RESUMO
BACKGROUND: Spinal muscular atrophy (SMA) is a rare genetic disease with a broad spectrum of severity. Although an early diagnosis of SMA is crucial to allow proper management of patients, the diagnostic delay is still an issue. Therefore, this study aimed to investigate the clinical correlates of SMA among primary care patients. METHODS: The Health Search Database (HSD) was adopted. To estimate the prevalence and incidence rate of SMA, a cohort study was conducted on the population (aged ≥6 years) being registered in HSD from 1 January 2000 up to 31 December 2019. To investigate the clinical correlates of SMA, a nested case-control study was performed. SMA cases have been classified according to a clinically based iterative process as "certain", "probable" or "possible". To test the association between clinical correlates and SMA cases a multivariate conditional logistic regression model was estimated. RESULTS: The SMA prevalence combining "certain", "probable" and "possible" cases was 5.1 per 100,000 in 2019 (i.e. 1.12 per 100,000 when limited to "certain" cases), while the yearly incidence rate ranged from 0.12 to 0.56 cases per 100,000. Comparing "certain" cases with matched controls, the presence of neurology visits (OR = 6.5; 95% CI: 1.6-25.6) and prescription of electromyography (OR = 4.6; 95% CI: 1.1-18.7) were associated with higher odds of SMA diagnosis. CONCLUSIONS: Our findings suggest that primary care databases may be used to enhance the early identification of SMA. Additional efforts are needed to exploit the electronic health records of general practitioners to allow early recognition of SMA.
Assuntos
Diagnóstico Tardio , Atrofia Muscular Espinal , Humanos , Estudos de Casos e Controles , Estudos de Coortes , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/epidemiologia , Itália/epidemiologia , Atenção Primária à SaúdeRESUMO
TBI is the main cause of death and disability in individuals aged 1-45 in Western countries. One of the main challenges of TBI at present is the lack of specific diagnostic biomarkers, especially for mild TBI (mTBI), which remains currently difficult to value in clinical practice. In this context MiRNAs may be important mediators of the profound molecular and cellular changes that occur after TBI in both the short and the long term. Recently, plasma miRNAs profiling in human TBI, have revealed dynamic temporal regulation of miRNA expression within the cortex. Aim of this study was to select a specific miRNAs panel for mTBI, by focusing the research on the prognostic meaning of miRNAs in the hours following the trauma, in order to be able to use this MIRNAs as potential biomarkers useful for monitoring the follow up of mild TBI. Serum levels of 17 miRNAs were measured by RT-quantitative polymerase chain reaction (qPCR) in 20 patients with mTBI at three different time-points (0 h, 24 h, 48 h) and in 10 controls. For 15 miRNAs we found a significant differences in the comparison among the three time points: for each of these miRNAs the values were greater at baseline and progressively reduced at 24 h and 48 h. These data allow us to consider the miRNAs included in panel as sensitive and specific biomarkers for mTBI, useful in monitoring the post-trauma period.
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Biomarcadores/sangue , Concussão Encefálica/genética , MicroRNA Circulante/genética , Adulto , Concussão Encefálica/sangue , Concussão Encefálica/fisiopatologia , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/genética , Lesões Encefálicas Traumáticas/fisiopatologia , MicroRNA Circulante/sangue , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Curva ROC , Transcriptoma/genéticaRESUMO
BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder, due to the loss of function of the survival motor neuron (SMN1) gene. The first treatment for the condition, recently approved, is based on the reduction of exon 7 skipping in mRNAs produced by a highly homologous gene (SMN2). The primary objective of the present study was to evaluate the applicability of the dosage of SMN gene produts in blood, as biomarker for SMA, and the safety of oral salbutamol, a beta2-adrenergic agonist modulating SMN2 levels. METHODS: We have performed a 1-year multicentre, double-blind, placebo-controlled study with salbutamol in 45 adult patients with SMA. Patients assumed 4 mg of salbutamol or placebo/three times a day. Molecular tests were SMN2 copy number, SMN transcript and protein levels. We have also explored the clinical effect, by the outcome measures available at the time of study design. RESULTS: Thirty-six patients completed the study. Salbutamol was safe and well tolerated. We observed a significant and progressive increase in SMN2 full-length levels in peripheral blood of the salbutamol-treated patients (p<0.00001). The exploratory analysis of motor function showed an improvement in most patients. CONCLUSIONS: Our data demonstrate safety and molecular efficacy of salbutamol. We provide the first longitudinal evaluation of SMN levels (both transcripts and protein) in placebo and in response to a compound modulating the gene expression: SMN transcript dosage in peripheral blood is reliable and may be used as pharmacodynamic marker in clinical trials with systemic compounds modifying SMN2levels. TRIAL REGISTRATION NUMBER: EudraCT no. 2007-001088-32.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Albuterol/uso terapêutico , Biomarcadores , Atrofia Muscular Espinal/tratamento farmacológico , Atrofia Muscular Espinal/genética , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/metabolismo , Proteína 1 de Sobrevivência do Neurônio Motor/metabolismo , Proteína 2 de Sobrevivência do Neurônio Motor/genética , Proteína 2 de Sobrevivência do Neurônio Motor/metabolismo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: In the last years, there has been increasing evidence of cardiac involvement in spinal muscular atrophy (SMA). Autonomic dysfunction has been reported in animal models and in several patients with types I and III SMA, these findings raising the question whether heart rate should be routinely investigated in all SMA patients. The aim of our study was to detect possible signs of autonomic dysfunction and, more generally, of cardiac involvement in types II and III SMA. PATIENTS AND METHODS: We retrospectively reviewed 24-hour electrocardiography (ECG) in 157 types II and III SMA patients (age range, 2-74 years). Of them, 82 also had echocardiography. RESULTS: None of the patients had signs of bradycardia, atrial fibrillation, or the other previously reported rhythm disturbances regardless of the age at examination or the type of SMA. Echocardiography was also normal. There were no signs of congenital cardiac defects with the exception of one patient with a history of ventricular septal defects. CONCLUSIONS: Our results suggest that cardiac abnormalities are not common in type II and type III SMA. These findings provide no evidence to support a more accurate cardiac surveillance or changes in the existing standards of care.
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Cardiopatias/diagnóstico , Cardiopatias/etiologia , Atrofias Musculares Espinais da Infância/complicações , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The aim of this study was to establish the possible effect of age, corticosteroid treatment and brain dystrophin involvement on motor function in young boys affected by Duchenne Muscular Dystrophy who were assessed using the North Star Ambulatory Assessment between the age of 4 and 7 years. The study includes 951 North Star assessments from 226 patients. Patients were subdivided according to age, to the site of mutation and therefore to the involvement of different brain dystrophin isoforms and to corticosteroids duration. There was a difference in the maximum North Star score achieved among patients with different brain dystrophin isoforms (p = 0.007). Patients with the involvement of Dp427, Dp140 and Dp71, had lower maximum NSAA scores when compared to those with involvement of Dp427 and Dp140 or of Dp427 only. The difference in the age when the maximum score was achieved in the different subgroups did not reach statistical significance. Using a linear regression model on all assessments we found that each of the three variables, age, site of mutation and corticosteroid treatment had an influence on the NSAA values and their progression over time. A second analysis, looking at 12-month changes showed that within this time interval the magnitude of changes was related to corticosteroid treatment but not to site of mutation. Our findings suggest that each of the considered variables appear to play a role in the progression of North Star scores in patients between the age of 4 and 7 years and that these should be carefully considered in the trial design of boys in this age range.
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Distrofina , Distrofia Muscular de Duchenne , Corticosteroides/uso terapêutico , Criança , Pré-Escolar , Distrofina/genética , Humanos , Masculino , Distrofia Muscular de Duchenne/tratamento farmacológico , Distrofia Muscular de Duchenne/genética , Mutação , Isoformas de Proteínas/genéticaRESUMO
Genetic modifiers of Duchenne muscular dystrophy (DMD) are variants located in genes different from the disease-causing gene DMD, but associated with differences in disease onset, progression, or response to treatment. Modifiers described so far have been tested mainly for associations with ambulatory function, while their effect on upper limb function, which is especially relevant for quality of life and independence in non-ambulatory patients, is unknown. We tested genotypes at several known modifier loci (SPP1, LTBP4, CD40, ACTN3) for association with Performance Upper Limb version 1.2 score in an Italian multicenter cohort, and with Brooke scale score in the Cooperative International Neuromuscular Group Duchenne Natural History Study (CINRG-DNHS), using generalized estimating equation (GEE) models of longitudinally collected data, with age and glucocorticoid treatment as covariates. CD40 rs1883832, previously linked to earlier loss of ambulation, emerged as a modifier of upper limb function, negatively affecting shoulder and distal domains of PUL (p = 0.023 and 0.018, respectively) in the Italian cohort, as well as of Brooke score (p = 0.018) in the CINRG-DNHS. These findings will be useful for the design and interpretation of clinical trials in DMD, especially for non-ambulatory populations.
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Distrofia Muscular de Duchenne , Actinina/genética , Estudos de Coortes , Genótipo , Humanos , Distrofia Muscular de Duchenne/genética , Qualidade de Vida , Extremidade SuperiorRESUMO
OBJECTIVE: The aim of this paper was to report the 2-year follow-up in type I patients treated with Nusinersen and to assess whether possible changes in motor function are related to the subtype, age, or SMN2 copy number. METHODS: Sixty-eight patients, with ages ranging from 0.20 to 15.92 years (mean: 3.96; standard deviation: +3.90) were enrolled in the study. All patients were assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the developmental section of the Hammersmith Infant Neurological Examination (HINE-2) at the time they started treatment and 12 and 24 months after that. RESULTS: For both CHOP and HINE-2 repeated measures analysis of variance showed a significant difference (P < 0.001) between baseline and 12 months, 12 months and 24 months, and baseline and 24-month scores for the whole group. When age subgroups (<210 days, <2 years, 2-4 years, 5-11 years, 12-18 years) were considered, on the CHOP INTEND the difference was significant between baseline and 24 months in all age subgroups. On the HINE-2, the difference between baseline and 24 months was significant in all the subgroups before the age of 4 years. Age was predictive of changes on both scales (P < 0.05), whereas SMN2 copy number and decimal classification were not. INTERPRETATION: Our results suggest that some improvement of motor function can be observed even after the first year of treatment. This is more obvious in the infants treated in the first 2 years but some improvement can also be found in older children.
Assuntos
Oligonucleotídeos/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Atrofias Musculares Espinais da Infância/tratamento farmacológico , Atrofias Musculares Espinais da Infância/fisiopatologia , Adolescente , Criança , Pré-Escolar , Seguimentos , Humanos , Lactente , Índice de Gravidade de Doença , Atrofias Musculares Espinais da Infância/genética , Proteína 2 de Sobrevivência do Neurônio Motor/genéticaRESUMO
The aim was to assess 3-year longitudinal data using 6MWT in 26 ambulant boys affected by DMD carrying nonsense mutations and to compare their results to other small mutations. We also wished to establish, within the nonsense mutations group, patterns of change according to several variables. Patients with nonsense mutations were categorized according to the stop codon type newly created by the mutation and also including the adjacent 5' (upstream) and 3' (downstream) nucleotides. No significant difference was found between nonsense mutations and other small mutations (p > 0.05) on the 6MWT. Within the nonsense mutations group, there was no difference in 6MWT when the patients were subdivided according to: Type of stop codon, frame status of exons involved, protein domain affected. In contrast, there was a difference when the stop codon together with the 3' adjacent nucleotide ("stop+4 model") was considered (p < 0.05) with patients with stop codon TGA and 3' adjacent nucleotide G (TGAG) having a more rapid decline. Our finding suggest that the stop+4 model may help in predicting functional changes. This data will be useful at the time of interpreting the long term follow up of patients treated with Ataluren that are becoming increasingly available.
Assuntos
Códon sem Sentido/genética , Distrofia Muscular de Duchenne/genética , Mutação/genética , Teste de Caminhada , Bélgica , Criança , Pré-Escolar , Distrofina/genética , Éxons , Humanos , Itália , Estudos Longitudinais , Masculino , Distrofia Muscular de Duchenne/fisiopatologia , OxidiazóisRESUMO
INTRODUCTION: The aim of this study was to report 36-month longitudinal changes using the North Star Ambulatory Assessment (NSAA) in ambulant patients affected by Duchenne muscular dystrophy amenable to skip exons 44, 45, 51 or 53. MATERIALS AND METHODS: We included 101 patients, 34 had deletions amenable to skip exon 44, 25 exon 45, 19 exon 51, and 28 exon 53, not recruited in any ongoing clinical trials. Five patients were counted to skip exon 51 and 53 since they had a single deletion of exon 52. RESULTS: The difference between subgroups (skip 44, 45, 51 and 53) was significant at 12 (p = 0.043), 24 (p = 0.005) and 36 months (p≤0.001). DISCUSSION: Mutations amenable to skip exons 53 and 51 had lower baseline values and more negative changes than the other subgroups while those amenable to skip exon 44 had higher scores both at baseline and at follow up. CONCLUSION: Our results confirm different progression of disease in subgroups of patients with deletions amenable to skip different exons. This information is relevant as current long term clinical trials are using the NSAA in these subgroups of mutations.
Assuntos
Distrofina/genética , Distrofia Muscular de Duchenne/genética , Mutação/genética , Criança , Progressão da Doença , Éxons/genética , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Homens , Distrofia Muscular de Duchenne/patologia , Índice de Gravidade de Doença , Caminhada/fisiologiaRESUMO
Mutations in the dysferlin gene lead to limb girdle muscular dystrophy 2B, Miyoshi myopathy and distal anterior compartment myopathy. A cohort of 36 patients affected by dysferlinopathy is described, in the first UK study of clinical, genetic, pathological and biochemical data. The diagnosis was established by reduction of dysferlin in the muscle biopsy and subsequent mutational analysis of the dysferlin gene. Seventeen mutations were novel; the majority of mutations were small deletions/insertions, and no mutational hotspots were identified. Sixty-one per cent of patients (22 patients) initially presented with limb girdle muscular dystrophy 2B, 31% (11 patients) with a Miyoshi phenotype, one patient with proximodistal mode of onset, one patient with muscle stiffness after exercise and one patient as a symptomatic carrier. A wider range of age of onset was noted than previously reported, with 25% of patients having first symptoms before the age of 13 years. Independent of the initial mode of presentation, in our cohort of patients the gastrocnemius muscle was the most severely affected muscle leading to an inability to stand on tiptoes, and lower limbs were affected more severely than upper limbs. As previous anecdotal evidence on patients affected by dysferlinopathy suggests good muscle prowess before onset of symptoms, we also investigated pre-symptomatic fitness levels of the patients. Fifty-three per cent of the patients were very active and sporty before the onset of symptoms which makes the clinical course of dysferlinopathy unusual within the different forms of muscular dystrophy and provides a challenge to understanding the underlying pathomechanisms in this disease.
Assuntos
Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Proteínas Musculares/deficiência , Proteínas Musculares/genética , Distrofia Muscular do Cíngulo dos Membros/epidemiologia , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/metabolismo , Adolescente , Adulto , Idade de Início , Idoso , Criança , Creatina Quinase/metabolismo , Análise Mutacional de DNA , Disferlina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Distrofia Muscular do Cíngulo dos Membros/patologia , Mutação , Fenótipo , Aptidão FísicaRESUMO
OBJECTIVE: The aim of this study was to use a structured questionnaire in a large cohort of Duchenne Muscular Dystrophy (DMD) patients to assess caregivers and patients views on respiratory function and to establish if their responses were related to the patients' age or level of functional impairment. METHODS: Questionnaires were administered to caregivers in 205 DMD patients of age between 3 and 36 years (115 ambulant, 90 non-ambulant), and to 64 DMD patients (3 ambulant, 61 non-ambulant) older than 18 years, subdivided into groups according to age, FVC, ambulatory and ventilatory status. RESULTS: Some differences were found in relation to FVC % values (p = 0.014), ambulatory (p = 0.043) and ventilatory status (p = 0.014). Nearly half of the caregivers expected deterioration over the next years, with the perspective of deterioration more often reported by caregivers of non-ambulant (p = 0.018) and ventilated patients (p = 0.004). Caregivers appeared to be aware of the relevance of respiratory function on quality of life (84%) showing willingness to enter possible clinical trials if these were aiming to stabilize the progression of respiratory function with a very high number of positive responses across the spectrum of age, FVC, ambulatory and ventilatory status. The boys older than 18 years showed similar results. CONCLUSIONS: Our study showed that the concern for respiratory function increases with age and with the reduction of FVC or the need for ventilation, but the need for intervention was acknowledged across the whole spectrum of age and functional status.
Assuntos
Cuidadores/psicologia , Avaliação da Deficiência , Saúde da Família , Distrofia Muscular de Duchenne , Ventilação não Invasiva , Qualidade de Vida , Respiração , Adulto , Criança , Deambulação com Auxílio/psicologia , Progressão da Doença , Feminino , Estado Funcional , Humanos , Masculino , Homens/psicologia , Distrofia Muscular de Duchenne/fisiopatologia , Distrofia Muscular de Duchenne/psicologia , Distrofia Muscular de Duchenne/terapia , Ventilação não Invasiva/métodos , Ventilação não Invasiva/psicologia , Medidas de Resultados Relatados pelo Paciente , Testes de Função Respiratória/métodos , Testes de Função Respiratória/psicologia , Capacidade VitalRESUMO
Gliomas represent over 70% of all brain tumors, they are highly invasive and structurally vascular neoplasms. Despite the latest technological advance in neuro-surgery the survival of patients with high-grade glioma remains poor. The lack of robust treatment options has propelled the search for new markers that may able allow the identification of patients who can benefit from molecularly targeted therapies. The Hippo signaling pathway is considered as a key regulator of tissue homeostasis, cell proliferation and apoptosis, and alterations of this pathway seem to contribute to tumorigenesis. Yes-associated protein (YAP1) is a downstream target of the Hippo pathway which acts as a transcription co-activator. In cancer, YAP1 has been reported to function either as an oncogene or tumor suppressor, depending on the cell context. The aim of this study was to examine the expression of YAP1, Survivin and LATS1 kinase activity in human astroglial tumors with different grades of malignancy. Moreover, we also investigated the expression of miR-221 and miR-10b and their relationship with core molecules of the Hippo pathway. Our results showed the overexpression of YAP1 and Survivin as well as a decreased activity of large tumor suppressor 1 (LATS1) in high-grade glioblastoma versus anaplastic astrocytoma and low-grade glioma. Furthermore, we also demonstrated that miR-221 and miR-10b are specifically involved in Hippo signaling via LATS1 regulation and that their knockdown significantly decreased glioma cell proliferation. This preliminary data confirmed the crucial role of the Hippo pathway in cancer and suggested that miR-221 and miR-10b could be potential therapeutic targets for glioma treatment.
Assuntos
Astrocitoma/genética , Neoplasias Encefálicas/genética , Glioblastoma/genética , MicroRNAs/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Astrócitos/patologia , Astrocitoma/diagnóstico , Astrocitoma/patologia , Astrocitoma/cirurgia , Encéfalo/citologia , Encéfalo/patologia , Encéfalo/cirurgia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Glioblastoma/diagnóstico , Glioblastoma/patologia , Glioblastoma/cirurgia , Via de Sinalização Hippo , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/genética , Survivina/genética , Survivina/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Sinalização YAPRESUMO
Dystrophinopathies are inherited diseases caused by mutations in the dystrophin (DMD) gene for which testing is mandatory for genetic diagnosis, reproductive choices and eligibility for personalized trials. We genotyped the DMD gene in our Italian cohort of 1902 patients (BMD n = 740, 39%; DMD n =1162, 61%) within a nationwide study involving 11 diagnostic centers in a 10-year window (2008-2017). In DMD patients, we found deletions in 57%, duplications in 11% and small mutations in 32%. In BMD, we found deletions in 78%, duplications in 9% and small mutations in 13%. In BMD, there are a higher number of deletions, and small mutations are more frequent than duplications. Among small mutations that are generally frequent in both phenotypes, 44% of DMD and 36% of BMD are nonsense, thus, eligible for stop codon read-through therapy; 63% of all out-of-frame deletions are eligible for single exon skipping. Patients were also assigned to Italian regions and showed interesting regional differences in mutation distribution. The full genetic characterization in this large, nationwide cohort has allowed us to draw several correlations between DMD/BMD genotype landscapes and mutation frequency, mutation types, mutation locations along the gene, exon/intron architecture, and relevant protein domain, with effects on population genetic characteristics and new personalized therapies.
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INTRODUCTION: The aim of this international collaborative effort was to report 36-month longitudinal changes using the 6MWT in ambulant patients affected by Duchenne muscular dystrophy amenable to skip exons 44, 45, 51 or 53. MATERIALS AND METHODS: Of the 92 patients included in the study, 24 had deletions amenable to skip exon 44, 27 exon 45, 18 exon 51, and 28 exon 53. Five patients with a single deletion of exon 52 were counted in both subgroups skipping exon 51 and 53. RESULTS: The difference between subgroups amenable to skip different exons was not significant at 12 months but became significant at both 24 (p≤0.05) and 36 months (p≤0.01). DISCUSSION: Mutations amenable to skip exon 53 had lower baseline values and more negative changes than the other subgroups while those amenable to skip exon 44 had better results both at baseline and at follow up. Deletions amenable to skip exon 45 were associated with a more variable pattern of progression. Single exon deletions were more often associated with less drastic changes but this was not always true in individual cases. CONCLUSION: Our results confirm that the progression of disease can differ between patients with different deletions, although the changes only become significant from 24 months onwards. This information is relevant because there are current clinical trials specifically targeting patients with these subgroups of mutations.
Assuntos
Distrofina/genética , Distrofia Muscular de Duchenne/genética , Mutação , Criança , Pré-Escolar , Estudos de Coortes , Progressão da Doença , Éxons , Humanos , Estudos Longitudinais , Masculino , Distrofia Muscular de Duchenne/fisiopatologia , Distrofia Muscular de Duchenne/terapia , Estudos Prospectivos , Deleção de Sequência , CaminhadaRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0218683.].
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This paper describes the pharmacological therapies and rehabilitative interventions received by 502 patients with Muscular Dystrophies, evaluated in relation to patient's socio-demographic and clinical variables, and geographical areas. Data were collected by the MD-Socio-Demographic and Clinical Schedule (MD-SC-CS) and by the Family Problems Questionnaire (FPQ). The most part of the enrolled patients were in drug treatment. The number of the medications increased in relation to patient's age, disability degree and duration of illness and was higher among patients with Duchenne Muscular Dystrophy (DMD) compared with Becker (BMD) or Limb-Girdle Muscular Dystrophies (LGMD). Steroids (deflazacort or prednisone) were the drug most frequently used, followed by cardiologic and bone metabolism drugs. In general, patients using steroids were younger and had a shorter duration of illness; patients using cardiac drugs and dietary supplements were older and had a longer duration of illness. Rehabilitative interventions were provided to about 70% (351/502) of patients, mainly DMD. Of these, physiotherapy was the more frequent treatment (96.6%) and was prevalently performed in rehabilitative centres (about 70% of patients) and at home in only 30%. Hydrokinetic-therapy was practiced by 6.8% of patients. Respiratory rehabilitation was provided to 47.0% of patients (165/351) and assisted mechanical ventilaventilation to 13.1% (46). The amount of rehabilitative interventions increased in relation to the patient's age, level of disability and duration of illness. Compared to Central and Northern Italy, in Southern Italy there was a higher attention to cardiological impairment as shown by a higher number of patients receiving heart drugs. No statistically significant differences concerning the possibility to have access to rehabilitative interventions were noted among the three geographical areas. However, patient living in Southern Italy tend to receive rehabilitation more often at home.
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Glucocorticoides/uso terapêutico , Distrofias Musculares/tratamento farmacológico , Distrofias Musculares/reabilitação , Modalidades de Fisioterapia , Adolescente , Fatores Etários , Conservadores da Densidade Óssea/uso terapêutico , Exercícios Respiratórios , Cardiotônicos/uso terapêutico , Criança , Terapia Combinada , Suplementos Nutricionais , Avaliação da Deficiência , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Itália , Masculino , Prednisona/uso terapêutico , Pregnenodionas/uso terapêutico , Respiração Artificial , Fatores de TempoRESUMO
Despite all the advances in diagnosis and management of Duchenne muscular dystrophy over the past 50 years, the average age at diagnosis in most countries in the world around is still around 4-5 years. This retrospective study investigates the age at diagnosis in Italy in the past 10 years. We report findings from 384 boys who were diagnosed with DMD from 2005 to 2014. The mean age at first medical contact, which raised the suspicion of DMD, was 31 months. The mean age at diagnosis was 41 months. The finding that more frequently brought to suspect a DMD was the incidental finding of consistent elevated creatine kinase serum level detected during routine assessments in children undergoing general anesthesia or with intercurrent illness. This was followed by motor delay and signs of muscle weakness. Initial concerns were raised by general pediatricians (29%), specialists at tertiary centers (35%) or first level hospitals (23%). In children presenting incidental elevated creatine kinase values the diagnosis was achieved earlier than in children presenting a developmental delay. The mean age at diagnosis in our cohort was about 10-12 months lower than that reported in other countries.
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Distrofia Muscular de Duchenne/diagnóstico , Biomarcadores/metabolismo , Criança , Pré-Escolar , Creatina Quinase/metabolismo , Diagnóstico Tardio , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/fisiopatologia , Seguimentos , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Itália , Masculino , Músculos/patologia , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/patologia , Distrofia Muscular de Duchenne/fisiopatologia , Melhoria de QualidadeRESUMO
This paper describes the psycho-social treatments received by 502 patients with MDs and their relatives, and the costs for care sustained by the families in the previous six month period. Data were collected by the MD-Care Schedule (MD-CS) and the Family Problems Questionnaire (FPQ). Psycho-educational interventions were provided to 72 patients (14.3%), and social/welfare support to 331 patients (65.9%). Social/welfare support was higher in patients with DMD or LGMD, in those showing more severe disability, and in patients who were in contact with centres located in Northern Italy. Psycho-educational interventions were received by 156 (31%) relatives, and social/welfare support by 55 (10.9%) and mainly provided by Family/Patients Associations (83.6%). Relatives with higher educational levels, who spent more daily hours in the assistance of patients with DMD, and in contact with centres in Central Italy more frequently benefited from psycho-educational interventions. In the previous year, costs for care were sustained by 314 (63.9%) relatives. Financial difficulties related to patient's condition, were higher in families of patients who needed more intensive rehabilitation and daily hours of caregiving, and in families who lived further away from the reference's centre. These results showed that psycho-social aspects of MDs care are only partially met in Italy, and that ad hoc supportive interventions for these patients and their families should be potentiated.
Assuntos
Cuidadores/psicologia , Efeitos Psicossociais da Doença , Distrofias Musculares/economia , Distrofias Musculares/psicologia , Sistemas de Apoio Psicossocial , Seguridade Social , Atividades Cotidianas , Adolescente , Adulto , Criança , Pré-Escolar , Prestação Integrada de Cuidados de Saúde , Honorários e Preços/estatística & dados numéricos , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Distrofias Musculares/reabilitação , Educação de Pacientes como Assunto , Adulto JovemRESUMO
BACKGROUND: The role of timed items, and more specifically, of the time to rise from the floor, has been reported as an early prognostic factor for disease progression and loss of ambulation. The aim of our study was to investigate the possible effect of the time to rise from the floor test on the changes observed on the 6MWT over 12 months in a cohort of ambulant Duchenne boys. SUBJECTS AND METHODS: A total of 487 12-month data points were collected from 215 ambulant Duchenne boys. The age ranged between 5.0 and 20.0 years (mean 8.48 ±2.48 DS). RESULTS: The results of the time to rise from the floor at baseline ranged from 1.2 to 29.4 seconds in the boys who could perform the test. 49 patients were unable to perform the test at baseline and 87 at 12 month The 6MWT values ranged from 82 to 567 meters at baseline. 3 patients lost the ability to perform the 6mwt at 12 months. The correlation between time to rise from the floor and 6MWT at baseline was high (r = 0.6, p<0.01). CONCLUSIONS: Both time to rise from the floor and baseline 6MWT were relevant for predicting 6MWT changes in the group above the age of 7 years, with no interaction between the two measures, as the impact of time to rise from the floor on 6MWT change was similar in the patients below and above 350 m. Our results suggest that, time to rise from the floor can be considered an additional important prognostic factor of 12 month changes on the 6MWT and, more generally, of disease progression.
Assuntos
Distrofia Muscular de Duchenne/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Progressão da Doença , Humanos , Masculino , Adulto JovemRESUMO
The Performance of Upper Limb was specifically designed to assess upper limb function in Duchenne muscular dystrophy. The aim of this study was to assess (1) a cohort of typically developing children from the age of 3years onwards in order to identify the age when the activities assessed in the individual items are consistently achieved, and (2) a cohort of 322 Duchenne children and young adults to establish the range of findings at different ages. We collected normative data for the scale validation on 277 typically developing subjects from 3 to 25years old. A full score was consistently achieved by the age of 5years. In the Duchenne cohort there was early involvement of the proximal muscles and a proximal to distal progressive involvement. The scale was capable of measuring small distal movements, related to activities of daily living, even in the oldest and weakest patients. Our data suggest that the assessment can be reliably used in both ambulant and non ambulant Duchenne patients in a multicentric setting and could therefore be considered as an outcome measure for future trials.