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Record W4307106827 · doi:10.1186/s13023-022-02547-8

Improved upper limb function in non-ambulant children with SMA type 2 and 3 during nusinersen treatment: a prospective 3-years SMArtCARE registry study

2022· article· en· W4307106827 on OpenAlexaff
Astrid Pechmann, Max Behrens, Katharina Dörnbrack, Adrian Tassoni, Franziska Wenzel, Sabine Stein, Sibylle Emilie Vogt, Daniela Zöller, Günther Bernert, Tim Hagenacker, Ulrike Schara‐Schmidt, Maggie C. Walter, Astrid Bertsche, Katharina Vill, Matthias Baumann, Manuela Baumgärtner, Isabell Cordts, Astrid Eisenkölbl, Marina Flotats‐Bastardas, Johannes Friese, René Günther, Andreas Hahn, Veronka Horber, Ralf A. Husain, Sabine Illsinger, Jörg Jahnel, Jessika Johannsen, Cornelia Köhler, Heike Kölbel, Monika Müller, Arpad von Moers, Annette Schwerin-Nagel, Christof Reihle, Kurt Schlachter, Gudrun Schreiber, Oliver Schwartz, Martin Smitka, Elisabeth Steiner, Regina Trollmann, Markus Weiler, Claudia Weiß, Gert Wiegand, Ekkehard Wilichowski, Andreas Ziegler, Hanns Lochmüller, Janbernd Kirschner, Bárbara Andres, Daniela Angelova-Toshkina, Daniela Banholzer, Christina Bant, Petra Baum, Sandra Baumann, Ute Baur, Benedikt Becker, Bettina Behring, Julia Bellut, Andrea Bevot, Jasmin Bischofberger, Lisa Bitzan, Bogdan Bjelica, Markus Blankenburg, Sandra Böger, Friederike Bonetti, Anke Bongartz, Svenja Brakemeier, Lisa Bratka, Nathalie Braun, Sarah Braun, Brigitte Brauner, Christa Bretschneider, Nadine Burgenmeister, Bea Burke, Sebahattin Çırak, Andrea Dall, Heike de Vries, Adela Della Marina, Jonas Denecke, Marcus Deschauer, Zylfie Dibrani, Uta Diebold, Lutz Dondit, Jessica Drebes, Joenna Driemeyer, Vladimir Dukic, Matthias Eckenweiler, Mirjam Eminger, Michal Fischer, Cornelia Fischer, Maren Freigang, Philippa Gaiser, Andrea Gangfuß, Stephanie Geitmann, Annette George, Magdalena Gosk-Tomek, Susanne Grinzinger, Kristina Gröning, Martin Groß, Anne‐Katrin Güttsches, Anna Hagenmeyer, H. Hartmann, Julia Haverkamp, Miriam Hiebeler, Annegret Hoevel, Georg F. Hoffmann, Britta Holtkamp, Dorothea Holzwarth, Annette Karolin Homma, Viola Horneff, Carolin Hörnig, Anna Hotter, Andrea Hubert, Peter Huppke, Eva Jansen, Lisa Jung, Nadja Kaiser, Stefan Kappel, Bolte Katharina, Johannes Koch, Stefan Kölke, Brigitte Korschinsky, Franziska Kostede, Karsten Krause, Hanna Küpper, Annina Lang, Irene Lange, Thorsten Langer, Yvonne Lechner, Helmar C. Lehmann, Christine Leypold, Paul Lingor, Jaqueline Lipka, Wolfgang N. Löscher, Antje Luiking, Gerrit Machetanz, Eva Malm, Κyriakos Martakis, Bettina Menzen, Moritz Metelmann, Gerd Meyer zu Hörste, Federica Montagnese, Kathrin Mörtlbauer, Petra Müller, Anne Müller, Anja Müller, Lars Hendrik Müschen, Christoph Neuwirth, Moritz Niesert, Josefine Pauschek, Elke Pernegger, Susanne Petri, Veronika Pilshofer, Barbara Plecko, Jürgen Pollok, Martin Preisel, Manuel Pühringer, Anna Lisa Quinten, S. Raffler, Barbara Ramadan, Mika Rappold, Christian Rauscher, Kerstin Reckmann, Tabea Reinhardt, Melanie Röder, Doris Roland-Schäfer, Erdmute Roth, Lena Ruß, Afshin Saffari, Mareike Schimmel, Melina Schlag, Beate Schlotter‐Weigel, Joanna Schneider, Jan-Christoph Schöne-Bake, David Schorling, Isabella Schreiner, Stephanie C. Schüssler, Michaela Schwarzbach, Michaela Schwippert, Luisa Semmler, Karin Smuda, Alina Sprenger-Svacina, Theresa Stadler, Paula Steffens, Daniela Steuernagel, Benjamin Stolte, Corinna Stoltenburg, Gehrke Tasch, Andreas Thimm, Elke Tiefenthaler, Raffi Topakian, Matthias Türk, Lieske van der Stam, Katia Vettori, Peter Vollmann, Matthias Vorgerd, Deike Weiss, Stephan Wenninger, Svea Werring, Maria Wessel, Ute Weyen, Sabine Wider, Nils Ole Wiebe, Anna Wiesenhofer, Sarah Wiethoff, Corinna Wirner, Camilla Wohnrade, Gilbert Wunderlich, Daniel Zeller, Michael Zemlin, Joachim Zobel

Bibliographic record

VenueOrphanet Journal of Rare Diseases · 2022
Typearticle
Languageen
FieldMedicine
TopicNeurogenetic and Muscular Disorders Research
Canadian institutionsOttawa HospitalChildren's Hospital of Eastern OntarioUniversity of Ottawa
FundersAlbert-Ludwigs-Universität FreiburgHarmony BiosciencesSarepta TherapeuticsF. Hoffmann-La RocheArgenxBiogenSpark TherapeuticsPTC TherapeuticsUltragenyx PharmaceuticalSanofiPfizer
KeywordsSMA*MedicineSpinal muscular atrophyMilestoneMotor functionPediatricsPhysical therapyDiseaseNeuromuscular diseasePhysical medicine and rehabilitationInternal medicine

Abstract

fetched live from OpenAlex

BACKGROUND: The development and approval of disease modifying treatments have dramatically changed disease progression in patients with spinal muscular atrophy (SMA). Nusinersen was approved in Europe in 2017 for the treatment of SMA patients irrespective of age and disease severity. Most data on therapeutic efficacy are available for the infantile-onset SMA. For patients with SMA type 2 and type 3, there is still a lack of sufficient evidence and long-term experience for nusinersen treatment. Here, we report data from the SMArtCARE registry of non-ambulant children with SMA type 2 and typen 3 under nusinersen treatment with a follow-up period of up to 38 months. METHODS: SMArtCARE is a disease-specific registry with data on patients with SMA irrespective of age, treatment regime or disease severity. Data are collected during routine patient visits as real-world outcome data. This analysis included all non-ambulant patients with SMA type 2 or 3 below 18 years of age before initiation of treatment. Primary outcomes were changes in motor function evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM). RESULTS: Data from 256 non-ambulant, pediatric patients with SMA were included in the data analysis. Improvements in motor function were more prominent in upper limb: 32.4% of patients experienced clinically meaningful improvements in RULM and 24.6% in HFMSE. 8.6% of patients gained a new motor milestone, whereas no motor milestones were lost. Only 4.3% of patients showed a clinically meaningful worsening in HFMSE and 1.2% in RULM score. CONCLUSION: Our results demonstrate clinically meaningful improvements or stabilization of disease progression in non-ambulant, pediatric patients with SMA under nusinersen treatment. Changes were most evident in upper limb function and were observed continuously over the follow-up period. Our data confirm clinical trial data, while providing longer follow-up, an increased number of treated patients, and a wider range of age and disease severity.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.010
Threshold uncertainty score0.426

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.007
GPT teacher head0.248
Teacher spread0.241 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations40
Published2022
Admission routes1
Has abstractyes

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