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Jennifer Frankovich, MD

  • Jennifer Frankovich

Specialties

Rheumatology

Work and Education

Professional Education

University of Nevada School of Medicine, Las Vegas, NV, 2001

Residency

Lucile Packard Children's Hospital, Palo Alto, CA, 2004

Fellowship

Lucile Packard Children's Hospital, Palo Alto, CA, 2008

Board Certifications

Pediatric Rheumatology, American Board of Pediatrics

Pediatrics, American Board of Pediatrics

All Publications

Palatal Petechiae in the Absence of Group A Streptococcus in Pediatric Patients with Acute-Onset Neuropsychiatric Deterioration: A Cohort Study. Journal of child and adolescent psychopharmacology Mahony, T., Sidell, D., Gans, H., Cooperstock, M., Brown, K., Cheung, J. M., Farhadian, B., Gustafson, M., Thienemann, M., Frankovich, J. 2017

Abstract

Palatal petechiae are 95% specific for streptococcal pharyngitis. Despite this, and despite prior research demonstrating that Group A Streptococcus (GAS) is a common antecedent to pediatric acute-onset neuropsychiatric syndrome (PANS) episodes, we anecdotally observed a low rate of documented GAS in patients with PANS and palatal petechiae. This retrospective chart review was conducted to formally report the rate of palatal petechiae and concurrent GAS in a cohort of patients with PANS and investigate other etiologic factors.The clinical notes of 112 patients seen at the Stanford PANS Clinic who met PANS research criteria were reviewed for mention of palatal petechiae. The medical records of patients who demonstrated palatal petechiae on physical examination were reviewed for signs of infection, a clinical history of trauma, and laboratory results that could indicate other causes of petechiae.Twenty-three patients had documented palatal petechiae on physical examination (ages 5-16, 13/23 [57%] male). Fifteen patients had a rapid GAS test and GAS culture in the Stanford PANS clinic, all with negative results. Evidence of recent GAS infection was found in 8/23 (32%) patients (elevated GAS titers [n=6] or documentation of a positive rapid GAS test at another facility [n=2]), one of whom also had potential herpes simplex virus (HSV) infection. One patient had potential HSV infection and recent palatal trauma. No patients had thrombocytopenia. 14/23 (61%) of patients with palatal petechiae had no discernable cause of petechiae. 10/19 (53%) of patients had antihistone antibodies.Despite the established relationship between palatal petechiae and GAS, no patient with palatal petechiae in our clinic tested positive for GAS and only 32% had evidence of recent GAS. Most did not have an identifiable cause for the palatal lesions. This finding suggests the potential for alternative causes of palatal petechiae or undetectable GAS in our patient population. The high prevalence of palatal petechiae without GAS infection suggests that the pathogenesis of PANS is multifactorial and may involve disruption or inflammation of the microvasculature. Additional research is needed to further elucidate these findings.

View details for DOI 10.1089/cap.2016.0153

View details for PubMedID 28387528

Clinical Management of Pediatric Acute-onset Neuropsychiatric Syndrome (PANS): Part II Use of Immunomodulatory Therapies Journal of Child and Adolescent Psychopharmacology Frankovich, J., Swedo, S., Murphy, T., Dale, R. C., Agalliu, D., Williams, K., Daines, M., Hornig, M., Chugani, H., Sanger, T., Muscal, E., Pasternack, M., Cooperstock, M., Gans, H., Zhang, Y., Cunningham, M., Bernstein, G., Bromberg, R., Willett, T., Brown, K., Farhadian, B., Chang, K., Geller, D., Hernandez, J., Sherr, J., et al 2017; 27 (7): 574-593

View details for DOI 10.1089/cap.2016.0148

Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part IPsychiatric and Behavioral Interventions Journal of Child and Adolescent Psychopharmacology Thienemann, M., Murphy, T., Leckman, J., Shaw, R., Williams, K., Kapphahn, C., Frankovich, J., Geller, D., Bernstein, G., Chang, K., Elia, J., Swedo, S. 2017; 27 (7): 566-573

View details for DOI 10.1089/cap.2016.0145

Course of Neuropsychiatric Symptoms After Introduction and Removal of Nonsteroidal Anti-Inflammatory Drugs: A Pediatric Observational Study. Journal of child and adolescent psychopharmacology Spartz, E. J., Freeman, G. M., Brown, K., Farhadian, B., Thienemann, M., Frankovich, J. 2017; 27 (7): 65259

Abstract

Accumulating evidence suggests that anti-inflammatory interventions can modulate neuropsychiatric symptoms. Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is characterized by an abrupt and dramatic onset of obsessive-compulsive (OC) symptoms and/or severely restrictive food intake and at least two coinciding, equally debilitating neuropsychiatric symptoms. When associated with group A Streptococcus, the syndrome is labeled Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS). Here, we describe the course of neuropsychiatric symptoms in patients diagnosed with PANS and PANDAS after introduction or removal of nonsteroidal anti-inflammatory drugs (NSAIDs).We reviewed the electronic medical records (EMR) of 218 consecutive patients evaluated in our Stanford PANS Clinic for patients who met strict PANS or PANDAS research criteria and received NSAIDs for arthritis, pain, and/or psychiatric symptoms. We describe neuropsychiatric symptoms that were noted in the EMR before, during, and after NSAIDs were introduced or removed as the sole change in pharmacologic treatment.Seventy-seven patients were included in the current study. Of the 52 trials in which NSAID addition was the sole change in treatment, 16 (31%) coincided with an improvement in patients' neuropsychiatric symptoms. Of the 57 trials in which removal of NSAID treatment was the sole change in treatment, 20 (35%) coincided with escalation in patients' neuropsychiatric symptoms. Thirty patients (39%) experienced side effects, mainly mild gastrointestinal symptoms, which self-resolved after removal of NSAID, reduction of dose, or change in NSAID.Improvement in neuropsychiatric symptoms was evident in roughly one-third of NSAID treatment trials. A randomized clinical trial will be necessary to confirm whether NSAIDs are successful in reducing neuropsychiatric symptoms in youth with PANS.

View details for DOI 10.1089/cap.2016.0179

View details for PubMedID 28696783

Effect of Early and Prophylactic Nonsteroidal Anti-Inflammatory Drugs on Flare Duration in Pediatric Acute-Onset Neuropsychiatric Syndrome: An Observational Study of Patients Followed by an Academic Community-Based Pediatric Acute-Onset Neuropsychiatric Syndrome Clinic. Journal of child and adolescent psychopharmacology Brown, K. D., Farmer, C., Freeman, G. M., Spartz, E. J., Farhadian, B., Thienemann, M., Frankovich, J. 2017; 27 (7): 61928

Abstract

Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is characterized by the sudden onset of severe obsessive-compulsive symptoms and/or eating restriction along with at least two coinciding neuropsychiatric symptoms. When associated with group A Streptococcus, the syndrome is labeled Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS). An abnormal immune response to infection and subsequent neuroinflammation is postulated to play an etiologic role. We evaluated the impact of nonsteroidal anti-inflammatory drug (NSAID) treatment on flare duration in PANS/PANDAS.Patient inclusion criteria: Patients were included if they had at least one neuropsychiatric deterioration ("flare") that met strict PANS/PANDAS research criteria and for which flare duration could be assessed. Flare inclusion criteria: Any flare that started before October 15, 2016 was included and followed until the flare resolved or until the end of our data collection (November 1, 2016). Flare exclusion criteria: Flares were excluded if they were incompletely resolved, treated with aggressive immunomodulation, or treated with NSAIDs late (>30 days of flare onset). Ninety-five patients met study inclusion criteria and collectively experienced 390 flares that met flare criteria. Data were analyzed using multilevel linear models, adjusting for demographics, disease, and treatment covariates.NSAID use was associated with a significantly shorter flare duration. Flares not treated with NSAIDs had a mean duration of approximately 12.2 weeks (95% CI: 9.3-15.1). Flares that occurred while the child was on NSAID maintenance therapy were approximately 4 weeks shorter than flares not managed with NSAIDs (95% CI: 1.85-6.24; p<0.0001). Flares treated with NSAIDs within 30 days of flare onset were approximately 2.6 weeks shorter than flares not managed with NSAIDs (95% CI: 0.43-4.68; p=0.02). Flares treated prophylactically and those treated early with NSAIDs did not differ in duration (p=0.26). Among the flares that received NSAID treatment within the first 30 days, earlier intervention was modestly associated with shorter flare durations (i.e., for each day that NSAID treatment was delayed, flare duration increased by 0.18 weeks; 95% CI: 0.03-0.33; p=0.02), though it was not statistically significant after controlling for covariates (p=0.06).NSAIDs given prophylactically or within 30 days of flare onset may shorten neuropsychiatric symptom duration in patients with new-onset and relapsing/remitting PANS and PANDAS. A randomized placebo-control clinical trial of NSAIDs in PANS is warranted to formally assess treatment efficacy.

View details for DOI 10.1089/cap.2016.0193

View details for PubMedID 28696786

Pediatric Acute-Onset Neuropsychiatric Syndrome Response to Oral Corticosteroid Bursts: An Observational Study of Patients in an Academic Community-Based PANS Clinic. Journal of child and adolescent psychopharmacology Brown, K., Farmer, C., Farhadian, B., Hernandez, J., Thienemann, M., Frankovich, J. 2017; 27 (7): 62939

Abstract

Sudden-onset severe obsessive-compulsive symptoms and/or severely restrictive food intake with at least two coinciding, similarly debilitating neuropsychiatric symptoms define Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). When associated with Group A Streptococcus, the syndrome is labeled Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS). An abnormal immune response to infection and subsequent neuroinflammation is postulated to play an etiologic role. Most patients have a relapsing-remitting course. Treatment outcome data for youth with PANS and PANDAS are limited.One hundred seventy-eight consecutive patients were seen in the Stanford PANS clinic between September 1, 2012 and January 15, 2016, of whom 98 met PANS or PANDAS criteria, had a single episode of PANS or relapsing/remitting course, and collectively experienced 403 flares. Eighty-five flares were treated with 102 total courses of oral corticosteroids of either short (4-5 days) or long (5 days-8 weeks) duration. Response to treatment was assessed within 14 days of initiating a short burst of corticosteroids and at the end of a long burst based on clinician documentation and patient questionnaires. Data were analyzed by using multilevel random-effects models.Patients experienced shorter flares when treated with oral corticosteroids (6.45.0 weeks vs. 11.48.6 weeks) than when not treated (p<0.001), even after controlling for presumed confounding variables, including age at flare, weeks since onset of PANS illness, sex, antibiotic treatment, prophylactic antibiotics, previous immunomodulatory treatment, maintenance anti-inflammatory therapy, psychiatric medications, and cognitive behavioral therapy (p<0.01). When corticosteroids were given for the initial PANS episode, flares tended to be shorter (10.35.7 weeks) than when not treated (16.59.6 weeks) (p=0.06). This difference was statistically significant after controlling for the relevant confounding variables listed earlier (p<0.01). Earlier use of corticosteroids was associated with shorter flare durations (p<0.001). Longer courses of corticosteroids were associated with a more enduring impact on the duration of neuropsychiatric symptom improvement (p=0.014).Corticosteroids may be a helpful treatment intervention in patients with new-onset and relapsing/remitting PANS and PANDAS, hastening symptom improvement or resolution. When corticosteroids are given earlier in a disease flare, symptoms improve more quickly and patients achieve clinical remission sooner. Longer courses of corticosteroids may result in more durable remissions. A double-blind placebo-controlled clinical trial of corticosteroids in PANS is warranted to formally assess treatment efficacy.

View details for DOI 10.1089/cap.2016.0139

View details for PubMedID 28714753

Clinical Evaluation of Youth with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): Recommendations from the 2013 PANS Consensus Conference. Journal of child and adolescent psychopharmacology Chang, K., Frankovich, J., Cooperstock, M., Cunningham, M. W., Latimer, M. E., Murphy, T. K., Pasternack, M., Thienemann, M., Williams, K., Walter, J., Swedo, S. E. 2015; 25 (1): 3-13

Abstract

On May 23 and 24, 2013, the First PANS Consensus Conference was convened at Stanford University, calling together a geographically diverse group of clinicians and researchers from complementary fields of pediatrics: General and developmental pediatrics, infectious diseases, immunology, rheumatology, neurology, and child psychiatry. Participants were academicians with clinical and research interests in pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS) in youth, and the larger category of pediatric acute-onset neuropsychiatric syndrome (PANS). The goals were to clarify the diagnostic boundaries of PANS, to develop systematic strategies for evaluation of suspected PANS cases, and to set forth the most urgently needed studies in this field. Presented here is a consensus statement proposing recommendations for the diagnostic evaluation of youth presenting with PANS.

View details for DOI 10.1089/cap.2014.0084

View details for PubMedID 25325534

View details for PubMedCentralID PMC4340805

An Electronic Health Record Investigation of Lenticulostriate Vasculopathy Features. American journal of perinatology Frankovich, J., Egan, M., Mahony, T., Benitz, W., Shaw, G. 2017; 34 (3): 253-258

Abstract

ObjectiveLenticulostriate vasculopathy (LSV) is characterized by linear hyperechogenicities in the basal ganglia found on the head ultrasounds of infants. We reviewed electronic health records of infants with and without LSV to investigate whether physician dictations indicated symptoms which could reflect subtle basal ganglia injury. Study DesignIn a case-control study, we analyzed data from 46 infants with LSV and 127 controls. Infants were stratified between term and preterm birth. Odds ratios (ORs) and 95% confidence intervals were calculated for tone abnormalities, apnea, feeding difficulties, seizures, and movement abnormalities in the presence of LSV. ResultsBoth term and preterm infants with LSV showed elevated risks for tone abnormalities (OR: 3.6 and 2.9, respectively). Term infants with LSV showed elevated risks for hypotonia (OR: 4.3), apnea (OR: 2.9), and feeding difficulties (OR: 4.1). Preterm infants with LSV showed elevated risks for truncal hypotonia (OR: 3.9) and hyperreflexia (OR: 3.9). ConclusionOur findings provide some evidence that LSV is associated with an increased risk of early signs of abnormal development, possibly relating to signs of subtle basal ganglia injury. Historically LSV has been considered incidental. The associations identified here suggest that LSV findings are worthy of further study.

View details for DOI 10.1055/s-0036-1585417

View details for PubMedID 27471823

Improvement of psychiatric symptoms in youth following resolution of sinusitis INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY Mahony, T., Sidell, D., Gans, H., Brown, K., Farhadian, B., Gustafson, M., Sherr, J., Thienemann, M., Frankovich, J. 2017; 92: 38-44

Abstract

Accumulating evidence supports a role for inflammation in psychiatric illness, and the onset or exacerbation of psychiatric symptoms may follow non-CNS infections. Here, we provide the first detailed description of obsessive-compulsive and related psychiatric symptoms arising concurrently with sinusitis.We reviewed the charts of 150 consecutive patients evaluated in our Pediatric Acute-onset Neuropsychiatric Syndromes clinic for documented sinusitis as defined by the American Academy of Pediatrics guidelines. Sinusitis treatments, sinonasal imaging, and neuropsychiatric symptoms before, during, and after sinusitis onset were noted. Patients were included in the final review if they had a clear diagnosis of isolated sinusitis (without concurrent illness and/or immunodeficiency), and were evaluated during an episode of sinusitis.10/150 (6.6%) patients had isolated sinusitis at the time of their neuropsychiatric deterioration. Eight patients received antibiotics to treat sinusitis, three of whom also received sinus surgery. Neuropsychiatric symptoms improved in all eight patients concurrent with resolution of sinusitis per parent report and clinician assessment. One patient did not follow through with recommended sinus surgery or antibiotics and her psychiatric symptoms persisted. One patient was lost to follow-up.Improvement of psychiatric symptoms correlated with resolution of sinus disease in this retrospective study. Identification, treatment, and resolution of underlying infections, including sinusitis, may have the potential to change the trajectory of some neuropsychiatric illnesses. Randomized clinical trials are needed.

View details for DOI 10.1016/j.ijporl.2016.10.034

View details for Web of Science ID 000393245100008

View details for PubMedID 28012531

Single amino acid charge switch defines clinically distinct proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1)-associated inflammatory diseases JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Holzinger, D., Fassl, S. K., de Jager, W., Lohse, P., Roehrig, U. F., Gattorno, M., Omenetti, A., Chiesa, S., Schena, F., Austermann, J., Vogl, T., Kuhns, D. B., Holland, S. M., Rodriguez-Gallego, C., Lopez-Almaraz, R., Arostegui, J. I., Colino, E., Roldan, R., Fessatou, S., Isidor, B., Poignant, S., Ito, K., Epple, H., Bernstein, J. A., Jeng, M., Frankovich, J., Lionetti, G., Church, J. A., Ong, P. Y., LaPlant, M., Abinun, M., Skinner, R., Bigley, V., Sachs, U. J., Hinze, C., Hoppenreijs, E., Ehrchen, J., Foell, D., Chae, J. J., Ombrello, A., Aksentijevich, I., Sunderkoetter, C., Roth, J. 2015; 136 (5): 1337-1345

Abstract

Hyperzincemia and hypercalprotectinemia (Hz/Hc) is a distinct autoinflammatory entity involving extremely high serum concentrations of the proinflammatory alarmin myeloid-related protein (MRP) 8/14 (S100A8/S100A9 and calprotectin).We sought to characterize the genetic cause and clinical spectrum of Hz/Hc.Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene sequencing was performed in 14 patients with Hz/Hc, and their clinical phenotype was compared with that of 11 patients with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. PSTPIP1-pyrin interactions were analyzed by means of immunoprecipitation and Western blotting. A structural model of the PSTPIP1 dimer was generated. Cytokine profiles were analyzed by using the multiplex immunoassay, and MRP8/14 serum concentrations were analyzed by using an ELISA.Thirteen patients were heterozygous for a missense mutation in the PSTPIP1 gene, resulting in a p.E250K mutation, and 1 carried a mutation resulting in p.E257K. Both mutations substantially alter the electrostatic potential of the PSTPIP1 dimer model in a region critical for protein-protein interaction. Patients with Hz/Hc have extremely high MRP8/14 concentrations (2045 1300 g/mL) compared with those with PAPA syndrome (116 74 g/mL) and have a distinct clinical phenotype. A specific cytokine profile is associated with Hz/Hc. Hz/Hc mutations altered protein binding of PSTPIP1, increasing interaction with pyrin through phosphorylation of PSTPIP1.Mutations resulting in charge reversal in the y-domain of PSTPIP1 (EK) and increased interaction with pyrin cause a distinct autoinflammatory disorder defined by clinical and biochemical features not found in patients with PAPA syndrome, indicating a unique genotype-phenotype correlation for mutations in the PSTPIP1 gene. This is the first inborn autoinflammatory syndrome in which inflammation is driven by uncontrolled release of members of the alarmin family.

View details for DOI 10.1016/j.jaci.2015.04.016

View details for Web of Science ID 000364787200024

View details for PubMedID 26025129

Multidisciplinary clinic dedicated to treating youth with pediatric acute-onset neuropsychiatric syndrome: presenting characteristics of the first 47 consecutive patients. Journal of child and adolescent psychopharmacology Frankovich, J., Thienemann, M., Pearlstein, J., Crable, A., Brown, K., Chang, K. 2015; 25 (1): 38-47

Abstract

Abrupt, dramatic onset obsessive-compulsive disorder (OCD) and/or eating restriction with at least two coinciding symptoms (anxiety, mood dysregulation, irritability/aggression/oppositionality, behavioral regression, cognitive deterioration, sensory or motor abnormalities, or somatic symptoms) defines pediatric acute-onset neuropsychiatric syndrome (PANS). Descriptions of clinical data in such youth are limited.We reviewed charts of 53 consecutive patients evaluated in our PANS Clinic; 47 met PANS symptom criteria but not all met the requirement for "acute onset." Patients meeting full criteria for PANS were compared with patients who had a subacute/insidious onset of symptoms.Nineteen of 47 (40%) patients in the study had acute onset of symptoms. In these patients, autoimmune/inflammatory diseases and psychiatric disorders were common in first-degree family members (71% and 78%, respectively). Most acute-onset patients had a relapsing/remitting course (84%), prominent sleep disturbances (84%), urinary issues (58%), sensory amplification (66%), gastrointestinal symptoms (42%), and generalized pain (68%). Inflammatory back pain (21%) and other arthritis conditions (28%) were also common. Suicidal and homicidal thoughts and gestures were common (44% and 17%, respectively) as were violent outbursts (61%). Group A streptococcus (GAS) was the most commonly identified infection at onset (21%) and during flares (74%). Rates of the abovementioned characteristics did not differ between the acute-onset group and the subacute/insidious-onset groups. Low levels of immunoglobulins were more common in the subacute/insidious-onset group (75%) compared with the acute-onset group (22%), but this was not statistically significant (p=0.06).In our PANS clinic, 40% of patients had acute onset of symptoms. However, those with and without acute onset of symptoms had similar symptom presentation, rates of inflammatory conditions, somatic symptoms, and violent thoughts and behaviors. GAS infections were the most commonly identified infection at onset and at symptom flares. Because of the wide variety of medical and psychiatric symptoms, youth with PANS may require a multidisciplinary team for adequate care management.

View details for DOI 10.1089/cap.2014.0081

View details for PubMedID 25695943

Five youth with pediatric acute-onset neuropsychiatric syndrome of differing etiologies. Journal of child and adolescent psychopharmacology Frankovich, J., Thienemann, M., Rana, S., Chang, K. 2015; 25 (1): 31-37

Abstract

Pediatric acute-onset neuropsychiatric syndrome (PANS) is diagnosed by the abrupt onset of new obsessive compulsive disorder (OCD) or food-restricting symptoms, and at least two of a variety of other neuropsychiatric symptoms. Detailed clinical presentation of youth with this condition has not yet been provided in the literature.We review the clinical charts of five youth meeting criteria for PANS in our PANS Clinic. These five patients were selected for differing underlying causes thought to be driving an inflammatory response that appeared to impact psychiatric symptoms.Five youth with varying potential etiologies impacting neuropsychiatric symptoms were identified. These youth were from 8 to 18 years old at the onset of their PANS illness, and had bacterial, autoimmune, and unknown etiologies. Treatment directed at presumed etiologies ranged from antibiotics to intravenous gamma globulin (IVIG) to other immunomodulatory regimens, and appeared to improve the psychiatric illness.Youth with PANS may present in differing ways, with psychiatric and physical symptoms overlapping with inflammatory or infectious diseases, pain syndromes, and other psychiatric diagnoses. Patients' psychiatric symptoms may respond to treatments targeting the underlying cause of physical illness. Faced with a pediatric patient demonstrating the abrupt onset or exacerbation of psychiatric and physical symptoms, clinicians should consider PANS in their differential diagnosis.

View details for DOI 10.1089/cap.2014.0056

View details for PubMedID 25695942

Pilot Study of Reproductive Health Counseling in a Pediatric Rheumatology Clinic ARTHRITIS CARE & RESEARCH Ronis, T., Frankovich, J., Yen, S., Sandborg, C., Chira, P. 2014; 66 (4): 631-635

View details for DOI 10.1002/acr.22159

View details for Web of Science ID 000333380400017

Pilot study of reproductive health counseling in a pediatric rheumatology clinic. Arthritis care & research Ronis, T., Frankovich, J., Yen, S., Sandborg, C., Chira, P. 2014; 66 (4): 631-635

Abstract

Objective: To assess perception and behavior after reproductive health counseling among adolescent patients in a tertiary care-based pediatric rheumatology clinic. Methods: Adolescent females seen at Stanford pediatric rheumatology clinic were prospectively enrolled during routine visits. At study start, standard clinic procedures for the following were reviewed with providers: 1) HEADSS (home, education, activities, drugs, sexual activity, and suicide/depression) assessment; 2) reproductive health counseling; and 3) medical record documentation. Patients were enrolled if providers indicated that they performed HEADSS assessment and reproductive health counseling. At enrollment, patients completed a survey to assess perceptions of reproductive health counseling. Chart review confirmed documented discussions. Follow-up survey 3-5 months after enrollment tracked reproductive health information seeking behavior. Results: Ninety females (ages 17 2 years old) participated. Almost all patients (99%) agreed that reproductive health was discussed. Seventy-one percent reported that pregnancy risks were discussed, 42% had recent concerns about reproductive health, and 33% reported their provider recommended that they seek further reproductive health care. Eighty-four patients completed follow-up phone surveys, with 25% reporting seeking further information on reproductive health concerns but merely 9.5% actually sought further care. Only 18% reported having ever asked their rheumatology provider for guidance regarding reproductive health care concerns. Conclusion: Routine reproductive health discussion and counseling are necessary in a rheumatology clinic; as in our experience, a substantial number of adolescents have concerns and actively seek reproductive health information. Despite these discussions, teens rarely pursued further reproductive health care. Further work to bridge this gap is needed.

View details for PubMedID 24022992

Pediatric plastic bronchitis: case report and retrospective comparative analysis of epidemiology and pathology. Case reports in pulmonology Kunder, R., Kunder, C., Sun, H. Y., Berry, G., Messner, A., Frankovich, J., Roth, S., Mark, J. 2013; 2013: 649365-?

Abstract

Plastic bronchitis (PB) is a pathologic condition in which airway casts develop in the tracheobronchial tree causing airway obstruction. There is no standard treatment strategy for this uncommon condition. We report an index patient treated using an emerging multimodal strategy of directly instilled and inhaled tissue plasminogen activator (t-PA) as well as 13 other cases of PB at our institution between 2000 and 2012. The majority of cases (n = 8) occurred in patients with congenital heart disease. Clinical presentations, treatments used, histopathology of the casts, and patient outcomes are reviewed. Further discussion is focused on the epidemiology of plastic bronchitis and a systematic approach to the histologic classification of casts. Comorbid conditions identified in this study included congenital heart disease (8), pneumonia (3), and asthma (2). Our institutional prevalence rate was 6.8 per 100,000 patients, and our case fatality rate was 7%.

View details for DOI 10.1155/2013/649365

View details for PubMedID 23662235

View details for PubMedCentralID PMC3639666

Profiling risk factors for chronic uveitis in juvenile idiopathic arthritis: a new model for EHR-based research. Pediatric rheumatology online journal Cole, T. S., Frankovich, J., Iyer, S., LePendu, P., Bauer-Mehren, A., Shah, N. H. 2013; 11 (1): 45-?

Abstract

Juvenile idiopathic arthritis is the most common rheumatic disease in children. Chronic uveitis is a common and serious comorbid condition of juvenile idiopathic arthritis, with insidious presentation and potential to cause blindness. Knowledge of clinical associations will improve risk stratification. Based on clinical observation, we hypothesized that allergic conditions are associated with chronic uveitis in juvenile idiopathic arthritis patients.This study is a retrospective cohort study using Stanford's clinical data warehouse containing data from Lucile Packard Children's Hospital from 2000-2011 to analyze patient characteristics associated with chronic uveitis in a large juvenile idiopathic arthritis cohort. Clinical notes in patients under 16years of age were processed via a validated text analytics pipeline. Bivariate-associated variables were used in a multivariate logistic regression adjusted for age, gender, and race. Previously reported associations were evaluated to validate our methods. The main outcome measure was presence of terms indicating allergy or allergy medications use overrepresented in juvenile idiopathic arthritis patients with chronic uveitis. Residual text features were then used in unsupervised hierarchical clustering to compare clinical text similarity between patients with and without uveitis.Previously reported associations with uveitis in juvenile idiopathic arthritis patients (earlier age at arthritis diagnosis, oligoarticular-onset disease, antinuclear antibody status, history of psoriasis) were reproduced in our study. Use of allergy medications and terms describing allergic conditions were independently associated with chronic uveitis. The association with allergy drugs when adjusted for known associations remained significant (OR 2.54, 95% CI 1.22-5.4).This study shows the potential of using a validated text analytics pipeline on clinical data warehouses to examine practice-based evidence for evaluating hypotheses formed during patient care. Our study reproduces four known associations with uveitis development in juvenile idiopathic arthritis patients, and reports a new association between allergic conditions and chronic uveitis in juvenile idiopathic arthritis patients.

View details for DOI 10.1186/1546-0096-11-45

View details for PubMedID 24299016

European ancestry decreases the risk of early onset, severe lupus nephritis in a single center, multiethnic pediatric lupus inception cohort LUPUS Frankovich, J. D., Hsu, J. J., Sandborg, C. I. 2012; 21 (4): 421-429

Abstract

To determine whether pediatric SLE patients without European ancestry are at higher risk for development of severe lupus nephritis (ISN/RPS class III, IV or V).Ninety-eight of 101 patients with pediatric SLE (age <18 years at diagnosis) were enrolled. Race/ethnicity of four grandparents, socioeconomic status (SES) and language proficiency were collected. The primary outcome was time to development of severe lupus nephritis.Based on patient report of four grandparent ancestry, 29% had at least one grandparent of European ancestry (14% had all four grandparents of European ancestry). Patients without European ancestry were 46% Hispanic, 47% Asian, and 3% African American. In the entire 98 patient cohort, 12% had 3 different ancestries. Patients without European ancestry had significantly lower SES levels and English proficiency. There was no significant difference between patients with or without European ancestry in duration of SLE, age of onset, and lag time between symptoms and diagnosis. Patients with at least one grandparent of European ancestry had a decreased risk of developing severe lupus nephritis, which remained significant after controlling for age, gender, SES and English proficiency (hazard ratio 0.4, 95% confidence interval 0.2-0.9).This study demonstrates that presence of at least one grandparent of European ancestry decreases the risk of severe lupus nephritis, a finding that is not explained by measurable socioeconomic differences and language barriers.

View details for DOI 10.1177/0961203312437805

View details for Web of Science ID 000301583400008

View details for PubMedID 22427363

Evidence-Based Medicine in the EMR Era NEW ENGLAND JOURNAL OF MEDICINE Frankovich, J., Longhurst, C. A., Sutherland, S. M. 2011; 365 (19): 1758-1759

View details for DOI 10.1056/NEJMp1108726

View details for Web of Science ID 000296762800003

View details for PubMedID 22047518

Maternal Autoimmunity and Neonatal Brain Abnormalities: Cerebral Dysmaturation, Diencephalon Abnormalities, and Lenticulostriate Vasculopathy 75th Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) / 46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals (ARHP) Frankovich, J. D., Barnes, P. D., Sandborg, C. I., Chakravarty, E. F. WILEY-BLACKWELL. 2011: S785S785
Autoinflammatory Diseases in the Neonate: Mimickers of Neonatal Infections NeoReviews Lionetti, G., Lapidus, S., Goldbach-Mansky, R., Frankovich, J. 2010; 11 (10): e566-e577

View details for DOI 10.1542/neo.11-10-e566

Acute hepatitis in three patients with systemic juvenile idiopathic arthritis taking interleukin-1 receptor antagonist PEDIATRIC RHEUMATOLOGY Canna, S., Frankovich, J., Higgins, G., Narkewicz, M. R., Nash, S. R., Hollister, J. R., Soep, J. B., Dragone, L. L. 2009; 7

Abstract

We investigated the etiology of acute hepatitis in three children with systemic Juvenile Idiopathic Arthritis (sJIA) taking Interleukin-1 receptor antagonist (IL1RA).Laboratory and clinical data for three children with sJIA diagnosed at ages 13 months to 8 years who developed acute hepatitis during treatment with IL1RA were reviewed for evidence of sJIA flare, infection, macrophage activation syndrome (MAS), malignancy, and drug reaction.In all patients, hepatitis persisted despite cessation of known hepatotoxic drugs and in absence of known infectious triggers, until discontinuation of IL1RA. Liver biopsies had mixed inflammatory infiltrates with associated hepatocellular injury suggestive of an exogenous trigger. At the time of hepatitis, laboratory data and liver biopsies were not characteristic of MAS. In two patients, transaminitis resolved within one week of discontinuing IL1RA, the third improved dramatically in one month.Although sJIA symptoms improved significantly on IL1RA, it appeared that IL1RA contributed to the development of acute hepatitis. Hepatitis possibly occurred as a result of an altered immune response to a typical childhood infection while on IL1RA. Alternatively, hepatitis could have represented an atypical presentation of MAS in patients with sJIA taking IL1RA. Further investigation is warranted to determine how anti-IL1 therapies alter immune responsiveness to exogenous triggers in patients with immune dysfunction such as sJIA. Our patients suggest that close monitoring for hepatic and other toxicities is indicated when treating with IL1RA.

View details for DOI 10.1186/1546-0096-7-21

View details for Web of Science ID 000273814800001

View details for PubMedID 20028520

Neonatal Lupus and Related Autoimmune Disorders of Infants NeoReviews Frankovich, J., Sandborg, C., Barnes, P., Hintz, S., Chakravarty, E. 2008; 9 (5): e206-e217

View details for DOI 10.1542/neo.9-5-e206

High-dose therapy and autologous hematopoietic cell transplantation in children with primary refractory and relapsed Hodgkin's disease: Atopy predicts idiopathic diffuse lung injury syndromes BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Frankovich, J., Donaldson, S. S., Lee, Y. B., Wong, R. M., Amylon, M., Verneris, M. R. 2001; 7 (1): 49-57

Abstract

The use of high-dose therapy (HDT) and autologous hematopoietic cell transplantation (AHCT) for children and adolescents with primary refractory and relapsed Hodgkin's disease is increasing. The purpose of this retrospective analysis was to: (1) evaluate the outcome of HDT and AHCT in pediatric patients with Hodgkin's disease, and (2) identify factors that predispose patients to the development of transplantation-related complications. We describe the experiences of 34 pediatric patients from a single institution with primary refractory or relapsed Hodgkin's disease. HDT regimens consisted of cyclophosphamide and etoposide combined with either carmustine, chloroethylcyclohexylnitrosurea, or fractionated total body irradiation. Kaplan-Meier survival predicts that 67% (95% confidence interval [CI] 47%-87%) of patients will be alive and disease-free at 5 years. Nine patients had disease recurrence, of whom 5 relapsed after 1 year (1.5-6.3 years). Five patients succumbed to treatment-related toxicities, of whom 4 died of pulmonary failure. Fifteen patients (44%) developed post-AHCT idiopathic diffuse lung injury syndrome: acute alveolitis (n = 2); diffuse alveolar hemorrhage (n = 2); acute respiratory distress syndrome (n = 2); delayed interstitial pneumonitis (n = 8); and bronchiolitis obliterans (n = 1). The following factors did not predict for the development of a diffuse lung injury syndrome in univariate analysis: prior treatment with bleomycin, pre-HDT pulmonary function tests, and prior thoracic irradiation. Of the patients in our cohort, 44% had a history of atopy (allergic rhinitis and/or asthma). Multivariate logistic analysis revealed that a preexisting history of atopy was highly predictive of idiopathic pulmonary complications (P = .0001, odds ratio = 21, CI 3.6-125). Our experience shows that HDT followed by AHCT results in durable remissions in two thirds of pediatric patients with refractory and relapsed Hodgkin's disease, and a history of atopy is associated with post-AHCT pulmonary complications.

View details for Web of Science ID 000166841300008

View details for PubMedID 11215699

DISSOCIATION OF MINOR SATELLITE FROM THE CENTROMERE IN MOUSE JOURNAL OF CELL SCIENCE Vig, B. K., Latour, D., Frankovich, J. 1994; 107: 3091-3095

Abstract

The minor satellite DNA of mouse is believed to constitute the centromere. We report that centromeres of some chromosomes in the Cl1D cells of mouse are not associated with this DNA even though the latter is present on these chromosomes. The satellite DNA was detected distally from the centromere and could not be mistaken as a component of the centromere. We also report that the site of the primary constriction may not always coincide with the site of the anti-kinetochore antibody reaction. Whereas the regions containing the major satellite decondense upon treatment with bisbenzimidazole (Hoechst 33258), the sites carrying minor satellite resist decondensing.

View details for Web of Science ID A1994PV95900012

View details for PubMedID 7535306

COMPARISON OF THE ACTIONS OF ACETYLCHOLINE AND BRL-38227 IN THE GUINEA-PIG CORONARY-ARTERY BRITISH JOURNAL OF PHARMACOLOGY Eckman, D. M., FRANKOVICH, J. D., Keef, K. D. 1992; 106 (1): 9-16

Abstract

1. The contractile and electrical responses to acetylcholine (ACh) in isolated segments of guinea-pig and rabbit coronary arteries were compared to those of the putative adenosine 5'-triphosphate (ATP)-dependent K+ channel opener, BRL 38227. 2. Both ACh and BRL 38227 produced concentration-dependent relaxation of vessel segments contracted with the H1-receptor agonist, 2-(2-aminoethyl)pyridine. 3. An IC90 of either vasodilator also produced 17-20 mV of hyperpolarization of the guinea-pig coronary artery. 4. Glibenclamide (1-35 microM) depolarized the guinea-pig coronary artery by 8-12 mV and antagonized BRL 38227- but not ACh-induced relaxation and hyperpolarization. 5. In the guinea-pig coronary artery, the K+ channel blockers phencyclidine (PCP, 100 microM), tetraethylammonium (TEA, 10 mM) and scorpion venom (8.7 micrograms ml-1) all significantly reduced ACh-induced relaxation and hyperpolarization whereas only PCP was an effective antagonist of both relaxation and hyperpolarization with BRL 38227. 6. Similar effects of glibenclamide and scorpion venom on ACh- and BRL 38227-induced relaxation were observed in the rabbit coronary artery. 7. Apamin (3.5 microM) was without effect on either the ACh- or BRL 38227-induced relaxation in the guinea-pig coronary artery. 8. In conclusion, the actions of BRL 38227 in coronary artery are compatible with its proposed effects on ATP-dependent K+ channels. In contrast, the results with ACh suggest that some step between the initial binding of ACh to endothelial muscarinic receptors and the final relaxation of the smooth muscle depends upon the opening of Ca(2+)-activated K+ channels.

View details for Web of Science ID A1992HT20900002

View details for PubMedID 1504734