Three-year quantitative magnetic resonance imaging and phosphorus magnetic resonance spectroscopy study in lower limb muscle in dysferlinopathy.

BACKGROUND: Natural history studies in neuromuscular disorders are vital to understand the disease evolution and to find sensitive outcome measures. We performed a longitudinal assessment of quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (31 P MRS) outcome measures and evaluated their relationship with function in lower limb skeletal muscle of dysferlinopathy patients. METHODS: Quantitative MRI/31 P MRS data were obtained at 3 T in two different sites in 54 patients and 12 controls, at baseline, and three annual follow-up visits. Fat fraction (FF), contractile cross-sectional area (cCSA), and muscle water T2 in both global leg and thigh segments and individual muscles and 31 P MRS indices in the anterior leg compartment were assessed. Analysis included comparisons between patients and controls, assessments of annual changes using a linear mixed model, standardized response means (SRM), and correlations between MRI and 31 P MRS markers and functional markers. RESULTS: Posterior muscles in thigh and leg showed the highest FF values. FF at baseline was highly heterogeneous across patients. In ambulant patients, median annual increases in global thigh and leg segment FF values were 4.1% and 3.0%, respectively (P < 0.001). After 3 years, global thigh and leg FF increases were 9.6% and 8.4%, respectively (P < 0.001). SRM values for global thigh FF were over 0.8 for all years. Vastus lateralis muscle showed the highest SRM values across all time points. cCSA decreased significantly after 3 years with median values of 11.0% and 12.8% in global thigh and global leg, respectively (P < 0.001). Water T2 values in ambulant patients were significantly increased, as compared with control values (P < 0.001). The highest water T2 values were found in the anterior part of thigh and leg. Almost all 31 P MRS indices were significantly different in patients as compared with controls (P < 0.006), except for pHw , and remained, similar as to water T2 , abnormal for the whole study duration. Global thigh water T2 at baseline was significantly correlated to the change in FF after 3 years (ρ = 0.52, P < 0.001). There was also a significant relationship between the change in functional score and change in FF after 3 years in ambulant patients (ρ = -0.55, P = 0.010). CONCLUSIONS: This multi-centre study has shown that quantitative MRI/31 P MRS measurements in a heterogeneous group of dysferlinopathy patients can measure significant changes over the course of 3 years. These data can be used as reference values in view of future clinical trials in dysferlinopathy or comparisons with quantitative MRI/S data obtained in other limb-girdle muscular dystrophy subtypes.

High folate levels in Aboriginal children after subsidised fruit and vegetables and mandatory folic acid fortification.

OBJECTIVE: To evaluate the impact of a fruit and vegetable (F&V) subsidy program for disadvantaged Aboriginal children in Australia, implemented alongside the introduction of mandatory folic acid fortification of bread-making flour. METHODS: A before-and-after evaluation was undertaken of a F&V subsidy program at three Aboriginal community-controlled health services in New South Wales. The program provided a weekly box of subsidised F&V linked to preventive health services and nutrition promotion for families. In this analysis, red blood cell (RBC) folate was assessed together with self-reported dietary intake at baseline and 12 months later in a cohort of 125 children (aged 0-17 years). RESULTS: No children had low RBC folate at baseline or at follow-up; however, 33 children (26%) exceeded the reference range of RBC folate at baseline and 38 children (30%) exceeded the reference range at follow-up. Mean RBC folate levels increased substantially in children at follow-up (mean RBC folate z-score increased +0.55 (95%CI 0.36-0.74). Change in F&V intake (p=0.196) and mean bread intake (p=0.676) were not statistically significant predictors for change in RBC folate levels. CONCLUSIONS: RBC folate levels increased among these disadvantaged Aboriginal children following mandatory folic acid fortification and participation in a subsidised F&V program. Even before mandatory folic acid fortification, none of these children had low RBC folate. IMPLICATIONS: The effect on health of mandatory fortification of foods with folate is not clear, hence, ongoing population-based monitoring of folate levels to assess the impact of mandatory folic acid fortification is important.

Health outcomes of a subsidised fruit and vegetable program for Aboriginal children in northern New South Wales.

OBJECTIVE: To evaluate the impact of a fruit and vegetable subsidy program on short-term health outcomes of disadvantaged Aboriginal children. DESIGN, SETTING AND PARTICIPANTS: A before-and-after study involving clinical assessments, health record audits and blood testing of all children aged 0-17 2013s (n = 167) from 55 participating families at baseline and after 12 months at three Aboriginal community-controlled health services in New South Wales. All assessments were completed between December 2008 and September 2010. INTERVENTION: A weekly box of subsidised fruit and vegetables linked to preventive health services and nutrition promotion at an Aboriginal Medical Service. MAIN OUTCOME MEASURES: Change in episodes of illness, health service and emergency department attendances, antibiotic prescriptions and anthropometry. RESULTS: There was a significant decrease in oral antibiotics prescribed (- 0.5 prescriptions/2013; 95% CI, - 0.8 to - 0.2) during 12 months of participation in the program compared with the 12 months before the program. The proportion of children classified as overweight or obese at baseline was 28.3% (38/134) and the proportion in each weight category did not change (P = 0.721) after 12 months. A small but significant increase in mean haemoglobin level (3.1 g/L; 95% CI, 1.4-4.8 g/L) was shown, although the proportion with iron deficiency (baseline, 41%; follow-up, 37%; P = 0.440) and anaemia (baseline, 8%; follow-up, 5%; P = 0.453) did not change significantly. CONCLUSION: it and vegetable subsidy program was associated with improvements in some indicators of short-term health status among disadvantaged Aboriginal children. A controlled trial is warranted to investigate the sustainability and feasibility of healthy food subsidy programs in Australia.

Boundaries and e-health implementation in health and social care.

BACKGROUND: The major problem facing health and social care systems globally today is the growing challenge of an elderly population with complex health and social care needs. A longstanding challenge to the provision of high quality, effectively coordinated care for those with complex needs has been the historical separation of health and social care. Access to timely and accurate data about patients and their treatments has the potential to deliver better care at less cost. METHODS: To explore the way in which structural, professional and geographical boundaries have affected e-health implementation in health and social care, through an empirical study of the implementation of an electronic version of Single Shared Assessment (SSA) in Scotland, using three retrospective, qualitative case studies in three different health board locations. RESULTS: Progress in effectively sharing electronic data had been slow and uneven. One cause was the presence of established structural boundaries, which lead to competing priorities, incompatible IT systems and infrastructure, and poor cooperation. A second cause was the presence of established professional boundaries, which affect staffs' understanding and acceptance of data sharing and their information requirements. Geographical boundaries featured but less prominently and contrasting perspectives were found with regard to issues such as co-location of health and social care professionals. CONCLUSIONS: To provide holistic care to those with complex health and social care needs, it is essential that we develop integrated approaches to care delivery. Successful integration needs practices such as good project management and governance, ensuring system interoperability, leadership, good training and support, together with clear efforts to improve working relations across professional boundaries and communication of a clear project vision. This study shows that while technological developments make integration possible, long-standing boundaries constitute substantial risks to IT implementations across the health and social care interface which those initiating major changes would do well to consider before committing to the investment.

Magnetocardiography for pharmacology safety studies requiring high patient throughput and reliability.

Recent guideline drafts of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) underline the necessity to test nonantiarrhythmic drugs for their potential to prolong the QT or the corrected QT (QTc) interval. The implementation of these guidelines requires a large amount of ECG measurements on animals and humans in preclinical and clinical phases of the drug development process. We propose the use of magnetocardiography (MCG) as a complementary method with particular advantages in high-throughput studies, where signal quality and reliability are key factors. Our proposal is based on a review of recent MCG studies investigating the repolarization phase and results of methodological work assessing QT interval parameters from the MCG. The applicability of MCG for pre-clinical in-vivo studies is demonstrated by the ease of measurement in unrestrained non-anesthetized rabbits, guinea pigs, and hamsters..

High-throughput screening for ion channel modulators.

Ion channels present a group of targets for major clinical indications, which have been difficult to address due to the lack of suitable rapid but biologically significant methodologies. To address the need for increased throughput in primary screening, the authors have set up a Beckman/Sagian core system to fully automate functional fluorescence-based assays that measure ion channel function. They apply voltage-sensitive fluorescent probes, and the activity of channels is monitored using Aurora's Voltage/Ion Probe Reader (VIPR). The system provides a platform for fully automated high-throughput screening as well as pharmacological characterization of ion channel modulators. The application of voltage-sensitive fluorescence dyes coupled with fluorescence resonance energy transfer is the basis of robust assays, which can be adapted to the study of a variety of ion channels to screen for both inhibitors and activators of voltage-gated and other ion channels.