Measurements of V/STOL aircraft noise mechanisms using pressure cross-correlation techniques in a reverberant wind tunnel

A 3.8 cm. model jet was operated in a wind tunnel with cross-flow in order to determine the effect on jet noise radiated characteristics. A method was developed for the determination of noise radiating characteristics of sources within reverberant wind tunnels; cross-correlation measurements were used. The averaging time in the cross-correlation is determined by the amount of background noise within the wind tunnel. It was found that cross-flow increases the radiated noise by 10 db. There was some indication of downstream radiation exceeding the sideline radiation

Aerosound from corner flow and flap flow

Noise generation at the edge of a wing flap is analyzed. The phenomenon as a single vortex moving around a corner in an incompressible, potential flow is modelled. Vortex image retarding effects are proposed as an explanation for small Strouhal numbers. The model surface pressures, sound pressures (using Curle's theory), and Mach number dependencies agree with wind tunnel experiments. A double pressure peak is found in the model (credited to image action) which is qualitatively similar to measured sound correlations. Incompressible flow aerosound calculations are discussed. The effects of a series of vortices moving in the same idealized potential flow are also studied. The vortices are assumed to be statistically independent so their intensities can be added. The frequency of appearance of the vortices are determined from measurements. Diffraction effects caused by the presence of the wing near the dipole sound radiators on the flap surfaces are included

Withdrawal from treatment as an outcome in the Isolde study of COPD

Objectives: To investigate the determinants of patient withdrawal from our study, and the effect of these withdrawals on the outcome of treatment with inhaled corticosteroids in patients with COPD. Design: A double-blind, placebo-controlled, randomized trial. Setting: Eighteen outpatient centers in the United Kingdom. Participants: Seven hundred fifty-one patients with stable COPD defined clinically as baseline postbronchodilator FEV1 > 0.8 L and < 85% predicted, FEV1/FVC ratio < 70%, and FEV1 change after albuterol < 10% of predicted. Intervention: Random assignment of either 500 micrograms bid of inhaled fluticasone propionate (FP)using a spacer device or an identical placebo inhaler. Treatment was continued for 3 years or until patients withdrew from follow-up. Measurements and results: Postbronchodilator FEV1 was measured on three occasions before randomization and every 3 months thereafter. Health status was assessed by the disease-specific St. George Respiratory Questionnaire (SGRQ) and the modified short-form 36 questionnaire (SF-36) at baseline and every 6 months. Three hundred thirty-nine patients withdrew, of whom 156 patients received FP. Prescription of frequent courses of oral prednisolone was the most common reason for withdrawing as specified in the protocol (69 patients in the FP group withdrew due to respiratory symptoms, compared with 93 patients in the placebo group). This explained the significantly greater dropout of placebo-treated patients that was most evident when FEV1 was < 50% predicted. Patients withdrawing had a significantly more rapid decline in health status, measured by both the SGRQ and the SF-36 (p < 0.001). Those withdrawing from the placebo group had a more rapid decline in FEV1 and more exacerbations than the FP-treated groups. Baseline FEV1 was lower in dropouts than in patients completing the study receiving placebo, but there was no difference between the respective groups receiving FP. Conclusions: Patients who withdrew from follow-up were those with the most rapidly deteriorating health status and lung function. Losing these patients from the final analysis can reduce the power of a study to achieve its primary end point

A vein bypass first <i>versus</i> a best endovascular treatment first revascularization strategy for patients with chronic limb-threatening ischaemia who require an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularization procedure to restore limb perfusion:the BASIL-2 within-trial health economic analysis

BACKGROUND: Chronic limb-threatening ischaemia (CLTI) places a considerable socioeconomic burden health and social care systems worldwide. The objective of this health economic analysis was to investigate the cost-effectiveness (CEA) and cost-utility (CUA) of a vein bypass (VB) first versus a best endovascular treatment (BET) first revascularization strategy in patients with CLTI who require an infra-popliteal revascularization procedure to restore limb perfusion.METHODS: CEA and CUA analyses were conducted from the perspective of the UK National Health Service. Patient-level resource use and health outcomes data collected from the BASIL-2 trial over 2-7 years of follow-up were utilized to estimate incremental cost-effectiveness ratios expressed as cost per amputation-free life year (AFLY) and cost per quality-adjusted life year (QALY). EQ-5D-5L was used to generate participant QALYs at 2 and 3 years.RESULTS: At two years, the mean(s.d.) discounted hospital cost was £15 742.59(16 182.60) and £13 273.66(15 446.92) in the VB-first and BET-first revascularization strategy groups respectively. The lower costs (-£2524.23, 95% c.i., -£5844.93 to £1131.52) in the BET-first group were mainly due to the reduced number of days in hospital and lower procedural costs. BET-first was also more effective leading to additional AFLYs (0.429, 95% c.i., 0.03 to 0.88) at 7 years and discounted QALYs (0.016, 95% c.i., -0.08 to 0.12) at 2 years.CONCLUSION: A best endovascular first revascularization strategy dominated a vein bypass first strategy in the cost-effectiveness and cost-utility analyses. The findings were robust across different scenarios and prespecified subgroups.</p

Plain versus drug balloon and stenting in severe ischaemia of the leg (BASIL-3):open label, three arm, randomised, multicentre, phase 3 trial

OBJECTIVE: To determine which primary endovascular revascularisation strategy represents the most clinically effective treatment for patients with chronic limb threatening ischaemia who require endovascular femoro-popliteal, with or without infra-popliteal, revascularisation.DESIGN: Three arm, open label, pragmatic, multicentre, randomised, phase 3 superiority trial (BASIL-3).SETTING: 35 UK NHS vascular units.PARTICIPANTS: Patients with chronic limb threatening ischaemia who required endovascular femoro-popliteal, with or without infra-popliteal, revascularisation.INTERVENTIONS: Participants were randomly assigned (1:1:1) to femoro-popliteal plain balloon angioplasty with or without bare metal stenting (PBA±BMS), drug coated balloon angioplasty with or without bare metal stenting (DCBA±BMS), or drug eluting stenting (DES) as their first revascularisation strategy.MAIN OUTCOME MEASURES: The primary outcome was amputation free survival defined as time to first major amputation or death from any cause. Secondary outcomes included the composite components of the primary outcome, major adverse limb events, major adverse cardiac events, and other prespecified clinical and patient reported outcome measures. Serious adverse events were collected up to 30 days after the first revascularisation procedure.RESULTS: Between 29 January 2016 and 31 August 2021, 481 participants were randomised (167 (35%) women, mean age 71.8 years (standard deviation 10.8)). Major amputation or death occurred in 106 of 160 (66%) participants in the PBA±BMS group, 97 of 161 (60%) in the DCBA±BMS group, and 93 of 159 (58%) in the DES group (adjusted hazard ratios: PBA±BMS v DCBA±BMS: 0.84, 97.5% confidence interval 0.61 to 1.16, P=0.22; PBA±BMS v DES: 0.83, 0.60 to 1.15, P=0.20). No differences in serious adverse events were reported between the groups.CONCLUSIONS: Neither DCBA±BMS nor DES conferred significant clinical benefit over PBA±BMS in the femoro-popliteal segment in patients with chronic limb threatening ischaemia undergoing endovascular femoro-popliteal, with or without infra-popliteal, revascularisation.TRIAL REGISTRATION: ISRCTN registry ISRCTN14469736.</p

Editor's Choice - Bypass versus Angioplasty for Severe Ischaemia of the Leg (BASIL) Prospective Cohort Study and the Generalisability of the BASIL-2 Randomised Controlled Trial

OBJECTIVE: The Bypass versus Angioplasty in Severe Ischaemia of the Leg-2 (BASIL-2) randomised controlled trial has shown that, for patients with chronic limb threatening ischaemia (CLTI) who require an infrapopliteal (IP) revascularisation a vein bypass (VB) first revascularisation strategy led to a 35% increased risk of major amputation or death when compared with a best endovascular treatment (BET) first revascularisation strategy. The study aims are to place the BASIL-2 trial within the context of the CLTI patient population as a whole and to investigate the generalisability of the BASIL-2 outcome data.METHODS: This was an observational, single centre prospective cohort study. Between 24 June 2014 and 31 July 2018, the BASIL Prospective Cohort Study (PCS) was performed which used BASIL-2 trial case record forms to document the characteristics, initial and subsequent management, and outcomes of 471 consecutive CLTI patients admitted to an academic vascular centre. Ethical approval was obtained, and all patients provided fully informed written consent. Follow up data were censored on 14 December 2022.RESULTS: Of the 238 patients who required an infrainguinal revascularisation, 75 (32%) had either IP bypass (39 patients) or IP BET (36 patients) outside BASIL-2. Seventeen patients were initially randomised to BASIL-2. A further three patients who did not have an IP revascularisation as their initial management were later randomised in BASIL-2. Therefore, 95/471 (20%) of patients had IP revascularisation (16% outside, 4% inside BASIL-2). Differences in amputation free survival, overall survival, and limb salvage between IP bypass and IP BET performed outside BASIL-2 were not subject to hypothesis testing due to the small sample size. Reasons for non-randomisation into the trial were numerous, but often due to anatomical and technical considerations.CONCLUSION: CLTI patients who required an IP revascularisation procedure and were subsequently randomised into BASIL-2 accounted for a small subset of the CLTI population as a whole. For a wide range of patient, limb, anatomical and operational reasons, most patients in this cohort were deemed unsuitable for randomisation in BASIL-2. The results of BASIL-2 should be interpreted in this context.</p

Vein bypass first vs. best endovascular treatment first revascularisation strategy for chronic limb-threatening ischaemia due to infra-popliteal disease:the BASIL-2 RCT

BACKGROUND: Chronic limb-threatening ischaemia with ischaemic pain and/or tissue loss.OBJECTIVE: To examine the clinical and cost-effectiveness of a vein bypass-first compared to a best endovascular treatment-first revascularisation strategy in preventing major amputation or death.DESIGN: Superiority, open, pragmatic, multicentre, phase III randomised trial.SETTING: Thirty-nine vascular surgery units in the United Kingdom, and one each in Sweden and Denmark.PARTICIPANTS: Patients with chronic limb-threatening ischaemia due to atherosclerotic peripheral arterial disease who required an infra-popliteal revascularisation, with or without an additional more proximal infra-inguinal revascularisation procedure, to restore limb perfusion.INTERVENTIONS: A vein bypass-first or a best endovascular treatment-first infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation strategy.MAIN OUTCOME MEASURES: The primary outcome was amputation-free survival. Secondary outcomes included overall survival, major amputation, further revascularisation interventions, major adverse limb event, health-related quality of life and serious adverse events.METHODS: Participants were randomised to a vein bypass-first or a best endovascular treatment-first revascularisation strategy. The original sample size of 600 participants (247 events) was based on a hazard ratio of 0.66 with amputation-free survival rates of 0.72, 0.62, 0.53, 0.47 and 0.35 in years 1-5 in the best endovascular treatment-first group with 90% power and alpha at p = 0.05. The sample size was revised to an event-based approach as a result of increased follow-up time due to slower than anticipated recruitment rates. Participants were followed up for a minimum of 2 years. A cost-effectiveness analysis was employed to estimate differences in total hospital costs and amputation-free survival between the groups. Additionally, a cost-utility analysis was carried out and the total cost and quality-adjusted life-years, 2 and 3 years after randomisation were used.RESULTS: Between 22 July 2014 and 30 November 2020, 345 participants were randomised, 172 to vein bypass-first and 173 to best endovascular treatment-first. Non-amputation-free survival occurred in 108 (63%) of 172 patients in the vein bypass-first group and 92 (53%) of 173 patients in the best endovascular treatment-first group [adjusted hazard ratio 1.35 (95% confidence interval 1.02 to 1.80); p = 0.037]. Ninety-one (53%) of 172 patients in the vein bypass-first group and 77 (45%) of 173 patients in the best endovascular treatment-first group died [adjusted hazard ratio 1.37 (95% confidence interval 1.00 to 1.87)]. Over follow-up, the economic evaluation discounted results showed that best endovascular treatment-first was associated with £1690 less hospital costs compared to vein bypass-first. The cost utility analysis showed that compared to vein bypass-first, best endovascular treatment-first was associated with £224 and £2233 less discounted hospital costs and 0.016 and 0.085 discounted quality-adjusted life-year gain after 2 and 3 years from randomisation.LIMITATIONS: Recruiting patients to the Bypass versus Angioplasty in Severe Ischaemia of the Leg Trial-2 trial was difficult and the target number of events was not achieved.CONCLUSIONS: A best endovascular treatment-first revascularisation strategy was associated with better amputation-free survival, which was largely driven by fewer deaths. Overall, the economic evaluation results suggest that best endovascular treatment-first dominates vein bypass-first in the cost-effectiveness analysis and cost-utility analysis as it was less costly and more effective than a vein bypass-first strategy.FUTURE WORK: The Bypass versus Angioplasty in Severe Ischaemia of the Leg Trial-2 investigators have a data sharing agreement with the BEst Surgical Therapy in patients with Chronic Limb threatening Ischaemia investigators. One output of this collaboration will be an individual patient data meta-analysis.STUDY REGISTRATION: Current Controlled Trials ISRCTN27728689.FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/35/45) and is published in full in Health Technology Assessment; Vol. 28, No. 65. See the NIHR Funding and Awards website for further award information.</p

A vein bypass first versus a best endovascular treatment first revascularisation strategy for patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation procedure to restore limb perfusion (BASIL-2):an open-label, randomised, multicentre, phase 3 trial

BACKGROUND: Chronic limb-threatening ischaemia is the severest manifestation of peripheral arterial disease and presents with ischaemic pain at rest or tissue loss (ulceration, gangrene, or both), or both. We compared the effectiveness of a vein bypass first with a best endovascular treatment first revascularisation strategy in terms of preventing major amputation and death in patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion.METHODS: Bypass versus Angioplasty for Severe Ischaemia of the Leg (BASIL)-2 was an open-label, pragmatic, multicentre, phase 3, randomised trial done at 41 vascular surgery units in the UK (n=39), Sweden (n=1), and Denmark (n=1). Eligible patients were those who presented to hospital-based vascular surgery units with chronic limb-threatening ischaemia due to atherosclerotic disease and who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion. Participants were randomly assigned (1:1) to receive either vein bypass (vein bypass group) or best endovascular treatment (best endovascular treatment group) as their first revascularisation procedure through a secure online randomisation system. Participants were excluded if they had ischaemic pain or tissue loss considered not to be primarily due to atherosclerotic peripheral artery disease. Most vein bypasses used the great saphenous vein and originated from the common or superficial femoral arteries. Most endovascular interventions comprised plain balloon angioplasty with selective use of plain or drug eluting stents. Participants were followed up for a minimum of 2 years. Data were collected locally at participating centres. In England, Wales, and Sweden, centralised databases were used to collect information on amputations and deaths. Data were analysed centrally at the Birmingham Clinical Trials Unit. The primary outcome was amputation-free survival defined as time to first major (above the ankle) amputation or death from any cause measured in the intention-to-treat population. Safety was assessed by monitoring serious adverse events up to 30-days after first revascularisation. The trial is registered with the ISRCTN registry, ISRCTN27728689.FINDINGS: Between July 22, 2014, and Nov 30, 2020, 345 participants (65 [19%] women and 280 [81%] men; median age 72·5 years [62·7-79·3]) with chronic limb-threatening ischaemia were enrolled in the trial and randomly assigned: 172 (50%) to the vein bypass group and 173 (50%) to the best endovascular treatment group. Major amputation or death occurred in 108 (63%) of 172 patients in the vein bypass group and 92 (53%) of 173 patients in the best endovascular treatment group (adjusted hazard ratio [HR] 1·35 [95% CI 1·02-1·80]; p=0·037). 91 (53%) of 172 patients in the vein bypass group and 77 (45%) of 173 patients in the best endovascular treatment group died (adjusted HR 1·37 [95% CI 1·00-1·87]). In both groups the most common causes of morbidity and death, including that occurring within 30 days of their first revascularisation, were cardiovascular (61 deaths in the vein bypass group and 49 in the best endovascular treatment group) and respiratory events (25 deaths in the vein bypass group and 23 in the best endovascular treatment group; number of cardiovascular and respiratory deaths were not mutually exclusive).INTERPRETATION: In the BASIL-2 trial, a best endovascular treatment first revascularisation strategy was associated with a better amputation-free survival, which was largely driven by fewer deaths in the best endovascular treatment group. These data suggest that more patients with chronic limb-threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion should be considered for a best endovascular treatment first revascularisation strategy.FUNDING: UK National Institute of Health Research Health Technology Programme.</p

A vein bypass first versus a best endovascular treatment first revascularization strategy for patients with chronic limb-threatening ischaemia who require an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularization procedure to restore limb perfusion:the BASIL-2 within-trial health economic analysis

BackgroundChronic limb-threatening ischaemia (CLTI) places a considerable socioeconomic burden health and social care systems worldwide. The objective of this health economic analysis was to investigate the cost-effectiveness (CEA) and cost-utility (CUA) of a vein bypass (VB) first versus a best endovascular treatment (BET) first revascularization strategy in patients with CLTI who require an infra-popliteal revascularization procedure to restore limb perfusion. Methods CEA and CUA analyses were conducted from the perspective of the UK National Health Service. Patient-level resource use and health outcomes data collected from the BASIL-2 trial over 2-7 years of follow-up were utilized to estimate incremental cost-effectiveness ratios expressed as cost per amputation-free life year (AFLY) and cost per quality-adjusted life year (QALY). EQ-5D-5L was used to generate participant QALYs at 2 and 3 years. Results At two years, the mean(s.d.) discounted hospital cost was £15 742.59(16 182.60) and £13 273.66(15 446.92) in the VB-first and BET-first revascularization strategy groups respectively. The lower costs (-£2524.23, 95% c.i., -£5844.93 to £1131.52) in the BET-first group were mainly due to the reduced number of days in hospital and lower procedural costs. BET-first was also more effective leading to additional AFLYs (0.429, 95% c.i., 0.03 to 0.88) at 7 years and discounted QALYs (0.016, 95% c.i., -0.08 to 0.12) at 2 years. Conclusion A best endovascular first revascularization strategy dominated a vein bypass first strategy in the cost-effectiveness and cost-utility analyses. The findings were robust across different scenarios and prespecified subgroups.<p/