Publications by authors named "Theresa Willett"

5 Publications

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Hypoferritinemia and iron deficiency in youth with pediatric acute-onset neuropsychiatric syndrome.

Pediatr Res 2020 Aug 3. Epub 2020 Aug 3.

Division of Allergy, Immunology, & Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA.

Background: Pediatric acute-onset neuropsychiatric syndrome (PANS) is an abrupt debilitating psychiatric illness. We anecdotally observed hypoferritinemia and iron deficiency in a subset of patients with PANS, prompting this study.

Methods: In this IRB-approved prospective cohort study, we included patients seen at the Stanford PANS Clinic who met study criteria. The prevalence of hypoferritinemia (using cut-offs of 7 ng/ml in children ≤ 15 years and 18 ng/ml in adolescents > 15 years) and iron deficiency was estimated. Differences in patients with and without hypoferritinemia during PANS flare were explored.

Results: Seventy-nine subjects (mean age of PANS onset of 8.7 years) met study criteria. Hypoferritinemia was observed in 27% and three quarters occurred during a PANS flare. Compared to patients without hypoferritinemia during PANS flare, patients with hypoferritinemia had worse global impairment, more comorbid inflammatory diseases, and exhibited a chronic course of PANS illness. The estimated prevalence of iron deficiency was 3-8% in the PANS cohort, 1.4-2.0-fold higher than in the age- and sex-matched U.S.

Population: More stringent ferritin level cut-offs than the comparison CDC dataset were used.

Conclusion: Hypoferritinemia and iron deficiency appear to be more common in PANS patients. More research is needed to confirm and understand this association.

Impact: Our study suggests hypoferritinemia and iron deficiency are more common in patients with pediatric acute-onset neuropsychiatric syndrome (PANS) than in the sex- and age-matched US population.Hypoferritinemia was commonly observed during a disease flare but not associated with dietary or demographic factors. In patients with PANS and iron deficiency, clinicians should consider possibility of inflammation as the cause especially if iron deficiency cannot be explained by diet and blood loss.Future research should include larger cohorts to corroborate our study findings and consider examining the iron dynamics on MRI brain imaging in order to better understand the pathophysiology of PANS.
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http://dx.doi.org/10.1038/s41390-020-1103-3DOI Listing
August 2020

Familial Clustering of Immune-Mediated Diseases in Children with Abrupt-Onset Obsessive Compulsive Disorder.

J Child Adolesc Psychopharmacol 2020 06 20;30(5):345-346. Epub 2020 Apr 20.

Stanford PANS/Immune Behavioral Health Clinic, PANS Research Program at Lucile Packard Children's Hospital, Palo Alto, California, USA.

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http://dx.doi.org/10.1089/cap.2019.0167DOI Listing
June 2020

The Burden of Caring for a Child or Adolescent With Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): An Observational Longitudinal Study.

J Clin Psychiatry 2018 12 11;80(1). Epub 2018 Dec 11.

Pediatric Divisions of Child & Adolescent Psychiatry, Stanford University School of Medicine, Palo Alto, California, USA.

Objective: To describe the longitudinal association between disease severity, time established in clinical treatment, and caregiver burden in a community-based patient population diagnosed with pediatric acute-onset neuropsychiatric syndrome (PANS).

Methods: The study included an observational longitudinal cohort design, with Caregiver Burden Inventories (CBIs) collected between April 2013 and November 2016 at the Stanford PANS multidisciplinary clinic. Inclusion criteria for this study were as follows: pediatric patients meeting strict PANS/pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) diagnostic criteria (n = 187), having a caregiver fill out at least 1 complete CBI during a disease flare (n = 114); and having family who lives locally (n = 97). For longitudinal analyses, only patients whose caregiver had filled out 2 or more CBIs (n = 94 with 892 CBIs) were included. In the study sample, most primary caregivers were mothers (69 [71.1%] of 97), the majority of PANS patients were male (58 [59.8%] of 97), and mean age at PANS onset was 8.8 years.

Results: In a patient's first flare tracked by the clinic, 50% of caregivers exceeded the caregiver burden score threshold used to determine respite need in care receiver adult populations. Longitudinally, flares, compared with quiescence, predicted increases in mean CBI score (6.6 points; 95% CI, 5.1 to 8.0). Each year established in clinic predicted decreased CBI score (-3.5 points per year; 95% CI, -2.3 to -4.6). Also, shorter time between PANS onset and entry into the multidisciplinary clinic predicted greater improvement in mean CBI score over time (0.7 points per year squared; 95% CI, 0.1 to 1.3). Time between PANS onset and treatment with antibiotics or immunomodulation did not moderate the relationship between CBI score and time in clinic.

Conclusions: PANS caregivers suffer high caregiver burden. Neuropsychiatric disease severity predicts increased caregiver burden. Caregiver burden tends to decrease over time in a group of patients undergoing clinical treatment at a specialty PANS clinic. This decrease could be independent of clinical treatment.
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http://dx.doi.org/10.4088/JCP.17m12091DOI Listing
December 2018

Psychometric Properties of the Pediatric Acute-Onset Neuropsychiatric Syndrome Global Impairment Score in Children and Adolescents with Pediatric Acute-Onset Neuropsychiatric Syndrome.

J Child Adolesc Psychopharmacol 2019 02 13;29(1):41-49. Epub 2018 Nov 13.

1 Stanford PANS Clinic and Research Program at Lucile Packard Children's Hospital, Stanford University School of Medicine , Palo Alto, California.

Objectives: This study validates the caregiver-rated Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) Global Impairment Score (GIS), a single-item, 0-100 scale, for use in PANS.

Methods: We collected longitudinal data from community patients meeting PANS criteria. We included 128 patients with 1926 GISs, each from a unique clinic visit. To assess discriminant validity, we compared GISs from patients with PANS with scores from a population of healthy controls. To evaluate external validity, we compared global impairment with a clinician-reported global measure-the Child Global Assessment Scale (CGAS)-using the Bland-Altman plots and correlation coefficients. Then, we evaluated associations between the PANS GIS and symptom-specific disease severity variables by fitting mixed models with repeated measures.

Results: The GIS shows excellent discriminant validity, distinguishing patients with PANS from healthy controls. The scores on the GIS show an acceptable level of agreement with the clinician-reported CGAS. The regression line in the Bland-Altman plot had a positive slope, indicating that parents tend to report higher disease severity than clinicians at higher levels of disease severity. Correlation was higher during disease remissions than during disease flares (r = -0.69 vs. r = -0.48). All disease severity scales predicted GIS in the expected direction.

Conclusion: The GIS has excellent discriminant validity and acceptable construct validity.
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http://dx.doi.org/10.1089/cap.2018.0029DOI Listing
February 2019

An effective second-generation outer surface protein A-derived Lyme vaccine that eliminates a potentially autoreactive T cell epitope.

Proc Natl Acad Sci U S A 2004 Feb 23;101(5):1303-8. Epub 2004 Jan 23.

Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.

The antigenic component of a common Lyme disease vaccine is recombinant outer surface protein A (rOspA) of Borrelia burgdorferi (Bb), the causative agent of Lyme disease. Coincidentally, patients with chronic, treatment-resistant Lyme arthritis develop an immune response against OspA, whereas those with acute Lyme disease usually do not. Treatment-resistant Lyme arthritis occurs in a subset of Lyme arthritis patients and is linked to HLA.DRB1*0401 (DR4) and related alleles. Recent work from our laboratory identified T cell crossreactivity between epitopes of OspA and lymphocyte function-associated antigen 1alpha(L) chain (LFA-1alpha(L)) in these patients. We generated a form of rOspA, FTK-OspA, in which the LFA-1alpha(L)/rOspA crossreactive T cell epitope was mutated to reduce the possible risk of autoimmunity in genetically susceptible individuals. FTK-OspA did not stimulate human or mouse DR4-restricted, WT-OspA-specific T cells, whereas it did stimulate antibody responses specific for WT-OspA that were similar to mice vaccinated WT-OspA. We show here that the protective efficacy of FTK-OspA is indistinguishable from that of WT-OspA in vaccination trials, as both C3H/HeJ and BALB/c FTK-OspA-vaccinated mice were protected from Bb infection. These data demonstrate that this rOspA-derived vaccine lacking the predicted cross-reactive T cell epitope, but retaining the capacity to elicit antibodies against infection, is effective in generating protective immunity.
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http://dx.doi.org/10.1073/pnas.0305680101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC337048PMC
February 2004