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Temporal and geographical patterns of nitazene detections in drug samples and biospecimens in the United States, 2019-2024

Zhu, David T; Fitzgerald, Nicole D; Palamar, Joseph J; Krotulski, Alex J
BACKGROUND AND AIMS/OBJECTIVE:Nitazenes are a novel subclass of synthetic opioids that have been increasingly implicated in the United States (US) overdose crisis. Despite their growing presence in the illicit drug supply, national trends have not been systematically evaluated. This study aimed to describe temporal and geographic patterns in nitazene detections and assess substances co-involved in nitazene-positive biospecimens. DESIGN/METHODS:Cross-sectional study using forensic data from two national sources: the US Drug Enforcement Administration's National Forensic Laboratory Information System (NFLIS) and the Center for Forensic Science Research & Education's (CFSRE) NPS Discovery Program. SETTING AND CASES/METHODS:Nitazene detections in all 50 US states and the District of Columbia between 2019 and 2024. MEASUREMENTS/METHODS:We quantified annual nitazene detections overall and by individual nitazene analog, US Census region and state. Temporal trends were modeled using piecewise linear regression with a Poisson distribution and log link, nationally and by region. NPS Discovery data were used to characterize substances co-involved with nitazene-positive biospecimens. FINDINGS/RESULTS:Between 2019 and 2024, 7117 nitazene analog reports were submitted to NFLIS, increasing from 43 in 2019 to 1905 in 2024. Counts rose sharply from 2019 to 2021 [count ratio = 7.32; 95% confidence interval (CI) = 2.22-24.20] but did not increase statistically significantly from 2021 to 2024 (count ratio = 1.08; 95% CI = 1.00-1.17). Early detections were predominated by isotonitazene (97.7% of NFLIS nitazene reports in 2019) but later shifted toward metonitazene and protonitazene (29.5% and 30.1%, respectively, in 2024). NPS Discovery identified 361 nitazene-positive biospecimens, increasing from 11 in 2019 to 113 in 2024, with counts increasing by approximately 45% per year (count ratio = 1.45; 95% CI = 1.23-1.71). Nearly all nitazene-positive biospecimens (98.3%) had at least one co-detected substance, most commonly fentanyl (54.6%). CONCLUSIONS:Nitazene detections increased sharply across the United States between 2019 and 2024, with shifting patterns in the prevalence of individual nitazenes and extensive polysubstance involvement. These findings highlight the need to strengthen drug testing capacity, expand epidemiological surveillance and implement targeted public health interventions to mitigate harms associated with this emerging class of synthetic opioids.
PMID: 41785913
ISSN: 1360-0443
CID: 6009132

Epilepsy advances in 2025

Ryvlin, Philippe; Friedman, Daniel
PMID: 41736251
ISSN: 1473-6551
CID: 6009932

Accelerating Toward Affordability: A Net Present Value Analysis Comparing Accelerated 3-Year With Traditional 4-Year MD Programs

Rivera, Rafael; Nalin, Peter; Vitto, Christina; Gonzalez-Flores, Alicia; Thomas, Prijo; Coe, Catherine L; Reboli, Annette; Cangiarella, Joan; Jones, Betsy; Leong, Shou Ling; Santen, Sally A
PURPOSE/OBJECTIVE:Increasing student costs and financial burden of medical education necessitate an exploration of economically viable alternatives. Accelerated 3-year MD programs (A3YPs) are a promising solution, offering shorter training and potentially lower debt. This study calculated the additional financial value and potential debt savings inherent in A3YPs vs traditional 4-year MD programs (4YPs), focusing on net present value (NPV) (ie, current worth of future cash flows). METHOD/METHODS:The authors used NPV analysis to evaluate the differential financial investment and expected future cash flows for A3YP students graduating from 8 US medical schools in 2022 compared with 4YP graduates. The analysis considered tuition costs, residency and practicing physician salaries, and medical educational debt as the basis for the financial calculations. The analysis extended from the first year of medical school in 2020 through 1 year of postresidency practice in 2026, assuming contiguous training with no gaps and no fellowship training, including 7 years for the A3YP timeline. RESULTS:Sixty-six students graduated A3YPs from the 8 participating schools in 2022 (range, 3-17 graduates per school; mean, 8 graduates). The NPV for A3YP graduates was $240,349 higher per graduate compared with 4YP graduates. The most significant contribution to this higher NPV was the additional year of physician-level salary received by A3YP graduates. Additional contributions included savings from avoiding a fourth year of tuition and lower loan repayment costs due to decreased medical educational debt for A3YP graduates. CONCLUSIONS:This study offers a novel contribution to the ongoing discourse regarding the financial implications of medical education by providing a comprehensive NPV analysis comparing A3YPs with traditional 4YPs. Accelerated 3-year programs offer considerable financial advantages over 4YPs, which has implications for reducing medical student indebtedness and potentially addressing physician workforce shortages. Further research is necessary to explore the specific impacts on individual schools and specialties.
PMID: 41723817
ISSN: 1938-808x
CID: 6009502

AO Spine Clinical Practice Recommendations: An Overview of the Current State of Fusion Surgery for Patients With Spinal Metastasis: Is Fusion Necessary?

Landriel, Federico; Cofano, Fabio; Hem, Santiago Matías; Karim, Syed Muhammed; Mehta, Ankit I; Barzilai, Ori; Dea, Nicolas; Gasbarrini, Alessandro; Goodwin, C Rory; Laufer, Ilya; Reynolds, Jeremy; Verlaan, Jorrit-Jan; Fisher, Charles G; Netzer, Cordula
Study DesignLiterature review with clinical recommendations.ObjectiveProviding a clear and concise overview based on the of key literature and consensus expert opinion on spinal fusion following stabilization for spine metastases and offer actionable recommendations on when to fuse and not fuse in this patient population.MethodsKey articles from the published literature on spinal metastases treated with stabilization followed by fusion were reviewed, and clinical recommendations were formulated. The recommendations are categorized as either strong or conditional based on an assessment of methodological quality and expert opinion. This assessment considers factors such as experience, risks, burdens, costs, patient values, and circumstances.ResultsFour articles were selected by practicing spinal oncology surgeons and each was evaluated for its methodological strength and its scientific evidence.ConclusionFusion rarely influences clinical outcomes in metastatic spine surgery. Treatment should prioritize mechanical stability, pain control, functional preservation, and timely continuation of oncologic therapy rather than pursuing bony arthrodesis. Fusion should be considered exclusively in select long-surviving patients, however routine attempts to enhance fusion or delay adjuvant therapy are not justified.[Formula: see text].
PMCID:12929080
PMID: 41725136
ISSN: 2192-5682
CID: 6009562

Monitoring outcomes of the first human whole eye allotransplant

Dedania, Vaidehi S; Shah, Alay R; Chinta, Sachin R; Tran, David L; Brodie, Scott E; Gelb, Bruce E; Ceradini, Daniel J; Rodriguez, Eduardo D
PURPOSE/OBJECTIVE:To describe the first successful whole eye transplantation (WET) in a human, performed with concurrent partial face transplantation, and to characterize postoperative outcomes. DESIGN/METHODS:Case report. PARTICIPANT/METHODS:A 46-year-old male with severe facial and ocular deficits following high-voltage electrical injury, including left eye enucleation and extensive soft tissue and aesthetic deformities. METHODS:Comprehensive preoperative evaluation, precise microsurgical techniques including vascular anastomosis and optic nerve coaptation, and serial postoperative assessments with optical coherence tomography (OCT), fluorescein angiography (FA), electroretinography (ERG), and visual evoked potentials (VEP). MAIN OUTCOME MEASURES/METHODS:Sustained globe viability, vascular perfusion, retinal structural integrity, and electrophysiological function. RESULTS:The transplanted globe demonstrated robust vascular perfusion and structural preservation over 12 months. Outer retinal function was maintained, as indicated by ERG, despite retinal nerve fiber layer loss and optic nerve transection. VEP confirmed absence of visual perception. The procedure achieved substantial aesthetic restoration. CONCLUSIONS:This study establishes the feasibility of WET in humans, with sustained globe viability and preserved outer retinal function. These findings serve as a critical step toward future exploration of ocular transplantation.
PMID: 41764690
ISSN: 1573-2622
CID: 6008102

A reduced TBX5-dependent gene regulatory network links atrial fibrillation and heart failure

Lazarevic, Sonja; Perez-Cervantes, Carlos; Wang, Zhezhen; Shen, Kaitlyn M; Gadek, Margaret; Xiao, Junhua; Yamaguchi, Naoko; Hall, Johnathon M; Koca, Yildiz; Chapski, Douglas J; Rosa-Garrido, Manuel; Rubino, Marcello; Nadadur, Rangarajan D; McKinsey, Timothy A; Vondriska, Thomas M; Ruthenburg, Alexander J; Pott, Sebastian; Park, David S; Moskowitz, Ivan P
Atrial fibrillation (AF) and heart failure (HF) frequently coexist and worsen one another's outcomes. To investigate shared molecular mechanisms, we compared atrial gene regulatory networks (GRNs) in the mouse Tbx5 conditional knockout (Tbx5 cKO) AF model and the transverse aortic constriction (TAC) HF model. Here we show highly correlated changes in atrial transcriptional and genomic profiles, including downregulated atrial Tbx5 expression in both mouse and human HF. More than 100 transcription factor genes were coordinately dysregulated in the atria of the Tbx5 cKO and TAC models. The wild-type atrial TBX5-driven GRN, including Klf15, a repressor of cardiomyocyte hypertrophy, was disrupted in Tbx5 cKO and TAC models. Conversely, a disease-specific network featuring Sox9 emerged in activated fibroblasts of Tbx5 cKO and TAC models. Our results identify coordinated disruption of TBX5-dependent atrial gene regulation in AF and HF, suggesting that a shared genomic injury response may underlie the reciprocal risk between these conditions.
PMID: 41731058
ISSN: 2731-0590
CID: 6009772

Adapting substance use treatment for black adolescents in the US legal system: protocol for a mixed-method, exploratory, feasibility and acceptability study using the eight-step ADAPT-ITT framework

Bryant, Brittany E; Tolou-Shams, Marina; Ezimora, Ifunanya; Zapolski, Tamika C; DiClemente, Ralph; Jordan, Ayana; Becker, Sara J; Squeglia, Lindsay M
INTRODUCTION/BACKGROUND:This community-led research study protocol emphasises placing black youth impacted by the legal system, their families and their communities at the forefront of substance use treatment development research and decision-making. The study, the Cultural Adaptation of a Substance Use Treatment (CAST) Project, challenges traditional top-down approaches to treatment creation, advocating for a grassroots model that centres community knowledge, values and active participation. METHODS AND ANALYSIS/METHODS:The CAST project is a US-based mixed-methods study with an exploratory design that examines the impact of racial discrimination on substance use in black youth impacted by the legal system. The study participants are black youth impacted by the legal system (N=15), parents of black youth impacted by the legal system (N=10) and community members who serve black youth (N=10) (total N=35 study participants). Study participants from each group (youth, parents and community members) will participate in three separate focus groups, respectively, to provide feedback on the culturally responsive content needed to best support black youth impacted by the legal system around substance use and mental health. The eight-step Assess, Decision, Adaptation, Production, Topical Expert, Integration, Training, Testing framework will be used as a guide to inform adaptations to the Motivational Enhancement Therapy and Cognitive Behavioural Therapy (MET/CBT12) for black youth impacted by the legal system. Once the cultural adaptation process has been completed, the study will conclude with an open feasibility and accessibility trial of the culturally adapted MET/CBT12 manual. The primary outcomes of this study are the feasibility and acceptability of the culturally adapted manual, measured by treatment attendance and participant feedback. Secondary outcomes include reductions in substance use and discrimination distress, and improvements in mental health symptoms. ETHICS AND DISSEMINATION/BACKGROUND:This study was approved by the Institutional Review Board (IRB) at the University of California, San Francisco (IRB Protocol Number: 23-40126). All study procedures will be conducted in accordance with the ethical standards outlined by the institutional review board. The results from this study will be shared through peer-reviewed publications, academic conferences, community forums and policy briefs to support broader implementation of culturally adapted adolescent substance use interventions that address discrimination-related stress and substance use among black individuals impacted by the legal system. TRIAL REGISTRATION NUMBER/BACKGROUND:NCT06003725.
PMCID:12958882
PMID: 41771593
ISSN: 2044-6055
CID: 6008322

Recommendations for the Deprescribing of Psychotropic Medications: A Consensus Statement From the American Society of Clinical Psychopharmacology Task Force

Goldberg, Joseph F; McIntyre, Roger S; Swartz, Holly A; Freeman, Marlene P; Mago, Rajnish; Citrome, Leslie; Rosenblat, Joshua D; Thase, Michael E; Tohen, Mauricio; Vieta, Eduard; Malhi, Gin S; Sajatovic, Martha; Shelton, Richard C; Macaluso, Matthew; Berk, Michael; Perlis, Roy H; Ostacher, Michael J; Khan, Arifulla; Iosifescu, Dan V; Sanacora, Gerard; Rubio, Jose Manuel; Kane, John M; Goodman, David W; Nierenberg, Andrew A; Correll, Christoph U; Kupka, Ralph; Kasper, Siegfried; Furukawa, Toshi A; Davis, Lori; Aaronson, Scott T; Gitlin, Michael J; Jha, Manish K; Cohen, Lawrence J; Papakostas, George I; Mitchell, Philip B; Gorwood, Philip; Gupta, Swapnil; Frye, Mark A; Young, Allan H; Zohar, Joseph; Steingard, Sandra; Zarate, Carlos A; Clayton, Anita H; ,
IMPORTANCE/UNASSIGNED:There is a need for greater recognition of clinical psychopharmacology endpoints, including instances where specific psychotropic medications may become unnecessary, redundant, contradictory, or otherwise inappropriate and therefore merit deprescribing. OBJECTIVE/UNASSIGNED:To address circumstances warranting psychotropic medication deprescribing. EVIDENCE REVIEW/UNASSIGNED:The American Society of Clinical Psychopharmacology convened a panel of 45 international psychopharmacology experts who developed and completed a multiround Delphi survey and conducted a focused literature review between January and May of 2025, in order to identify areas of consensus or disagreement on key aspects of the deprescribing of psychotropic medications. These included collaborative risk-benefit assessments with patients; pharmacokinetic and pharmacodynamic factors; pharmacogenomics; distinguishing redundant or conflictual from complementary mechanisms of action; managing adverse effects; assuring medication adherence; drug tolerance or tachyphylaxis; medication misuse; and the psychological context and ramifications of deprescribing. FINDINGS/UNASSIGNED:Consensus was achieved on 44 of 50 final Delphi statements (88%). Panelists unanimously agreed that components of a pharmacotherapy regimen should undergo periodic review to ensure that treatments target relevant symptoms and have favorable risk-benefit ratios. Key points of consensus were that deprescribing: (1) should not occur without first assessing medication adherence; (2) merits consideration if less than partial therapeutic response is apparent, or if treatment goals have been reached and relapse prevention is not a long-term objective; (3) involves psychological ramifications that warrant attention; (4) should be followed by close clinical monitoring; and (5) risk-benefit decisions should ideally involve active patient participation within a shared decision-making model. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Through this Consensus Statement, the Task Force identified circumstances in which the selective elimination of certain psychotropic medications may be clinically indicated. Empirical trials are needed to assess the implementation of deprescribing protocols and gauge their safe, effective, and acceptable outcomes.
PMID: 41739481
ISSN: 2574-3805
CID: 6010102

A Primer for Pediatric Plastic Surgeons on Pediatric Head and Neck Malignancies: Part III-Common Management Strategies for Pediatric Head and Neck Tumors

Najafali, Daniel; Pozin, Michael; Oakes, Benjamin; Kraguljac, Simo; Whittles, Jordan; Seif, Hana; Seif, Muhammad; Yu, Jason W; Hajjar, Fouad; Flores, Roberto; Lopez, Joseph
LEARNING OBJECTIVES/OBJECTIVE:After studying this article, the participant should be able to (1) understand the nonsurgical and surgical techniques and advancements in the management of pediatric head and neck cancers, (2) describe the common management strategies used in pediatric head and neck cancers, and (3) Understand therapies to target head and neck cancers within pediatric patient populations. SUMMARY/CONCLUSIONS:Pediatric head and neck cancer management is complex and often requires a multidisciplinary approach. Management goals aim to deliver a multimodal treatment approach that integrates surgery with concurrent medical management through adjuvant and/or neoadjuvant chemotherapy and/or radiation therapy. Patients in remission should be monitored closely for recurrence or long-term treatment complications. Harmonizing a multidisciplinary approach between pediatric oncologists, hematologists, radiologists, pathologists, and surgeons is a priority. This review discusses advances in management strategies used for common pediatric head and neck malignancies, with a focus on surgical and medical techniques as well as treatment complications that can arise.
PMID: 41734336
ISSN: 1536-3708
CID: 6009862

Development and evaluation of a multilingual caregiver electronic rounds summary

Glick, Alexander F; Kuzma, Nicholas C; Rosenbluth, Glenn; Kats, Daniel J; Yin, H Shonna; Zheng, Andy Weng; Fan, Angela L; D'Anna, Rachel; Elborki, Marwa; Gray, Kathryn P; Texler, Cara; Micalizzi, Dale; Kane, Joelle; Haskell, Helen; McDonald, Sally Coghlan; Abu-Rish Blakeney, Erin; Bismilla, Zia; Alvarado-Little, Wilma; Khan, Alisa; ,
BACKGROUND:Health literacy-informed and language-concordant written materials can promote caregiver understanding of care plans although are not commonly used in inpatient rounds. OBJECTIVES/OBJECTIVE:We sought to develop and evaluate a health literacy-informed, multilingual electronic real-time summary of rounds for hospitalized patients (the Rounds eSummary). METHODS:A multidisciplinary team developed the Rounds eSummary using health literacy, communication, and language equity best practices and multiple rounds of piloting. To generate the eSummary, clinicians completed a link with closed-ended options for various rounds components (e.g., illness severity, plan), caregiver's preferred language, and contact information. This generated an electronic PDF rounds summary (15 possible languages) emailed or texted to the family. We used descriptive statistics to analyze eSummaries (n = 437) created from October 25, 2024 to February 1, 2025. Separately, for a purposive sample of English eSummaries (n = 12) that represented different diagnoses and plans, two independent raters examined reading grade level (average of five formulas), understandability, and actionability (Patient Education Materials Assessment Tool for Printable Materials). RESULTS:Rounds eSummaries were generated in eight languages across three sites; the most common languages were English (89%), Spanish (6.2%), and Portuguese (1.8%). Plans commonly included medicines (42%), nutrition (30%), and oxygen (24%). More than half (61%) were accessed at least once by the patient/caregiver; of the eSummaries accessed, the average engagement time was 29.1 s (standard deviation 25.2). The average reading grade level was 6.8 (standard deviation 0.6, range 5.8-7.8). Overall understandability and actionability scores were 87% and 60%, respectively. CONCLUSION/CONCLUSIONS:We designed a usable Rounds eSummary that addressed language and health literacy barriers. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov identifier: NCT05591066.
PMID: 41736487
ISSN: 1553-5606
CID: 6009952