Publications by authors named "Ann M Firestine"

Objectives: HLA DQA1*05 has been associated with the development of anti-drug antibodies (ADA) to tumor necrosis factor antagonists (anti-TNF) and treatment failure among adults with Crohn's disease (CD). However, findings from other studies have been inconsistent with limited pediatric data.

Methods: We analyzed banked serum from patients with CD < 21 years of age enrolled in COMBINE, a multi-center, prospective randomized trial of anti-TNF monotherapy vs.

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Background: Higher drug levels and combination therapy with low-dose oral methotrexate (LD-MTX) may reduce anti-tumor necrosis factor (TNF) treatment failure in pediatric Crohn's disease. We sought to (1) evaluate whether combination therapy with LD-MTX was associated with higher anti-TNF levels, (2) evaluate associations between anti-TNF levels and subsequent treatment failure, and (3) explore the effect of combination therapy on maintenance of remission among patients with therapeutic drug levels (>5 µg/mL for infliximab and >7.5 µg/mL for adalimumab).

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Background: Children with inflammatory bowel disease (IBD) may have diminished serologic response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and increased risk for subsequent severe coronavirus disease 2019 (COVID-19) infection. We sought to describe outcomes among those who developed SARS-CoV-2 infection following vaccination, characterize SARS-CoV-2 antibodies 1 year post-vaccination, and identify factors associated with durable serologic response.

Methods: We recruited children with IBD who received ≥2 doses of SARS-CoV-2 vaccine and prospectively collected data on (1) demographics, IBD characteristics, and therapy and (2) SARS-CoV-2 vaccination, testing, and infection symptoms.

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Article Synopsis
  • Obesity in pediatric Crohn's disease (PCD) patients may impact their response to anti-tumor necrosis factor (TNF) treatment, especially with adalimumab (ADA) compared to infliximab (IFX).
  • In a study involving 224 participants, higher body mass index (BMI) was linked to higher treatment failure rates and lower ADA levels in patients receiving ADA therapy, but not in those on IFX.
  • This suggests standard ADA dosages might be inadequate for overweight and obese children with PCD, highlighting the need for tailored dosing strategies.
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Introduction: Disparities in the recruitment of minority populations in research are well-documented. However, the degree of participation and retention of minorities following enrollment is less known, particularly in decentralized studies. Although decentralized clinical research methods may allow researchers to engage broader study populations with less participation burden, they may present different retention challenges.

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Article Synopsis
  • A multicenter trial was conducted to compare the effectiveness of tumor necrosis factor inhibitors combined with oral methotrexate versus those without methotrexate in pediatric patients with Crohn's disease.
  • The study involved 297 participants, revealing that combination therapy did not significantly improve treatment outcomes for infliximab initiators, but did show a longer time to treatment failure for adalimumab initiators.
  • Although combination therapy led to more adverse events overall, it resulted in fewer serious adverse events, with no significant differences reported in patient-reported outcomes of pain and fatigue.
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Article Synopsis
  • - The study aimed to explore the emotional impacts of two meditation methods—mindfulness and loving-kindness—among midlife adults, measuring their daily practice and emotional responses over nine weeks.
  • - Results showed that both meditation types significantly increased positive emotions without affecting negative emotions, with a stronger effect observed for loving-kindness meditation.
  • - The findings highlight a clear connection between the amount and frequency of meditation practice and improvements in emotional wellbeing, supporting the use of these meditation techniques for enhancing mental health.
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Research in human social genomics has identified a conserved transcriptional response to adversity (CTRA) characterized by up-regulated expression of pro-inflammatory genes and down-regulated expression of Type I interferon- and antibody-related genes. This report seeks to identify the specific aspects of positive psychological well-being that oppose such effects and predict reduced CTRA gene expression. In a new confirmation study of 122 healthy adults that replicated the approach of a previously reported discovery study, mixed effect linear model analyses identified a significant inverse association between expression of CTRA indicator genes and a summary measure of eudaimonic well-being from the Mental Health Continuum - Short Form.

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To identify molecular mechanisms underlying the prospective health advantages associated with psychological well-being, we analyzed leukocyte basal gene expression profiles in 80 healthy adults who were assessed for hedonic and eudaimonic well-being, as well as potentially confounded negative psychological and behavioral factors. Hedonic and eudaimonic well-being showed similar affective correlates but highly divergent transcriptome profiles. Peripheral blood mononuclear cells from people with high levels of hedonic well-being showed up-regulated expression of a stress-related conserved transcriptional response to adversity (CTRA) involving increased expression of proinflammatory genes and decreased expression of genes involved in antibody synthesis and type I IFN response.

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