المؤلفون: Anna G. Mayhew, Meredith K. James, Ursula Moore, Helen Sutherland, Marni Jacobs, Jia Feng, Linda Pax Lowes, Lindsay N. Alfano, Robert Muni Lofra, Laura E. Rufibach, Kristy Rose, Tina Duong, Luca Bello, Irene Pedrosa-Hernández, Scott Holsten, Chikako Sakamoto, Aurélie Canal, Nieves Sánchez-Aguilera Práxedes, Simone Thiele, Catherine Siener, Bruno Vandevelde, Brittney DeWolf, Elke Maron, Heather Gordish-Dressman, Heather Hilsden, Michela Guglieri, Jean-Yves Hogrel, Andrew M. Blamire, Pierre G. Carlier, Simone Spuler, John W. Day, Kristi J. Jones, Diana X. Bharucha-Goebel, Emmanuelle Salort-Campana, Alan Pestronk, Maggie C. Walter, Carmen Paradas, Tanya Stojkovic, Madoka Mori-Yoshimura, Elena Bravver, Jordi Díaz-Manera, Elena Pegoraro, Jerry R. Mendell, Volker Straub

المصدر: Frontiers in Neurology, Vol 13 (2022)

مصطلحات موضوعية: limb girdle muscular dystrophy, dysferlinopathy, PROMs, quality of life, clinical outcome assessments, Neurology. Diseases of the nervous system, RC346-429

الوصف: Dysferlinopathy is a muscular dystrophy with a highly variable functional disease progression in which the relationship of function to some patient reported outcome measures (PROMs) has not been previously reported. This analysis aims to identify the suitability of PROMs and their association with motor performance.Two-hundred and four patients with dysferlinopathy were identified in the Jain Foundation's Clinical Outcome Study in Dysferlinopathy from 14 sites in 8 countries. All patients completed the following PROMs: Individualized Neuromuscular Quality of Life Questionnaire (INQoL), International Physical Activity Questionnaire (IPAQ), and activity limitations for patients with upper and/or lower limb impairments (ACTIVLIMs). In addition, nonambulant patients completed the Egen Klassifikation Scale (EK). Assessments were conducted annually at baseline, years 1, 2, 3, and 4. Data were also collected on the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) and Performance of Upper Limb (PUL) at these time points from year 2. Data were analyzed using descriptive statistics and Rasch analysis was conducted on ACTIVLIM, EK, INQoL. For associations, graphs (NSAD with ACTIVLIM, IPAQ and INQoL and EK with PUL) were generated from generalized estimating equations (GEE). The ACTIVLIM appeared robust psychometrically and was strongly associated with the NSAD total score (Pseudo R2 0.68). The INQoL performed less well and was poorly associated with the NSAD total score (Pseudo R2 0.18). EK scores were strongly associated with PUL (Pseudo R2 0.69). IPAQ was poorly associated with NSAD scores (Pseudo R2 0.09). This study showed that several of the chosen PROMs demonstrated change over time and a good association with functional outcomes. An alternative quality of life measure and method of collecting data on physical activity may need to be selected for assessing dysferlinopathy.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fneur.2022.828525/fullTest; https://doaj.org/toc/1664-2295Test

الوصول الحر: https://doaj.org/article/0470816544d14c339d5608df7267ca17Test

المؤلفون: Catherine Siener, Marisa Birkmeier, Heather Gordish-Dressman, Erik K Henricson, Tina Duong, Cinrg-Dnhs Investigators, Alicia Fernandez-Fernandez, Craig M. McDonald, Jennifer Canbek, Leslie Nelson

المصدر: Journal of Neuromuscular Diseases

مصطلحات موضوعية: Research Report, Duchenne muscular dystrophy, Male, medicine.medical_specialty, Supine position, Minimal Clinically Important Difference, MCID, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Clinical endpoint, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Child, Retrospective Studies, business.industry, Minimal clinically important difference, Muscle weakness, medicine.disease, time function tests, Muscular Dystrophy, Duchenne, Standard error, Neurology, Disease Progression, Functional status, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, Natural history study

الوصف: Background: Duchenne muscular dystrophy (DMD) is a rare x-linked recessive genetic disorder affecting 1 in every 5000–10000 [1, 2]. This disease leads to a variable but progressive sequential pattern of muscle weakness that eventually causes loss of important functional milestones such as the ability to walk. With promising drugs in development to ameliorate the effects of muscle weakness, these treatments must be associated with a clinically meaningful functional change. Objective: The objective of this analysis is to determine both distribution, minimal detectable change (MDC), and anchor-based, minimal clinically important difference, (MCID) of 12 month change values in standardized time function tests (TFT) used to monitor disease progression in DMD. Method: This is a retrospective analysis of prospectively collected data from a multi-center prospective natural history study with the Cooperative International Neuromuscular Research Group (CINRG). This study calculated MDC and MCID values for 3 commonly used timed function tests typically used to monitor disease progression; supine to stand (STS), 10 meter walk/run (10MWT), and 4 stair climb (4SC). MDC used standard error of measurement (SEM) while MCID measurements used the Vignos scale as an anchor to determine clinical change in functional status. Results: All 3 TFT were significantly important clinical endpoints to detect MDC and MCID changes. MDC and MCID 12 month changes were significant in 10MWT (–0.138, –0.212), Supine to Stand (–0.026, –0.023) and 4 stair climb (–0.034, –0.035) with an effect size greater or close to 0.2. Conclusion: The 3 TFT are clinically meaningful endpoints used to establish change in DMD. MCID values were higher than MDC values indicating that an anchor-based approach using Vignos as a clinically meaningful loss of lower extremity abilities is appropriate to assess change in boys with DMD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f3a561d7377c58a89c038d67077f2b77Test
http://europepmc.org/articles/PMC8673528Test

المؤلفون: Anna G. Mayhew, Meredith K. James, Ursula Moore, Helen Sutherland, Marni Jacobs, Jia Feng, Linda Pax Lowes, Lindsay N. Alfano, Robert Muni Lofra, Laura E. Rufibach, Kristy Rose, Tina Duong, Luca Bello, Irene Pedrosa-Hernández, Scott Holsten, Chikako Sakamoto, Aurélie Canal, Nieves Sánchez-Aguilera Práxedes, Simone Thiele, Catherine Siener, Bruno Vandevelde, Brittney DeWolf, Elke Maron, Heather Gordish-Dressman, Heather Hilsden, Michela Guglieri, Jean-Yves Hogrel, Andrew M. Blamire, Pierre G. Carlier, Simone Spuler, John W. Day, Kristi J. Jones, Diana X. Bharucha-Goebel, Emmanuelle Salort-Campana, Alan Pestronk, Maggie C. Walter, Carmen Paradas, Tanya Stojkovic, Madoka Mori-Yoshimura, Elena Bravver, Jordi Díaz-Manera, Elena Pegoraro, Jerry R. Mendell, Volker Straub

مصطلحات موضوعية: Neurology and Neuromuscular Diseases, Neurogenetics, limb girdle muscular dystrophy, dysferlinopathy, PROMs, quality of life, clinical outcome assessments

الوصف: Dysferlinopathy is a muscular dystrophy with a highly variable functional disease progression in which the relationship of function to some patient reported outcome measures (PROMs) has not been previously reported. This analysis aims to identify the suitability of PROMs and their association with motor performance.Two-hundred and four patients with dysferlinopathy were identified in the Jain Foundation's Clinical Outcome Study in Dysferlinopathy from 14 sites in 8 countries. All patients completed the following PROMs: Individualized Neuromuscular Quality of Life Questionnaire (INQoL), International Physical Activity Questionnaire (IPAQ), and activity limitations for patients with upper and/or lower limb impairments (ACTIVLIMs). In addition, nonambulant patients completed the Egen Klassifikation Scale (EK). Assessments were conducted annually at baseline, years 1, 2, 3, and 4. Data were also collected on the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) and Performance of Upper Limb (PUL) at these time points from year 2. Data were analyzed using descriptive statistics and Rasch analysis was conducted on ACTIVLIM, EK, INQoL. For associations, graphs (NSAD with ACTIVLIM, IPAQ and INQoL and EK with PUL) were generated from generalized estimating equations (GEE). The ACTIVLIM appeared robust psychometrically and was strongly associated with the NSAD total score (Pseudo R 2 0.68). The INQoL performed less well and was poorly associated with the NSAD total score (Pseudo R 2 0.18). EK scores were strongly associated with PUL (Pseudo R 2 0.69). IPAQ was poorly associated with NSAD scores (Pseudo R 2 0.09). This study showed that several of the chosen PROMs demonstrated change over time and a good association with functional outcomes. An alternative quality of life measure and method of collecting data on physical activity may need to be selected for assessing dysferlinopathy.

العلاقة: https://figshare.com/articles/dataset/Table_1_Assessing_the_Relationship_of_Patient_Reported_Outcome_Measures_With_Functional_Status_in_Dysferlinopathy_A_Rasch_Analysis_Approach_docx/19335725Test

الإتاحة: https://doi.org/10.3389/fneur.2022.828525.s001Test
https://figshare.com/articles/dataset/Table_1_Assessing_the_Relationship_of_Patient_Reported_Outcome_Measures_With_Functional_Status_in_Dysferlinopathy_A_Rasch_Analysis_Approach_docx/19335725Test

المؤلفون: Helen E. Stephens, Robert A. English, Mary Proffitt Bunnell, Merit Cudkowicz, Katherine A Fetterman, Catherine Siener, Julaine Florence, Patricia L. Andres, Eric A. Macklin, Zachary Simmons, Edward J. Kasarskis, Margaret Allred, Travis Haines

المصدر: Muscle & Nerve. 56:710-715

مصطلحات موضوعية: Male, Longitudinal study, medicine.medical_specialty, Physiology, Vital Capacity, Muscle Strength Dynamometer, Isometric exercise, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Muscle nerve, Physical medicine and rehabilitation, Rating scale, Isometric Contraction, Physiology (medical), medicine, Humans, Longitudinal Studies, Muscle Strength, 030212 general & internal medicine, Amyotrophic lateral sclerosis, Alsfrs r, business.industry, Amyotrophic Lateral Sclerosis, Outcome measures, Middle Aged, medicine.disease, Sample size determination, Female, Neurology (clinical), business, 030217 neurology & neurosurgery

الوصف: Introduction: Improved outcome measures are essential to efficiently screen the growing number of potential amyotrophic lateral sclerosis (ALS) therapies. Methods: This longitudinal study of 100 (70 male) participants with ALS compared Accurate Test of Limb Isometric Strength (ATLIS), using a fixed, wireless load cell, with ALS Functional Rating Scale-Revised (ALSFRS-R) and vital capacity (VC). Results: Participants enrolled at 5 U.S. sites. Data were analyzed from 66 participants with complete ATLIS, ALSFRS-R, and VC data over at least 3 visits. Change in ATLIS was less variable both within- and among-person than change in ALSFRS-R or VC. Additionally, participants who had normal ALSFRS-R arm and leg function averaged 12 to 32% below expected strength values measured by ATLIS. Conclusions: ATLIS was more sensitive to change than ALSFRS-R or VC and could decrease sample size requirements by approximately one-third. The ability of ATLIS to detect prefunctional change has potential value in early trials. Muscle Nerve 56: 710–715, 2017

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::13f1d603d7ed183262ab876140876badTest
https://doi.org/10.1002/mus.25586Test

المؤلفون: Benjamin D Schwartz, Kanneboyina Nagaraju, Avital Cnaan, Andrea L. Smith, Katharine Bushby, Catherine Siener, Lauren P. Morgenroth, Michela Guglieri, Mark Jaros, Phil Shale, John M. McCall, Heather Gordish-Dressman, Laurel J Mengle-Gaw, Nancy L. Kuntz, Edward C. Smith, Jean K. Mah, Diana Castro, Jesse M. Damsker, Craig M. McDonald, John N. van den Anker, Laurie S. Conklin, Paula R. Clemens, Yoram Nevo, Eric P. Hoffman, Richard S. Finkel, Mar Tulinius, Antonio Arrieta, Maya Shimony, Monique M. Ryan, Richard D. Webster

المصدر: Neurology

مصطلحات موضوعية: 0301 basic medicine, Male, medicine.medical_specialty, Duchenne muscular dystrophy, Anti-Inflammatory Agents, Administration, Oral, Gastroenterology, Article, Bone remodeling, 03 medical and health sciences, 0302 clinical medicine, Prednisone, Internal medicine, medicine, Humans, Muscular dystrophy, Adverse effect, Child, Glucocorticoids, business.industry, medicine.disease, 3. Good health, Deflazacort, Muscular Dystrophy, Duchenne, 030104 developmental biology, Treatment Outcome, Child, Preschool, Prednisolone, Biomarker (medicine), Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers, medicine.drug

الوصف: ObjectiveTo study vamorolone, a first-in-class steroidal anti-inflammatory drug, in Duchenne muscular dystrophy (DMD).MethodsAn open-label, multiple-ascending-dose study of vamorolone was conducted in 48 boys with DMD (age 4–ResultsOral administration of vamorolone at all doses tested was safe and well tolerated over the 24-week treatment period. The 2.0–mg/kg/d dose group met the primary efficacy outcome of improved muscle function (time to stand; 24 weeks of vamorolone treatment vs natural history controls), without evidence of most adverse effects of glucocorticoids. A biomarker of bone formation, osteocalcin, increased in vamorolone-treated boys, suggesting possible loss of bone morbidities seen with glucocorticoids. Biomarker outcomes for adrenal suppression and insulin resistance were also lower in vamorolone-treated patients with DMD relative to published studies of glucocorticoid therapy.ConclusionsDaily vamorolone treatment suggested efficacy at doses of 2.0 and 6.0 mg/kg/d in an exploratory 24-week open-label study.Classification of evidenceThis study provides Class IV evidence that for boys with DMD, vamorolone demonstrated possible efficacy compared to a natural history cohort of glucocorticoid-naive patients and appeared to be tolerated.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b4ac8ee470e10009787fc6003bae2474Test
https://pubmed.ncbi.nlm.nih.gov/31451516Test

المؤلفون: Pallavi Anand, Catherine Siener, Alina Nicorici, Jerry R. Mendell, Kevin M. Flanigan, Leslie Nelson, Linda Lowes, Anne M. Connolly, Mary Michaeleen Cradock, Craig M. Zaidman, Paul T. Golumbek, Craig M. McDonald, Linda Johnson, Susan T. Iannaccone, Lindsay N. Alfano, Richard S. Finkel, Julaine Florence, Nancy L. Kuntz

المصدر: Musclenerve. 59(6)

مصطلحات موضوعية: 0301 basic medicine, Male, Weakness, Pediatrics, medicine.medical_specialty, Physiology, Duchenne muscular dystrophy, Prednisolone, Gross motor skill, Cushingoid, 030105 genetics & heredity, Weight Gain, Cohort Studies, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Physiology (medical), medicine, Humans, Glucocorticoids, Muscle Weakness, business.industry, Infant, medicine.disease, Muscular Dystrophy, Duchenne, Bayley iii, Case-Control Studies, Child, Preschool, Cohort, Disease Progression, Neurology (clinical), medicine.symptom, business, Linear growth, 030217 neurology & neurosurgery, medicine.drug

الوصف: Introduction Glucocorticosteroids (GC) are effective in slowing weakness in boys with Duchenne muscular dystrophy (DMD). Methods This is a multisite, 1-year, open-label trial of twice-weekly prednisolone (5 mg/kg/dose) in infants/young boys (0.4-2.4 years) with DMD. We compared changes in Bayley III Scales of Infant Development (Bayley-III) with untreated boys followed for 1 year (historical control cohort [HCC]). Twenty-three of 25 participants completed the study. Results Treated boys gained an average of 0.5 points on the Bayley-III gross motor scaled score (GMSS) compared with the HCC who, on average, declined 1.3 points (P = 0.03). All boys maintained linear growth, and none developed Cushingoid features. Excessive weight gain occurred in 13 of 23 (56%) boys. Discussion This study provides evidence that twice-weekly GC is well tolerated in infants and young boys with DMD and improves GMSS. Excessive weight gain is a potential risk. Longer follow-up is required to determine whether early GC initiation is feasible in most infants/boys with DMD. Muscle Nerve 59:650-657, 2019.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6a064ff1d5823ce9581d0883723138beTest
https://pubmed.ncbi.nlm.nih.gov/30993732Test

المؤلفون: Jeanine Schierbecker, Catherine Siener, Julaine Florence, John W. Day, Janet Quigley, Alina Nicorici, Linda Johnson, Amy Pasternak, Lindsay N. Alfano, Anne M. Connolly, Jerry R. Mendell, Elizabeth C. Malkus, Linda Lowes, Craig M. McDonald, Craig M. Zaidman, Kevin M. Flanigan, Basil T. Darras, Jason M. Kelecic, Peter B. Kang, Paul T. Golumbek, Peter I. Karachunski, J. Philip Miller, Rebecca K. Gadeken, Pallavi Anand

المصدر: Muscle & Nerve. 54:681-689

مصطلحات موضوعية: Change over time, Vital capacity, medicine.medical_specialty, Physiology, business.industry, Duchenne muscular dystrophy, Repeated measures design, medicine.disease, Clinical trial, 03 medical and health sciences, Cellular and Molecular Neuroscience, FEV1/FVC ratio, Grip strength, 0302 clinical medicine, Physiology (medical), medicine, Physical therapy, 030212 general & internal medicine, Neurology (clinical), Non ambulatory, business, 030217 neurology & neurosurgery

الوصف: Introduction Outcomes sensitive to change over time in non-ambulatory boys/men with Duchenne muscular dystrophy (DMD) are not well-established. Methods Subjects (n = 91; 16.8 ± 4.5 years old) were assessed at baseline and 6-month intervals for 2 years. We analyzed all subjects using an intent-to-treat model and a subset of stronger subjects with Brooke Scale score ≤4, using repeated measures. Results Eight patients (12-33 years old) died during the study. Sixty-six completed 12-month follow-up, and 51 completed 24-month follow-up. Those taking corticosteroids performed better at baseline, but rates of decline were similar. Forced vital capacity percent predicted (FVC% predicted) declined significantly only after 2 years. However, Brooke and Egen Klassifikation (EK) Scale scores, elbow flexion, and grip strength declined significantly over both 1 and 2 years. Conclusion Brooke and EK Scale scores, elbow flexion, and grip strength were outcomes most responsive to change. FVC% predicted was responsive to change over 2 years. Corticosteroids benefited non-ambulatory DMD subjects but did not affect decline rates of measures tested here. Muscle Nerve 54: 681-689, 2016.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::556f1f805d18be5c206ef1122e1b8aecTest
https://doi.org/10.1002/mus.25089Test

المؤلفون: M. Guglieri, J. Mah, Catherine Siener, Nancy L. Kuntz, J. Damsker, Craig M. McDonald, Diana Castro, Monique M. Ryan, Yoram Nevo, Paula R. Clemens, Eric P. Hoffman, L. Mengle-Gaw, Edward J. Smith, Richard D. Webster, Lauren P. Morgenroth, P. Shale, Heather Gordish-Dressman, Mar Tulinius, Kanneboyina Nagaraju, Richard S. Finkel

المصدر: Neuromuscular Disorders. 29:S166

مصطلحات موضوعية: medicine.medical_specialty, Neurology, business.industry, Duchenne muscular dystrophy, Internal medicine, Pediatrics, Perinatology and Child Health, Cardiology, Medicine, Neurology (clinical), business, medicine.disease, Genetics (clinical), Function (biology)

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::c40abead7c7553c99b71b7bacd252e64Test
https://doi.org/10.1016/j.nmd.2019.06.452Test

المؤلفون: John W. Day, Elizabeth C. Malkus, Craig M. McDonald, Janet Quigley, Kevin M. Flanigan, Basil T. Darras, Linda Lowes, Lindsay N. Alfano, Alina Nicorici, Jerry R. Mendell, Paul T. Golumbek, Linda Johnson, Peter I. Karachunski, Peter B. Kang, J. Philip Miller, Catherine Siener, Craig M. Zaidman, Julaine Florence, Jason M. Kelecic, Anne M. Connolly, Jeanine Schierbecker, Amy Pasternak

المصدر: Muscle & Nerve. 51:522-532

مصطلحات موضوعية: musculoskeletal diseases, medicine.medical_specialty, Physiology, business.industry, Duchenne muscular dystrophy, Treatment outcome, medicine.disease, Therapeutic trial, Pulmonary function testing, Cellular and Molecular Neuroscience, Quality of life, Physiology (medical), Multicenter trial, Physical therapy, Medicine, Neurology (clinical), Non ambulatory, Young adult, business

الوصف: Background Therapeutic trials in Duchenne muscular dystrophy (DMD) often exclude non-ambulatory individuals. Here we establish optimal and reliable assessments in a multicenter trial.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::b92b255e728363a16bdfd45e5094a5f8Test
https://doi.org/10.1002/mus.24346Test

المؤلفون: S. Richardson, E. Kimber, H. Kim, Diana Castro, H. Johnson, A. C. Tesi Rocha, Matthias Eckenweiler, C. Manzitti, John W. Day, R. De Sanctis, M. Gormley, Mar Tulinius, Mirac Yildirim, C. M. Temucin, M. Gratacos Vinola, S. Matsumaru, F. Weber-Guzman, J. Kitsuwa-Lowe, Lavinia Fanelli, T. Sato, W. C. Virginia, J. H. Hsu, S. Nagata, A. Michoulas, Sally Dunaway, Mariacristina Scoto, R. Shell, R. Laine, D. DiBella, C. King, Jacqueline Montes, Haluk Topaloglu, Maryam Oskoui, Didem Ardicli, K. Rupprich, C. Stella, F. Dorban, Alan C Farrow-Gillespie, S. A. Choi, T. Ikai, W. C. Liang, N. Matsushima, PH Lister, Arnaud Vanlander, N. Rausch, T. T. Duong, Marika Pane, Melissa Gibbons, M. M. Homi, A. K. Kroksmark, B. Andres, Kristin J. Krosschell, S. Patnaik, L. Welsh, Eduardo F. Tizzano, M. Gallardo, Michèle Mayer, Sarada Sakamuri, W. Liew, T. Spain, M. Yang, Kayoko Saito, Edward C. Smith, L. Sanabria, Astrid Pechmann, H. Kaneko, Leslie Nelson, Basil T. Darras, C. Milleson, Janbernd Kirschner, R. Arakawa, Margot Morrison, Y. Kaburagi, P. Dinunzio, C. K.W. Joseph, M. Chadehumbe, Craig M. Zaidman, S. Nicolarsen, Hyung Ik Shin, Alberto Garaventa, James J. Dowling, J. S. Lee, K. Booker, A. Takeshita, D. McElroy, K. Carroll, D. Vens, Y. Chiba, L. Wand, C. Kelly, Luke Smith, H. Shimomura, M. Srour, J. B. Bodensteriner, B. Rippberger, A. Herbert, Eugenio Mercuri, H. Jo, J. Turner, A. Camuto, N. Parziale, J. O'Brien, N. Nelson, E. Serdaroglu, Jong-Hee Chae, V. Tahon, E. Toro Tamargo, L. Weimer, T. Voit, L. W.M. Wendy, J. Rambaud, G. Gilbert, C. Zimmerman, S. Kramer, D. McFall, Jennifer Perez, N. Berthon-Jones, Jessica Taytard, Marco Luigetti, J. Pisco Domingos, R. Van Der Looven, Genevieve D'Souza, C. Berde, E. Roland, M. de Los Angeles Tormos Munoz, J. Zigmont, S. Baily, S. Gilabert, H. Nakatsukasa, S. Trest, Bahadır Konuşkan, H. A. Ferreira Sampaio, Z. John Zhong, G. VanderVeen, V. Allen, C. Aguilar, N. Taniguchi, G. Ordonez, Elizabeth Kichula, F. Shu, M. N. Chui-San, M. Zinn, Anne M. Connolly, Ian R. Woodcock, Ayşe Karaduman, R. Haldenby, K. Hirasawa, F. Munell Casadesus, L.D.M. Peña, Vamshi K. Rao, Allan M. Glanzman, Claudia A. Chiriboga, A. Martinez Bermejo, John F. Brandsema, S. Epinosa Garcia, M. K. Schroth, T. Shibano, Richard Gee, Valeria Ricotti, Y. Ito, Y. Tanaka, S. Arpin, C. S. Yan, L. Schottlaender, Marco Piastra, M. Kauk, Francesco Muntoni, K. Sugimoto, Öznur Yilmaz, K. DeCock, Kathryn Selby, T. Yanagishita, Concetta Palermo, H. W. Chung, B. Taicher, Jiri Vajsar, K. Zilke, R. Gadeken, A. Yamauchi, Marta Bertoli, Nancy L. Kuntz, T. Tachikawa, C. Johnson, A. Mayhew, Jahannaz Dastgir, Y. J. Jong, P. C. Chou, G. Rivera, T. N. Shun, Y. H. Ju, N. Holuba La Marca, M. Toms, Matthew Civitello, Eugene Schneider, C. Lilien, S. Ito, C. Skura, Y. Yvonne, K. O'Reardon, Barry S. Russman, Janet Quigley, J. W. Said, B. Planas Pascual, R. J. Ramamurthi, Wildon Farwell, V. Selby, W. Y. Connie, M. Souris, Nicholas E. Johnson, M. Miki, N. Sponemann, Andrei Constantinescu, K. Mayne, H. H. Shih, B. Sanjanwala, Teresa Gidaro, D. Berry, Gihan Tennekoon, A. G. Le Moing, Danielle Ramsey, C. Poulin, S. Goldman, K. Watson, H. L. Teoh, N. J. Palacios, Tai-Heng Chen, A. C. Chung, Terri Carry, J. Coates, D. Zielinski, R. Vialle, F. G. Yildiz Sarikaya, Marcus Krüger, M. del Mar Garcia Romero, E. Michael, E. D. Austin, J. Janas, K. Engelstad, S. Y. Kim, M. Alavarez Molinero, Leon G. Epstein, Monique M. Ryan, Jean Flickinger, D. Benjamin, S. Wider, C. S. Davis, Jena M. Krueger, I. J.K. Janice, Darryl C. De Vivo, M. del Mar Melendez Plumed, Y. Takeshima, C. Gunbey, Serena Sivo, A. Christiaens, Q. Ollievier, Elizabeth Mirek, D. Stanford, Susan T. Iannaccone, Jonathan E. Kurz, D. Cook, C. S. Ng, A. Koka, V. Chau, M. del Pilar Tirado Requero, M. B. Gomez Garcia de la Banda, E. M. Yiu, Amy Pasternak, Rosangel Cruz, S. So, S. I. Pascual Pascual, V. G. Haliloglu, E. S. Schroers, P. Jachertz, C. Ortiz-Miller, Sandra Coppens, J. Lee, M. Popolizio, Michael Doumit, Rachel Salazar, Michelle A. Farrar, Peter G. Fuhr, M. Pedermonte, L. S. Lord-Halvorson, W. Leon, Y. S. Zeng, L. D'Argenzio, Russell J. Butterfield, C. Blomgren, Erika Finanger, S. Shea, Paola Tacchetti, N. Y. Ki, H. W. Choi, K. Oriyama, S. Wittevrongel, Catherine Siener, K. Mizuochi, M. Cowie, R. Van Coster, E. Gargaun, S. M. Scuplak, Sibylle Vogt, S. Stein, Tim Harrington, P. M. Ingelmo, J. Wootton, M. Tanyildiz, A. F. Rucian, Jonathan Marra, C. Frank Bennett, Claire L Wood, Nicolas Deconinck, Adnan Y. Manzur, Helene Verhelst, B. Purse, P. L. Léger, J. Cappell, S. Aziz-Zaman, H. Y. Wang, Claudio Bruno, S. Garcia Guixot, Robert Muni Lofra, Federica Trucco, S. M. Chun, Catherine E. Roberts, Ulrike Schara, Walter G. Bradley, K. L. De Valle, E. De Vos voor, S. Borell, A. Lim, Sophelia H. S. Chan, L. Rao, M. Shichiji, S. Rooze, T. M. Newcomb, Fouad Al-Ghamdi, Chiara Fiorillo, J. D. Endsley, L. Y. Sigurdardottir, Pallavi Anand, A. Zuffi, Julie A. Parsons, M. Kasper, A. Nishikawa, Sarah Gheuens, S. Turgeon-Desilet, T. Fujino, L. Staudt, Y. C. Wu, Jacinda B. Sampson, Paola Lanteri, Stephanie DeArmey, Partha S. Ghosh, Alexandra C. Ross, L. Adang, Laurent Servais, V. Tran, Alan Bielsky, Y. Otani, Navil F. Sethna, J. Hen, Perry B. Shieh, N. Fukuda, N. Miller, K. Eto, S. Paulose, Niklas Darin, C. Sabapathy, Robert J. Graham, Christopher Proud, Richard S. Finkel, Alexander G. Khandji, A. Della Marina, Adrian Murphy, Kathie M. Bishop, Tejaswi Kandula, Valentina Lanzillotta, Heather Szelag, Kalliopi Sofou, Y. H. Chou, Heike Koelbel, J. Eldblom, T. Lee, M. M. Martinez Moreno, Volker Straub, Laura E. Case, A. Lindstedt, G. Gili, A. Frank, H. C.C. Alvin, A. Ganfuss, Karen Herbert, Paul T. Golumbek, D. Villano, B. Wenderickx, B. C. Lim, W. S. Son

المساهمون: Schara, Ulrike (Beitragende*r), Ganfuss, Andrea (Beitragende*r), Koelbel, Heike (Beitragende*r), Rupprich, Katrin (Beitragende*r), Schroers, Ester Sarah (Beitragende*r), Sponemann, Nina (Beitragende*r), Çocuk Sağlığı ve Hastalıkları

مصطلحات موضوعية: Male, 0301 basic medicine, Pathology, Movement disorders, animal diseases, Messenger, Oligonucleotides, Medizin, Spinal Muscular Atrophies of Childhood, 0302 clinical medicine, Age of Onset, Disease-Free Survival, Double-Blind Method, Female, Humans, Infant, Injections, Spinal, Motor Skills, Oligonucleotides, Antisense, RNA, Messenger, Respiration, Artificial, Survival Analysis, Survival of Motor Neuron 2 Protein, Medicine (all), Respiration, General Medicine, Settore MED/26 - NEUROLOGIA, medicine.anatomical_structure, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Artificial, Nusinersen, medicine.symptom, medicine.medical_specialty, Spinal, Injections, 03 medical and health sciences, Atrophy, General & Internal Medicine, Settore MED/41 - ANESTESIOLOGIA, medicine, Antisense, Survival analysis, business.industry, Spinal muscular atrophy, Motor neuron, medicine.disease, nervous system diseases, 030104 developmental biology, nervous system, RNA, Infantile onset, Age of onset, business, 030217 neurology & neurosurgery

الوصف: Background: Spinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre–messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. Methods: We conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. Results: In the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P Conclusions: Among infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug.

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الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a1902aea91371408a707bf0d8e637462Test
https://www.ncbi.nlm.nih.gov/pubmed/29091570Test