bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of the enhanced adult DIVA score in an emergency department: A prospective observational study
Authors: Petta Domenica , Longobucco Yari , Magi Camilla Elena , El Aoufy Khadija , Forciniti Carolina , Lucchini Alberto , Iovino Paolo , Amato Carla , Iozzo Pasquale , Rasero Laura , Bambi Stefano
Published: January 2025

Background:

Short peripheral catheter (SPC) placement is a routine invasive procedure in clinical settings that is crucial for administering fluids, medications, or blood components. Approximately 11% of adult patients arriving at the Emergency Department (ED) experience difficulties with intravenous access (DIVA), necessitating advanced techniques for successful placement. The Enhanced Adult DIVA (EA-DIVA) score serves as a validated tool to promptly identify patients with DIVA. This study aimed to determine the prevalence of DIVA in the ED by using the EA-DIVA scale, evaluate the time required for venous cannulation in patients with and without DIVA, and establish EA-DIVA score thresholds for the adoption of ultrasound-guided techniques.

Methods:

This prospective observational study was conducted from May 2023 to January 2024 at the ED of Empoli Hospital, Italy. This study focused on adult patients requiring SPC placement. The nursing staff at the ED performed SPC placements using standard techniques according to clinical protocols.

Results:

Among 1280 patients, 29.22% required more than one attempt at cannulation independently from their EA-DIVA score, with 12.58% scoring an EA-DIVA of 8 or higher. The time and attempts needed for successful cannulation increased with higher EA-DIVA scores, and ultrasound-guided techniques were more time-consuming but beneficial for these patients. An optimal threshold of 6 on the EA-DIVA scale balanced high sensitivity (96.52%) and specificity (81.37%) for identifying patients who would benefit from ultrasound guidance, minimizing failed attempts and optimizing resource use.

Conclusion:

The EA-DIVA scale, originally validated in a preoperative setting, was effectively implemented for the first time in the ED. This study established a lower cutoff score for expert intervention utilizing ultrasound guidance compared with previous applications of the EA-DIVA scale. Further validation across diverse clinical settings and among healthcare providers with varying expertise in vascular access is necessary to confirm these findings and broaden their applicability.
What is authoritarianism? A justificatory account
Authors: Motchoulski Alexander
Published: January 2025

Authoritarian social movements and governments have brought about some of the greatest horrors in human history. Naturally, research in the social sciences has aimed at developing an understanding of authoritarianism. Certain kinds of authoritarian things, like personalities or governments, are better understood as a consequence, but a general concept of authoritarianism remains absent. I develop a general account of the concept of political authoritarianism which I call justificatory authoritarianism. According to this view, authoritarianism is a justification of the imposition of political power over others by appeal to a prospect for considerable collective benefit, and that justification serves to suspend or suppress constraints on the exercise of political power.
Translanguaging in transnational digital Arabic heritage language education
Authors: Amro Lana , Iversen Jonas Yassin
Published: January 2025

Due to globalisation and migration, the Arabic-speaking population in Europe has rapidly increased over the past few decades. To maintain the Arabic language, children across Europe attend community-based heritage language education. With the development of new communication technologies, digital Arabic heritage language education is gaining popularity. Although previous research from community-based Arabic heritage language education in physical educational settings indicate that some translanguaging is taking place, little is known about how the digital setting of online Arabic heritage language teaching influences language practices and pedagogies. Hence, this article investigates the following research question: How does a heritage language teacher of Arabic use translanguaging as a pedagogy in digital heritage language education? To answer this question, a digital linguistic ethnography over 7 months was conducted, involving digital classroom observations, interviews with one teacher and five students and the collection of documents. Adopting a translinguistic perspective, the analysis shows how the teacher capitalised on students’ translingual resources to create a safe space, challenging language hierarchies and supporting the development of literacy skills in Modern Standard Arabic. Based on these findings, we discuss how the online teaching setting contributes to shaping the language practices of the digital classroom.
Credible Claims: The Effect of Committee Positioning on Congressional Credit Claiming
Authors: McLaughlin Peter T. , Barron Nathan T.
Published: January 2025

Members of Congress routinely seek to improve their institutional position to increase their influence over policy outcomes. Prominent among those policy outcomes is the distribution of federal spending projects, where members can simultaneously secure local particularistic spending and its consequential electoral benefits. While institutional position facilitates the receipt of these policy goods, it is less clear whether representatives’ position facilitates the receipt of the associated electoral benefits. We test whether a representative’s signaling of policy influence through references to committee positioning increases the effectiveness of credit claiming for particularistic spending. Using a survey experiment, we measure how respondents change their approval and effectiveness ratings for a member of Congress when presented with different versions of real-world credit claiming press releases. Overall, we find that signaling influence vis-à-vis committee positioning has an undetectable effect on the effectiveness of credit claiming. This research highlights an important challenge faced by members of Congress in publicizing their roles in favorable policy actions.
Patients’ views and experiences of the first community pharmacy-based medication therapy management clinic in the Middle East and North Africa (MENA): A qualitative study
Authors: Hadi Muhammad Abdul , Albabtain Basmah , Bawazeer Ghada , Paudyal Vibhu , Cheema Ejaz , Alqahtani Abdulaziz , Bahatheq Ahmed
Published: January 2025

Objective:

This qualitative study aimed to describe patients’ experiences of a community pharmacy (CP)–based medication therapy management program (MTM).

Methods:

Qualitative, semistructured, face-to-face interviews were conducted with a purposive sample of patients with uncontrolled diabetes who received care at a CP-based MTM clinic. Interviews were conducted in the MTM clinic of Health Kingdom CP in Riyadh City, Kingdom of Saudi Arabia by a research pharmacist using an interview guide. Data collection was continued until data saturation. All interviews were audiorecorded, transcribed verbatim, and analyzed thematically.

Key findings:

A total of 16 patients, of whom more than half were male, were interviewed between October 2021 and March 2022. The mean ± standard deviation age of the patients was 52.0 ± 8.9 years, whereas the mean number of years since the first diagnosis of diabetes was 11.2 ± 7.3 years. Three main themes emerged from the interviews: perceived benefits and outcomes of the program, factors driving positive patient experiences, and challenges and recommendations for enhancing MTM service. Generally, patients were satisfied with the quality of advanced care that they received at the clinic and recognized the importance of the pharmacist’s role. Furthermore, the program was perceived by patients as an opportunity to transition to a healthier lifestyle. Patients also highlighted a few barriers related to follow-up, such as accessibility, and issues with the service, such as long waiting times. Finally, there were some suggestions for patient improvement. These include expanding the clinic space, initiating educational and follow-up messages, and cooperating with other specialists as required.

Conclusions:

Patients received the MTM program very positively with noticeable health benefits. Barriers to effective follow-up and care should be addressed before implementing this service in wider community pharmacies in Saudi Arabia and beyond.
Military influences on the evolution of clinical trials throughout history
Authors: Malshy Kamil , Steinmetz Alexis , Yuen Kit , Bandari Jathin , Rabinowitz Ronald
Published: January 2025

Clinical trials of drugs, procedures, and other therapies play a crucial role in advancing medical science by evaluating the safety, efficacy, and optimal use of medical interventions. The design and implementation of these trials have evolved significantly over time, reflecting advancements in medicine, ethics, and methodology. Early historical examples, such as King Nebuchadnezzar II’s and his captives’ dietary experiment and Ambroise Paré’s treatment of gunshot wounds, laid some foundational principles of trial design. The momentum of clinical trial development increased notably with James Lind’s 1747 trial for scurvy and continued to progress during World War I with innovations in blood transfusion techniques. World War II (WWII) marked a pivotal moment with breakthroughs in oncology, including the development of the first modern chemotherapeutic agents derived from mustard gas and the introduction of the randomized controlled trial, credited to British epidemiologist Austin Bradford Hill, which revolutionized trial design. More recent conflicts, such as those in Vietnam, Iraq, and Afghanistan, have driven advancements in trauma care, heroin addiction treatment, and hemorrhage management. In response to historical abuses committed by the Nazis during WWII, the evolution of clinical trials has increasingly emphasized ethical standards, particularly informed consent, starting with the Doctors’ Trial and the Nuremberg Code. This article discusses how military needs and wartime innovations have shaped modern clinical research, highlighting the interplay between military imperatives and medical progress. Ultimately, clinical trials play an essential role in advancing medical science and improving patient outcomes.
Exploring the value of queer archives in queer criminology: Interrogating narratives of incarceration and offending
Authors: Ball Matthew
Published: January 2025

This article explores the potential of queer archival material to disrupt and nuance dominant criminological narratives on a range of criminal justice-related issues in the lives of queer people. It does so in two contexts: regarding narratives focused on queer experiences of incarceration; and narratives focused on queer offending. Research on queer experiences of incarceration suggests that queer people are particularly at risk of homophobic and transphobic abuse and assault in prison, and that they must repress their sexuality and gender in prison. And research on queer pathways to offending highlights the interconnections between criminal justice contact, offending, and forms of inequality that characterise queer lives, positioning queer offending as largely driven by those inequalities and their resulting harms. By engaging with a unique collection of queer archival materials, specifically the correspondence of incarcerated queer people, this article queers those dominant narratives. It does so by paying particular attention to the experiences of the only transgender correspondent in this collection. That person’s experiences very clearly illustrate the complex intersections between queer lives and criminal justice and the subsequent need to queer the dominant narratives in this space. Additionally, their experiences illuminate how archival materials in queer criminology foster the emergence of complexity and nuance in our analyses and offer new directions for queer political reform and activism in crime and justice contexts.
Patient perspective: Is intensive screening of women at high risk of breast cancer evidence-based medicine or déjà vu?
Authors: Fairman Kathleen A
Published: January 2025

In 2023, a breast cancer risk assessment and a subsequent positive test for the BRCA-2 genetic mutation brought me to the uncomfortable intersection of a longstanding career as an advocate for high-quality medical evidence to support shared patient-provider decision making and a new role as a high-risk patient. My search for studies of available risk-management options revealed that the most commonly recommended approach for women with a ⩾20% lifetime breast cancer risk, intensive screening including annual mammography and/or magnetic resonance imaging beginning at age 25–40 years, was supported only by cancer-detection statistics, with almost no evidence on patient-centered outcomes—mortality, physical and psychological morbidity, or quality of life—compared with standard screening or a surgical alternative, bilateral risk-reducing mastectomy. In this commentary, I explore parallels between the use of the intensive screening protocol and another longstanding women’s health recommendation based on limited evidence, the use of hormone therapy (HT) for postmenopausal chronic disease prevention, which was sharply curtailed after the publication of the groundbreaking Women’s Health Initiative trial in 2002. These declines in HT utilization were followed by marked decreases in breast cancer incidence, providing a compelling lesson on the critical importance of a solid evidentiary basis for women’s health decisions. Known harms accompanying the benefits of breast screening—overdiagnosis, psychological effects, and mammography-associated radiation-exposure risks—make empirical measurement of patient-centered outcomes essential. Yet, published research on intensive screening of women at high breast cancer risk has largely ignored these outcomes, leaving patients, providers, and guideline developers lacking the evidence needed for best practice. Outcomes research is both feasible and urgently needed to inform care decisions and health policy for this patient population.
Percutaneous treatment of de Quervain’s disease using Sono-Instruments®: A feasibility study
Authors: Moungondo Fabian , Boushnak Mohammad O. , Feipel Véronique
Published: January 2025

We investigated the safety and effectiveness of percutaneous release for de Quervain’s disease using Sono-Instruments® in cadaveric specimens. The mean procedure duration was 4 minutes, and complete release was achieved in all specimens.
Sleep and breathing in children with Joubert syndrome and a review of other rare congenital hindbrain malformations
Authors: Ju-Wang Jia-Der , Dempsey Jennifer C. , Zhang Cristian , Doherty Daniel , Witmans Manisha , Tablizo Mary Anne , Chen Maida Lynn
Published: January 2025

Background:

Joubert syndrome (JS) is an autosomal recessive disorder with a distinctive mid-hindbrain malformation known as the “molar tooth sign” which involves the breathing control center and its connections with other structures. Literature has reported significant respiratory abnormalities which included hyperpnea interspersed with apneic episodes during wakefulness. Larger-scale studies looking at polysomnographic findings or subjective reports of sleep problems in this population have not yet been published.

Objectives:

The primary objectives were (1) compare a large group of children with JS and their unaffected siblings for caregiver-reported sleep difficulties. Secondary objectives were (1) present new polysomnography (PSG) data on our JS cohort; (2) review sleep disordered breathing (SDB) in other rare congenital hindbrain anatomic abnormalities.

Design:

We conducted a cross-sectional study on a cohort of 109 families affected by JS.

Methods:

Pediatric Sleep Questionnaire (PSQ) and the Children’s Sleep Habits Questionnaire (CSHQ) along with general medical health information focused on respiratory and sleep problems were mailed to all patients and families. Caregivers were asked to complete the survey for both children with JS and unaffected siblings, if any. Baseline diagnostic PSG was retrospectively reviewed for those with available studies, and the sleep parameters were compared to a referent cohort.

Results:

Study participants with JS were older than their unaffected siblings ( p = 0.02). Genetic mutations were available for 41 out of 118 individuals, with the most common mutation being MKS3 (31.4%). Patients with JS had higher scores in the PSQ compared to their unaffected siblings ( p < 0.001). PSG data showed severe SDB with apnea-hypopnea index (AHI) of 23 ± 15 events/h in patients with JS. Events were primarily obstructive (obstructive AHI 18 ± 15 events/h vs central AHI 4 ± 4 events/h). Abnormal sleep architecture with increased arousal indices, decreased efficiency, and more time awake and in light sleep or wakefulness when compared to the referent data.

Conclusion:

SDB is common and severe in patients with JS, and the significantly greater obstructive component reported in this cohort makes it necessary to perform complete PSG studies to address or prevent clinical manifestations in this at-risk population. PSQ could represent a viable method to screen for SDB in JS.
Impact of Post-Stroke Post-Traumatic Stress Disorder
Authors: Renati Swetha , Raju Sanita , Makarova Alena , Hairston Marla , Beba Abadal Kanita , Bozeman Andrea , Chen Henian , Cen Weiliang , Rose David Z. , Burgin W. Scott
Published: January 2025

Introduction

Post-Traumatic Stress Disorder (PTSD) is associated with exposure to traumatic events, especially in the military setting. However, patients who experience stroke may develop anxiety about their stroke event and may re-experience transient neurological symptoms as a result. A significant portion develop the persistent and disabling symptoms of PTSD.

Methods

At the University of South Florida, we conducted a single-center, IRB-approved, observational pilot study of 20 adult patients who were diagnosed with stroke or transient ischemic attack (TIA) in the previous 31 days to 1 year. Patients completed the post-traumatic stress disorder checklist-5 (PCL-5), Patient Health Questionnaire-9 (PHQ-9), Stroke specific Quality of Life Scale (SS-QOL-12), Modified Rankin Scale of disability (mRS), and National Institutes of Health Stroke Scale (NIHSS) and provided blood and saliva samples.

Results

All 20 subjects completed the PCL-5 and 19 subjects completed the follow up scales. Seven patients (35%) were found to have Post-Stroke Post-Traumatic Stress Disorder (PS-PTSD). Higher PCL-5 scores were significantly correlated with lower SS-QOL scores indicating worse quality of life (r = −0.709, P = .001) and higher PHQ-9 scores representing symptoms of depression (r = 0.727, P < 0.001).

Conclusion

Post-Stroke Post-Traumatic Stress Disorder (PS-PTSD) is prevalent after stroke and TIA with patients experiencing concurrent depressive symptoms, correlating with a worsened quality of life.
Long-Term Effectiveness of Dupilumab in Severe Uncontrolled Chronic Rhinosinusitis with Nasal Polyps: A Multicenter Retrospective Study
Authors: Russo Paolo , Bassano Edoardo , Menichetti Marcella , Lucidi Daniela , Minniti Rosa Maria , Cigarini Elisa , Menabue Silvia , Marchioni Daniele , Perano Daniele , Ghidini Angelo
Published: January 2025

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex immunological disease associated with significant morbidity and reduced health-related quality of life. Dupilumab is an anti-T2-inflammatory biological drug registered for chronic rhinosinusitis with nasal polyps, indicated by integrated care pathways when optimal medico-surgical treatment yields insufficient control of sinonasal symptoms.

Objective

The purpose of this study was to confirm the long-term efficacy of dupilumab in the treatment of severe uncontrolled CRSwNP.

Methods

Multicentric data collection of patients with severe uncontrolled CRSwNP treated with Dupilumab was retrospectively performed. Mixed Model Anova test was used to evaluate the effect of the biological therapy in the improvement of nasal polyp score and quality of life measured with Sinonasal Outcome Test-22 (SNOT-22) and visual analog scale (VAS) scores.

Results

The study showed a statistically significant and progressive improvement in the Nasal Polyp Score with a decrease from a median baseline value of 6 (IQR 5-6) to 0 (IQR 0-2) at 24 months. Furtherly, optimal results were found for SNOT-22 scores from baseline (62 ± 19) to 6 months (15± 11), with further variations on each successive timepoint remaining below the minimal clinically important difference. VAS scores of nasal obstruction, rhinorrhea, sleep disorders, and craniofacial pain, demonstrated consistent and significant improvements over time until one year of treatment, confirming substantial relief for the most pertinent symptoms of the condition

Conclusions

The results of this study show high therapeutic efficacy and safety of dupilumab for severe CRswNP particularly in the first 6-12 months, with sustained benefits up to 24 months.
The Significance of Fractional Exhaled Nitric Oxide, Fractional Nasal Exhaled Nitric Oxide and Lung Function Tests in Children with Moderate-to-Severe Allergic Rhinitis
Authors: Li Wanying , Jia Wanyu , Yi Xiaowen , Li Peng , Song Chunlan
Published: January 2025

Purpose

Fractional nasal exhaled NO (FnNO), fractional exhaled NO (FeNO) and lung function tests were performed in children with moderate-to-severe persistent allergic rhinitis (AR) to investigate the significance of the above indices in the assessment and diagnosis of children with AR.

Methods

A total of 135 children with persistent AR were selected and divided into moderate-to-severe and mild groups; serum total immunoglobulin E (IgE), peripheral blood eosinophil counts (EOS), FnNO, FeNO, and lung function tests were performed.

Results

Children in the moderate-to-severe group had increased levels of FnNO and FeNO and decreased levels of forced expiratory flow at 75% of forced vital capacity as a percentage of the predicted value (FEF75%) and maximum mid-term expiratory flow as a percentage of the predicted value (MMEF%) . IgE in children with AR was positively correlated with FeNO and FnNO and negatively correlated with FEF75% . EOS was positively correlated with FnNO. FeNO was negatively correlated with FEF75% and forced expiratory flow at 50% of forced vital capacity as a percentage of the predicted value (FEF50%). FnNO was negatively correlated with FEF75%, FEF50%, and MMEF%.

Conclusion

FnNO, FeNO, and pulmonary function tests may help assess disease severity and level of disease control in children with persistent AR.
Use of wood-based panels in engineered flooring: A bibliometric and systematic review
Authors: Martins Romulo Henrique , Felício Peres Duran Afonso José , Cabral Matheus Roberto , de Campos Cristiane Inácio , Fiorelli Juliano
Published: January 2025

Engineered wood flooring has increased in popularity since its introduction in the 1970’s. This is primarily due to its resistance and good appearance, similar to natural wood. This type of flooring can be made in solid-sawn timber (hardwood) or alternative materials such as plywood or particleboard. This work presents a systematic literature review on using wood-based panels as a support layer in engineered wood flooring. It outlines a profile of the publications through a bibliometric review. The review considered the entire spectrum of panels generally available for this type of application (particleboard, fiberboard, plywood, and veneer). This resulted in 26 articles selected from the Web of Science and Engineering Village databases. In this context, OSB panels (Oriented Strand Board) made of wood strands were highlighted in the articles as a possible alternative to sawn wood and plywood, mainly in terms of the dimensional stability of the floor. The moisture variation and its effects on the performance of floors is a cause for concern. Thus, the article presents a state-of-the-art analysis of the application of wood panels in the fabrication of engineered wood flooring, its main characteristics, and notes regarding gaps and future works.
Experiences of Patients and Families Living with Krabbe Disease
Authors: Koto Yuta , Yamashita Wakana , Kitamura Kumiko , Sakai Norio
Published: January 2025

The challenges faced by patients with Krabbe disease remain unelucidated. This study aimed to identify these challenges and facilitate the development of methods for assessing the quality of life. This qualitative descriptive study used in-person or online semistructured interviews from March to December 2022 using a qualitative content analysis approach. Data were collected from one patient each for the late infantile, juvenile, and adult types of Krabbe disease. In total, 249 codes were extracted from the verbatim transcripts and integrated into 40 subcategories and eight categories. The categories were integrated into three themes: the impact of symptoms on daily life, challenges for healthcare systems, and challenges faced by family members. Patients experienced physical symptoms, social life challenges, and medical care difficulties. Additionally, families felt burdened caring for these patients. In conclusion, support systems for patients and their families during treatment and in their living environments should be developed to aid in managing these challenges. Moreover, a comprehensive scale that accurately reflects the social challenges faced by these patients and their families is needed.
Patient and Family Experience: Targets for Improvements in Care and Communication in the ICU
Authors: LaGrotte Caitlin A. , Baldwin Caitlin , Hunter Krystal , Damuth Emily , Loperfido Nancy , Moosavi Tatheer , Parker Pearl , Puri Nitin
Published: January 2025

This process improvement project sought to further explore the experience of patients and family members within an intensive care unit (ICU) hospital setting to develop specific interventions that can be executed to provide better patient-centered outcome. We surveyed 103 family members using the satisfaction with care subscale of Family Satisfaction with the ICU survey (FS-ICU) (validated ICU experience survey). 103 patients also completed FS-ICU subscale with a modification to make it applicable to patients. Additional questions explored their interest in supportive services and factors contributing to distress with the goal of understanding the gaps in multidisciplinary care and supportive services. Overall, the findings of this project emphasize the importance of (1) understanding patients’ experience and satisfaction with care, in addition to families’, (2) gathering data with measurement tools that is specific enough to the care environment allowing for unique feedback and areas for improvement, and (3) identifying psychological needs and faith-based support to intervene on challenging experiences.
Evolution of a patient safety program in an academic medical center
Authors: Bishop Phyllis , Didion Lisa , Whitfield Candice , Henderson J Michael
Published: January 2025

Background

The Academic Medical Center earned a 1-Star CMS designation and received an F on the Leapfrog Safety Grade in 2015, which led to leadership setting Clinical Quality Improvement as the #1 Strategic Priority. This paper presents the evolution of a structured patient safety program as a component of this plan to direct and motivate employees to succeed in reducing patient harm.

Methods

Data-driven quality improvement using simple, timely, actionable data drillable scorecards available to all employees was the cornerstone of the above strategic priority. A comprehensive patient safety program was developed utilizing three phases: Error Prevention Training, Improved Event Reporting, and the Chasing Zero Harm initiative.

Results

Improvement was achieved in Culture of Safety Survey domains of overall safety, event reporting, nonpunitive response to errors, and hand-off communication. Patient safety indicators and hospital-acquired infections improved on the Medical Center's internal scorecard and public reported data by >60%. These resulted in improvement in Leapfrog Safety Score from an F in 2015 to a B in 2023, and increase from CMS 1-Star to 2-Star rank in 2023. Adverse event reports and review with follow up increased by 45% between 2018 and 2023. A Chasing Zero harm program was initiated following establishment of these steps.

Discussion

A successful patient safety program, predicated on high reliability, can successfully be built with leadership commitment, development of safety culture, and performance improvement.
Stroke Prevention in Hispanic Children with Sickle Cell Anemia: the SACRED trial
Authors: Nieves Rosa , Latham Teresa , Marte Nicolle Marie , Berges Morales Melissa , Sanchez Luisanna M. , Urcuyo Gabriela , Florencio Carla , González Guaschino Carla , DelVillar Paola , Chen Lin Sheena , Pierre Ramirez Daniel Alejandro , Reyes Paula , Marinez J Manuel , Matos Euladys , Jeste Neelum Dilip , Stuber Susan E , Schultz William H , Lane Adam , Mena Rafael , Ware Russell E.
Published: January 2025

Sickle cell anemia (SCA) is recognized globally, but little is known about affected Hispanic populations. In partnership with Dominican Republic, a Hispanic Caribbean Island with a large SCA population, a TCD screening program provided hydroxyurea to children with conditional velocities. Building local capacity, ten Dominican medical graduates were certified in TCD examinations and trained in hydroxyurea management. Stroke Avoidance for Children in REpública Dominicana trial (SACRED, NCT02769845) enrolled 283 children with average age 8.7±3.4 years and 130 (46%) females. At initial screening, treatment-naïve children with conditional velocities (170-199 cm/sec) were younger (6.6±2.7 versus 8.9±3.4 years, p=.0002) and more anemic (hemoglobin 7.4±0.8 versus 8.0±1.2 g/dL, p=.0046) than children with normal screening velocities (<170 cm/sec). Among 57 treatment-naïve children receiving six months of fixed-dose hydroxyurea at 20 mg/kg/day, average TCD velocities decreased 20 cm/sec and 61% became normal. Compared to fixed-dose hydroxyurea, dose escalation to maximum tolerated dose (MTD) led to fewer sickle-related events with incidence rate ratio 0.59, 95% Confidence Intervals 0.36-0.98, p=0.0420. At MTD, TCD benefits were sustained over 5 years, with 81% reverting to normal and average TCD velocity decrease of 27 cm/sec. Brain MRI documented substantial baseline parenchymal disease; during hydroxyurea treatment 10% developed new vasculopathy, plus one stroke and one death. SACRED documents a high burden of cerebrovascular disease among Hispanic children with SCA, but also demonstrates the feasibility of partnership to establish TCD screening programs, the utility of hydroxyurea to reduce TCD velocities and reduce stroke risk, and the sustained benefits of hydroxyurea dose escalation.
Phase I study of CD19 CAR T-cell therapy harboring a fully human scFv in CAR-naïve adult B-ALL patients
Authors: Gauthier Jordan , Liang Emily C. , Huang Jennifer J. , Kimble Erik Lesley , Hirayama Alexandre V. , Fiorenza Salvatore , Voutsinas Jenna M , Wu Qian (Vicky) , Jaeger-Ruckstuhl Carla A , Pender Barbara S. , Kirchmeier Delaney R. , Torkelson Aiko , Braathen Kristina , Basom Ryan , Shadman Mazyar , Kopmar Noam E. , Cassaday Ryan D. , Riddell Stanley R. , Maloney David G , Turtle Cameron J
Published: January 2025

CD19-directed chimeric antigen receptor-engineered (CD19 CAR) T-cell therapy elicits high response rates but fails to induce durable responses in most adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). In a previous clinical trial (NCT01865617), we observed anti-CAR immune responses associated with impaired in vivo CAR T-cell expansion after second infusions. Because these CD8+ T-cell responses were predominantly directed at peptides derived from the murine single chain variable fragment (scFv) in the CAR, we conducted a clinical trial investigating the safety and efficacy of CD19 CAR T-cells engineered with a CAR incorporating a fully human scFv (JCAR021) in adults with R/R B-ALL (NCT03103971). Twenty-three patients received lymphodepletion chemotherapy and JCAR021 infusion. Nineteen patients developed CRS (any grade, 83%; grade 2, 61%) and 12 developed neurotoxicity (52%; grade ≥3, 35%). The overall response and CR/CRi rates were 82% and 64%, respectively. We observed MRD-negative marrow responses in 82% of those with marrow disease and extramedullary responses by PET-CT in 79% (CR, 50%) of those with measurable FDG-avid disease. The median duration of remission (DOR) was 10 months with a 4-year DOR probability of 29%. Four patients underwent allo-HCT while in CR/CRi after JCAR021. Durable remissions were observed in patients with low marrow disease burden. In contrast, the DOR was limited in those with high marrow burden, highlighting a remaining critical need to identify new strategies to prolong remissions. We observed similar outcomes in CAR-naïve adult B-ALL patients receiving CD19 CAR T-cells expressing a fully human or murine scFv-containing CAR.
Predicting rifampicin resistance inM. tuberculosisusing machine learning informed by protein structural and chemical features
Authors: Lynch Charlotte I , Adlard Dylan , Fowler Philip W
Published: January 2025

Background

Rifampicin remains a key antibiotic in the treatment of tuberculosis. Despite advances in cataloguing resistance-associated variants (RAVs), novel and rare mutations in the relevent gene,rpoB, will be encountered in clinical samples, complicating the task of using genetics to predict whether a sample is resistant or not to rifampicin. We have trained a series of machine learning models with the aim of complementing genetics-based drug susceptibility testing.

Methods

We built a Test+Train dataset comprising 219 susceptible mutations and 46 RAVs. Features derived from the structure of the RNA polymerase or the change in chemistry introduced by the mutation were considered, however, only a few, notably the distance from the rifampicin binding site, were found to be predictive on their own. Due to the paucity of RAVs we used Monte Carlo cross-validation with 50 repeats to train four different machine learning models.

Results

All four models behaved similarly with sensitivities and specificities in the range 0.84–0.88 and 0.94–0.97 although we preferred the ensemble of Decision Tree models as they are easy to inspect and understand. We showed that measuring distances from molecular dynamics simulations did not improve performance.

Conclusions

It is possible to predict whether a mutation inrpoBconfers resistance to rifampicin using a machine learning model trained on a combination of structural, chemical and evolutionary features, however performance is moderate and training is complicated by the lack of data.
Effects of eHealth exercise on paediatric suppurative lung diseases: a systematic review and meta-analysis
Authors: Mavronasou Aspasia , Kortianou Eleni A. , Sapouna Vaia , Douros Konstantinos , Spinou Arietta
Published: January 2025

Background

Utilizing information and communication technologies through eHealth in exercise programs could support their delivery and improve clinical outcomes in children and adolescents with chronic suppurative lung diseases (CSLDs). This study aimed to systematically investigate the effects of eHealth exercise programs on clinical outcomes for this population.

Methods

Five databases were searched from inception to April 12, 2024. Two researchers independently screened the retrieved results and rated the methodological quality of the included studies using the revised Cochrane Risk of Bias tool for randomized trials and the Risk of Bias in Non-Randomized Studies – of Interventions tool. The quality of evidence was graded using the GRADE approach. A narrative synthesis of findings was performed, and a meta-analysis was conducted to evaluate the effects of eHealth exercise programs on clinical outcomes that had data from ≥2 studies.

Results

Seven studies used eHealth exercise programs through active video games (n=3), videoconferencing (n=3), and a digital spirometer (n=1) lasting from 3 to 12 weeks. Five studies had participants with cystic fibrosis (CF). Results showed a greater improvement in the 6-minute walk test following the intervention compared to the control group; pooled estimate mean difference [37.2 meters (95%CI: 7.91 to 66.48), p=0.013]. Pulmonary function, exercise capacity, balance, peripheral and respiratory muscle strength, and HRQoL were also improved. Still, most studies involved a considerable risk of bias.

Conclusions

eHealth exercise programs can improve clinical outcomes in children and adolescents with CF. Further research is needed for other pediatric populations with CSLDs and also for comparisons with conventional exercise programs.
Feasibility and inter-reporter variability of submaximal outcomes derived from cardiopulmonary exercise testing in people with advanced cystic fibrosis lung disease
Authors: Urquhart Don S , Jamieson Patrick , Burns Paul , Braun Julia , Hebestreit Helge , Radtke Thomas
Published: January 2025

Background

Cardiopulmonary exercise testing (CPET) provides prognostic information in people with advanced cystic fibrosis lung disease (pwACFLD). This project aimed to ascertain feasibility and inter-reporter variability in the identification of submaximal CPET outcomes for pwACFLD as potential predictors of prognosis where no peak exercise data are available.

Methods

We utilised data from an international retrospective multicentre study involving pwACFLD, for whom raw CPET data were available. Two experienced operators independently reviewed and analysed CPET tests with a focus on three pre-defined measures: oxygen uptake (V̇O2) at the anaerobic threshold (AT), the breathing reserve index at the AT (BRIAT), and the slope of the minute ventilation to carbon dioxide production ratio (V̇E/V̇CO2-slope). We calculated intra-class correlation coefficients (ICC) with their 95% confidence intervals (CI), and limits of agreement using the Bland-Altman method.

Results

The original cohort included 174 pwACFLD. Among those, raw CPET data were available for 101 individuals, of which 89 tests were of sufficient technical quality for submaximal analysis. In 72 out of 89 technically-acceptable tests (81%), the AT could be confidently identified by both operators. Furthermore, ICCs indicated good-to-excellent inter-reporter agreement for V̇O2at the AT [ICC (95% CI) 0.79 (0.62 to 0.88)], the V̇E/V̇CO2-slope [0.95, 0.93 to 0.97)], and BRIAT [0.76, 0.63 to 0.85].

Conclusions

Submaximal CPET data can be reliably obtained in most pwACFLD by trained CPET operators. Future studies may ascertain the prognostic value of submaximal CPET outcomes in pwACFLD.
Utility of Diaphragm Dome Height as a Marker of Operational Lung Volume Changes, Disease Burden and Exacerbations in Patients with Mild-to-Moderate COPD: An Observational Study Within the CanCOLD Cohort
Authors: Beydoun Sarah A. , Iorio Olivia C. , Genkin Daniel , Li Pei Z , Doiron Dany , Maltais François , Bourbeau Jean , Tan Wan , Sin Don D. , Aaron Shawn D. , Chapman Kenneth R. , Hernandez Paul , Marciniuk Darcy D. , O'Donnell Denis E. , Walker Brandie L. , Kirby Miranda , Ross Bryan A.
Published: January 2025

Background

Dynamic hyperinflation is central to dyspnoea, exercise limitation, and exacerbations in chronic obstructive pulmonary disease (COPD). While studied previously in moderate-severe COPD, the relevance of diaphragm dome height on clinically important outcomes has been under-investigated in mild-to-moderate COPD.

Methods

Canadian Cohort Obstructive Lung Disease participants with spirometry-confirmed COPD, symptom-limited incremental cardiopulmonary exercise testing, and computed tomography image data were included. Base-to-apex left and right diaphragm dome height (DDH) was automatically segmented, with increased height implying less flattening and thus less hyperinflation. Dynamic hyperinflation was defined as ≥150 mL reduction in inspiratory capacity (IC) from rest to peak-exercise. Cross-sectional linear regression models were fitted between left and right DDH (predictor variables) with peak IC (ICpeak), peak workload (Wpeak), FEV1, and CAT score (outcome variables), and in longitudinal (Anderson-Gill) models with “symptom-based” and “event-based” exacerbations. Results are reported as parameter estimates or hazard ratios with 95%CIs per interquartile range dome height increment.

Results

Among 304 participants (mean age 64.7±10.3, 41.8% female, 44.4% with mild COPD), each left and right DDH increment, respectively, was associated with ICpeak(0.21[0.13,0.29]L, 0.13[0.07,0.19]L), Wpeak(9.54[5.03,14.04]W, 6.04[2.45,9.62]W), FEV1(0.17[0.10,0.25]L, 0.08[0.02,0.14]L), and CAT score (−1.36[−2.39,−0.33], −0.82[−1.63,0.00]). Left DDH alone was associated with both symptom-based (HR: 0.82[0.74,0.91]) and event-based (0.83[0.73,0.95]) exacerbations. Of 167/304 participants with confirmed dynamic hyperinflation (ΔIC=−0.47±0.25 L), left DDH alone was associated with all outcomes (ICpeak, Wpeak, FEV1, CAT, and symptom-based/event-based exacerbations).

Conclusions

Left DDH appears to be a clinically important marker for operational lung volume changes, lung function, exercise performance, disease burden, and exacerbations in mild-to-moderate COPD.
Value of combining lung ultrasound score with oxygenation and functional indices in determining weaning timing for critically ill pediatric patients
Authors: Hao Ximeng , Duan Hongnian , Li Qiushuang , Wang Dan , Yin Xin , Di Zhiyan , Du Shanshan
Published: January 2025

Objective

This study aims to investigate the predictive effectiveness of bedside lung ultrasound score (LUS) in conjunction with rapid shallow breathing index (RSBI) and oxygenation index (P/F ratio) for weaning pediatric patients from mechanical ventilation.

Methods

This was a retrospective study. Eighty-two critically ill pediatric patients, who were admitted to the Pediatric Intensive Care Unit (PICU) and underwent mechanical ventilation from January 2023 to April 2024, were enrolled in this study. Prior to weaning, all patients underwent bedside LUS, with concurrent measurements of their RSBI and P/F ratio. Patients were followed up for weaning outcomes and categorized into successful and failed weaning groups based on these outcomes. Differences in clinical baseline data, LUS scores, RSBI and P/F ratios between the two groups were compared. The predictive value of LUS scores, RSBI and P/F ratios for weaning outcomes was assessed using receiver operating characteristic (ROC) curves and the area under the curve (AUC).

Results

Out of the 82 subjects, 73 (89.02%) successfully weaned, while 9 (10.98%) failed. No statistically significant differences were observed in age, gender, BMI, and respiratory failure-related comorbidities between the successful and failed weaning groups (P > 0.05). Compared to the successful weaning group, the failed weaning group exhibited longer hospital and intubation durations, higher LUS and RSBI, and lower P/F ratios, with statistically significant differences (P < 0.05). An LUS score ≥ 15.5 was identified as the optimal cutoff for predicting weaning failure, with superior predictive power compared to RSBI and P/F ratios. The combined use of LUS, RSBI and P/F ratios for predicting weaning outcomes yielded a larger area under the curve, indicating higher predictive efficacy.

Conclusion

The LUS demonstrates a high predictive value for the weaning outcomes of pediatric patients on mechanical ventilation.
Chronic and infectious respiratory mortality and short-term exposures to four types of pollen taxa in older adults in Michigan, 2006-2017
Authors: Larson Peter S. , Steiner Allison L. , O’Neill Marie S. , Baptist Alan P. , Gronlund Carina J.
Published: January 2025

Introduction

Levels of plant-based aeroallergens are rising as growing seasons lengthen and intensify with anthropogenic climate change. Increased exposure to pollens could increase risk for mortality from respiratory causes, particularly among older adults. We determined short-term, lag associations of four species classes of pollen (ragweed, deciduous trees, grass pollen and evergreen trees) with respiratory mortality (all cause, chronic and infectious related) in Michigan, USA.

Methods

We obtained records for all Michigan deaths from 2006-2017 from the Michigan Department of Health and Human Services (MDHHS). Deaths from infectious and chronic respiratory-related causes were selected using International Classification of Diseases (ICD-10) codes. Pollen data were obtained from a prognostic model of daily pollen concentrations at 25 km resolution. Case-crossover models with distributed lag non-linear crossbases for pollen were used to estimate associations between lags of daily pollen concentrations with mortality and to explore effect modification by sex and racial groups.

Results

127,163 deaths were included in the study. Cumulative daily high concentrations (90th percentile) of deciduous broadleaf, grass and ragweed were associated with all-cause respiratory mortality at early lags with e.g., a 1.81 times higher risk of all respiratory deaths at cumulative 7 day lag exposure to deciduous broadleaf pollen at the 90th percentile (95% confidence interval: 1.04, 3.15). Exposure to high concentrations of grass and ragweed pollens was associated with increased risk for death from chronic respiratory causes. No association was found for any pollen species with death from infectious respiratory causes though there was a positive but non-significant association of exposure to deciduous broadleaf and ragweed pollens. We found no evidence to suggest effect modification by race or sex.

Conclusions

Modelled exposures to high concentrations of pollen taxa were associated with increased all-cause and chronic respiratory mortality among older adults. Results suggest that pollen exposure may become more important to respiratory mortality as the temperatures increase and pollen seasons lengthen.