178 results on '"Mark Gorman"'
Search Results
2. Proposal to optimize evaluation and treatment of Febrile infection‐related epilepsy syndrome (FIRES): A Report from FIRES workshop
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Sookyong Koh, Elaine Wirrell, Annamaria Vezzani, Rima Nabbout, Eyal Muscal, Marios Kaliakatsos, Ronny Wickström, James J. Riviello, Andreas Brunklaus, Eric Payne, Antonio Valentin, Elizabeth Wells, Jessica L. Carpenter, Kihyeong Lee, Yi‐Chen Lai, Krista Eschbach, Craig A. Press, Mark Gorman, Coral M. Stredny, William Roche, and Tara Mangum
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anakinra ,cytokines ,epileptic encephalopathy ,immune activation ,neuroinflammation ,new‐onset refractory status epilepticus ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Febrile infection‐related epilepsy syndrome (FIRES) is a rare catastrophic epileptic encephalopathy that presents suddenly in otherwise normal children and young adults causing significant neurological disability, chronic epilepsy, and high rates of mortality. To suggest a therapy protocol to improve outcome of FIRES, workshops were held in conjunction with American Epilepsy Society annual meeting between 2017 and 2019. An international group of pediatric epileptologists, pediatric neurointensivists, rheumatologists and basic scientists with interest and expertise in FIRES convened to propose an algorithm for a standardized approach to the diagnosis and treatment of FIRES. The broad differential for refractory status epilepticus (RSE) should include FIRES, to allow empiric therapies to be started early in the clinical course. FIRES should be considered in all previously healthy patients older than two years of age who present with explosive onset of seizures rapidly progressing to RSE, following a febrile illness in the preceding two weeks. Once FIRES is suspected, early administrations of ketogenic diet and anakinra (the IL‐1 receptor antagonist that blocks biologic activity of IL‐1β) are recommended.
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- 2021
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3. miRNA contributions to pediatric‐onset multiple sclerosis inferred from GWAS
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Brooke Rhead, Xiaorong Shao, Jennifer S. Graves, Tanuja Chitnis, Amy T. Waldman, Timothy Lotze, Teri Schreiner, Anita Belman, Lauren Krupp, Benjamin M. Greenberg, Bianca Weinstock–Guttman, Gregory Aaen, Jan M. Tillema, Moses Rodriguez, Janace Hart, Stacy Caillier, Jayne Ness, Yolanda Harris, Jennifer Rubin, Meghan S. Candee, Mark Gorman, Leslie Benson, Soe Mar, Ilana Kahn, John Rose, T. Charles Casper, Hong Quach, Diana Quach, Catherine Schaefer, Emmanuelle Waubant, Lisa F. Barcellos, and the US Network of Pediatric MS Centers
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Objective Onset of multiple sclerosis (MS) occurs in childhood for approximately 5% of cases (pediatric MS, or ped‐MS). Epigenetic influences are strongly implicated in MS pathogenesis in adults, including the contribution from microRNAs (miRNAs), small noncoding RNAs that affect gene expression by binding target gene mRNAs. Few studies have specifically examined miRNAs in ped‐MS, but individuals developing MS at an early age may carry a relatively high burden of genetic risk factors, and miRNA dysregulation may therefore play a larger role in the development of ped‐MS than in adult‐onset MS. This study aimed to look for evidence of miRNA involvement in ped‐MS pathogenesis. Methods GWAS results from 486 ped‐MS cases and 1362 controls from the U.S. Pediatric MS Network and Kaiser Permanente Northern California membership were investigated for miRNA‐specific signals. First, enrichment of miRNA‐target gene network signals was evaluated using MIGWAS software. Second, SNPs in miRNA genes and in target gene binding sites (miR−SNPs) were tested for association with ped‐MS, and pathway analysis was performed on associated target genes. Results MIGWAS analysis showed that miRNA‐target gene signals were enriched in GWAS (P = 0.038) and identified 39 candidate biomarker miRNA‐target gene pairs, including immune and neuronal signaling genes. The miR‐SNP analysis implicated dysregulation of miRNA binding to target genes in five pathways, mainly involved in immune signaling. Interpretation Evidence from GWAS suggests that miRNAs play a role in ped‐MS pathogenesis by affecting immune signaling and other pathways. Candidate biomarker miRNA‐target gene pairs should be further studied for diagnostic, prognostic, and/or therapeutic utility.
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- 2019
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4. Effective stakeholder engagement: design and implementation of a clinical trial (SWOG S1415CD) to improve cancer care
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Sarah Barger, Sean D. Sullivan, Ari Bell-Brown, Brad Bott, Anne Marie Ciccarella, John Golenski, Mark Gorman, Judy Johnson, Karma Kreizenbeck, Florence Kurttila, Ginny Mason, Jamie Myers, Carole Seigel, James L. Wade, Guneet Walia, Kate Watabayashi, Gary H. Lyman, and Scott D. Ramsey
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Stakeholder engagement ,Patient engagement ,Oncology ,Clinical trial ,Cancer ,Cancer care delivery research ,Medicine (General) ,R5-920 - Abstract
Abstract Background The Fred Hutchinson Cancer Research Center has engaged an External Stakeholder Advisory Group (ESAG) in the planning and implementation of the TrACER Study (S1415CD), a five-year pragmatic clinical trial assessing the effectiveness of a guideline-based colony stimulating factor standing order intervention. The trial is being conducted by SWOG through the National Cancer Institute Community Oncology Research Program in 45 clinics. The ESAG includes ten patient partners, two payers, two pharmacists, two guideline experts, four providers and one medical ethicist. This manuscript describes the ESAG’s role and impact on the trial. Methods During early trial development, the research team assembled the ESAG to inform plans for each phase of the trial. ESAG members provide feedback and engage in problem solving to improve trial implementation. Each year, members participate in one in-person meeting, web conferences and targeted email discussion. Additionally, they complete a survey that assesses their satisfaction with communication and collaboration. The research team collected and reviewed stakeholder input from 2014 to 2018 for impact on the trial. Results The ESAG has informed trial design, implementation and dissemination planning. The group advised the trial’s endpoints, regimen list and development of cohort and usual care arms. Based on ESAG input, the research team enhanced patient surveys and added pharmacy-related questions to the component application to assess order entry systems. ESAG patient partners collaborated with the research team to develop a patient brochure and study summary for clinic staff. In addition to identifying recruitment strategies and patient-oriented platforms for publicly sharing results, ESAG members participated as co-authors on this manuscript and a conference poster presentation highlighting stakeholder influence on the trial. The annual satisfaction survey results suggest that ESAG members were satisfied with the methods, frequency and target areas of their engagement in the trial during project years 1–3. Conclusions Diverse stakeholder engagement has been essential in optimizing the design, implementation and planned dissemination of the TrACER Study. The lessons described in the manuscript may assist others to effectively partner with stakeholders on clinical research.
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- 2019
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5. Calm in the midst of cytokine storm: a collaborative approach to the diagnosis and treatment of hemophagocytic lymphohistiocytosis and macrophage activation syndrome
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Olha Halyabar, Margaret H. Chang, Michelle L. Schoettler, Marc A. Schwartz, Ezgi H. Baris, Leslie A. Benson, Catherine M. Biggs, Mark Gorman, Leslie Lehmann, Mindy S. Lo, Peter A. Nigrovic, Craig D. Platt, Gregory P. Priebe, Jared Rowe, Robert P. Sundel, Neeraj K. Surana, Katja G. Weinacht, Alison Mann, Jenny Chan Yuen, Patricia Meleedy-Rey, Amy Starmer, Taruna Banerjee, Fatma Dedeoglu, Barbara A. Degar, Melissa M. Hazen, and Lauren A. Henderson
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Macrophage activation syndrome (MAS) ,Hemophagocytic lymphohistiocytosis (HLH) ,Quality improvement research ,Evidence-based guideline ,Pediatrics ,RJ1-570 ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) were historically thought to be distinct entities, often managed in isolation. In fact, these conditions are closely related. A collaborative approach, which incorporates expertise from subspecialties that previously treated HLH/MAS independently, is needed. We leveraged quality improvement (QI) techniques in the form of an Evidence-Based Guideline (EBG) to build consensus across disciplines on the diagnosis and treatment of HLH/MAS. Methods A multidisciplinary work group was convened that met monthly to develop the HLH/MAS EBG. Literature review and expert opinion were used to develop a management strategy for HLH/MAS. The EBG was implemented, and quality metrics were selected to monitor outcomes. Results An HLH/MAS clinical team was formed with representatives from subspecialties involved in the care of patients with HLH/MAS. Broad entry criteria for the HLH/MAS EBG were established and included fever and ferritin ≥500 ng/mL. The rheumatology team was identified as the “gate-keeper,” charged with overseeing the diagnostic evaluation recommended in the EBG. First-line medications were recommended based on the acuity of illness and risk of concurrent infection. Quality metrics to be tracked prospectively based on time to initiation of treatment and clinical response were selected. Conclusion HLH/MAS are increasingly considered to be a spectrum of related conditions, and joint management across subspecialties could improve patient outcomes. Our experience in creating a multidisciplinary approach to HLH/MAS management can serve as a model for care at other institutions.
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- 2019
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6. Health-related quality of life in children with inflammatory brain disease
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Elina Liu, Marinka Twilt, Pascal N. Tyrrell, Anastasia Dropol, Shehla Sheikh, Mark Gorman, Susan Kim, David A. Cabral, Rob Forsyth, Heather Van Mater, Suzanne Li, Adam M. Huber, Elizabeth Stringer, Eyal Muscal, Dawn Wahezi, Mary Toth, Pavla Dolezalova, Katerina Kobrova, Goran Ristic, and Susanne M. Benseler
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Pediatrics ,Inflammatory brain disease ,CNS vasculitis ,Health-related quality of life ,Quality of life ,RJ1-570 ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Objective To quantify the impact of inflammatory brain diseases in the pediatric population on health-related quality of life, including the subdomains of physical, emotional, school and social functioning. Methods This was a multicenter, observational cohort study of children (
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- 2018
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7. Identifying treatment options for BRAFV600 wild-type metastatic melanoma: A SU2C/MRA genomics-enabled clinical trial.
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Patricia M LoRusso, Aleksandar Sekulic, Jeffrey A Sosman, Winnie S Liang, John Carpten, David W Craig, David B Solit, Alan H Bryce, Jeffrey A Kiefer, Jessica Aldrich, Sara Nasser, Rebecca Halperin, Sara A Byron, Mary Jo Pilat, Scott A Boerner, Diane Durecki, William P D Hendricks, Daniel Enriquez, Tyler Izatt, Jonathan Keats, Christophe Legendre, Svetomir N Markovic, Amy Weise, Fatima Naveed, Jessica Schmidt, Gargi D Basu, Shobana Sekar, Jonathan Adkins, Erica Tassone, Karthigayini Sivaprakasam, Victoria Zismann, Valerie S Calvert, Emanuel F Petricoin, Leslie Anne Fecher, Christopher Lao, J Paul Eder, Nicholas J Vogelzang, Jane Perlmutter, Mark Gorman, Barbara Manica, Lisa Fox, Nicholas Schork, Daniel Zelterman, Michelle DeVeaux, Richard W Joseph, C Lance Cowey, and Jeffrey M Trent
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Medicine ,Science - Abstract
Although combination BRAF and MEK inhibitors are highly effective for the 40-50% of cutaneous metastatic melanomas harboring BRAFV600 mutations, targeted agents have been ineffective for BRAFV600wild-type (wt) metastatic melanomas. The SU2C Genomics-Enabled Medicine for Melanoma Trial utilized a Simon two-stage optimal design to assess whether comprehensive genomic profiling improves selection of molecular-based therapies for BRAFV600wt metastatic melanoma patients who had progressed on standard-of-care therapy, which may include immunotherapy. Of the response-evaluable patients, binimetinib was selected for 20 patients randomized to the genomics-enabled arm, and nine were treated on the alternate treatment arm. Response rates for 27 patients treated with targeted recommendations included one (4%) partial response, 18 (67%) with stable disease, and eight (30%) with progressive disease. Post-trial genomic and protein pathway activation mapping identified additional drug classes that may be considered for future studies. Our results highlight the complexity and heterogeneity of metastatic melanomas, as well as how the lack of response in this trial may be associated with limitations including monotherapy drug selection and the dearth of available single and combination molecularly-driven therapies to treat BRAFV600wt metastatic melanomas.
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- 2021
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8. Admixture mapping reveals evidence of differential multiple sclerosis risk by genetic ancestry.
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Calvin Chi, Xiaorong Shao, Brooke Rhead, Edlin Gonzales, Jessica B Smith, Anny H Xiang, Jennifer Graves, Amy Waldman, Timothy Lotze, Teri Schreiner, Bianca Weinstock-Guttman, Gregory Aaen, Jan-Mendelt Tillema, Jayne Ness, Meghan Candee, Lauren Krupp, Mark Gorman, Leslie Benson, Tanuja Chitnis, Soe Mar, Anita Belman, Theron Charles Casper, John Rose, Manikum Moodley, Mary Rensel, Moses Rodriguez, Benjamin Greenberg, Llana Kahn, Jennifer Rubin, Catherine Schaefer, Emmanuelle Waubant, Annette Langer-Gould, and Lisa F Barcellos
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Genetics ,QH426-470 - Abstract
Multiple sclerosis (MS) is an autoimmune disease with high prevalence among populations of northern European ancestry. Past studies have shown that exposure to ultraviolet radiation could explain the difference in MS prevalence across the globe. In this study, we investigate whether the difference in MS prevalence could be explained by European genetic risk factors. We characterized the ancestry of MS-associated alleles using RFMix, a conditional random field parameterized by random forests, to estimate their local ancestry in the largest assembled admixed population to date, with 3,692 African Americans, 4,915 Asian Americans, and 3,777 Hispanics. The majority of MS-associated human leukocyte antigen (HLA) alleles, including the prominent HLA-DRB1*15:01 risk allele, exhibited cosmopolitan ancestry. Ancestry-specific MS-associated HLA alleles were also identified. Analysis of the HLA-DRB1*15:01 risk allele in African Americans revealed that alleles on the European haplotype conferred three times the disease risk compared to those on the African haplotype. Furthermore, we found evidence that the European and African HLA-DRB1*15:01 alleles exhibit single nucleotide polymorphism (SNP) differences in regions encoding the HLA-DRB1 antigen-binding heterodimer. Additional evidence for increased risk of MS conferred by the European haplotype were found for HLA-B*07:02 and HLA-A*03:01 in African Americans. Most of the 200 non-HLA MS SNPs previously established in European populations were not significantly associated with MS in admixed populations, nor were they ancestrally more European in cases compared to controls. Lastly, a genome-wide search of association between European ancestry and MS revealed a region of interest close to the ZNF596 gene on chromosome 8 in Hispanics; cases had a significantly higher proportion of European ancestry compared to controls. In conclusion, our study established that the genetic ancestry of MS-associated alleles is complex and implicated that difference in MS prevalence could be explained by the ancestry of MS-associated alleles.
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- 2019
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9. The use of chemotherapeutics for the treatment of keloid scars
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Christopher David Jones, Luke Guiot, Mike Samy, Mark Gorman, and Hamid Tehrani
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Keloid ,hypertrophic scar ,chemotherapeutic agents ,Dermatology ,RL1-803 - Abstract
Keloid scars are pathological scars, which develop as a result of exaggerated dermal tissue proliferation following cutaneous injury and often cause physical, psychological and cosmetic problems. Various theories regarding keloidogenesis exist, however the precise pathophysiological events remain unclear. Many different treatment modalities have been implicated in their management, but currently there is no entirely satisfactory method for treating all keloid lesions. We review a number of different chemotherapeutic agents which have been proposed for the treatment of keloid and hypertrophic scars while giving insight into some of the novel chemotherapeutic drugs which are currently being investigated. Non-randomized trials evaluating the influence of different chemotherapeutic agents, such as 5-fluorouracil (5-FU); mitomycin C; bleomycin and steroid injection, either alone or in combination with other chemotherapeutic agents or alternative treatment modalities, for the treatment of keloids were identified using a predefined PubMed search strategy. Twenty seven papers were identified. Scar improvement ≥50% was found in the majority of cases treated with 5-FU, with similar results found for mitomycin C, bleomycin and steroid injection. Combined intralesional 5-FU and steroid injection produced statistically significant improvements when compared to monotherapy. Monotherapy recurrence rates ranged from 0-47% for 5-FU, 0-15% for bleomycin and 0-50% for steroid injection. However, combined therapy in the form of surgical excision and adjuvant 5-FU or steroid injections demonstrated lower recurrence rates; 19% and 6% respectively. Currently, most of the literature supports the use of combination therapy (usually surgery and adjuvant chemotherapy) as the mainstay treatment of keloids, however further investigation is necessary to determine success rates over longer time frames. Furthermore, there is the potential for novel therapies, but further investigation is required to elucidate their true efficacy.
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- 2015
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10. A Left-Sided Prevalence of Lentigo Maligna: A UK Based Observational Study and Review of the Evidence
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Mark Gorman, Andrew Hart, and Bipin Mathew
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Dermatology ,RL1-803 - Abstract
Skin cancer has been shown to present asymmetrically, prevalent on the left side of the body, more so in subtypes of cutaneous melanoma such as lentigo maligna. Biases have been linked to cumulative UV light exposure and automobile driving patterns. Though left-right ratios have previously correlated with the side men or women tend to position themselves or countries drive on, more recent trends indicate a consistent left-sided bias. To clarify reasons for changing trends, a review of the evidence base and LM’s laterality in a UK cohort (99 cases 2000–2011) was conducted for the first time. The strong correlation of left-sided excess, found in both genders (ratios 1.381–1.5, P
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- 2015
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11. Adverse orthopedic effect of exogenous estrogens on men undergoing cross-gender hormonal therapy
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Muhammad Adil Abbas Khan, Zain A. Sobani, and Mark Gorman
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Published
- 2011
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12. Convolutional AutoEncoders for Anomaly Detection in Semiconductor Manufacturing.
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Mark Gorman, Xuemei Ding, Liam P. Maguire, and Damien Coyle
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- 2023
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13. Characteristics of pediatric patients with multiple sclerosis and related disorders infected with SARS-CoV-2
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Teri Schreiner, Molly Wilson-Murphy, Jan Mendelt-Tillema, Michael Waltz, Rachel Codden, Leslie Benson, Mark Gorman, Manu Goyal, Lauren Krupp, Tim Lotze, Soe Mar, Jayne Ness, Mary Rensel, Shelly Roalstad, Moses Rodriguez, John Rose, Nikita Shukla, Emmanuelle Waubant, Yolanda Wheeler, T Charles Casper, and Tanuja Chitnis
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Neurology ,Neurology (clinical) - Abstract
Background: Pediatric patients with multiple sclerosis (POMS) and related disorders, clinically isolated syndrome (CIS), myelin oligodendrocyte glycoprotein antibody disorder (MOGAD), and neuromyelitis optica spectrum disorder (NMOSD), are commonly treated with immunosuppressants. Understanding the impact of SARS-CoV-2 infection in patients may inform treatment decisions. Objective: Characterize SARS-CoV-2 infection prevalence and severity among a cohort of patients with POMS and related disorders, as well as the impact of disease-modifying therapies (DMTs). Methods: POMS and related disorders patients enrolled in a large, prospective registry were screened for COVID-19 during standard-of-care neurology visits. If confirmed positive of having infection, further analysis was undertaken. Results: Six hundred and sixty-nine patients were surveyed between March 2020 and August 2021. There were 73 confirmed COVID-19 infections. Eight of nine hospitalized patients (89%), and all patients admitted to the ICU were treated with B cell depleting therapy. The unadjusted odds ratio of hospitalization among those who tested positive of having had COVID-19 was 15.27 among those on B-cell-depleting therapy ( p = 0.016). Conclusions: B-cell-depleting treatment was associated with a higher risk of COVID-19, higher rates of hospitalization, and ICU admission, suggesting this therapy carries a higher risk of severe infection in POMS and related disorders.
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- 2023
14. Anomaly Detection in Batch Manufacturing Processes Using Localized Reconstruction Errors From 1-D Convolutional AutoEncoders
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Mark Gorman, Xuemei Ding, Liam Maguire, and Damien Coyle
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semiconductor manufacturing ,Deep learning ,Condensed Matter Physics ,reconstruction error ,convolutional autoencoder ,Industrial and Manufacturing Engineering ,Electronic, Optical and Magnetic Materials ,Electrical and Electronic Engineering ,fault detection and classification - Abstract
Multivariate batch time-series data sets within Semiconductor manufacturing processes present a difficult environment for effective Anomaly Detection (AD). The challenge is amplified by the limited availability of ground truth labelled data. In scenarios where AD is possible, black box modelling approaches constrain model interpretability. These challenges obstruct the widespread adoption of Deep Learning solutions. The objective of the study is to demonstrate an AD approach which employs 1-Dimensional Convolutional AutoEncoders (1d-CAE) and Localised Reconstruction Error (LRE) to improve AD performance and interpretability. Using LRE to identify sensors and data that result in the anomaly, the explainability of the Deep Learning solution is enhanced. The Tennessee Eastman Process (TEP) and LAM 9600 Metal Etcher datasets have been utilised to validate the proposed framework. The results show that the proposed LRE approach outperforms global reconstruction errors for similar model architectures achieving an AUC of 1.00. The proposed unsupervised learning approach with AE and LRE improves model explainability which is expected to be beneficial for deployment in semiconductor manufacturing where interpretable and trustworthy results are critical for process engineering teams.
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- 2023
15. The Saving Mysteries of Jesus Christ: A Christology in the Wesleyan Tradition
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Edgardo Colón-Emeric, Mark Gorman and Edgardo Colón-Emeric, Mark Gorman
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- 2019
16. A new look at cognitive functioning in pediatric MS
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Lauren B, Krupp, Emmanuelle, Waubant, Michael, Waltz, T Charles, Casper, Anita, Belman, Yolanda, Wheeler, Jayne, Ness, Jennifer, Graves, Mark, Gorman, Leslie, Benson, Soe, Mar, Manu, Goyal, Teri, Schreiner, Bianca, Weinstock-Guttman, Moses, Rodriguez, Jan-Mendelt, Tillema, Timothy, Lotze, Greg, Aaen, Mary, Rensel, John, Rose, Tanuja, Chitinis, Allan, George, and Leigh E, Charvet
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Neurology ,Neurology (clinical) - Abstract
Objective: Cognitive involvement in pediatric multiple sclerosis (MS) relative to adult MS is less defined. This study advances our understanding by measuring cognitive performances in pediatric MS, adult MS, and pediatric healthy controls. Methods: Consecutive relapsing pediatric MS participants from the United States Network of Pediatric MS Centers were compared with pediatric healthy controls and adults with relapsing MS. Participants were compared on two screening batteries: the Brief International Cognitive Assessment for MS and the Cogstate Brief Battery. Results were transformed to age-normative z scores. Results: The pediatric groups (MS vs. Healthy Controls) did not differ on either battery’s composite mean score or individual test scores ( ps > 0.32), nor in the proportions impaired on either battery, Brief International Cognitive Assessment for MS (26% vs. 24%, p = 0.83); Cogstate Brief Battery (26% vs. 32%, p = 0.41). The pediatric versus adult MS group even after controlling for differences in disease duration performed better on the Brief International Cognition Assessment for MS composite ( p = 0.03), Symbol Digit Modalities Test ( p = 0.02), Rey Auditory Verbal Learning Test ( p = 0.01), and Cogstate choice reaction time ( p Conclusion: Pediatric MS patients do not differ from healthy pediatric controls on cognitive screens but perform better than adults with MS.
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- 2022
17. An Evidence-Based Guideline Improves Outcomes for Patients With Hemophagocytic Lymphohistiocytosis and Macrophage Activation Syndrome
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Maria L. Taylor, Kacie J. Hoyt, Joseph Han, Leslie Benson, Siobhan Case, Mia T. Chandler, Margaret H. Chang, Craig Platt, Ezra M. Cohen, Megan Day-Lewis, Fatma Dedeoglu, Mark Gorman, Jonathan S. Hausmann, Erin Janssen, Pui Y. Lee, Jeffrey Lo, Gregory P. Priebe, Mindy S. Lo, Esra Meidan, Peter A. Nigrovic, Jordan E. Roberts, Mary Beth F. Son, Robert P. Sundel, Maria Alfieri, Jenny Chan Yeun, Damilola M. Shobiye, Barbara Degar, Joyce C. Chang, Olha Halyabar, Melissa M. Hazen, and Lauren A. Henderson
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C-Reactive Protein ,Rheumatology ,Macrophage Activation Syndrome ,Immunology ,Humans ,Immunology and Allergy ,Child ,Lymphohistiocytosis, Hemophagocytic ,Biomarkers ,Retrospective Studies - Abstract
ObjectiveTo compare clinical outcomes in children with hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) who were managed before and after implementation of an evidence-based guideline (EBG).MethodsA management algorithm for MAS-HLH was developed at our institution based on literature review, expert opinion, and consensus building across multiple pediatric subspecialties. An electronic medical record search retrospectively identified hospitalized patients with MAS-HLH in the pre-EBG (October 15, 2015, to December 4, 2017) and post-EBG (January 1, 2018, to January 21, 2020) time periods. Predetermined outcome metrics were evaluated in the 2 cohorts.ResultsAfter the EBG launch, 57 children were identified by house staff as potential patients with MAS-HLH, and rheumatology was consulted for management. Ultimately, 17 patients were diagnosed with MAS-HLH by the treating team. Of these, 59% met HLH 2004 criteria, and 94% met 2016 classification criteria for MAS complicating systemic juvenile idiopathic arthritis. There was a statistically significant reduction in mortality from 50% before implementation of the EBG to 6% in the post-EBG cohort (P = 0.02). There was a significant improvement in time to 50% reduction in C-reactive protein level in the post-EBG vs pre-EBG cohorts (log-rank P < 0.01). There were trends toward faster time to MAS-HLH diagnosis, faster initiation of immunosuppressive therapy, shorter length of hospital stay, and more rapid normalization of MAS-HLH–related biomarkers in the patients post-EBG.ConclusionWhile the observed improvements may be partially attributed to advances in treatment of MAS-HLH that have accumulated over time, this analysis also suggests that a multidisciplinary treatment pathway for MAS-HLH contributed meaningfully to favorable patient outcomes.
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- 2022
18. Longitudinal Cognitive Screening Findings in Pediatric MS vs. Pediatric Controls and Adult MS in a Multi-center Cohort (S31.008)
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Kimberly O’Neill, Leigh Charvet, Michael Waltz, Theron Casper, Allan George, Leslie Benson, Mark Gorman, Manu Goyal, Soe Mar, Jayne Ness, Teri Schreiner, Emmanuelle Waubant, Bianca Weinstock-Guttman, Yolanda Wheeler, Gregory Aaen, Aaron Abrams, Tanuja Chitnis, Timothy Lotze, Mary Rensel, Moses Rodriguez, John Rose, Nikita Shukla, Jan-Mendelt Tillema, and Lauren Krupp
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- 2023
19. Real-world effectiveness of switching treatment after initial platform injectable disease-modifying therapies in pediatric multiple sclerosis in the US (P14-3.008)
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Aaron Abrams, Michael Waltz, Theron Casper, Gregory Aaen, Leslie Benson, Leigh Charvet, Tanuja Chitnis, Carla Francisco, Mark Gorman, Manu Goyal, Jennifer Graves, Lauren Krupp, Timothy Lotze, Soe Mar, Mary Rensel, Moses Rodriguez, John Rose, Alice Rutatangwa, Teri Schreiner, Nikita Shukla, Jan-Mendelt Tillema, Bianca Weinstock-Guttman, Yolanda Wheeler, Emmanuelle Waubant, and Kristen Krysko
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- 2023
20. 0421 Synchronous Virtual Cognitive Behavioral Therapy for Insomnia: Preliminary Results of Sleep Pattern Changes among Cancer Survivors
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Kimberly Arditte Hall, Yan Ma, Michael Goldstein, Tony Cunningham, Elyse Park, Mark Gorman, Amy Comander, and Daniel Hall
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Physiology (medical) ,Neurology (clinical) - Abstract
Introduction For cancer survivors, insomnia is a frequent and distressing concern. Cognitive behavioral therapy for insomnia (CBT-I) is an effective treatment, yet in-person care can be difficult for cancer survivors to access for a variety of socioeconomic, medical and logistical reasons. In a pilot randomized clinical trial, four, weekly sessions of virtually-delivered, synchronous CBT-I were feasible, acceptable, and seemingly efficacious for reducing insomnia among cancer survivors (vs. an enhanced usual care control). The aim of this secondary analysis was to characterize daily patterns in sleep diary metrics during the intervention phase. Methods Adults who had completed treatment for any non-metastatic cancer and had chronic insomnia (DSM-5 criteria and Insomnia Severity Index score Results Among 20 cancer survivors who received CBT-I (mean age 51.2 ± 17.1 years, 90% female), model fit indices indicated that across sleep metrics, linear growth models provided a better fit to the data than either quadratic or cubic growth models. Significant linear improvement was observed for SQ (B = 0.02, t = 3.60, p < 0.001), SE (B = 0.16, t = 2.01, p = 0.046), and SOL (B = -0.41, t = -2.47, p = 0.01), but not TIB, TST, or WASO (ts < 1.12, ps > 0.26). Conclusion Findings elucidate how sleep may be expected to change over the course CBT-I, in particular for the growing population of cancer survivors seeking virtual care for insomnia. The strengths, limitations, and potential modifications to optimize the intervention across sleep metrics will be discussed. Support (if any) This work was conducted with support from the American Cancer Society (Massachusetts General Hospital Institutional Research Grant, PI: Hall).
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- 2023
21. Gene–environment interactions increase the risk of pediatric-onset multiple sclerosis associated with ozone pollution
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Amin Ziaei, Amy M Lavery, Xiaorong MA Shao, Cameron Adams, T Charles Casper, John Rose, Meghan Candee, Bianca Weinstock-Guttman, Greg Aaen, Yolanda Harris, Jennifer Graves, Leslie Benson, Mark Gorman, Mary Rensel, Soe Mar, Tim Lotze, Benjamin Greenberg, Tanuja Chitnis, Janace Hart, Amy T Waldman, Lisa F Barcellos, and Emmanuelle Waubant
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Multiple Sclerosis ,Genotype ,ozone pollution ,Clinical Sciences ,Neurodegenerative ,Autoimmune Disease ,Article ,Ozone ,Risk Factors ,Clinical Research ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Genetic Predisposition to Disease ,CD86 ,Climate-Related Exposures and Conditions ,Aetiology ,Child ,gene–environment interaction ,Pediatric ,Neurology & Neurosurgery ,Neurosciences ,DRB1*15 ,Brain Disorders ,gene-environment interaction ,Neurology ,Gene-Environment Interaction ,B7-2 Antigen ,Neurology (clinical) ,Pediatric onset ,HLA-DRB1 Chains - Abstract
Background: We previously reported a relationship between air pollutants and increased risk of pediatric-onset multiple sclerosis (POMS). Ozone is an air pollutant that may play a role in multiple sclerosis (MS) pathoetiology. CD86 is the only non-HLA gene associated with POMS for which expression on antigen-presenting cells (APCs) is changed in response to ozone exposure. Objectives: To examine the association between county-level ozone and POMS, and the interactions between ozone pollution, CD86, and HLA- DRB1*15, the strongest genetic variant associated with POMS. Methods: Cases and controls were enrolled in the Environmental and Genetic Risk Factors for Pediatric MS study of the US Network of Pediatric MS Centers. County-level-modeled ozone data were acquired from the CDC’s Environmental Tracking Network. Participants were assigned ozone values based on county of residence. Values were categorized into tertiles based on healthy controls. The association between ozone tertiles and having MS was assessed by logistic regression. Interactions between tertiles of ozone level and the GG genotype of the rs928264 (G/A) single nucleotide polymorphism (SNP) within CD86, and the presence of DRB1*15:01 ( DRB1*15) on odds of POMS were evaluated. Models were adjusted for age, sex, genetic ancestry, and mother’s education. Additive interaction was estimated using relative excess risk due to interaction (RERI) and attributable proportions (APs) of disease were calculated. Results: A total of 334 POMS cases and 565 controls contributed to the analyses. County-level ozone was associated with increased odds of POMS (odds ratio 2.47, 95% confidence interval (CI): 1.69–3.59 and 1.95, 95% CI: 1.32–2.88 for the upper two tertiles, respectively, compared with the lowest tertile). There was a significant additive interaction between high ozone tertiles and presence of DRB1*15, with a RERI of 2.21 (95% CI: 0.83–3.59) and an AP of 0.56 (95% CI: 0.33–0.79). Additive interaction between high ozone tertiles and the CD86 GG genotype was present, with a RERI of 1.60 (95% CI: 0.14–3.06) and an AP of 0.37 (95% CI: 0.001–0.75) compared to the lowest ozone tertile. AP results indicated that approximately half of the POMS risk in subjects can be attributed to the possible interaction between higher county-level ozone carrying either DRB1*15 or the CD86 GG genotype. Conclusions: In addition to the association between high county-level ozone and POMS, we report evidence for additive interactions between higher county-level ozone and DRB1*15 and the CD86 GG genotype. Identifying gene–environment interactions may provide mechanistic insight of biological processes at play in MS susceptibility. Our work suggests a possible role of APCs for county-level ozone-induced POMS risk.
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- 2022
22. Silent findings: Examination of asymptomatic demyelination in a pediatric US cohort
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Vikram Bhise, Michael Waltz, T. Charles Casper, Gregory Aaen, Leslie Benson, Tanuja Chitnis, Mark Gorman, Manu S. Goyal, Yolanda Wheeler, Timothy Lotze, Soe Mar, Mary Rensel, Aaron Abrams, Moses Rodriguez, John Rose, Teri Schreiner, Nikita Shukla, Emmanuelle Waubant, Bianca Weinstock-Guttman, Jayne Ness, Lauren Krupp, and Jan Mendelt-Tillema
- Subjects
Neurology ,Neurology (clinical) ,General Medicine - Published
- 2023
23. Proposal to optimize evaluation and treatment of Febrile infection‐related epilepsy syndrome (FIRES): A Report from FIRES workshop
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Elaine C. Wirrell, Jessica L. Carpenter, Eyal Muscal, Andreas Brunklaus, Elizabeth Wells, Rima Nabbout, Ronny Wickström, James J. Riviello, William P Roche, Krista Eschbach, Annamaria Vezzani, Mark Gorman, Coral M. Stredny, Marios Kaliakatsos, Antonio Valentin, Eric T. Payne, Tara K. Mangum, Sookyong Koh, Craig A. Press, Yi-Chen Lai, and Kihyeong Lee
- Subjects
Drug Resistant Epilepsy ,Pediatrics ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Status epilepticus ,lcsh:RC346-429 ,Seizures, Febrile ,immune activation ,neuroinflammation ,Epilepsy ,Status Epilepticus ,Cannabidiol ,Humans ,Medicine ,new‐onset refractory status epilepticus ,Young adult ,Child ,Special Report ,lcsh:Neurology. Diseases of the nervous system ,Anakinra ,business.industry ,Epileptic encephalopathy ,Infant ,medicine.disease ,cytokines ,Interleukin 1 Receptor Antagonist Protein ,Febrile infection related epilepsy syndrome ,epileptic encephalopathy ,Immune System Diseases ,Special Reports ,Neurology ,Child, Preschool ,Epilepsy syndromes ,Encephalitis ,Neurology (clinical) ,medicine.symptom ,Diet, Ketogenic ,business ,Epileptic Syndromes ,anakinra ,medicine.drug ,Ketogenic diet - Abstract
Febrile infection‐related epilepsy syndrome (FIRES) is a rare catastrophic epileptic encephalopathy that presents suddenly in otherwise normal children and young adults causing significant neurological disability, chronic epilepsy, and high rates of mortality. To suggest a therapy protocol to improve outcome of FIRES, workshops were held in conjunction with American Epilepsy Society annual meeting between 2017 and 2019. An international group of pediatric epileptologists, pediatric neurointensivists, rheumatologists and basic scientists with interest and expertise in FIRES convened to propose an algorithm for a standardized approach to the diagnosis and treatment of FIRES. The broad differential for refractory status epilepticus (RSE) should include FIRES, to allow empiric therapies to be started early in the clinical course. FIRES should be considered in all previously healthy patients older than two years of age who present with explosive onset of seizures rapidly progressing to RSE, following a febrile illness in the preceding two weeks. Once FIRES is suspected, early administrations of ketogenic diet and anakinra (the IL‐1 receptor antagonist that blocks biologic activity of IL‐1β) are recommended.
- Published
- 2021
24. A Single Stage Composite Cleft Septorhinoplasty for Correction of the Mature Unilateral Cleft Nose Deformity - The Gujrat Technique
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Diaa Othman, Mark Gorman, Muhammad Adil Abbas Khan, Yangmyung Ma, Dujanah Siddique Bhatti, Sadia Rafiq, Hussan Berkhez Shami, George Lye, Michael McBride, and Muhammad Riaz
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Otorhinolaryngology ,Oral Surgery - Abstract
Objective To evaluate the results of a single stage composite cleft septorhinoplasty procedure (“The Gujrat Technique”) to correct the exaggerated cleft nose deformity after completion of nasal growth in an adult patient cohort. Methods Adult patients with a residual unilateral cleft nasal deformity were deemed eligible for the proposed “Gujrat Technique”. Over a 10-year period (2007–2017), 96 adult patients underwent this composite cleft septorhinoplasty as a single stage operation. Post-operative nasal symmetry evaluation was undertaken using the validated computer program ‘SymNose’. Functional outcome and patient satisfaction were assessed using Nasal Obstruction Symptom Evaluation scale and Rhinoplasty Outcome Evaluation (ROE) questionnaires respectively. Various statistical analysis methods were used to validate the obtained results. Results Due to poor compliance with follow-up, post-operative assessments were undertaken in only 32 patients. The single group study design using the non-parametric matching pairs Wilcoxon Sign test (p Conclusion The individual components of "The Gujrat Technique" are not novel but their combination in this adult unilateral cleft rhinoplasty cohort has demonstrated a high patient satisfaction with its aesthetic appeal and functional versatility. In the background of limited resources and unpredictable patient follow up, the simplicity, reproducibility and cost effectiveness of this technique make it a practical reconstructive option.
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- 2022
25. Improved relapse recovery in paediatric compared to adult multiple sclerosis
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Howard L. Weiner, Tanuja Chitnis, Mary Rensel, Shelly Roalstad, Jayne Ness, John W. Rose, Moses Rodriguez, Jennifer Graves, Yolanda Harris, Anita Belman, Bianca Weinstock-Guttman, Leslie Benson, Timothy Lotze, Manu S. Goyal, Jan Mendelt Tillema, Mark Gorman, T. Charles Casper, Emmanuelle Waubant, Greg Aaen, Lauren B. Krupp, Teri Schreiner, and Soe Mar
- Subjects
Adult ,Male ,0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Younger age ,Adolescent ,Cohort Studies ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,immune system diseases ,Epidemiology ,Humans ,Medicine ,Disabled Persons ,Longitudinal Studies ,Prospective Studies ,Child ,Prospective cohort study ,Paediatric patients ,Expanded Disability Status Scale ,business.industry ,Multiple sclerosis ,Recovery of Function ,Middle Aged ,Multiple Sclerosis, Chronic Progressive ,medicine.disease ,Functional system ,nervous system diseases ,030104 developmental biology ,Secondary progressive multiple sclerosis ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
Incomplete relapse recovery contributes to disability accrual and earlier onset of secondary progressive multiple sclerosis. We sought to investigate the effect of age on relapse recovery. We identified patients with multiple sclerosis from two longitudinal prospective studies, with an Expanded Disability Status Scale (EDSS) score within 30 days after onset of an attack, and follow-up EDSS 6 months after attack. Adult patients with multiple sclerosis (n = 632) were identified from the Comprehensive Longitudinal Investigations in Multiple Sclerosis at Brigham study (CLIMB), and paediatric patients (n = 132) from the US Network of Paediatric Multiple Sclerosis Centers (NPMSC) registry. Change in EDSS was defined as the difference in EDSS between attack and follow-up. Change in EDSS at follow-up compared to baseline was significantly lower in children compared to adults (P = 0.001), as were several functional system scores. Stratification by decade at onset for change in EDSS versus age found for every 10 years of age, EDSS recovery is reduced by 0.15 points (P
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- 2020
26. Pediatric Multiple Sclerosis Severity Score in a large US cohort
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Manikum Moodley, Emmanuelle Waubant, Teri Schreiner, Jayne Ness, Mark Gorman, Lauren B. Krupp, Michael Waltz, Moses Rodriguez, Jan Mendelt Tillema, Jennifer Graves, Mary Rensel, Manu S. Goyal, John W. Rose, T. Charles Casper, Timothy Lotze, Yolanda Harris, Greg Aaen, Bianca Weinstock-Guttman, Brigitte Hurtubise, Jonathan D. Santoro, Soe Mar, Tanuja Chitnis, Anita Belman, Shelly Roalstad, and Leslie Benson
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Male ,medicine.medical_specialty ,Multiple Sclerosis ,Time Factors ,Adolescent ,Severity of Illness Index ,Article ,Disease activity ,Disability Evaluation ,03 medical and health sciences ,0302 clinical medicine ,Disease severity ,Recurrence ,Internal medicine ,medicine ,Retrospective analysis ,Humans ,030212 general & internal medicine ,Age of Onset ,Child ,Retrospective Studies ,Expanded Disability Status Scale ,business.industry ,Multiple sclerosis ,Disease progression ,Infant ,Symbol digit modalities test ,medicine.disease ,United States ,Child, Preschool ,Cohort ,Disease Progression ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
ObjectiveTo characterize disease severity and distribution of disability in pediatric-onset multiple sclerosis (POMS) and to develop an optimized modeling scale for measuring disability, we performed a multicenter retrospective analysis of disability scores in 873 persons with POMS over time and compared this to previously published data in adults with multiple sclerosis (MS).MethodsThis was a retrospective analysis of prospectively collected data collected from 12 centers of the US Network of Pediatric MS Centers. Patients were stratified by the number of years from first symptoms of MS to Expanded Disability Status Scale (EDSS) assessment and an MS severity score (Pediatric Multiple Sclerosis Severity Score [Ped-MSSS]) was calculated per criteria developed by Roxburgh et al. in 2005.ResultsIn total, 873 patients were evaluated. In our cohort, 52%, 19.4%, and 1.5% of all patients at any time point reached an EDSS of 2.0, 3.0, and 6.0. Comparison of our Ped-MSSS scores and previously published adult Multiple Sclerosis Severity Scores (MSSS) showed slower progression of Ped-MSSS with increasing gaps between higher EDSS score and years after diagnosis. Decile scores in our POMS cohort for EDSS of 2.0, 3.0, and 6.0 were 8.00/9.46/9.94, 7.86/9.39/9.91, and 7.32/9.01/9.86 at 2, 5, and 10 years, respectively. Notable predictors of disease progression in both EDSS and Ped-MSSS models were ever having a motor relapse and EDSS at year 1. Symbol Digit Modalities Test (SDMT) scores were inversely correlated with duration of disease activity and cerebral functional score.ConclusionsPersons with POMS exhibit lower EDSS scores compared to persons with adult-onset MS. Use of a Ped-MSSS model may provide an alternative to EDSS scoring in clinical assessment of disease severity and disability accrual.
- Published
- 2020
27. Rituximab in patients with pediatric multiple sclerosis and other demyelinating disorders of the CNS: Practical considerations
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Margherita Nosadini, Kevin Rostasy, Mark Gorman, Barbara Kornek, Lauren B. Krupp, Brenda Banwell, Tanuja Chitnis, Silvia Tenembaum, Russell C. Dale, Kristen M. Krysko, Angelo Ghezzi, Jonatan Salzer, Emmanuelle Waubant, Teri Schreiner, and Amit Bar-Or
- Subjects
Central Nervous System ,medicine.medical_specialty ,Central nervous system ,Multiple sclerosis ,03 medical and health sciences ,rituximab ,0302 clinical medicine ,children ,medicine ,Humans ,In patient ,030212 general & internal medicine ,Child ,Demyelinating Disorder ,Intensive care medicine ,business.industry ,Antigens, CD20 ,medicine.disease ,Clinical Practice ,medicine.anatomical_structure ,Neurology ,Multiple sclerosis, children, rituximab ,Rituximab ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Anti-CD20 therapies have established efficacy in the treatment of immune-mediated neurological and non-neurological diseases. Rituximab, one of the first B-cell-directed therapies, is relatively inexpensive compared to newer anti-CD20 molecules, is available in many countries, and has been used off-label in pediatric patients with neuroimmune conditions. The objective of this paper is to describe the experience with rituximab in pediatric multiple sclerosis and other inflammatory immune-mediated disorders of the central nervous system (CNS), and to define a protocol for its use in clinical practice, in particular addressing doses, interval of administration, duration of treatment, and tests to perform at baseline and during follow-up.
- Published
- 2020
28. The pathology of central nervous system inflammatory demyelinating disease accompanying myelin oligodendrocyte glycoprotein autoantibody
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Hans Lassmann, Mark Gorman, Sonja Hochmeister, Jan Mendelt Tillema, Claudia F. Lucchinetti, Romana Höftberger, Sean J. Pittock, Damir Joldic, A. Sebastian Lopez-Chiriboga, Verena Endmayr, Yong Guo, and Eoin P. Flanagan
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,CNS demyelination ,Biopsy ,Pathology and Forensic Medicine ,Myelin oligodendrocyte glycoprotein ,White matter ,Multiple sclerosis ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Myelin ,0302 clinical medicine ,immune system diseases ,Central Nervous System Diseases ,Acute disseminated encephalomyelitis ,medicine ,MOG ,Humans ,Aged ,Autoantibodies ,Original Paper ,biology ,business.industry ,Neuromyelitis Optica ,Middle Aged ,medicine.disease ,White Matter ,Hyperintensity ,Oligodendrocyte ,Oligodendroglia ,030104 developmental biology ,medicine.anatomical_structure ,Astrocytes ,Immunoglobulin G ,biology.protein ,Female ,Myelin-Oligodendrocyte Glycoprotein ,Neurology (clinical) ,Autopsy ,Demyelination ,business ,030217 neurology & neurosurgery - Abstract
We sought to define the pathological features of myelin oligodendrocyte glycoprotein (MOG) antibody associated disorders (MOGAD) in an archival autopsy/biopsy cohort. We histopathologically analyzed 2 autopsies and 22 brain biopsies from patients with CNS inflammatory demyelinating diseases seropositive for MOG-antibody by live-cell-based-assay with full length MOG in its conformational form. MOGAD autopsies (ages 52 and 67) demonstrate the full spectrum of histopathological features observed within the 22 brain biopsies (median age, 10 years; range, 1–66; 56% female). Clinical, radiologic, and laboratory characteristics and course (78% relapsing) are consistent with MOGAD. MOGAD pathology is dominated by coexistence of both perivenous and confluent white matter demyelination, with an over-representation of intracortical demyelinated lesions compared to typical MS. Radially expanding confluent slowly expanding smoldering lesions in the white matter as seen in MS, are not present. A CD4+ T-cell dominated inflammatory reaction with granulocytic infiltration predominates. Complement deposition is present in all active white matter lesions, but a preferential loss of MOG is not observed. AQP4 is preserved, with absence of dystrophic astrocytes, and variable oligodendrocyte and axonal destruction. MOGAD is pathologically distinguished from AQP4-IgG seropositive NMOSD, but shares some overlapping features with both MS and ADEM, suggesting a transitional pathology. Complement deposition in the absence of selective MOG protein loss suggest humoral mechanisms are involved, however argue against endocytic internalization of the MOG antigen. Parallels with MOG-EAE suggest MOG may be an amplification factor that augments CNS demyelination, possibly via complement mediated destruction of myelin or ADCC phagocytosis.
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- 2020
29. Scoring System to Optimize Pioglitazone Therapy After Stroke Based on Fracture Risk
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Silvio E. Inzucchi, Amber Stuart, Peter D. Guarino, Karen L. Furie, David M. Kent, Jennifer L. Dearborn, Mark Gorman, Lawrence H. Young, Walter N. Kernan, Robin Conwit, and Catherine M. Viscoli
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Advanced and Specialized Nursing ,medicine.medical_specialty ,business.industry ,Absolute risk reduction ,Bone fracture ,030204 cardiovascular system & hematology ,Placebo ,medicine.disease ,Article ,03 medical and health sciences ,0302 clinical medicine ,Relative risk ,Internal medicine ,Diabetes mellitus ,medicine ,Cardiology ,Neurology (clinical) ,Myocardial infarction ,Cardiology and Cardiovascular Medicine ,business ,Pioglitazone ,Stroke ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background and Purpose— The insulin sensitizer, pioglitazone, reduces cardiovascular risk in patients after an ischemic stroke or transient ischemic attack but increases bone fracture risk. We conducted a secondary analysis of the IRIS trial (Insulin Resistance Intervention After Stroke) to assess the effect of pretreatment risk for fracture on the net benefits of pioglitazone therapy. Methods— IRIS was a randomized placebo-controlled trial of pioglitazone that enrolled patients with insulin resistance but without diabetes mellitus within 180 days of an ischemic stroke or transient ischemic attack. Participants were recruited at 179 international centers from February 2005 to January 2013 and followed for a median of 4.8 years. Fracture risk models were developed from patient characteristics at entry. Within fracture risk strata, we quantified the effects of pioglitazone compared with placebo by estimating the relative risks and absolute 5-year risk differences for fracture and stroke or myocardial infarction. Results— The fracture risk model included points for age, race-ethnicity, sex, body mass index, disability, and medications. The relative increment in fracture risk with pioglitazone was similar in the lower ( Conclusions— A simple point score identifying patients at low risk for fracture may assist in selecting patients with a favorable benefit-risk profile for pioglitazone therapy after ischemic stroke or transient ischemic attack.
- Published
- 2019
30. Opinion and Special Articles: Cerebellar Ataxia and Liver Failure Complicating IPEX Syndrome
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Steven Jacobson, Joshua Rim, Robert Roger Lebel, Melissa Byler, Klaus Werner, Ariane Soldatos, Luigi Notarangelo, Emily Leibovitch, and Mark Gorman
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Adult ,Diarrhea ,Male ,medicine.medical_specialty ,Cerebellar Ataxia ,Anemia ,medicine.medical_treatment ,Neutropenia ,Opinion and Special Articles ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Exome Sequencing ,medicine ,Diabetes Mellitus ,Humans ,Enteropathy ,030212 general & internal medicine ,Exome sequencing ,Cerebellar ataxia ,business.industry ,Immunosuppression ,Forkhead Transcription Factors ,Genetic Diseases, X-Linked ,IPEX syndrome ,medicine.disease ,Dermatology ,Magnetic Resonance Imaging ,Pedigree ,Diabetes Mellitus, Type 1 ,Immune System Diseases ,Eczematous dermatitis ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Liver Failure - Abstract
Immunodysregulation, polyendocrinopathy, and enteropathy, X-linked (IPEX) syndrome is an autoimmune condition caused by mutations in the Forkhead Box P3 ( FOXP3 ) gene, which maps to chromosome Xp11.23 (OMIM #304790).1 It typically presents within the first year of life with watery diarrhea, eczematous dermatitis, and endocrinopathy (most commonly diabetes mellitus).1 Most children have other autoimmune phenomena including Coombs-positive anemia, thrombocytopenia, neutropenia, and tubular nephropathy.1 Bone marrow transplantation is the only definitive cure for IPEX syndrome.2 Neurologic involvement in IPEX syndrome has not been well characterized in the literature, based on a current Ovid MEDLINE search. Without aggressive immunosuppression or bone marrow transplantation, the majority of affected boys die within the first 1 to 2 years of life from metabolic derangements or sepsis.1 Diagnosis is based on clinical features and whole exome sequencing that reveals a pathogenic FOXP3 variant.1
- Published
- 2020
31. Vitamin D genes influence MS relapses in children
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Lisa F. Barcellos, Leslie Benson, Amy Waldman, Benjamin Greenberg, Bianca Weinstock-Guttman, Janace Hart, Mark Gorman, Tanuja Chitnis, Jennifer Graves, Moses Rodriguez, Gregory Aaen, T. Charles Casper, Jan Mendelt Tillema, John W. Rose, Jayne Ness, Emmanuelle Waubant, Xiaorong Shao, Teri Schreiner, Lauren Krupp, Mar Soe, Anita Belman, Hong Quach, and Timothy Lotze
- Subjects
Risk ,Male ,medicine.medical_specialty ,Multiple Sclerosis ,Adolescent ,Clinical Sciences ,vitamin D ,Neurodegenerative ,Polymorphism, Single Nucleotide ,Autoimmune Disease ,Article ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Clinical Research ,Epidemiology ,Complementary and Integrative Health ,medicine ,Vitamin D and neurology ,Genetics ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Vitamin D ,Genetic risk ,Polymorphism ,Child ,Gene ,030304 developmental biology ,Nutrition ,0303 health sciences ,Neurology & Neurosurgery ,business.industry ,Multiple sclerosis ,Prevention ,Neurosciences ,Single Nucleotide ,medicine.disease ,Brain Disorders ,Neurology ,Immunology ,Female ,epidemiology ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,pediatric multiple sclerosis - Abstract
Objective:The aim of this study was to determine whether a vitamin D genetic risk score (vitDGRS) is associated with 25-hydroxyvitamin D (25(OH)D) level and multiple sclerosis (MS) relapses in children.Methods:DNA samples were typed for single nucleotide polymorphisms (SNPs) from four genes previously identified to be associated with 25(OH)D levels. SNPs with strong associations with 25(OH)D after multiple comparison correction were used to create a genetic risk score (vitDGRS). Cox regression models tested associations of vitDGRS with relapse hazard.Results:Two independent SNPs within or near GC and NADSYN1/DHCR7 genes were strongly associated with 25(OH)D levels in the discovery cohort ( n = 182) after Bonferroni correction. The vitDGRS of these SNPs explained 4.5% of the variance of 25(OH)D level after adjustment for genetic ancestry. Having the highest versus lowest vitDGRS was associated with 11 ng/mL lower 25(OH)D level (95% confidence interval (CI) = −17.5, −4.5, p = 0.001) in the discovery cohort. Adjusting for ancestry, sex, disease-modifying therapy (DMT), and HLA-DRB1*15 carrier status, the highest versus lowest vitDGRS was associated with 2.6-fold (95% CI = 1.37, 5.03, p = 0.004) and 2.0-fold (95% CI = 0.75, 5.20, p = 0.16) higher relapse hazard in the discovery and replication cohorts, respectively.Conclusion:The vitDGRS identifies children at greater risk of relapse. These findings support a causal role for vitamin D in MS course.
- Published
- 2020
32. Adherence to study drug in a stroke prevention trial'?
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Catherine M. Viscoli, Walter N. Kernan, Akshatha Kiran, Mark Gorman, and Karen L. Furie
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Male ,medicine.medical_specialty ,Randomization ,Time Factors ,Myocardial Infarction ,Placebo ,Drug Administration Schedule ,Article ,Medication Adherence ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Recurrence ,Risk Factors ,Internal medicine ,medicine ,Secondary Prevention ,Humans ,Hypoglycemic Agents ,Adverse effect ,Stroke ,Pioglitazone ,business.industry ,Rehabilitation ,Drug holiday ,Middle Aged ,medicine.disease ,Discontinuation ,Clinical trial ,Treatment Outcome ,Ischemic Attack, Transient ,Surgery ,Female ,Neurology (clinical) ,Insulin Resistance ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Objective Standards for reporting and analyzing adherence to medical therapy have recently improved due to international consensus efforts. If applied to clinical trial research in patients with stroke, these improvements have the potential to identify when in the sequence of trial operations participants are at risk for non-adherence and opportunities to safeguard adherence. Methods We analyzed three phases of adherence according to the European Society for Patient Adherence, COMpliance, and Persistence (ESPACOMP) Medication Adherence Reporting Guideline (EMERGE) taxonomy in the Insulin Resistance Intervention after Stroke (IRIS) trial: initiation (did patient start drug), implementation (did patient take a drug holiday, defined as temporary cessation lasting ≥14 days), and persistence (did patient prematurely and permanently discontinue drug). IRIS was a randomized, placebo controlled, double-blind trial testing pioglitazone to prevent stroke or myocardial infarction in patients with a recent ischemic stroke or transient ischemic attack. Adherence was classified by self-report. Researchers used coaching algorithms to seek adherence recovery if participants went off drug. Results During 2005-2013, 3876 participants were enrolled from 179 sites in seven countries and followed for a mean of 4.8 years. Less than 1% of participants in each group did not initiate study drug. 20% of patients assigned to pioglitazone and 17% assigned to placebo took at least one drug holiday. 36% and 30%, respectively, discontinued the study drug prematurely with or without a prior holiday. The risk for stopping the study drug (temporarily or permanently) in the first year after randomization was twice the risk in each of the subsequent four years. This was true both for patients assigned to active therapy and placebo. More participants assigned to pioglitazone, compared to placebo, took a drug holiday or permanently stopped study drug, but the difference in rates of discontinuation was only evident in year one. In years two through five, rates of discontinuation were similar in the two treatment groups. The difference in rates during year one was the result of adverse effects related to the active study drug, pioglitazone. During the remainder of the trial, the attribution of discontinuations to adverse effects potentially related to pioglitazone was reduced but still higher in those assigned to active drug. Other reasons for discontinuation were similar between treatment groups and were largely unrelated to pharmacodynamic effects of the study drug. Rates of discontinuation varied widely among research sites. Conclusion Patients in a drug trial for stroke prevention are at greatest risk for premature drug discontinuation early after randomization. Reasons for discontinuation change over time. Variable discontinuation rates among sites suggests that adherence can be improved by using best practices from high-performing sites.
- Published
- 2020
33. Use of newer disease-modifying therapies in pediatric multiple sclerosis in the US
- Author
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Kristen M, Krysko, Jennifer, Graves, Mary, Rensel, Bianca, Weinstock-Guttman, Gregory, Aaen, Leslie, Benson, Tanuja, Chitnis, Mark, Gorman, Manu, Goyal, Lauren, Krupp, Timothy, Lotze, Soe, Mar, Moses, Rodriguez, John, Rose, Michael, Waltz, T, Charles Casper, and Emmanuelle, Waubant
- Subjects
Male ,medicine.medical_specialty ,Multiple Sclerosis ,Adolescent ,Article ,Cohort Studies ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Natalizumab ,Daclizumab ,Internal medicine ,Teriflunomide ,medicine ,Humans ,030212 general & internal medicine ,Practice Patterns, Physicians' ,Child ,Clinically isolated syndrome ,business.industry ,Multiple sclerosis ,medicine.disease ,Fingolimod ,United States ,Tolerability ,chemistry ,Child, Preschool ,Female ,Rituximab ,Neurology (clinical) ,business ,Immunosuppressive Agents ,030217 neurology & neurosurgery ,medicine.drug - Abstract
ObjectiveTo characterize the use and safety of newer disease-modifying therapies (DMTs) in children with multiple sclerosis (MS) and clinically isolated syndrome (CIS) treated under 18 years of age.MethodsThis is a cohort study including children with MS or CIS followed at 12 outpatient practices participating in the US Network of Pediatric MS Centers. DMT use, including duration, dose, and side effects, was analyzed. Newer DMTs were defined as agents receiving Food and Drug Administration approval or with increased use in adult MS after 2005.ResultsAs of July 2017, 1,019 pediatric patients with MS (n = 748) or CIS (n = 271) were enrolled (65% female, mean onset 13.0 ± 3.9 years, mean follow-up 3.5 ± 3.1 years, median 1.6 visits per year). Of these, 78% (n = 587) with MS and 11% (n = 31) with CIS received DMT before 18 years of age. This consisted of at least one newer DMT in 42%, including dimethyl fumarate (n = 102), natalizumab (n = 101), rituximab (n = 57), fingolimod (n = 37), daclizumab (n = 5), and teriflunomide (n = 3). Among 17%, the initial DMT prescribed was a newer agent (36 dimethyl fumarate, 30 natalizumab, 22 rituximab, 14 fingolimod, 2 teriflunomide). Over the last 10 years, the use of newer agents has increased, particularly in those ≥12 years and to lesser extent in those ConclusionNewer DMTs are often used in pediatric MS, and have similar short-term safety, tolerability, and side effect profiles as in adults. These findings may help inform pediatric MS management.
- Published
- 2018
34. Urban air quality and associations with pediatric multiple sclerosis
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Amy M. Lavery, Manikum Moodley, Jayne Ness, Leslie Benson, Jennifer Rubin, Yolanda Harris, Lauren Krupp, John W. Rose, Tanuja Chitnis, Soe Mar, T. Charles Casper, Mary Rensel, Ilana Kahn, Amy Waldman, Benjamin Greenberg, Emmanuelle Waubant, Anita Belman, Mark Gorman, Moses Rodriguez, Timothy Lotze, Shelly Roalstad, Bianca Weinstock-Guttman, Greg Aaen, Leigh Charvet, Jennifer Graves, Manu S. Goyal, Meghan Candee, Jan Mendelt Tillema, and Teri Schreiner
- Subjects
Fine particulate ,Inventory system ,010501 environmental sciences ,01 natural sciences ,03 medical and health sciences ,0302 clinical medicine ,Air pollutants ,Criteria air contaminants ,Environmental health ,11. Sustainability ,Medicine ,Risk factor ,Air quality index ,Research Articles ,0105 earth and related environmental sciences ,business.industry ,General Neuroscience ,Multiple sclerosis ,Particulates ,medicine.disease ,3. Good health ,13. Climate action ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Research Article - Abstract
Background We previously identified air quality as a risk factor of interest for pediatric multiple sclerosis. The purpose of this study is to more closely examine the association between the six criteria air pollutants and pediatric MS as well as identify specific areas of toxic release using data from the Toxic Release Inventory. Methods Pediatric MS cases (N = 290) and healthy controls (N = 442) were included as part of an ongoing case–control study. We used the National Emissions Inventory system to estimate particulate exposure by county of residence for each participant. Proximity to Toxic Release Inventory (TRI) sites was also assessed using ArcGIS mapping tools. Risk‐Screening Environmental Indicators (RSEI) classified counties at risk to exposure of environmental toxic releases. Results Fine particulate matter (PM 2.5), carbon monoxide (CO), sulfur dioxide (SO 2), and lead air emissions were associated with increased odds for pediatric MS (P < 0.01) for those residing within 20 miles of an MS center. Most study participants (75%) resided within 5 miles of at least one TRI site; however, the mean total pounds of stack air releases was higher for sites near MS cases (81,000 tons) compared to those near healthy controls (35,000 tons, P = 0.002). Average RSEI scores did not differ significantly between cases and controls. Conclusion Out of several air pollutants examined, we show that fine particulate matter and three other criteria pollutants (SO 2, CO, and lead) were statistically associated with higher odds for pediatric MS.
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- 2018
35. Heart Failure After Ischemic Stroke or Transient Ischemic Attack in Insulin-Resistant Patients Without Diabetes Mellitus Treated With Pioglitazone
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Catherine M. Viscoli, Anne M. Lovejoy, Erica S. Spatz, Daniel Jacoby, Steven Pfau, Silvio E. Inzucchi, Gregory G. Schwartz, J. Dawn Abbott, Frederick S. Ling, Walter N. Kernan, Lawrence H. Young, Jeptha P. Curtis, Daniel M. Kolansky, Robin Conwit, Karen L. Furie, and Mark Gorman
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Male ,medicine.medical_specialty ,Time Factors ,medicine.drug_class ,030204 cardiovascular system & hematology ,Risk Assessment ,Article ,Brain Ischemia ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Double-Blind Method ,Risk Factors ,Physiology (medical) ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Hypoglycemic Agents ,Insulin ,030212 general & internal medicine ,Israel ,Thiazolidinedione ,Stroke ,Aged ,Aged, 80 and over ,Heart Failure ,Pioglitazone ,business.industry ,Australia ,Insulin resistant ,Middle Aged ,medicine.disease ,Europe ,Hospitalization ,Treatment Outcome ,Ischemic Attack, Transient ,Heart failure ,North America ,Cardiology ,Female ,Thiazolidinediones ,Insulin Resistance ,Cardiology and Cardiovascular Medicine ,Risk assessment ,business ,medicine.drug - Abstract
Background: The IRIS trial (Insulin Resistance Intervention After Stroke) demonstrated that pioglitazone reduced the risk for both cardiovascular events and diabetes mellitus in insulin-resistant patients. However, concern remains that pioglitazone may increase the risk for heart failure (HF) in susceptible individuals. Methods: In IRIS, patients with insulin resistance but without diabetes mellitus were randomized to pioglitazone or placebo (1:1) within 180 days of an ischemic stroke or transient ischemic attack and followed for ≤5 years. To identify patients at higher HF risk with pioglitazone, we performed a secondary analysis of IRIS participants without HF history at entry. HF episodes were adjudicated by an external review, and treatment effects were analyzed using time-to-event methods. A baseline HF risk score was constructed from a Cox model estimated using stepwise selection. Baseline patient features (individually and summarized in risk score) and postrandomization events were examined as possible modifiers of the effect of pioglitazone. Net cardiovascular benefit was estimated for the composite of stroke, myocardial infarction, and hospitalized HF. Results: Among 3851 patients, the mean age was 63 years, and 65% were male. The 5-year HF risk did not differ by treatment (4.1% pioglitazone, 4.2% placebo). Risk for hospitalized HF was low and not significantly greater in pioglitazone compared with placebo groups (2.9% versus 2.3%, P =0.36). Older age, atrial fibrillation, hypertension, obesity, edema, high C-reactive protein, and smoking were risk factors for HF. However, the effect of pioglitazone did not differ across levels of baseline HF risk (hazard ratio [95% CI] for pioglitazone versus placebo for patients at low, moderate, and high risk: 1.03 [0.61–1.73], 1.10 [0.56–2.15], and 1.08 [0.58–2.01]; interaction P value=0.98). HF risk was increased in patients with versus those without incident myocardial infarction in both groups (pioglitazone: 31.4% versus 2.7%; placebo: 25.7% versus 2.4%; P P P =0.007). Conclusions: In IRIS, with surveillance and dose adjustments, pioglitazone did not increase the risk of HF and conferred net cardiovascular benefit in patients with insulin resistance and cerebrovascular disease. The risk of HF with pioglitazone was not modified by baseline HF risk. The IRIS experience may be instructive for maximizing the net benefit of this therapy. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00091949.
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- 2018
36. Heterogeneity in association of remote herpesvirus infections and pediatric MS
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Yolanda Harris, Jayne Ness, Teri Schreiner, Manikum Moodley, Jan Mendelt Tillema, Lisa F. Barcellos, Amy Waldman, Benjamin Greenberg, Manu S. Goyal, Gregory Aaen, Michael Waltz, Alice Rutatangwa, Lauren Krupp, Judith A. James, Anita Belman, John W. Rose, Timothy Lotze, Tanuja Chitnis, Emmanuelle Waubant, Jennifer Graves, Janace Hart, Meghan Candee, Mary Rensel, Theron Charles Casper, Bardia Nourbakhsh, Bianca Weinstock-Guttman, Mark Gorman, Ilana Kahn, Moses Rodriguez, Xiaorong Shao, Leslie Benson, Jennifer Rubin, and Soe Mar
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Clinically isolated syndrome ,business.industry ,General Neuroscience ,Multiple sclerosis ,Confounding ,Congenital cytomegalovirus infection ,medicine.disease ,Logistic regression ,Virus ,3. Good health ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Antigen ,Internal medicine ,medicine ,Neurology (clinical) ,Genetic risk ,business ,Research Articles ,030217 neurology & neurosurgery ,Research Article - Abstract
Objective While prior Epstein–Barr virus (EBV) infection has been consistently associated with subsequent risk of developing multiple sclerosis (MS), the association with other common herpesviruses has been more controversial. Our objectives were to determine whether remote infection with EBV and other common herpesviruses affect the susceptibility to pediatric MS and if there are interactions between genetic and demographic factors and viral infections. Methods Cases with pediatric‐onset MS or clinically isolated syndrome within 4 years of disease onset, and controls were recruited from 16 American pediatric MS centers. Logistic regression models adjusted for potential confounders assessed the association between case status and serological evidence for past infection with EBV, cytomegalovirus (CMV), Herpes Simplex viruses‐1 (HSV‐1) and ‐2. We determined the heterogeneity of the effect of viral infection on the risk of having MS according to race, ethnicity and HLA‐DRB1:1501 status. Results A total of 356 pediatric cases and 493 controls were recruited. In multivariable models, EBV‐viral capsid antigen (VCA) seropositivity was associated with increased odds of having MS by 7.4 times (95% CI: 4.5–12.0, P < 0.001). Seropositivity for HSV‐1 was also associated with increased odds of having MS (OR 1.54, 95% CI: 1.06–2.25, P = 0.025) but this increase was seen only in Whites (OR = 2.18, 95% CI 1.35–3.52, P < 0.001) and those negative for HLA‐DRB1*1501 (OR = 1.89, 95% CI 1.17–3.03, P = 0.009). The effect of remote EBV infection on the risk of pediatric MS depended on race and HLA‐DRB1*15:01 status. Interpretation EBV seropositivity is strongly associated with pediatric MS, as is HSV‐1 seropositivity in subjects negative for HLA‐DRB1*15:01. Our report of interactions between select viral exposures, and age, race and DRB1 status suggests a complex effect of environmental and genetic risk factors on MS development.
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- 2018
37. Real-World Effectiveness of Initial Disease-Modifying Therapies in Pediatric Multiple Sclerosis
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Anita Belman, Jayne Ness, Mark Gorman, Jan Mendelt Tillema, Gregory Aaen, T. Charles Casper, Kristen M. Krysko, Teri Schreiner, Manu S. Goyal, Yolanda Harris, Jennifer Graves, Moses Rodriguez, Michael Waltz, Lauren Krupp, Soe Mar, Manikum Moodley, Tanuja Chitnis, Leslie Benson, Emmanuelle Waubant, Timothy Lotze, Mary Rensel, Alice Rutatangwa, Bianca Weinstock-Guttman, and John W. Rose
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Multiple Sclerosis ,Adolescent ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Natalizumab ,Adjuvants, Immunologic ,Internal medicine ,Teriflunomide ,medicine ,Humans ,Prospective Studies ,Glatiramer acetate ,Prospective cohort study ,Child ,Propensity Score ,Clinically isolated syndrome ,business.industry ,Hazard ratio ,Fingolimod ,030104 developmental biology ,Treatment Outcome ,Neurology ,chemistry ,Ocrelizumab ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Immunosuppressive Agents ,medicine.drug ,Demyelinating Diseases - Abstract
OBJECTIVE To assess real-world effectiveness of initial treatment with newer compared to injectable disease-modifying therapies (DMTs) on disease activity in pediatric multiple sclerosis (MS) and clinically isolated syndrome (CIS). METHODS This is a cohort study of children with MS/CIS followed at 12 clinics in the US Network of Pediatric MS Centers, who received initial therapy with newer (fingolimod, dimethyl fumarate, teriflunomide, natalizumab, rituximab, ocrelizumab) or injectable (interferon-β, glatiramer acetate) DMTs. Propensity scores (PSs) were computed, including preidentified confounders. Relapse rate while on initial DMT was modeled with negative binomial regression, adjusted for PS-quintile. Time to new/enlarging T2-hyperintense and gadolinium-enhancing lesions on brain magnetic resonance imaging were modeled with midpoint survival analyses, adjusted for PS-quintile. RESULTS A total of 741 children began therapy before 18 years, 197 with newer and 544 with injectable DMTs. Those started on newer DMTs were older (15.2 vs injectable 14.4 years, p = 0.001) and less likely to have a monofocal presentation. In PS-quintile-adjusted analysis, those on newer DMTs had a lower relapse rate than those on injectables (rate ratio = 0.45, 95% confidence interval (CI) = 0.29-0.70, p
- Published
- 2019
38. Cognitive processing speed in pediatric-onset multiple sclerosis: Baseline characteristics of impairment and prediction of decline
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Jayne Ness, Leslie Benson, Asya I. Wallach, Teri Schreiner, Timothy Lotze, Lauren Krupp, Emmanuelle Waubant, Michael Waltz, Moses Rodriguez, Tanuja Chitnis, Jan M. Tillema, Mark Gorman, Jennifer Graves, Leigh Charvet, Anita Belman, Manikum Moodley, Yolanda Harris, John W. Rose, Mary Rensel, Gregory Aaen, T. Charles Casper, Bianca Weinstock-Guttman, and Soe Mar
- Subjects
Adult ,Male ,medicine.medical_specialty ,Multiple Sclerosis ,Pediatric onset ,Audiology ,Neuropsychological Tests ,050105 experimental psychology ,03 medical and health sciences ,0302 clinical medicine ,Cognition ,medicine ,Humans ,0501 psychology and cognitive sciences ,Cognitive Dysfunction ,Cognitive impairment ,Child ,Aged ,business.industry ,Multiple sclerosis ,05 social sciences ,Symbol digit modalities test ,medicine.disease ,Neurology ,Baseline characteristics ,Neurology (clinical) ,business ,Cognition Disorders ,030217 neurology & neurosurgery - Abstract
Background: Cognitive impairment occurs in approximately one-third of pediatric-onset multiple sclerosis (POMS) patients. The Symbol Digit Modalities Test (SDMT), a widely used cognitive screen in adults, has yet to be incorporated early into the standard care of POMS. Objective: To screen for cognitive impairment early in the course of POMS and analyze predictive factors. Methods: Of the 955 POMS or clinically isolated syndrome (CIS) patients prospectively assessed from March 2014 to July 2018, 500 POMS and 116 CIS patients met inclusion criteria (disease onset before the age of 18, one or more SDMTs, and 8 years or older at the time of testing). Those with relapse were analyzed separately from those who were relapse-free. Results: At initial assessment, the mean (interquartile range (IQR)) age at symptom onset was 13.5 years (12.0, 15.9) and the mean (±SD) disease duration was 3.0 ± 2.9 years. Impaired processing speed occurred in 23.4% of POMS and in 16.4% of CIS. On serial testing ( n = 383, mean follow-up: 1.8 years), 14.1% had clinically meaningful decline predicted by older age of multiple sclerosis (MS) onset and male gender. Disease relapse or steroid use led to transient worsening on the SDMT. Conclusion: Early in the disease, some POMS and CIS patients are at risk for cognitive impairment and subsequent decline.
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- 2019
39. Older People, Mobility and Transport in Low- and Middle-Income Countries: A Review of the Research
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Sion Jones, Mark Gorman, and Jeffrey Turner
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Mobilities ,poverty ,media_common.quotation_subject ,Geography, Planning and Development ,TJ807-830 ,Context (language use) ,Management, Monitoring, Policy and Law ,TD194-195 ,Renewable energy sources ,older people ,03 medical and health sciences ,0302 clinical medicine ,State (polity) ,Political science ,0502 economics and business ,Development economics ,gender ,GE1-350 ,030212 general & internal medicine ,media_common ,050210 logistics & transportation ,Poverty ,Environmental effects of industries and plants ,Renewable Energy, Sustainability and the Environment ,05 social sciences ,mobility ,Environmental sciences ,Quantitative analysis (finance) ,disability ,ageing ,transport ,Survey data collection ,Older people ,urban ,Qualitative research - Abstract
Older populations are rising globally, which in high-income countries has helped to generate a growing literature on the impact of ageing on travel requirements and transport policy. This article aims to provide an initial assessment of the state of knowledge on the impact on transportation policy and usage of the increasing numbers of older people in low- and middle-income countries (LAMICs), through a review of the literature relating to older people and transportation. As both the academic and policy/practice-related literature specifically addressing ageing and transport in LAMICs is limited, the study looks beyond transportation to assess the state of knowledge regarding the ways in which older people&rsquo, s mobility is affected by issues, such as health, well-being, social (dis)engagement and gender. We find significant knowledge gaps, resulting in an evidence base to support the implementation of policy is lacking. Most research in low-income countries (LICs) is either broad quantitative analysis based on national survey data or small-scale qualitative studies. We conclude that, although study of the differing contexts of ageing in LAMICs as they relate to older people&rsquo, s mobilities and transport use has barely begun, institutions which both make and influence policymaking recognise the existence of significant knowledge gaps. This should provide the context in which research agendas can be established.
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- 2019
40. Neuroimmune disorders of the central nervous system in children in the molecular era
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Amy Waldman, Benjamin Greenberg, Adeline Vanderver, Russel C. Dale, Elizabeth Wells, Jan M. Tillema, Mark Gorman, Ann Hyslop, Amit Bar-Or, Robert C. Tasker, E. Ann Yeh, Bibi Bielekova, Brenda Banwell, Beau M. Ances, William D. Gaillard, Ariane Soldatos, Yael Hacohen, Josep Dalmau, Susanne M. Benseler, Carlos A. Pardo, and Sean J. Pittock
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0301 basic medicine ,Adolescent ,Neuroimmunomodulation ,Extramural ,business.industry ,Immune regulation ,Demyelinating Autoimmune Diseases, CNS ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,030104 developmental biology ,0302 clinical medicine ,Immune System Diseases ,Central Nervous System Diseases ,Basic research ,Clinical investigation ,Animals ,Encephalitis ,Humans ,Medicine ,Neurology (clinical) ,Child ,business ,Neuroscience ,Biomarkers ,030217 neurology & neurosurgery - Abstract
Immune-mediated disorders of the CNS in children are a complex group of demyelinating, inflammatory, parainfectious and postinfectious disorders with heterogeneous pathobiological mechanisms and clinical manifestations, often associated with fundamental derangement in immune regulation. In this Review, we aim to provide an update on our knowledge of neuroimmune disorders and highlight areas of research that are priorities for improving clinical management. We outline the clinical features of neuroimmune disorders, the current approaches to their treatment and new approaches in development. We then consider the pathological features, including biomarkers, pathological mechanisms and genetics, and discuss the value of immune assays in clinical investigation and basic research. On the basis of current knowledge and techniques, we propose four research priorities: rigorous and consistent collection of core clinical data, cooperative investigation of treatments, development of biological assays and genetic studies. These priorities should help us to achieve the shared goal of precision medicine for neuroimmune disorders. However, multicentre research and the creation of clinical consortia for these rare disorders will be necessary, and we hope that this Review serves as a call to action that is timely given current exciting advances in neuroimmune therapeutics.
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- 2018
41. Distance from Home to Research Center: A Barrier to In-Person Visits but Not Treatment Adherence in a Stroke Trial
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Mark Gorman, Linnea A. Polgreen, Catherine M. Viscoli, Enrique C. Leira, Walter N. Kernan, and collab
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Male ,Rural Population ,medicine.medical_specialty ,Epidemiology ,Logistic regression ,Health Services Accessibility ,Article ,03 medical and health sciences ,0302 clinical medicine ,Intervention (counseling) ,Secondary Prevention ,medicine ,Humans ,Generalizability theory ,030212 general & internal medicine ,Stroke ,Aged ,Aged, 80 and over ,Clinical Trials as Topic ,Pioglitazone ,business.industry ,Middle Aged ,medicine.disease ,United States ,Treatment Adherence and Compliance ,Clinical trial ,Family medicine ,Female ,Residence ,Neurology (clinical) ,Rural area ,business ,030217 neurology & neurosurgery ,Research center - Abstract
Background and Purpose: Clinical trials often seek to enroll patients from both urban and rural areas to safeguard the generalizability of results. However, maintaining contact with patients who live away from a recruitment site, including rural areas, can be challenging. In this research we examine the effect of distance between patient and study centers on treatment adherence and retention. Methods: Secondary analysis of 2,466 participants in the Insulin Resistance Intervention after Stroke trial who were enrolled from research sites in the United States. Driving distance between the zipcodes of patient’s reported place of residence and the study center was calculated. Outcome measures were loss to follow-up, completion of annual in-person visits, adherence to preventive therapy, and adherence to study drug in the first 3 years of participation. Logistic regression models were used to adjust for confounders. Results: Distance from residence to research center was not associated with loss to follow-up, adherence to study drug, or adherence to preventive therapy (p > 0.05 for each). However, patients who lived farther from the research center (>120 miles), compared to patients who lived closer (Conclusions: Distance between patient and study center was an independent predictor of missed in-person visits but not with adherence to study treatment or preventive care.
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- 2018
42. Including Distal Motor Function within the NIHSS: Correlation with Motor Arm Function and IV rt-PA Treatment Response
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Stephanie R. Shaftman, Kathryn F. Kirchoff-Torres, Mark Gorman, Aron Egelko, Steven R. Levine, David Tanne, Srinath Ramaswamy, and Victor Zach
- Subjects
medicine.medical_specialty ,Treatment response ,Treatment outcome ,Motor function ,Correlation ,Fibrinolytic Agents ,Arm function ,Internal medicine ,Humans ,Medicine ,cardiovascular diseases ,Stroke ,NIH stroke scale ,business.industry ,Rehabilitation ,medicine.disease ,Treatment Outcome ,Tissue Plasminogen Activator ,Arm ,Cardiology ,Administration, Intravenous ,Surgery ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business - Abstract
The Distal Motor Function (DMF) sub-score of the NIH Stroke Scale (NIHSS) was measured in the NINDS rt-PA Stroke Trials but is currently not included in the NIHSS. The correlation of DMF with the NIHSS Motor Arm Function (MAF) sub-score, the effect of IV tPA treatment on DMF, and whether adding DMF changes the utility of the NIHSS have not been analyzed.MAF and DMF sub-scores were retrieved from the original NINDS rt-PA Stroke Trials for both sides of the body at baseline, 2 hours, 24 hours, 7-10 days, and 3 months after IV tPA treatment. MAF and DMF scores were correlated using Spearman correlation. Clustering of DMF and MAF scores was determined using a Bentler Comparative Fit Index (CFI) to estimate variation in NIHSS when adding DMF. The effect of IV tPA on DMF and MAF was assessed using a linear model comparing changes in scores from baseline to 3 months.MAF and DMF were highly correlated (p 0.0001) across all time points for both dichotomous and continuous data on both sides. Intravenous tPA accounted for 21% of the change in DMF (p 0.014, RIncluding DMF to the NIHSS does not appear to be of additional value. After IV tPA treatment, proximal and distal motor function in upper extremity strongly correlate over time but greater improvement in MAF is noted. Further research is needed on the role of IV tPA on minor strokes with deficits of DMF.
- Published
- 2021
43. Contribution of dietary intake to relapse rate in early paediatric multiple sclerosis
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Timothy Lotze, John W. Rose, Tanuja Chitnis, Soe Mar, Yolanda Harris, Charles T. Casper, Gregory Aaen, Lisa F. Barcellos, Anita Belman, Amy Waldman, Mark Gorman, Jayne Ness, Jennifer Graves, Suzan L. Carmichael, Lauren Krupp, Teri Schreiner, Janace Hart, Saeedeh Azary, Emmanuelle Waubant, Shelly Roalstad, Leslie Benson, Jan Mendelt Tillema, Moses Rodriguez, and Bianca Weinstock Guttman
- Subjects
Male ,High energy ,Fat intake ,Saturated fat ,Relapsing-Remitting ,Neurodegenerative ,Medical and Health Sciences ,0302 clinical medicine ,Risk Factors ,Vegetables ,030212 general & internal medicine ,Child ,Pediatric ,relapse ,Clinically isolated syndrome ,Dietary intake ,Psychiatry and Mental health ,Child, Preschool ,Neurological ,Female ,medicine.medical_specialty ,Multiple Sclerosis ,Disease onset ,Adolescent ,Relapse rate ,Autoimmune Disease ,03 medical and health sciences ,Multiple Sclerosis, Relapsing-Remitting ,Clinical Research ,Internal medicine ,medicine ,Vitamin D and neurology ,Humans ,Preschool ,Nutrition ,Neurology & Neurosurgery ,business.industry ,Prevention ,Multiple sclerosis ,Psychology and Cognitive Sciences ,Neurosciences ,medicine.disease ,Dietary Fats ,United States ,Diet ,Brain Disorders ,Surgery ,Vegetable intake ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
ObjectiveThe role of diet in multiple sclerosis (MS) course remains largely unknown. Children with MS have a higher relapse rate compared with MS in adults. Thus, studying the effect of diet on relapse rate in this age group is likely to provide more robust answers.MethodsThis is a multicentre study done at 11 paediatric MS centres in the USA. Patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome (CIS) with disease onset before 18 years of age and duration of less than 4 years were included in this study. Dietary intake during the week before enrolment was assessed with the validated Block Kids Food Screener. The outcome of the study was time from enrolment to the next relapse. 219 patients with paediatric RRMS or CIS were enrolled. Each 10% increase in energy intake from fat increased the hazard of relapse by 56% (adjusted HR 1.56, 95% CI 1.05 to 2.31, p=0.027), and in particular each 10% increase in saturated fat tripled this hazard (adjusted HR: 3.37, 95% CI 1.34 to 8.43, p=0.009). In contrast, each additional one cup equivalent of vegetable decreased the hazard of relapse by 50% (adjusted HR: 0.50, 95% CI 0.27 to 0.91, p=0.024). These associations remained with mutual adjustment and persisted when adjusting for baseline 25(OH) vitamin D serum level. Other studied nutrients were not associated with relapse.ConclusionsThis study suggests that in children with MS, high energy intake from fat, especially saturated fat, may increase the hazard to relapse, while vegetable intake may be independently protective.
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- 2017
44. Genetic risk factors for pediatric-onset multiple sclerosis
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Tanuja Chitnis, Moses Rodriguez, Emmanuelle Waubant, Ingrid Kockum, Jayne Ness, Lisa F. Barcellos, Jennifer Rubin, Jan M. Tillema, Lauren Krupp, Diana Quach, Stacy J. Caillier, Gregory Aaen, Leslie Benson, Yolanda Harris, T. Charles Casper, Shelly Roalstad, Teri Schreiner, Soe Mar, Tomas Olsson, Jan Hillert, Amy Waldman, Benjamin Greenberg, Milena A. Gianfrancesco, Jennifer Graves, Bianca Weinstock-Guttman, Meghan Candee, Xiaorong Shao, Ling Shen, Anita Belman, Janace Hart, Pernilla Stridh, Timothy Lotze, Brooke Rhead, Ilana Kahn, Mark Gorman, Catherine Schaefer, Lars Alfredsson, John W. Rose, Anna Karin Hedström, and Hong Quach
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Multiple Sclerosis ,Pediatric onset ,Bioinformatics ,Major histocompatibility complex ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Epidemiology ,Humans ,Medicine ,Genetic Predisposition to Disease ,Genetic Testing ,Genetic risk ,Sweden ,biology ,business.industry ,Multiple sclerosis ,Genetic variants ,Odds ratio ,medicine.disease ,Logistic Models ,030104 developmental biology ,Neurology ,Etiology ,biology.protein ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,HLA-DRB1 Chains - Abstract
Background: Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology. Objective: We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS. Methods: Cases with onset Results: HLA–DRB1*15:01 was strongly associated with POMS (odds ratio (OR)meta = 2.95, p −16). Furthermore, 28 of 104 non-MHC variants studied (23%) were associated ( p avg = 1.24 vs 1.13, respectively), though the difference was not significant. The wGRS was strongly associated with POMS (ORmeta = 2.77, 95% confidence interval: 2.33, 3.32, p −16) and higher, on average, when compared to adult cases. Additional class III risk variants in the MHC region associated with POMS were revealed after accounting for HLA–DRB1*15:01 and HLA–A*02. Conclusion: Pediatric and adult MS share many genetic variants suggesting similar biological processes are present. MHC variants beyond HLA–DRB1*15:01 and HLA–A*02 are also associated with POMS.
- Published
- 2017
45. Effects of pioglitazone on cognitive function in patients with a recent ischaemic stroke or TIA: a report from the IRIS trial
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Karen L. Furie, Peter D. Guarino, David Tanne, Catherine M. Viscoli, Silvio E. Inzucchi, Anne M. Lovejoy, Mark Gorman, Lawrence H. Young, Walter N. Kernan, Robin Conwit, and Gary A. Ford
- Subjects
Male ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,Vascular risk ,Placebo ,03 medical and health sciences ,Cognition ,0302 clinical medicine ,Insulin resistance ,Double-Blind Method ,Risk Factors ,Internal medicine ,Ischaemic stroke ,medicine ,Humans ,Hypoglycemic Agents ,In patient ,Longitudinal Studies ,Stroke ,Pioglitazone ,business.industry ,Middle Aged ,medicine.disease ,Psychiatry and Mental health ,Ischemic Attack, Transient ,Physical therapy ,Female ,Thiazolidinediones ,Surgery ,Neurology (clinical) ,Insulin Resistance ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
IntroductionPatients with cerebrovascular disease are at increased risk for cognitive dysfunction. Modification of vascular risk factors, including insulin resistance, could improve poststroke cognitive function.MethodsIn the Insulin Resistance Intervention after Stroke (IRIS) trial, patients with a recent ischaemic stroke or transient ischaemic attack (TIA) were randomised to pioglitazone (target 45 mg daily) or placebo. All patients were insulin resistant based on a Homeostasis Model Assessment-Insulin Resistance score >3.0. For this preplanned analysis of cognitive function, we examined the Modified Mini-Mental State Examination (3MS) score (maximum score, 100) during follow-up. Patients were tested at baseline and annually for up to 5 years. Longitudinal mixed model methods were used to compare changes in the 3MS over time.ResultsOf the 3876 IRIS participants, 3398 had a 3MS score at baseline and at least once during follow-up and were included in the analysis. Median 3MS score at baseline was 97 (IQR 93–99). The average overall least squared mean 3MS score increased by 0.27 in the pioglitazone group and by 0.29 in the placebo group (mean difference between treatment groups −0.02; 95% CI −0.33 to 0.28, p=0.88).ConclusionsAmong insulin-resistant patients with a recent ischaemic stroke or TIA, pioglitazone did not affect cognitive function, as measured by the 3MS, over 5 years.Trial registrationClinicalTrials.gov NCT00091949; Results.
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- 2017
46. Smoking cessation and outcome after ischemic stroke or TIA
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Katherine A, Epstein, Catherine M, Viscoli, J David, Spence, Lawrence H, Young, Silvio E, Inzucchi, Mark, Gorman, Brett, Gerstenhaber, Peter D, Guarino, Anand, Dixit, Karen L, Furie, Walter N, Kernan, and Howard S, Kirshner
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,Myocardial Infarction ,030204 cardiovascular system & hematology ,Article ,Cohort Studies ,Coronary artery disease ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,Myocardial infarction ,Stroke ,Aged ,Proportional Hazards Models ,Proportional hazards model ,business.industry ,Smoking ,Hazard ratio ,Middle Aged ,medicine.disease ,Ischemic Attack, Transient ,Cohort ,Physical therapy ,Smoking cessation ,Female ,Smoking Cessation ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Cohort study - Abstract
Objective:To assess whether smoking cessation after an ischemic stroke or TIA improves outcomes compared to continued smoking.Methods:We conducted a prospective observational cohort study of 3,876 nondiabetic men and women enrolled in the Insulin Resistance Intervention After Stroke (IRIS) trial who were randomized to pioglitazone or placebo within 180 days of a qualifying stroke or TIA and followed up for a median of 4.8 years. A tobacco use history was obtained at baseline and updated during annual interviews. The primary outcome, which was not prespecified in the IRIS protocol, was recurrent stroke, myocardial infarction (MI), or death. Cox regression models were used to assess the differences in stroke, MI, and death after 4.8 years, with correction for adjustment variables prespecified in the IRIS trial: age, sex, stroke (vs TIA) as index event, history of stroke, history of hypertension, history of coronary artery disease, and systolic and diastolic blood pressures.Results:At the time of their index event, 1,072 (28%) patients were current smokers. By the time of randomization, 450 (42%) patients had quit smoking. Among quitters, the 5-year risk of stroke, MI, or death was 15.7% compared to 22.6% for patients who continued to smoke (adjusted hazard ratio 0.66, 95% confidence interval 0.48–0.90).Conclusion:Cessation of cigarette smoking after an ischemic stroke or TIA was associated with significant health benefits over 4.8 years in the IRIS trial cohort.
- Published
- 2017
47. Dietary factors and pediatric multiple sclerosis: A case-control study
- Author
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Teri Schreiner, Michael Waltz, Emmanuelle Waubant, Suzan L. Carmichael, Brandon Seminatore, Jan Mendelt Tillema, Jamie McDonald, Janace Hart, Anita Belman, Shelly Roalstad, Yolanda Harris, Mark Gorman, Bianca Weinstock-Guttman, Soe Mar, Amy Waldman, Benjamin Greenberg, Meghan Candee, Ilana Kahn, Julia Pakpoor, John W. Rose, Gregory Aaen, T. Charles Casper, Jennifer Graves, Moses Rodriguez, Tanuja Chitnis, Jayne Ness, Lauren Krupp, Timothy Lotze, Jennifer Rubin, and Leslie Benson
- Subjects
Male ,medicine.medical_specialty ,Pediatrics ,Multiple Sclerosis ,Neurology ,Adolescent ,Dietary factors ,Logistic regression ,Diet Surveys ,Article ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Humans ,Medicine ,030212 general & internal medicine ,Child ,Dietary iron ,Clinically isolated syndrome ,medicine.diagnostic_test ,business.industry ,Multiple sclerosis ,Case-control study ,Magnetic resonance imaging ,medicine.disease ,Diet ,Case-Control Studies ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Background: The role of diet in multiple sclerosis (MS) is largely uncharacterized, particularly as it pertains to pediatric-onset disease. Objective: To determine the association between dietary factors and MS in children. Methods: Pediatric MS patients and controls were recruited from 16 US centers (MS or clinically isolated syndrome onset before age 18, Results: In total, 312 cases and 456 controls were included (mean ages 15.1 and 14.4 years). In unadjusted analyses, there was no difference in intake of fats, proteins, carbohydrates, sugars, fruits, or vegetables. Dietary iron was lower in cases ( p = 0.04), and cases were more likely to consume below recommended guidelines of iron (77.2% of cases vs 62.9% of controls, p Conclusion: Pediatric MS cases may be less likely to consume sufficient iron compared to controls, and this warrants broader study to characterize a temporal relationship. No other significant difference in intake of most dietary factors was found.
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- 2017
48. Evaluating the association of allergies with multiple sclerosis susceptibility risk and disease activity in a pediatric population
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Leslie Benson, Moses Rodriguez, Tanuja Chitnis, Lisa F. Barcellos, Teri Schreiner, Jennifer Graves, Timothy Lotze, Greg Aaen, Emmanuelle Waubant, Michael Waltz, Theron Charles Casper, Ilana Kahn, Yolanda Harris, John W. Rose, Jan Mendelt Tillema, Katelyn Kavak, Anita Belman, Mark Gorman, Amy Waldman, Benjamin Greenberg, Meghan Candee, Cody S. Olsen, Bianca Weinstock-Guttman, Soe Mar, Shelly Roalstad, Jennifer Rubin, Theresa Bourne, Jayne Ness, and Lauren Krupp
- Subjects
Male ,Allergy ,Pediatrics ,medicine.medical_specialty ,Multiple Sclerosis ,Disease onset ,Adolescent ,Article ,Cohort Studies ,Disease activity ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Hypersensitivity ,medicine ,Humans ,030212 general & internal medicine ,Genetic risk ,Asthma ,business.industry ,Multiple sclerosis ,medicine.disease ,Neurology ,Case-Control Studies ,Cohort ,Female ,Disease Susceptibility ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Pediatric population - Abstract
Background Multiple sclerosis (MS) and allergies are both considered to be related to imbalanced Th1 and Th2 immune responses. Previous studies evaluating the relationship between MS and allergies provide conflicting results. Objective To assess allergies and asthma as risk factors for MS and as predictors of MS relapses in a pediatric cohort. Methods The environment and genetic risk factors for pediatric MS study is a national case-control project with 16 participating US sites. An environmental questionnaire is used that includes history of allergies in the first five years of life. Case-control data are entered in the pediatric MS Network database and cases at 12 of the 16 sites enter relapse data prospectively. Annualized relapse rate was calculated for patients with follow-up and adjusted for age at disease onset, gender, race, ethnicity, and use of disease-modifying therapy (DMT). Results We included 271 cases (mean age at disease onset of 15.7 years and 62% female) and 418 controls. Relapse data were available for 193 cases. There was no difference in prevalence of allergies or asthma between cases and controls. Patients with food allergies had fewer relapses compared to patients without food allergies (0.14 vs 0.48, p = 0.01). Conclusions While allergies and asthma are not associated with pediatric MS, cases with food allergies have fewer relapses compared to those without food allergies.
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- 2017
49. Risk factors for non-adherence to disease-modifying therapy in pediatric multiple sclerosis
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Carolyn E. Schwartz, Victoria E. Powell, Brenda Banwell, Lauren Mednick, Emmanuelle Waubant, Gulay Alper, E. Ann Yeh, Teri Schreiner, Soe Mar, Mary Rensel, Jean K. Mah, Austin Noguera, Stephanie A. Grover, Mark Gorman, and Amy Waldman
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Male ,Parents ,medicine.medical_specialty ,Multiple Sclerosis ,Adolescent ,Disease ,Article ,Medication Adherence ,Poor adherence ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,Risk Factors ,medicine ,Humans ,Immunologic Factors ,030212 general & internal medicine ,Child ,Intensive care medicine ,business.industry ,Multiple sclerosis ,medicine.disease ,Self Efficacy ,Non adherence ,Cross-Sectional Studies ,Neurology ,North America ,Female ,Self Report ,Neurology (clinical) ,business ,Psychosocial ,030217 neurology & neurosurgery - Abstract
Background:Adherence to disease-modifying therapies (DMTs) in pediatric multiple sclerosis (MS) is not well understood. We examined the prevalence and risk factors for poor adherence in pediatric MS.Methods:This cross-sectional study recruited youth with MS from 12 North American pediatric MS clinics. In addition to pharmacy-refill data, patients and parents completed self-report measures of adherence and quality of life. Additionally, patients completed measures of self-efficacy and well-being. Factor analysis and linear regression methods were used.Results:A total of 66 youth (mean age, 15.7 years) received MS DMTs (33% oral, 66% injectable). Estimates of poor adherence (i.e. missing >20% of doses) varied by source: pharmacy 7%, parent 14%, and patient 41%. Factor analysis yielded two composites: adherence summary and parental involvement in adherence. Regressions revealed that patients with better self-reported physical functioning were more adherent. Parents were more likely to be involved in adherence when their child had worse parent-reported PedsQL School Functioning and lower MS Self-Efficacy Control. Oral DMTs were associated with lesser parental involvement in adherence.Conclusion:Rates of non-adherence varied by information source. Better self-reported physical functioning was the strongest predictor of adherence. Parental involvement in adherence was associated with worse PedsQL School Functioning and lower MS Self-Efficacy-measured confidence in controlling MS.
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- 2017
50. Distinct effects of obesity and puberty on risk and age at onset of pediatric MS
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Teri Schreiner, Bianca Weinstock-Guttman, Madhusmita Misra, Tanuja Chitnis, Amy Waldman, Benjamin Greenberg, Charlie Casper, Jayne Ness, Leslie Benson, Moses Rodriguez, Anita Belman, Lauren Krupp, Meghan Candee, Timothy Lotze, Soe Mar, Jennifer Rubin, John W. Rose, Mark Gorman, Jennifer Graves, Gregory Aaen, Cody S. Olsen, Emmanuelle Waubant, and Jan M. Tillema
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Pediatrics ,Overweight ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,Sexual maturity ,Risk factor ,Research Articles ,2. Zero hunger ,business.industry ,General Neuroscience ,medicine.disease ,Obesity ,Confidence interval ,3. Good health ,030104 developmental biology ,Endocrinology ,Menarche ,Neurology (clinical) ,medicine.symptom ,Age of onset ,business ,Body mass index ,030217 neurology & neurosurgery ,Research Article - Abstract
Objective The aim of this study was to examine the relative contributions of body mass index (BMI) and pubertal measures for risk and age of onset of pediatric MS. Methods Case–control study of 254 (63% female) MS cases (onset
- Published
- 2016
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