Atrofia muscular espinal: Contribuciones para el conocimiento, prevención y tratamiento de la enfermedad y para la organización de familias

Este resumen refiere el trabajo realizado durante casi dos décadas dedicadas a la atención, investigación y experiencia en la atrofia muscular espinal (AME), una enfermedad de las neuronas motoras de la médula espinal. Casi todo el mundo conoce la poliomielitis, producida por el ataque de un virus a las neuronas motoras de la médula espinal. Los avances científicos han erradicado prácticamente la poliomielitis en nuestros niños y hoy en día constituye una enfermedad del pasado gracias a la vacunación. Si tuviéramos que describir la AME en pocas palabras la definiríamos como una poliomielitis mucho más agresiva que afecta a todo el cuerpo (a diferencia de la polio que era localizada) y a causa de un gen que está ausente o no funciona como corresponde.A diferencia de la polio, esta enfermedad genética está lejos de ser erradicada. Con una incidencia aproximada de 1/6000 a 1/10000 nacimientos, y una frecuencia de portadores de 1/40-1/60, la AME es considerada una de las principales causas hereditarias de mortalidad infantil. La AME presenta un patrón de herencia autosómico recesivo, es decir se necesitan dos copias del gen alterado para que se manifieste. Ese gen es el Survival Motor Neuron 1 (SMN1) localizado en el brazo largo del cromosoma 5 (5q13). La AME es siempre grave e invalidante y se clasifica en tres grupos (tipo I o aguda, tipo II o intermedio y tipo III crónica) de acuerdo con las manifestaciones clínicas, la edad de aparición de las mismas y su evolución

RegistrAME: the Spanish self-reported patient registry of spinal muscular atrophy

Patient registry; Self-reported registry; Spinal muscular atrophyRegistre de pacients; Registre autoinformat; Atròfia muscular espinalRegistro de pacientes; Registro autoinformado; Atrofia muscular espinalBackground Spinal Muscular Atrophy (SMA) is a rare neuromuscular disorder characterized by progressive degeneration of motor neurons and muscle weakness resulting in premature death or severe motor disability. Over the last decade, SMA has dramatically changed thanks to new advances in care and the emergence of disease-specific treatments. RegistrAME is a self-reported specific disease registry with an accurate curation system. It has collected data on SMA patients in Spain since 2015, gathering demographic, clinical, and patient-reported outcome data, all of which are patient-relevant. RegistrAME is part of the TREAT NMD network. This study aims to describe the advantages and disadvantages of a self–reported SMA registry, as well as the different variables of interest in the health status of RegistrAME patients. Results In total, 295 living patients with a confirmed diagnosis of SMA-5q were included (aged 1 to 77 years; mean 20.28). Half of the patients (50.2%) were ≥ 16 years old; 22.03% were type 1, 48.47% were type 2, 28.82% were type 3, and 0.7% were type 4. All functional statuses (non-sitter, sitter, and walkers) could be observed in each SMA type. Adult patients harbored the least aggressive SMA types, however, they presented the greatest level of disability. Patients with SMA type 1 had scoliosis surgery about five years earlier than patients with SMA type 2. None of the type 1 patients who achieved ambulation were wheelchair-free outdoors. This was also evident in 62.5% of type 2 walker patients and 44% of type 3 walker patients. Of the SMA type 1 patients, 40% had a gastrostomy (of which 84% had two SMN2 copies). One in five children with SMA type 1 (one to seven years of age) were ventilation-free. Conclusions The information provided by RegistrAME in a “real-world” setting allows better management of family expectations, an adequate approach to the disease and patients’ needs, as well as a better understanding of the impact of the disease. It also helps monitor the evolution of care, which will result in the need for updated guidelines.Funding for this project was provided by FundAME

MANAJEMEN PEMBINAAN PERPUSTAKAAN KELURAHAN DI KOTA BANDUNG

Dinas Perpustakaan dan Kearsipan (Dispusip) Kota Bandung merupakan suatu bentuk dari perpustakaan umum yang memiliki fungsi membina perpustakaan. Pemberdayaan perpustakaan kelurahan di Kota Bandung saat ini belum terealisasi sesuai dengan jumlah kelurahan yang terdapat di kota Bandung sebanyak 151 kelurahan. Perpustakaan kelurahan dapat menjalankan fungsinya dengan baik sesuai dengan fungsi perpustakaan dengan penerapan fungsi manajemen perpustakaan. Masalah yang menjadi kajian pada penelitian ini bagaimana implementasi manajemen pembinaan perpustakaan kelurahan di Kota Bandung oleh Dispusip Kota Bandung. Tujuan penelitian ini yaitu untuk mendeskripsikan mengenai perencanaan, pengorganisasian, penggerakan dan pengawasan pembinaan perpustakaan kelurahan oleh Dispusip Kota Bandung. Metode yang digunakan pada penelitian ini adalah metode kualitatif dengan pendekatan studi kasus. Partisipan dalam penelitian ini terdiri atas tiga informan yang bertindak sebagai pustakawan dan key informan sebagai Kepala Bidang Pengembangan Perpustakaan dan Kearsipan menggunakan teknik purposive sampling. Instrumen penelitian yang digunakan adalah wawancara, observasi dan studi dokumentasi. Teknik analisis data yang digunakan adalah data reduction, data display, dan conclusion drawing (verification). Berdasarkan hasil penelitian yaitu sebuah konstuksi model manajemen pembinaan perpustakaan kelurahan yang menunjukkan bahwa kegiatan pembinaan perpustakaan kelurahan oleh Dispusip Kota Bandung relevan dengan fungsi manajemen. Fungsi perencanaan, pengorganisasian, penggerakan kegiatan manajemen pembinaan perpustakaan kelurahan di Kota Bandung terealisasi cukup baik. Namun pada fungsi pengawasan belum berjalan secara optimal, hal ini dikarenakan oleh keterbatasan sumber daya manusia yang dimiliki oleh Dispusip Kota Bandung. Program pembinaan ini diharapkan dapat mewujudkan penyelenggaraan perpustakaan kelurahan dan dapat memberikan kontribusi terhadap perbaikan/ penyempurnaan manajemen pembinaan perpustakaan oleh Dispusip Kota Bandung. ;--- Dinas Perpustakaan dan Kearsipan (Dispusip) Kota Bandung is a form of public library, which function is to develop urban village libraries. Currently, the empowerment of urban village libraries in 151 village in Bandung City is not realized yet. Urban village libraries can perform its functions properly in accordance with the implementation of library management functions. The problem of this study is how Dispusip Kota Bandung manages the implementation of urban village libraries coaching in Bandung City. The purpose of this study is to describe the planning, organizing, actuating, and controlling of urban village libraries coaching by Dispusip Kota Bandung. The research method used in this study is qualitative method with a case study approach. The subjects of this study consist of three informants who act as a librarian and a key informant as a Head of Library and Archive Development by using purposive sampling technique. The research instruments used in this study are interviews, observations, and documentation studies. This study uses data analysis technique of data reduction, data display, and conclusion drawing (verification). Based on the study of a model construction of urban village libraries coaching, the result is that the coaching activities of urban village libraries done by Dispusip Kota Bandung is relevant to the management functions. The functions of planning, organizing, and actuating of village libraries coaching activities in Bandung City are realized quite well. However, the function of controlling has not run optimally. This is due to the limitations of human resources owned by Dispusip Kota Bandung. This coaching program is expected to be able to realize the enforcement of urban village libraries and to give contribution to the improvement of library coaching management done by Dispusip Kota Bandung

Combination disease-modifying treatment in spinal muscular atrophy: A proposed classification

Spinal muscular atrophyAtròfia muscular espinalAtrofia muscular espinalWe sought to devise a rational, systematic approach for defining/grouping survival motor neuron-targeted disease-modifying treatment (DMT) scenarios. The proposed classification is primarily based on a two-part differentiation: initial DMT, and persistence/discontinuation of subsequent DMT(s). Treatment categories were identified: monotherapy add-on, transient add-on, combination with onasemnogene abeparvovec, bridging to onasemnogene abeparvovec, and switching to onasemnogene abeparvovec. We validated this approach by applying the classification to the 443 patients currently in the RESTORE registry and explored the demographics of these different groups of patients. This work forms the basis to explore the safety and efficacy profile of the different combinations of DMT in SMA

Unusual context of CENPJ variants and primary microcephaly : compound heterozygosity and nonconsanguinity in an Argentinian patient

Primary microcephaly (MCPH) is a genetically heterogeneous disorder showing an autosomal recessive mode of inheritance. Patients with MCPH present head circumference values two or three standard deviations (SDs) significantly below the mean for age- and sex-matched populations. MCPH is associated with a nonprogressive mild to severe intellectual disability, with normal brain structure in most patients, or with a small brain and gyri without visceral malformations. We present the case of an adult patient born from Argentinian nonconsanguineous healthy parents. He had a head circumference >5 SD below the mean, cerebral neuroimaging showing hypoplasia of the corpus callosum, bilateral migration disorder with heterotopia of the sylvian fissure and colpocephaly. The patient was compound heterozygous for pathogenic variants in the CENPJ gene (c.289dupA inherited from his mother and c.1132 C > T inherited from his father). Our patient represents an uncommon situation for the usual known context of CENPJ and MCPH, including family origin (Argentinian), pedigree (nonconsanguineous), and genotype (a compound heterozygous case with two variants predicting a truncated protein). Next-generation sequencing studies applied in a broader spectrum of clinical presentations of MCPH syndromes may discover additional similar patients and families

Practical guidelines to manage discordant situations of SMN2 copy number in patients with spinal muscular atrophy

Objective Assessment of SMN2 copy number in patients with spinal muscular atrophy (SMA) is essential to establish careful genotype-phenotype correlations and predict disease evolution. This issue is becoming crucial in the present scenario of therapeutic advances with the perspective of SMA neonatal screening and early diagnosis to initiate treatment, as this value is critical to stratify patients for clinical trials and to define those eligible to receive medication. Several technical pitfalls and interindividual variations may account for reported discrepancies in the estimation of SMN2 copy number and establishment of phenotype-genotype correlations. Methods We propose a management guide based on a sequence of specified actions once SMN2 copy number is determined for a given patient. Regardless of the method used to estimate the number of SMN2 copies, our approach focuses on the manifestations of the patient to recommend how to proceed in each case. Results We defined situations according to SMN2 copy number in a presymptomatic scenario of screening, in which we predict the possible evolution, and when a symptomatic patient is genetically confirmed. Unexpected discordant cases include patients having a single SMN2 copy but noncongenital disease forms, 2 SMN2 copies compatible with type II or III SMA, and 3 or 4 copies of the gene showing more severe disease than expected. Conclusions Our proposed guideline would help to systematically identify discordant SMA cases that warrant further genetic investigation. The SMN2 gene, as the main modifier of SMA phenotype, deserves a more in-depth study to provide more accurate genotype-phenotype correlations

Clinical Trial Readiness for Spinal Muscular Atrophy: Experience of an International Educational-Training Initiative

Several successful clinical trials have been conducted in spinal muscular atrophy (SMA) over recent years which have led to the approval of splicing modifiers and gene transfer therapies. With an increasing number of other agents progressing through pre-clinical and clinical development, increasing worldwide clinical trial readiness is becoming essential.SMA Europe initiated a clinical trial readiness project, which included the development of a pilot face-to-face educational-training initiative for clinical specialists and physiotherapists involved in SMA, with an emphasis on the patient perspective. Participants were selected through two surveys and, ahead of the meeting, a mock protocol with specific questions was provided. The initiative involved a series of presentations, role-play and interactive exercises. We describe here our experience and evaluation of this educational-training initiative, emphasising scientific aspects, psychosocial implications and level of satisfaction.From a participant, patient and industry perspective, such training was considered successful and met the objective, which was to improve clinical trial readiness in emerging sites. Resource planning, ethical considerations and communication with patients were identified as three important topics for future training. This initiative highlights the need to develop a training programme to achieve clinical trial readiness across Europe and showcases a collaborative effort with different stakeholders, clinicians, patient advocacy groups and sponsors to address an important issue

A Digital Pattern Methodology supporting Railway Industries in Portfolio Management

The object of this paper is the development of a decision support system involved in the bidding for invitations to tender in the railway field. The proposed methodology is based on the characterization of the whole train and its components, through several attributes according to a digital pattern approach. In particular some key components were chosen such as the traction motor, the bogie and the auxiliary equipment converter. The system measures the extent to which the products offered by the company fit the one required by the customer, comparing the homologous attributes. Such analysis is called ‘adopt/adapt/innovate’ (AAI). In this way it is possible to identify products already designed that fully or partly fit what required, obtaining huge benefits in terms of effectiveness and efficiency