockwave Medical. Dr P.A.S. receives research grant support from Contego Medical, Inspire MD, Philips, Micromedical Solutions, Endologix, Shockwave Medical, W.L. Gore and is an unpaid consultant to Shockwave Medical and W.L. Gore.

Objective: Despite global reductions in hepatitis B virus (HBV) prevalence, an estimated 6.2 million children are infected, two-thirds of whom live in the WHO Africa region. We sought to characterize childhood HBV to inform elimination efforts in the Democratic Republic of Congo (DRC), one of the largest and most populous African countries., Methods: Using the most recent (2013-14) nationally representative Demographic and Health Survey in the DRC, we analyzed HBV surface antigen (HBsAg) on dried blood spots and associated survey data from children aged 6-59 months. We estimated HBsAg-positivity prevalence nationally, regionally, and by potential correlates of infection. We evaluated spatial variation in HBsAg-positivity prevalence, overall and by age, sex, and vaccination status., Findings: Using data from 5,679 children, we found national HBsAg-positivity prevalence was 1.3% (95% CI: 0.9%-1.7%), but ranged from 0.0% in DRC's capital city province, Kinshasa, to 5.6% in northwestern Sud-Ubangi Province. Prevalence among boys (1.8%, 95% CI: 1.2%-2.7%) was double that among girls (0.7%, 95%CI: 0.4%-1.3%). Tetanus antibody-negativity, rurality, and lower household wealth were also significantly associated with higher HBsAg-positivity prevalence. We observed no difference in prevalence by age. Children had higher HBsAg-positivity odds if living with ≥1 HBsAg-positive adult household member (OR: 2.3, 95%CI: 0.7-7.8), particularly an HBsAg-positive mother (OR: 7.2, 95%CI:1.6-32.2)., Conclusion: In the largest national survey of HBV among children and household contacts in the DRC, we found that childhood HBV prevalence was 10-60 times the global target of 0.1%. We highlight specific regions and populations for further investigation and focused prevention efforts.

Post-Acute Sequelae of SARS-CoV-2 infection (PASC), also known as Long-COVID, encompasses a variety of complex and varied outcomes following COVID-19 infection that are still poorly understood. We clustered over 600 million condition diagnoses from 14 million patients available through the National COVID Cohort Collaborative (N3C), generating hundreds of highly detailed clinical phenotypes. Assessing patient clinical trajectories using these clusters allowed us to identify individual conditions and phenotypes strongly increased after acute infection. We found many conditions increased in COVID-19 patients compared to controls, and using a novel method to associate patients with clusters over time, we additionally found phenotypes specific to patient sex, age, wave of infection, and PASC diagnosis status. While many of these results reflect known PASC symptoms, the resolution provided by this unprecedented data scale suggests avenues for improved diagnostics and mechanistic understanding of this multifaceted disease., Competing Interests: Competing Interests The authors declare no competing interests.

Background: To understand how body composition in those with elevated body mass index impacts left ventricular function decline during cancer treatment, we determined the association between baseline body mass index (BMI), intra-abdominal adipose tissue (IAT) and subcutaneous adipose tissue (SAT) with baseline to 3-month left ventricular ejection fraction (LVEF) change among women receiving potentially cardiotoxic chemotherapy for breast cancer, lymphoma, or sarcoma., Methods: Women underwent potentially cardiotoxic chemotherapy, such as doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab, for treatment of breast cancer, lymphoma, or sarcoma. We obtained magnetic resonance images (MRIs) of body composition and cardiac function prior to treatment, and then a repeat MRI for cardiac function assessment at three months into treatment. Analyses and assessment of abdominal adipose tissue volumes and LVEF outcomes were conducted by independent reviewers blinded to all patient identifiers. A general linear model was created to examine associations between adipose tissue depots, BMI, and 3-month LVEF change., Results: Women (n = 210) aged 56 ± 11 years with breast cancer, lymphoma, and sarcoma were enrolled (n = 195, 14, 1 respectively). Baseline BMI, IAT, and SAT fat were independently associated with 3-month LVEF declines (p = 0.001 to 0.025 for all). After adjusting for baseline cardiovascular disease risk factors, BMI, IAT, and SAT, BMI remained the only variable associated with 3-month LVEF decline (p = 0.047)., Conclusions: These results suggest that factors other than abdominal adipose tissue or traditional cardiovascular risk factors may contribute to 3-month declines in LVEF among women with elevated BMI receiving potentially cardiotoxic chemotherapy. Further investigation should be conducted on psychosocial stress, physical activity, sleep, or diet., Trial Registration: DETECTIV_NCT01719562, WF99112, & WF97415-NCT02791581., (© 2024. The Author(s).)

Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous, motile ciliopathy, characterized by neonatal respiratory distress, recurrent upper and lower respiratory tract infections, subfertility, and laterality defects. Diagnosis relies on a combination of tests for confirmation, including nasal nitric oxide (nNO) measurements, high-speed videomicroscopy analysis (HSVMA), immunofluorescent staining, axonemal ultrastructure analysis via transmission electron microscopy (TEM), and genetic testing. Notably, there is no single gold standard confirmatory or exclusionary test. Currently, 54 causative genes involved in cilia assembly, structure, and function have been linked to PCD; this rare disease has a spectrum of clinical manifestations and emerging genotype-phenotype relationships. In this review, we provide an overview of the structure and function of motile cilia, the emerging genetics and pathophysiology of this rare disease, as well as clinical features associated with motile ciliopathies, novel diagnostic tools, and updates on genotype-phenotype relationships in PCD.

Introduction: The surge in virtual care during the pandemic was accompanied by an increase in telehealth data of interest to policy stakeholders and other health care decision makers. However, these data often require substantial preprocessing and targeted analyses to be usable. By deliberately evaluating telehealth services with stakeholder perspectives in mind, telehealth researchers can more effectively inform clinical and policy decision making. Objective: To examine existing literature on telehealth measurement and evaluation and develop a new policy-oriented framework to guide telehealth researchers. Materials and Methods: A systematic rapid review of literature on telehealth measurement and evaluation was conducted by two independent reviewers in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The findings were analyzed and applied to the Supporting Pediatric Research on Outcomes and Utilization of Telehealth Evaluation and Measurement (STEM) Framework through the lens of key health care delivery decision makers to create a STEM Policy Framework Results: An initial search yielded 2,324 peer-reviewed articles and gray literatyre from 2012 to 2022, of which 56 met inclusion criteria. These measured and evaluated telehealth access (41.5%), quality (32.1%), cost (15.1%), experience (5.7%), and utilization (5.7%), consistent with the STEM Framework domains, but there was no universal approach. The STEM Policy Framework focuses this literature by describing data measures for each domain from the perspectives of five stakeholders. Conclusions: Literature describing measurement and evaluation approaches for telehealth is limited and not standardized, with few considering policy stakeholder perspectives. With this proposed STEM Policy Framework, we aim to improve this body of literature and support researchers seeking to inform telehealth policy through their work.

Three-dimensional (3D) modeling is a recent, innovative approach to teaching anatomy. There is little literature, however, to suggest how 3D modeling is best used to teach students and whether or not students can gain the same level of understanding as they might use more traditional, hands-on, teaching methods. This study evaluated the use of a 3D modeling software in both a flipped classroom curriculum and as an active learning tool in comparison to traditional, physical model-based teaching. Pre- and post-course content-based assessments were used to evaluate students' learning. Our findings indicated no significant difference between standard and flipped classroom learning; however, the students who used 3D modeling software as an active learning tool significantly underperformed students in the standard group (F(2,1060) = 112.43, p < 0.0001). These findings suggest that these technologies may not yet be useful as a primary means of instruction. Possible explanations may include cognitive overload in navigating the system, intrinsic limitations of the software, or other factors. Further development and research of these technologies is necessary prior to their adoption into teaching practices in anatomy., (© 2024 American Association for Anatomy.)

Background: Levetiracetam is an antiseizure medication used for several seizure types in adults and children aged 1 month and older; however, due to a lack of data, pharmacokinetic (PK) variability of levetiracetam is not adequately characterized in certain populations, particularly neonates, children younger than 2 years of age, and children older than 2 years of age with obesity., Objective: This study aimed to address the gap by leveraging PK data from two prospective standard-of-care pediatric trials (n = 88) covering an age range from 1 month to 19 years, including those with obesity (64%), and applying a physiologically based PK (PBPK) modeling framework., Methods: A published PBPK model of levetiracetam for children aged 2 years and older was extended to pediatric patients younger than 2 years of age and patients older than 2 years of age with obesity by accounting for the obesity and age-related changes in PK using PK-Sim ® software. The prospective pediatric data, along with the literature data for neonates and children younger than 2 years of age, were used to evaluate the extended PBPK models., Results: Overall, 82.4% of data fell within the 90% interval of model-predicted concentrations, with an average fold error within twofold of the accepted criteria. PBPK modeling revealed that children with obesity had lower weight-normalized clearances (0.053 L/h/kg) on average than children without obesity (0.063 L/h/kg). The effect of maturation was well-characterized, resulting in comparable PBPK-simulated, weight-normalized clearances for neonates and children younger than 2 years of age reported from the literature., Conclusions: PBPK modeling simulations revealed that the current US FDA-labeled pediatric dosing regimen listed in the prescribing information can produce the required exposure of levetiracetam in these target populations with dose adjustments for children with obesity aged 4 years to younger than 16 years., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The Ataxia Global Initiative (AGI) aims to serve as a platform to facilitate clinical trial readiness for the hereditary ataxias. Clinical trials for these diseases have been hampered by the lack of objective measures to study disease onset, progression, and treatment efficacy. While these issues are not unique to the genetic ataxias, the relative rarity of these diseases makes the need for such measures even more pressing to achieve statistical power in clinical trials. In this report, we have described the efforts of the AGI fluid biomarker working group (WG) in developing uniform protocols for biomarker sampling and storage, both for human and preclinical studies in mice. By reducing collection variability, we anticipate reduced noise in downstream biomarker analysis that will improve statistical power and minimize the necessary sample size. The emphasis has been on defining and standardizing the sampling and pre-analytical work-up of minimal set of biological samples, specifically blood plasma and serum, keeping in mind the need for harmonization of collection and storage that can be achieved with relatively limited cost and resources. An optional package is detailed for those centers that have the resources and commitment for additional biofluids/sample processing and storage. Finally, we have delineated similar standardized protocols for mice that will be important for preclinical studies in the field., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neoadjuvant cisplatin-based chemotherapy is standard of care for muscle-invasive bladder cancer (MIBC). Immune checkpoint inhibition (ICI) alone, and ICI in combination with chemotherapy, have demonstrated promising pathologic response (

Background: The implementation of digital breast tomosynthesis has increased the detection of radial scar (RS). Managing this finding may be experienced as a clinical dilemma in daily practice. Breast Contrast-Enhanced MRI (CE-BMR) is a known modality in case of problem-solving tool for mammographic abnormalities. However, the data about AD and CE-BMR are scant., Objective: The purpose was to estimate the benefit of CE-BMR in the setting of RS detected mammographically through a systematic review and meta-analysis of the literature., Methods: A search of MEDLINE and EMBASE databases were conducted in 2022. Based on the PRISMA guidelines, an analysis was performed. The primary endpoint was the correlation between CE-BMR findings and definite outcome for RS (pure RS versus RS associated with atypia or malignancy)., Results: Three studies were available. The negative predictive value (NPV) was 100% for each., Conclusion: The high NPV could allow for deferral of a biopsy in favor of a short-interval imaging follow-up in the setting of a negative CE-BMR., 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 Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Here, we present a series of illustrated capsules from the State of the Art (SOA) speakers at the 2024 International Society on Thrombosis and Haemostasis Congress in Bangkok, Thailand. This year's Congress marks the first time that the International Society on Thrombosis and Haemostasis has held its flagship scientific meeting in Southeast Asia and is the first to be organized by an international Planning Committee. The Bangkok program will feature innovative science and clinical updates from around the world, reflecting the diversity and multidisciplinary growth of our field. In these illustrated SOA capsules, you will find an exploration of novel models of thrombosis and bleeding and biomaterial discoveries that can trigger or block coagulation. Thromboinflammation is now understood to drive many disease states, and the SOA speakers cover cellular and coagulation responses to COVID-19 and other infections. The theme of crosstalk between coagulation and inflammation expands with capsules on protein S signaling, complement, and fibrinolytic inhibitors. Novel agents for hemophilia and thrombosis prevention are introduced. Challenging clinical conditions are also covered, such as inherited platelet disorders and antiphospholipid antibody syndrome. The scientific program in Bangkok will also showcase the work of clinicians and scientists from all parts of the world and chronicle real-world challenges. For example, 2 SOA capsules address the diagnosis and management of von Willebrand disease in low-income settings. Take some time to browse through these short illustrated reviews; we're sure that you'll be entertained, educated, and inspired to further explore the world of thrombosis and hemostasis., (© 2024 The Authors.)

Problem: Bacterial vaginosis (BV) disproportionally impacts Black and Hispanic women, placing them at risk for HIV, sexually transmitted infections and preterm birth. It is unknown whether there are differences by genetic ancestry in BV risk or whether polymorphisms associated with BV risk differ by ancestry., Methods: Women's Interagency HIV Study (WIHS) participants with longitudinal Nugent scores were dichotomized as having (n = 319, Nugent 7-10) or not having BV (n = 367, Nugent 0-3). Genetic ancestry was defined by clustering of principal components from ancestry informative markers and further stratified by BV status. 627 single nucleotide polymorphisms (SNPs) across 41 genes important in mucosal defense were identified in the WIHS GWAS. A logistic regression analysis was adjusted for nongenetic predictors of BV and self-reported race/ethnicity to assess associations between genetic ancestry and genotype., Results: Self-reported race and genetic ancestry were associated with BV risk after adjustment for behavioral factors. Polymorphisms in mucosal defense genes including syndecans, cytokines and toll-like receptors (TLRs) were associated with BV in all ancestral groups., Conclusions: The common association of syndecan, cytokine and TLR genes and the importance of immune function and inflammatory pathways in BV, suggests these should be targeted for further research on BV pathogenesis and therapeutics., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Rationale: Family caregivers of patients with acute cardiorespiratory failure are at high risk for distress, which is typically defined as the presence of psychological symptoms such as anxiety, depression, or posttraumatic stress. Interventions to reduce caregiver distress and increase wellness have been largely ineffective to date. An incomplete understanding of caregiver wellness and distress may hinder efforts at developing effective support interventions. Objectives: To allow family caregivers to define their experiences of wellness and distress 6 months after patient intensive care unit (ICU) admission and to identify moderators that influence wellness and distress. Methods: Primary family caregivers of adult patients admitted to the medical ICU with acute cardiorespiratory failure were invited to participate in a semistructured interview 6 months after ICU admission as part of a larger prospective cohort study. Interview guides were used to assess caregiver perceptions of their own well-being, record caregiver descriptions of their experiences of family caregiving, and identify key stress events and moderators that influenced well-being during and after the ICU admission. This study was guided by the Chronic Traumatic Stress Framework conceptual model, and data were analyzed using the five-step framework approach. Results: Among 21 interviewees, the mean age was 58 years, 67% were female, and 76% were White. Nearly half of patients (47%) had died before the caregiver interview. At the time of the interview, 9 caregivers endorsed an overall sense of distress, 10 endorsed a sense of wellness, and 2 endorsed a mix of both. Caregivers defined their experiences of wellness and distress as multidimensional and composed of four main elements: 1 ) positive versus negative physical and psychological outcomes, 2 ) high versus low capacity for self-care, 3 ) thriving versus struggling in the caregiving role, and 4 ) a sense of normalcy versus ongoing life disruption. Postdischarge support from family, friends, and the community at large played a key role in moderating caregiver outcomes. Conclusions: Caregiver wellness and distress are multidimensional and extend beyond the absence or presence of psychological outcomes. Future intervention research should incorporate novel outcome measures that include elements of self-efficacy, preparedness, and adaptation and optimize postdischarge support for family caregivers.

Objective: Infants with high birthweight have increased risk for adverse outcomes at birth and across childhood. Prenatal risks to healthy food access may increase odds of high birthweight. We tested whether having a poor neighborhood food environment and/or food insecurity had associations with high birthweight., Methods: We analyzed cross-sectional baseline data in Greenlight Plus, an obesity prevention trial across six US cities (n = 787), which included newborns with a gestational age greater than 34 weeks and a birthweight greater than 2500 g. We assessed neighborhood food environment using the Place-Based Survey and food insecurity using the US Household Food Security Module. We performed logistic regression analyses to assess the individual and additive effects of risk factors on high birthweight. We adjusted for potential confounders: infant sex, race, ethnicity, gestational age, birthing parent age, education, income, and study site., Results: Thirty-four percent of birthing parents reported poor neighborhood food environment and/or food insecurity. Compared to those without food insecurity, food insecure families had greater odds of delivering an infant with high birthweight (adjusted odds ratios [aOR] 1.96, 95% confidence intervals [CI]: 1.01, 3.82) after adjusting for poor neighborhood food environment, which was not associated with high birthweight (aOR 1.35, 95% CI: 0.78, 2.34). Each additional risk to healthy food access was associated with a 56% (95% CI: 4%-132%) increase in high birthweight odds., Conclusions: Prenatal risks to healthy food access may increase high infant birthweight odds. Future studies designed to measure neighborhood factors should examine infant birthweight outcomes in the context of prenatal social determinants of health., 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 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: During the COVID-19 pandemic, there was an increase in the number of unhoused individuals in Asheville, North Carolina resulting in more tent encampments.Understanding the physical, mental, and socially determined health characteristics associated with being unhoused can help guide stakeholders with policy development, healthcare program planning, and funding decisions to support unhoused individuals., Methods: In this study, we used an observational cross-section methodology. Using a convenience sample approach, we interviewed 101 participants who were receiving services from 2 emergency hotel shelters, a day center, and a resource center. Data were analyzed using descriptive statistics, and open-ended responses were collected and grouped to provide context., Results: Most participants were White (71%) and identified as male (76%). Over 60% reported having a high school education or advanced degree. Of the participants, 76% reported being unhoused for more than 6 months, and their last permanent housing was in Western North Carolina. Dental disease, chronic pain, and hypertension were common physical conditions. PTSD, depression, and anxiety were common mental health conditions. A lack of transportation was the most noted socially determined challenge. Marijuana, methamphetamine, and alcohol were the most often used substances, where methamphetamine was noted to be particularly problematic for the participants., Conclusion: Understanding the physical, mental, and social issues of the complex unhoused population can assist policymakers, healthcare providers, and other stakeholders in addressing challenges and testing improvement strategies., Competing Interests: Conflicts of Interest: The authors declare they have no conflicts of interest., (© 2024 HCA Physician Services, Inc. d/b/a Emerald Medical Education.)

The severe acute respiratory syndrome coronavirus 2 pandemic is characterized by the emergence of novel variants of concern (VOCs) that replace ancestral strains. Here, we dissect the complex selective pressures by evaluating variant fitness and adaptation in human respiratory tissues. We evaluate viral properties and host responses to reconstruct forces behind D614G through Omicron (BA.1) emergence. We observe differential replication in airway epithelia, differences in cellular tropism, and virus-induced cytotoxicity. D614G accumulates the most mutations after infection, supporting zoonosis and adaptation to the human airway. We perform head-to-head competitions and observe the highest fitness for Gamma and Delta. Under these conditions, RNA recombination favors variants encoding the B.1.617.1 lineage 3' end. Based on viral growth kinetics, Alpha, Gamma, and Delta exhibit increased fitness compared to D614G. In contrast, the global success of Omicron likely derives from increased transmission and antigenic variation. Our data provide molecular evidence to support epidemiological observations of VOC emergence., Competing Interests: Declaration of interests R.S.B. is a member of advisory boards for VaxArt, Takeda, and Invivyd; has consulted for Gilead; and has collaborative projects with Gilead, J&J, and Hillevax focused on unrelated projects., (Copyright © 2024. Published by Elsevier Inc.)

Background: Generalized myasthenia gravis (gMG) is a chronic, unpredictable disease associated with high treatment and disease burdens, with a need for more effective and well-tolerated treatments., Objectives: To evaluate the long-term safety, tolerability, and efficacy of zilucoplan in a mild-to-severe, acetylcholine receptor autoantibody-positive (AChR+) gMG population., Design: Ongoing, multicenter, phase III open-label extension (OLE) study., Methods: Eligible patients had completed a qualifying randomized, placebo-controlled phase II or phase III zilucoplan study and received daily, self-administered subcutaneous 0.3 mg/kg zilucoplan. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Secondary efficacy endpoints included change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score., Results: In total, 200 patients enrolled. At the cut-off date (8 September 2022), median (range) exposure to zilucoplan in RAISE-XT was 1.2 (0.11-4.45) years. Mean age at OLE baseline was 53.3 years. A total of 188 (94%) patients experienced a TEAE, with the most common being MG worsening ( n  = 52, 26%) and COVID-19 ( n  = 49, 25%). In patients who received zilucoplan 0.3 mg/kg in the parent study, further improvements in MG-ADL score continued through to Week 24 (least squares mean change [95% confidence interval] from double-blind baseline -6.06 [-7.09, -5.03]) and were sustained through to Week 60 (-6.04 [-7.21, -4.87]). In patients who switched from placebo in the parent study, rapid improvements in MG-ADL score were observed at the first week after switching to zilucoplan; further improvements were observed at Week 24, 12 weeks after switching (-6.46 [-8.19, -4.72]), and were sustained through to Week 60 (-6.51 [-8.37, -4.65]). Consistent results were observed in other efficacy endpoints., Conclusion: Zilucoplan demonstrated a favorable long-term safety profile, good tolerability, and sustained efficacy through to Week 60 with consistent benefits in a broad AChR+ gMG population. Additional long-term data will be available in future analyses., Trial Registration: ClinicalTrials.gov identifier: NCT04225871 (https://clinicaltrials.gov/ct2/show/NCT04225871)., (© The Author(s), 2024.)

N6-Methyladenosine (m6A) is the most abundant posttranscriptional modification, and its contribution to cancer evolution has recently been appreciated. Renal cancer is the most common adult genitourinary cancer, approximately 85% of which is accounted for by the clear cell renal cell carcinoma (ccRCC) subtype characterized by VHL loss. However, it is unclear whether VHL loss in ccRCC affects m6A patterns. In this study, we demonstrate that VHL binds and promotes METTL3/METTL14 complex formation while VHL depletion suppresses m6A modification, which is distinctive from its canonical E3 ligase role. m6A RNA immunoprecipitation sequencing (RIP-Seq) coupled with RNA-Seq allows us to identify a selection of genes whose expression may be regulated by VHL-m6A signaling. Specifically, PIK3R3 is identified to be a critical gene whose mRNA stability is regulated by VHL in a m6A-dependent but HIF-independent manner. Functionally, PIK3R3 depletion promotes renal cancer cell growth and orthotopic tumor growth while its overexpression leads to decreased tumorigenesis. Mechanistically, the VHL-m6A-regulated PIK3R3 suppresses tumor growth by restraining PI3K/AKT activity. Taken together, we propose a mechanism by which VHL regulates m6A through modulation of METTL3/METTL14 complex formation, thereby promoting PIK3R3 mRNA stability and protein levels that are critical for regulating ccRCC tumorigenesis.

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine, as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In 'VI: ways of being-in the office with patients', authors address the following themes: 'Patient-centred care-cultivating deep listening skills', 'Doctor as witness', 'Words matter', 'Understanding others-metaphor and its use in medicine', 'Communicating with patients-making good use of time', 'The patient-centred medical home-aspirations for the future', 'Routine, ceremony or drama?' and 'The life course'. May readers better appreciate the nuances of patient care through these essays., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Pharmacokinetic models rarely undergo external validation in vulnerable populations such as critically ill infants, thereby limiting the accuracy, efficacy, and safety of model-informed dosing in real-world settings. Here, we describe an opportunistic approach using dried blood spots (DBS) to evaluate a population pharmacokinetic model of metronidazole in critically ill preterm infants of gestational age (GA) ≤31 weeks from the Metronidazole Pharmacokinetics in Premature Infants (PTN&#95;METRO, NCT01222585) study. First, we used linear correlation to compare 42 paired DBS and plasma metronidazole concentrations from 21 preterm infants [mean (SD): post natal age 28.0 (21.7) days, GA 26.3 (2.4) weeks]. Using the resulting predictive equation, we estimated plasma metronidazole concentrations (ePlasma) from 399 DBS collected from 122 preterm and term infants [mean (SD): post natal age 16.7 (15.8) days, GA 31.4 (5.1) weeks] from the Antibiotic Safety in Infants with Complicated Intra-Abdominal Infections (SCAMP, NCT01994993) trial. When evaluating the PTN&#95;METRO model using ePlasma from the SCAMP trial, we found that the model generally predicted ePlasma well in preterm infants with GA ≤31 weeks. When including ePlasma from term and preterm infants with GA >31 weeks, the model was optimized using a sigmoidal Emax maturation function of postmenstrual age on clearance and estimated the exponent of weight on volume of distribution. The optimized model supports existing dosing guidelines and adds new data to support a 6-hour dosing interval for infants with postmenstrual age >40 weeks. Using an opportunistic DBS to externally validate and optimize a metronidazole population pharmacokinetic model was feasible and useful in this vulnerable population., Competing Interests: R.L.R. and E.J.T. are supported by the NICHD under Award Number T32HD104576. The spouse of R.L.R. has financial relationships with Merck & Co, Inc. and Biogen. S.J.B. receives support from the National Institutes of Health, the US Food and Drug Administration, the Childhood Arthritis and Rheumatology Research Alliance, Purdue Pharma, consulting for UCB and Rutgers, and serves on an NIH Data Safety Monitoring Board. M.C.W. receives support for research from the NIH [1U24-MD016258], National Institute of Allergy and Infectious Diseases [HHSN272201500006I, 1K24-AI143971], FDA [5U18-FD006298], and industry for drug development in adults and children. M.J.S. reports research support from Pfizer and Merck. C.P.H. receives salary support for research from NIH, FDA, the Burroughs Wellcome Fund, and other sponsors for drug development in adults and children (https://dcri.org/about-us/conflict-of-interest/). R.G.G. has received support from the NIH, the FDA, the Centers for Disease Control, and industry for research services (https://dcri.org/about-us/conflict-of-interest/). C.B. receives research support from the NIH and Aerogen. J.M.B. receives research support from NICHD (R01HD097081). H.C. receives support for research from the NIH (1R01HD109784). M.M.L. receives support from grant K24 HL143283. G.M.S. receives research support from NIH, Thrasher Research Fund, Airway Therapeutics, and ICON Clinical Research. J.H.W. is consulting for Roche Diagnostics, Inc. R.C., L.C.D., N.H., A.L., F.M., M.S., A.T., S.V., C.E.L.D., and C.H. report no funding.

Neuropathic pain is a chronic condition representing a significant burden for society. It is estimated 1 out of 10 people over the age of 30 that in the US have been diagnosed with neuropathic pain. Most of the available treatments for neuropathic pain have moderate efficacy over time which limit their use; therefore, other therapeutic approaches are needed for patients. Spinal cord stimulation is an established and cost-effective modality for treating severe chronic pain. In this article we will review the current approved indications for the use of spinal cord stimulation in the US and the novel therapeutic options which are now available using this therapy., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale: Existing literature describing differences in survival following percutaneous coronary intervention (PCI) by patient sex, race-ethnicity and the role of socioeconomic characteristics (SEC) is limited., Aims and Objectives: Evaluate differences in 1-year survival after PCI by sex and race-ethnicity, and explore the contribution of SEC to observed differences., Methods: Using a 20% sample of Medicare claims data for beneficiaries aged 65+, we identified fee-for-service patients who received PCI from 2007 to 2015. We performed logistic regression to assess how sex and race-ethnicity relate to procedural indication, inpatient versus outpatient setting, and 1-year mortality. We evaluated whether these relationships are moderated by sequentially controlling for factors including age, comorbidities, presence of acute myocardial infarction (AMI), county SEC, medical resource availability and inpatient versus outpatient procedural status., Results: We identified 300,491 PCI procedures, of which 94,863 (31.6%) were outpatient. There was a significant transition to outpatient PCI during the study period, especially for men compared with women and White patients compared with Black patients. Black patients were 3.50 percentage points (p < 0.001) and women were 3.41 percentage points (p < 0.001) more likely than White and male patients to undergo PCI at the time of AMI, which typically occurs in the inpatient setting. Controlling for age and calendar year, Black patients were 2.87 percentage points more likely than non-Hispanic White patients to die within 1 year after PCI. After controlling for Black-White differences in comorbidities, the differences in 1-year mortality decreased to 0.95 percentage points, which then became nonsignificant when further controlling for county resources and state of residence., Conclusion: Women were more likely to experience PCI in the setting of AMI and had less transition to outpatient care during the period. Black patients experienced higher 1-year mortality following PCI, which is explained by differences in baseline comorbidities, county medical resources, and state of residence., (© 2023 John Wiley & Sons Ltd.)

Objective: This study aimed to assess the efficacy of the neurokinin 3 receptor antagonist, fezolinetant, according to several intrinsic (individual related) and extrinsic (external influence) factors that may influence the frequency and severity of moderate-to-severe vasomotor symptoms (VMS) using pooled 12-week data from SKYLIGHT 1 and 2., Methods: SKYLIGHT 1 and 2 were two phase 3, randomized, double-blind studies conducted from July 2019 to August 2021 (SKYLIGHT 1) or April 2021 (SKYLIGHT 2). Participants were initially randomized to receive daily doses of placebo, fezolinetant 30 mg, or fezolinetant 45 mg. After 12 weeks, placebo participants were rerandomized to receive fezolinetant 30 mg or 45 mg, whereas those receiving fezolinetant continued on the same dose. Change in VMS frequency from baseline to week 12 was used to assess efficacy according to several intrinsic and extrinsic factors. Overall efficacy and safety were also investigated., Results: Overall, 1,022 individuals were included. Fezolinetant was efficacious in reducing VMS frequency across all intrinsic and extrinsic factors. Efficacy was most notable for participants who self-identify as Black (least squares mean difference for fezolinetant 45 mg versus placebo, -3.67; 95% CI, -5.32 to -2.01), current smokers (-3.48; -5.19 to -1.77), and current alcohol users (-3.48; -4.42 to -2.54). Overall efficacy was -2.51 (95% CI, -3.20 to -1.82) for fezolinetant 45 mg versus placebo. Similar findings were observed for the fezolinetant 30 mg dose. Comparable incidences of treatment-emergent adverse events were observed for placebo (132 of 342 individuals [38.6%]), fezolinetant 30 mg (132 of 340 individuals [38.8%]), and fezolinetant 45 mg (135 of 340 individuals [39.7%])., Conclusions: None of the intrinsic and extrinsic factors analyzed substantially reduced the efficacy response to fezolinetant in SKYLIGHT 1 and 2. These data provide additional confidence for using fezolinetant in a diverse population of individuals with VMS., Competing Interests: Financial disclosure/conflicts of interest: N.S. is a study investigator, member of a scientific advisory board, and consultant for Astellas; a member of a medical advisory board for Amazon (Project Ember); a member of a scientific advisory board for MenoGeniX and QUE Oncology; a consultant for Ansh Labs; an associate editor for Menopause; and a past president of the Society for Reproductive Investigation. R.E.N. has past financial relationships (lecturer, member of advisory boards, and/or consultant) with Boehringer Ingelheim, Eli Lilly, Endoceutics, Exeltis, Novo Nordisk, Palatin Technologies, Pfizer, Procter & Gamble, Teva Women's Health, and Zambon; has ongoing relationships with Abbott, Astellas, Bayer HealthCare, Fidia, Gedeon Richter, HRA Pharma, Merck & Co, Organon, Shionogi, and Theramex; and serves as president elect of the International Menopause Society. G.N-.P. is a member of a scientific advisory board for Astellas and Ferring Pharmaceuticals; has received research funding from the American Association of Medical Colleges, Merck, and NICHD; is the vice president of Diversity, Equity and Structural Change for the Society for Reproductive Investigation; is the program committee chair for the American Society of Reproductive Medicine; holds committee membership of the Endocrine Society; and is an associate editor for Frontiers in Endocrinology. M.E., D.D.K., Y.Y., and F.D.O. are employees of Astellas Pharma Inc., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The Menopause Society.)

Aims: To determine contemporary incidence rates and risk factors for major adverse events in youth-onset T1D and T2D., Methods: Participant interviews were conducted once during in-person visits from 2018 to 2019 in SEARCH (T1D: N = 564; T2D: N = 149) and semi-annually from 2014 to 2020 in TODAY (T2D: N = 495). Outcomes were adjudicated using harmonized, predetermined, standardized criteria., Results: Incidence rates (events per 10,000 person-years) among T1D participants were: 10.9 ophthalmologic; 0 kidney; 11.1 nerve, 3.1 cardiac; 3.1 peripheral vascular; 1.6 cerebrovascular; and 15.6 gastrointestinal events. Among T2D participants, rates were: 40.0 ophthalmologic; 6.2 kidney; 21.2 nerve; 21.2 cardiac; 10.0 peripheral vascular; 5.0 cerebrovascular and 42.8 gastrointestinal events. Despite similar mean diabetes duration, complications were higher in youth with T2D than T1D: 2.5-fold higher for microvascular, 4.0-fold higher for macrovascular, and 2.7-fold higher for gastrointestinal disease. Univariate logistic regression analyses in T1D associated age at diagnosis, female sex, HbA1c and mean arterial pressure (MAP) with microvascular events. In youth-onset T2D, composite microvascular events associated positively with MAP and negatively with BMI, however composite macrovascular events associated solely with MAP., Conclusions: In youth-onset diabetes, end-organ events were infrequent but did occur before 15 years diabetes duration. Rates were higher and had different risk factors in T2D versus T1D., 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 B.V. All rights reserved.)

Objectives: To examine the association of prestroke continuity of care (COC) with postdischarge health care utilization and expenditures., Study Population: The study population included 2233 patients with a diagnosis of stroke or a transient ischemic attack hospitalized in one of 41 hospitals in North Carolina between March 2016 and July 2019 and discharged directly home from acute care., Methods: COC was assessed from linked Centers for Medicare and Medicaid Services Medicare claims using the Modified, Modified Continuity Index. Logistic regressions and 2-part models were used to examine the association of prestroke primary care COC with postdischarge health care utilization and expenditures., Results: Relative to patients in the first (lowest) COC quartile, patients in the second and third COC quartiles were more likely [21% (95% CI: 8.5%, 33.5%) and 33% (95% CI: 20.5%, 46.1%), respectively] to have an ambulatory care visit within 14 days. Patients in the highest COC quartile were more likely to visit a primary care provider but less likely to see a stroke specialist. Highest as compared with lowest primary care COC quartile was associated with $45 lower (95% CI: $14, $76) average expenditure for ambulatory care visits within 30 days postdischarge. Patients in the highest, as compared with the lowest, primary care COC quartile were 36% less likely (95% CI: 8%, 64%) to be readmitted within 30 days postdischarge and spent $340 less (95% CI: $2, $678) on unplanned readmissions., Conclusions: These findings underscore the importance of primary care COC received before stroke hospitalization to postdischarge care and expenditures., Competing Interests: P.D. and C.B.: Ownership in Care Directions, LLC. The remaining authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Dysarthria is a common manifestation across cerebellar ataxias leading to impairments in communication, reduced social connections, and decreased quality of life. While dysarthria symptoms may be present in other neurological conditions, ataxic dysarthria is a perceptually distinct motor speech disorder, with the most prominent characteristics being articulation and prosody abnormalities along with distorted vowels. We hypothesized that uncertainty of vowel predictions by an automatic speech recognition system can capture speech changes present in cerebellar ataxia. Speech of participants with ataxia (N=61) and healthy controls (N=25) was recorded during the "picture description" task. Additionally, participants' dysarthric speech and ataxia severity were assessed on a Brief Ataxia Rating Scale (BARS). Eight participants with ataxia had speech and BARS data at two timepoints. A neural network trained for phoneme prediction was applied to speech recordings. Average entropy of vowel tokens predictions (AVE) was computed for each participant's recording, together with mean pitch and intensity standard deviations (MPSD and MISD) in the vowel segments. AVE and MISD demonstrated associations with BARS speech score (Spearman's rho=0.45 and 0.51), and AVE demonstrated associations with BARS total (rho=0.39). In the longitudinal cohort, Wilcoxon pairwise signed rank test demonstrated an increase in BARS total and AVE, while BARS speech and acoustic measures did not significantly increase. Relationship of AVE to both BARS speech and BARS total, as well as the ability to capture disease progression even in absence of measured speech decline, indicates the potential of AVE as a digital biomarker for cerebellar ataxia., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Weight loss may benefit older adults with obesity. However, it is unknown whether individuals with different frailty phenotypes have different outcomes following weight loss. Community-dwelling adults aged ≥65 ( n  = 53) with a body mass index ≥30 kg/m 2 were recruited for a six-month, single-arm, technology-based weight loss study. A 45-item frailty index identified frailty status using subjective and objective measures from a baseline geriatric assessment. At baseline, n  = 22 participants were classified as pre-frail (41.5%) and n  = 31 were frail (58.5%), with no differences in demographic characteristics. While weight decreased significantly in both groups (pre-frail: 90.8 ± 2.7 kg to 85.5 ± 2.4 kg ( p  < 0.001); frail: 102.7 ± 3.4 kg to 98.5 ± 3.3 kg ( p  < 0.001), no differences were observed between groups for changes in weight ( p  = 0.30), appendicular lean mass/height 2 ( p  = 0.47), or fat-free mass ( p  = 0.06). Older adults with obesity can safely lose weight irrespective of frailty status using a technology-based approach. Further investigation is needed to determine whether the impact of specific lifestyle interventions differ by frailty status.

Human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) is the most common HPV-associated cancer in the United States, with a rapid increase in incidence over the last two decades. The burden of HPV+ HNSCC is likely to continue to rise, and given the long latency between infection and the development of HPV+ HNSCC, it is estimated that the effect of the HPV vaccine will not be reflected in HNSCC prevalence until 2060. Efforts have begun to decrease morbidity of standard therapies for this disease, and its improved characterization is being leveraged to identify and target molecular vulnerabilities. Companion biomarkers for new therapies will identify responsive tumors. A more basic understanding of two mechanisms of HPV carcinogenesis in the head and neck has identified subtypes of HPV+ HNSCC that correlate with different carcinogenic programs and that identify tumors with good or poor prognosis. Current development of biomarkers that reliably identify these two subtypes, as well as biomarkers that can detect recurrent disease at an earlier time, will have immediate clinical application.

Introduction/background: Phosphatase and tensin homolog (PTEN) genomic deletions and transmembrane protease, serine 2/v-ets avian erthyroblastosis virus E26 oncogene homolog (ERG) rearrangements are two of the most common genetic abnormalities associated with prostate cancer. Prior studies have demonstrated these alterations portend worse clinical outcomes. Our objective is to evaluate the impact of biopsy-determined PTEN losses and TMPRSS2-ERG fusion on biochemical progression-free survival (bPFS) and overall survival (OS) in patients who receive SBRT for localized prostate cancer., Methods/materials: Patients received SBRT for localized prostate cancer on a prospective quality-of-life (QoL) and cancer outcomes study. For each patient, the single biopsy core with the highest grade/volume of cancer was evaluated for PTEN and ERG abnormalities. Differences in baseline patient and disease characteristics between groups were analyzed using ANOVA for age and χ 2 for categorical groupings. bPFS and OS were calculated using the Kaplan Meier (KM) method with Log-Rank test comparison between groups. Predictors of bPFS and OS were identified using the Cox proportional hazards method. For all analyses, p < 0.05 was considered statistically significant., Results: Ninety-nine consecutive patients were included in the analysis with a median follow-up of 72 months. A statistically significant improvement in bPFS ( p = 0.018) was observed for wild type ERG patients with an estimated 5-year bPFS of 94.1% vs. 72.4%. Regarding PTEN mutational status, significant improvements in were observed in both bPFS (p = 0.006) and OS (p < 0.001), with estimated 5-year bPFS rates of 91.0% vs. 67.9% and 5-year OS rates of 96.4% vs. 79.4%. When including both ERG and PTEN mutational status in the analysis, there were statistically significant differences in both bPFS (p = 0.011) and OS (p < 0.001). The estimated 5-year bPFS rates were 100%, 76.6%, 72.9%, and 63.8% for patients with ERG+/PTEN+, ERG-/PTEN+, ERG+/PTEN-, and ERG-/PTEN- phenotypes respectively. The estimated 5-year OS rates were 93.9%, 100%, 80.0%, and 78.7% for patients with ERG+/PTEN+, ERG-/PTEN+, ERG+/PTEN-, and ERG-/PTEN- phenotypes respectively., Conclusion: ERG rearrangements and PTEN deletions detected on biopsy samples are associated with poorer oncologic outcomes in prostate cancer patients treated with SBRT and merit further study in a dedicated prospective trial., Competing Interests: SC serves as a consultant for Accuray Sunnyvale, CA and Boston Scientific Marlborough, MA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer CZ declared a past co-authorship with the authors AK and SC to the handling editor. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Repka, Sholklapper, Zwart, Danner, Ayoob, Yung, Lei, Collins, Kumar, Suy, Hankins, Kishan and Collins.)

Background: Reducing healthcare disparities among children is extremely important given the potential impact of these disparities on long-term health-related quality of life (HRQL). Race and parental socioeconomic status (SES) are associated with child HRQL, but these associations have not been studied in infants born extremely preterm (EP), a population at increased risk for physical, cognitive, and psychosocial impairments. Achieving health equity for infants born EP across their life course requires identifying the impact of racism and SES on HRQL., Objective: We aimed to evaluate the association between self-reported maternal race, SES factors, and HRQL among 10-year-old children born EP., Design/methods: Participants were identified from an ongoing multicenter prospective longitudinal study of Extremely Low Gestational Age Newborns (ELGAN Study), born between 2002 and 2004, and evaluated at 10 years of age using the Pediatric quality of life (QoL) Inventory completed by their parent or guardian, assessing physical, emotional, social, school, and total (composite) QoL domains. Multivariable regression models were used to evaluate the relationship between QoL scores and self-identified maternal race, adjusting for SES factors (education level, marital status, and public insurance)., Results: Of 1,198 study participants who were alive at 10 years of age, 863 (72.0%) were evaluated at 10 years of age. Differences in mean 10-year QoL scores across racial groups were observed and were significant on univariate analysis. However, these associations attenuated when adjusted for the marital status, public insurance status, and education status of mothers. A comparison of children with English as the primary language spoken at home vs. any other language revealed a significant difference only in school QoL, in which non-English language was associated with more favorable school QoL scores., Conclusions: Among 10-year-old children born EP, differences in parent-reported QoL were associated with maternal SES factors but not with race. Our results suggest that interventions designed to improve the SES of mothers may enhance the QoL of children born EP. Furthermore, these results underscore that race is a social construct, rather than a biological variable, as we work toward greater equity in care provision., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Call, Oran, O'Shea, Jensen, Frazier, Vaidya, Shenberger, Gogcu, Msall, Kim, Jalnapurkar, Fry and Singh.)

Objective. Sensory feedback is critical for effectively controlling brain-machine interfaces and neuroprosthetic devices. Spinal cord stimulation (SCS) is proposed as a technique to induce artificial sensory perceptions in rodents, monkeys, and humans. However, to realize the full potential of SCS as a sensory neuroprosthetic technology, a better understanding of the effect of SCS pulse train parameter changes on sensory detection and discrimination thresholds is necessary. Approach. Here we investigated whether stimulation periodicity impacts rats' ability to detect and discriminate SCS-induced perceptions at different frequencies. Main results. By varying the coefficient of variation (CV) of interstimulus pulse interval, we showed that at lower frequencies, rats could detect highly aperiodic SCS pulse trains at lower amplitudes (i.e. decreased detection thresholds). Furthermore, rats learned to discriminate stimuli with subtle differences in periodicity, and the just-noticeable differences from a highly aperiodic stimulus were smaller than those from a periodic stimulus. Significance. These results demonstrate that the temporal structure of an SCS pulse train is an integral parameter for modulating sensory feedback in neuroprosthetic applications., (Creative Commons Attribution license.)

Objectives: Evaluate the effect of anterior fixation on infection in patients with operative pelvic fractures and bladder or urethral injuries., Design: Retrospective., Setting: Eight centers., Patient Selection Criteria: Adult patients with closed pelvic fractures with associated bladder or urethral injuries treated with anterior plating (AP), intramedullary screw (IS), or no anterior internal fixation (NAIF, including external fixation or no fixation)., Outcome Measures and Comparisons: Deep infection., Results: There were 81 extraperitoneal injuries and 57 urethral injuries. There was no difference in infection between fixation groups across all urologic injuries (AP: 10.8%, IS: 0%, NAIF: 4.9%, P = 0.41). There was a higher rate of infection in the urethral injury group compared with extraperitoneal injuries (14.0% vs. 2.5%, P = 0.016). Among extraperitoneal injuries, specifically, there was no difference in deep infection related to fixation (AP: 2.6%, IS 0%, NAIF: 2.9%, P = 0.99). Among urethral injuries, there was no statistical difference in deep infection related to fixation (AP: 23.1%, IS: 0%, NAIF: 7.4%, P = 0.21). There was a higher rate of suprapubic catheter (SPC) use in urethral injuries compared with extraperitoneal injuries (57.9% vs. 4.9%, P < 0.0001). In the urethral injury group, SPC use did not have a statistically significant difference in infection rate (SPC: 18.2% vs. No SPC: 8.3%, P = 0.45). Early removal of the SPC before or during the definitive orthopaedic intervention did not significantly affect infection rate (early: 0% vs. delayed: 25.0%, P = 0.16)., Conclusions: Surgeons should approach operative pelvic fractures with associated urologic injuries with caution given the high risk of infection. Further work must be done to elucidate the effect of anterior implants and SPC use and duration., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aimed to describe perspectives from stakeholders involved in the Medicaid system in North Carolina regarding substance use disorder (SUD) treatment policy changes during the coronavirus disease 2019 pandemic., Methods: We conducted semistructured interviews in early 2022 with state agency representatives, Medicaid managed care organizations, and Medicaid providers (n = 22) as well as 3 focus groups of Medicaid beneficiaries with SUD (n = 14). Interviews and focus groups focused on 4 topics: policies, meeting needs during COVID, demand for SUD services, and staffing., Results: Overall, policy changes, such as telehealth and take-home methadone, were considered beneficial, with participants displaying substantial support for both policies. Shifting demand for services, staffing shortages, and technology barriers presented significant challenges. Innovative benefits and services were used to adapt to these challenges, including the provision of digital devices and data plans to improve access to telehealth., Conclusions: Perspectives from Medicaid stakeholders, including state organizations to beneficiaries, support the continuation of SUD policy changes that occurred. Staffing shortages remain a substantial barrier. Based on the participants' positive responses to the SUD policy changes made during the coronavirus disease 2019 pandemic, such as take-home methadone and telehealth initiation of buprenorphine, these changes should be continued. Additional steps are needed to ensure payment parity for telehealth services., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 American Society of Addiction Medicine.)

Background: Platinum-based neoadjuvant chemotherapy (NAC) is standard for patients with muscle-invasive bladder cancer (MIBC). Pathologic response (complete: ypT0N0 and partial: