Improving the safety of resuscitative endovascular balloon occlusion of the aorta - Compliant versus semi-compliant balloon systems.

OBJECTIVES: Resuscitative endovascular balloon occlusion of the aorta is an alternative to resuscitative thoracotomy in non-compressible torso haemorrhage. Low-profile, compliant balloon catheter systems have been developed, which can be deployed without the need for fluoroscopy. However, concern exists for over inflation and aortic injury, especially as compliant balloon material can stretch reducing syringe feedback and limiting the effectiveness of a safety valve. An alternative material would be a semi-compliant balloon material, but its performance is unknown. The aim of this study was to compare the inflation characteristics of compliant versus semi-compliant balloon systems and to determine whether a pressure relief safety valve can be practically applied to a semi-compliant balloon catheter as a safety device. METHODS: This was an ex vivo study using porcine segments of thoracic aorta. The study consisted of two phases. The first phase involved intermittent inflation of six compliant balloon and six semi-compliant balloon balloons until balloon or aortic rupture. In the second phase, six semi-compliant balloons with the pressure-relief valve set at 0.45 atmospheres were inflated in the aortas until the valve release, followed by injection with additional 30 mL. Data including pressure, volume, balloon working length, diameter and circumferential stretch ratio were collected. RESULTS: At failure, mean balloon volume was almost double in compliant balloon group vs semi-compliant balloon group - 49.83 mL (±23.25) and 25.16 mL (±8.93), respectively (p = 0.004), with 36% increase in working length in the compliant balloon group - 81.17 mm (±19.11) vs 59.49 (±4.86) for semi-compliant balloon (p = 0.023). When plotted, the relationship pattern between volume and pressure fit a linear model for the compliant balloon, and a quadratic model for the semi-compliant balloon. Following attempted over inflation with the pressure valve, there was no change in parameters before and after attempted over inflation. CONCLUSIONS: The inflation profile differs between balloon designs. In contrast to semi-compliant balloons, compliant balloons will accommodate more volume to mitigate increase in pressure. This does not completely eliminate the risk of over inflation. The inflation characteristics of the semi-compliant balloon permit pairing it with a safety valve, which could lead to a development of a safer balloon technology in the future.

Educational Impact of a Pulsatile Human Cadaver Circulation Model for Endovascular Training.

OBJECTIVES: The face and construct validity of a novel pulsatile human cadaver model (PHCM) was recently demonstrated for endovascular training. This study aimed to assess the model's educational impact. METHODS: Twenty-four endovascular novices were recruited and split into two equal training groups: PHCM and virtual reality simulator (VRS). Each candidate performed eight consecutive training attempts of endovascular renal artery catheterisation on their designated model, and a final crossover attempt on the alternate model. Performances were video recorded and scored using a validated scoring tool by two independent endovascular experts, blinded to the candidate's identity and attempt number. Each participant was given a task specific checklist score (TSC), global rating score (GRS), and overall procedure score (OPS). RESULTS: In the PHCM group average OPS improved gradually from 19.42 (TSC 8.58, GRS 10.83) to 39.50 (TSC 15.00, GRS 24.5) over eight attempts (p < .0005). In the VRS group OPS improved from 20.54 (TSC 10.29, GRS 10.25) to 36.04 (TSC 14.21, GRS 21.88) between the first and eighth attempts (p < .0005), with limited improvement after the second attempt. PHCM training significantly improved OPS on their VRS crossover attempt (p ≤ .0001), achieving a similar OPS to candidates who had completed VRS training (p = .398). VRS training significantly improved OPS on PHCM (p < 0.05); however, OPS was significantly worse than candidates who had completed PHCM training (p ≤ .001). CONCLUSIONS: PHCM training has a longer learning curve, with gradual improvement, reflecting the enhanced difficulty of a more realistic model. These results support the use of PHCM preceded by VRS training, prior to performing endovascular surgery on patients.

Protocol for a systematic review and individual patient data meta-analysis of prognostic factors of foot ulceration in people with diabetes: the international research collaboration for the prediction of diabetic foot ulcerations (PODUS).

BACKGROUND: Diabetes-related lower limb amputations are associated with considerable morbidity and mortality and are usually preceded by foot ulceration. The available systematic reviews of aggregate data are compromised because the primary studies report both adjusted and unadjusted estimates. As adjusted meta-analyses of aggregate data can be challenging, the best way to standardise the analytical approach is to conduct a meta-analysis based on individual patient data (IPD).There are however many challenges and fundamental methodological omissions are common; protocols are rare and the assessment of the risk of bias arising from the conduct of individual studies is frequently not performed, largely because of the absence of widely agreed criteria for assessing the risk of bias in this type of review. In this protocol we propose key methodological approaches to underpin our IPD systematic review of prognostic factors of foot ulceration in diabetes.Review questions;1. What are the most highly prognostic factors for foot ulceration (i.e. symptoms, signs, diagnostic tests) in people with diabetes?2. Can the data from each study be adjusted for a consistent set of adjustment factors?3. Does the model accuracy change when patient populations are stratified according to demographic and/or clinical characteristics? METHODS: MEDLINE and EMBASE databases from their inception until early 2012 were searched and the corresponding authors of all eligible primary studies invited to contribute their raw data. We developed relevant quality assurance items likely to identify occasions when study validity may have been compromised from several sources. A confidentiality agreement, arrangements for communication and reporting as well as ethical and governance considerations are explained.We have agreement from the corresponding authors of all studies which meet the eligibility criteria and they collectively possess data from more than 17000 patients. We propose, as a provisional analysis plan, to use a multi-level mixed model, using "study" as one of the levels. Such a model can also allow for the within-patient clustering that occurs if a patient contributes data from both feet, although to aid interpretation, we prefer to use patients rather than feet as the unit of analysis. We intend to only attempt this analysis if the results of the investigation of heterogeneity do not rule it out and the model diagnostics are acceptable. DISCUSSION: This review is central to the development of a global evidence-based strategy for the risk assessment of the foot in patients with diabetes, ensuring future recommendations are valid and can reliably inform international clinical guidelines.

Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism in high-risk patients.

BACKGROUND: It has been suggested that combined modalities (methods of treatment) are more effective than single modalities in preventing venous thromboembolism (defined as deep vein thrombosis and pulmonary embolism, or both) in high-risk patients. OBJECTIVES: To assess the efficacy of intermittent pneumatic leg compression combined with pharmacological prophylaxis versus single modalities in preventing venous thromboembolism in high-risk patients. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases (PVD) Group searched their Specialized Register (last searched 17 July 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched The Cochrane Library 2008, Issue 3). We searched the reference lists of relevant articles to identify additional trials. SELECTION CRITERIA: Randomized controlled trials (RCTs) or controlled clinical trials (CCTs) of combined intermittent pneumatic leg compression and pharmacological interventions used to prevent venous thromboembolism in high-risk patients. DATA COLLECTION AND ANALYSIS: Data extraction was undertaken independently by two review authors using data extraction sheets. MAIN RESULTS: Eleven studies, six of them randomized controlled trials, were identified. The trials included 7431 patients, in total. Compared with compression alone, the use of combined modalities reduced significantly the incidence of both symptomatic pulmonary embolism (PE) (from about 3% to 1%; odds ratio (OR) 0.39, 95% confidence interval (CI) 0.25 to 0.63) and deep vein thrombosis (DVT) (from about 4% to 1%; OR 0.43, 95% CI 0.24 to 0.76). Compared with pharmacological prophylaxis alone, the use of combined modalities significantly reduced the incidence of DVT (from 4.21% to 0.65%; OR 0.16, 95% CI 0.07 to 0.34) but the included studies were underpowered with regard to PE. The comparison of compression plus pharmacological prophylaxis versus compression plus aspirin showed a non-significant reduction in PE and DVT in favor of the former group. Repeat analysis restricted to the RCTs confirmed the above findings. AUTHORS' CONCLUSIONS: Compared with compression alone, combined prophylactic modalities decrease significantly the incidence of venous thromboembolism. Compared with pharmacological prophylaxis alone, combined modalities reduce significantly the incidence of DVT but the effect on PE is unknown. The results of the current review support, especially in high-risk patients, the use of combined modalities. More studies on their role in PE prevention, compared with pharmacological prophylaxis alone, are urgently needed.

Homocysteine activates platelets in vitro.

The mechanism of thrombogenicity in hyperhomocysteinemia remains controversial. The authors investigated the association between elevated plasma homocysteine levels, platelet function, and blood coagulation. Blood was collected from healthy subjects and patients with critical limb ischemia. Basal platelet counts and platelet aggregation as well as flow cytometry were performed to assess spontaneous- and agonist-induced platelet aggregation as well as P-selectin and Glycoprotein IIb/IIIa expression at different homocysteine concentrations. Thromboelastography was performed, and platelet shape change was assessed, using a channelyzer, by measuring median platelet volume. Lactate dehydrogenase was measured, to indirectly assess red blood cell membrane integrity, after homocysteine exposure. The study results suggest that platelet activation and hypercoagulability occur after exposure to homocysteine, especially in patients with critical limb ischemia. Homocysteine concentrations of approximately 50 micromol/L appear to be the level at which these changes occur in vitro, and this effect on platelets appears to be indirect.

Platelet activation in bypass surgery for critical limb ischemia.

Platelet activation contributes to graft occlusion after bypass surgery. This study investigated platelet activation status before, during, and after bypass. Blood was taken preoperatively from patients undergoing femoro-popliteal bypass and at incision, after dissection, after ischemia, after reperfusion, 24 hours after surgery, and almost 2 years after bypass (and given aspirin or warfarin). Platelet aggregation was measured using a turbidimetric method and platelet activation with flow cytometry. Statistical analysis was performed using Mann-Whitney U and Wilcoxon's tests. Resting platelet activation was similar between controls and patients undergoing bypass. Platelet activation decreased at incision but remained highly reactive. Platelet aggregation increased after dissection and the ischemic phase but significantly decreased after reperfusion. Platelet aggregation and activation were increased at 24 hours and subsequently after bypass. Platelets in critical limb ischemia exist in the primed state and become activated by minimum stimuli. Increased platelet activation occurs after bypass grafting for critical limb ischemia despite adjunctive therapy.

A systematic review and individual patient data meta-analysis of prognostic factors for foot ulceration in people with diabetes: the international research collaboration for the prediction of diabetic foot ulcerations (PODUS).

BACKGROUND: Annual foot risk assessment of people with diabetes is recommended in national and international clinical guidelines. At present, these are consensus based and use only a proportion of the available evidence. OBJECTIVES: We undertook a systematic review of individual patient data (IPD) to identify the most highly prognostic factors for foot ulceration (i.e. symptoms, signs, diagnostic tests) in people with diabetes. DATA SOURCES: Studies were identified from searches of MEDLINE and EMBASE. REVIEW METHODS: The electronic search strategies for MEDLINE and EMBASE databases created during an aggregate systematic review of predictive factors for foot ulceration in diabetes were updated and rerun to January 2013. One reviewer applied the IPD review eligibility criteria to the full-text articles of the studies identified in our literature search and also to all studies excluded from our aggregate systematic review to ensure that we did not miss eligible IPD. A second reviewer applied the eligibility criteria to a 10% random sample of the abstract search yield to check that no relevant material was missed. This review includes exposure variables (risk factors) only from individuals who were free of foot ulceration at the time of study entry and who had a diagnosis of diabetes mellitus (either type 1 or type 2). The outcome variable was incident ulceration. RESULTS: Our search identified 16 cohort studies and we obtained anonymised IPD for 10. These data were collected from more than 16,000 people with diabetes worldwide and reanalysed by us. One data set was kept for independent validation. The data sets contributing IPD covered a range of temporal, geographical and clinical settings. We therefore selected random-effects meta-analysis, which assumes not that all the estimates from each study are estimates of the same underlying true value, but rather that the estimates belong to the same distribution. We selected candidate variables for meta-analysis using specific criteria. After univariate meta-analyses, the most clinically important predictors were identified by an international steering committee for inclusion in the primary, multivariable meta-analysis. Age, sex, duration of diabetes, monofilaments and pulses were considered most prognostically important. Meta-analyses based on data from the entire IPD population found that an inability to feel a 10-g monofilament [odds ratio (OR) 3.184, 95% confidence interval (CI) 2.654 to 3.82], at least one absent pedal pulse (OR 1.968, 95% CI 1.624 to 2.386), a longer duration of a diagnosis of diabetes (OR 1.024, 95% CI 1.011 to 1.036) and a previous history of ulceration (OR 6.589, 95% CI 2.488 to 17.45) were all predictive of risk. Female sex was protective (OR 0.743, 95% CI 0.598 to 0.922). LIMITATIONS: It was not possible to perform a meta-analysis using a one-step approach because we were unable to procure copies of one of the data sets and instead accessed data via Safe Haven. CONCLUSIONS: The findings from this review identify risk assessment procedures that can reliably inform national and international diabetes clinical guideline foot risk assessment procedures. The evidence from a large sample of patients in worldwide settings show that the use of a 10-g monofilament or one absent pedal pulse will identify those at moderate or intermediate risk of foot ulceration, and a history of foot ulcers or lower-extremity amputation is sufficient to identify those at high risk. We propose the development of a clinical prediction rule (CPR) from our existing model using the following predictor variables: insensitivity to a 10-g monofilament, absent pedal pulses and a history of ulceration or lower-extremities amputations. This CPR could replace the many tests, signs and symptoms that patients currently have measured using equipment that is either costly or difficult to use. STUDY REGISTRATION: This study is registered as PROSPERO CRD42011001841. FUNDING: The National Institute for Health Research Health Technology Assessment programme.