Methodological considerations for a randomised controlled trial of podiatry care in rheumatoid arthritis: lessons from an exploratory trial

<p>Abstract</p> <p>Background</p> <p>Whilst evidence exists to support the use of single treatments such as orthoses and footwear, the effectiveness of podiatry-led care as a complex intervention for patients with rheumatoid arthritis (RA) related foot problems is unknown. The aim of this study was to undertake an exploratory randomised controlled parallel arm clinical trial (RheumAFooT) to inform the design and implementation of a definitive trial and to understand the potential benefits of this care.</p> <p>Methods</p> <p>Patients with a definite diagnosis of RA, stable drug management 3 months prior to entry, and a current history of foot problems (pain, deformity, stiffness, skin or nail lesions, or footwear problems) were recruited from a hospital outpatient rheumatology clinic and randomised to receive 12 months of podiatry treatment or no care. The primary outcome was change in foot health status using the impairment/footwear (LFIS_IF) and activity limitation/participation restriction (LFIS_AP) subscales of the Leeds Foot Impact Scale. Disease Activity Score (DAS), Health Assessment Questionnaire (HAQ) score and walking speed (m/s) were also recorded.</p> <p>Results</p> <p>Of the 80 patients identified, 64 patients were eligible to participate in the pilot and 34 were recruited. 16 patients were randomised to receive podiatry led foot care and 18 received no care. Against a backdrop of stable disease (DAS and HAQ scores), there was a statistically significant between group difference in the change in foot health status for foot impairment (LFIS_IF) but not activity/participation (LFIS_AP) or function (walking speed) over 12 months. In the podiatry arm, 1 patient declined treatment following randomisation (did not want additional hospital visits) and 3 self-withdrew (lost to follow-up). Patients received an average of 3 consultations for assessment and treatment comprising routine care for skin and nail lesions (n = 3), foot orthoses (n = 9), footwear referral to the orthotist (n = 5), and ultrasound guided intra-articular steroid injection (n = 1).</p> <p>Conclusion</p> <p>In this exploratory trial patients were difficult to recruit (stable drug management and co-morbid disease) and retain (lack of benefit/additional treatment burden) but overall the intervention was safe (no adverse reactions). Twelve months of podiatry care maintained but did not improve foot health status. These observations are important for the design and implementation of a definitive randomised controlled trial.</p> <p>Trial Registration</p> <p>ISRCTN: 01982076</p

Novel metallic implantation technique for osteochondral defects of the medial talar dome: A cadaver study

BACKGROUND AND PURPOSE: A metallic inlay implant (HemiCAP) with 15 offset sizes has been developed for the treatment of localized osteochondral defects of the medial talar dome. The aim of this study was to test the following hypotheses: (1) a matching offset size is available for each talus, (2) the prosthetic device can be reproducibly implanted slightly recessed in relation to the talar cartilage level, and (3) with this implantation level, excessive contact pressures on the opposite tibial cartilage are avoided. METHODS: The prosthetic device was implanted in 11 intact fresh-frozen human cadaver ankles, aiming its surface 0.5 mm below cartilage level. The implantation level was measured at 4 margins of each implant. Intraarticular contact pressures were measured before and after implantation, with compressive forces of 1,000-2,000 N and the ankle joint in plantigrade position, 10 dorsiflexion, and 14 plantar flexion. RESULTS: There was a matching offset size available for each specimen. The mean implantation level was 0.45 (SD 0.18) mm below the cartilage surface. The defect area accounted for a median of 3% (0.02-18) of the total ankle contact pressure before implantation. This was reduced to 0.1% (0.02-13) after prosthetic implantation. INTERPRETATION: These results suggest that the implant can be applied clinically in a safe way, with appropriate offset sizes for various talar domes and without excessive pressure on the opposite cartilag

Therapeutic Potential of HDL in Cardioprotection and Tissue Repair

Epidemiological studies support a strong association between high-density lipoprotein (HDL) cholesterol levels and heart failure incidence. Experimental evidence from different angles supports the view that low HDL is unlikely an innocent bystander in the development of heart failure. HDL exerts direct cardioprotective effects, which are mediated via its interactions with the myocardium and more specifically with cardiomyocytes. HDL may improve cardiac function in several ways. Firstly, HDL may protect the heart against ischaemia/reperfusion injury resulting in a reduction of infarct size and thus in myocardial salvage. Secondly, HDL can improve cardiac function in the absence of ischaemic heart disease as illustrated by beneficial effects conferred by these lipoproteins in diabetic cardiomyopathy. Thirdly, HDL may improve cardiac function by reducing infarct expansion and by attenuating ventricular remodelling post-myocardial infarction. These different mechanisms are substantiated by in vitro, ex vivo, and in vivo intervention studies that applied treatment with native HDL, treatment with reconstituted HDL, or human apo A-I gene transfer. The effect of human apo A-I gene transfer on infarct expansion and ventricular remodelling post-myocardial infarction illustrates the beneficial effects of HDL on tissue repair. The role of HDL in tissue repair is further underpinned by the potent effects of these lipoproteins on endothelial progenitor cell number, function, and incorporation, which may in particular be relevant under conditions of high endothelial cell turnover. Furthermore, topical HDL therapy enhances cutaneous wound healing in different models. In conclusion, the development of HDL-targeted interventions in these strategically chosen therapeutic areas is supported by a strong clinical rationale and significant preclinical data.status: publishe

The Utility of Ultrasound for Diagnosing Purulent Infections of the Upper Extremity

BACKGROUND: The purpose of this study was to determine the test characteristics of formal ultrasound when used to diagnose upper extremity soft tissue abscess in the setting of suspected infection. METHODS: We completed a retrospective chart review of all patients who had formal ultrasounds at our institution for the indication of diagnosing upper extremity abscess between July 2010 and July 2013. Using presence of purulence as the gold standard for diagnosis of abscess, we calculated the test characteristics of ultrasound. We then performed a series of logistic regression models with ultrasound being the independent variable of interest. RESULTS: Using search criteria consistent with upper extremity abscess, we identified 512 patients who underwent ultrasound examinations during our study period. Of these, 178 met the enrollment criteria. Ultrasound reports revealed 110 negative findings, 37 definitively positive findings, and 31 ambiguous findings. Forty-four patients had a final diagnosis of abscess, and 15 of these patients had negative or ambiguous ultrasounds. The sensitivity of definitively positive ultrasound was 65.9 %. The specificity was 94.0 %. Positive predictive value (PPV) of a definitively positive ultrasound result was 78.4 %, and negative predictive value (NPV) of a definitively negative result was 90 %. Logistic regression demonstrated a statistically significant association between definitively positive ultrasound and abscess, but no association between ambiguous ultrasound and abscess after adjustment for significant covariates. CONCLUSIONS: Ultrasound is not a sensitive method to detect the presence of abscess in the setting of upper extremity infection. However, in this population of patients with suspected abscess, the negative predictive value was high with and without the inclusion of ambiguous results, suggesting reasonable utility of ultrasound as a rule-out test. LEVEL OF EVIDENCE: Diagnostic study, Level I

An In Vitro Comparison of the Incorporation, Growth, and Chondrogenic Potential of Human Bone Marrow versus Adipose Tissue Mesenchymal Stem Cells in Clinically Relevant Cell Scaffolds Used for Cartilage Repair.

AIM: To compare the incorporation, growth, and chondrogenic potential of bone marrow (BM) and adipose tissue (AT) mesenchymal stem cells (MSCs) in scaffolds used for cartilage repair. METHODS: Human BM and AT MSCs were isolated, culture expanded, and characterised using standard protocols, then seeded into 2 different scaffolds, Chondro-Gide or Alpha Chondro Shield. Cell adhesion, incorporation, and viable cell growth were assessed microscopically and following calcein AM/ethidium homodimer (Live/Dead) staining. Cell-seeded scaffolds were treated with chondrogenic inducers for 28 days. Extracellular matrix deposition and soluble glycosaminoglycan (GAG) release into the culture medium was measured at day 28 by histology/immunohistochemistry and dimethylmethylene blue assay, respectively. RESULTS: A greater number of viable MSCs from either source adhered and incorporated into Chondro-Gide than into Alpha Chondro Shield. In both cell scaffolds, this incorporation represented less than 2% of the cells that were seeded. There was a marked proliferation of BM MSCs, but not AT MSCs, in Chondro-Gide. MSCs from both sources underwent chondrogenic differentiation following induction. However, cartilaginous extracellular matrix deposition was most marked in Chondro-Gide seeded with BM MSCs. Soluble GAG secretion increased in chondrogenic versus control conditions. There was no marked difference in GAG secretion by MSCs from either cell source. CONCLUSION: Chondro-Gide and Alpha Chondro Shield were permissive to the incorporation and chondrogenic differentiation of human BM and AT MSCs. Chondro-Gide seeded with BM MSCs demonstrated the greatest increase in MSC number and deposition of a cartilaginous tissue