A Systematic Review of the Uptake and Adherence Rates to Supervised Exercise Programs in Patients with Intermittent Claudication

Background Intermittent claudication (IC) is a common and debilitating symptom of peripheral arterial disease and is associated with a significant reduction in a sufferer's quality of life. Guidelines recommend a supervised exercise program (SEP) as the primary treatment option; however, anecdotally there is a low participation rate for exercise in this group of patients. We undertook a systematic review of the uptake and adherence rates to SEPs for individuals with IC. Methods The MEDLINE, Embase, and PubMed databases were searched up to January 2015 for terms related to supervised exercise in peripheral arterial disease. The review had 3 aims: first, to establish the rates of uptake to SEPs, second, the rates of adherence to programs, and finally to determine the reasons reported for poor uptake and adherence. Separate inclusion and/or exclusion criteria were applied in selecting reports for each aim of the review. Results Only 23 of the 53 potentially eligible articles for uptake analysis identified on literature searches reported any details of screened patients (n = 7,517) with only 24.2% of patients subsequently recruited to SEPs. Forty-five percent of screen failures had no reason for exclusion reported. Sixty-seven articles with 4,012 patients were included for analysis of SEP adherence. Overall, 75.1% of patients reportedly completed an SEP; however, only one article defined a minimal attendance required for SEP completion. Overall, 54.1% of incomplete adherence was due to patient withdrawal and no reason for incomplete adherence was reported for 16% of cases. Conclusions Reporting of SEP trials was poor with regard to the numbers of subjects screened and reasons for exclusions. Only approximately 1 in 3 screened IC patients was suitable for and willing to undertake SEP. Levels of adherence to SEPs and definitions of satisfactory adherence were also lacking in most the current literature. Current clinical guidelines based on this evidence base may not be applicable to most IC patients and changes to SEPs may be needed to encourage and/or retain participants

The Impact of Vein Mechanical Compliance on Arteriovenous Fistula Outcomes

© 2016 Elsevier Inc. Background Arteriovenous fistulae (AVFs) are the preferred access for hemodialysis but suffer a high early failure rate. The aim of this study was to determine how venous distensibility, as measured in vitro, relates to early outcomes of AVF formed with the sampled vein. Methods Ethical approval was obtained for all aspects of this study. During AVF formation a circumferential segment of the target vein was sampled. Mechanical stress testing of the venous segments was undertaken using a dynamic mechanical analyzer, with progressive stress loading at 2 N/min to a maximum of 10 N or until sample disruption. Stress-strain curves were obtained for vein samples and Young's modulus (YM) calculated. Duplex assessment of the fistulae was undertaken at 30 days. Results Thirty patients consented to participate with 29 samples obtained for analysis. Statistical comparison of YM demonstrated no relationship with common cardiovascular risk factors or dialysis status. Subject age greater than 65 was the only patient factor which showed a significant difference in YM (P = 0.05). Furthermore, a negative correlation was confirmed between age and YM (Pearson's r = -0.465, P < 0.05). Nine of the 29 subjects suffered an early AVF failure. Mann-Whitney U testing for differences in distribution reported that YM was significantly higher in those fistulas which failed (P < 0.005). Conclusions Reduced venous compliance appears to result in higher failure rates of AVFs. With the advancement of clinical tools such as speckle tracing ultrasound identification of vessel compliance in vivo may produce valuable additional information for clinicians planning AVF surgery

Extracorporeal shockwave therapy for the treatment of lower limb intermittent claudication: Study protocol for a randomised controlled trial (the SHOCKWAVE 1 trial)

© 2017 The Author(s). Background: Peripheral arterial disease (PAD) has a population prevalence of 4.6% with intermittent claudication (IC) presenting as one of the earliest and most common symptoms. PAD has detrimental effects on patients' walking ability in terms of maximum walking distance (MWD) and pain-free walking distance (PFWD). Research has suggested extracorporeal shockwave therapy (ESWT) may induce angiogenesis in treated tissue; therefore, our objective is to assess the tolerability and efficacy of ESWT as a novel treatment of intermittent claudication. Methods/design: Patients with unilateral claudication will be randomised to receive either ESWT (PiezoWave 2 shockwave system) or sham treatment to the calf muscle bulk three times per week for 3 weeks. All patients are blinded to treatment group, and all assessments will be performed by a masked assessor. Treatment tolerability using a visual analogue scale, ankle-brachial pressure index, MWD, PFWD and safety will all be formally assessed as outcome measures at baseline and at 4, 8 and 12 weeks follow-up. Discussion: This trial will be the first of its kind in terms of methodology in relation to ESWT for intermittent claudication. A double-masked randomised controlled trial will provide useful information about the potential for the use of ESWT as a non-invasive treatment option and the need for further robust research. Trial registration: ClinicalTrials.gov, NCT02652078. Registered on 17 October 2014

A systematic review and meta-analysis of systemic intraoperative anticoagulation during arteriovenous access formation for dialysis

Purpose: Surgical arteriovenous fistula (AVF) or graft (AVG) is preferred to a central venous catheter for dialysis access. Surgical access may suffer thrombosis early after placement and systemic anticoagulation during surgical access formation may increase patency rates but would be expected to increase bleeding-related complications. A systematic review and meta-analysis of randomised controlled trials was conducted to examine the impact of systemic anticoagulation on access surgery perioperative bleeding and patency rates. Methods: We included randomised controlled trials testing systemic anticoagulation during access formation versus a control group without systemic anticoagulation reporting bleeding complications and access patency. Medline, Embase, CENTRAL and CINAHL were searched up to March 2015. Risk of bias was assessed using the Cochrane risk of bias tool and the Jadad score. Meta-analysis was performed using Cochrane Revman ® software. Results: Searches identified 445 reports of which four randomised studies involving 411 participants were included. Three studies pertained to AVF only and one included both AVF and AVG. Systemic anticoagulation led to increased bleeding events in all access [four trials; risk ratio (RR) 7.18; confidence interval (CI), 2.41 to 21.38; p < 0.001]. Patency was not improved for all access (four trials; RR, 0.64; CI, 0.37 to 1.09; p = 0.10) but was improved when AVF analysed alone (three trials; RR, 0.57; CI, 0.33 to 0.97; p = 0.04). Conclusions: The use of intraoperative systemic anticoagulation during access formation is associated with a highly significant increased risk of bleeding-related complications. A significant improvement in AVF patency was seen, though not when AVF and AVG were analysed together

#5 - Identifying cellular mechano-biological responses to PEG-based hydrogels

Cells sense and respond to mechanical stimuli from their external environment through a process called mechanotransduction. Focal adhesions are integrin-containing, multiprotein structures through which mechanical force is transmitted between the extracellular matrix and the interacting cell. Cells convert the transmitted force into biological responses including migration, proliferation and differentiation. The Garcia lab has previously engineered an integrin-specific hydrogel system resulting in changes in mesenchymal stem cell (MSC) gene expression, secretome, and ultimately regenerative capacity in a murine bone repair model. However, the mechano-biological mechanism driving this cell response to varying hydrogel biophysical and biochemical properties has yet to be studied. Here we have developed relationships between various hydrogel properties and cellular responses (cell adhesion, YAP localization, cell area, and cell shape). We engineered PEG-based hydrogel systems with two different polymerization chemistries, malemide and norbornene, to explore the effect of hydrogel chemistry on MSC cell adhesion and spreading. Using rheology, we demonstrated that hydrogel mechanical properties can be tuned by altering the weight percent of PEG macromer, while adhesion ligand type and density had no effect on hydrogel mechanical properties. PEG-4MAL gels were used for the remaining studies because that chemistry resulted in improved spreading and cell adhesion over norbornene hydrogels. By varying the density of RGD, the adhesive ligand for αvβ3 integrin, on the hydrogels, we showed that higher RGD densities resulted in greater YAP nuclear localization. We sought to understand the mechano-biological signaling pathway involved in YAP nuclear localization by inhibiting ROCK and FAK, proteins critical in mechanosensing via focal adhesion complexes. The inhibition of ROCK, and FAK decreased cell spread area, increased cell circularity and decreased YAP nuclear localization. Taken together this data demonstrates that external signals from PEG-based hydrogels as well as the intracellular signaling cascades involving ROCK and FAK can modulate YAP mechanosensing in MSCs

Proximity Effects and Nonequilibrium Superconductivity in Transition-Edge Sensors

We have recently shown that normal-metal/superconductor (N/S) bilayer TESs (superconducting Transition-Edge Sensors) exhibit weak-link behavior.1 Here we extend our understanding to include TESs with added noise-mitigating normal-metal structures (N structures). We find TESs with added Au structures also exhibit weak-link behavior as evidenced by exponential temperature dependence of the critical current and Josephson-like oscillations of the critical current with applied magnetic field. We explain our results in terms of an effect converse to the longitudinal proximity effect (LoPE)1, the lateral inverse proximity effect (LaiPE), for which the order parameter in the N/S bilayer is reduced due to the neighboring N structures. Resistance and critical current measurements are presented as a function of temperature and magnetic field taken on square Mo/Au bilayer TESs with lengths ranging from 8 to 130 {\mu}m with and without added N structures. We observe the inverse proximity effect on the bilayer over in-plane distances many tens of microns and find the transition shifts to lower temperatures scale approximately as the inverse square of the in- plane N-structure separation distance, without appreciable broadening of the transition width. We also present evidence for nonequilbrium superconductivity and estimate a quasiparticle lifetime of 1.8 \times 10-10 s for the bilayer. The LoPE model is also used to explain the increased conductivity at temperatures above the bilayer's steep resistive transition.Comment: 10 pages, 8 figure

Extreme low-lying carotid bifurcations

A 52-year-old male with no past medical history was referred to the transient ischaemic attack (TIA) clinic following an event at home. The transient symptoms were of an inability to move his left arm and leg for a period of approximately 15 minutes. The patient denied any numbness of the face, headaches or blurring of vision. A careful history revealed two previous transient attacks of blurred vision approximately 1–2 years prior to this presentation. He had no other co-morbidities or associated syndromes. Given this history, suggestive of TIA(s) in the right anterior circulation, an ultrasound examination of the carotid vessels was performed to include or exclude an atherosclerotic source of embolus. The ultrasound scan demonstrated an extremely short common carotid artery (CCA) of just 2.5 cm on the right, with apparently normal flows and velocities in both the external and internal carotids (ECA and ICA) but poor views of the bifurcation. Similarly, the flows and velocities in the left ICA and ECA were also normal, with the carotid bulb lying low in the base of the neck, so further imaging with a magnetic resonance angiogram (MRA) was performed (Panel A) to clarify the anatomic and ultrasound findings. This confirmed extremely low-lying bilateral carotid bifurcations (highlighted in Panel A). The short, right-side CCA bifurcates at the level of C7/T1 (Panel B) and the left carotid bifurcation is at the level of C6/C7 (Panel C)