Peripheral arterial disease (PAD) – A challenging manifestation of atherosclerosis

The diagnosis of peripheral arterial disease (PAD) is not always evident as symptoms and signs may show great variation. As all grades of PAD are linked to both an increased risk for cardiovascular complications and adverse limb events, awareness of the condition and knowledge about diagnostic measures, prevention and treatment is crucial. This article presents in a condensed form information on PAD and its management

Cancer and stroke : commonly encountered by clinicians, but little evidence to guide clinical approach

The association between stroke and cancer is well-established. Because of an aging population and longer survival rates, the frequency of synchronous stroke and cancer will become even more common. Different pathophysiologic mechanisms have been proposed how cancer or cancer treatment directly or via coagulation disturbances can mediate stroke. Increased serum levels of D-dimer, fibrin degradation products, and CRP are more often seen in stroke with concomitant cancer, and the clot retrieved during thrombectomy has a more fibrin- and platelet-rich constitution compared with that of atherosclerotic etiology. Multiple infarctions are more common in patients with active cancer compared with those without a cancer diagnosis. New MRI techniques may help in detecting typical patterns seen in the presence of a concomitant cancer. In ischemic stroke patients, a newly published cancer probability score can help clinicians in their decision-making when to suspect an underlying malignancy in a stroke patient and to start cancer-screening studies. Treating stroke patients with synchronous cancer can be a delicate matter. Limited evidence suggests that administration of intravenous thrombolysis appears safe in non-axial intracranial and non-metastatic cancer patients. Endovascular thrombectomy is probably rather safe in these patients, but probably futile in most patients placed on palliative care due to their advanced disease. In this topical review, we discuss the epidemiology, pathophysiology, and prognosis of ischemic and hemorrhagic strokes as well as cerebral venous thrombosis and concomitant cancer. We further summarize the current evidence on acute management and secondary preventive therapy.Peer reviewe

Effectiveness of bedside investigations to diagnose peripheral artery disease among people with diabetes mellitus: A systematic review.

As a progressive disease process, early diagnosis and ongoing monitoring and treatment of lower limb peripheral artery disease (PAD) is critical to reduce the risk of diabetes-related foot ulcer (DFU) development, non-healing of wounds, infection and amputation, in addition to cardiovascular complications. There are a variety of non-invasive tests available to diagnose PAD at the bedside, but there is no consensus as to the most diagnostically accurate of these bedside investigations or their reliability for use as a method of ongoing monitoring. Therefore, the aim of this systematic review was to first determine the diagnostic accuracy of non-invasive bedside tests for identifying PAD compared to an imaging reference test and second to determine the intra- and inter-rater reliability of non-invasive bedside tests in adults with diabetes. A database search of Medline and Embase was conducted from 1980 to 30 November 2022. Prospective and retrospective investigations of the diagnostic accuracy of bedside testing in people with diabetes using an imaging reference standard and reliability studies of bedside testing techniques conducted in people with diabetes were eligible. Included studies of diagnostic accuracy were required to report adequate data to calculate the positive likelihood ratio (PLR) and negative likelihood ratio (NLR) which were the primary endpoints. The quality appraisal was conducted using the Quality Assessment of Diagnostic Accuracy Studies and Quality Appraisal of Reliability quality appraisal tools. From a total of 8517 abstracts retrieved, 40 studies met the inclusion criteria for the diagnostic accuracy component of the review and seven studies met the inclusion criteria for the reliability component of the review. Most studies investigated the diagnostic accuracy of ankle -brachial index (ABI) (N = 38). In people with and without DFU, PLRs ranged from 1.69 to 19.9 and NLRs from 0.29 to 0.84 indicating an ABI 1.3, TBI of <0.70, and absent or monophasic pedal Doppler waveforms are useful to identify the presence of disease. The ability of the tests to exclude disease is variable and although reliability may be acceptable, evidence of error in the measurements means test results that are within normal limits should be considered with caution and in the context of other vascular assessment findings (e.g., pedal pulse palpation and clinical signs) and progress of DFU healing

The intersocietal IWGDF, ESVS, SVS guidelines on peripheral artery disease in people with diabetes and a foot ulcer.

Diabetes related foot complications have become a major cause of morbidity and are implicated in most major and minor amputations globally. Approximately 50% of people with diabetes and a foot ulcer have peripheral artery disease (PAD) and the presence of PAD significantly increases the risk of adverse limb and cardiovascular events. The International Working Group on the Diabetic Foot (IWGDF) has published evidence based guidelines on the management and prevention of diabetes related foot complications since 1999. This guideline is an update of the 2019 IWGDF guideline on the diagnosis, prognosis and management of peripheral artery disease in people with diabetes mellitus and a foot ulcer. For this guideline the IWGDF, the European Society for Vascular Surgery and the Society for Vascular Surgery decided to collaborate to develop a consistent suite of recommendations relevant to clinicians in all countries. This guideline is based on three new systematic reviews. Using the Grading of Recommendations, Assessment, Development, and Evaluation framework clinically relevant questions were formulated, and the literature was systematically reviewed. After assessing the certainty of the evidence, recommendations were formulated which were weighed against the balance of benefits and harms, patient values, feasibility, acceptability, equity, resources required, and when available, costs. Through this process five recommendations were developed for diagnosing PAD in a person with diabetes, with and without a foot ulcer or gangrene. Five recommendations were developed for prognosis relating to estimating likelihood of healing and amputation outcomes in a person with diabetes and a foot ulcer or gangrene. Fifteen recommendations were developed related to PAD treatment encompassing prioritisation of people for revascularisation, the choice of a procedure and post-surgical care. In addition, the Writing Committee has highlighted key research questions where current evidence is lacking. The Writing Committee believes that following these recommendations will help healthcare professionals to provide better care and will reduce the burden of diabetes related foot complications

Performance of non-invasive bedside vascular testing in the prediction of wound healing or amputation among people with foot ulcers in diabetes: A systematic review.

INTRODUCTION The presence of peripheral artery disease (PAD) confers a significantly increased risk of failure to heal and major lower limb amputation for people with diabetes-related foot ulcer (DFU). Determining performance of non-invasive bedside tests for predicting likely DFU outcomes is therefore key to effective risk stratification of patients with DFU and PAD to guide management decisions. The aim of this systematic review was to determine the performance of non-invasive bedside tests for PAD to predict DFU healing, healing post-minor amputation, or need for minor or major amputation in people with diabetes and DFU or gangrene. METHODS A database search of Medline and Embase was conducted from 1980 to 30 November 2022. Prospective studies that evaluated non-invasive bedside tests in patients with diabetes, with and without PAD and foot ulceration or gangrene to predict the outcomes of DFU healing, minor amputation, and major amputation with or without revascularisation, were eligible. Included studies were required to have a minimum 6-month follow-up period and report adequate data to calculate the positive likelihood ratio (PLR) and negative likelihood ratio for the outcomes of DFU healing, and minor and major amputation. Methodological quality was assessed using the Quality in Prognosis Studies tool. RESULTS From 14,820 abstracts screened 28 prognostic studies met the inclusion criteria. The prognostic tests evaluated by the studies included: ankle-brachial index (ABI) in 9 studies; ankle pressures in 10 studies, toe-brachial index in 4 studies, toe pressure in 9 studies, transcutaneous oxygen pressure (TcPO2 ) in 7 studies, skin perfusion pressure in 5 studies, continuous wave Doppler (pedal waveforms) in 2 studies, pedal pulses in 3 studies, and ankle peak systolic velocity in 1 study. Study quality was variable. Common reasons for studies having a moderate or high risk of bias were poorly described study participation, attrition rates, and inadequate adjustment for confounders. In people with DFU, toe pressure ≥30 mmHg, TcPO2 ≥25 mmHg, and skin perfusion pressure of ≥40 mmHg were associated with a moderate to large increase in pretest probability of healing in people with DFU. Toe pressure ≥30 mmHg was associated with a moderate increase in healing post-minor amputation. An ABI using a threshold of ≥0.9 did not increase the pretest probability of DFU healing, whereas an ABI <0.5 was associated with a moderate increase in pretest probability of non-healing. Few studies investigated amputation outcomes. An ABI <0.4 demonstrated the largest increase in pretest probability of a major amputation (PLR ≥10). CONCLUSIONS Prognostic capacity of bedside testing for DFU healing and amputation is variable. A toe pressure ≥30 mmHg, TcPO2 ≥25 mmHg, and skin perfusion pressure of ≥40 mmHg are associated with a moderate to large increase in pretest probability of healing in people with DFU. There are little data available evaluating the prognostic capacity of bedside testing for healing after minor amputation or for major amputation in people with DFU. Current evidence suggests that an ABI <0.4 may be associated with a large increase in risk of major amputation. The findings of this systematic review need to be interpreted in the context of limitations of available evidence, including varying rates of revascularisation, lack of post-revascularisation bedside testing, and heterogenous subpopulations

Effectiveness of revascularisation for the ulcerated foot in patients with diabetes and peripheral artery disease: A systematic review.

INTRODUCTION Peripheral artery disease (PAD) is associated with an increased likelihood of delayed or non-healing of a diabetes-related foot ulcer, gangrene, and amputation. The selection of the most effective surgical technique for revascularisation of the lower limb in this population is challenging and there is a lack of conclusive evidence to support the choice of intervention. This systematic review aimed to determine, in people with diabetes and tissue loss, if direct revascularisation is superior to indirect revascularisation and if endovascular revascularisation is superior to open revascularisation for the outcomes of wound healing, minor or major amputation, and adverse events including mortality. METHODS Title and abstract searches of Medline, Embase, PubMed, and EBSCO were conducted from 1980 to 30th November 2022. Cohort and case-control studies and randomised controlled trials reporting comparative outcomes of direct (angiosome) revascularisation (DR) and indirect revascularisation (IR) or the comparative outcomes of endovascular revascularisation and open or hybrid revascularisation for the outcomes of healing, minor amputation, and major amputation in people with diabetes, PAD and tissue loss (including foot ulcer and/or gangrene) were eligible. Methodological quality was assessed using the Cochrane risk-of-bias tool for randomised trials, the ROBINS-I tool for non-randomised studies, and Newcastle-Ottawa Scale for observational and cohort studies where details regarding the allocation to intervention groups were not provided. RESULTS From a total 7086 abstracts retrieved, 26 studies met the inclusion criteria for the comparison of direct angiosome revascularisation (DR) and indirect revascularisation (IR), and 11 studies met the inclusion criteria for the comparison of endovascular and open revascularisation. One study was included in both comparisons. Of the included studies, 35 were observational (31 retrospective and 4 prospective cohorts) and 1 was a randomised controlled trial. Cohort study quality was variable and generally low, with common sources of bias related to heterogeneous participant populations and interventions and lack of reporting of or adjusting for confounding factors. The randomised controlled trial had a low risk of bias. For studies of DR and IR, results were variable, and it is uncertain if one technique is superior to the other for healing, prevention of minor or major amputation, or mortality. However, the majority of studies reported that a greater proportion of participants receiving DR healed compared with IR, and that IR with collaterals may have similar outcomes to DR for wound healing. For patients with diabetes, infrainguinal PAD, and an adequate great saphenous vein available for use as a bypass conduit who were deemed suitable for either surgical procedure, an open revascularisation first approach was superior to endovascular therapy to prevent a major adverse limb event or death (Hazard Ratio: 0.72; 95% CI 0.61-0.86). For other studies of open and endovascular approaches, there was generally no difference in outcomes between the interventions. CONCLUSIONS The majority of available evidence for the effectiveness of DR and IR and open and endovascular revascularisation for wound healing and prevention of minor and major amputation and adverse events including mortality in people with diabetes, PAD and tissue loss is inconclusive, and the certainty of evidence is very low. Data from one high quality randomised controlled trial supports the use of open over endovascular revascularisation to prevent a major limb event and death in people with diabetes, infrainguinal disease and tissue loss who have an adequate great saphenous vein available and who are deemed suitable for either approach

Efficacy of brief behavioral counselling by allied health professionals to promote physical activity in people with peripheral arterial disease (BIPP): study protocol for a multi-center randomized controlled trial

Background: Physical activity is recommended for people with peripheral arterial disease (PAD), and can improve walking capacity and quality of life; and reduce pain, requirement for surgery and cardiovascular events. This trial will assess the efficacy of a brief behavioral counselling intervention delivered by allied health professionals to improve physical activity in people with PAD. Methods: This is a multi-center randomised controlled trial in four cities across Australia. Participants (N = 200) will be recruited from specialist vascular clinics, general practitioners and research databases and randomised to either the control or intervention group. Both groups will receive usual medical care, a written PAD management information sheet including advice to walk, and four individualised contacts from a protocol-trained allied health professional over 3 months (weeks 1, 2, 6, 12). The control group will receive four 15-min telephone calls with general discussion about PAD symptoms and health and wellbeing. The intervention group will receive behavioral counselling via two 1-h face-to-face sessions and two 15-min telephone calls. The counselling is based on the 5A framework and will promote interval walking for 3 × 40 min/week. Assessments will be conducted at baseline, and 4, 12 and 24 months by staff blinded to participant allocation.Objectively assessed outcomes include physical activity (primary), sedentary behavior, lower limb body function, walking capacity, cardiorespiratory fitness, event-based claudication index, vascular interventions, clinical events, cardiovascular function, circulating markers, and anthropometric measures. Self-reported outcomes include physical activity and sedentary behavior, walking ability, pain severity, and health-related quality of life. Data will be analysed using an intention-to-treat approach. An economic evaluation will assess whether embedding the intervention into routine care would likely be value for money. A cost-effectiveness analysis will estimate change in cost per change in activity indicators due to the intervention, and a cost-utility analysis will assess change in cost per quality-adjusted life year. A full uncertainty analysis will be undertaken, including a value of information analysis, to evaluate the economic case for further research. Discussion: This trial will evaluate the efficacy and cost-effectiveness of a brief behavioral counselling intervention for a common cardiovascular disease with significant burden. Trial registration: ACTRN 12614000592640 Australian New Zealand Clinical Trials Registry. Registration Date 4 June 2014