Publications by authors named "J-P Simon"

Article Synopsis
  • * A phase I clinical trial using the gamma-secretase inhibitor (GSI) crenigacestat alongside anti-BCMA CAR T-cells showed that GSI affected the tumor microenvironment, particularly altering monocyte populations and their gene expression.
  • * The study also found that some patients had monoallelic deletion of the BCMA gene after previous treatments, which correlated with shorter progression-free survival, highlighting the need to investigate GSIs with BCMA-targeted therapies for better outcomes. *
View Article and Find Full Text PDF

Importance: The overdose epidemic continues in the US, with 107 941 overdose deaths in 2022 and countless lives affected by the addiction crisis. Although widespread efforts to train and support physicians to implement medications and other evidence-based substance use disorder interventions have been ongoing, adoption of these evidence-based practices (EBPs) by physicians remains low.

Objective: To describe physician-reported reasons for reluctance to address substance use and addiction in their clinical practices using screening, treatment, harm reduction, or recovery support interventions.

View Article and Find Full Text PDF

Background: The majority of out-of-hospital cardiac arrests (OHCAs) occur among individuals in the general population, for whom there is no established strategy to identify risk. In this study, we assess the use of electronic health record (EHR) data to identify OHCA in the general population and define salient factors contributing to OHCA risk.

Methods: The analytical cohort included 2366 individuals with OHCA and 23 660 age- and sex-matched controls receiving health care at the University of Washington.

View Article and Find Full Text PDF

Objective: The aim of this study was to demonstrate whether lasofoxifene improves vaginal signs/symptoms of genitourinary syndrome of menopause.

Methods: Two identical, phase 3 trials randomized postmenopausal women with moderate to severe vaginal symptoms to oral lasofoxifene 0.25 or 0.

View Article and Find Full Text PDF

Atypical chemokine receptor 3 (ACKR3), formerly referred to as CXCR7, is considered to be an interesting drug target. In this study, we report on the synthesis, pharmacological characterization and radiolabeling of VUF15485, a new ACKR3 small-molecule agonist, that will serve as an important new tool to study this -arrestin-biased chemokine receptor. VUF15485 binds with nanomolar affinity (pIC = 8.

View Article and Find Full Text PDF

Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities.

View Article and Find Full Text PDF

Black cisgender women (hereafter referred to as "women") have disproportionately high rates of HIV infection yet low rates of pre-exposure prophylaxis (PrEP) utilization. Barriers to PrEP uptake exist at the system, provider, and individual/client level. To learn how existing training and advertising can be adapted to address race- and sex-based gaps within PrEP service delivery, we conducted focus groups with providers and Black women.

View Article and Find Full Text PDF
Article Synopsis
  • A study compared two blood transfusion strategies for patients with myocardial infarction and low hemoglobin: a restrictive strategy (transfusion if hemoglobin <7 or 8 g/dL) and a liberal strategy (transfusion if hemoglobin <10 g/dL).
  • Involving 3,504 patients, results showed that the liberal group received significantly more transfusions but did not experience a reduced risk of death or recurrent myocardial infarction at 30 days compared to the restrictive group.
  • The findings suggest that while the liberal strategy may not improve outcomes, the potential risks of the restrictive strategy remain uncertain, indicating the need for further research.
View Article and Find Full Text PDF

Background: Sleep disturbance is a prominent symptom of atopic dermatitis (AD) and can result in insomnia, daytime fatigue, drowsiness, reduced productivity and impaired quality of life (QoL).

Objectives: The Dupilumab Effect on Sleep in AD Patients (DUPISTAD) phase IV randomized double-blinded placebo-controlled study evaluated the impact of dupilumab treatment on sleep and other patient- and physician-reported outcomes.

Methods: Adults with moderate-to-severe AD were randomized 2 : 1 to dupilumab 300 mg once every 2 weeks (q2w) or placebo for 12 weeks; concomitant topical corticosteroids were permitted.

View Article and Find Full Text PDF

The organic electronic ion pump (OEIP) is an on-demand electrophoretic drug delivery device, that via electronic to ionic signal conversion enables drug delivery without additional pressure or volume changes. The fundamental component of OEIPs is their polyelectrolyte membranes which are shaped into ionic channels that conduct and deliver ionic drugs, with high spatiotemporal resolution. The patterning of these membranes is essential in OEIP devices and is typically achieved using laborious microprocessing techniques.

View Article and Find Full Text PDF

Background: Questions remain concerning the rapidity of immune responses and the durability and safety of vaccines used to prevent Zaire Ebola virus disease.

Methods: We conducted two randomized, placebo-controlled trials - one involving adults and one involving children - to evaluate the safety and immune responses of three vaccine regimens against Zaire Ebola virus disease: Ad26.ZEBOV followed by MVA-BN-Filo 56 days later (the Ad26-MVA group), rVSVΔG-ZEBOV-GP followed by placebo 56 days later (the rVSV group), and rVSVΔG-ZEBOV-GP followed by rVSVΔG-ZEBOV-GP 56 days later (the rVSV-booster group).

View Article and Find Full Text PDF

Background: Teens with attention deficit-hyperactivity disorder (ADHD) are at increased risk for motor vehicle collisions. A computerized skills-training program to reduce long glances away from the roadway, a contributor to collision risk, may ameliorate driving risks among teens with ADHD.

Methods: We evaluated a computerized skills-training program designed to reduce long glances (lasting ≥2 seconds) away from the roadway in drivers 16 to 19 years of age with ADHD.

View Article and Find Full Text PDF

Background: A polypill that includes key medications associated with improved outcomes (aspirin, angiotensin-converting-enzyme [ACE] inhibitor, and statin) has been proposed as a simple approach to the secondary prevention of cardiovascular death and complications after myocardial infarction.

Methods: In this phase 3, randomized, controlled clinical trial, we assigned patients with myocardial infarction within the previous 6 months to a polypill-based strategy or usual care. The polypill treatment consisted of aspirin (100 mg), ramipril (2.

View Article and Find Full Text PDF

Background: Better understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management.

Methods: Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness.

View Article and Find Full Text PDF

In Fall 2020, universities saw extensive transmission of SARS-CoV-2 among their populations, threatening health of the university and surrounding communities, and viability of in-person instruction. Here we report a case study at the University of Illinois at Urbana-Champaign, where a multimodal "SHIELD: Target, Test, and Tell" program, with other non-pharmaceutical interventions, was employed to keep classrooms and laboratories open. The program included epidemiological modeling and surveillance, fast/frequent testing using a novel low-cost and scalable saliva-based RT-qPCR assay for SARS-CoV-2 that bypasses RNA extraction, called covidSHIELD, and digital tools for communication and compliance.

View Article and Find Full Text PDF

Background: Although complete nidal obliteration of brain arteriovenous malformations (AVM) is generally presumed to represent durable cure, postobliteration hemorrhage, and AVM recurrence have become increasingly recognized phenomena. The goal of the study was to define hemorrhage and nidal recurrence risks of obliterated AVMs treated with stereotactic radiosurgery (SRS).

Methods: This is a retrospective cohort study from the International Radiosurgery Research Foundation comprising AVM patients treated between 1987 and 2020.

View Article and Find Full Text PDF
Article Synopsis
  • Staphylococcus aureus often causes problems for people with atopic dermatitis (AD) and makes their condition worse.
  • A study tested a new treatment called ATx201, which helps reduce S. aureus on the skin without harming good bacteria.
  • The results showed that using ATx201 ointment was very effective in reducing S. aureus and improving skin health in patients with AD.
View Article and Find Full Text PDF
Article Synopsis
  • Mitochondrial DNA (mtDNA) is mostly inherited from mothers, and typically there are multiple identical copies in cells; however, some medical techniques can introduce varying mtDNA, creating a state known as divergent nonpathologic mtDNA heteroplasmy (DNPH).
  • Research on DNPH in engineered mice revealed that it disrupts mitochondrial function, causing serious health issues in critical tissues, especially the heart and muscles, which leads to conditions like pulmonary hypertension and heart failure.
  • The severity of these health problems is influenced by the genetic makeup of the nucleus, suggesting that medical practices involving mtDNA should carefully consider donor-recipient compatibility.
View Article and Find Full Text PDF

Excess liver fat, called hepatic steatosis, is a leading risk factor for end-stage liver disease and cardiometabolic diseases but often remains undiagnosed in clinical practice because of the need for direct imaging assessments. We developed an abdominal MRI-based machine-learning algorithm to accurately estimate liver fat (correlation coefficients, 0.97-0.

View Article and Find Full Text PDF

Gut bacteria modulate the response to immune checkpoint blockade (ICB) treatment in cancer, but the effect of diet and supplements on this interaction is not well studied. We assessed fecal microbiota profiles, dietary habits, and commercially available probiotic supplement use in melanoma patients and performed parallel preclinical studies. Higher dietary fiber was associated with significantly improved progression-free survival in 128 patients on ICB, with the most pronounced benefit observed in patients with sufficient dietary fiber intake and no probiotic use.

View Article and Find Full Text PDF

Background: Patterns of dual antiplatelet therapy (DAPT) use beyond 1 year post-myocardial infarction (MI) have not been well studied.

Methods: TIGRIS (NCT01866904) was a prospective, multi-center (369 centers in 24 countries), observational study of patients 1 to 3 years post-MI. We sought to identify the prevalence and determinants of DAPT use ≥1 year post-MI in patients enrolled in TIGRIS.

View Article and Find Full Text PDF

Background: The Brighton Collaboration Global Alignment of Immunization Safety in Pregnancy (GAIA) project developed case definitions for the assessment of adverse events in mothers and infants following maternal immunization. This study evaluated the applicability of these definitions to data collected in routine clinical care and research trial records across 7 sites in high-resource settings.

Methods: Data collection forms were designed and used to retrospectively abstract the key elements of the GAIA definitions from records for 5 neonatal and 5 maternal outcomes, as well as gestational age.

View Article and Find Full Text PDF

Treatment with combined immune checkpoint blockade (CICB) targeting CTLA-4 and PD-1 is associated with clinical benefit across tumor types, but also a high rate of immune-related adverse events. Insights into biomarkers and mechanisms of response and toxicity to CICB are needed. To address this, we profiled the blood, tumor and gut microbiome of 77 patients with advanced melanoma treated with CICB, with a high rate of any ≥grade 3 immune-related adverse events (49%) with parallel studies in pre-clinical models.

View Article and Find Full Text PDF

Despite direct viral effect, the pathogenesis of coronavirus disease 2019 (COVID-19) includes an overproduction of cytokines including interleukin 6 (IL-6). Therefore, tocilizumab (TOC), a monoclonal antibody against IL-6 receptors, was considered as a possible therapeutic option. Patients were selected from the SARSTer database, containing 2332 individuals with COVID-19.

View Article and Find Full Text PDF

Background: Despite treatment guidance endorsing shortened dual antiplatelet therapy (DAPT) duration in high bleeding risk (HBR) patients after drug-eluting stents, limited evidence exists to support these recommendations. The present study was designed to examine the safety and effectiveness of 1-month DAPT duration following percutaneous coronary intervention with zotarolimus-eluting stents in HBR patients.

Methods: Onyx ONE Clear was a prospective, multicenter, nonrandomized study evaluating the safety and effectiveness of 1-month DAPT followed by single antiplatelet therapy in HBR patients undergoing percutaneous coronary intervention with Resolute Onyx drug-eluting stents.

View Article and Find Full Text PDF