Early VEGF testing in inflammatory neuropathy avoids POEMS syndrome misdiagnosis and associated costs

BACKGROUND: Prompt diagnosis and early treatment prevents disability in Polyneuropathy Organomegaly Endocrinopathy Monoclonal-protein and Skin Changes (POEMS) syndrome. Delay in diagnosis is common with 55% of patients initially incorrectly diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Patients are often treated with intravenous immunoglobulin which is both expensive and ineffective in the treatment of POEMS. Testing patients with acquired demyelinating neuropathy with serum vascular endothelial growth factor (VEGF) more accurately identifies POEMS syndrome than the current standard of care. Incorporating VEGF testing into screening could prevent misdiagnosis and reduce costs. METHODS: We used observed treatment information for patients in the University College London Hospital's POEMS syndrome database (n=100) and from the National Immunoglobulin Database to estimate costs associated with incorrect CIDP diagnoses across our cohort. We conducted a model-based cost-effectiveness analysis to compare the current diagnostic algorithm with an alternative which includes VEGF testing for all patients with an acquired demyelinating neuropathy. RESULTS: Treatment associated with an incorrect CIDP diagnosis led to total wasted healthcare expenditures of between £808 550 and £1 111 756 across our cohort, with an average cost-per-POEMS-patient misdiagnosed of £14 701 to £20 214. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy would lead to annual cost-savings of £107 398 for the National Health Service and could prevent misdiagnosis in 16 cases per annum. CONCLUSIONS: Misdiagnosis in POEMS syndrome results in diagnostic delay, disease progression and significant healthcare costs. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy is a cost-effective strategy allowing for early POEMS diagnosis and potentially enabling prompt disease-directed therapy

Cooperative motion and growing length scales in supercooled confined liquids

Using molecular dynamics simulations we investigate the relaxation dynamics of a supercooled liquid close to a rough as well as close to a smooth wall. For the former situation the relaxation times increase strongly with decreasing distance from the wall whereas in the second case they strongly decrease. We use this dependence to extract various dynamical length scales and show that they grow with decreasing temperature. By calculating the frequency dependent average susceptibility of such confined systems we show that the experimental interpretation of such data is very difficult.Comment: 7 pages of Latex, 3 figure

Dewetting of Glassy Polymer Films

Dynamics and morphology of hole growth in a film of power hardening viscoplastic solid (yield stress ~ [strain-rate]^n) is investigated. At short-times the growth is exponential and depends on the initial hole size. At long-times, for n > 1/3, the growth is exponential with a different exponent. However, for n < 1/3, the hole growth slows; the hole radius approaches an asymptotic value as time tends to infinity. The rim shape is highly asymmetric, the height of which has a power law dependence on the hole radius (exponent close to unity for 0.25 < n < 0.4). The above results explain recent intriguing experiments of Reiter, Phys. Rev. Lett, 87, 186101 (2001).Comment: 4 pages, 5 figures, RevTe

Slow dynamics near glass transitions in thin polymer films

The $\alpha$-process (segmental motion) of thin polystyrene films supported on glass substrate has been investigated in a wider frequency range from 10$^{-3}$ Hz to 10$^4$ Hz using dielectric relaxation spectroscopy and thermal expansion spectroscopy. The relaxation rate of the $\alpha$-process increases with decreasing film thickness at a given temperature above the glass transition. This increase in the relaxation rate with decreasing film thickness is much more enhanced near the glass transition temperature. The glass transition temperature determined as the temperature at which the relaxation time of the $\alpha$-process becomes a macroscopic time scale shows a distinct molecular weight dependence. It is also found that the Vogel temperature has the thickness dependence, i.e., the Vogel temperature decreases with decreasing film thickness. The expansion coefficient of the free volume $\alpha_f$ is extracted from the temperature dependence of the relaxation time within the free volume theory. The fragility index $m$ is also evaluated as a function of thickness. Both $\alpha_f$ and $m$ are found to decrease with decreasing film thickness.Comment: 9 pages, 7 figures, and 2 table

Prevalence and course of endocrinopathy in POEMS syndrome

CONTEXT: POEMS syndrome is a rare multisystem disorder characterised by polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma-proliferative disorder and skin changes among other features. OBJECTIVE: To describe the prevalence and course of the endocrine dysfunction in the context of POEMS. DESIGN: Cohort study with systematic review of the endocrinopathy in POEMS. SETTING: 75 patients with POEMS were evaluated by the multidisciplinary team at our tertiary specialist centre. PATIENTS: Endocrine data was available for 59 patients who attended the clinic from 06/1999 to 05/2018. INTERVENTIONS: All patients had regular endocrine screening including testing for diabetes, pituitary and thyroid dysfunction and assessment of bone metabolism. MAIN OUTCOME MEASURE: Prevalence and survival time to develop endocrinopathy in POEMS. RESULTS: Thirty-four (63%) patients presented with an endocrinopathy at point of POEMS diagnosis and 54 (92%) had at least one endocrine abnormality at follow-up. The median follow-up was 4.4[1.5, 7.9] years. The most common endocrine abnormality was hypogonadism in 68%, followed by hyperprolactinaemia (56%), hypothyroidism (54%), abnormal glucose metabolism (24%), adrenal insufficiency (17%) and high IGF-1 levels (15%). Spontaneous resolution of endocrine abnormalities at the end of follow-up was observed: 14% in hypogonadism, 42% in hyperprolactinaemia, 34% in hypothyroidism and 38% in high IGF-1 levels. CONCLUSIONS: Endocrinopathy was found in 63% of patients at diagnosis and in 92% of patients during follow-up in our cohort, therefore patients with POEMS should be systematically assessed for endocrinopathy. The most common deficiencies were hypogonadism and hypothyroidism, however normalisation of the endocrinopathy can occur so on-going treatment should remain under review

Nitrous oxide-induced myeloneuropathy: a case series.

BACKGROUND: Nitrous oxide (N2O) is the second most common recreational drug used by 16- to 24-year-olds in the UK. Neurological symptoms can occur in some people that use N2O recreationally, but most information comes from small case series. METHODS: We describe 119 patients with N2O-myeloneuropathy seen at NHS teaching hospitals in three of the UK's largest cities: London, Birmingham and Manchester. This work summarises the clinical and investigative findings in the largest case series to date. RESULTS: Paraesthesia was the presenting complaint in 85% of cases, with the lower limbs more commonly affected than the upper limbs. Gait ataxia was common, and bladder and bowel disturbance were frequent additional symptoms. The mid-cervical region of the spinal cord (C3-C5) was most often affected on MRI T2-weighted imaging. The number of N2O canisters consumed per week correlated with methylmalonic acid levels in the blood as a measure of functional B12 deficiency (rho (ρ)=0.44, p=0.04). CONCLUSIONS: Preventable neurological harm from N2O abuse is increasingly seen worldwide. Ease of access to canisters and larger cylinders of N2O has led to an apparent rise in cases of N2O-myeloneuropathy in several areas of the UK. Our results highlight the range of clinical manifestations in a large group of patients to improve awareness of risk, aid early recognition, and promote timely treatment

'You were quiet - I did all the marching': Research processes involved in hearing the voices of South Asian girls

This article is available open access through the publisher’s website at the link below. Copyright @ 2011 A B Academic Publishers.This article provides insights into the outcomes of reflection following two interview approaches used to explore narratives of the lived, individual experiences of South-Asian girls living in West London. In attempting to illuminate and re-present the cultural experiences as told by these girls, the choice of interview approach became critical in allowing the voices to be effectively heard (Rogers, 2005). This article therefore considers how a semi-structured interview approach offered valuable insights into the girls' experiences but became constraining for both researcher and participant in unveiling the complexity and depth of their lives. These constraints emerged through reflection by both participants and researcher. As a result of reflexivity during the research process, the researcher moved towards the use of research conversations during the second phase of the study. Ultimately the study revealed how the girls felt empowered by the opportunity to narrate their individual experiences and tell of their lives. In narrating their reflections on being part of the research, there was a clear recognition that the process facilitated the articulation of new voices and ‘multi-voicedness’ (Moen, 2006

‘It’s never okay to say no to teachers’: children’s research consent and dissent in conforming schools contexts

This article examines the limits to children giving research consent in everyday school contexts that emphasises their conformity to comply with adult expectations, and highlights children’s competence and agency in navigating this conformity through different practices of dissent. It draws on research into children’s agency, using a multimodal ethnography of Year 1 classrooms in two English primary schools. The article includes a reflexive methodological focus, exploring the extent to which I counter the schools’ emphasis on conformity. This includes creating visuals for children to practice consent; positioning myself as the researcher in a non‐teacher role, as ‘least adult’ and the one who ‘least knows’; and designing interview spaces markedly different from classrooms. The article examines how children navigate conforming discourses by finding different ways to dissent in the research. Firstly, children demonstrate a sophisticated awareness of the cultural norms of indicating refusals beyond saying the word ‘No’. Secondly, children achieve unnoticeablity, by which they absent themselves from the ‘on‐task’ classroom culture, and by extension the research process. Thirdly, they engage in playful dissent, demonstrating their political knowingness of the classroom social order. The article discusses the implications for educational research when the values of consent are in conflict with a schooling focused on conformity. This includes emphasising the limits of consent procedures, paying closer attention to how researchers recognise and respond ethically to children’s multiple practices of dissent, and using research to disrupt problematic power structures in education settings that limit possibilities for children’s consent

Mechanical Properties of Glassy Polyethylene Nanofibers via Molecular Dynamics Simulations

The extent to which the intrinsic mechanical properties of polymer fibers depend on physical size has been a matter of dispute that is relevant to most nanofiber applications. Here, we report the elastic and plastic properties determined from molecular dynamics simulations of amorphous, glassy polymer nanofibers with diameter ranging from 3.7 to 17.7 nm. We find that, for a given temperature, the Young’s elastic modulus E decreases with fiber radius and can be as much as 52% lower than that of the corresponding bulk material. Poisson’s ratio ν of the polymer comprising these nanofibers was found to decrease from a value of 0.3 to 0.1 with decreasing fiber radius. Our findings also indicate that a small but finite stress exists on the simulated nanofibers prior to elongation, attributable to surface tension. When strained uniaxially up to a tensile strain of ε = 0.2 over the range of strain rates and temperatures considered, the nanofibers exhibit a yield stress σy between 40 and 72 MPa, which is not strongly dependent on fiber radius; this yield stress is approximately half that of the same polyethylene simulated in the amorphous bulk.DuPont MIT AllianceDuPont (Firm) (Young Professor Award