tbuckley/cabot-search huggingface dataset:
Adverse Safety Events in Emergency Medical Services Care of Children With Out-of-Hospital Cardiac Arrest
Authors: Carl O. Eriksson, Nathan Bahr, Garth Meckler, Matthew Hansen, Grace Walker-Stevenson, Ahamed Idris, Tom P. Aufderheide, Mohamud R. Daya, Ericka L. Fink, Jonathan Jui, Maureen Luetje, Christian Martin-Gill, Steven Mcgaughey, Jon Pelletier, Danny Thomas, Jeanne-Marie Guise, Tabria Harrod, Amanda Schoonover, Jon Ivankovic
Journal: JAMA Network Open (2024)

Importance Survival for children with out-of-hospital cardiac arrest (OHCA) remains poor despite improvements in adult OHCA survival. Objective To characterize the frequency of and factors associated with adverse safety events (ASEs) in pediatric OHCA. Design, Setting, and Participants This population-based retrospective cohort study examined patient care reports from 51 emergency medical services (EMS) agencies in California, Georgia, Oregon, Pennsylvania, Texas, and Wisconsin for children younger than 18 years with an OHCA in which resuscitation was attempted by EMS personnel between 2013 and 2019. Medical record review was conducted from January 2019 to April 2022 and data analysis from October 2022 to February 2023. Main Outcomes and Measure Severe ASEs during the patient encounter (eg, failure to give an indicated medication, 10-fold medication overdose). Results A total of 1019 encounters of EMS-treated pediatric OHCA were evaluated; 465 patients (46%) were younger than 12 months. At least 1 severe ASE occurred in 610 patients (60%), and 310 patients (30%) had 2 or more. Neonates had the highest frequency of ASEs. The most common severe ASEs involved epinephrine administration (332 [30%]), vascular access (212 [19%]), and ventilation (160 [14%]). In multivariable logistic regression, the only factor associated with severe ASEs was young age. Neonates with birth-related and non–birth-related OHCA had greater odds of a severe ASE compared with adolescents (birth-related: odds ratio [OR], 7.0; 95% CI, 3.1-16.1; non–birth-related: OR, 3.4; 95% CI, 1.2-9.6). Conclusions and Relevance In this large geographically diverse cohort of children with EMS-treated OHCA, 60% of all patients experienced at least 1 severe ASE. The odds of a severe ASE were higher for neonates than adolescents and even higher when the cardiac arrest was birth related. Given the national increase in out-of-hospital births and ongoing poor outcomes of OHCA in young children, these findings represent an urgent call to action to improve care delivery and training for this population.
UNCAN.eu: Toward a European Federated Cancer Research Data Hub
Authors: Michael Boutros, Michael Baumann, Anna Bigas, Linda Chaabane, Julien Guérin, Jens K. Habermann, Aurélien Jobard, Pier Giuseppe Pelicci, Oliver Stegle, Giovanni Tonon, Alfonso Valencia, Eva C. Winkler, Patricia Blanc, Ruggero De Maria, Rene H. Medema, Peter Nagy, Josep Tabernero, Eric Solary
Journal: Cancer Discovery (2024)

To enable a collective effort that generates a new level of UNderstanding CANcer (UNCAN.eu) [Cancer Discov (2022) 12 (11): OF1], the European Union supports the creation of a sustainable platform that connects cancer research across Member States. A workshop hosted in Heidelberg gathered European cancer experts to identify ongoing initiatives that may contribute to building this platform and discuss the governance and long-term evolution of a European Federated Cancer Data Hub.
Early-Stage Chronic Kidney Disease and Related Health Care Spending
Authors: Naomi Sakoi, Yuichiro Mori, Yusuke Tsugawa, Junko Tanaka, Shingo Fukuma
Journal: JAMA Network Open (2024)

Importance The global burden of chronic kidney disease (CKD) is substantial and potentially leads to higher health care resource use. Objective To examine the association between early-stage CKD and health care spending and its changes over time in the general population. Design, Setting, and Participants Cohort study using nationwide health checkup and medical claims data in Japan. Participants included individuals aged 30 to 70 years with estimated glomerular filtration rates (eGFR) of 30 mL/min/1.73 m 2 or greater at the baseline screening in 2014. Data analyses were conducted from April 2021 to October 2023. Exposure The CKD stages at baseline, defined by the eGFR and proteinuria, were as follows: eGFR of 60 mL/min/1.73 m 2 or greater without proteinuria, eGFR of 60 mL/min/1.73 m 2 or greater with proteinuria, eGFR of 30 to 59 mL/min/1.73 m 2 without proteinuria, and eGFR of 30 to 59 mL/min/1.73 m 2 with proteinuria. Main Outcome and Measures The primary outcome was excess health care spending, defined as the absolute difference in health care spending according to the baseline CKD stages (reference group: eGFR ≥60 mL/min/1.73 m 2 without proteinuria) in the baseline year (2014) and in the following 5 years (2015 to 2019). Results Of the 79 988 participants who underwent a health checkup (mean [SD] age, 47.0 [9.4] years; 22 027 [27.5%] female), 2899 (3.6%) had an eGFR of 60 mL/min/1.73 m 2 or greater with proteinuria, 1116 (1.4%) had an eGFR of 30 to 59 mL/min/1.73 m 2 without proteinuria, and 253 (0.3%) had an eGFR of 30 to 59 mL/min/1.73 m 2 with proteinuria. At baseline, the presence of proteinuria and an eGFR less than 60 mL/min/1.73 m 2 were associated with greater excess health care spending (adjusted difference, $178; 99% CI, $6-$350 for proteinuria; $608; 99% CI, $233-$983 for an eGFR of 30-59 mL/min/1.73 m 2 ; and $1254; 99% CI, $134-$2373 for their combination). The study consistently found excess health care spending over the following 5 examined years. Conclusions and Relevance In this cohort study of nationwide health checkup and medical claims data in Japan, early-stage CKD was associated with excess health care spending over the 5 examined years, and the association was more pronounced with a more advanced disease stage.
Mediating Factors in the Association of Maternal Educational Level With Pregnancy Outcomes
Authors: Tormod Rogne, Dipender Gill, Zeyan Liew, Xiaoting Shi, Vilde Hatlevoll Stensrud, Tom Ivar Lund Nilsen, Stephen Burgess
Journal: JAMA Network Open (2024)

Lower educational attainment is associated with increased risk of adverse pregnancy outcomes, but it is unclear which pathways mediate this association.
Incorporating metabolic activity, taxonomy and community structure to improve microbiome-based predictive models for host phenotype prediction
Authors: Mahsa Monshizadeh, Yuzhen Ye
Journal: Gut Microbes (2024)

We developed MicroKPNN, a prior-knowledge guided interpretable neural network for microbiome-based human host phenotype prediction. The prior knowledge used in MicroKPNN includes the metabolic activities of different bacterial species, phylogenetic relationships, and bacterial community structure, all in a shallow neural network. Application of MicroKPNN to seven gut microbiome datasets (involving five different human diseases including inflammatory bowel disease, type 2 diabetes, liver cirrhosis, colorectal cancer, and obesity) shows that incorporation of the prior knowledge helped improve the microbiome-based host phenotype prediction. MicroKPNN outperformed fully connected neural network-based approaches in all seven cases, with the most improvement of accuracy in the prediction of type 2 diabetes. MicroKPNN outperformed a recently developed deep-learning based approach DeepMicro, which selects the best combination of autoencoder and machine learning approach to make predictions, in all of the seven cases. Importantly, we showed that MicroKPNN provides a way for interpretation of the predictive models. Using importance scores estimated for the hidden nodes, MicroKPNN could provide explanations for prior research findings by highlighting the roles of specific microbiome components in phenotype predictions. In addition, it may suggest potential future research directions for studying the impacts of microbiome on host health and diseases. MicroKPNN is publicly available at https://github.com/mgtools/MicroKPNN.
Current evidence on the efficacy of mental health smartphone apps for symptoms of depression and anxiety. A meta‐analysis of 176 randomized controlled trials
Authors: Jake Linardon, John Torous, Joseph Firth, Pim Cuijpers, Mariel Messer, Matthew Fuller‐Tyszkiewicz
Journal: World Psychiatry (2024)

The mental health care available for depression and anxiety has recently undergone a major technological revolution, with growing interest towards the potential of smartphone apps as a scalable tool to treat these conditions. Since the last comprehensive meta‐analysis in 2019 established positive yet variable effects of apps on depressive and anxiety symptoms, more than 100 new randomized controlled trials (RCTs) have been carried out. We conducted an updated meta‐analysis with the objectives of providing more precise estimates of effects, quantifying generalizability from this evidence base, and understanding whether major app and trial characteristics moderate effect sizes. We included 176 RCTs that aimed to treat depressive or anxiety symptoms. Apps had overall significant although small effects on symptoms of depression (N=33,567, g=0.28, p&lt;0.001; number needed to treat, NNT=11.5) and generalized anxiety (N=22,394, g=0.26, p&lt;0.001, NNT=12.4) as compared to control groups. These effects were robust at different follow‐ups and after removing small sample and higher risk of bias trials. There was less variability in outcome scores at post‐test in app compared to control conditions (ratio of variance, RoV=–0.14, 95% CI: –0.24 to –0.05 for depressive symptoms; RoV=–0.21, 95% CI: –0.31 to –0.12 for generalized anxiety symptoms). Effect sizes for depression were significantly larger when apps incorporated cognitive behavioral therapy (CBT) features or included chatbot technology. Effect sizes for anxiety were significantly larger when trials had generalized anxiety as a primary target and administered a CBT app or an app with mood monitoring features. We found evidence of moderate effects of apps on social anxiety (g=0.52) and obsessive‐compulsive (g=0.51) symptoms, a small effect on post‐traumatic stress symptoms (g=0.12), a large effect on acrophobia symptoms (g=0.90), and a non‐significant negative effect on panic symptoms (g=–0.12), although these results should be considered with caution, because most trials had high risk of bias and were based on small sample sizes. We conclude that apps have overall small but significant effects on symptoms of depression and generalized anxiety, and that specific features of apps – such as CBT or mood monitoring features and chatbot technology – are associated with larger effect sizes.
Letter to the Editor: Concerns regarding the use of fatty liver index in studies of lean NAFLD
Authors: Frhaan M. Zahrawi, Wajahat Z. Mehal
Journal: Hepatology (2024)

To the editor, I am writing to draw attention to a methodological concern in the paper by Nabi et al.1 The authors utilize the Fatty Liver Index (FLI) as a tool to diagnose NAFLD. The FLI incorporates body mass index, waist circumference, GGT, and triglycerides. The authors then segregate individuals with low body mass index as lean NAFLD. In the lean NAFLD population, this will unintentionally select individuals with elevated GGT, triglycerides, or both. Individuals with low body mass index and NAFLD without elevations in GGT or triglycerides will not make the cutoff of the FLI to make a diagnosis of NAFLD (obese individuals with normal GGT can meet the FLI cutoff). The study excludes lean NAFLD with normal GGT, whereas obese NAFLD with normal and elevated GGT are included. This would be expected to result in a lean NAFLD population with a higher degree of liver fibrosis due to the known association of elevated GGT with liver fibrosis.2 The findings of this study are therefore likely representative of lean NAFLD with high GGT and not all lean NAFLD.
Goals and benefits in topical treatment for psoriasis: development and pilot validation of a patient-reported outcomes tool, the Patient Benefit Index for Topical Treatment (PBI-TOP)
Authors: Christine Blome, Lennart Hülswitt, Anna Meineke, Matthias Augustin, Frenz Ohm, Judith Rusch, Toni Maria Janke
Journal: British Journal of Dermatology (2024)

Abstract Background Topical agents are an essential component of psoriasis therapy. Objectives To develop a new version of the patient-reported Patient Benefit Index assessing the importance and achievement of treatment goals in topical psoriasis therapy in adult patients (PBI-TOP). Methods Through semi-structured interviews, focus groups and free-text questionnaires, patients reported their needs in topical treatment. Based on qualitative content analysis, items were developed by a consensus group and were refined in cognitive debriefing interviews. A pilot validation assessed the PBI-TOP and convergent criteria [Dermatology Life Quality Index (DLQI); Psoriasis Area and Severity Index (PASI); affected Body Surface Area (BSA)]. Results Thirty patients (26–72 years, mean 47; 60% male) reported various treatment goals relating to the themes ‘effectiveness’ and ‘characteristics of the preparation’. Twenty patients took part in cognitive debriefings (22–84 years, mean 50.6, 50% male). There were 154 patients who participated in the pilot validation (18–85 years, mean 46.9, 63.6% male). An importance-weighted total score on overall effectiveness and three subscales based on exploratory factor analysis were defined: effectiveness on symptoms, effectiveness on quality of life (QoL), and characteristics of the preparation. All scores showed excellent internal consistency (α &amp;gt; 0.9). The global effectiveness score correlated significantly with DLQI (r = –0.41), PASI (r = –0.32) and BSA (r = –0.22). The effectiveness subscales (symptoms; QoL) correlated significantly with DLQI (r = –0.41; –0.32) and PASI (r = –0.27; –0.33). The score on characteristics of the preparation correlated significantly with the DLQI (r = –0.34). Conclusions The PBI-TOP showed good feasibility and favourable psychometric characteristics in this pilot validation.
Is It Time to Incorporate Liquid Biopsy into High-Risk Cancer Surveillance Protocols in Li–Fraumeni Syndrome?
Authors: Alicia Latham, Suzanne P. MacFarland, Michael F. Walsh, Kara N. Maxwell, Zsofia K. Stadler
Journal: Cancer Discovery (2024)

Summary: In the first prospective study evaluating circulating tumor DNA (ctDNA) for early cancer detection, Wong, Luo, and colleauges demonstrate the feasibility of liquid biopsy as an augmentation to current surveillance protocols for patients with Li–Fraumeni syndrome, an inherited cancer predisposition associated with high cancer risk in both pediatric and adult populations. Though additional clinical validation in larger cohorts is needed, this research highlights that a multimodal approach is likely necessary to improve the sensitivity of liquid biopsy assays for early cancer detection. See related article by Wong, Lou et al., p. 104 (9).
Bispecific T-cell Engagers in Metastatic Castration-Resistant Prostate Cancer
Authors: Chadi Hage Chehade, Georges Gebrael, Neeraj Agarwal
Journal: Cancer Discovery (2024)

Summary: To date, immune targeting agents have provided limited benefits in patients with metastatic prostate cancer. Bispecific T-cell engagers, especially targeting STEAP1, have shown encouraging results in preclinical and phase I studies and thus represent a novel and promising treatment option in this setting. See related article by Nolan-Stevaux et al., p. 90 (7). See related article by Kelly et al., p. 76 (8).
NADPH Oxidase‐Like Nanozyme for High‐Efficiency Tumor Therapy Through Increasing Glutathione Consumption and Blocking Glutathione Regeneration
Authors: Di Han, Binbin Ding, Pan Zheng, Meng Yuan, Yulong Bian, Hao Chen, Meifang Wang, Mengyu Chang, Abdulaziz A. Al Kheraif, Ping'an Ma, Jun Lin
Journal: Advanced Healthcare Materials (2024)

Abstract To counteract the high level of reactive oxygen species (ROS) caused by rapid growth, tumor cells resist oxidative stress by accelerating the production and regeneration of intracellular glutathione (GSH). Numerous studies focus on the consumption of GSH, but the regeneration of GSH will enhance the reduction level of tumor cells to resist oxidative stress. Therefore, inhibiting the regeneration of GSH; while, consuming GSH is of great significance for breaking the redox balance of tumor cells. Herein, a simple termed MnO x ‐coated Au (AMO) nanoflower, as a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) nanoenzyme, is reported for efficient tumor therapy. Au nanoparticles exhibit the capability to catalyze the oxidation of NADPH, hindering GSH regeneration; while, concurrently functioning as a photothermal agent. During the process of eliminating intracellular GSH, MnO x releases Mn 2+ that subsequently engages in Fenton‐like reactions, ultimately facilitating the implementation of chemodynamic therapy (CDT). Overall, this NOX enzyme‐based nanoplatform enhances ROS generation and disrupts the state of reduction equilibrium, inducing apoptosis and ferroptosis by blocking GSH regeneration and increasing GSH consumption, thereby achieving collaborative treatments involving photothermal therapy (PTT), CDT, and catalytic therapy. This research contributes to NADPH and GSH targeted tumor therapy and showcases the potential of nanozymes.
How should psychotherapy proceed when adjoined with psychedelics?
Authors: Marc J. Weintraub, David J. Miklowitz
Journal: World Psychiatry (2024)

one year 1 .In conclusion, our re-analysis using the IPCW Kaplan-Meier method shows a much higher cumulative remission rate (i.e., 87.5% within a year after the initiation of treatment) than the 67% reported in the original STAR*D paper.This promising finding provides an opportunity to revisit the therapeutic potential of currently available treatment options for MDD, and underscores the relevance of employing sequential treatments until remission is achieved.
Covid-19 has cut UK life expectancy by around half a year, data suggest
Authors: Adrian O’Dowd
Journal: BMJ (2024)

Covid-19 has cut UK life expectancy by around half a year, data suggest Adrian O'DowdLife expectancy in the UK seems to have reduced by around half a year per person, falling to levels last seen in 2010, partly because of the covid-19 pandemic, new data suggest.
ErbB3 Governs Endothelial Dysfunction in Hypoxia-Induced Pulmonary Hypertension
Authors: Jin-Song Bian, Jingyu Chen, Junting Zhang, Jianxin Tan, Yuan Chen, Xusheng Yang, Yiying Li, Lin Deng, Rongchang Chen, Xiaowei Nie
Journal: Circulation (2024)

BACKGROUND: Pulmonary hypertension, characterized by vascular remodeling, currently lacks curative therapeutic options. The dysfunction of pulmonary artery endothelial cells plays a pivotal role in the initiation and progression of pulmonary hypertension (PH). ErbB3 (human epidermal growth factor receptor 3), also recognized as HER3, is a member of the ErbB family of receptor tyrosine kinases. METHODS: Microarray, immunofluorescence, and Western blotting analyses were conducted to investigate the pathological role of ErbB3. Blood samples were collected for biomarker examination from healthy donors or patients with hypoxic PH. The pathological functions of ErbB3 were further validated in rodents subjected to chronic hypoxia- and Sugen-induced PH, with or without adeno-associated virus-mediated ErbB3 overexpression, systemic deletion, or endothelial cell–specific ErbB3 knockdown. Primary human pulmonary artery endothelial cells and pulmonary artery smooth muscle cells were used to elucidate the underlying mechanisms. RESULTS: ErbB3 exhibited significant upregulation in the serum, lungs, distal pulmonary arteries, and pulmonary artery endothelial cells isolated from patients with PH compared with those from healthy donors. ErbB3 overexpression stimulated hypoxia-induced endothelial cell proliferation, exacerbated pulmonary artery remodeling, elevated systolic pressure in the right ventricle, and promoted right ventricular hypertrophy in murine models of PH. Conversely, systemic deletion or endothelial cell–specific knockout of ErbB3 yielded opposite effects. Coimmunoprecipitation and proteomic analysis identified YB-1 (Y-box binding protein 1) as a downstream target of ErbB3. ErbB3 induced nuclear translocation of YB-1 and subsequently promoted hypoxia-inducible factor 1/2α transcription. A positive loop involving ErbB3-periostin-hypoxia–inducible factor 1/2α was identified to mediate the progressive development of this disease. MM-121, a human anti-ErbB3 monoclonal antibody, exhibited both preventive and therapeutic effects against hypoxia-induced PH. CONCLUSIONS: Our study reveals, for the first time, that ErbB3 serves as a novel biomarker and a promising target for the treatment of PH.
Family Physician–to–Hospital Specialist Electronic Consultation and Access to Hospital Care
Authors: Ken M. M. Peeters, Loïs A. M. Reichel, Dennis M. J. Muris, Jochen W. L. Cals
Journal: JAMA Network Open (2024)

Globally, health care systems face challenges in managing health care costs while maintaining access to hospital care, quality of care, and a good work balance for caregivers. Electronic consultations (e-consultations)-defined as asynchronous, consultative communication between family physicians and hospital specialists-may offer advantages to face these challenges.
Analysis of a Medication Safety Intervention in the Pediatric Emergency Department
Authors: Margaret E. Samuels-Kalow, Randall Tassone, William Manning, Rebecca Cash, Laura Davila-Parrilla, Bryan D. Hayes, Stephen Porter, Carlos A. Camargo
Journal: JAMA Network Open (2024)

Importance Strategies to reduce medication dosing errors are crucial for improving outcomes. The Medication Education for Dosing Safety (MEDS) intervention, consisting of a simplified handout, dosing syringe, dose demonstration and teach-back, was shown to be effective in the emergency department (ED), but optimal intervention strategies to move it into clinical practice remain to be described. Objective To describe implementation of MEDS in routine clinical practice and associated outcomes. Design, Setting, and Participants This mixed-methods interrupted time series study of MEDS was conducted April 2021 to December 2022 in an academic pediatric ED using a hybrid type 1 design. Parents and guardians of children aged 90 days to 11.9 years who were discharged with acetaminophen, ibuprofen, or both were eligible for inclusion in the quantitative portion. Clinicians from a diversity of role groups (attending physician, resident, and nurse) were eligible for the qualitative portion. Exposures The study was conducted in 5 stages (baseline, intervention 1, washout, intervention 2, and sustainability phases). The 2 intervention phases taught clinical staff the MEDS intervention using different implementation strategies. During the intervention 1 phase, in-depth interviews were conducted until thematic saturation was reached; results were analyzed using thematic analysis. Interviews informed intervention 2 phase interventions. Main Outcomes and Measures The primary outcome was any error (defined as dosing or frequency error) at a 48- to 72-hour follow-up phone call. Results There were 256 participants (median [IQR] child age, 1.7 [3.0-7.0] years; median [IQR] parent and guardian age, 36.0 [31.0-41.0] years; 200 females among parents and guardians [78.1%]) who consented and completed follow-up. At baseline, 44 of 68 participants (64.7%) made an error compared with 34 of 65 participants (52.3%) during intervention 1, 31 of 63 participants (49.X%) during intervention 2, and 34 of 60 participants (57.X%) during sustainability. After adjustment for language and health literacy, the adjusted odds ratio for error during the combined intervention phases was 0.52 (95% CI, 0.28-0.97) compared with baseline. Conclusions and Relevance This study found that both MEDS intervention phases were associated with decreased risk of error and that some improvement was sustained without active intervention. These findings suggest that attempts to develop simplified, brief interventions may be associated with improved medication safety for children after discharge from the ED.