Foot ulcer recurrence, plantar pressure and footwear adherence in people with diabetes and Charcot midfoot deformity: A cohort analysis.

AIMS: To investigate people with Charcot midfoot deformity with regard to plantar pressure, footwear adherence and plantar foot ulcer recurrence. METHODS: Twenty people with diabetes, Charcot midfoot deformity, plantar foot ulcer history and custom-made footwear were assessed with regard to barefoot and in-shoe plantar pressures during walking, footwear adherence (% of daily steps over 7-day period) and plantar foot ulcer recurrence over 18 months. In a cohort design, they were compared to 118 people without Charcot foot (non-Charcot foot group) with custom-made footwear and similar ulcer risk factors. RESULTS: Median (interquartile range) barefoot midfoot peak pressures were significantly higher in the Charcot foot group than in the non-Charcot foot group [756 (260-1267) vs 146 (100-208) kPa; P<0.001]. In-shoe midfoot peak pressures were not significantly higher in the Charcot foot group [median (interquartile range) 152 (104-201) vs 119 (94-160) kPa] and significantly lower for all other foot regions. Participants in the Charcot foot group were significantly more adherent, especially at home, than participants in the non-Charcot foot group [median (interquartile range) 94.4 (85.4-95.0)% vs. 64.3 (25.4-85.7)%; P=0.001]. Ulcers recurred in 40% of the Charcot foot group and in 47% of the non-Charcot foot group (P=0.63); midfoot ulcers recurred significantly more in the Charcot foot group (4/8) than in the non-Charcot foot group (1/55; P=0.001). CONCLUSIONS: Effective offloading and very high footwear adherence were found in people with diabetes and Charcot midfoot deformity. While this may help protect against plantar foot ulcer recurrence, a large proportion of such people still experience ulcer recurrence. Further improvements in adherence and custom-made footwear design may be required to improve clinical outcome.

Oxygen cost of walking, physical activity, and sedentary behaviours in rheumatoid arthritis.

OBJECTIVES: To evaluate the oxygen cost of gait and measure physical activity profiles, including time spent sedentary, in people with rheumatoid arthritis (RA) and matched controls. METHOD: We recruited 19 people with RA and 19 controls matched for age, sex, and body mass index (BMI). Demographic details and clinical characteristics of the RA population were recorded. Oxygen uptake per metre walked (oxygen cost) was measured in the laboratory using a portable gas analyser. Activity profiles including the number of steps per day, time spent sedentary (sitting or lying down), and intensity of walking were recorded over 5 days using an activity monitor, from which physical activity was classified by intensity categories. Levels of pain, fatigue, anxiety, and depression were recorded. RESULTS: People with RA walked with a slower self-selected gait speed (p < 0.001) than controls but there was no difference in the oxygen cost of walking (p = 0.992) between the groups. People with RA took fewer steps (p < 0.001), had increased sedentary time (p = 0.029) and lower time walking at cadences commensurate with moderate to vigorous physical activity (MVPA) compared to controls (p < 0.001). Pain, fatigue, and depression were higher in the RA group (all p < 0.001). CONCLUSIONS: The oxygen cost of walking in this cohort of people with RA was similar to that of matched controls but there was an increase in time spent sedentary and a reduction in time spent at cadences commensurate with MVPA. Clinical symptoms such as depression, pain, and fatigue may explain the changes in activity/sedentary behaviours in people with RA and require further investigation.

Achilles tendon biomechanics in psoriatic arthritis patients with ultrasound proven enthesitis.

OBJECTIVE: To investigate Achilles tendon (AT) biomechanics in psoriatic arthritis (PsA) patients with ultrasound confirmed features of enthesitis. METHOD: PsA patients and healthy control subjects underwent three-dimensional (3D) gait analysis to measure walking speed, rotational joint motion and the moments, power, and AT force at the ankle-subtalar joint complex. The Glasgow Ultrasound Enthesitis Scoring System (GUESS) was used to score the presence of enthesophytes, erosions, retrocalcaneal bursitis, and tendon thickening. Power Doppler ultrasound signal (PDUS) was used to detect active disease. Peripheral joint arthritis, acute-phase reactants, global health, disability, and foot impairments were recorded. A core set of biomechanical variables that influence the insertion of the AT and indirect estimates of tendon loading were compared between PsA patients and control subjects with and without enthesitis. RESULTS: Forty-two PsA patients with a mean disease duration of 10.6 (SD 9.4) years and 29 control subjects were studied. Seventeen (40%) PsA patients had clinically detectable AT entheseal pain. Twenty-eight (67%) PsA patients and nine (31%) control subjects had one or more GUESS enthesitis features, predominantly enthesophytes. PsA patients with enthesitis walked significantly more slowly than control subjects (p = 0.019) and generated lower peak ankle joint moments (p = 0.006), power (p = 0.001), and AT force (p = 0.003). Ankle-subtalar joint complex motion was comparable and no between-group differences were found for peak dorsiflexion (p = 0.59), eversion (p = 0.05), and internal rotation (p = 0.19). CONCLUSIONS: In this group of PsA patients, the AT insertional angle was not influenced by ankle-subtalar joint motion in those with and without enthesitis. Moreover, the PsA patients with enthesitis had significantly lower AT loading.

Effect of lateral wedged insoles on the knee internal contact forces in medial knee osteoarthritis.

BACKGROUND: Lateral wedge insoles (LWIs) are non-surgical interventions used in medial knee osteoarthritis (KOA) aiming at restoring correct joint biomechanics. However, the mechanical efficacy of LWIs, based on modulation of the external knee adduction moment, is partially proved and high variability in response to these devices was observed. RESEARCH QUESTION: The principal aim of the study was to employ subject-specific musculoskeletal models to investigate the immediate effect of LWIs on the medial compressive force (MCF) in a population with medial KOA and varus alignment. METHODS: Fifteen adults (8 healthy controls age 56±3.4, BMI 25.2±2.2, hip-knee-ankle angle -1.3±2.3; and 7 KOA participants age 62±6.6, BMI 31.7±3.9, hip-knee-ankle angle 6.3±2) were recruited. Subject-specific LWIs were designed in CAD based on shape capture of the foot and manufactured via 3D printing. The required degree of heel post was added to the orthotic shell to create insoles with 0°, 5° and 10° of lateral wedge. Gait data were collected for each condition and a musculoskeletal model implemented in the Anybody Modeling System estimated the CFs normalised per bodyweight. The effect of the LWIs with respect to the baseline on the peak and the impulse of the MCF were tested with a Wilcoxon non-parametric test for paired samples. RESULTS: For the KOA group, LWIs did not reduce significantly the impulse and the peak of the MCF. No dose-response trend according to the degree of wedging was observed. A high inter-subject variability was found: the impulse of the MCF varied between -12%, +10%, the peak between -5%, +7%. Moreover, LWIs had no consistent effect on shifting the load from the medial to the lateral compartment. SIGNIFICANCE: Subject-specific response to LWIs in a cohort of medial KOA patients was observed. Further studies are necessary to maximise the mechanical effect of LWIs on restoring normal knee joint mechanics.

Gait alteration strategies for knee osteoarthritis: a comparison of joint loading via generic and patient-specific musculoskeletal model scaling techniques.

Gait modifications and laterally wedged insoles are non-invasive approaches used to treat medial compartment knee osteoarthritis. However, the outcome of these alterations is still a controversial topic. This study investigates how gait alteration techniques may have a unique effect on individual patients; and furthermore, the way we scale our musculoskeletal models to estimate the medial joint contact force may influence knee loading conditions. Five patients with clinical evidence of medial knee osteoarthritis were asked to walk at a normal walking speed over force plates and simultaneously 3D motion was captured during seven conditions (0°-, 5°-, 10°-insoles, shod, toe-in, toe-out, and wide stance). We developed patient-specific musculoskeletal models, using segmentations from magnetic resonance imaging to morph a generic model to patient-specific bone geometries and applied this morphing to estimate muscle insertion sites. Additionally, models were created of these patients using a simple linear scaling method. When examining the patients' medial compartment contact force (peak and impulse) during stance phase, a 'one-size-fits-all' gait alteration aimed to reduce medial knee loading did not exist. Moreover, the different scaling methods lead to differences in medial contact forces; highlighting the importance of further investigation of musculoskeletal modeling methods prior to use in the clinical setting.

The optimal assessment of the rheumatoid arthritis hindfoot: a comparative study of clinical examination, ultrasound and high field MRI.

OBJECTIVES: The aim of this pilot study was to compare clinical examination (CE) and ultrasound (US) with high field MRI (as the reference standard) for the detection of rearfoot and midtarsal joint synovitis and secondly tenosynovitis of the ankle tendons in patients with established rheumatoid arthritis (RA). METHODS: Patients with RA (as determined by the modified American College of Rheumatology (ACR) criteria) with symptoms of midfoot and rearfoot disease were recruited. Demographic data were collected. All underwent CE, US and high field MRI (with intravenous gadolinium contrast) of their right foot. Percentage exact agreement (PEA), sensitivity and specificity were calculated for CE and US when compared to MRI. Inter-reader reliability for CE and US was also assessed. RESULTS: Compared to the gold standard of MRI, for CE (joint synovitis) the ranges for sensitivity, specificity and PEA were 55-83%, 23-46% and 46-60%, and for US were 64-89%, 60-80% and 64-78%, respectively. Compared to the gold standard of MRI, for CE (tenosynovitis) the ranges for sensitivity, specificity and PEA were 0-100%, 20-91% and 55-91%, and for US were 0-67%, 86-100% and 59-86%, respectively. CONCLUSION: CE was sensitive but US more specific in identifying hindfoot pathology in RA when compared to the reference standard of MRI. There was poor interobserver variability between ultrasonographers suggesting a need for standardisation of acquisition and interpretation of US images of the hindfoot.

Biomechanics of the foot in rheumatoid arthritis: identifying abnormal function and the factors associated with localised disease 'impact'.

BACKGROUND: Rheumatoid arthritis is a chronic inflammatory joint disease which affects the joints and soft-tissues of the foot and ankle. The aim of this study was to evaluate biomechanical foot function and determine factors associated with localised disease burden in patients with this disease. METHODS: Seventy-four rheumatoid arthritis patients (mean (standard deviation) age, 56 years (12); median (interquartile range) disease duration, 13 (5,19)) and 54 able-bodied adults (mean (standard deviation) age, 55 years (12)) completed the Leeds foot impact scale. Biomechanical foot function was measured using three-dimensional instrumented gait analysis. Disease activity score, the number of swollen and tender foot joints, and rearfoot and forefoot deformity were recorded. Sequential multiple linear regression was undertaken to identify independent predictors of foot disease burden. FINDINGS: The median (interquartile range) Leeds foot impact scale scores in the impairment and activity/participation subscales were 13 (10,14) and 17 (12,22) for the rheumatoid arthritis and 1 (0,3) and 0 (0,1) for the able-bodied adults, P<0.0001 both subscales. The patients had significantly higher numbers of swollen (P<0.0001) and tender foot joints (P<0.0001) and greater rearfoot (P<0.0001) and forefoot (P<0.0001) deformity. Rheumatoid arthritis patients walked slower (P<0.0001) and had altered biomechanical foot function. Sequential regression analysis revealed that when the effects of global disease activity and disease duration were statistically controlled for, foot pain, the number of swollen foot joints and walking speed, and foot pain and walking speed were able to predict disease burden on the Leeds foot impact scale impairment (P<0.0005) and Leeds foot impact scale activity/participation (P<0.0005) subscales, respectively. INTERPRETATION: In this cohort of rheumatoid arthritis patients, foot pain, swollen foot joint count and walking speed were identified as independent predictors of impairment and activity limitation and participation restriction. The foot disease burden model comprises important elements of pain, inflammatory and functional (biomechanical) factors.

Virtually optimized insoles for offloading the diabetic foot: A randomized crossover study.

Integration of objective biomechanical measures of foot function into the design process for insoles has been shown to provide enhanced plantar tissue protection for individuals at-risk of plantar ulceration. The use of virtual simulations utilizing numerical modeling techniques offers a potential approach to further optimize these devices. In a patient population at-risk of foot ulceration, we aimed to compare the pressure offloading performance of insoles that were optimized via numerical simulation techniques against shape-based devices. Twenty participants with diabetes and at-risk feet were enrolled in this study. Three pairs of personalized insoles: one based on shape data and subsequently manufactured via direct milling; and two were based on a design derived from shape, pressure, and ultrasound data which underwent a finite element analysis-based virtual optimization procedure. For the latter set of insole designs, one pair was manufactured via direct milling, and a second pair was manufactured through 3D printing. The offloading performance of the insoles was analyzed for forefoot regions identified as having elevated plantar pressures. In 88% of the regions of interest, the use of virtually optimized insoles resulted in lower peak plantar pressures compared to the shape-based devices. Overall, the virtually optimized insoles significantly reduced peak pressures by a mean of 41.3kPa (p<0.001, 95% CI [31.1, 51.5]) for milled and 40.5kPa (p<0.001, 95% CI [26.4, 54.5]) for printed devices compared to shape-based insoles. The integration of virtual optimization into the insole design process resulted in improved offloading performance compared to standard, shape-based devices. CLINICAL TRIAL REGISTRATION: ISRCTN19805071, www.ISRCTN.org.

The epidermal growth factor receptor and its inhibition in cancer therapy.

Much effort has been expended in the search for inhibitors of signalling molecules that may prove to be important therapeutically in cancer. The epidermal growth factor receptor (EGFR) family and their associated ligands has been one such area extensively investigated. The complex nature of EGFR biology allows for potential opportunities for EGFR inhibitors in a number of areas of cancer therapy, including proliferative, angiogenic, invasive, and metastatic aspects. Much positive evidence of likely benefit has already been gathered from a multiplicity of laboratory experiments. Clinical trials are now urgently required to further evaluate the advantages of such agents.

ICI 176,334: a novel non-steroidal, peripherally selective antiandrogen.

Pure antiandrogens, like flutamide, antagonize androgen action both peripherally and centrally at the hypothalamic-pituitary axis, which leads to an increase in LH and testosterone secretion. A new non-steroidal antiandrogen ICI 176,334 [2RS)-4'-cyano-3-(4-fluorophenylsulphonyl)-2-hydroxy-2-methyl-3'- trifluoromethyl)propion-anilide) has now been discovered which causes regression of the accessory sex organs but does not increase serum concentrations of LH and androgens. ICI 176,334 binds to rat prostate androgen receptors with an affinity around fourfold that of hydroxyflutamide. When administered s.c. concurrently with testosterone propionate (200 micrograms/kg) for 7 days to immature castrated rats, ICI 176,334 (10 mg/kg) significantly (P less than 0.001) inhibited growth of the seminal vesicles and ventral prostate gland. Oral administration of ICI 176,334 at doses of 1, 5 and 25 mg/kg for 14 days to adult rats caused a dose-related reduction in accessory sex organ weights but had no effect on the testes. None of these doses caused a significant increase in serum LH and testosterone. Flutamide was around fourfold less potent and significantly increased serum LH and testosterone at the higher doses. ICI 176,334 was well tolerated. ICI 176,334 should, therefore, prove useful for the treatment of androgen-responsive benign and malignant diseases.

Nonsteroidal progestins and antiprogestins related to flutamide.

From the dual progestin/antiandrogenic properties of certain synthetic steroids (e.g. cyproterone acetate), it was apparent that the progesterone (P) and androgen (A) receptors must have some common ligand binding features. The nonsteroidal antiandrogen (aA) hydroxyflutamide was therefore considered a possible starting point for medicinal chemistry aimed at antiprogestin (aP) activity. Various modifications to the side chain and aryl ring substituents of flutamide yielded both P and aP activity, but always coupled with varying degrees of A or aA activity. Mineralocorticoid activity was present in some structures, but glucocorticoid and antiglucorticoid activities were not detected. Species (rat, rabbit and monkey) and chiral differences presented formidable difficulties in developing simple structure activity patterns, and low ( < 1%) in vitro uterine receptor binding belied in vivo potency of some aPs. One of the most active aPs, ZM172406, the R enantiomer of ZM150271, N-(3-chloro-4-cyanophenyl)-3,3, 3-trifluoro-2-hydroxy-2-methylpropanamide, had comparable oral potency to mifepristone in rats and monkeys. The racemate ZM150271 was an effective abortifacient during early pregnancy in pigtailed monkeys (3 x 10 mg/kg) but less effective in cynomolgus monkeys. One of the most active progestins (Pn), ZM182345, N-(4-nitro-3-trifluoromethylphenyl)-4-phenyl-2-hydroxy-2-trifluoromet hyl-pentanamide, was at least as potent as P in rats and rabbits but also possessed A activity.

The risk of foot ulceration in people with diabetes screened in community settings: findings from a cohort study.

BACKGROUND: Annual foot checks are recommended in patients with diabetes mellitus (DM) to identify those at risk of foot ulceration. Systematic reviews have found few studies evaluating the predictive value of tests in community-based diabetic populations. AIM: To quantify the predictive value of clinical risk factors in relation to foot ulceration in a community population. METHODS: A cohort of 1192 people with diabetes receiving care in community settings was recruited and a screening procedure, covering symptoms, signs and diagnostic tests was conducted at baseline. At an average 1-year follow-up patients who developed a foot ulcer were identified by an independent blind assessor. Multivariable analysis was performed to identify clinical predictors of foot ulceration. FINDINGS: The incidence of foot ulceration was 1.93% [95% confidence interval (CI) 1.27-2.89). Three time-independent clinical predictors with five factors were selected: previous amputation [odds ratio (OR) 14.7, 95% CI 3.1-69.5), use of insulin before 3 months with inability to distinguish between cool and cold temperatures (OR 2.97, 95% CI 1.9-4.5) and failure to obtain at least one blood pressure reading for the calculation of ankle-brachial index with the failure to feel touch with a 10-g monofilament (OR 1.7, 95% CI 1.3-2.2). INTERPRETATION: Recommendations for annual diabetic foot check in low-risk, community-based patients should be reviewed as absolute events of ulceration are low. The accuracy of foot risk assessment tools to predict ulceration requires evaluation in randomized controlled trials with concurrent economic evaluations.

A novel device for improving marker placement accuracy.

BACKGROUND: Repeatability of marker placement has been acknowledged as a major factor affecting the reliability of multi-segment foot models. A novel device is proposed that is intended to reduce marker placement error and its effect on the reliability of inter-segmental foot kinematic data is investigated. METHOD: The novel device was tested on eight healthy subjects. Landmarks were identified and indicated on the subject's foot at the start of testing using pen, and these points were used to guide placement. Markers were twice attached by a podiatrist using a standard approach, and twice by a researcher who used the novel device. Replacement accuracy and the kinematic reliability of the foot model data for both techniques were analysed. RESULTS: The mean marker placement variability using the novel device placement device was 1.1mm (SD 0.28) compared to 1.4mm (SD 0.23) when using standard placement techniques. Results suggest that these reductions in placement error tended to improve the overall reliability of the multi-segment data from the foot model. DISCUSSION: The novel device is a simple and inexpensive tool for improving the placement consistency of skin-mounted markers.

The FOOTSTEP self-management foot care programme: are rheumatoid arthritis patients physically able to participate?

BACKGROUND: The FOOTSTEP self-management foot care programme is a clinical and cost-effective programme for basic foot care in the elderly. The aim of this study was to determine if patients with rheumatoid arthritis (RA) would be physically able to participate. METHODS: A consecutive cohort of RA patients undergoing podiatry care underwent tests for sight, reach and grip strength to determine their physical ability to undertake self-managed foot care. RESULTS: Thirty RA patients (10 male, 20 female), with a median age of 61 years (range 42 to 84) and disease duration of 10 years (range one to 40), were recruited. All patients passed the sight test, whereas the reach and grip tests were passed by 77% and 67% of patients, respectively. Only 57% of patients passed all the physical tests. Patients who failed the physical tests were older, and had longer disease duration and higher physical disability, pain and general health scores but these were not statistically different. CONCLUSIONS: Just over half the patients in this present cohort may be physically able to undertake some aspects of self-managed foot care, including nail clipping and filing, callus filing and daily hygiene and inspection.

A survey of foot problems in juvenile idiopathic arthritis.

BACKGROUND: Evidence suggests that foot problems are common in juvenile idiopathic arthritis (JIA), with prevalence estimates over 90%. The aim of this survey was to describe foot-related impairment and disability associated with JIA and foot-care provision in patients managed under modern treatment paradigms, including disease-modifying anti-rheumatic drugs (DMARDs) and biologic therapies. METHODS: The Juvenile Arthritis Foot Disability Index (JAFI), Child Health Assessment Questionnaire (CHAQ), and pain visual analogue scale (VAS) were recorded in 30 consecutive established JIA patients attending routine outpatient clinics. Foot deformity score, active/limited joint counts, walking speed, double-support time (s) (DS) and step length symmetry index % (SI) were also measured. Foot-care provision in the preceding 12 months was determined from medical records. RESULTS: Sixty-three per cent of children reported some foot impairment, with a median (range) JAFI subscale score of 1 (0-3); 53% reported foot-related activity limitation, with a JAFI subscale score of 1 (0-4); and 60% reported participation restriction, with a JAFI subscale score of 1 (0-3). Other reported variables were CHAQ 0.38 (0-2), VAS pain 22 (0-79), foot deformity 6 (0-20), active joints 0 (0-7), limited joints 0 (0-31), walking speed 1.09 m/s (0.84-1.38 m/s), DS 0.22 s (0.08-0.26 s) and SI +/-4.0% (+/-0.2-+/-31.0%). A total of 23/30 medical records were reviewed and 15/23 children had received DMARDS, 8/23 biologic agents and 20/23 multiple intra-articular corticosteroid injections. Ten children received specialist podiatry care comprising footwear advice, orthotic therapy and silicone digital splints together with intrinsic muscle strengthening exercises. CONCLUSION: Despite frequent use of DMARD/biologic therapy and specialist podiatry-led foot care, foot-related impairment and disability persists in some children with JIA.