Publications
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Cowie MR, 2017, Digital health comes of age, Dialogues in Cardiovascular Medicine, Vol: 22, Pages: 27-28, ISSN: 1272-9949
Cowie MR, Gallagher AM, 2017, Sleep disordered breathing and heart failure what does the future hold?, JACC: Heart Failure, Vol: 5, Pages: 715-723, ISSN: 2213-1779
Most patients with heart failure (HF) have sleep-disordered breathing (SDB), with central (rather than obstructive) sleep apnea becoming the predominant form in patients with more severe disease. Cyclical apnea and hypopneas are associated with sleep disturbance, hypoxemia, hemodynamic changes, and sympathetic activation. These patients have a worse prognosis than those without SDB. Mask-based therapies of positive airway pressure targeted at SDB can improve measures of sleep quality and can partially normalize the sleep and respiratory physiology. However, recent randomized trials of cardiovascular outcomes in central sleep apnea in chronic HF with reduced ejection fraction have had neutral findings or suggested the possibility of harm, likely from an increased rate of sudden death. Further randomized outcome studies are required to determine whether mask-based treatment is appropriate for patients with chronic HF with reduced ejection fraction and obstructive sleep apnea, for patients with heart failure with preserved ejection fraction, and for patients with decompensated heart failure. New therapies for sleep apnea (e.g., implantable phrenic nerve stimulators) also require robust assessment. No longer can the surrogate endpoints of improvement in respiratory and sleep metrics be taken as adequate therapeutic outcome measures in patients with HF and sleep apnea.
Vukadinovic AN, Vukadinovic D, Borer J, et al., 2017, Heart rate and its reduction in chronic heart failure and beyond, European Journal of Heart Failure, Vol: 19, Pages: 1230-1241, ISSN: 1388-9842
Heart rate (HR) is associated with cardiovascular outcomes in all the stages of the cardiovascular continuum as well as in patients with pulmonary, cerebrovascular, and renal disease, sepsis, cancer, and erectile dysfunction. In patients with cardiovascular disease, but also in the general population, increased HR represents an important indicator of mortality with each acceleration of HR over 70 b.p.m. increasing the risk. In patients in sinus rhythm with chronic heart failure with reduced ejection fraction (HFrEF), a HR >70 b.p.m. increased the risk of hospitalization, and >75 b.p.m. the risk of cardiovascular death as shown in the Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial (SHIFT). Reducing HR with ivabradine by 11 b.p.m. (placebo‐controlled) reduced the primary composite endpoint (cardiovascular death and hospitalization for worsening heart failure). Ivabradine was well tolerated showing benefit irrespective of age or diabetes status, and also in the presence of low systolic blood pressure and severe heart failure (SHIFT trial). Therefore, HR qualifies as a modifiable risk factor in heart failure. In patients with stable coronary disease, HR is a risk marker but HR reduction with ivabradine does not improve outcomes. The role of selective HR lowering remains unclear in patients with pulmonary, renal, cerebrovascular, and other diseases, as the potential benefit of interventions on HR has not been explored in these conditions. Future studies should scrutinize if HR reduction improves outcomes, defining HR as a potential risk factor and therapeutic target in other conditions beyond heart failure.
Kouranos V, Minz M, Danylenko O, et al., 2017, Echocardiographic parameters in suspected cardiac sarcoidosis patients-the role of speckle tracking strain analysis in the diagnosis of cardiac sarcoidosis, EUROPEAN RESPIRATORY JOURNAL, Vol: 50, ISSN: 0903-1936
Steeds RP, Cowie MR, Rana BS, et al., 2017, Report from the Annual Conference of the British Society of Echocardiography, November 2016, Queen Elizabeth II Conference Centre, London, ECHO RESEARCH AND PRACTICE, Vol: 4, Pages: M1-M16, ISSN: 2055-0464
Monahan M, Barton P, Taylor CJ, et al., 2017, MICE or NICE? An economic evaluation of clinical decision rules in the diagnosis of heart failure in primary care, International Journal of Cardiology, Vol: 241, Pages: 255-261, ISSN: 0167-5273
BackgroundDetection and treatment of heart failure (HF) can improve quality of life and reduce premature mortality. However, symptoms such as breathlessness are common in primary care, have a variety of causes and not all patients require cardiac imaging. In systems where healthcare resources are limited, ensuring those patients who are likely to have HF undergo appropriate and timely investigation is vital.DesignA decision tree was developed to assess the cost-effectiveness of using the MICE (Male, Infarction, Crepitations, Edema) decision rule compared to other diagnostic strategies to identify HF patients presenting to primary care.MethodsData from REFER (REFer for EchocaRdiogram), a HF diagnostic accuracy study, was used to determine which patients received the correct diagnosis decision. The model adopted a UK National Health Service (NHS) perspective.ResultsThe current recommended National Institute for Health and Care Excellence (NICE) guidelines for identifying patients with HF was the most cost-effective option with a cost of £4400 per quality adjusted life year (QALY) gained compared to a “do nothing” strategy. That is, patients presenting with symptoms suggestive of HF should be referred straight for echocardiography if they had a history of myocardial infarction or if their NT-proBNP level was ≥ 400 pg/ml. The MICE rule was more expensive and less effective than the other comparators. Base-case results were robust to sensitivity analyses.ConclusionsThis represents the first cost-utility analysis comparing HF diagnostic strategies for symptomatic patients. Current guidelines in England were the most cost-effective option for identifying patients for confirmatory HF diagnosis. The low number of HF with Reduced Ejection Fraction patients (12%) in the REFER patient population limited the benefits of early detection.
Morgan JM, Kitt S, Gill J, et al., 2017, Remote management of heart failure using implantable electronic devices, European Heart Journal, Vol: 38, Pages: 2352-2360, ISSN: 1522-9645
AimsRemote management of heart failure using implantable electronic devices (REM-HF) aimed to assess the clinical and cost-effectiveness of remote monitoring (RM) of heart failure in patients with cardiac implanted electronic devices (CIEDs).Methods and resultsBetween 29 September 2011 and 31 March 2014, we randomly assigned 1650 patients with heart failure and a CIED to active RM or usual care (UC). The active RM pathway included formalized remote follow-up protocols, and UC was standard practice in nine recruiting centres in England. The primary endpoint in the time to event analysis was the 1st event of death from any cause or unplanned hospitalization for cardiovascular reasons. Secondary endpoints included death from any cause, death from cardiovascular reasons, death from cardiovascular reasons and unplanned cardiovascular hospitalization, unplanned cardiovascular hospitalization, and unplanned hospitalization. REM-HF is registered with ISRCTN (96536028). The mean age of the population was 70 years (range 23–98); 86% were male. Patients were followed for a median of 2.8 years (range 0–4.3 years) completing on 31 January 2016. Patient adherence was high with a drop out of 4.3% over the course of the study. The incidence of the primary endpoint did not differ significantly between active RM and UC groups, which occurred in 42.4 and 40.8% of patients, respectively [hazard ratio 1.01; 95% confidence interval (CI) 0.87–1.18; P = 0.87]. There were no significant differences between the two groups with respect to any of the secondary endpoints or the time to the primary endpoint components.ConclusionAmong patients with heart failure and a CIED, RM using weekly downloads and a formalized follow up approach does not improve outcomes.
Khan H, Di Salvo G, Kralj-Hans I, et al., 2017, Left atrial appendage exclusion as treatment strategy of ablation in longstanding persistent atrial fibrillation does not adversely affect the left atrial function in human, Publisher: OXFORD UNIV PRESS, Pages: 1095-1096, ISSN: 0195-668X
Griffin EA, Wonderling D, Ludman AJ, et al., 2017, Cost-Effectiveness Analysis of Natriuretic Peptide Testing and Specialist Management in Patients with Suspected Acute Heart Failure, VALUE IN HEALTH, Vol: 20, Pages: 1025-1033, ISSN: 1098-3015
ObjectivesTo determine the cost-effectiveness of natriuretic peptide (NP) testing and specialist outreach in patients with acute heart failure (AHF) residing off the cardiology ward.MethodsWe used a Markov model to estimate costs and quality-adjusted life-years (QALYs) for patients presenting to hospital with suspected AHF. We examined diagnostic workup with and without the NP test in suspected new cases, and we examined the impact of specialist heart failure outreach in all suspected cases. Inputs for the model were derived from systematic reviews, the UK national heart failure audit, randomized controlled trials, expert consensus from a National Institute for Health and Care Excellence guideline development group, and a national online survey. The main benefit from specialist care (cardiology ward and specialist outreach) was the increased likelihood of discharge on disease-modifying drugs for people with left ventricular systolic dysfunction, which improve mortality and reduce re-admissions due to worsened heart failure (associated with lower utility). Costs included diagnostic investigations, admissions, pharmacological therapy, and follow-up heart failure care.ResultsNP testing and specialist outreach are both higher cost, higher QALY, cost-effective strategies (incremental cost-effectiveness ratios of £11,656 and £2,883 per QALY gained, respectively). Combining NP and specialist outreach is the most cost-effective strategy. This result was robust to both univariate deterministic and probabilistic sensitivity analyses.ConclusionsNP testing for the diagnostic workup of new suspected AHF is cost-effective. The use of specialist heart failure outreach for inpatients with AHF residing off the cardiology ward is cost-effective. Both interventions will help improve outcomes for this high-risk group.
Miro O, Peacock FW, McMurray JJ, et al., 2017, European Society of Cardiology - Acute Cardiovascular Care Association position paper on safe discharge of acute heart failure patients from the emergency department, EUROPEAN HEART JOURNAL-ACUTE CARDIOVASCULAR CARE, Vol: 6, Pages: 311-320, ISSN: 2048-8726
Halliday BP, Gulati A, Ali A, et al., 2017, Association between mid-wall late gadolinium enhancement and sudden cardiac death in patients with dilated cardiomyopathy and mild and moderate left ventricular systolic dysfunction, Circulation, Vol: 135, Pages: 2106-2115, ISSN: 0009-7322
Background—Current guidelines only recommend the use of an implantable cardioverter defibrillator (ICD) in patients with dilated cardiomyopathy (DCM) for the primary prevention of sudden cardiac death (SCD) in those with a left ventricular ejection fraction (LVEF)<35%. However, registries of out-of-hospital cardiac arrests demonstrate that 70-80% of such patients have a LVEF>35%. Patients with a LVEF>35% also have low competing risks of death from non-sudden causes. Therefore, those at high-risk of SCD may gain longevity from successful ICD therapy. We investigated whether late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) identified patients with DCM without severe LV systolic dysfunction at high-risk of SCD.Methods—We prospectively investigated the association between mid-wall late gadolinium enhancement (LGE) and the pre-specified primary composite outcome of SCD or aborted SCD amongst consecutive referrals with DCM and a LVEF≥40% to our center between January 2000 and December 2011, who did not have a pre-existing indication for ICD implantation.Results—Of 399 patients (145 women, median age 50 years, median LVEF 50%, 25.3% with LGE) followed for a median of 4.6 years, 18 of 101 (17.8%) patients with LGE reached the pre-specified end-point, compared to 7 of 298 (2.3%) without (HR 9.2; 95% CI 3.9-21.8; p<0.0001). Nine patients (8.9%) with LGE compared to 6 (2.0%) without (HR 4.9; 95% CI 1.8-13.5; p=0.002) died suddenly, whilst 10 patients (9.9%) with LGE compared to 1 patient (0.3%) without (HR 34.8; 95% CI 4.6-266.6; p<0.001) had aborted SCD. Following adjustment, LGE predicted the composite end-point (HR 9.3; 95% CI 3.9-22.3; p<0.0001), SCD (HR 4.8; 95% CI 1.7-13.8; p=0.003) and aborted SCD (HR 35.9; 95% CI 4.8-271.4; p<0.001). Estimated hazard ratios for the primary end-point for patients with a LGE extent of 0-2.5%, 2.5-5% and >5% compared to those without LGE were 10.6 (95%CI 3.9-29.4), 4.9 (9
McDonald K, O'Hanlon R, Savage HO, et al., 2017, Sleep-disordered breathing in chronic heart failure is highly variable when measured remotely using a novel non-contact biomotion sensor, European Journal of Heart Failure, Vol: 19, Pages: 688-690, ISSN: 1388-9842
Mc Cambridge J, Keane C, Walshe M, et al., 2017, Twenty percent of patients with acute decompensated heart failure (ADHF) do not receive appropriate treatment in the emergency department (ED), Publisher: WILEY, Pages: 385-385, ISSN: 1388-9842
Komajda MM, Cowie MR, Tavazzi L, et al., 2017, Optimisation of guidelines adherence is associated with better prognosis in outpatients with heart failure with low ejection fraction (HFrEF): the QUALIFY registry, Publisher: WILEY, Pages: 403-403, ISSN: 1388-9842
Regan DD, Quigley E, Keane C, et al., 2017, Mapping heart failure: patient-level costs of an integrated care pathway, Publisher: WILEY, Pages: 406-406, ISSN: 1388-9842
Mc Cambridge J, Keane C, Walshe M, et al., 2017, Missed opportunity to minimise risk of admission with acute decompensated heart failure (ADHF) during pre-hospital phase of care, Publisher: WILEY, Pages: 522-522, ISSN: 1388-9842
Linde C, Tang A, Cowie MR, et al., 2017, Physical activity measured with implanted devices predicts heart failure outcomes, Publisher: WILEY, Pages: 347-347, ISSN: 1388-9842
Riley J, Keane C, Walshe M, et al., 2017, The patient view of hospitalisation with acute heart failure. Results from a qualitative study of the acute heart failure pathway., Publisher: WILEY, Pages: 207-207, ISSN: 1388-9842
Price S, Platz E, Cullen L, et al., 2017, Echocardiography and lung ultrasonography for the assessment and management of acute heart failure, Nature Reviews Cardiology, Vol: 14, Pages: 426-440, ISSN: 1759-5002
Echocardiography is increasingly recommended for the diagnosis and assessmentof patients with severe cardiac disease, including acute heart failure. Although previouslyconsidered to be within the realm of cardiologists, the development of ultrasonographytechnology has led to the adoption of echocardiography by acute care clinicians across a rangeof specialties. Data from echocardiography and lung ultrasonography can be used to improvediagnostic accuracy, guide and monitor the response to interventions, and communicateimportant prognostic information in patients with acute heart failure. However, without theappropriate skills and a good understanding of ultrasonography, its wider application to the mostacutely unwell patients can have substantial pitfalls. This Consensus Statement, prepared by theAcute Heart Failure Study Group of the ESC Acute Cardiovascular Care Association, reviewsthe existing and potential roles of echocardiography and lung ultrasonography in the assessmentand management of patients with acute heart failure, highlighting the differences fromestablished practice where relevant.
Patel HC, Hayward C, Dungu JN, et al., 2017, Assessing the Eligibility Criteria in Phase III Randomized Controlled Trials of Drug Therapy in Heart Failure With Preserved Ejection Fraction: The Critical Play-Off Between a "Pure" Patient Phenotype and the Generalizability of Trial Findings, JOURNAL OF CARDIAC FAILURE, Vol: 23, Pages: 517-524, ISSN: 1071-9164
Aims:To investigate the effect of the different eligibility criteria used by phase III clinical studies in heart failure with preserved ejection fraction (HFpEF) on patient selection, phenotype, and survival.Methods and Results:We applied the key eligibility criteria of 7 phase III HFpEF studies (Digitalis Investigation Group Ancillary, Candesartan in Patients With Chronic Heart Failure and Preserved Left-Ventricular Ejection Fraction, Perindopril in Elderly People With Chronic Heart Failure, Irbesartan in Heart Failure With Preserved Systolic Function, Japanese Diastolic Heart Failure, Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist, and Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF; ongoing]) to a typical and well-characterized HFpEF population (n = 557) seen in modern European cardiological practice. Follow-up was available for a minimum of 24 months in each patient. Increasing the number of study eligibility criteria identifies a progressively smaller group of patients from real-life practice suitable for recruitment into clinical trials; using the J-DHF criteria, 81% of our clinic patients would have been eligible, whereas the PARAGON-HF criteria significantly reduced this proportion to 32%. The patients identified from our clinical population had similar mortality rates using the different criteria, which were consistently higher than those reported in the actual clinic trials.Conclusions:Trial eligibility criteria have become stricter with time, which reduces the number of eligible patients, affecting both generalizability of any findings and feasibility of completing an adequately powered trial. We could not find evidence that the additional criteria used in more recent randomized trials in HFpEF have identified patients at higher risk of all-cause mortality.
Cowie MR, 2017, SLEEP-DISORDERED BREATHING AND CARDIAC DISEASE, Hurst's the Heart, 14th Edition: Two Volume Set, Editors: Fuster, Harrington, Narula, Eapen, Publisher: McGraw-Hill Education / Medical, ISBN: 9780071843249
Other enhancements include the addition of textual features such as Practice Points, Common Clinical Questions, and an increased number of the acclaimed Hurst’s diagrams. • NEW TO THIS EDITION: Section on Metabolic Disorders and ...
Cowie MR, Filippatos GS, Garcia MDLAA, et al., 2017, New medicinal products for chronic heart failure: advances in clinical trial design and efficacy assessment, European Journal of Heart Failure, Vol: 19, Pages: 718-727, ISSN: 1388-9842
Despite the availability of a number of different classes of therapeutic agents with proven efficacy in heart failure, the clinical course of heart failure patients is characterized by a reduction in life expectancy, a progressive decline in health-related quality of life and functional status, as well as a high risk of hospitalization. New approaches are needed to address the unmet medical needs of this patient population. The European Medicines Agency (EMA) is undertaking a revision of its Guideline on Clinical Investigation of Medicinal Products for the Treatment of Chronic Heart Failure. The draft version of the Guideline was released for public consultation in January 2016. The Cardiovascular Round Table of the European Society of Cardiology (ESC), in partnership with the Heart Failure Association of the ESC, convened a dedicated two-day workshop to discuss three main topic areas of major interest in the field and addressed in this draft EMA guideline: (i) assessment of efficacy (i.e. endpoint selection and statistical analysis); (ii) clinical trial design (i.e. issues pertaining to patient population, optimal medical therapy, run-in period); and (iii) research approaches for testing novel therapeutic principles (i.e. cell therapy). This paper summarizes the key outputs from the workshop, reviews areas of expert consensus, and identifies gaps that require further research or discussion. Collaboration between regulators, industry, clinical trialists, cardiologists, health technology assessment bodies, payers, and patient organizations is critical to address the ongoing challenge of heart failure and to ensure the development and market access of new therapeutics in a scientifically robust, practical and safe way.
Cowie MR, 2017, Withdrawing ASV therapy in clinical practice: trials and tribulations, SLEEP MEDICINE, Vol: 37, Pages: 208-209, ISSN: 1389-9457
Griffiths A, Paracha N, Davies A, et al., 2017, Analyzing Health-Related Quality of Life Data to Estimate Parameters for Cost-Effectiveness Models: An Example Using Longitudinal EQ-5D Data from the SHIFT Randomized Controlled Trial, Advances in Therapy, Vol: 34, Pages: 753-764, ISSN: 0741-238X
IntroductionThe aim of this article is to discuss methods used to analyze health-related quality of life (HRQoL) data from randomized controlled trials (RCTs) for decision analytic models. The analysis presented in this paper was used to provide HRQoL data for the ivabradine health technology assessment (HTA) submission in chronic heart failure.MethodsWe have used a large, longitudinal EuroQol five-dimension questionnaire (EQ-5D) dataset from the Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial (SHIFT) (clinicaltrials.gov: NCT02441218) to illustrate issues and methods. HRQoL weights (utility values) were estimated from a mixed regression model developed using SHIFT EQ-5D data (n = 5313 patients). The regression model was used to predict HRQoL outcomes according to treatment, patient characteristics, and key clinical outcomes for patients with a heart rate ≥75 bpm.ResultsIvabradine was associated with an HRQoL weight gain of 0.01. HRQoL weights differed according to New York Heart Association (NYHA) class (NYHA I–IV, no hospitalization: standard care 0.82–0.46; ivabradine 0.84–0.47). A reduction in HRQoL weight was associated with hospitalizations within 30 days of an HRQoL assessment visit, with this reduction varying by NYHA class [−0.07 (NYHA I) to −0.21 (NYHA IV)].ConclusionThe mixed model explained variation in EQ-5D data according to key clinical outcomes and patient characteristics, providing essential information for long-term predictions of patient HRQoL in the cost-effectiveness model. This model was also used to estimate the loss in HRQoL associated with hospitalizations. In SHIFT many hospitalizations did not occur close to EQ-5D visits; hence, any temporary changes in HRQoL associated with such events would not be captured fully in observed RCT evidence, but could be predicted in our cost-effectiveness analysis using the mixed model. Given the large reduction in hospitalizations associated with ivab
Cowie MR, 2017, The heart failure epidemic: a UK perspective, Echo Research and Practice, Vol: 4, Pages: R15-R20, ISSN: 2055-0464
Heart failure is appropriately described as an epidemic, with 1–2% of health care expenditure being directed at its management. In England, the National Institute for Health and Care Excellence (NICE) has issued guidance on the best practice for the diagnosis and treatment of acute and chronic heart failure. Echocardiography is key to the diagnosis of the underlying cardiac abnormalities, and access to this (with our without biochemical testing using natriuretic peptides) is key to high-quality and speedy diagnosis. New models of care aim to speed up access to echocardiography, but a shortage of technically trained staff remains a limiting factor in improving standards of care. The NHS audits the quality of care and outcome for patients admitted to hospital with heart failure, and this continues to show wide variation in practice, particularly, where patients are not reviewed by the local heart failure multidisciplinary team. Recently, the All Party Parliamentary Group on Cardiac Disease issued 10 suggestions for improvement in care for patients with heart failure – access to echocardiography being one of the key suggestions. Time will tell as to whether this support from law makers will assist in the implementation of NICE-recommended standards of care consistently across the country.
Cowie MR, Lopatin YM, Saldarriaga C, et al., 2017, The Optimize Heart Failure Care Program: Initial lessons from global implementation, International Journal of Cardiology, Vol: 236, Pages: 340-344, ISSN: 0167-5273
Hospitalization for heart failure (HF) places a major burden on healthcare services worldwide, and is a strong predictor of increased mortality especially in the first three months after discharge. Though undesirable, hospitalization is an opportunity to optimize HF therapy and advise clinicians and patients about the importance of continued adherence to HF medication and regular monitoring.The Optimize Heart Failure Care Program (www.optimize-hf.com), which has been implemented in 45 countries, is designed to improve outcomes following HF hospitalization through inexpensive initiatives to improve prescription of appropriate drug therapies, patient education and engagement, and post-discharge planning. It includes best practice clinical protocols for local adaptation, pre- and post-discharge checklists, and ‘My HF Passport’, a printed and smart phone application to improve patient understanding of HF and encourage involvement in care and treatment adherence.Early experience of the Program suggests that factors leading to successful implementation include support from HF specialists or ‘local leaders’, regular educational meetings for participating healthcare professionals, multidisciplinary collaboration, and full integration of pre- and post-hospital discharge checklists across care services. The Program is helping to raise awareness of HF and generate useful data on current practice. It is showing how good evidence-based care can be achieved through the use of simple clinician and patient-focused tools. Preliminary results suggest that optimization of HF pharmacological therapy is achievable through the Program, with little new investment. Further data collection will lead to a greater understanding of the impact of the Program on HF care and key indicators of success.
Cowie MR, Simon M, Klein L, et al., 2017, The cost-effectiveness of real-time pulmonary artery pressure monitoring in heart failure patients: a European perspective, EUROPEAN JOURNAL OF HEART FAILURE, Vol: 19, Pages: 661-669, ISSN: 1388-9842
Harper AR, Cowie MR, 2017, Remote monitoring for heart failure: the story moves on, EUROPEAN HEART JOURNAL, Vol: 38, Pages: 310-311, ISSN: 0195-668X
Mueller C, Christ M, Cowie M, et al., 2017, European Society of Cardiology-Acute Cardiovascular Care Association Position paper on acute heart failure: A call for interdisciplinary care, EUROPEAN HEART JOURNAL-ACUTE CARDIOVASCULAR CARE, Vol: 6, Pages: 81-86, ISSN: 2048-8726
Atalla A, Carlisle TW, Simonds AK, et al., 2017, Sleepiness and activity in heart failure patients with reduced ejection fraction and central sleep-disordered breathing, SLEEP MEDICINE, Vol: 34, Pages: 217-223, ISSN: 1389-9457
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