Patients’ experiences of lupus related foot problems : a qualitative investigation

Background: Systemic lupus erythematosus (SLE) can present with a variety of symptoms. Previous research has shown there is a high prevalence of lower limb and foot problems in patients with SLE associated with the musculoskeletal, vascular and neurological changes. Furthermore, there is a high prevalence of infections affecting the feet and a range of common skin and nail problems. However, it is not known how these foot problems impact upon people’s lives. Therefore, we aimed to explore this using a qualitative approach. Method: Following ethical approval, 12 participants were recruited who had a diagnosis of SLE, current and/or past experience of foot problems and were over 18 years in age. Following consent, interviews were carried out with an interpretivist phenomenological approach to both data collection and analysis. Results: Seven themes provide insight into: foot problems and symptoms; the impact of these foot problems and symptoms on activities; disclosure and diagnosis of foot problems; treatment of foot problems and symptoms; perceived barriers to professional foot care; unanswered questions about feet and foot care; and identification of the need for professional foot care and foot care advice. Conclusion: These participants tend to “self-treat” rather than disclose that they may need professional foot care. A lack of focus upon foot health within a medical consultation is attributed to the participant’s belief that it is not within the doctor’s role, even though it is noted to contribute to reduced daily activity. There is a need for feet to be included as a part of patient monitoring and for foot health management to be made accessible for people with SLE

Cell type-specific plasticity of striatal projection neurons in parkinsonism and L-DOPA-induced dyskinesia

The striatum is widely viewed as the fulcrum of pathophysiology in Parkinson’s disease (PD) and L-DOPA-induced dyskinesia (LID). In these disease states, the balance in activity of striatal direct pathway spiny projection neurons (dSPNs) and indirect pathway spiny projection neurons (iSPNs) is disrupted, leading to aberrant action selection. However, it is unclear whether countervailing mechanisms are engaged in these states. Here we report that iSPN intrinsic excitability and excitatory corticostriatal synaptic connectivity were lower in PD models than normal; ​L-DOPA treatment restored these properties. Conversely, dSPN intrinsic excitability was elevated in tissue from PD models and suppressed in LID models. Although the synaptic connectivity of dSPNs did not change in PD models, it fell with ​L-DOPA treatment. In neither case, however, was the strength of corticostriatal connections globally scaled. Thus, SPNs manifested homeostatic adaptations in intrinsic excitability and in the number but not strength of excitatory corticostriatal synapses

Training the next generation of clinical researchers: Evaluation of a graduate podiatrist research internship in rheumatology

Background: The aim of this study was to evaluate the effectiveness of the Arthritis Research UK funded graduate internship scheme for podiatrists and to explore the experiences of interns and mentors. Methods: Nine new graduates completed the internship programme (July 2006-June 2010); six interns and two mentors participated in this study. The study was conducted in three phases. Phase 1: quantitative survey of career and research outcomes for interns. Phase 2 and 3: qualitative asynchronous interviews through email to explore the experiences of interns and mentors. Interpretive phenomenological analysis (IPA) of coded transcripts identified recurring themes. Results: Research outputs included ten peer reviewed publications with authorial contributions from interns, 23 conference abstract presentations and one subsequent 'Jewel in the Crown' award at the British Society for Rheumatology Conference. Career progression includes two National Institute for Health research (NIHR) PhD fellowships, two Arthritis Research UK PhD fellowships, one NIHR Master of Research fellowship and one specialist rheumatology clinical post. Two interns are members of NIHR and professional body committees. Seven important themes arose from the qualitative phases: perceptions of the internship pre-application; internship values; maximising personal and professional development; psychosocial components of the internship; the role of mentoring and networking; access to research career pathways; perceptions of future developments for the internship programme. The role of mentorship and the peer support network have had benefits that have persisted beyond the formal period of the scheme. Conclusions: The internship model appears to have been perceived to have been valuable to the interns' careers and may have contributed significantly to the broader building of capacity in clinical research in foot and ankle rheumatology. We believe the model has potential to be transferable across health disciplines and on national and international scales

Results of a national foot health survey of patients with Systemic Lupus Erythematosus

Background: SLE can affect many tissues throughout the body. Anecdotally, it is suggested that people with SLE experience a range of complications in the foot and lower limb, including vascular impairment (e.g. RP), neurological impairment, poor tissue viability (e.g. ulceration), infection and foot pain. However, to date, the precise prevalence of foot complications experienced by people with SLE has not been described. The aim of this survey was to determine self-reported foot and lower limb complications experienced by people with SLE. Methods: The survey was developed via patient and practitioner focus groups. A consensus approach was used to generate items and to formulate themes, categories, question format and survey structure. The survey was checked for face and content validity prior to cognitive debriefing to ensure usability and understanding. Consecutive patients with a confirmed diagnosis of SLE meeting the inclusion criteria attending any of seven UK clinical sites or members of Lupus UK were invited to participate. Ethical approval and participant informed consent was obtained. Results: A total of 182 survey responses were completed. For all responders, the most frequent age range was 40–49 years, mean BMI was 27 (S.D. 7) and mean disease duration was 15 years (S.D. 10). A number of vascular complications were reported, including intermittent claudication [n ¼ 100 (55%)], RP [n ¼ 94 (52%)] and splinter haemorrhage [n ¼ 39 (21%)]. Overall, 164 patients (90%) reported experiencing symptoms of peripheral vascular complications. Symptoms of peripheral neuropathy were reported by 30 patients (16%), while a fall as a consequence of neuropathic symptoms was reported by 45 patients (25%). A range of skin and nail complications were reported, including callus or corns [n ¼ 130 (71%)], onychocryptosis [n ¼ 69 (38%)], rashes or blistering [n ¼ 62 (34%)] and ulceration [n ¼ 45 (25%)]. A high prevalence of infection was reported; a history of viral infection (verrucae pedis) or fungal infection (tinea pedis) was reported by 77 patients (42%), bacterial infection by 28 patients (15%) and onychomycosis by 65 patients (36%). Overall, 170 patients (93%) reported having experienced some form of tissue viability complication. Foot joint pain, stiffness and swelling was reported by 145 (80%), 136 (75%) and 94 (52%) patients, respectively. Foot-related walking impairment was reported by 67 patients (37%). Only 60 patients (33%) reported having ever been asked about their feet by a medical professional. Seventy-seven patients (42%) reported that they would benefit from the provision of general foot health care advice. Conclusion: A large number of people with SLE report vascular complications, impaired tissue viability, musculoskeletal problems and foot pain, as well as a range of infections and conditions of the skin and nails. Despite this, foot health assessment by professionals was infrequent. These results highlight the need to undertake clinical studies investigating lower limb pathologies in SLE

Common measure of quality of life for people with systemic sclerosis across seven European countries: A cross-sectional study

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. Objectives the aim of this study was to adapt the Systemic Sclerosis Quality of Life Questionnaire (SScQoL) into six European cultures and validate it as a common measure of quality of life in systemic sclerosis (SSc). Methods this was a seven-country (Germany, France, Italy, Poland, Spain, Sweden and UK) cross-sectional study. A forward–backward translation process was used to adapt the English SScQoL into target languages. SScQoL was completed by patients with SSc, then data were validated against the rasch model. to correct local response dependency, items were grouped into the following subscales: function, emotion, sleep, social and pain and reanalysed for fit to the model, unidimensionality and cross-cultural equivalence. Results the adaptation of the SScQoL was seamless in all countries except Germany. Cross-cultural validation included 1080 patients with a mean age 58.0 years (Sd 13.9) and 87% were women. Local dependency was evident in individual country data. Grouping items into testlets corrected the local dependency in most country specific data. Fit to the model, reliability and unidimensionality was achieved in six-country data after cross-cultural adjustment for Italy in the social subscale. the SScQoL was then calibrated into an interval level scale. Conclusion the individual SScQoL items have translated well into five languages and overall, the scale maintained its construct validity, working well as a five-subscale questionnaire. Measures of quality of life in SSc can be directly compared across five countries (France, Poland Spain, Sweden and UK). data from Italy are also comparable with the other five countries although require an adjustment

Prediction of Emerging Technologies Based on Analysis of the U.S. Patent Citation Network

The network of patents connected by citations is an evolving graph, which provides a representation of the innovation process. A patent citing another implies that the cited patent reflects a piece of previously existing knowledge that the citing patent builds upon. A methodology presented here (i) identifies actual clusters of patents: i.e. technological branches, and (ii) gives predictions about the temporal changes of the structure of the clusters. A predictor, called the {citation vector}, is defined for characterizing technological development to show how a patent cited by other patents belongs to various industrial fields. The clustering technique adopted is able to detect the new emerging recombinations, and predicts emerging new technology clusters. The predictive ability of our new method is illustrated on the example of USPTO subcategory 11, Agriculture, Food, Textiles. A cluster of patents is determined based on citation data up to 1991, which shows significant overlap of the class 442 formed at the beginning of 1997. These new tools of predictive analytics could support policy decision making processes in science and technology, and help formulate recommendations for action

Pressure and pain In Systemic sclerosis/Scleroderma - an evaluation of a simple intervention (PISCES): randomised controlled trial protocol

Background: foot problems associated with Systemic Sclerosis (SSc)/Scleroderma have been reported to be both common and disabling. There are only limited data describing specifically, the mechanical changes occurring in the foot in SSc. A pilot project conducted in preparation for this trial confirmed the previous reports of foot related impairment and reduced foot function in people with SSc and demonstrated a link to mechanical etiologies. To-date there have been no formal studies of interventions directed at the foot problems experienced by people with Systemic Sclerosis. The primary aim of this trial is to evaluate whether foot pain and foot-related health status in people with Systemic Sclerosis can be improved through the provision of a simple pressure-relieving insole. Methods: the proposed trial is a pragmatic, multicenter, randomised controlled clinical trial following a completed pilot study. In four participating centres, 140 consenting patients with SSc and plantar foot pain will be randomised to receive either a commercially available pressure relieving and thermally insulating insole, or a sham insole with no cushioning or thermal properties. The primary end point is a reduction in pain measured using the Foot Function Index Pain subscale, 12 weeks after the start of intervention. Participants will complete the primary outcome measure (Foot Function Index pain sub-scale) prior to randomisation and at 12 weeks post randomisation. Secondary outcomes include participant reported pain and disability as derived from the Manchester Foot Pain and Disability Questionnaire and plantar pressures with and without the insoles in situ. Discussion: this trial protocol proposes a rigorous and potentially significant evaluation of a simple and readily provided therapeutic approach which, if effective, could be of a great benefit for this group of patients

Suppression of a charge density wave ground state in high magnetic fields: spin and orbital mechanisms

The charge density wave (CDW) transition temperature in the quasi-one dimensional (Q1D) organic material of (Per)$_2$Au(mnt)$_2$ is relatively low (TCDW = 12 K). Hence in a mean field BCS model, the CDW state should be completely suppressed in magnetic fields of order 30 - 40 T. To explore this possibility, the magnetoresistance of (Per)$_2$Au(mnt)$_2$ was investigated in magnetic fields to 45 T for 0.5 K < T < 12 K. For fields directed along the Q1D molecular stacking direction, TCDW decreases with field, terminating at about ~ 37 T for temperatures approaching zero. Results for this field orientation are in general agreement with theoretical predictions, including the field dependence of the magnetoresistance and the energy gap, $\Delta_{CDW}$. However, for fields tilted away from the stacking direction, orbital effects arise above 15 T that may be related to the return of un-nested Fermi surface sections that develop as the CDW state is suppressed. These findings are consistent with expectations that quasi-one dimensional metallic behavior will return outside the CDW phase boundary.Comment: 12 pages, 5 figure

Clinical trajectories of hand function impairment in systemic sclerosis: an unmet clinical need across disease subsets

Background Hand involvement is an early manifestation of systemic sclerosis (SSc), culprit of diagnosis and classification, and recognised major driver of disability. Impairment of hand function burdens both limited and diffuse cutaneous subsets and therefore could be targeted as ‘basket’ endpoint in SSc. Nevertheless, its natural history in current standard of care is not well characterised, limiting the design of targeted trials. The aim of this study is to describe prevalence, natural history and clinical factors associated with hand function deterioration in a longitudinal, multicentre, observational SSc cohort. Methods Hand function was captured through the validated Cochin Hand Function Scale in patients consecutively enrolled in a multicentre observational study and observed over 24 months. Minimal clinically important differences and patient acceptable symptom state were analysed as previously described. Results Three hundred and ninety-six consecutive patients were enrolled from 10 centres; 201 with complete follow-up data were included in the analysis. Median (IQR) disease duration was 5 (2–11) years. One hundred and five (52.2%) patients reported clinically significant worsening. Accordingly, the proportion of patients reporting unacceptable hand function increased over 2 years from 27.8% to 35.8% (p<0.001). Least absolute shrinkage and selection operator analysis identified male gender, disease subset, Raynaud’s Condition Score, tenosynovitis and pain, as some of the key factors associated with worsening hand involvement. Conclusions Hand function deteriorates over time in more than 50% of SSc patients despite available therapies. The analysis of factors associated with hand function worsening supports the involvement of both inflammation, vascular and fibrotic processes in hand involvement, making it a hallmark clinical manifestation of SSc. Our data are poised to inform the design of intervention studies to target this major driver of disability in SSc

Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson's disease

Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa (L-dopa) therapy for Parkinson's disease (PD). L-dopa-induced dyskinesia (LID) are ultimately experienced by the vast majority of patients. In addition, psychiatric conditions often manifested as compulsive behaviours, are emerging as a serious problem in the management of L-dopa therapy. The present review attempts to provide an overview of our current understanding of dyskinesia and other L-dopa-induced dysfunctions, a field that dramatically evolved in the past twenty years. In view of the extensive literature on LID, there appeared a critical need to re-frame the concepts, to highlight the most suitable models, to review the central nervous system (CNS) circuitry that may be involved, and to propose a pathophysiological framework was timely and necessary. An updated review to clarify our understanding of LID and other L-dopa-related side effects was therefore timely and necessary. This review should help in the development of novel therapeutic strategies aimed at preventing the generation of dyskinetic symptoms