Training and orthotic effects related to functional electrical stimulation of the peroneal nerve in stroke.

OBJECTIVE: To examine the evidence for a training effect on the lower limb of functional electrical stimulation. DESIGN: Cohort study. PATIENTS: A total of 133 patients >6 months post-stroke. METHODS: Training and orthotic effects were determined from walking speed over 10 m, associated minimal and substantial clinically important differences (i.e. >0.05 and >0.10 m/s), and Functional Ambulation Category (FAC), ranging from household walking to independent walking in the community. RESULTS: An overall significant (p < 0.01) training effect was found that was not a clinically important difference (0.02 m/s); however, "community" FAC (≥ 0.8 m/s) and "most limited community walkers" FAC (0.4-0.58 m/s), but not "household walkers" (< 0.4 m/s), benefitted from a clinically important difference. A highly significant (p< 0.001), substantial clinically important orthotic effect (0.10 m/s) was found. In terms of overall improvement of one or more FACs, 23% achieved this due to a training effect, compared with 43% due to an orthotic effect. CONCLUSION: The findings suggest that functional electrical stimulation provides a training effect in those who are less impaired. Further work, which optimizes the use of the device for restoration of function, rather than as an orthotic device, will provide greater clarity on the effectiveness of functional electrical stimulation for eliciting a training effect

CNS inflammation other than multiple sclerosis: how likely is diagnosis?

The incidence, diagnostic landscape, and workload impact of CNS inflammatory diseases other than multiple sclerosis (MS) (CIDOMS) in a tertiary setting is unknown. We describe a retrospective case series of 64 patients identified over a 2-year period (2009–2010) at the Wessex Neurological Centre in the United Kingdom, accounting for 4% of all patients seen at the center. As expected, neurosarcoidosis and neuromyelitis optica (NMO) were the most common diagnoses reached (14% each); other diagnoses singly accounted for <10%. However, the likeliest diagnostic outcome (strikingly, in 25%) was nondiagnosis, despite intensive investigation and a mean follow-up period of 3 years. Undiagnosed patients with CIDOMS represented the largest workload of the neurology center

Quality of life and cost effectiveness following the use of Functional Electrical Stimulation (FES) of the peroneal nerve for people with multiple sclerosis

There is a large gap in quality of life for people with MS and the general population. FES is an effective intervention for dropped foot reducing falls by 72% (1), with a mean usage of 4.9 years (2). Improving health related quality of life and cost effectiveness are a priority for the national health system in the UK, who have set a cost effectiveness threshold of £20,000(€24,218) per Quality Adjusted Life Year (QALY) under which interventions will be considered. Method: 45 people with multiple sclerosis (mean age 53, range 40-70) and foot drop completed the EQ-5D-5L (Euroqol) quality of life questionnaire before and after using FES for 20 weeks. Index values were calculated using the latest available value set and checked with the crosswalk value set (3). QALY gain was calculated by multiplying the utility value by the average length of time of FES use, discounted at 3.5% per year. The mean cost minus the expected cost saving due to falls prevention was divided by the QALY gain to give the mean net cost per QALY. Results: The mean index value before treatment (0.542) was highly significant compared to after treatment (0.656) (t=-4.68, p< 0.001), providing a utility value of 0.114 which works out to 0.542 when extrapolated to 4.9 years. The cost of providing FES for 4.9 years is £3095(€3,742)(1), giving a cost per QALY of £5,705(€6,901). However, it is estimated that the reduction of falls may result in a cost saving of £375(€454) per year, bringing the net cost to £1,256(€1,519) and cost per QALY to £2,316(€2,801). Conclusion: These preliminary results must be treated with caution as the data used was taken from three different studies. Nevertheless the analysis indicates that FES is associated with improved health related quality of life and is well within cost effectiveness thresholds

Cytokinin Acts through the Auxin Influx Carrier AUX1 to Regulate Cell Elongation in the Root

Hormonal interactions are crucial for plant development. In Arabidopsis, cytokinins inhibit root growth through effects on cell proliferation and cell elongation. Here, we define key mechanistic elements in a regulatory network by which cytokinin inhibits root cell elongation in concert with the hormones auxin and ethylene. The auxin importer AUX1 functions as a positive regulator of cytokinin responses in the root; mutation of AUX1 specifically affects the ability of cytokinin to inhibit cell elongation but not cell proliferation. AUX1 is required for cytokinin-dependent changes of auxin activity in the lateral root cap associated with the control of cell elongation. Cytokinin regulates root cell elongation through ethylene-dependent and -independent mechanisms, both hormonal signals converging on AUX1 as a regulatory hub. An autoregulatory circuit is identified involving the control of ARR10 and AUX1 expression by cytokinin and auxin, this circuit potentially functioning as an oscillator to integrate the effects of these two hormones. Taken together, our results uncover several regulatory circuits controlling interactions of cytokinin with auxin and ethylene, and support a model in which cytokinin regulates shootward auxin transport to control cell elongation and root growth

Who would most benefit from improved integrated care? : Implementing an analytical strategy in South Somerset

Conclusions: The linked dataset makes it possible to understand existing patterns of health and social care utilisation and to analyse variation in annual costs, for the whole population and for sub-groups, in total and by setting. This has made it possible to identify who would most benefit from improved integrated care and to calculate capitated budgets to support financial integration. Aims: The Symphony Project is designed to identify which groups of the South Somerset population in England would most benefit from greater integration across primary, community, acute and social care settings. Methods: We analysed linked health and social care data for the entire South Somerset population for the financial year 2012/2013. The data captured acute, primary, community, mental health and social care utilisation and costs; demographic characteristics; and indicators of morbidity for each individual. We employed generalized linear models to analyse variation in annual health and social care costs for all 114,874 members of the South Somerset population and for 1458 individuals with three or more selected chronic conditions. Results: We found that multi-morbidity, not age, was the key driver of health and social care costs. Moreover, the number of chronic conditions is as useful as information about specific conditions at predicting costs. We are able to explain 7% of the variation in total annual costs for population as a whole, and 14% of the variation for those with three or more conditions. We are best able to explain primary care costs, but explanatory power is poor for mental health and social care costs

Novel picornavirus in turkey poults with hepatitis, California, USA

To identify a candidate etiologic agent for turkey viral hepatitis, we analyzed samples from diseased turkey poults from 8 commercial flocks in California, USA, that were collected during 2008–2010. High-throughput pyrosequencing of RNA from livers of poults with turkey viral hepatitis (TVH) revealed picornavirus sequences. Subsequent cloning of the ≈9-kb genome showed an organization similar to that of picornaviruses with conservation of motifs within the P1, P2, and P3 genome regions, but also unique features, including a 1.2-kb sequence of unknown function at the junction of P1 and P2 regions. Real-time PCR confirmed viral RNA in liver, bile, intestine, serum, and cloacal swab specimens from diseased poults. Analysis of liver by in situ hybridization with viral probes and immunohistochemical testing of serum demonstrated viral nucleic acid and protein in livers of diseased poults. Molecular, anatomic, and immunologic evidence suggests that TVH is caused by a novel picornavirus, tentatively named turkey hepatitis virus

Clinical progression of progressive supranuclear palsy: impact of trials bias and phenotype variants.

Funder: Cambridge Brain BankProgressive supranuclear palsy causes diverse clinical presentations, including classical Richardson's syndrome and several variant phenotypes. Clinical trials of disease-modifying therapies have recently been completed, with more planned for the next 2 years. However, many people with progressive supranuclear palsy do not meet eligibility criteria for these clinical trials. Understanding clinical progression with different phenotypes would improve trial design and enhance the accuracy of risk-benefit and cost-benefit assessments of new treatments for progressive supranuclear palsy. We set out to determine rates of motor and cognitive progression of possible, probable and definite progressive supranuclear palsy, with different phenotypes, from a representative cohort in a regional UK healthcare service. Longitudinal clinical data from people with Richardson's syndrome and variant phenotypes were analysed using linear mixed-modelling, using both the full and modified versions of the Progressive Supranuclear Palsy Rating Scale, Mini-Mental State Examination and the revised Addenbrooke's Cognitive Examination. Subgroup analyses considered patients meeting recent Phase II trial entry criteria and patients with neuropathological confirmation. Two hundred and twenty-seven patients [male = 59%, mean age (±standard deviation), 71.8 (±7.0) years] were followed for a mean 21.6 (±15.6) months. One hundred and seventy-four (77%) had Richardson's syndrome at the outset, 25 had cortical variant presentations (13%, frontal, corticobasal, speech and language variants) and 28 had subcortical variant presentations (14%, parkinsonism, postural instability and gait freezing variants). Across all participants, annual progression in Richardson's syndrome was faster than variant phenotypes on the Mini-Mental State Examination (-1.8 versus -0.9/year, P = 0.005) and revised Addenbrooke's Cognitive Examination (-5.3 versus -3.0/year, P = 0.01) but not the Progressive Supranuclear Palsy Rating Scale (9.0 versus 7.1/year, P = 0.2) nor the modified Progressive Supranuclear Palsy Rating Scale (2.7 versus 2.3/year, P = 0.4). However, for those with more than 1 years' follow-up, a significant difference was observed between Richardson's syndrome and variant phenotypes in Progressive Supranuclear Palsy Rating Scale (8.7 versus 6.3/year, P = 0.04). Survival was longer in variant phenotypes than Richardson's syndrome [7.3 (±3.9) versus 5.6 (±2.0) years, P = 0.02]. Pathologically confirmed cases (n = 49) supported these findings. Patients meeting basic trial-eligibility criteria (n = 129) progressed faster on the Progressive Supranuclear Palsy Rating Scale than trial-not-eligible patients (10.1 versus 6.1/year, P = 0.001). In conclusion, phenotypes other than Richardson's syndrome show slower progression and longer survival. Trial criteria do not select representative progressive supranuclear palsy cases. This has implications for trial design, and application of trial results to clinically more diverse patient populations