Exploring the Reporting Standards of Randomised Controlled Trials Involving Endovascular Interventions for Peripheral Arterial Disease: A Systematic Review.

OBJECTIVE: Endovascular technology innovation requires rigorous evaluation in high quality randomised controlled trials (RCTs). However, due to numerous methodological challenges, RCTs evaluating endovascular interventions are complex and potentially difficult to design, conduct, and report. This systematic review aimed to assess the quality of reporting of RCTs for endovascular interventions for lower limb peripheral arterial disease (PAD). DATA SOURCES AND REVIEW METHODS: A systematic review of Medline, Embase, and the Cochrane Library databases from inception to December 2021 was performed to identify RCTs including participants with PAD undergoing any infrainguinal lower limb endovascular intervention. Study data were extracted and assessed against the Consolidating Standards of Reporting Trials extension for Non-Pharmacological Treatments (CONSORT-NPT) and the Template for Intervention Description and Replication (TIDieR) checklists. Descriptive statistics were used to summarise general study details and reporting standards of the trials. RESULTS: After screening 6 567 abstracts and 526 full text articles, 112 eligible studies were identified, reporting on 228 different endovascular devices and techniques. Details judged sufficient to replicate the investigated intervention were provided for 47 (21%) interventions. It was unclear whether the description was reported with sufficient details in a further 56 (24%), and the description was judged inadequate in 125 (55%). Any intervention descriptions were provided for 184 (81%), with variable levels of detail (some in 134 [59%] and precise in 50 [22%]). Standardisation of intervention or some aspect of this was reported in 25 (22%) trials, but only one specified that adherence to the study protocol would be monitored. CONCLUSION: The quality of the reporting standards of RCTs investigating lower limb endovascular treatments is severely limited because the interventions are poorly described, standardised, and reported. PROSPERO registration number: CRD42022288214.

Editor's Choice -- European Society for Vascular Surgery (ESVS) 2024 Clinical Practice Guidelines on the Management of Abdominal Aorto-Iliac Artery Aneurysms.

OBJECTIVE: The European Society for Vascular Surgery (ESVS) has developed clinical practice guidelines for the care of patients with aneurysms of the abdominal aorta and iliac arteries in succession to the 2011 and 2019 versions, with the aim of assisting physicians and patients in selecting the best management strategy. METHODS: The guideline is based on scientific evidence completed with expert opinion on the matter. By summarising and evaluating the best available evidence, recommendations for the evaluation and treatment of patients have been formulated. The recommendations are graded according to a modified European Society of Cardiology grading system, where the strength (class) of each recommendation is graded from I to III and the letters A to C mark the level of evidence. RESULTS: A total of 160 recommendations have been issued on the following topics: Service standards, including surgical volume and training; Epidemiology, diagnosis, and screening; Management of patients with small abdominal aortic aneurysm (AAA), including surveillance, cardiovascular risk reduction, and indication for repair; Elective AAA repair, including operative risk assessment, open and endovascular repair, and early complications; Ruptured and symptomatic AAA, including peri-operative management, such as permissive hypotension and use of aortic occlusion balloon, open and endovascular repair, and early complications, such as abdominal compartment syndrome and colonic ischaemia; Long term outcome and follow up after AAA repair, including graft infection, endoleaks and follow up routines; Management of complex AAA, including open and endovascular repair; Management of iliac artery aneurysm, including indication for repair and open and endovascular repair; and Miscellaneous aortic problems, including mycotic, inflammatory, and saccular aortic aneurysm. In addition, Shared decision making is being addressed, with supporting information for patients, and Unresolved issues are discussed. CONCLUSION: The ESVS Clinical Practice Guidelines provide the most comprehensive, up to date, and unbiased advice to clinicians and patients on the management of abdominal aorto-iliac artery aneurysms.

Surgical Techniques of, and Outcomes after, Distal Muscle Stabilization in Transfemoral Amputation: A Systematic Review and Narrative Synthesis.

BACKGROUND: Distal muscle stabilization, such as myodesis (suturing muscles to bone) or myoplasty (suturing agonistic-antagonistic muscles together), can aid residual limb stabilization, provide a good soft-tissue covering, and increase rehabilitation potential. However, surgical practice varies due to scant clinical data. The aim of this review is to summarize and evaluate the literature regarding techniques and associated outcomes of distal muscle stabilization in transfemoral amputation (TFA). METHODS: A systematic review and narrative synthesis was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Resources, including observational studies, nonobservational scientific papers, conference proceedings, and textbooks, detailing techniques of TFA distal muscle stabilization were identified from standard medical repositories and library search. A supplementary search of YouTube and Google was undertaken to identify additional resources. Quality assessment was undertaken using Risk Of Bias In Nonrandomized Studies-of Interventions; Authority, Accuracy, Coverage, Objectivity, Date, Significance; and modified-Discern tools. RESULTS: Forty seven resources were identified, including 17 journal articles, 17 textbooks, 5 educational websites/eBooks, 5 videos, 2 online presentations, and 1 webpage. Thirty seven described myodesis, 11 described myoplasty, and 6 described closure without distal muscle stabilization. Eight observational studies presented outcome data for 302 TFAs. No studies comparing closure with or without distal muscle stabilization were identified. All papers describing myodesis secured the adductors to the femur, and most also secured the quadriceps and/or hamstrings to this complex. Number of femoral drill holes varied from 1 to 6. Early wound complications occurred in 17% of amputations, whereas myodesis failure occurred in 9.5%. Prosthetic fitting rates were 73% and, where reported, 100% of patients maintained neutral femoral alignment. CONCLUSIONS: Distal muscle stabilization, particularly myodesis, is a commonly described technique for TFA, although operative techniques are heterogenous. There is a paucity of outcome data, and no studies comparing it to closures without distal muscle stabilization. However, these low-quality data suggest wound healing rates are equivalent to TFA without distal muscle stabilization while demonstrating improvement to patients' rehabilitation potential.

Editor's Choice - Quality Assessment of European Society for Vascular Surgery Clinical Practice Guidelines.

OBJECTIVE: An increasing number of clinical practice guidelines (CPGs) have emerged over recent years. To have clinical utility, they need to be rigorously developed and scientifically robust. Instruments have been developed to assess the quality of clinical guideline development and reporting. The aim of this study was to evaluate CPGs from the European Society for Vascular Surgery (ESVS) using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. METHODS: CPGs published by the ESVS during the period January 2011 to January 2023 were included. Two independent reviewers assessed the guidelines after receiving training in the use and application of the AGREE II instrument. Inter-reviewer reliability was assessed with the intraclass correlation coefficient. Maximum scaled scores were 100. Statistical analysis was performed using SPSS Statistics v.26. RESULTS: Sixteen guidelines were included in the study. Good inter-reviewer score reliability was found on statistical analysis (> 0.9). The mean ± standard deviation domain scores were 68.1 ± 20.3% for scope and purpose, 57.1 ± 21.1% for stakeholder involvement, 67.8 ± 19.5% for rigour of development, 78.1 ± 20.6% for clarity of presentation, 50.3 ± 15.4% for applicability, 77.6 ± 17.6% for editorial independence, and 69.8 ± 20.1% for overall quality. Stakeholder involvement and applicability have improved in quality over time but are still the lowest scoring domains. CONCLUSION: Most ESVS clinical guidelines are of high quality and reporting. There is scope for improvement, specifically by addressing the domains of stakeholder involvement and clinical applicability.

Clinical Effects of Tourniquet Use for Nontraumatic Major Lower Limb Amputation: A Two-Center Retrospective Cohort Study.

BACKGROUND: To investigate the effect of tourniquet use on outcomes after major lower limb amputation (MLLA) due to peripheral arterial disease or complications from diabetes mellitus. METHODS: In this 2-center retrospective observational study, vascular patients who underwent MLLA between January 1, 2016 and December 31, 2020 at 2 UK hospitals were identified using operating theater databases. Hospital databases were used to access medical records, operation notes, and laboratory reports. The use of a tourniquet in each MLLA was noted. The primary outcome was postoperative hemoglobin (Hb) drop (g/L). Secondary outcomes were units of allogeneic blood transfused perioperatively, 90-day revision rates, 90-day wound breakdown rates, surgical site infection (SSI) rates (at 30 days), and 90-day mortality. A follow-up index (a measure of follow-up completeness) was calculated for all 30-day and 90-day outcomes. RESULTS: Four hundred seventy two patients underwent MLLA, of which 124 had a tourniquet applied. The median postoperative Hb drop was significantly lower in the tourniquet group compared to the nontourniquet group (13 [interquartile range 5-22] g/L vs. 20 [interquartile range 11-28] g/L; P ≤ 0.001). Thirty three point one percent (41) of tourniquet patients received a blood transfusion perioperatively, compared to 35.6% (124) of nontourniquet patients (P = 0.82). Sixteen percent (76) of patients required surgical revision within 90 days, with no significant difference between the tourniquet and nontourniquet group (20.2% tourniquet vs. 14.7% no tourniquet; P = 0.15). SSI rates (12.0% tourniquet vs. 10.6% no tourniquet, P = 0.66) and 90-day mortality (6.5% tourniquet vs. 10.1% no tourniquet; P = 0.23) were similar. Multivariable regression demonstrated that tourniquet use was independently associated with a reduced hemoglobin drop (ß = -4.671, 95% confidence interval -7.51 to -1.83, P ≤ 0.001) but was not associated with wound breakdown, revision surgery, or SSI. Hypertension, SSI, and below-knee amputation using the skew flap technique were all significant predictors of revision surgery. All follow-up indices were ≥ 0.97. CONCLUSIONS: Tourniquet use in MLLA was associated with a significantly lower fall in postoperative Hb without evidence of harm in terms of SSI, wound breakdown/revision rates, or mortality.

Amputation and advance care plans: An observational study exploring decision making and long-term outcomes in a vascular centre.

BACKGROUND: Half of those undergoing major lower limb amputation for peripheral arterial disease die within 1 year. Advance care planning reduces days in hospital and increases the chance of dying in a preferred place. AIM: To investigate the prevalence and content of advance care planning for people having a lower limb amputation due to acute or chronic limb-threatening ischaemia or diabetes. Secondary aims were to explore its association with mortality, and length of hospital stay. DESIGN: A retrospective observational cohort study. The intervention was advance care planning. SETTING/PARTICIPANTS: Patients admitted to the South West England Major Arterial Centre between 1 January 2019 and 1 January 2021 who received unilateral or bilateral below, above, or through knee amputation due to acute or chronic limb-threatening ischaemia or diabetes. RESULTS: 116 patients were included in the study. 20.7% (n = 24) died within 1 year. 40.5% (n = 47) had an advance care planning discussion of which all included cardiopulmonary resuscitation decisions with few exploring other options. Patients who were more likely to have advance care planning discussions were ≥75 years (aOR = 5.58, 95%CI 1.56-20.0), female (aOR = 3.24, 95%CI 1.21-8.69), and had multimorbidity (Charlson Comorbidity Index ≥5, aOR = 2.97, 95%CI 1.11-7.92). Discussions occurred more often in the emergency pathway and were predominantly initiated by physicians. Advance care planning was associated with increased mortality (aHR = 2.63, 95%CI 1.01, 5.02) and longer hospital stay (aHR = 0.52, 95%CI 0.32-0.83). CONCLUSIONS: Despite a high risk of death for all patients in the months following amputation, advance care planning occurred in fewer than half of people and mostly focused on resuscitation.

Systematic review and narrative synthesis of surveillance practices after endovascular intervention for lower limb peripheral arterial disease.

OBJECTIVE: The optimal timing and modality of surveillance after endovascular intervention for peripheral arterial disease is controversial, and no randomized trial to assess the value of peripheral endovascular intervention has ever been performed. The aim of this systematic review was to examine the practice of surveillance after peripheral endovascular intervention in randomized trials. METHODS: We used the Medline, Embase, Cochrane Library, and WHO trial registry databases in this systematic review of the literature to capture surveillance strategies used in randomized trials comparing endovascular interventions. Surveillance protocols were assessed for completeness, modalities used, duration, and intensity. RESULTS: Ninety-six different surveillance protocols were reported in 103 trials comparing endovascular interventions. Protocol specification was incomplete in 32% of trials. The majority of trials used multiple surveillance modalities (mean of 3.46 modalities), most commonly clinical examination (96%), ankle-brachial index (80%), duplex ultrasound examination (75%), and digital subtraction angiography (51%). Trials involving infrapopliteal lesions used more angiographic surveillance than trials with femoropopliteal lesions (P = .006). The median number of surveillance visits in the first 12 months after intervention was three and the mean surveillance duration was 21 months. Trials treating infrapopliteal vessels had a higher surveillance intensity compared with those treating femoropopliteal lesions in the first 12 months after endovascular intervention (mean 5 vs 3 surveillance visits; P = .017). Trials with drug-eluting devices had longer surveillance duration compared with those without (mean 26 vs 19 months; P = .020). CONCLUSIONS: There is a high level of variation in the modality, duration, and intensity of surveillance protocols used in randomized trials comparing different types of peripheral endovascular arterial intervention. Further research is required to determine the value and impact of postprocedural surveillance on patient outcomes.

Short-term risk prediction after major lower limb amputation: PERCEIVE study.

BACKGROUND: The accuracy with which healthcare professionals (HCPs) and risk prediction tools predict outcomes after major lower limb amputation (MLLA) is uncertain. The aim of this study was to evaluate the accuracy of predicting short-term (30 days after MLLA) mortality, morbidity, and revisional surgery. METHODS: The PERCEIVE (PrEdiction of Risk and Communication of outcomE following major lower limb amputation: a collaboratIVE) study was launched on 1 October 2020. It was an international multicentre study, including adults undergoing MLLA for complications of peripheral arterial disease and/or diabetes. Preoperative predictions of 30-day mortality, morbidity, and MLLA revision by surgeons and anaesthetists were recorded. Probabilities from relevant risk prediction tools were calculated. Evaluation of accuracy included measures of discrimination, calibration, and overall performance. RESULTS: Some 537 patients were included. HCPs had acceptable discrimination in predicting mortality (931 predictions; C-statistic 0.758) and MLLA revision (565 predictions; C-statistic 0.756), but were poor at predicting morbidity (980 predictions; C-statistic 0.616). They overpredicted the risk of all outcomes. All except three risk prediction tools had worse discrimination than HCPs for predicting mortality (C-statistics 0.789, 0.774, and 0.773); two of these significantly overestimated the risk compared with HCPs. SORT version 2 (the only tool incorporating HCP predictions) demonstrated better calibration and overall performance (Brier score 0.082) than HCPs. Tools predicting morbidity and MLLA revision had poor discrimination (C-statistics 0.520 and 0.679). CONCLUSION: Clinicians predicted mortality and MLLA revision well, but predicted morbidity poorly. They overestimated the risk of mortality, morbidity, and MLLA revision. Most short-term risk prediction tools had poorer discrimination or calibration than HCPs. The best method of predicting mortality was a statistical tool that incorporated HCP estimation.

A Systematic Review and Meta-Analysis on the Impact of High On-Treatment Platelet Reactivity on Clinical Outcomes for Patients Taking ADP Receptor Inhibitors Following Lower Limb Arterial Endovascular Intervention.

OBJECTIVE: Adenosine diphosphate (ADP) receptor inhibitors such as clopidogrel are known to be less effective at reducing platelet function for some patients because of a phenomenon called high on-treatment platelet reactivity (HTPR). However, the clinical effect of this for patients undergoing endovascular intervention for peripheral arterial disease is unclear. The aim of this study was to assess the impact of ADP receptor inhibitor HTPR on clinical outcomes following lower limb arterial endovascular intervention for peripheral arterial disease. METHODS: A systematic review and meta-analysis was performed. Primary outcomes included all cause mortality and major bleeding. Secondary outcomes were major adverse cardiovascular events, major adverse limb events, restenosis, and target lesion revascularisation. Outcome quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. RESULTS: There were 10 eligible studies including 1 444 patients included in the meta-analysis. The most commonly tested ADP receptor inhibitor was clopidogrel (seven studies). The pooled rate of ADP receptor inhibitor HTPR was 29% (95% CI 27 - 32). The meta-analysis showed that ADP receptor inhibitor HTPR was associated with a greater risk of major adverse limb events (OR 6.25, 95% CI 2.09 - 18.68, p = .001) and a trend towards a higher all cause mortality (OR 1.71, 95% CI 0.99 - 2.94, p = .050) and more major adverse cardiovascular events (OR 4.23, 95% CI 0.46 - 38.92, p = .20) after endovascular intervention. Overall strength of evidence was very low for all outcomes. CONCLUSION: ADP receptor inhibitor HTPR was associated with worse clinical outcomes after lower limb endovascular intervention for peripheral arterial disease. Prospective studies are required to determine the impact of modifying the antithrombotic regimen on clinical outcomes.

Editor's Choice - Systematic Review and Narrative Synthesis of Randomised Controlled Trials Supporting Implantable Devices for Vascular and Endovascular Procedures.

OBJECTIVE: To identify implantable devices currently used for vascular and endovascular procedures, to ascertain how many have randomised controlled trial (RCT) evidence available, and to assess the quality of that evidence. DATA SOURCES: MEDLINE, Embase, DARE, PROSPERO, clinical trial registries, and Cochrane databases. REVIEW METHODS: A list of current devices used in both vascular and endovascular procedures was generated by searching conference proceedings, manufacturer catalogues, and websites. MEDLINE, Embase, DARE, PROSPERO, clinical trial registries, and Cochrane databases were searched from inception up to June 2020. The primary outcome was the availability of RCTs to support the use of a vascular implantable device. RCTs were then quality assessed using the Cochrane risk of bias tool. RESULTS: A total of 116 current vascular implantable devices were identified. The systematic literature review identified 165 RCTs. Eighty-three of the RCTs (50.3%) applied to 33 of the 116 (28.4%) current implantable devices. When grouped by device type, eight of the 13 types (62%) had at least one RCT performed. There was a high risk of bias across the majority of the RCTs, with only nine (5.4%) deemed to be at low risk of bias. Only 22 (13.3%) RCTs had a clear safety outcome. CONCLUSION: Sixty-two per cent of implantable device types for use in vascular and endovascular interventions had at least one RCT available to show equivalence to previous devices or safety. RCTs were generally of low quality and are decreasing in frequency with time. With medical implantable device failure being increasingly recognised as causing significant harm to patients worldwide, there is a clear need for a more robust implantable device regulation and approval systems.

Antithrombotic Therapy for Aortic Aneurysms: A Systematic Review and Meta-Analysis.

OBJECTIVES: The role of antithrombotic therapy in the management of aortic and peripheral aneurysms is unclear. This systematic review and meta-analysis aimed to assess the impact of antithrombotics on clinical outcomes for aortic and peripheral aneurysms. METHODS: Medline, Embase, and CENTRAL databases were searched. Randomised controlled trials and observational studies investigating the effect of antithrombotic therapy on clinical outcomes for patients with any aortic or peripheral artery aneurysm were included. RESULTS: Fifty-nine studies (28 with antiplatelet agents, 12 anticoagulants, two intra-operative heparin, and 16 any antithrombotic agent) involving 122 102 patients were included. Abdominal aortic aneurysm (AAA) growth rate was not significantly associated with the use of antiplatelet therapy (SMD -0.36 mm/year; 95% CI -0.75 - 0.02; p = .060; GRADE certainty: very low). Antithrombotics were associated with increased 30 day mortality for patients with AAAs undergoing intervention (OR 2.30; 95% CI 1.51 - 3.51; p < .001; GRADE certainty: low). Following intervention, antiplatelet therapy was associated with reduced long term all cause mortality (HR 0.84; 95% CI 0.76 - 0.92; p < .001; GRADE certainty: moderate), whilst anticoagulants were associated with increased all cause mortality (HR 1.64; 95% CI 1.14 - 2.37; p = .008; GRADE certainty: very low), endoleak within three years (OR 1.99; 95% CI 1.10 - 3.60; p = .020; I2 = 60%; GRADE certainty: very low), and an increased re-intervention rate at one year (OR 3.25; 95% CI 1.82 - 5.82; p < .001; I2 = 35%; GRADE certainty: moderate). Five studies examined antithrombotic therapy for popliteal aneurysms. Meta-analysis was not possible due to heterogeneity. CONCLUSIONS: There was a lack of high quality data examining antithrombotic therapy for patients with aneurysms. Antiplatelet therapy was associated with a reduction in post-intervention all cause mortality for AAA, whilst anticoagulants were associated with an increased risk of all cause mortality, endoleak, and re-intervention. Large, well designed trials are still required to determine the therapeutic benefits of antithrombotic agents in this setting.

The OAC3-PAD Risk Score Predicts Major Bleeding Events one Year after Hospitalisation for Peripheral Artery Disease.

OBJECTIVE: There is a paucity of evidence concerning the risk of bleeding after hospitalisation for symptomatic peripheral artery disease (PAD) in everyday clinical practice, as randomised clinical trials commonly exclude patients with heightened risk. The current study aimed to develop a pragmatic risk score that enables prediction of major bleeding during the first year after index discharge. METHODS: Unselected retrospective data from the second largest insurance fund in Germany, BARMER, were used to identify patients with a first hospitalisation for PAD registered between 1 January 2010 and 31 December 2018. Within a separate training cohort, final predictors were selected using penalised Cox regression (least absolute shrinkage and selection operator with ten fold cross validation) with one year major bleeding requiring hospitalisation as outcome. The risk score was internally validated. Four different risk groups were constructed. RESULTS: A total of 81 930 patients (47.2% female, 72.3 years) underwent hospitalisation for symptomatic PAD. After one year, 1 831 (2.2%) of the patients had a major bleeding event. Independent predictors were previous oral anticoagulation, age over 80, chronic limb threatening ischaemia, congestive heart failure, severe chronic kidney disease, previous bleeding event, anaemia, and dementia. The OAC3-PAD risk score exhibited adequate calibration and discrimination between four risk groups (c = 0.69, 95% confidence interval 0.67 - 0.71) from low risk (1.3%) to high risk (6.4%). CONCLUSION: A pragmatic risk score was developed to predict the individual major bleeding risk classifying a fifth of the cohort as high risk patients. Individual prediction scores such as the one proposed here may help to inform the risk and benefit of intensified antithrombotic strategies.

A systematic review of outcome reporting for interventions to treat people with diabetic foot ulceration.

BACKGROUND: Diabetic foot ulceration (DFU) is a challenging clinical problem that affects up to a quarter of patients with diabetes in their lifetime. An agreed set of outcomes for assessing treatments or interventions for DFU has not previously been considered. The aim of this study was to identify outcomes that are reported in clinical studies assessing a treatment or intervention for DFU, to inform the development of a core outcome set (COS). METHODS: Systematic literature searches were performed between January 2016 and March 2019. The search strategy was pre-registered with PROSPERO (CRD42019128250). Two authors independently screened abstracts for full text review. Outcomes were extracted from selected papers verbatim and categorized into domains according to established taxonomy. Consistency of outcome reporting was assessed. Overlapping outcomes were merged independently to condense the extracted list of outcomes for use in forthcoming consensus processes. RESULTS: Of 4645 abstracts identified, 114 studies met the inclusion criteria. There were 69 randomized studies, 40 prospective studies and 5 protocols. Some 948 outcomes were extracted verbatim. Outcome reporting was consistent for 474 (53%) outcomes. De-duplication left 714 unique verbatim outcomes across 33 domains. Merging of overlapping unique verbatim outcomes established 95 merged outcomes. CONCLUSION: This study describes contemporary outcomes reported in studies assessing interventions for DFU. Outcome reporting is considered to be poor as it was consistent in just over half of outcomes extracted. Merging of outcomes has identified 95 outcomes that can be taken forward in the development of a COS.

Systematic Review and Meta-Analysis of the Effect of Perineural Catheters in Major Lower Limb Amputations.

OBJECTIVE: Controlling pain after major lower limb amputation (MLLA) is of critical importance to patients and clinicians. The aim of this systematic review and meta-analysis was to assess the effect of perineural catheters (PNCs) on post-operative pain, post-operative morphine requirement, in-hospital mortality, long term phantom limb pain, and chronic stump pain. METHODS: A systematic review using PubMed, EMBASE via OVID and the Cochrane library from database inception (1946) to 20 October 2020 was performed according to PRISMA guidelines. Studies involving patients undergoing MLLA which reported on post-operative morphine requirement, pain scores, in-hospital mortality, phantom limb pain (PLP), and chronic stump pain were included. Studies comparing PNC use with epidural or wound site local anaesthetic infusions were excluded. Outcome data were extracted from individual studies and meta-analysis was performed using a random effects (Mantel-Haenszel) model for dichotomous data using an odds ratio (OR) summary statistic with 95% confidence intervals (CI), and with an inverse variance random effects model for continuous data using a standardised mean difference (SMD) summary statistic with 95% CIs. Sensitivity analyses were performed for post-operative pain scores and post-operative morphine requirement. Study quality was assessed using the Downs and Black score, and outcomes were assessed using the GRADE tool. RESULTS: Ten studies reporting on 731 patients were included, with 350 patients receiving a PNC and 381 receiving standard care. PNC use is associated with a reduction in post-operative pain (SMD -0.30, 95% CI -0.58 - -0.01, p = .040, I2 = 54%, GRADE quality of evidence: low) and post-operative morphine requirements (SMD -0.63, 95% CI -1.03 - -0.23, p = .002, I2 = 75%, GRADE quality of evidence: moderate), although the effect of PNC on reduced post-operative morphine requirements is lost on sensitivity analysis of randomised trials only (p = .40). No demonstrable effect was found on in-hospital mortality, PLP, or chronic stump pain (GRADE quality of evidence: low). CONCLUSION: PNC use in amputees is associated with a significant reduction in post-operative pain scores and post-operative morphine requirements, although this latter finding is lost on sensitivity analysis of randomised trials only.

Patient Reported Outcome Measures for Major Lower Limb Amputation Caused by Peripheral Artery Disease or Diabetes: A Systematic Review.

OBJECTIVE: Most major lower limb amputations are related to peripheral artery disease (PAD) or diabetes. Just 40% of patients who undergo major lower limb amputation will use a prosthesis yet measures of surgical success commonly focus on prosthesis use. Patient reported outcome measures (PROMs) are valuable to comprehensively evaluate health related quality of life (HRQL) after surgery. This systematic review aimed to identify and describe PROMs available to assess HRQL in patients after amputation for PAD or diabetes. METHODS: A search was conducted based on the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) for systematic reviews of PROMs. Ovid MEDLINE, Ovid EMBASE, PsycINFO, CINAHL, and Cochrane CENTRAL were also searched from inception until August 2019. Included were articles describing the development, measurement properties, or evaluation of HRQL via a PROM in adult patients after amputation for PAD or diabetes. Studies of amputation exclusively for trauma or malignancy were excluded. Data were collected on study characteristics, PROM characteristics (generic/disease specific), and properties of amputation specific PROMs. RESULTS: Of 3 317 abstracts screened, 111 full text articles were assessed for eligibility and 64 included. Fifty-six studies evaluated HRQL, with 23 (46%) of these using an amputation specific PROM to do so. Eleven different amputation specific PROMs were identified, 10 (91%) of which were developed only for prosthesis users. One measure was suitable for use in all patients after amputation. This "Amputee single item mobility measure" includes a single item evaluating mobility. Nine studies reported some psychometric testing of an amputation specific PROM. CONCLUSION: A well tested, multidimensional PROM applicable to wheelchair and prosthetic users after amputation is lacking and urgently needed for studies in this field. Future work to develop an appropriate measure is required.

A Systematic Review and Narrative Synthesis of Risk Prediction Tools Used to Estimate Mortality, Morbidity, and Other Outcomes Following Major Lower Limb Amputation.

OBJECTIVE: The decision to undertake a major lower limb amputation can be complex. This review evaluates the performance of risk prediction tools in estimating mortality, morbidity, and other outcomes following amputation. METHODS: A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The MEDLINE, Embase, and Cochrane databases were searched to identify studies reporting on risk prediction tools that predict outcomes following amputation. Outcome measures included the accuracy of the risk tool in predicting a range of post-operative complications, including mortality (both short and long term), peri-operative morbidity, need for re-amputation, and ambulation success. A narrative synthesis was performed in accordance with the Guidance on the Conduct of Narrative Synthesis In Systematic Reviews. RESULTS: The search identified 518 database records. Twelve observational studies, evaluating 13 risk prediction tools in a total cohort of 61 099 amputations, were included. One study performed external validation of an existing risk prediction tool, while all other studies developed novel tools or modified pre-existing generic calculators. Two studies conducted external validation of the novel/modified tools. Nine tools provided risk estimations for mortality, two tools provided predictions for post-operative morbidity, two for likelihood of ambulation, and one for re-amputation to the same or higher level. Most mortality prediction tools demonstrated acceptable discrimination performance with C statistic values ranging from 0.65 to 0.81. Tools estimating the risk of post-operative complications (0.65 - 0.74) and necessity for re-amputation (0.72) also performed acceptably. The Blatchford Allman Russell tool demonstrated outstanding discrimination for predicting functional mobility outcomes post-amputation (0.94). Overall, most studies were at high risk of bias with poor external validity. CONCLUSION: This review identified several risk prediction tools that demonstrate acceptable to outstanding discrimination for objectively predicting an array of important post-operative outcomes. However, the methodological quality of some studies was poor, external validation studies are generally lacking, and there are no tools predicting other important outcomes, especially quality of life.

The Development and Usability of the AMPREDICT Decision Support Tool: A Mixed Methods Study.

OBJECTIVE: Amputation level decision making in patients with chronic limb threatening ischaemia is challenging. Currently, evidence relies on published average population risks rather than individual patient risks. The result is significant variation in the distribution of amputation levels across health systems, geographical regions, and time. Clinical decision support has been shown to enhance decision making, especially complex decision making. The goal of this study was to translate the previously validated AMPREDICT prediction models by developing and testing the usability of the AMPREDICT Decision Support Tool (DST), a novel, web based, clinical DST that calculates individual one year post-operative risk of death, re-amputation, and probability of achieving independent mobility by amputation level. METHODS: A mixed methods approach was used. Previously validated prediction models were translated into a web based DST with additional content and format developed by an expert panel. Tool usability was assessed using the Post-Study System Usability Questionnaire (PSSUQ; a 16 item scale with scores ranging from 1 to 7, where lower scores indicate greater usability) by 10 clinician end users from diverse specialties, sex, geography, and clinical experience. Think aloud, semi-structured, qualitative interviews evaluated the AMPREDICT DST's look and feel, user friendliness, readability, functionality, and potential implementation challenges. RESULTS: The PSSUQ overall and subscale scores were favourable, with a mean overall total score of 1.57 (standard deviation [SD] 0.69) and a range from 1.00 to 3.21. The potential clinical utility of the DST included (1) assistance in counselling patients on amputation level decisions, (2) setting outcome expectations, and (3) use as a tool in the academic environment to facilitate understanding of factors that contribute to various outcome risks. CONCLUSION: After extensive iterative development and testing, the AMPREDICT DST was found to demonstrate strong usability characteristics and clinical relevance. Further evaluation will benefit from integration into an electronic health record with assessment of its impact on physician and patient shared amputation level decision making.

Prognostic Risk Modelling for Patients Undergoing Major Lower Limb Amputation: An Analysis of the UK National Vascular Registry.

OBJECTIVE: Major lower limb amputation is the highest risk lower limb procedure in vascular surgery. Despite this, few high quality studies have examined factors contributing to mortality. The aim was to identify independent risk factors for peri-operative morbidity and mortality and develop reliable models for estimating risk. METHODS: All patients undergoing lower limb amputation above the ankle entered into the UK National Vascular Registry (January 2014-December 2016) were included. Missing data were handled using multiple imputation. Models were developed to evaluate independent risk factors for mortality (the primary outcome) and morbidity using logistic regression, minimising the Bayesian information criterion to balance complexity and model fit. Ethical approval for the study was granted (Wales REC 3 ref:16/WA/0353). RESULTS: All 9549 above ankle joint amputations in the registry were included. Overall, 865 patients (9.1%) died before leaving hospital. Independent factors associated with mortality were emergency admission, bilateral operation, age, American Society of Anesthesiologists' grade, abnormal electrocardiogram, and increased white cell count or creatinine (p < .01 for all). Independent factors reducing mortality were transtibial operation, increased albumin or patient weight, and previous ipsilateral revascularisation procedures (p < .01 for all). A risk model incorporating these factors had good discrimination (C-statistic 0.79, 95% confidence interval 0.77-0.80) and excellent calibration. Morbidity rates were high, with 6.6%, 9.7%, and 4.3% of patients suffering cardiac, respiratory, and renal complications, respectively. The risk model was also predictive of morbidity outcomes (C-statistics 0.74, 0.69, and 0.74, respectively). CONCLUSION: Morbidity and mortality after lower limb amputation are high in the UK. Some potentially modifiable factors for quality improvement initiatives have been identified and accurate predictive models that could assist patient counselling and decision making have been developed.

Early and Long Term Outcomes Following Long Posterior Flap vs. Skew Flap for Below Knee Amputations.

OBJECTIVE: To compare outcomes between long posterior flap (LPF) and skew flap (SF) amputation over a 13 year period. METHODS: This was a retrospective observational cohort study. Consecutive patients undergoing a LPF or SF below knee amputation (BKA) over a 13 year period at one hospital were identified. Both techniques were performed regularly, depending on tissue loss and surgeon preference. The primary outcome was surgical revision of any kind. Secondary outcomes included revision to above knee amputation (AKA), length of hospital stay (LOS), and mortality. A smaller cohort of patients who were alive and unilateral below knee amputees were contacted to ascertain prosthetic use and functional status. RESULTS: In total, 242 BKAs were performed in 212 patients (125 LPF and 117 SF; median follow up 25.8 months). Outcomes for the two groups were equivalent for surgical revision of any kind (27 LPF vs. 31 SF; p = .37), revision to an AKA (18 LPF vs. 14 SF; p = .58), LOS (29 days for LPF vs. 28 days for SF; p = .83), and median survival (23.9 months for LPF vs. 28.8 months for SF; p = .89). Multivariable analysis found amputation type had no effect on any outcome. Functional scores from a smaller cohort of 40 unilateral amputees who were contactable demonstrated improved outcomes with the LPF vs. the SF (p = .038). CONCLUSION: Both techniques appear equivalent for rates of surgical residual limb failure. Functional outcomes may be better with the LPF.

Antiplatelet and Anticoagulant Use in Randomised Trials of Patients Undergoing Endovascular Intervention for Peripheral Arterial Disease: Systematic Review and Narrative Synthesis.

OBJECTIVE: Randomised trials of new devices for peripheral arterial endovascular intervention are published regularly. The evidence for which antiplatelet and/or anticoagulant (antithrombotic) therapy to use after an intervention is lacking. The aim of this systematic review was to examine the antithrombotic regimens in randomised trials for peripheral arterial endovascular intervention to understand choices made and trends with time or type of device. METHODS: Data sources were the Medline, Embase, and Cochrane Library databases. Randomised trials including participants with peripheral arterial disease undergoing any endovascular arterial intervention were included. Trial methods were assessed to determine whether an antithrombotic protocol had been specified, its completeness, and the agent(s) prescribed. Antithrombotic therapy protocols were classed as peri-procedural (preceding and during intervention), immediate post-procedural (up to 30 days following intervention), and maintenance post-procedural (therapy continuing beyond 30 days). RESULTS: Ninety-four trials were included in narrative synthesis. Study quality was low. None of the trials justified their antithrombotic therapy protocol. Only 29% of trials had complete peri-procedural antithrombotic protocols, and 34% had complete post-procedural protocols. In total, 64 different peri-procedural protocols, and 51 separate post-procedural protocols were specified. Antiplatelet monotherapy and unfractionated heparin were the most common regimen choices in the peri-procedural setting, and dual antiplatelet therapy (55%) was most commonly utilised post procedure. Over time there has been an increasing tendency to use dual therapy (p < .001). This corresponds with the introduction of newer technologies and trials focussed on below knee intervention. CONCLUSION: Randomised trials comparing different types of peripheral endovascular arterial intervention have a high level of heterogeneity in their antithrombotic regimens. Antiplatelet therapy needs to be standardised in trials comparing endovascular technologies to reduce potential confounding. To do this, an independent randomised trial specifically examining antiplatelet therapy following peripheral arterial endovascular intervention is needed.