Long-term follow-up of 17 patients with childhood Pompe disease treated with enzyme replacement therapy

Objectives: Pompe disease is a progressive metabolic myopathy for which enzyme replacement therapy (ERT) was approved in 2006. While various publications have examined the effects of ERT in classic-infantile patients and in adults, little has been published on ERT in children with non-classic presentations. Study design: This prospective study was conducted from June 1999 to May 2015. Seventeen patients from various countries participated. Outcome measures comprised muscle function (6-minute walk test, quick motor-function test (QMFT)), muscle strength (hand-held dynamometry; manual muscle testing), and lung function (FVC sitting and supine). For each outcome measure, we used linear mixed-effects models to calculate the difference at group level between the start of therapy and 7 years of ERT. Patients’ individual responses over time were also evaluated. Results: Eleven males and six females started ERT at ages between 1.1 and 16.4 years (median 11.9 years); 82% of them carried the common c.-32-13T > G GAA gene variant on one allele. At group level, distance walked increased by 7.4 percentage points (p < 0.001) and QMFT scores increased by 9.2 percentage points (p = 0.006). Muscle strength scores seemed to remain stable. Results on lung function were more variable. Patients’ individual data show that the proportion of patients who stabilized or improved during treatment ranged between 56 and 69% for lung function outcomes and between 71 and 93% for muscle strength and muscle function outcomes. Conclusions: We report a positive effect of ERT in patients with childhood Pompe disease at group level. For some patients

Drepanosticta hamalaineni spec. nov and Sulcosticta sierramadrensis spec. nov from the Northern Sierra Madre Natural Park, Luzon, the Philippines (Zygoptera: Platystictidae)

Conservation Biology - ol

Knowledge, Food and Place: a way of producing a way of knowing

The article examines the dynamics of knowledge in the valorisation of local food, drawing on the results from the CORASON project (A cognitive approach to rural sustainable development: the dynamics of expert and lay knowledge), funded by the EU under its Framework Programme 6. It is based on the analysis of several in-depth case studies on food relocalisation carried out in 10 European countries

Molecular dynamics simulations of a fully hydrated dipalmitoyl phosphatidylcholine bilayer with different macroscopic boundary conditions and parameters

We compared molecular dynamics simulations of a bilayer of 128 fully hydrated phospholipid (DPPC) molecules, using different parameters and macroscopic boundary conditions. The same system was studied under constant pressure, constant volume, and constant surface tension boundary conditions, with two different sets of charges, the single point charge (SPC) and extended single point charge (SPC/E) water model and two different sets of Lennard-Jones parameters for the interaction between water and methyl/methylene. Some selected properties of the resulting bilayer systems are compared to each other, previous simulations, and experimental data. It is concluded that in relatively high water concentration it is possible to use ab initio derived charges with constant pressure boundary conditions. The SPC water model gives a larger area per head group and a broader interface than the SPC/E model. Increasing the repulsion between water oxygens and CH2/CH3 groups has a large effect on the width of the interface and the area per head group. There is little difference between simulations with constant pressure and constant surface tension. The use of constant volume, using a reasonable estimate for the initial box dimensions, easily introduces artefacts. (C) 1996 American Institute of Physics

Discontinuation of enzyme replacement therapy in adults with Pompe disease: Evaluating the European POmpe Consortium stop criteria

Enzyme replacement therapy for Pompe disease received market authorization in 2006. To implement this costly treatment in the Netherlands in the most sensible way, a multidisciplinary expert committee was installed. We evaluated decision making in adult patients in relation to the European POmpe Consortium stop criteria. Of 125 adult Pompe patients, 111 started treatment; subsequently treatment stopped in 24 patients (21%). In 10 patients, treatment was discontinued for medical or personal reasons, as defined in the six stop criteria (median treatment duration: 2.1 years, range: 0.3–14.6 years). Three of these patients continued follow-up (follow-up: 1.3–8.0 years), these patients did not display a more rapid decline after discontinuation. In 14 of 24 patients, therapy ended at time of death. In 10 patients death was related to Pompe disease (median treatment duration: 7.2 years, range: 0.4–10.3 years). All 10 patients were severely affected at start of treatment, treatment had elicited positive effects in eight. The European POmpe Consortium guidelines worked well in decision making on stopping treatment. However, (re)evaluation of the rationale for continuation of treatment in advanced disease stage is not addressed. We suggest to add this to the treatment evaluation and to handle treatment decisions in a multidisciplinary expert team

Implementing Exercise = Medicine in routine clinical care; needs for an online tool and key decisions for implementation of Exercise = Medicine within two Dutch academic hospitals

BACKGROUND: There is much evidence to implement physical activity interventions for medical reasons in healthcare settings. However, the prescription of physical activity as a treatment, referring to as 'Exercise is Medicine' (E = M) is currently mostly absent in routine hospital care in The Netherlands. To support E = M prescription by clinicians in hospitals, this study aimed: (1) to develop an E = M-tool for physical activity advice and referrals to facilitate the E = M prescription in hospital settings; and (2) to provide an E = M decision guide on key decisions for implementation to prepare for E = M prescription in hospital care. METHODS: A mixed method design was used employing a questionnaire and face-to-face interviews with clinicians, lifestyle coaches and hospital managers, a patient panel and stakeholders to assess the needs regarding an E = M-tool and key decisions for implementation of E = M. Based on the needs assessment, a digital E = M-tool was developed. The key decisions informed the development of an E = M decision guide. RESULTS: An online supportive tool for E = M was developed for two academic hospitals. Based on the needs assessment, linked to the different patients' electronic medical records and tailored to the two local settings (University Medical Center Groningen, Amsterdam University Medical Centers). The E = M-tool existed of a tool algorithm, including patient characteristics assessed with a digital questionnaire (age, gender, PA, BMI, medical diagnosis, motivation to change physical activity and preference to discuss physical activity with their doctor) set against norm values. The digital E = M-tool provided an individual E = M-prescription for patients and referral options to local PA interventions in- and outside the hospital. An E = M decision guide was developed to support the implementation of E = M prescription in hospital care. CONCLUSIONS: This study provided insight into E = M-tool development and the E = M decision-making to support E = M prescription and facilitate tailoring towards local E = M treatment options, using strong stakeholder participation. Outcomes may serve as an example for other decision support guides and interventions aimed at E = M implementation

Implementing Exercise = Medicine in routine clinical care; needs for an online tool and key decisions for implementation of Exercise = Medicine within two Dutch academic hospitals

Background There is much evidence to implement physical activity interventions for medical reasons in healthcare settings. However, the prescription of physical activity as a treatment, referring to as 'Exercise is Medicine' (E = M) is currently mostly absent in routine hospital care in The Netherlands. To support E = M prescription by clinicians in hospitals, this study aimed: (1) to develop an E = M-tool for physical activity advice and referrals to facilitate the E = M prescription in hospital settings; and (2) to provide an E = M decision guide on key decisions for implementation to prepare for E = M prescription in hospital care. Methods A mixed method design was used employing a questionnaire and face-to-face interviews with clinicians, lifestyle coaches and hospital managers, a patient panel and stakeholders to assess the needs regarding an E = M-tool and key decisions for implementation of E = M. Based on the needs assessment, a digital E = M-tool was developed. The key decisions informed the development of an E = M decision guide. Results An online supportive tool for E = M was developed for two academic hospitals. Based on the needs assessment, linked to the different patients' electronic medical records and tailored to the two local settings (University Medical Center Groningen, Amsterdam University Medical Centers). The E = M-tool existed of a tool algorithm, including patient characteristics assessed with a digital questionnaire (age, gender, PA, BMI, medical diagnosis, motivation to change physical activity and preference to discuss physical activity with their doctor) set against norm values. The digital E = M-tool provided an individual E = M-prescription for patients and referral options to local PA interventions in- and outside the hospital. An E = M decision guide was developed to support the implementation of E = M prescription in hospital care. Conclusions This study provided insight into E = M-tool development and the E = M decision-making to support E = M prescription and facilitate tailoring towards local E = M treatment options, using strong stakeholder participation. Outcomes may serve as an example for other decision support guides and interventions aimed at E = M implementation.</p