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

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

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

Working through the pain… and getting on with it — some patients’ experiences of living with Lupus-related foot problems

Background: Along with its skin manifestations, SLE can present with a variety of musculoskeletal signs and symptoms and vascular problems that can affect the feet. Furthermore, there is the potential for reduced tissue viability, leading to thinning of the skin and/or callus formation. Further, systemic resistance to viral, bacterial and fungal infections may be reduced and, together with poor tissue viability, create the opportunity for these infections to proliferate in the feet. A recent survey by the same authors (unpublished) has shown a high prevalence of these infections, with many experiencing the impact of vascular and musculoskeletal problems. To date there is no research that has explored the impact of foot problems on people’s lives. Methods: Following ethical approval, 12 participants who fulfilled the inclusion criteria were recruited: diagnosed with SLE (ACR diagnosis), current and/or past experience of foot/lower limb problems and age �18 years. Consent was obtained and then conversational-style interviews were carried out with an interpretivistic phenomenological approach. The interviews were digitally recorded and complemented by field notes. An opening question was used for all participants: ‘Tell me about your experiences of having foot problems?’ If necessary, further trigger questions were used in order to maintain the conversation and the focus on foot problems. Data were transcribed verbatim and analysed using a thematic framework approach. The transcripts were verified by the participants and were analysed by a second researcher in order to add to the credibility of the analyses. Results: The data was organized into seven themes: Foot problems and symptoms—what they are and the feeling associated with them; Experiences of foot problems being diagnosed; Impact of foot problems on activities; Treatment of foot symptoms/problems; Perceived obstacles to professional foot care; Unanswered questions about feet and foot care; and Recognition of the need for professional foot care and foot care advice. These people experienced a wide variety of foot problems that impact significantly on activities. Some reported working through the pain in order to achieve visible normality while experiencing the negative emotions of anger, frustration and anxiety. Although some had experienced professional foot care, there were obstacles to the foot problems being diagnosed, resulting in many unanswered questions and some inappropriate selfmanagement. Conclusion: Despite reporting foot pain, negative emotions and activity restrictions related to their foot symptoms, people with SLE tend to get on with it and self-treat rather than seeking professional foot care. The lack of focus on the feet in the medical consultation is caused by the participants’ belief that it is not the consultant’s role. There is a clear need for foot assessments to be included in the medical consultation and for professional foot care to be provided

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

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

Optostimulation of striatonigral terminals in substantia nigra induces dyskinesia that increases after L‐DOPA in a mouse model of Parkinson's disease

Background and Purpose: L-DOPA-induced dyskinesia (LID) remains a major complication of L-DOPA therapy in Parkinson's disease. LID is believed to result from inhibition of substantia nigra reticulata (SNr) neurons by GABAergic striatal projection neurons that become supersensitive to dopamine receptor stimulation after severe nigrostriatal degeneration. Here, we asked if stimulation of direct medium spiny neuron (dMSN) GABAergic terminals at the SNr can produce a full dyskinetic state similar to that induced by L-DOPA. Experimental Approach: Adult C57BL6 mice were lesioned with 6-hydroxydopamine in the medial forebrain bundle. Channel rhodopsin was expressed in striatonigral terminals by ipsilateral striatal injection of adeno-associated viral particles under the CaMKII promoter. Optic fibres were implanted on the ipsilateral SNr. Optical stimulation was performed before and 24 hr after three daily doses of L-DOPA at subthreshold and suprathreshold dyskinetic doses. We also examined the combined effect of light stimulation and an acute L-DOPA challenge. Key Results: Optostimulation of striatonigral terminals inhibited SNr neurons and induced all dyskinesia subtypes (optostimulation-induced dyskinesia [OID]) in 6-hydroxydopamine animals, but not in sham-lesioned animals. Additionally, chronic L-DOPA administration sensitised dyskinetic responses to striatonigral terminal optostimulation, as OIDs were more severe 24 hr after L-DOPA administration. Furthermore, L-DOPA combined with light stimulation did not result in higher dyskinesia scores than OID alone, suggesting that optostimulation has a masking effect on LID. Conclusion and Implications: This work suggests that striatonigral inhibition of basal ganglia output (SNr) is a decisive mechanism mediating LID and identifies the SNr as a target for managing LID.Fil: Keifman, Ettel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Consejo Superior de Investigaciones Científicas; EspañaFil: Ruiz De Diego, Irene. Consejo Superior de Investigaciones Científicas; EspañaFil: Pafundo, Diego Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Paz, Rodrigo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Solís, Oscar. Consejo Superior de Investigaciones Científicas; EspañaFil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Moratalla, Rosario. Consejo Superior de Investigaciones Científicas; Españ