Imperial College London

MsEmanuelaFalaschetti

Faculty of MedicineSchool of Public Health

Research Fellow in Clinical Trial Statistics
 
 
 
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Contact

 

+44 (0)20 7594 1846e.falaschetti

 
 
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Location

 

Stadium HouseWhite City Campus

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Summary

 

Publications

Publication Type
Year
to

60 results found

Patel B, Mumby S, Johnson N, Falaschetti E, Hansen J, Adcock I, McAuley D, Takata M, Karbing DS, Jabaudon M, Schellengowski P, Rees SEet al., 2021, Decision support system to evaluate VENTilation in the Acute Respiratory Distress Syndrome (DeVENT study) – Trial Protocol, medRxiv

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The Acute Respiratory Distress Syndrome (ARDS) occurs in response to a variety of insults, and mechanical ventilation is life-saving in this setting, but ventilator induced lung injury can also contribute to the morbidity and mortality in the condition. The Beacon Caresystem is a model-based bedside decision support system using mathematical models tuned to the individual patient’s physiology to advise on appropriate ventilator settings. Personalised approaches using individual patient description may be particularly advantageous in complex patients, including those who are difficult to mechanically ventilate and wean, in particular ARDS.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We will conduct a multi-centre international randomised, controlled, allocation concealed, open, pragmatic clinical trial to compare mechanical ventilation in ARDS patients following application of the Beacon Caresystem to that of standard routine care to investigate whether use of the system results in a reduction in driving pressure across all severities and phases of ARDS.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>Despite 20 years of clinical trial data showing significant improvements in ARDS mortality through mitigation of ventilator induced lung injury, there remains a gap in its personalised application at the bedside. Importantly, the protective effects of higher positive end-expiratory pressure (PEEP) were noted only when there were associated decreases in driving pressure. Hence, the pressures set on the ventilator should be determined by the diseased lungs’ pressure-volume relationship which is often unknown or difficult to determine. Knowledge of extent of recruitable lung could improve the ventilator driving pressure. H

Journal article

Glaysher M, Ward J, Aldhwayan M, Ruban A, Prechtl CG, Fisk HL, Chhina N, Al-Najim W, Smith C, Klimowska-Nassar N, Johnson N, Falaschetti E, Goldstone AP, Miras AD, Byrne JP, Calder PC, Teare Jet al., 2021, The effect of a duodenal-jejunal bypass liner on lipid profile and blood concentrations of long chain polyunsaturated fatty acids, Clinical Nutrition, Vol: 40, Pages: 2343-2354, ISSN: 0261-5614

Background & aimsDuodenal-jejunal bypass liners (DJBLs) prevent absorption in the proximal small intestine, the site of fatty acid absorption. We sought to investigate the effects of a DJBL on blood concentrations of essential fatty acids (EFAs) and bioactive polyunsaturated fatty acids (PUFAs).MethodsSub-study of a multicentre, randomised, controlled trial with two treatment groups. Patients aged 18–65 years with type-2 diabetes mellitus and body mass index 30–50 kg/m2 were randomised to receive a DJBL for 12 months or best medical therapy, diet and exercise. Whole plasma PUFA concentrations were determined at baseline, 10 days, 6 and 11.5 months; data were available for n = 70 patients per group.ResultsWeight loss was significantly greater in the DJBL group compared to controls after 11.5 months: total body weight loss 11.3 ± 5.3% versus 6.0 ± 5.7% (mean difference [95% CI] = 5.27% [3.75, 6.80], p < 0.001). Absolute concentrations of both EFAs, linoleic acid and α-linolenic acid, and their bioactive derivatives, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, were significantly lower in the DJBL group than in the control group at 6 and 11.5 months follow-up. Total serum cholesterol, LDL-cholesterol and HDL-cholesterol were also significantly lower in the DJBL group.ConclusionOne year of DJBL therapy is associated with superior weight loss and greater reductions in total serum cholesterol and LDL-cholesterol, but also depletion of EFAs and their longer chain derivatives. DJBL therapy may need to be offset by maintaining an adequate dietary intake of PUFAs or by supplementation.

Journal article

Ruban A, Glaysher MA, Miras AD, Goldstone AP, Prechtl CG, Johnson N, Li J, Aldhwayan M, Aldubaikhi G, Glover B, Lord J, Onyimadu O, Falaschetti E, Klimowska-Nassar N, Ashrafian H, Byrne J, Teare JPet al., 2020, A duodenal sleeve bypass device added to intensive medical therapy for obesity with type 2 diabetes: a RCT, Efficacy and Mechanism Evaluation, Vol: 7, Pages: 1-130, ISSN: 2050-4365

BackgroundThe EndoBarrier® (GI Dynamics Inc., Boston, MA, USA) is an endoluminal duodenal–jejunal bypass liner developed for the treatment of patients with obesity and type 2 diabetes mellitus. Meta-analyses of its effects on glycaemia and weight have called for larger randomised controlled trials with longer follow-up.ObjectivesThe primary objective was to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level reduction of ≥ 20%. The secondary objectives were to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level of < 42 mmol/mol, blood pressure of < 135/85 mmHg, and the effectiveness on total body weight loss. Additional secondary outcomes were to investigate the cost-effectiveness and mechanism of action of the effect of a duodenal–jejunal bypass liner on brain reward system responses, insulin sensitivity, eating behaviour and metabonomics.DesignA multicentre, open-label, randomised controlled trial.SettingImperial College Healthcare NHS Trust and University Hospital Southampton NHS Foundation Trust.ParticipantsPatients aged 18–65 years with a body mass index of 30–50 kg/m2 and with inadequately controlled type 2 diabetes mellitus who were on oral glucose-lowering medications.InterventionsParticipants were randomised equally to receive intensive medical therapy alongside a duodenal–jejunal bypass liner device (n = 85) or intensive medical therapy alone for 12 months (n = 85), and were followed up

Journal article

Lyon A, Babalis D, Morley-Smith AC, Hedger M, Suarez Barrientos A, Foldes G, Couch LS, Chowdhury RA, Tzortzis KN, Peters NS, Rog-Zielinska EA, Yang YH, Welch S, Bowles CT, Rahman Haley S, Bell AR, Rice A, Sasikaran T, Johnson NA, Falaschetti E, Parameshwar J, Lewis C, Tsui S, Simon A, Pepper J, Rudy JJ, Zsebo KM, MacLeod KT, Terracciano CM, Hajjar RJ, Banner N, Harding SEet al., 2020, Investigation of the safety and feasibility of AAV1/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device – the SERCA-LVAD TRIAL, Gene Therapy, Vol: 27, Pages: 579-590, ISSN: 0969-7128

The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. Enrolled subjects were randomised to receive a single intracoronary infusion of 1x1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort, which may help guide future trial design.

Journal article

Glaysher M, Ward J, Aldhwayan M, Ruban A, Prechtl C, Fisk H, Gelauf C, Chhina N, Al-Najim W, Smith C, Klimowska-Nassar N, Johnson N, Goldstone A, Miras A, Patel M, Byrne J, Calder P, Teare Jet al., 2020, The effect of a duodenal-jejunal bypass liner device (Endobarrier (R)) on lipid profile and blood concentrations of long chain polyunsaturated fatty acids, 11th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: S16-S17, ISSN: 0960-8923

Conference paper

Mann I, Sasikaran T, Sandler B, Babalis D, Johnson N, Falaschetti E, Copley A, Tayebjee M, Todd D, Shepherd E, McCready J, Poulter N, Kanagaratnam Pet al., 2019, Ablation versus anti-arrhythmic therapy for reducing all hospital episodes from recurrent atrial fibrillation (AVATAR-AF): design and rationale, American Heart Journal, Vol: 214, Pages: 36-45, ISSN: 0002-8703

Atrial Fibrillation (AF) ablation using the cryoballoon is effective at reducing symptomatic AF episodes. The prevalence of AF is increasing with the aging population and access to such treatment would be enhanced by reducing the resource requirements. Relinquishing electrical mapping of the pulmonary veins (PV) removes the need for PV catheters, electrical recording equipment and staff trained in using this equipment. Moreover, the majority of complications are peri-procedural so overnight hospitalization maybe unnecessary. We tested this streamlined approach to AF ablation against medical therapy using the endpoint of time to all hospital episodes. METHODS: The AVATAR-AF study is a prospective, multicenter, randomized controlled trial testing the primary hypothesis that AF ablation done without PV mapping or overnight hospitalization is more effective than anti-arrhythmic drugs at reducing all hospital episodes related to recurrent atrial arrhythmias. We included a third arm to test a secondary hypothesis that confirming PV entrance block as per consensus guidelines can improve outcomes. Three hundred twenty-one patients with documented paroxysmal AF will be randomized in a 1:1:1 manner to one of three investigation arms: (1) AVATAR protocol cryoballoon ablation without assessment of acute PV isolation or overnight hospitalization; (2) medical therapy with anti-arrhythmic drugs; or (3) conventional cryoballoon ablation with assessment of acute PV isolation. The primary endpoint is defined as the time to all hospital episodes (including outpatient consultation) related to treatment for atrial arrhythmia. CONCLUSION: The AVATAR-AF study will determine whether the resource utilization for AF ablation can be reduced whilst maintaining superiority over medical therapy.

Journal article

Poulter NR, Savopoulos C, Anjum A, Apostolopoulou M, Chapman N, Cross M, Falaschetti E, Fotiadis S, James RM, Kanellos I, Szigeti M, Thom S, Sever P, Thompson D, Hatzitolios AIet al., 2018, Randomized crossover trial of the impact of morning or evening dosing of antihypertensive agents on 24-hour ambulatory blood pressure: the HARMONY trial, Hypertension, Vol: 72, Pages: 870-873, ISSN: 0194-911X

Some data suggest that nocturnal dosing of antihypertensive agents may reduce cardiovascular outcomes more than daytime dosing. This trial was designed to evaluate whether ambulatory blood pressure monitoring levels differ by timing of drug dosing. Patients aged 18 to 80 years with reasonably controlled hypertension (≤150/≤90 mm Hg) on stable therapy of ≥1 antihypertensive agent were recruited from 2 centers in London and Thessaloniki. Patients were randomized to receive usual therapy either in the morning (6 am–11 am) or evening (6 pm–11 pm) for 12 weeks when participants crossed over to the alternative timing for a further 12 weeks. Clinic blood pressures and a 24-hour recording were taken at baseline, 12, and 24 weeks and routine blood tests were taken at baseline. The study had 80% power to detect 3 mm Hg difference in mean 24-hour systolic blood pressure (α=0.05) by time of dosing. A 2-level hierarchical regression model adjusted for center, period, and sequence was used. Of 103 recruited patients (mean age, 62; 44% female), 95 patients (92%) completed all three 24-hour recordings. Mean 24-hour systolic and diastolic blood pressures did not differ between daytime and evening dosing. Similarly, morning and evening dosing had no differential impact on mean daytime (7 am–10 pm) and nighttime (10 pm–7 am) blood pressure levels nor on clinic levels. Stratification by age (≤65/≥65 years) or sex did not affect results. In summary, among hypertensive patients with reasonably well-controlled blood pressure, the timing of antihypertensive drug administration (morning or evening) did not affect mean 24-hour or clinic blood pressure levels.

Journal article

Keene D, Arnold A, Shun-Shin MJ, Howard JP, Sohaib SA, Moore P, Tanner M, Quereshi N, Muthumala A, Chandresekeran B, Foley P, Leyva F, Adhya S, Falaschetti E, Tsang H, Vijayaraman P, Cleland JGF, Stegemann B, Francis DP, Whinnett ZIet al., 2018, Rationale and design of the randomized multicentre His Optimized Pacing Evaluated for Heart Failure (HOPE-HF) trial, ESC Heart Failure, Vol: 5, Pages: 965-976, ISSN: 2055-5822

AIMS: In patients with heart failure and a pathologically prolonged PR interval, left ventricular (LV) filling can be improved by shortening atrioventricular delay using His-bundle pacing. His-bundle pacing delivers physiological ventricular activation and has been shown to improve acute haemodynamic function in this group of patients. In the HOPE-HF (His Optimized Pacing Evaluated for Heart Failure) trial, we are investigating whether these acute haemodynamic improvements translate into improvements in exercise capacity and heart failure symptoms. METHODS AND RESULTS: This multicentre, double-blind, randomized, crossover study aims to randomize 160 patients with PR prolongation (≥200 ms), LV impairment (EF ≤ 40%), and either narrow QRS (≤140 ms) or right bundle branch block. All patients receive a cardiac device with leads positioned in the right atrium and the His bundle. Eligible patients also receive a defibrillator lead. Those not eligible for implantable cardioverter defibrillator have a backup pacing lead positioned in an LV branch of the coronary sinus. Patients are allocated in random order to 6 months of (i) haemodynamically optimized dual chamber His-bundle pacing and (ii) backup pacing only, using the non-His ventricular lead. The primary endpoint is change in exercise capacity assessed by peak oxygen uptake. Secondary endpoints include change in ejection fraction, quality of life scores, B-type natriuretic peptide, daily patient activity levels, and safety and feasibility assessments of His-bundle pacing. CONCLUSIONS: Hope-HF aims to determine whether correcting PR prolongation in patients with heart failure and narrow QRS or right bundle branch block using haemodynamically optimized dual chamber His-bundle pacing improves exercise capacity and symptoms. We aim to complete recruitment by the end of 2018 and report in 2020.

Journal article

Dissanayake S, Nagel M, Falaschetti E, Suggett Jet al., 2018, Are valved holding chambers (VHCs) interchangeable? An in vitro evaluation of VHC equivalence, PULMONARY PHARMACOLOGY & THERAPEUTICS, Vol: 48, Pages: 179-184, ISSN: 1094-5539

Journal article

Glaysher M, Mohanaruban A, Prechtl CG, Goldstone AP, Miras AD, Lord J, Chhina N, Falaschetti E, Johnson NA, Al-Najim W, smith C, Li JV, Patel M, Ahmed AR, Moore M, Poulter NR, Bloom S, Darzi A, Le Roux C, Byrne JP, teare Jet al., 2017, A randomised controlled trial of a duodenal-jejunal bypass sleeve device (EndoBarrier) compared with standard medical therapy for the management of obese subjects with type 2 diabetes mellitus, BMJ Open, Vol: 7, ISSN: 2044-6055

Introduction The prevalence of obesity and obesity-related diseases, including type 2 diabetes mellitus (T2DM), is increasing. Exclusion of the foregut, as occurs in Roux-en-Y gastric bypass, has a key role in the metabolic improvements that occur following bariatric surgery, which are independent of weight loss. Endoscopically placed duodenal-jejunal bypass sleeve devices, such as the EndoBarrier (GI Dynamics, Lexington, Massachusetts, USA), have been designed to create an impermeable barrier between chyme exiting the stomach and the mucosa of the duodenum and proximal jejunum. The non-surgical and reversible nature of these devices represents an attractive therapeutic option for patients with obesity and T2DM by potentially improving glycaemic control and reducing their weight.Methods and analysis In this multicentre, randomised, controlled, non-blinded trial, male and female patients aged 18–65 years with a body mass index 30–50 kg/m2 and inadequately controlled T2DM on oral antihyperglycaemic medications (glycosylated haemoglobin (HbA1c) 58–97 mmol/mol) will be randomised in a 1:1 ratio to receive either the EndoBarrier device (n=80) for 12 months or conventional medical therapy, diet and exercise (n=80). The primary outcome measure will be a reduction in HbA1c by 20% at 12 months. Secondary outcome measures will include percentage weight loss, change in cardiovascular risk factors and medications, quality of life, cost, quality-adjusted life years accrued and adverse events. Three additional subgroups will investigate the mechanisms behind the effect of the EndoBarrier device, looking at changes in gut hormones, metabolites, bile acids, microbiome, food hedonics and preferences, taste, brain reward system responses to food, eating and addictive behaviours, body fat content, insulin sensitivity, and intestinal tissue gene expression.

Journal article

Leong KMW, chow J-J, Ng FS, Falaschetti E, Qureshi N, Koa-Wing M, Linton N, Whinnett Z, Lefroy D, Davies DW, Lim PB, Peters N, Kanagaratnam P, Varnava Aet al., 2017, Comparison of the Prognostic Usefulness of the European Society of Cardiology and American Heart Association/American College of Cardiology Foundation Risk Stratification Systems for Patients With Hypertrophic Cardiomyopathy, American Journal of Cardiology, Vol: 121, Pages: 349-355, ISSN: 0002-9149

Implantable cardio-defibrillators (ICDs) have proven benefit in preventing sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HC), making risk stratification essential. Data on the predictive accuracy on the European Society of Cardiology (ESC) risk scoring system has been conflicting. We independently evaluated the ESC risk scoring system in our cohort of HC patients from a large tertiary centre and compared this to previous guidance by the American College of Cardiology Foundation and Heart Association (ACCF/AHA). Risk factor profiles, 5-year SCD risk estimates and ICD recommendations as defined by the ACCF/AHA and ESC guidelines, were retrospectively ascertained for 288 HC patients with and without SCD or equivalent events at our centre. In the SCD group (n=14), a significantly higher proportion of patients would not have met the criteria for an ICD implant using the ESC scoring algorithm than ACCF/AHA guidance (43%vs7%, p=0.029). In those without SCD events (n=274), a larger proportion of individuals not requiring an ICD was identified using the ESC risk score model compared to the ACCF/AHA model (82%vs57%; p<0.0001). Based on risk stratification criteria alone, 5 more individuals with a previously aborted SCD event would not have received an ICD with the ESC risk model than the ACCF/AHA risk model. In conclusion, we found that the current ESC scoring system potentially leaves more high-risk patients unprotected from sudden death in our cohort of patients.

Journal article

Bicknell CD, Kiru G, Falaschetti E, Powell J, Poulter N, the AARDVARK Collaboratorset al., 2016, An evaluation of the effect of an angiotensin-converting enzyme inhibitor on the growth rate of small abdominal aortic aneurysms: A randomised placebo controlled trial (AARDVARK), European Heart Journal, Vol: 37, Pages: 3213-3221, ISSN: 1522-9645

Aims The AARDVARK (Aortic Aneurysmal Regression of Dilation: Value of ACE-Inhibition on RisK) trial investigated whether ACE-inhibition reduces small abdominal aortic aneurysms (AAA) growth rate, independent of blood pressure (BP) lowering.Methods and results A three-arm, multi-centre, single-blind, and randomized controlled trial (ISRCTN51383267) was conducted in 14 hospitals in England. Subjects aged ≥55 years with AAA diameter 3.0–5.4 cm were randomized 1:1:1 to receive perindopril arginine 10 mg, or amlodipine 5 mg, or placebo and followed 3–6 monthly over 2 years. The primary outcome was aneurysm growth rate (based on external antero-posterior ultrasound measurements in the longitudinal plane), determined by multi-level modelling to provide maximum likelihood estimates. Two hundred and twenty-four subjects were randomized (2011–2013) to placebo (n = 79), perindopril (n = 73), or amlodipine (n = 72). Mean (SD) changes in mid-trial systolic BP (12 months) were 0.5 (14.3) mmHg, P = 0.78 compared with baseline, −9.5 (13.1) mmHg (P < 0.001), and −6.7 (12.0) mmHg (P < 0.001), respectively. No significant differences in the modelled annual growth rates were apparent [1.68 mm (SE 0.2), 1.77 mm (0.2), and 1.81 mm (0.2), respectively]. The estimated difference in annual growth between the perindopril and placebo groups was 0.08 mm (CI −0.50, 0.65). Similar numbers of AAAs in each group reached 5.5 cm diameter and/or underwent elective surgery: 11 receiving placebo, 10 perindopril, and 11 amlodipine.Conclusion Small AAA growth rates were lower than anticipated, but there was no significant impact of perindopril compared with placebo or placebo and amlodipine, combined despite more effective BP lowering.

Journal article

Hughes AD, Falaschetti E, Witt N, Wijetunge S, Thom SA, Tillin T, Aldington SJ, Chaturvedi Net al., 2016, Association of Retinopathy and Retinal Microvascular Abnormalities With Stroke and Cerebrovascular Disease., Stroke, ISSN: 0039-2499

BACKGROUND AND PURPOSE: Abnormalities of the retinal circulation may be associated with cerebrovascular disease. We investigated associations between retinal microvascular abnormalities and (1) strokes and subclinical cerebral infarcts and (2) cerebral white matter lesions in a UK-based triethnic population-based cohort. METHODS: A total of 1185 participants (age, 68.8±6.1 years; 77% men) underwent retinal imaging and cerebral magnetic resonance imaging. Cerebral infarcts and white matter hyperintensities were identified on magnetic resonance imaging, retinopathy was graded, and retinal vessels were measured. RESULTS: Higher retinopathy grade (odds ratio [OR], 1.40 [95% confidence interval (95% CI), 1.16-1.70]), narrower arteriolar diameter (OR, 0.98 [95% CI, 0.97-0.99]), fewer symmetrical arteriolar bifurcations (OR, 0.84 [95% CI, 0.75-0.95]), higher arteriolar optimality deviation (OR, 1.16 [95% CI, 1.00-1.34]), and more tortuous venules (OR, 1.20 [95% CI, 1.09-1.32]) were associated with strokes/infarcts and white matter hyperintensities. Associations with quantitative retinal microvascular measures were independent of retinopathy. CONCLUSIONS: Abnormalities of the retinal microvasculature are independently associated with stroke, cerebral infarcts, and white matter lesions.

Journal article

Poulter N, Anjum A, Cross M, Falaschetti E, Savopoulos C, Kanellos I, Szigeti M, Thom S, Hatzitolios Aet al., 2016, LBOS 01-01A COMPARISON OF THE IMPACT OF MORNING OR NIGHT DELIVERY OF ANTIHYPERTENSIVE AGENTS ON 24 HOUR ABPM LEVELS: A RANDOMISED CROSS-OVER TRIAL (HARMONY)., Pages: e547-e547

OBJECTIVE: Some data suggest that nocturnal rather than daytime dosing of antihypertensive agents may have beneficial effects on consequent cardiovascular outcomes. This trial was designed to evaluate whether ABPM levels differ by timing of drug dosing, as a possible explanation for these observations. DESIGN AND METHOD: 103 male or female patients aged 18-80 years with "controlled" hypertension (≤150/≤90 mmHg) for at least three months on stable therapy of ≥1 antihypertensive agent were recruited from two centres; London and Thessaloniki. Patients were randomised to receive their usual therapy either in the morning or evening (6am-11am/6pm-11pm) for 12 weeks, then participants crossed-over to the alternative timing of drug administration for a further 12 weeks.Clinic BPs using standardised methodology and a 24 hour ABPM recording were taken at baseline, 12 and 24 weeks along with completion of the EQ-5D-5L quality of life questionnaire. The study was powered to detect 3mmHg difference in mean 24h SBP with 80% power and α = 0.05 significance level, and reached the target sample size. Regression model was used to calculate confidence intervals adjusted to centre, period (visit) and sequence (group). RESULTS: 95 patients (92%) completed all three ABPM recordings. The mean age of recruits was 52 years and 44% were female.24 hour systolic and diastolic BPs did not differ between daytime and nocturnal dosing (table). Similarly, there was no impact on mean daytime (7.00am-10.00pm) or night time (10pm-7.00am) ABPM levels, nor on clinic BP levels.Stratification by age (<65/≥65 years) and by gender did not affect the results. CONCLUSIONS: In patients with stable BP levels and hypertension diagnosed at least one year ago, the timing of antihypertensive drug administration (morning or evening) did not affect the mean 24 hour ABPM levels recorded.

Conference paper

Poulter NR, Anjum A, Cross M, Falaschetti E, Savopoulos C, Szigeti M, Thom S, Hatzitolios Aet al., 2016, A COMPARISON OF THE IMPACT OF MORNING OR NIGHT DELIVERY OF ANTIHYPERTENSIVE AGENTS ON 24 HOUR AMBULATORY BLOOD PRESSURE MONITORING (ABPM) LEVELS: A RANDOMISED CROSS-OVER TRIAL, [OP.LB01.07] A COMPARISON OF THE IMPACT OF MORNING OR NIGHT DELIVERY OF ANTIHYPERTENSIVE AGENTS ON 24 HOUR AMBULATORY BLOOD PRESSURE MONITORING (ABPM) LEVELS: A RANDOMISED CROSS-OVER TRIAL, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E37-E38, ISSN: 0263-6352

Conference paper

Lear R, Riga C, Godfrey AD, Falaschetti E, Cheshire NJ, Van Herzeele I, Norton C, Vincent C, Darzi AW, Bicknell CD, LEAP Study Collaboratorset al., 2016, Multicentre observational study of surgical system failures in aortic procedures and their effect on patient outcomes, British Journal of Surgery, Vol: 103, Pages: 1467-1475, ISSN: 1365-2168

BACKGROUND: Vascular surgical care has changed dramatically in recent years with little knowledge of the impact of system failures on patient safety. The primary aim of this multicentre observational study was to define the landscape of surgical system failures, errors and inefficiency (collectively termed failures) in aortic surgery. Secondary aims were to investigate determinants of these failures and their relationship with patient outcomes. METHODS: Twenty vascular teams at ten English hospitals trained in structured self-reporting of intraoperative failures (phase I). Failures occurring in open and endovascular aortic procedures were reported in phase II. Failure details (category, delay, consequence), demographic information (patient, procedure, team experience) and outcomes were reported. RESULTS: There were strong correlations between the trainer and teams for the number and type of failures recorded during 88 procedures in phase I. In 185 aortic procedures, teams reported a median of 3 (i.q.r. 2-6) failures per procedure. Most frequent failures related to equipment (unavailability, failure, configuration, desterilization). Most major failures related to communication. Fourteen failures directly harmed 12 patients. Significant predictors of an increased failure rate were: endovascular compared with open repair (incidence rate ratio (IRR) for open repair 0·71, 95 per cent c.i. 0·57 to 0·88; P = 0·002), thoracic aneurysms compared with other aortic pathologies (IRR 2·07, 1·39 to 3·08; P < 0·001) and unfamiliarity with equipment (IRR 1·52, 1·20 to 1·91; P < 0·001). The major failure total was associated with reoperation (P = 0·011), major complications (P = 0·029) and death (P = 0·027). CONCLUSION: Failure in aortic procedures is frequently caused by issues with team-wo

Journal article

Kiru G, Bicknell C, Falaschetti E, Powell J, Poulter Net al., 2016, An evaluation of the effect of an angiotensin-converting enzyme inhibitor on the growth rate of small abdominal aortic aneurysms: a randomised placebo-controlled trial (AARDVARK), Health Technology Assessment, Vol: 20, ISSN: 1366-5278

BACKGROUND: Although data are inconsistent, angiotensin-converting enzyme inhibitors (ACE-Is) have been associated with a reduced incidence of abdominal aortic aneurysm (AAA) rupture in analysis of administrative databases. OBJECTIVES: (1) To investigate whether or not the ACE-I perindopril (Coversyl arginine, Servier) reduces small AAA growth rate and (2) to evaluate blood pressure (BP)-independent effects of perindopril on small AAA growth and to compare the repeatability of measurement of internal and external aneurysm diameters. DESIGN: A three-arm, multicentre, single-blind, randomised placebo-controlled trial. SETTING: Fourteen hospitals in England. PARTICIPANTS: Men or women aged ≥ 55 years with an AAA of 3.0-5.4 cm in diameter by internal or external measurement according to ultrasonography and who met the trial eligibility criteria. INTERVENTIONS: Patients were randomised to receive 10 mg of perindopril arginine daily, 5 mg of the calcium channel blocker amlodipine daily or placebo daily. MAIN OUTCOME MEASURES: The primary outcome was AAA diameter growth using external measurements in the longitudinal plane, which in-trial studies suggested was the preferred measure. Secondary outcome measures included AAA rupture, AAA repair, modelling of the time taken for the AAA to reach the threshold for intervention (5.5 cm) or referral for surgery, tolerance of study medication (measured by compliance, adverse events and quality of life) and a comparison of the repeatability of measures of internal and external AAA diameter. Patients were followed up every 3-6 months over 2 years. RESULTS: In total, 227 patients were recruited and randomised into the three groups, which were generally well matched at baseline. Multilevel modelling was used to determine the maximum likelihood estimates for AAA diameter growth. No significant differences in the estimates of annual growth were apparent [1.68 (standard error 0.02) mm, 1.77 (0.

Journal article

Poulter N, Anjum A, Cross M, Falaschetti E, Savopoulos C, Kanellos I, Szigeti M, Thom S, Hatzitolios Aet al., 2016, LBOS 01-01A COMPARISON OF THE IMPACT OF MORNING OR NIGHT DELIVERY OF ANTIHYPERTENSIVE AGENTS ON 24 HOUR ABPM LEVELS: A RANDOMISED CROSS-OVER TRIAL (HARMONY).

Conference paper

Poulter N, Anjum A, Cross M, Falaschetti E, Savopoulos C, Szigeti M, Thom S, Hatzitolios Aet al., 2016, A comparison of the impact of morning or night delivery of antihypertensive agents on 24 hour ambulatory blood pressure monitoring (ABPM) levels: a randomised cross-over trial, Pages: 641-641

Conference paper

Warwick J, Falaschetti E, Rockwood K, Mitnitski A, Thijs L, Beckett N, Bulpitt C, Peters Ret al., 2015, Lack of evidence that frailty modifies the positive impact of antihypertensive treatment in very elderly people, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 880-880, ISSN: 0195-668X

Conference paper

Warwick J, Falaschetti E, Rockwood K, Mitnitski A, Thijs LB, Beckett NS, Bulpitt CJB, Peters RMet al., 2015, No evidence that frailty modifies the positive impact of antihypertensive treatment in very elderly people: An investigation of the impact of frailty upon treatment effect in the HYpertension in the Very Elderly Trial (HYVET) study, a double-blind, placebo-controlled study of antihypertensives in people with hypertension aged 80 and over, BMC Medicine, Vol: 13, ISSN: 1741-7015

Background: Treatment for hypertension with antihypertensive medication has been shown to reduce stroke, cardiovascular events, and mortality in older adults, but there is concern that such treatment may not be appropriate in frailer older adults. To investigate whether there is an interaction between effect of treatment for hypertension and frailty in older adults, we calculated the frailty index (FI) for all available participants from the HYpertension in the Very Elderly Trial (HYVET) study, a double-blind, placebo-controlled study of antihypertensives in people with hypertension aged 80 and over, and obtained frailty adjusted estimates of the effect of treatment with antihypertensive medication on risk of stroke, cardiovascular events, and mortality. Methods: Participants in HYVET were randomised 1:1 to active treatment with indapamide sustained release 1.5 mg ± perindopril 2 to 4 mg or to matching placebo. Data relating to blood pressure, comorbidities, cognitive function, depression, and quality of life were collected at entry into the study and at subsequent follow-up visits. The FI was calculated at entry, based on 60 potential deficits. The distribution of FI was similar to that seen in population studies of adults aged 80 years and above (median FI, 0.17; IQR, 0.11-0.24). Cox regression was used to assess the impact of FI at entry to the study on subsequent risk of stroke, total mortality, and cardiovascular events. Models were stratified by region of recruitment and adjusted for sex and age at entry. Extending these models to include a term for a possible interaction between treatment for hypertension and FI provided a formula for the treatment effect as a function of FI. For all three models, the point estimates of the hazard ratios for the treatment effect decreased as FI increased, although to varying degrees and with varying certainty. Results: We found no evidence of an interaction between effect of treatment for hypertension and frailty as me

Journal article

Hughes AD, Falaschetti E, Tillin T, Aldington SJ, Chaturvedi Net al., 2015, Diabetic retinopathy and retinal arteriolar narrowing and rarefaction are associated with stroke and subclinical cerebrovascular disease in Southall and Brent Revisited (SABRE), a tri-ethnic population based cohort, DIABETIC MEDICINE, Vol: 32, Pages: 28-28, ISSN: 0742-3071

Journal article

Hughes AD, Falaschetti E, Aldington SJ, Tillin T, Chaturvedi Net al., 2015, Prevalence of diabetic retinopathy and retinal microvascular abnormalities in European, South Asian and African Caribbean people in UK, DIABETIC MEDICINE, Vol: 32, Pages: 57-57, ISSN: 0742-3071

Journal article

Falaschetti E, Mindell J, Knott C, Poulter Net al., 2014, Hypertension management in England: a serial cross-sectional study from 1994 to 2011, The Lancet, Vol: 383, Pages: 1912-1919, ISSN: 0140-6736

BackgroundHypertension is the leading risk factor contributing to the global burden of disease. We aimed to assess the change in blood pressure management between 1994 and 2011 in England with a series of annual surveys.MethodsWe did a serial cross-sectional study of five Health Survey for England surveys based on nationally representative samples of non-institutionalised adults (aged ≥16 years). Mean blood pressure levels and rates of awareness, treatment, and control of hypertension were assessed. Hypertension was defined as systolic blood pressure 140 mm Hg or higher, diastolic blood pressure 90 mm Hg or higher, or receiving treatment for high blood pressure.FindingsThe mean blood pressure levels of men and women in the general population and among patients with treated hypertension progressively improved between 1994 and 2011. In patients with treated hypertension, blood pressure improved from 150·0 (SE 0·59)/80·2 (0·27) mm Hg to 135·4 (0·58)/73·5 (0·41) mm Hg. Awareness, treatment, and control rates among men and women combined also improved significantly across each stage of this 17-year period, with the prevalence of control among treated patients almost doubling from 33% (SE 1·4) in 1994 to 63% (1·7) in 2011. Nevertheless, of all adults with survey-defined hypertension in 2011, hypertension was controlled in only 37%.InterpretationIf the same systematic improvement in all aspects of hypertension management continues until 2022, 80% of patients with treated hypertension will have controlled blood pressure levels with a potential annual saving of about 50 000 major cardiovascular events.

Journal article

Joffres M, Falaschetti E, Gillespie C, Robitaille C, Loustalot F, Poulter N, McAlister FA, Johansen H, Baclic O, Campbell Net al., 2013, Hypertension prevalence, awareness, treatment and control in national surveys from England, the USA and Canada, and correlation with stroke and ischaemic heart disease mortality: a cross-sectional study, BMJ Open, Vol: 3, ISSN: 2044-6055

Objective: Comparison of recent national survey dataon prevalence, awareness, treatment and control ofhypertension in England, the USA and Canada, andcorrelation of these parameters with each countrystroke and ischaemic heart disease (IHD) mortality.Design: Non-institutionalised population surveys.Setting and participants: England (2006 n=6873),the USA (2007–2010 n=10 003) and Canada (2007–2009 n=3485) aged 20–79 years.Outcomes: Stroke and IHD mortality rates wereplotted against countries’ specific prevalence data.Results: Mean systolic blood pressure (SBP) washigher in England than in the USA and Canada in allage–gender groups. Mean diastolic blood pressure(DBP) was similar in the three countries before age 50and then fell more rapidly in the USA, being the lowestin the USA. Only 34% had a BP under 140/90 mm Hgin England, compared with 50% in the USA and66% in Canada. Prehypertension and stages 1 and 2hypertension prevalence figures were the highest inEngland. Hypertension prevalence (≥140 mm Hg SBPand/or ≥90 mm Hg DBP) was lower in Canada(19·5%) than in the USA (29%) and England (30%).Hypertension awareness was higher in the USA (81%)and Canada (83%) than in England (65%). Englandalso had lower levels of hypertension treatment (51%;USA 74%; Canada 80%) and control (<140/90 mm Hg;27%; the USA 53%; Canada 66%). Canada had thelowest stroke and IHD mortality rates, Englandthe highest and the rates were inversely related to themean SBP in each country and strongly related to theblood pressure indicators, the strongest relationshipbeing between low hypertension awareness and strokemortality.Conclusions: While the current prevention efforts inEngland should result in future-improved figures,especially at younger ages, these data still showimportant gaps in the management of hypertension inthese countries, with consequences on stroke and IHDmortality

Journal article

Charakida M, Jones A, Falaschetti E, Khan T, Finer N, Sattar N, Hingorani A, Lawlor DA, Smith GD, Deanfield JEet al., 2012, Childhood Obesity and Vascular Phenotypes A Population Study, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 60, Pages: 2643-2650, ISSN: 0735-1097

Journal article

Asher L, Aresu M, Falaschetti E, Mindell Jet al., 2012, Most older pedestrians are unable to cross the road in time: a cross-sectional study, AGE AND AGEING, Vol: 41, Pages: 690-694, ISSN: 0002-0729

Journal article

Quanjer PH, Hall GL, Stanojevic S, Cole TJ, Stocks Jet al., 2012, Age- and height-based prediction bias in spirometry reference equations, EUROPEAN RESPIRATORY JOURNAL, Vol: 40, Pages: 190-197, ISSN: 0903-1936

Journal article

Jones A, Charakida M, Falaschetti E, Hingorani AD, Finer N, Masi S, Donald AE, Lawlor DA, Smith GD, Deanfield JEet al., 2012, Adipose and Height Growth Through Childhood and Blood Pressure Status in a Large Prospective Cohort Study, HYPERTENSION, Vol: 59, Pages: 919-+, ISSN: 0194-911X

Journal article

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