The impact of rheumatoid arthritis on foot function in the early stages of disease: a clinical case series

BACKGROUND Foot involvement occurs early in rheumatoid arthritis but the extent to which this impacts on the structure and function leading to impairment and foot related disability is unknown. The purpose of this study was to compare clinical disease activity, impairment, disability, and foot function in normal and early rheumatoid arthritis (RA) feet using standardised clinical measures and 3D gait analysis. METHODS Twelve RA patients with disease duration ≤2 years and 12 able-bodied adults matched for age and sex underwent 3D gait analysis to measure foot function. Disease impact was measured using the Leeds Foot impact Scale (LFIS) along with standard clinical measures of disease activity, pain and foot deformity. For this small sample, the mean differences between the groups and associated confidence intervals were calculated using the t distribution RESULTS Moderate-to-high foot impairment and related disability were detected amongst the RA patients. In comparison with age- and sex-matched controls, the patients with early RA walked slower (1.05 m/s Vs 1.30 m/s) and had a longer double-support phase (19.3% Vs 15.8%). In terminal stance, the heel rise angle was reduced in the patients in comparison with normal (-78.9° Vs -85.7°). Medial arch height was lower and peak eversion in stance greater in the RA patients. The peak ankle plantarflexion power profile was lower in the patients in comparison with the controls (3.4 W/kg Vs 4.6 W/kg). Pressure analysis indicated that the RA patients had a reduced lesser toe contact area (7.6 cm2 Vs 8.1 cm2), elevated peak forefoot pressure (672 kPa Vs 553 kPa) and a larger mid-foot contact area (24.6 cm2 Vs 19.4 cm2). CONCLUSION Analysis detected small but clinically important changes in foot function in a small cohort of RA patients with disease duration <2 years. These were accompanied by active joint disease and impairment and disability

Syntheses and Properties of Two-Dimensional, Dicationic Nonlinear Optical Chromophores Based on Pyrazinyl Cores

Six new dicationic 2D nonlinear optical (NLO) chromophores with pyrazinyl-pyridinium electron acceptors have been synthesized by nucleophilic substitutions of 2,6-dichloropyrazine with pyridyl derivatives. These compounds have been characterized as their PF_6^− salts by using various techniques including electronic absorption spectroscopy and cyclic voltammetry. Large red shifts in the intense, π → π* intramolecular charge-transfer (ICT) transitions on replacing −OMe with –Nme_2 substituents arise from the stronger π-electron donor ability of the latter. Each compound shows a number of redox processes which are largely irreversible. Single crystal X-ray structures have been determined for five salts, including two nitrates, all of which adopt centrosymmetric packing arrangements. Molecular first hyperpolarizabilities β have been determined by using femtosecond hyper-Rayleigh scattering at 880 and 800 nm, and depolarization studies show that the NLO responses of the symmetric species are strongly 2D, with dominant “off-diagonal” β_(zyy) components. Stark (electroabsorption) spectroscopic measurements on the ICT bands afford estimated static first hyperpolarizabilities β_0. The directly and indirectly derived β values are large, and the Stark-derived β_0 response for one of the new salts is several times greater than that determined for (E)-4′-(dimethylamino)-N-methyl-4-stilbazolium hexafluorophosphate. These Stark spectroscopic studies also permit quantitative comparisons with related 2D, binuclear RuII ammine complex salts

Syntheses and Properties of Salts of Chromophores with Ferrocenyl Electron Donor Groups and Quaternary Nitrogen Acceptors

A series of five new dipolar cations has been synthesized with ferrocenyl (Fc) electron donor groups connected to N-arylpyridinium, N-methylquinolinium, N-methylbenzothiazolium, or N-methylacridinium acceptors. Together with their known N-methylpyridinium analogue, these chromophores have been characterized as their PF_6^− salts by using various techniques including electronic absorption spectroscopy and cyclic voltammetry. Nine single-crystal X-ray structures have been determined, including two polymorphs of one salt obtained from a single crystallization experiment, and two of these are polar materials. A highly favorable degree of dipolar alignment for bulk NLO effects is observed in one case. Molecular quadratic nonlinear optical (NLO) responses have been determined by using femtosecond hyper-Rayleigh scattering (HRS) at 1300 nm and also via Stark (electroabsorption) spectroscopic studies on the intense π → π^* intraligand and d → π^* metal-to-ligand charge-transfer bands. A broad correlation between the electron acceptor strength and the HRS-derived first hyperpolarizabilities β and the static first hyperpolarizabilities β0 estimated from the Stark data is evident. This is the first time that meaningful (albeit indirectly determined) β_0 data have been reported for Fc compounds, allowing quantitative comparisons with the chromophore in the technologically important material (E)-4′-(dimethylamino)-N-methyl-4-stilbazolium (DAS) tosylate. The observed β_0 values are in several cases similar to that of [DAS]PF_6, and possibly even larger in one instance

Quadratic and Cubic Nonlinear Optical Properties of Salts of Diquat-Based Chromophores with Diphenylamino Substituents

A series of chromophoric salts has been prepared in which 4-(diphenylamino)phenyl (Dpap) electron donor groups are connected to electron-accepting diquaternized 2,2′-bipyridyl (diquat) units. The main aim is to combine large quadratic and cubic nonlinear optical (NLO) effects in potentially redox-switchable molecules with 2D structures. The chromophores have been characterized as their PF_6^− salts by using various techniques including electronic absorption spectroscopy and cyclic voltammetry. The visible absorption spectra are dominated by intense π → π* intramolecular charge-transfer (ICT) bands, and all of the compounds show two reversible or quasireversible diquat-based reductions and partially reversible Dpap oxidations. Single crystal X-ray structures have been obtained for one salt and for the precursor compound (E)-4-(diphenylamino)cinnamaldehyde, both of which adopt centrosymmetric space groups. First hyperpolarizabilities β have been measured by using hyper-Rayleigh scattering (HRS) with a 800 nm laser, and Stark (electroabsorption) spectroscopy of the ICT bands affords estimated static first hyperpolarizabilities β_0. The directly and indirectly derived β values are large and generally increased substantially for the bis-Dpap derivatives when compared with their monosubstituted analogues. Polarized HRS studies show that the NLO responses of the disubstituted species are dominated by “off-diagonal” β_(zyy) components. Lengthening the diquaternizing alkyl unit lowers the electron-acceptor strength and therefore increases the ICT energies and decreases the E_(1/2) values for diquat reduction. However, compensating increases in the ICT intensity prevent significant decreases in the Stark-based β_0 responses. Cubic NLO properties have been measured by using the Z-scan technique over a wavelength range of 520−1600 nm, revealing relatively high two-photon absorption cross-sections of up to 730 GM at 620 nm for one of the disubstituted chromophores

The time-dependent accumulation of protoporphyrin IX fluorescence in nodular basal cell carcinoma following application of methyl aminolevulinate with an oxygen pressure injection device

Clinical TrialJournal ArticleAuthor's post-print is subject to a Creative Commons Attribution Non-Commercial No Derivatives LicenseTopical protoporphyrin (PpIX)-induced photodynamic therapy (PDT) relies on the penetration of the prodrug into the skin lesion and subsequent accumulation of the photosensitizer. Methyl aminolevulinate (MAL)-PDT is an established treatment for thinner and superficial non-melanoma skin cancers (NMSCs) but for the treatment of the thicker nodular basal cell carcinoma (nBCC) enhanced penetration of the prodrug is required. This study employed a new higher pressure, oxygen pressure injection (OPI) device, at the time of Metvix® application with a view to enhancing the penetration of MAL into the tumors. Each patient had Metvix® applied to a single nBCC followed by application of a higher pressure OPI device. Following different time intervals (0, 30, 60, 120 or 180 min) the tumors were excised. The maximum depth and area of MAL penetration achieved in each lesion was measured using PpIX fluorescence microscopy. As expected, an increase in the depth of MAL-induced PpIX accumulation and area of tumor sensitized was observed over time; when the Metvix® cream was applied for 0, 30, 60, 120 and 180 min the median depth of PpIX fluorescence was 0%, 21%, 26.5%, 75.5% and 90%, respectively and the median area of tumor sensitized was 0%, 4%, 6%, 19% and 60%, respectively. As the investigation presented here did not include a control arm, the relative depths of fluorescence observed in this study were statistically compared (using the non-parametric Mann Whitney U test) with the results of our previous study where patients had Metvix® cream applied either with or without the standard pressure OPI device. When the higher pressure OPI device was employed compared to without OPI this increase was observed to be greater following 30, 120, and 180 min although overall not significantly (p=0.835). In addition, no significant difference between the higher pressure OPI device employed here and the previously investigated standard pressure OPI device was observed (p=0.403). However, when the results for both OPI devices were combined and compared to the standard treatment (no OPI employed) group, although the difference did not reach significance (p=0.531) a consistent and substantial increase in the depth of PpIX fluorescence was observed, therefore employment of an OPI device during topical MAL-PDT protocols warrants further investigation as a technique for enhancing MAL penetration

Energy Production in the Formation of a Finite Thickness Cosmic String

The classical electromagnetic modes outside a long, straight, superconducting cosmic string are calculated, assuming the string to be surrounded by a superconducting cylindric surface of radius R. Thereafter, by use of a Bogoliubov-type argument, the electromagnetic energy W produced per unit length in the lowest two modes is calculated when the string is formed "suddenly". The essential new element in the present analysis as compared with prior work of Parker [Phys. Rev. Lett. {\bf 59}, 1369 (1987)] and Brevik and Toverud [Phys. Rev. D {\bf 51}, 691 (1995)], is that the radius {\it a} of the string is assumed finite, thus necessitating Neumann functions to be included in the fundamental modes. We find that the theory is changed significantly: W is now strongly concentrated in the lowest mode $(m,s)=(0,1)$, whereas the proportionality $W \propto (G\mu /t)^2$ that is characteristic for zero-width strings is found in the next mode (1,1). Here G is the gravitational constant, $\mu$ the string mass per unit length, and t the GUT time.Comment: 20 pages, LaTeX, no figure

Tofacitinib in Patients With Psoriatic Arthritis and Metabolic Syndrome: A Post hoc Analysis of Phase 3 Studies

Objective: Metabolic syndrome (MetS) is a cluster of concurrent risk factors for cardiovascular disease and type 2 diabetes. This post hoc analysis explored key efficacy and safety endpoints in patients with psoriatic arthritis (PsA) and MetS treated with tofacitinib. Methods: Tofacitinib 5 and 10 mg twice daily and placebo data were pooled from two Phase 3 studies (OPAL Broaden [12 months; ClinicalTrials.gov identifier NCT01877668]; OPAL Beyond [6 months; ClinicalTrials.gov identifier NCT01882439]); patients received one background conventional synthetic disease‐modifying antirheumatic drug. Patients were stratified by baseline presence/absence of MetS. Efficacy and safety were reported to month 3 (tofacitinib and placebo) and 6 (tofacitinib only). Efficacy outcomes included: American College of Rheumatology (ACR)20/50/70, Health Assessment Questionnaire‐Disability Index (HAQ‐DI) response, Psoriasis Area Severity Index (PASI)75 response, and enthesitis/dactylitis resolution rates; and changes from baseline (Δ) in C‐reactive protein, HAQ‐DI, Patient’s/Physician’s Global Assessment of Arthritis, and patient‐reported outcomes. Safety outcomes included treatment‐emergent all‐causality adverse events (AEs), Δ in lipid/hepatic values, and liver parameter increases. Results: Of 710 patients, 41.4% (n = 294) had baseline MetS. All efficacy outcomes improved with both tofacitinib doses versus placebo, to month 3; tofacitinib efficacy was consistent to month 6, regardless of MetS status. MetS did not appear to affect the incidence of AEs or Δ in lipid/hepatic values with tofacitinib up to month 3 or 6. Arterial thromboembolism and myocardial infarction (adjudicated major adverse cardiovascular events) were each reported once in tofacitinib‐treated patients with MetS. Conclusion: Regardless of baseline MetS status, tofacitinib showed greater efficacy versus placebo in patients with active PsA. The tofacitinib safety profile appeared similar in patients with versus without MetS

'Choosing shoes': a preliminary study into the challenges facing clinicians in assessing footwear for rheumatoid patients

Background: Footwear has been accepted as a therapeutic intervention for the foot affected by rheumatoid arthritis (RA). Evidence relating to the objective assessment of footwear in patients with RA is limited. The aims of this study were to identify current footwear styles, footwear characteristics, and factors that influence footwear choice experienced by patients with RA. Methods: Eighty patients with RA were recruited from rheumatology clinics during the summer months. Clinical characteristics, global function, and foot impairment and disability measures were recorded. Current footwear, footwear characteristics and the factors associated with choice of footwear were identified. Suitability of footwear was recorded using pre-determined criteria for assessing footwear type, based on a previous study of foot pain. Results: The patients had longstanding RA with moderate-to severe disability and impairment. The foot and ankle assessment demonstrated a low-arch profile with both forefoot and rearfoot structural deformities. Over 50% of shoes worn by patients were opentype footwear. More than 70% of patients’ footwear was defined as being poor. Poor footwear characteristics such as heel rigidity and sole hardness were observed. Patients reported comfort (17%) and fit (14%) as important factors in choosing their own footwear. Only five percent (5%) of patients wore therapeutic footwear. Conclusions: The majority of patients with RA wear footwear that has been previously described as poor. Future work needs to aim to define and justify the specific features of footwear that may be of benefit to foot health for people with RA

Vacuum Polarization in the Spacetime of a Scalar-Tensor Cosmic String

We study the vacuum polarization effect in the spacetime generated by a magnetic flux cosmic string in the framework of a scalar-tensor gravity. The vacuum expectation values of the energy-momentum tensor of a conformally coupled scalar field are calculated. The dilaton's contribution to the vacuum polarization effect is shown explicitly.Comment: 11 pages, LATEX file, 2 eps figure

Exercise therapy after corticosteroid injection for moderate to severe shoulder pain: large pragmatic randomised trial

Objective To compare the effectiveness of subacromial corticosteroid injection combined with timely exercise and manual therapy (injection plus exercise) or exercise and manual therapy alone (exercise only) in patients with subacromial impingement syndrome