5 research outputs found
Neurofilament Light and Its Association With CNS Involvement in Patients With Classic Infantile Pompe Disease
Fatigue after a first attack of suspected multiple sclerosis
Background: Fatigue is reported by more than 75% of multiple sclerosis (MS) patients. In an earlier study, we showed that fatigue is not only a common symptom in patien
Effects of higher and more frequent dosing of alglucosidase alfa and immunomodulation on long-term clinical outcome of classic infantile Pompe patients
The aim of this study was to compare the long-term outcome of classic infantile Pompe patients treated with 20 mg/kg alglucosidase alfa every other week (eow) to those treated with 40 mg/kg/week, and to study the additional effect of immunomodulation. Six patients received 20 mg/kg eow and twelve 40 mg/kg/week. Five patients were cross-reactive immunologic material (CRIM)-negative, two in the 20 mg, three in the 40 mg group. We compared (ventilator-free) survival, motor outcome, infusion associated reactions (IARs), and antibody formation. From 2012 on patients >2 months in the 40 mg group also received immunomodulation with rituximab, methotrexate, and intravenous immunoglobulin (IVIG) in an enzyme replacement therapy (ERT)-naĂŻve setting. Survival was 66% in the 20 mg group and 92% in the 40 mg group. Ventilator-free survival was 50% and 92%. Both CRIM-negative patients in the 20 mg group died, whereas all three are alive in the 40 mg group. In the 20 mg group, 67% learned to walk compared with 92% in the 40 mg group. At the age of 3 years, 33% and 92% were able to walk. Peak antibody titers ranged from 1:1250 to 1:31 250 in the 20 mg group and from 1:250 to 1:800 000 in the 40 mg group. Five patients of the 40 mg group of whom two CRIM-negative also received immunomodulation. B-cell recovery was observed between 5.7 and 7.9 months after the last dose of rituximab. After B-cell recovery titers of patients with and without immunomodulation were similar (ranges 1:6 250-1:800 000 and 1:250-1:781 250). This study shows that classic infantile patients treated with 40 mg/kg/week from the start to end have a better (ventilator-free) survival and motor outcome. Immunomodulation did not prevent antibody formation in our study
Diffusion tensor imaging of the brain in Pompe disease
Enzyme replacement therapy has drastically changed prospects of patients with Pompe disease, a progressive metabolic myopathy. As classic infantile patients survive due to treatment, they exhibit progressive white matter abnormalities, while brain involvement in late-onset patients is not fully elucidated. To study the underlying microstructure of white matter, we acquired structural (T1, T2, FLAIR) and diffusion tensor imaging (DTI) of the brain in 12 classic infantile patients (age 5–20 years) and 18 late-onset Pompe patients (age 11–56 years). Structural images were scored according to a rating scale for classic infantile patients. Fractional anisotropy (FA) and mean diffusivity (MD) from classic infantile patients were compared to a reference population, using a Wilcoxon signed-rank, one sample test. Effect sizes (Hedges’ G) were used to compare DTI metrics across different tracts. For late-onset patients, results were compared to (reported) tractography data on normal aging. In classic infantile patients, we found a significant lower FA and higher MD (p < 0.01) compared to the reference population. Large-association fibers were most severely affected. Classic infantile patients with advanced white matter abnormalities on structural MRI showed the largest deviations from the reference population. FA and MD were similar for younger and older late-onset patients in large WM-association fibers. We conclude that, while no deviations from typical neurodevelopment were found in late-onset patients, classic infantile Pompe patients showed quantifiable, substantially altered white matter microstructure, which corresponded with disease stage on structural MRI. DTI holds promise to monitor therapy response in future therapies targeting the brain
Effectiveness and implementation of SHared decision-making supported by OUTcome information among patients with breast cancer, stroke and advanced kidney disease: SHOUT study protocol of multiple interrupted time series
Introduction Within the value-based healthcare framework, outcome data can be used to inform patients about (treatment) options, and empower them to make shared decisions with their health care professional. To facilitate shared decision-making (SDM) supported by outcome data, a multicomponent intervention has been designed, including patient decision aids on the organisation of post-treatment surveillance (breast cancer); discharge location (stroke) and treatment modality (advanced kidney disease), and training on SDM for health care professionals. The SHared decision-making supported by OUTcome information (SHOUT) study will examine the effectiveness of the intervention and its implementation in clinical practice. Methods and analysis Multiple interrupted time series will be used to stepwise implement the intervention. Patients diagnosed with either breast cancer (N=630), stroke (N=630) or advanced kidney disease (N=473) will be included. Measurements will be performed at baseline, three (stroke), six and twelve (breast cancer and advanced kidney disease) months. Trends on outcomes will be measured over a period of 20 months. The primary outcome will be patients' perceived level of involvement in decision-making. Secondary outcomes regarding effectiveness will include patient-reported SDM, decisional conflict, role in decision-making, knowledge, quality of life, preferred and chosen care, satisfaction with the intervention, healthcare utilisation and health outcomes. Outcomes regarding implementation will include the implementation rate and a questionnaire on the health care professionals' perspective on the implementation process. Ethics and dissemination The Medical research Ethics Committees United in Nieuwegein, the Netherlands, has confirmed that the Medical Research Involving Human Subjects Act does not apply to this study. Bureau Onderzoek & Innovatie of Santeon, the Netherlands, approved this study. The results will contribute to insight in and knowledge on the use of outcome data for SDM, and can stimulate sustainable implementation of SDM. Trial registration number NL8374, NL8375 and NL8376