Ankle brachial index for the diagnosis of lower limb peripheral arterial disease

Background Peripheral arterial disease (PAD) of the lower limb is common, with prevalence of both symptomatic and asymptomatic disease estimated at 13% in the over 50 age group. Symptomatic PAD affects about 5% of individuals in Western populations between the ages of 55 and 74 years. The most common initial symptom of PAD is muscle pain on exercise that is relieved by rest and is attributed to reduced lower limb blood flow due to atherosclerotic disease (intermittent claudication). The ankle brachial index (ABI) is widely used by a variety of healthcare professionals, including specialist nurses, physicians, surgeons and podiatrists working in primary and secondary care settings, to assess signs and symptoms of PAD. As the ABI test is non‐invasive and inexpensive and is in widespread clinical use, a systematic review of its diagnostic accuracy in people presenting with leg pain suggestive of PAD is highly relevant to routine clinical practice. Objectives To estimate the diagnostic accuracy of the ankle brachial index (ABI) ‐ also known as the ankle brachial pressure index (ABPI) ‐ for the diagnosis of peripheral arterial disease in people who experience leg pain on walking that is alleviated by rest. Search methods We carried out searches of the following databases in August 2013: MEDLINE (Ovid SP),Embase (Ovid SP), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO), Latin American and Caribbean Health Sciences (LILACS) (Bireme), Database of Abstracts of Reviews of Effects and the Health Technology Assessment Database in The Cochrane Library, the Institute for Scientific Information (ISI) Conference Proceedings Citation Index ‐ Science, the British Library Zetoc Conference search and Medion. Selection criteria We included cross‐sectional studies of ABI in which duplex ultrasonography or angiography was used as the reference standard. We also included cross‐sectional or diagnostic test accuracy (DTA) cohort studies consisting of both prospective and retrospective studies.Participants were adults presenting with leg pain on walking that was relieved by rest, who were tested in primary care settings or secondary care settings (hospital outpatients only) and who did not have signs or symptoms of critical limb ischaemia (rest pain, ischaemic ulcers or gangrene).The index test was ABI, also called the ankle brachial pressure index (ABPI) or the Ankle Arm Index (AAI), which was performed with a hand‐held doppler or oscillometry device to detect ankle vessels. We included data collected via sphygmomanometers (both manual and aneroid) and digital equipment. Data collection and analysis Two review authors independently replicated data extraction by using a standard form, which included an assessment of study quality, and resolved disagreements by discussion. Two review authors extracted participant‐level data when available to populate 2×2 contingency tables (true positives, true negatives, false positives and false negatives).After a pilot phase involving two review authors working independently, we used the methodological quality assessment tool the Quality Assessment of Diagnostic Accuracy Studies‐2 (QUADAS‐2), which incorporated our review question ‐ along with a flow diagram to aid reviewers' understanding of the conduct of the study when necessary and an assessment of risk of bias and applicability judgements. Main results We screened 17,055 records identified through searches of databases. We obtained 746 full‐text articles and assessed them for relevance. We scrutinised 49 studies to establish their eligibility for inclusion in the review and excluded 48, primarily because participants were not patients presenting solely with exertional leg pain, investigators used no reference standard or investigators used neither angiography nor duplex ultrasonography as the reference standard. We excluded most studies for more than one reason.Only one study met the eligibility criteria and provided limb‐level accuracy data from just 85 participants (158 legs). This prospective study compared the manual doppler method of obtaining an ABI (performed by untrained personnel) with the automated oscillometric method. Limb‐level data, as reported by the study, indicated that the accuracy of the ABI in detecting significant arterial disease on angiography is superior when stenosis is present in the femoropopliteal vessels, with sensitivity of 97% (95% confidence interval (CI) 93% to 99%) and specificity of 89% (95% CI 67% to 95%) for oscillometric ABI, and sensitivity of 95% (95% CI 89% to 97%) and specificity of 56% (95% CI 33% to 70%) for doppler ABI. The ABI threshold was not reported. Investigators attributed the lower specificity for doppler to the fact that a tibial or dorsalis pedis pulse could not be detected by doppler in 12 of 27 legs with normal vessels or non‐significant lesions. The superiority of the oscillometric (automated) method for obtaining an ABI reading over the manual method with a doppler probe used by inexperienced operators may be a clinically important finding. Authors' conclusions Evidence about the accuracy of the ankle brachial index for the diagnosis of PAD in people with leg pain on exercise that is alleviated by rest is sparse. The single study included in our review provided only limb‐level data from a few participants. Well‐designed cross‐sectional studies are required to evaluate the accuracy of ABI in patients presenting with early symptoms of peripheral arterial disease in all healthcare settings. Another systematic review of existing studies assessing the use of ABI in alternative patient groups, including asymptomatic, high‐risk patients, is required.Publisher PDFPeer reviewe

D-dimer test for excluding the diagnosis of pulmonary embolism

Background Pulmonary embolism (PE) can occur when a thrombus (blood clot) travels through the veins and lodges in the arteries of the lungs, producing an obstruction. People who are thought to be at risk include those with cancer, people who have had a recent surgical procedure or have experienced long periods of immobilisation and women who are pregnant. The clinical presentation can vary, but unexplained respiratory symptoms such as difficulty breathing, chest pain and an increased respiratory rate are common. D‐dimers are fragments of protein released into the circulation when a blood clot breaks down as a result of normal body processes or with use of prescribed fibrinolytic medication. The D‐dimer test is a laboratory assay currently used to rule out the presence of high D‐dimer plasma levels and, by association, venous thromboembolism (VTE). D‐dimer tests are rapid, simple and inexpensive and can prevent the high costs associated with expensive diagnostic tests. Objectives To investigate the ability of the D‐dimer test to rule out a diagnosis of acute PE in patients treated in hospital outpatient and accident and emergency (A&E) settings who have had a pre‐test probability (PTP) of PE determined according to a clinical prediction rule (CPR), by estimating the accuracy of the test according to estimates of sensitivity and specificity. The review focuses on those patients who are not already established on anticoagulation at the time of study recruitment. Search methods We searched 13 databases from conception until December 2013. We cross‐checked the reference lists of relevant studies. Selection criteria Two review authors independently applied exclusion criteria to full papers and resolved disagreements by discussion. We included cross‐sectional studies of D‐dimer in which ventilation/perfusion (V/Q) scintigraphy, computerised tomography pulmonary angiography (CTPA), selective pulmonary angiography and magnetic resonance pulmonary angiography (MRPA) were used as the reference standard. • Participants: Adults who were managed in hospital outpatient and A&E settings and were suspected of acute PE were eligible for inclusion in the review if they had received a pre‐test probability score based on a CPR. • Index tests: quantitative, semi quantitative and qualitative D‐dimer tests. • Target condition: acute symptomatic PE. • Reference standards: We included studies that used pulmonary angiography, V/Q scintigraphy, CTPA and MRPA as reference standard tests. Data collection and analysis Two review authors independently extracted data and assessed quality using Quality Assessment of Diagnostic Accuracy Studies‐2 (QUADAS‐2). We resolved disagreements by discussion. Review authors extracted patient‐level data when available to populate 2 × 2 contingency tables (true‐positives (TPs), true‐negatives (TNs), false‐positives (FPs) and false‐negatives (FNs)). Main results We included four studies in the review (n = 1585 patients). None of the studies were at high risk of bias in any of the QUADAS‐2 domains, but some uncertainty surrounded the validity of studies in some domains for which the risk of bias was uncertain. D‐dimer assays demonstrated high sensitivity in all four studies, but with high levels of false‐positive results, especially among those over the age of 65 years. Estimates of sensitivity ranged from 80% to 100%, and estimates of specificity from 23% to 63%. Authors' conclusions A negative D‐dimer test is valuable in ruling out PE in patients who present to the A&E setting with a low PTP. Evidence from one study suggests that this test may have less utility in older populations, but no empirical evidence was available to support an increase in the diagnostic threshold of interpretation of D‐dimer results for those over the age of 65 years.Publisher PDFPeer reviewe

Little Association between Intracranial Arterial Stenosis and Lacunar Stroke

Atheromatous middle cerebral artery (MCA) stenosis could cause lacunar stroke by occluding lenticulostriate artery origins, but atheroma is common, and previous studies lacked suitable controls. We aimed to determine if intracranial atheroma was more common in lacunar than in cortical ischaemic stroke. We recruited patients with lacunar stroke and controls with mild cortical stroke, confirmed the stroke subtype with magnetic resonance imaging and used transcranial Doppler ultrasound imaging to record flow velocity and focal stenoses in the basal intracranial arteries 1 month after stroke. We compared ipsi- and contralateral MCA mean flow velocities between stroke subtypes and tested for associations using linear mixed models. Amongst 67 lacunar and 67 mild cortical strokes, mean age 64 and 67 years, respectively, we found no difference in MCA mean flow velocity between cortical and lacunar patients. Increasing age and white matter lesion scores were independently associated with lower MCA flow velocities (0.2 cms−1 fall in velocity per year increase in age, p = 0.045; 3.75 cms−1 fall in flow velocity per point increase in white matter lesion score, p = 0.004). We found no intracranial arterial stenoses. MCA atheromatous stenosis is unlikely to be a common cause of lacunar stroke in white populations. Falling velocities with increasing white matter lesion scores may reflect progressive brain tissue loss leaving less tissue to supply

Patient-specific detection of cerebral blood flow alterations as assessed by arterial spin labeling in drug-resistant epileptic patients

Electrophysiological and hemodynamic data can be integrated to accurately and precisely identify the generators of abnormal electrical activity in drug-resistant focal epilepsy. Arterial Spin Labeling (ASL), a magnetic resonance imaging (MRI) technique for quantitative noninvasive measurement of cerebral blood flow (CBF), can provide a direct measure of variations in cerebral perfusion associated with the epileptic focus. In this study, we aimed to confirm the ASL diagnostic value in the identification of the epileptogenic zone, as compared to electrical source imaging (ESI) results, and to apply a template-based approach to depict statistically significant CBF alterations. Standard video-electroencephalography (EEG), high-density EEG, and ASL were performed to identify clinical seizure semiology and noninvasively localize the epileptic focus in 12 drug-resistant focal epilepsy patients. The same ASL protocol was applied to a control group of 17 healthy volunteers from which a normal perfusion template was constructed using a mixed-effect approach. CBF maps of each patient were then statistically compared to the reference template to identify perfusion alterations. Significant hypo- and hyperperfused areas were identified in all cases, showing good agreement between ASL and ESI results. Interictal hypoperfusion was observed at the site of the seizure in 10/12 patients and early postictal hyperperfusion in 2/12. The epileptic focus was correctly identified within the surgical resection margins in the 5 patients who underwent lobectomy, all of which had good postsurgical outcomes. The combined use of ESI and ASL can aid in the noninvasive evaluation of drug-resistant epileptic patients

Neuropsychiatric symptoms as a sign of small vessel disease progression in cognitive impairment

BACKGROUND: Neuropsychiatric symptoms associate cross-sectionally with cerebral small vessel disease but it is not clear whether these symptoms could act as early clinical markers of small vessel disease progression. We investigated whether longitudinal change in Neuropsychiatric Inventory (NPI) scores associated with white matter hyperintensity (WMH) progression in a memory clinic population. MATERIAL AND METHODS: We included participants from the prospective Sunnybrook Dementia Study with Alzheimer's disease and vascular subtypes of mild cognitive impairment and dementia with two MRI and ≥ 1 NPI. We conducted linear mixed-effects analyses, adjusting for age, atrophy, vascular risk factors, cognition, function, and interscan interval. RESULTS: At baseline (n=124), greater atrophy, age, vascular risk factors and total NPI score were associated with higher baseline WMH volume, while longitudinally, all but vascular risk factors were associated. Change in total NPI score was associated with change in WMH volume, χ2 = 7.18, p = 0.007, whereby a one-point change in NPI score from baseline to follow-up was associated with a 0.0017 change in normalized WMH volume [expressed as cube root of (WMH volume cm³ as % intracranial volume)], after adjusting for age, atrophy, vascular risk factors and interscan interval. CONCLUSIONS: In memory clinic patients, WMH progression over 1–2 years associated with worsening neuropsychiatric symptoms, while WMH volume remained unchanged in those with stable NPI scores in this population with low background WMH burden

Cerebral perivascular spaces visible on magnetic resonance imaging: Development of a qualitative rating scale and its observer reliability

BACKGROUND: Perivascular spaces (PVS) are an important component of cerebral small vessel disease (SVD), several inflammatory disorders, hypertension and blood-brain barrier breakdown, but are difficult to quantify. A recent international collaboration of SVD experts has highlighted the need for a robust, easy-to-use PVS rating scale for the effective investigation of the diagnostic and prognostic significance of PVS. The purpose of the current study was to develop and extend existing PVS scales to provide a more comprehensive scale for the measurement of PVS in the basal ganglia, centrum semiovale and midbrain, and to test its intra- and inter-rater agreement, assessing reasons for discrepancy. METHODS: We reviewed previously published PVS scales, including site of PVS assessed, rating method, and size and morphological criteria. Retaining key features, we devised a more comprehensive scale in order to improve the reliability of PVS rating. Two neuroradiologists tested the new scale in MRI brain scans of 60 patients from two studies (stroke, ageing population), chosen to represent a full range of PVS, and demonstrating concomitant features of SVD such as lacunes and white matter hyperintensities. We rated basal ganglia, centrum semiovale, and midbrain PVS. Basal ganglia and centrum semiovale PVS were rated 0 (none), 1 (1–10), 2 (11–20), 3 (21–40) and 4 (>40), and midbrain PVS were rated 0 (none visible) or 1 (visible). We calculated kappa statistics for rating, assessed consistency in use of PVS categories (Bhapkar test) and reviewed sources of discrepancy. RESULTS: Intra- and inter-rater kappa statistics were highest for basal ganglia PVS (range 0.76–0.87 and 0.8–0.9, respectively) than for centrum semiovale PVS (range 0.68–0.75 and 0.61–0.8, respectively) or midbrain PVS (inter-rater range 0.51–0.52). Inter-rater consistency was better for basal ganglia compared to centrum semiovale PVS (Bhapkar statistic 2.49–3.72, compared to 6.79–21.08, respectively). Most inter-rater disagreements were due to very faint PVS, coexisting extensive white matter hyperintensities (WMH) or the presence of lacunes. CONCLUSIONS: We developed a more inclusive and robust visual PVS rating scale allowing rating of all grades of PVS severity on structural brain imaging. The revised PVS rating scale has good observer reliability for basal ganglia and centrum semiovale PVS, best for basal ganglia PVS, and moderate reliability for midbrain PVS. Agreement is influenced by PVS severity and the presence of background features of SVD. The current scale can be used in further studies to assess the clinical implications of PVS

Higher intraocular pressure is associated with slower axial growth in children with non-pathological high myopia

ObjectivesTo investigate the association between intraocular pressure (IOP) and axial elongation rate in highly myopic children from the ZOC-BHVI High Myopia Cohort Study.Methods162 eyes of 81 healthy children (baseline spherical equivalent: −6.25 D to −15.50 D) aged 7–12 years with non-pathological high myopia were studied over five biennial visits. The mean (SD) follow-up duration was 5.2 (3.3) years. A linear mixed-effects model (LMM) was used to assess the association between IOP (at time point t−1) and axial elongation rate (annual rate of change in AL from t−1 to t), controlling for a pre-defined set of covariates including sex, age, central corneal thickness, anterior chamber depth and lens thickness (at t−1). LMM was also used to assess the contemporaneous association between IOP and axial length (AL) at t, controlling for the same set of covariates (at t) as before.ResultsHigher IOP was associated with slower axial growth (β = −0.01, 95% CI −0.02 to −0.005, p = 0.001). There was a positive contemporaneous association between IOP and AL (β = 0.03, 95% CI 0.01–0.05, p = 0.004), but this association became progressively less positive with increasing age, as indicated by a negative interaction effect between IOP and age on AL (β = −0.01, 95% CI −0.01 to −0.003, p = 0.001).ConclusionsHigher IOP is associated with slower rather than faster axial growth in children with non-pathological high myopia, an association plausibly confounded by the increased influence of ocular compliance on IOP

Association between Striatal Brain Iron Deposition, Microbleeds and Cognition 1 Year After a Minor Ischaemic Stroke

Brain iron deposits (IDs) are inversely associated with cognitive function in community-dwelling older people, but their association with cognition after ischemic stroke, and whether that differs from microbleeds, is unknown. We quantified basal ganglia IDs (BGID) and microbleeds (BMBs) semi-automatically on brain magnetic resonance images from patients with minor stroke (NIHSS < 7), at presentation and 12 months after stroke. We administered the National Adult Reading Test (NART, estimates premorbid or peak adult cognition) and the Revised Addenbrooke’s Cognitive Examination (ACE-R; current cognition) at 1 and 12 months after stroke. We adjusted analyses for baseline cognition, age, gender, white matter hyperintensity (WMH) volume and vascular risk factors. In 200 patients, mean age 65 years, striatal IDs and BMBs volumes did not change over the 12 months. Baseline BGID volumes correlated positively with NART scores at both times (ρ = 0.19, p < 0.01). Baseline and follow-up BGID volumes correlated positively with age (ρ = 0.248, p < 0.001 and ρ = 0.271, p < 0.001 respectively), but only baseline (and not follow-up) BMB volume correlated with age (ρ = 0.129, p < 0.05). Both smoking and baseline WMH burden predicted verbal fluency and visuospatial abilities scores (B = −1.13, p < 0.02 and B = −0.22, p = 0.001 respectively) at 12 months after stroke. BGIDs and BMBs are associated differently with cognition post-stroke; studies of imaging and post-stroke cognition should adjust for premorbid cognition. The positive correlation of BGID with NART may reflect the lower premorbid cognition in patients with stroke at younger vs older ages