Prevalence of peripheral arterial disease in patients at non-high cardiovascular risk. Rationale and design of the PANDORA study

<p>Abstract</p> <p>Background</p> <p>Lower extremity peripheral arterial disease (PAD) is a marker of widespread atherosclerosis. Individuals with PAD, most of whom do not show typical PAD symptoms ('asymptomatic' patients), are at increased risk of cardiovascular ischaemic events. American College of Cardiology/American Heart Association guidelines recommend that individuals with asymptomatic lower extremity PAD should be identified by measurement of ankle-brachial index (ABI). However, despite its associated risk, PAD remains under-recognised by clinicians and the general population and office-based ABI detection is still poorly-known and under-used in clinical practice. The Prevalence of peripheral Arterial disease in patients with a non-high cardiovascular disease risk, with No overt vascular Diseases nOR diAbetes mellitus (PANDORA) study has a primary aim of assessing the prevalence of lower extremity PAD through ABI measurement, in patients at non-high cardiovascular risk, with no overt cardiovascular diseases (including symptomatic PAD), or diabetes mellitus. Secondary objectives include documenting the prevalence and treatment of cardiovascular risk factors and the characteristics of both patients and physicians as possible determinants for PAD under-diagnosis.</p> <p>Methods/Design</p> <p>PANDORA is a non-interventional, cross-sectional, pan-European study. It includes approximately 1,000 primary care participating sites, across six European countries (Belgium, France, Greece, Italy, The Netherlands, Switzerland). Investigator and patient questionnaires will be used to collect both right and left ABI values at rest, presence of cardiovascular disease risk factors, current pharmacological treatment, and determinants for PAD under-diagnosis.</p> <p>Discussion</p> <p>The PANDORA study will provide important data to estimate the prevalence of asymptomatic PAD in a population otherwise classified at low or intermediate risk on the basis of current risk scores in a primary care setting.</p> <p>Trial registration number</p> <p>Clinical Trials.gov Identifier: NCT00689377.</p

The morbidity and mortality following a diagnosis of peripheral arterial disease: Long-term follow-up of a large database

BACKGROUND: Awareness of the significance of peripheral arterial disease is increasing, but quantitative estimates of the ensuing burden and the impact of other risk factors remains limited. The objective of this study was to fill this need. METHODS: Morbidity and mortality were examined in 16,440 index patients diagnosed with peripheral arterial disease in Saskatchewan, Canada between 1985 and 1995. Medical history and patient characteristics were available retrospectively to January 1980 and follow-up was complete to March 1998. Crude and adjusted event rates were calculated and Kaplan-Meier survival curves estimated. Cox proportional hazards analyses were conducted to examine the effect of risk factors on these rates. Patients suffering a myocardial infarction or ischemic stroke in Saskatchewan provided two reference populations. RESULTS: Half of the index patients were male; the majority was over age 65; 73% had at least one additional risk factor at index diagnosis; 10% suffered a subsequent stroke, another 10% a myocardial infarction, and 49% died within the mean follow-up of 5.9 years. Annual mortality (8.2%) was higher among patients with PAD than after a myocardial infarction (6.3%) but slightly lower than that in patients suffering a stroke (11.3%). Index patients with comorbid disease (e.g., diabetes) were at highest risk of death and other events. CONCLUSION: A diagnosis of peripheral arterial disease is critical evidence of more widespread atherothrombotic disease, with substantial risks of subsequent cardiovascular events and death. Given that the majority has additional comorbidities, these risks are further increased

A new efficient trial design for assessing reliability of ankle-brachial index measures by three different observer groups

BACKGROUND: The usual method of assessing the variability of a measure such as the ankle brachial index (ABI) as a function of different observer groups is to obtain repeated measurements. Because the number of possible observer-subject combinations is impractically large, only a few small studies on inter- and intraobserver variability of ABI measures have been carried out to date. The present study proposes a new and efficient study design. This paper describes the study methodology. METHODS: Using a partially balanced incomplete block design, six angiologists, six primary-care physicians and six trained medical office assistants performed two ABI measurements each on six individuals from a group of 36 unselected subjects aged 65–70 years. Each test subject is measured by one observer from each of the three observer groups, and each observer measures exactly six of the 36 subjects in the group. Each possible combination of two observers occurs exactly once per patient and is not repeated on a second subject. The study involved four groups of 36 subjects (144), plus standbys. RESULTS: The 192 volunteers present at the study day were similar in terms of demographic characteristics and vascular risk factors: mean age 68.6 ± 1.7; mean BMI 29.1 ± 4.6; mean waist-hip ratio 0.92 ± 0.09; active smokers 12%; hypertension 60.9%; hypercholesterolemia 53.4%; diabetic 17.2%. A complete set of ABI measurements (three observers performing two Doppler measurements each) was obtained from 108 subjects. From all other subjects at least one ABI measurement was obtained. The mean ABI was 1.08 (± 0.13), 15 (7.9%) volunteers had an ABI <0.9, and none had an ABI >1.4, i.e. a ratio that may be associated with increased stiffening of the arterial walls. CONCLUSION: This is the first large-scale study investigating the components of variability and thus reliability in ABI measurements. The advantage of the new study design introduced here is that only one sixth of the number of theoretically possible measurements is required to obtain information about measurement errors. Bland-Altman plots show that there are only small differences and no systematic bias between the observers from three occupational groups with different training backgrounds

Prevalence of peripheral arterial disease in subjects with moderate cardiovascular risk: Italian results from the PANDORA study Data from PANDORA (Prevalence of peripheral Arterial disease in subjects with moderate CVD risk, with No overt vascular Diseases nor Diabetes mellitus)

<p>Abstract</p> <p>Background</p> <p>The PANDORA study has recently examined the prevalence of low ankle brachial index (ABI) in subjects with moderate risk of cardiovascular disease. This sub-analysis of the PANDORA study examines the prevalence of asymptomatic peripheral arterial disease (PAD), as determined by ABI, in Italian subjects presenting with moderate cardiovascular risk, in the absence of diabetes or overt vascular disease.</p> <p>Methods</p> <p>PANDORA is a non-interventional, cross-sectional study that was performed in 6 European countries, involving subjects with at least one cardiovascular (CV) risk factor. The primary objective was to evaluate the prevalence of asymptomatic PAD using ABI. For this post-hoc sub-analysis, data were extracted for subjects enrolled in Italy, comprising 51.5% (n = 5298) of subjects from the original PANDORA study. Secondary objectives were to establish the prevalence and treatment of CV risk factors.</p> <p>Results</p> <p>The mean age was 63.9 years and 22.9% (95% CI 21.7-24.0) of subjects presented with asymptomatic PAD. A range of risk factors comprising smoking, hypertension, low HDL-cholesterol, family history of coronary heart disease and habit of moderate-high alcohol intake were significantly associated with asymptomatic PAD (p < 0.0001). Statin treatment had the lowest incidence in Italian subjects. Furthermore, patients treated with statins were significantly less likely to have asymptomatic PAD than those who were not (p = 0.0001).</p> <p>Conclusions</p> <p>Asymptomatic PAD was highly prevalent in Italian subjects, the majority of whom were not candidates for ABI assessment according to current guidelines. Findings from this study suggest that these patients should be carefully examined in clinical practice and ABI measured so that therapeutic interventions known to decrease their CV risk may be offered.</p> <p>Trial registration number</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00689377">NCT00689377</a></p

Screen or not to screen for peripheral arterial disease: Guidance from a decision model

__Abstract__ Background: Asymptomatic Peripheral Arterial Disease (PAD) is associated with greater risk of acute cardiovascular events. This study aims to determine the cost-effectiveness of one time only PAD screening using Ankle Brachial Index (ABI) test and subsequent anti platelet preventive treatment (low dose aspirin or clopidogrel) in individuals at high risk for acute cardiovascular events compared to no screening and no treatment using decision analytic modelling. Methods. A probabilistic Markov model was developed to evaluate the life time cost-effectiveness of the strategy of selective PAD screening and consequent preventive treatment compared to no screening and no preventive treatment. The analysis was conducted from the Dutch societal perspective and to address decision uncertainty, probabilistic sensitivity analysis was performed. Results were based on average values of 1000 Monte Carlo simulations and using discount rates of 1.5% and 4% for effects and costs respectively. One way sensitivity analyses were performed to identify the two most influential model parameters affecting model outputs. Then, a two way sensitivity analysis was conducted for combinations of values tested for these two most influential parameters. Results: For the PAD screening strategy, life years and quality adjusted life years gained were 21.79 and 15.66 respectively at a lifetime cost of 26,548 Euros. Compared to no screening and treatment (20.69 life years, 15.58 Quality Adjusted Life Ye

Peripheral artery disease assessed by ankle-brachial index in patients with established cardiovascular disease or at least one risk factor for atherothrombosis - CAREFUL Study: A national, multi-center, cross-sectional observational study

<p>Abstract</p> <p>Background</p> <p>To investigate the presence of peripheral artery disease (PAD) via the ankle brachial index (ABI) in patients with known cardiovascular and/or cerebrovascular diseases or with at least one risk factor for atherothrombosis.</p> <p>Methods</p> <p>Patients with a history of atherothrombotic events, or aged 50-69 years with at least one cardiovascular risk factor, or > = 70 years of age were included in this multicenter, cross-sectional, non-interventional study (DIREGL04074). Demographics, medical history, physical examination findings, and physician awareness of PAD were analyzed. The number of patients with low ABI (< = 0.90) was analyzed.</p> <p>Results</p> <p>A total of 530 patients (mean age, 63.4 ± 8.7 years; 50.2% female) were enrolled. Hypertension and dyslipidemia were present in 88.7% and 65.5% of patients, respectively. PAD-related symptoms were evident in about one-third of the patients, and at least one of the pedal pulses was negative in 6.5% of patients. The frequency of low ABI was 20.0% in the whole study population and 30% for patients older than 70 years. Older age, greater number of total risk factors, and presence of PAD-related physical findings were associated with increased likelihood of low ABI (<it>p </it>< 0.001). There was no gender difference in the prevalence of low ABI, PAD symptoms, or total number of risk factors. Exercise (33.6%) was the most common non-pharmacological option recommended by physicians, and acetylsalicylic acid (ASA) (45.4%) was the most frequently prescribed medication for PAD.</p> <p>Conclusion</p> <p>Our results indicate that advanced age, greater number of total risk factors and presence of PAD-related physical findings were associated with increased likelihood of low ABI. These findings are similar to those reported in similar studies of different populations, and document a fairly high prevalence of PAD in a Mediterranean country.</p

Evaluation of the Frails' Fall Efficacy by Comparing Treatments (EFFECT) on reducing fall and fear of fall in moderately frail older adults: study protocol for a randomised control trial

<p>Abstract</p> <p>Background</p> <p>Falls are common in frail older adults and often result in injuries and hospitalisation. The Nintendo^®Wii™ is an easily available exercise modality in the community which has been shown to improve lower limb strength and balance. However, not much is known on the effectiveness of the Nintendo^®Wii™ to improve fall efficacy and reduce falls in a moderately frail older adult. Fall efficacy is the measure of fear of falling in performing various daily activities. Fear contributes to avoidance of activities and functional decline.</p> <p>Methods</p> <p>This randomised active-control trial is a comparison between the Nintendo WiiActive programme against standard gym-based rehabilitation of the older population. Eighty subjects aged above 60, fallers and non-fallers, will be recruited from the hospital outpatient clinic. The primary outcome measure is the Modified Falls Efficacy Scale and the secondary outcome measures are self-reported falls, quadriceps strength, walking agility, dynamic balance and quality of life assessments.</p> <p>Discussions</p> <p>The study is the first randomised control trial using the Nintendo Wii as a rehabilitation modality investigating a change in fall efficacy and self-reported falls. Longitudinally, the study will investigate if the interventions can successfully reduce falls and analyse the cost-effectiveness of the programme.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12610000576022.aspx">ACTRN12610000576022</a></p

Communication in bacteria: an ecological and evolutionary perspective

Individual bacteria can alter their behaviour through chemical interactions between organisms in microbial communities - this is generally referred to as quorum sensing. Frequently, these interactions are interpreted in terms of communication to mediate coordinated, multicellular behaviour. We show that the nature of interactions through quorum-sensing chemicals does not simply involve cooperative signals, but entails other interactions such as cues and chemical manipulations. These signals might have a role in conflicts within and between species. The nature of the chemical interaction is important to take into account when studying why and how bacteria react to the chemical substances that are produced by other bacteria

The Molecular Epidemiology and Evolution of Murray Valley Encephalitis Virus: Recent Emergence of Distinct Sub-lineages of the Dominant Genotype 1

© 2015 Williams et al. Background: Recent increased activity of the mosquito-borne Murray Valley encephalitis virus (MVEV) in Australia has renewed concerns regarding its potential to spread and cause disease. Methodology/Principal Findings: To better understand the genetic relationships between earlier and more recent circulating strains, patterns of virus movement, as well as the molecular basis of MVEV evolution, complete pre-membrane (prM) and Envelope (Env) genes were sequenced from sixty-six MVEV strains from different regions of the Australasian region, isolated over a sixty year period (1951–2011). Phylogenetic analyses indicated that, of the four recognized genotypes, only G1 and G2 are contemporary. G1 viruses were dominant over the sampling period and found across the known geographic range of MVEV. Two distinct sub-lineages of G1 were observed (1A and 1B). Although G1B strains have been isolated from across mainland Australia, Australian G1A strains have not been detected outside northwest Australia. Similarly, G2 is comprised of only Western Australian isolates from mosquitoes, suggesting G1B and G2 viruses have geographic or ecological restrictions. No evidence of recombination was found and a single amino acid substitution in the Env protein (S332G) was found to be under positive selection, while several others were found to be under directional evolution. Evolutionary analyses indicated that extant genotypes of MVEV began to diverge from a common ancestor approximately 200 years ago. G2 was the first genotype to diverge, followed by G3 and G4, and finally G1, from which subtypes G1A and G1B diverged between 1964 and 1994. Conclusions/Significance: The results of this study provides new insights into the genetic diversity and evolution of MVEV. The demonstration of co-circulation of all contemporary genetic lineages of MVEV in northwestern Australia, supports the contention that this region is the enzootic focus for this virus