C-Reactive Protein Changes in Adult and Pediatric People With Cystic Fibrosis During Treatment of Pulmonary Exacerbations.

Objective: Although studies have examined changes in C-reactive protein (CRP) during pulmonary exacerbations (PEX) in people with cystic fibrosis (PwCF), few have evaluated CRP profiles across age groups. Here, we characterize age-related CRP responses to PEX treatment.

Methods: We measured CRP concentrations at the beginning and end of intravenous (IV) antibiotic therapy for PEX in 100 pediatric and 147 adult PwCF at 10 US CF Centers.

The CD123 antibody-drug conjugate pivekimab sunirine exerts profound activity in preclinical models of pediatric acute lymphoblastic leukemia.

Antibody-drug conjugates (ADCs) combining monoclonal antibodies with cytotoxic payloads are a rapidly emerging class of immune-based therapeutics with the potential to improve the treatment of cancer, including children with relapse/refractory acute lymphoblastic leukemia (ALL). CD123, the α subunit of the interleukin-3 receptor, is overexpressed in ALL and is a potential therapeutic target. Here, we show that pivekimab sunirine (PVEK), a recently developed ADC comprising the CD123-targeting antibody, G4723A, and the cytotoxic payload, DGN549, was highly effective in vivo against a large panel of pediatric ALL patient-derived xenograft (PDX) models ( = 39).

Qualitative understanding of experiences of people with cystic fibrosis in a treatment discontinuation trial: The QUEST study.

Background: As people with cystic fibrosis (PWCF) live longer due to the breakthrough drug elexacaftor-tezacaftor-ivacaftor (ETI), they have questioned whether other CF therapies could be safely discontinued. SIMPLIFY was the first prospective, randomized trial to evaluate non-inferiority of discontinuing versus continuing two therapies. The QUEST (Qualitative Understanding of Experiences in the SIMPLIFY Trial) study was conducted to understand experiences of PWCF enrolled in SIMPLIFY, including why they joined, perceptions of randomization, decision-making around study withdrawal, and considerations for future discontinuation studies.

The third generation AKR1C3-activated prodrug, ACHM-025, eradicates disease in preclinical models of aggressive T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that expresses high levels of the enzyme aldo-keto reductase family 1 member C3 (AKR1C3). To exploit this finding, we developed a novel prodrug, ACHM-025, which is selectively activated by AKR1C3 to a nitrogen mustard DNA alkylating agent. We show that ACHM-025 has potent in vivo efficacy against T-ALL patient-derived xenografts (PDXs) and eradicated the disease in 7 PDXs.

Co-designing a blueprint for spreading person-centered, Whole Health care to HIV specialty care settings: a mixed methods protocol.

Background: Since 2013, the Veterans Health Administration (VHA) has advanced a person-centered, Whole Health (WH) System of Care, a shift from a disease-oriented system to one that prioritizes "what matters most" to patients in their lives. Whole Health is predicated on patient-provider interactions marked by a multi-level understanding of health and trusted relationships that promote well-being. Presently, WH implementation has been focused largely in primary care settings, yet the goal is to effect a system-wide transformation of care so that Veterans receive WH across VHA clinical settings, including specialty care.

Working with Miraculous Mice: Mus musculus as a Model Organism.

The laboratory mouse has been described as a "miracle" model organism, providing a window by which we may gain an understanding of ourselves. Since the first recorded mouse experiment in 1664, the mouse has become the most used animal model in biomedical research. Mice are ideally suited as a model organism because of their small size, short gestation period, large litter size, and genetic similarity to humans.

Implementation of collaborative care for depression in VA HIV clinics: Translating Initiatives for Depression into Effective Solutions (HITIDES): protocol for a cluster-randomized type 3 hybrid effectiveness-implementation trial.

Background: Depression is the most diagnosed mental health condition among people living with HIV. Collaborative care is an effective intervention for depression, typically delivered in primary care settings. The HIV Translating Initiatives for Depression into Effective Solutions (HITIDES) clinical intervention involves a depression care team housed off-site that supports depression care delivery by HIV care providers.

Self-reported chronic therapy use after 24-weeks of follow-up by participants who completed the simplify randomized, controlled trial.

Background: Highly effective CFTR modulator therapy (HEMT) has improved the health of many people with cystic fibrosis (pwCF), offering opportunities to discontinue burdensome therapies. SIMPLIFY included randomized, controlled trials that confirmed non-inferiority of discontinuing versus continuing dornase alfa (DA) or hypertonic saline (HS) for 6 weeks in pwCF on HEMT. In this study of post-trial treatment use by SIMPLIFY participants, we hypothesized that randomization to discontinue DA or HS during the trial would be associated with a higher likelihood of non-use of each medication during follow-up.

Modeling short visual events through the BOLD moments video fMRI dataset and metadata.

Studying the neural basis of human dynamic visual perception requires extensive experimental data to evaluate the large swathes of functionally diverse brain neural networks driven by perceiving visual events. Here, we introduce the BOLD Moments Dataset (BMD), a repository of whole-brain fMRI responses to over 1000 short (3 s) naturalistic video clips of visual events across ten human subjects. We use the videos' extensive metadata to show how the brain represents word- and sentence-level descriptions of visual events and identify correlates of video memorability scores extending into the parietal cortex.

Impact of Discontinuing Both Hypertonic Saline and Dornase Alfa after Elexacaftor-Tezacaftor-Ivacaftor in Cystic Fibrosis.

Evaluating approaches to reduce treatment burden is a research priority among people with cystic fibrosis on highly effective modulators, including elexacaftor-tezacaftor-ivacaftor (ETI). We sought to evaluate the impact of discontinuing both hypertonic saline (HS) and dornase alfa (DA) versus continuing both therapies among a subgroup of participants in the SIMPLIFY study who sequentially participated in trials evaluating the independent clinical effects of discontinuing HS and DA. SIMPLIFY participants ≥12 years old on ETI and constituting a subgroup using both HS and DA at study entry were randomized to the HS or DA trial and then randomized 1:1 to continue or discontinue the applicable therapy for 6 weeks.

Negative clinic experiences as a barrier to care for people with HIV and their impact on patient preferences for intervention support: a qualitative study in Cape Town, South Africa.

We conducted qualitative research among people with HIV (PWH) and care providers in Cape Town, South Africa to understand the impact of negative clinic experiences on adherence and support preferences. In-depth interviews were conducted with 41 patients with an unsuppressed viral load or a treatment gap, and focus group discussions with physicians, nurses, counselors, and community health workers. Questions addressed treatment history and adherence barriers, then participants evaluated evidence-based adherence interventions for potential scale up.

A Phase 1 Study of Intravenous EGFR-ErbituxEDVsMIT in Children with Solid or CNS Tumours Expressing Epidermal Growth Factor Receptor.

Background: Recurrent or refractory solid and central nervous system (CNS) tumours in paediatric patients have limited treatment options and carry a poor prognosis. The EnGeneIC Dream Vector (EDV) is a novel nanocell designed to deliver cytotoxic medication directly to the tumour. The epidermal growth factor receptor is expressed in several CNS and solid tumours and is the target for bispecific antibodies attached to the EDV.

Association between CFTR modulators and changes in iron deficiency markers in cystic fibrosis.

Background: Iron deficiency (ID) is a common extrapulmonary manifestation in cystic fibrosis (CF). CF transmembrane conductance regulator (CFTR) modulator therapies, particularly highly-effective modulator therapy (HEMT), have drastically improved health status in a majority of people with CF. We hypothesize that CFTR modulator use is associated with improved markers of ID.

Diffusion of excellence: evaluating a system to identify, replicate, and spread promising innovative practices across the Veterans health administration.

Introduction: The Veterans Health Administration (VHA) Diffusion of Excellence (DoE) program provides a system to identify, replicate, and spread promising practices across the largest integrated healthcare system in the United States. DoE identifies innovations that have been successfully implemented in the VHA through a Shark Tank style competition. VHA facility and regional directors bid resources needed to replicate promising practices.

Usability Testing of Situation Awareness Clinical Decision Support in the Intensive Care Unit.

Objective:  Our objective was to evaluate the usability of an automated clinical decision support (CDS) tool previously implemented in the pediatric intensive care unit (PICU) to promote shared situation awareness among the medical team to prevent serious safety events within children's hospitals.

Methods:  We conducted a mixed-methods usability evaluation of a CDS tool in a PICU at a large, urban, quaternary, free-standing children's hospital in the Midwest. Quantitative assessment was done using the system usability scale (SUS), while qualitative assessment involved think-aloud usability testing.

The effect of discontinuing hypertonic saline or dornase alfa on mucociliary clearance in elexacaftor/tezacaftor/ivacaftor treated people with cystic fibrosis: The SIMPLIFY-MCC Study.

Many people with CF (pwCF) desire a reduction in inhaled treatment burden after initiation of elexacaftor/tezacaftor/ivacaftor. The randomized, open-label SIMPLIFY study showed that discontinuing hypertonic saline (HS) or dornase alfa (DA) was non-inferior to continuation of each treatment with respect to change in lung function over a 6-week period. In this SIMPLIFY substudy, we used gamma scintigraphy to determine whether discontinuation of either HS or DA was associated with deterioration in the rate of in vivo mucociliary clearance (MCC) in participants ≥12 years of age.

Reducing epilepsy diagnostic and treatment gaps: Standardized paediatric epilepsy training courses for health care professionals.

Aim: To evaluate improvement in knowledge and clinical behaviour among healthcare professionals after attendance at paediatric epilepsy training (PET) courses.

Method: Since 2005, 1-day PET courses have taught evidence-based paediatric epilepsy management to doctors and nurses in low-, middle-, and high-income countries. A cohort study was performed of 7528 participants attending 252 1-day PET courses between 2005 and 2020 in 17 low-, middle-, and high-income countries, and which gathered data from participants immediately after the course and then 6 months later.

Implementation of Direct-to-Patient Mobile Teledermatology in VA.

Background: Innovative technology can enhance patient access to healthcare but must be successfully implemented to be effective.

Objective: We evaluated Department of Veterans Affairs' (VA's) implementation of My VA Images, a direct-to-patient asynchronous teledermatology mobile application enabling established dermatology patients to receive follow-up care remotely instead of in-person.

Design /participants/approach: Following pilot testing at 3 facilities, the app was introduced to 28 facilities (4 groups of 7) every 3 months using a stepped-wedge cluster-randomized design.