Differences by Sex in the Workup of Children at High Risk for Multiple Sclerosis (1917)
Bibliographic record
Abstract
Objective: To determine whether there are differences by sex in the workup of children at high risk for multiple sclerosis (MS). Background: Differences by sex in patterns of investigation have been reported for various autoimmune diseases in adults. We identified children who underwent brain MRI scans for reasons other than suspected MS, but their MRIs showed typical MRI features of MS. This scenario has been termed radiologically isolated syndrome (RIS). We previously reported that 42% of children with RIS developed a first clinical demyelinating event in a median of 2 years. Oligoclonal bands in spinal fluid, and asymptomatic spinal cord lesions on MRI were associated with the subsequent development of a first clinical demyelinating event. Design/Methods: We analyzed a historical cohort of children (<18 years) with RIS enrolled in an international longitudinal study. All children met 2010 MRI criteria for dissemination in space (DIS) on index scans (Ped-RIS). All scans also met 2017 DIS criteria on MRI. We used Fisher’s exact test for univariate analyses and created multivariable Cox proportional hazards models for time to a first clinical demyelinating event. Results: We included 89 children with Ped-RIS of whom 67% were girls. Boys were less likely than girls to undergo a lumbar puncture (LP; 55% vs 75%, p=0.05), but were similarly likely to have an MRI of the spinal cord (90% vs 77%, p=0.14). Boys remained less likely to undergo an LP even after adjustment for age, race, country of residence, indication for initial MRI, and having an MRI that met 2005 criteria for DIS (surrogate marker for number of lesions; adjusted hazard ratio 0.44, 95% C.I. 0.23–0.85, p=0.02). Conclusions: Boys with Ped-RIS were less likely than girls to undergo an LP, a procedure that aids risk stratification for MS and is of clinical importance. The reasons for this difference require further study. Disclosure: Dr. Makhani has nothing to disclose. Dr. Lebrun-Frenay has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting fees, honoraria or scientific committee support: Bayer Schering, Biogen, Genzyme, Merck Serono, Novartis, Teva. Dr. Siva has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck, Novartis, Teva, Genzyme, Bayer, Roche, Biogen Idec/Gen Ilac-Turkey.Dr. Wassmer has nothing to disclose. Dr. Narula has nothing to disclose. Dr. Mar has nothing to disclose. Dr. Santoro has nothing to disclose. Dr. Ahsan has nothing to disclose. Dr. Tenembaum has nothing to disclose. Dr. Brenton has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis.Dr. Cabre has nothing to disclose. Dr. Carra-Dalliere has nothing to disclose. Dr. Ciron has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck%2C%20Roche%2C%20Biogen%2C%20Novartis%2C%20Teva. Dr. De Seze has nothing to disclose. Dr. Deiva has nothing to disclose. Dr. Durand Dubief has nothing to disclose. Dr. Inglese has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis Pharmaceuticals, National Multiple Sclerosis Society, Noto Foundation, NIH, and Teva Neuroscience.Dr. Langille has nothing to disclose. Dr. Mathey has nothing to disclose. Dr. Neuteboom has nothing to disclose. Dr. Palavra has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Sanofi-Genzyme, Merck, Novartis and Teva Pharmaceuticals. Dr. Palavra has received research support from Biogen. Dr. Pelletier has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jean Pelletier has received compensation for consulting services and speaking honoraria from Biogen, Roche, MedDay, Sanofi-Genzyme, Merck, Novartis and Teva Pharmaceuticals. Dr. Pelletier has received research support from Jean Pelletier received a research grant from Biogen, Roche and Merck. Dr. Pohl has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting and speaker’s honoraria and support for attending conferences from Novartis Pharma AG, Forward Pharma, Biogen-Idec, Merck-Serono, Teva and Eisei. Dr. Reich has received research support from Vertex.Dr. Rojas has nothing to disclose. Dr. Shabanova has nothing to disclose. Dr. Shapiro has nothing to disclose. Dr. Thompson-Stone has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Homer and Conway, P.C. Dr. Thouvenot has nothing to disclose. Dr. Tinore has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Almirall, Biogen-Idec, Genzyme, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Viela Bio and Teva Pharmaceuticals. Dr. Tinore has received personal compensation in an editorial capacity for co-editor of Multiple Sclerosis Journal-ETC. Dr. Tinore has received research support from Biogen-Idec, Genzyme, Merck-Serono, Novartis. Dr. Uygunoglu has nothing to disclose. Dr. Vargas has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals, Biogen, Octapharma. Dr. Vargas has received research support from Teva Pharmaceuticals. Dr. Venkateswaran has nothing to disclose. Dr. Verhelst has nothing to disclose. Dr. Vermersch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Almirall, Biogen, Celgene, Merck Serono, Novartis, Roche, Sanofi, Servier, and Teva. Dr. Vermersch has received research support from Almirall, Biogen, Celgene, Merck Serono, Novartis, Roche, Sanofi, Servier, and Teva.Dr. Azevedo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi-Genzyme, Genentech, EMD Serono, and Alexion Pharmaceuticals.Dr. Kantarci has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis and Biogen. Dr. Kantarci has received research support from Biogen, the Multiple Sclerosis Society, the Mayo Foundation, and the Hilton Foundation. Dr. Okuda has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acorda Therapeutics, Genentech, Genzyme, Teva, consulted for Bayer, EMD Serono, Genzyme, Novartis, served on the speakers’ bureau for Acorda Therapeutics. Dr. Okuda has received research support from Biogen. Dr. Pelletier has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, EMD Serono, Novartis, Roche, and Sanofi-Genzyme. Dr. Pelletier has received research support from Biogen, EMD Serono, Novartis, Roche, and Sanofi-Genzyme. Dr. (OFSEP) has nothing to disclose. Dr. (SFSEP) has nothing to disclose. Dr. (RISC) has nothing to disclose. Dr. Consortium (PARIS) has nothing to disclose.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".