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BACKGROUND: After receiving a diagnosis of a neuromuscular condition, patients have to make their way through a convoluted network of community and state resources as health care shifts from being family and child centered to adult focused. This study examined the barriers to successful transition from patient and clinician perspectives. METHODS: Adolescents with a primary diagnosis of a neuromuscular condition who were aged 16 years and over in Queensland, Australia, and who had started the transition process were eligible. Surveys were collected over six months and statistics used to characterize survey responses. RESULTS: There was a high degree of anxiety reported about the transition, with almost 50% of patients and families surveyed reporting concerns about moving across to the adult hospital system. The main barriers to effective transition identified by clinicians were limited time (84%), clinic space (58%), and a lack of an identified transition coordinator (79%). CONCLUSIONS: This study has provided a checklist to assist patients with neuromuscular disorders in transitioning from pediatric to adult care. A new model has been developed to enable a slow, personalized transition that is led by a multidisciplinary team.
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BACKGROUND: Spinal muscular atrophy (SMA) is a devastating motor neuron disorder causing progressive muscle weakness and respiratory insufficiency. We present the initial Australian experiences implementing the expanded access programme (EAP) to enable preapproval access to nusinersen, the first disease-modifying therapy, for SMA type 1. METHODS: An Australian multicentre, open-label EAP for nusinersen enrolled patients with infantile-onset SMA type 1 from November 2016 to September 2017. Standard-of-care medical therapy and treatment with intrathecal nusinersen were provided to all patients. Clinical and diagnostic characteristics, molecular genetics, treatment administered, and functional motor outcomes were assessed. RESULTS: A total of 20 patients with SMA type 1 met the inclusion criteria, of whom 16 consented and received nusinersen treatment. Median time to diagnosis from symptom onset was 5.0 months and was correlated with age of onset (r=0.54, P<0.05). Management shifts included proactive nutritional and pulmonary support in all newly diagnosed patients with increased complexity of decision making. Supplemental nutrition with or without nocturnal non-invasive ventilation was implemented during follow-up in new diagnoses with age of onset <3 months and 2 SMN2 copies. CONCLUSIONS: The nusinersen EAP highlights difficulties in achieving early diagnosis and/or prevention, the evolution of optimal clinical care in a time of uncertain prognostication, resource implications and ethical issues in clinical practice for SMA type 1. These challenges are broadly relevant to the realisation of all novel therapeutics in neurological disorders.
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Accesibilidad a los Servicios de Salud , Oligonucleótidos/uso terapéutico , Atrofias Musculares Espinales de la Infancia/diagnóstico , Atrofias Musculares Espinales de la Infancia/tratamiento farmacológico , Factores de Edad , Australia , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Prospectivos , Resultado del TratamientoRESUMEN
AIM: Ataxia-telangiectasia (A-T) is a rare genomic syndrome resulting in severe disability. Chronic childhood disorders can profoundly influence growth and development. Nutrition-related issues in A-T are not well described, and there are no nutritional guidelines. This study investigated the nutrition-related characteristics and behaviours of Australian A-T patients attending a national clinic. METHODS: A cross-sectional analysis of 13 A-T patients (nine females; aged: 4-23 years): nutritional status was assessed by anthropometric and body cell mass (BCM) calculations. Parents reported their child's diet history and physical and behavioural factors that affect nutrition including fatigue and need for assistance. RESULTS: Ten (77%) had short stature (height for age z scores <-1), and seven (54%) were underweight for height (weight/height z scores <-1). Significant malnutrition (BCM z scores <-2) was detected in nine (69%) including the one adult who was severely malnourished. Malnutrition increased significantly with age (BCM for height z scores and age, r = -0.937, P < 0.001). Eight (62%) patients ate poorly compared with estimated energy requirement for weight. Poor diet quality was characterised by high fat and sugar choices. Parents reported significant nutritional barriers as chronic tiredness and the need for care giver assistance with meals. CONCLUSIONS: This study confirms profound malnutrition in Australian A-T patients. Poor intakes and diet quality suggest the need for early nutrition intervention. Ongoing support for families and early discussions on tube feeding are required to address changing needs in childhood and likely nutritional decline into adulthood. A prospective study is required to assess feasibility and effectiveness of nutrition interventions in young people with A-T.
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Ataxia Telangiectasia/complicaciones , Desnutrición/etiología , Estado Nutricional , Adolescente , Australia , Índice de Masa Corporal , Niño , Preescolar , Estudios Transversales , Fatiga/etiología , Conducta Alimentaria , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
PURPOSE: VEGF-A blockade has been clinically validated as a treatment for human cancers. Angiopoietin-2 (Ang-2) expression has been shown to function as a key regulator of tumor angiogenesis and metastasis. EXPERIMENTAL DESIGN: We have applied the recently developed CrossMab technology for the generation of a bispecific antibody recognizing VEGF-A with one arm based on bevacizumab (Avastin), and the other arm recognizing Ang-2 based on LC06, an Ang-2 selective human IgG1 antibody. The potency of Ang-2-VEGF CrossMab was evaluated alone and in combination with chemotherapy using orthotopic and subcutaneous xenotransplantations, along with metastasis analysis by quantitative real-time Alu-PCR and ex vivo evaluation of vessels, hypoxia, proliferation, and apoptosis. The mechanism of action was further elucidated using Western blotting and ELISA assays. RESULTS: Ang-2-VEGF-A CrossMab showed potent tumor growth inhibition in a panel of orthotopic and subcutaneous syngeneic mouse tumors and patient or cell line-derived human tumor xenografts, especially at later stages of tumor development. Ang-2-VEGF-A CrossMab treatment led to a strong inhibition of angiogenesis and an enhanced vessel maturation phenotype. Neoadjuvant combination with chemotherapy resulted in complete tumor regression in primary tumor-bearing Ang-2-VEGF-A CrossMab-treated mice. In contrast to Ang-1 inhibition, anti-Ang-2-VEGF-A treatment did not aggravate the adverse effect of anti-VEGF treatment on physiologic vessels. Moreover, treatment with Ang-2-VEGF-A CrossMab resulted in inhibition of hematogenous spread of tumor cells to other organs and reduced micrometastatic growth in the adjuvant setting. CONCLUSION: These data establish Ang-2-VEGF-A CrossMab as a promising antitumor, antiangiogenic, and antimetastatic agent for the treatment of cancer.