Long-term follow-up of fenestrated endovascular repair for juxtarenal aortic aneurysm.

BACKGROUND: Fenestrated endovascular aneurysm repair (FEVAR) is increasingly being used for juxtarenal aortic aneurysms. The aim of this study was to review long-term results and assess the importance of changing stent-graft design on outcomes. METHODS: This was a retrospective review of all patients who underwent FEVAR within a single unit over 12 years (February 2003 to December 2015). Kaplan-Meier analysis of survival, and freedom from target vessel loss, aneurysm expansion, graft-related endoleak and secondary intervention was performed. Comparison between outcomes of less complex grafts (fewer than 3 fenestrations) and more complex grafts (3 or 4 fenestrations) was undertaken. RESULTS: Some 173 patients underwent FEVAR; median age was 76 (i.q.r. 70-79) years and 90·2 per cent were men. Median aneurysm diameter was 63 (59-71) mm and median follow-up was 34 (16-50) months. The adjusted primary technical operative success rate was 95·4 per cent. The in-hospital mortality rate was 5·2 per cent; there was no known aneurysm-related death during follow-up. Median survival was 7·1 (95 per cent c.i. 5·2 to 8·1) years and overall survival was 60·1 per cent (104 of 173). There was a trend towards an increasing number of fenestrations in the graft design over time. In-hospital mortality appeared higher when more complex stent-grafts were used (8 versus 2 per cent for stent-grafts with 3-4 versus fewer than 3 fenestrations; P = 0·059). Graft-related endoleaks were more common following deployment of stent-grafts with three or four fenestrations (12 of 90 versus 6 of 83; P < 0·001). CONCLUSION: Fenestrated endovascular aneurysm repair for juxtarenal aneurysm is associated with few aneurysm-related deaths in the long term. Significant numbers of secondary interventions are required, but the majority of these can be performed using an endovascular approach.

The use of fenestrated and branched endovascular aneurysm repair for juxtarenal and thoracoabdominal aneurysms: a systematic review and cost-effectiveness analysis.

BACKGROUND: Patients with large abdominal aortic aneurysms (AAAs) are usually offered reparative treatment given the high mortality risk. There is uncertainty about how to treat juxtarenal AAAs (JRAAAs) or thoracoabdominal aortic aneurysms (TAAAs). Endovascular repair of an abdominal aortic aneurysm (EVAR) is often seen as safer and easier than open surgical repair (OSR). However, endovascular treatment of JRAAAs or TAAAs requires specially manufactured stent grafts, with openings to allow blood to reach branches of the aorta. Commissioners are receiving increasing requests for fenestrated EVAR (fEVAR) and branched EVAR (bEVAR), but it is unclear whether or not the extra cost of fEVAR or bEVAR is justified by advantages for patients. OBJECTIVE(S): To assess the clinical effectiveness, safety and cost-effectiveness of fEVAR and bEVAR in comparison with conventional treatment (i.e. no surgery) or OSR for two populations: JRAAAs and TAAAs. DATA SOURCES: Resources were searched from inception to October 2013, including MEDLINE (OvidSP), EMBASE (OvidSP) and the Cochrane Central Register of Controlled Trials (Wiley) and, additionally, for cost-effectiveness, NHS Economic Evaluation Database (NHS EED; Wiley) and EconLit (EBSCOhost). Conference abstracts were also searched. REVIEW METHODS: Studies were included based on an intervention of either fEVAR or bEVAR and a comparator of either OSR or no surgery. For clinical effectiveness, observational studies were excluded only if they were not comparative, i.e. explicitly selected on the basis of prognosis. RESULTS: For clinical effectiveness, searches retrieved 5253 records before deduplication. Owing to overlap between the databases, 1985 duplicate records were removed. Of the remaining 3268 records, based on titles and abstracts, 3244 records were excluded, leaving 24 publications to be ordered. All 24 studies were excluded as none of them satisfied the inclusion criteria. Sixteen studies were excluded on study design, six on intervention and two on comparator. Five out of 16 studies excluded on study design reported a comparison. However, all of the studies acknowledged that they had groups that were not comparable at baseline given that they had selectively assigned younger, fitter patients to OSR. Therefore, these studies were considered 'non-comparative'. For cost-effectiveness, searches identified 104 references before deduplication. Owing to overlap between the databases, 34 duplicate records were removed. Of the remaining 70 records, seven were included for the full assessment based on initial screening. After a full-text review, no studies were included. Because of the lack of clinical effectiveness evidence and difficulty in estimating costs given the rapidly changing and variable technology, a cost-effectiveness analysis (CEA) was not performed. Instead a detailed description of modelling methods was provided. CONCLUSIONS: Despite a thorough search, no studies could be found that met the inclusion criteria. All studies that compared either fEVAR or bEVAR with either OSR or no surgery explicitly selected patients based on prognosis, i.e. essentially the populations for each comparator were not the same. Despite not being able to conduct a CEA, we have provided detailed methods for the conduct if data becomes available. FUTURE WORK: We recommend at least one clinical trial to provide an unbiased estimate of effect for fEVAR/bEVAR compared with OSR or no surgery. This trial should also collect data for a CEA. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013006051. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Patch variability following carotid endarterectomy: a survey of Great Britain and Ireland.

INTRODUCTION: Evidence suggests a clinical benefit with patch angioplasty after carotid endarterectomy (CEA). The UK National Vascular Database has demonstrated variation in practice but does not record technical details. This study was intended to define indications and technique of patching after CEA. METHODS: An electronic questionnaire was emailed to all 402 members of the Vascular Society of Great Britain and Ireland. The email could not be received by 23 and 14 did not perform CEA. Some questions allowed multiple answers. Fisher's exact test was used for statistical analysis. RESULTS: There were 187 responses (51%). Fifteen members (8%) performed eversion CEA, which obviates patching. Of all the respondents, 121 surgeons (65%) always use a patch. Seventy of these (58%) use the full patch width (median: 8 mm, range: 4-10 mm). Fourteen (12%) variably trimmed the patch (median: 7.5 mm, range: 5-10 mm) and 34 (28%) routinely trimmed (median: 6 mm, range: 3-20 mm). Selective patching, dependent on internal carotid artery diameter, was performed by 48 respondents (26%), 23 of whom specified a median artery threshold diameter of 5 mm (range: 3-8 mm). General anaesthesia was always or usually used by 83 surgeons (45%), local anaesthesia by 77 (41%) and the remainder followed patient choice. Obligatory patching is performed by 68 of the 83 respondents (82%) who prefer general anaesthesia whereas only 40 of the 77 surgeons (52%) who use local anaesthesia always patch (p<0.0001). CONCLUSIONS: There is a variable rate of patching after CEA in the UK, which appears dependent on the vessel size and mode of anaesthesia. There are also differences in the patch width adopted.

Anchoring barbs and balloon expandable stents: what is the risk of perforation and failed stent deployment?

PURPOSE: Balloon expandable stents may on occasion be deployed in close proximity to the anchoring barbs of endovascular grafts. The aim of this study was to determine the risk and effect of balloon perforation by anchoring barbs and to assess whether these risks are different if the balloon is protected by a covered stent mounted upon it. METHODS: A bench-top model was developed to mimic the penetration of anchoring barbs into the lumen of medium sized blood vessels. The model allowed variation of angle and depth of vessel penetration. Both bare balloons and those with covered stents mounted upon them were tested in the model to determine whether there was a risk of perforation and which factors increased or decreased this risk. RESULTS: All combinations of barb angle and depth caused balloon perforation but this was most marked when the barb was placed perpendicular to the long axis of the balloon. When the deployment of covered stents was attempted balloon perforation occurred in some cases but full stent deployment was achieved in all cases where the perforation was in the portion of the balloon covered by the stent. The only situation in which stent deployment failed was where the barb was intentionally placed in the uncovered portion of the balloon. This resulted in only partial deployment of the stent. CONCLUSIONS: Balloon rupture is a distinct possibility when deploying balloon-expandable stents in close proximity to anchoring barbs. Care should be taken in this circumstance to ensure that the barb is well away from the uncovered portion of the balloon.

Surveillance after EVAR based on duplex ultrasound and abdominal radiography.

INTRODUCTION: Computed tomography angiography (CTA) is considered the gold standard imaging technique for surveillance following endovascular aneurysm repair (EVAR). Limitations of CTA include cost, risk of contrast nephropathy and radiation exposure. A modified surveillance protocol involving annual duplex ultrasound (DUS) and abdominal radiography (AXR) was introduced, with CTA performed only if abnormalities were identified or DUS was undiagnostic. METHODS: Prospective records were maintained on patients undergoing infra-renal EVAR at a UK, tertiary referral centre. All patients enrolled with at least one-year follow-up were reviewed. Primary outcomes identified were aneurysm rupture and aneurysm-related complications. Secondary outcomes included number of CTAs avoided and cost. RESULTS: Median follow-up was 36 months (range 12-57) for 194 patients. The total number of sets of surveillance imaging was 412 of which 70 (17%) required CTA. Abnormalities were found in 30 patients, 18 confirmed by CTA. Eleven patients required secondary intervention, three initially identified by AXR, three by DUS, three by both DUS and AXR, and two by CTA following undiagnostic DUS. No patient presented with rupture or aneurysm-related complications not identified by modified surveillance. Mean annual savings were €223. CONCLUSION: EVAR surveillance based on DUS and AXR is feasible and safe. The complimentary nature of AXR and DUS is demonstrated.

Fascial closure following percutaneous endovascular aneurysm repair.

INTRODUCTION: There are potential benefits of percutaneous over open femoral access for endovascular aneurysm repair (EVAR). Subsequent arterial closure using percutaneous devices is costly, whilst open repair risks potential wound complications and delayed discharge. The technique of fascial closure has perceived advantages but its efficacy is unclear. The aim of this study was to assess the safety and durability of fascial closure after EVAR. METHODS: Patients undergoing EVAR using devices up to 24 French were considered. Exclusion criteria included morbid obesity, high bifurcation, previous surgery, inadvertent high puncture, arteries < 5 mm and surgeon preference. The primary outcome measure was immediate technical success. All patients were followed-up clinically and with duplex at one and twelve months to determine secondary complications. RESULTS: Over a one-year period fascial closure of 69 common femoral arteries was attempted in 38 patients undergoing EVAR. Nine primary failures were due to haemorrhage in eight arteries and thrombosis in one artery; all had immediate, uncomplicated open revision. Of the 60 (87%) successful procedures, all had duplex surveillance at one month. Four pseudoaneurysms were identified, all treated conservatively. At one year, 61 fascial closures (88%) were imaged, four patients had died and two were lost to follow-up. Three of the pseudoaneurysms had resolved, the fourth patient had died (unrelated). No other complication attributable to fascial closure was found at either one or twelve months. CONCLUSION: Fascial closure is a safe, durable and cost-effective method of arterial closure following EVAR. Success and complication rates are comparable to other techniques.

Measurement of pulsatile haemodynamic forces in a model of a bifurcated stent graft for abdominal aortic aneurysm repair.

The longitudinal haemodynamic force (LF) acting on a bifurcated stent graft for abdominal aortic aneurysm repair has been estimated previously using a simple one-dimensional analytical model based on the momentum equation which assumes steady flow of an inviscid fluid. Using an instrumented stent-graft model an experimental technique was developed to measure the LF under pulsatile flow conditions. The physical stent-graft model, with main trunk diameter of 30mm and limb diameters of 12 mm, was fabricated from aluminium. Strain gauges were bonded on to the main trunk to determine the longitudinal strain which is related to the LF. After calibration, the model was placed in a pulsatile flow system with 40 per cent aqueous glycerol solution as the circulating fluid. The LF was determined using a Wheatstone bridge signal-conditioning circuit. The signals were averaged over 590 cardiac cycles and saved to a personal computer for subsequent processing. The LF was strongly dependent on the pressure but less so on the flowrate. The measured forces were higher than those predicted by the simplified mathematical model by about 6-18 per cent during the cardiac cycle. The excess measured forces are due to the viscous drag and the effect of pulsatile flow. The peak measured LF in this model of 30 mm diameter may exceed the fixation force of some current clinical endovascular stent grafts.

Wholly endovascular repair of thoracoabdominal aneurysm.

BACKGROUND: The aim was to evaluate a wholly endovascular approach to the repair of thoracoabdominal aortic aneurysm (TAAA). METHODS: Six patients (median age 71 years) underwent wholly endovascular repair of TAAA (maximum diameter 56-85 mm) employing individually customized endografts. Procedures were performed under general anaesthesia, with spinal drainage in five patients. Patients were followed by serial computed tomography, plain radiography and duplex imaging for a median of 17 (range 8-44) months. RESULTS: All grafts were deployed as intended, with preservation of all target vessels. There were no postoperative deaths, strokes or paraplegia. One patient suffered a silent myocardial infarction. In two patients a persistent paraostial endoleak was treated by further balloon dilatation of the stent within the endograft fenestration. Imaging before discharge confirmed aneurysm exclusion in all patients. Two patients required late secondary intervention to abolish endoleaks due to side-branch disconnection. One patient suffered late occlusion of the coeliac axis without clinical sequelae, and late occlusion of a solitary renal artery in another resulted in dependence on dialysis. There have been no late deaths and all aneurysms remain excluded. CONCLUSION: Wholly endovascular TAAA repair is relatively safe, but long-term follow-up is required to establish its durability.

Fenestrated endovascular repair for juxtarenal aortic aneurysm.

BACKGROUND: The outcome of fenestrated endovascular aneurysm repair (F-EVAR) was evaluated. METHODS: Between February 2003 and December 2006, 45 patients (median age 73 (range 53-85) years) underwent primary (41) or secondary (four) F-EVAR for an abdominal aortic aneurysm with infrarenal neck anatomy unsuitable for a standard stent-graft. Median aneurysm diameter was 68 (range 55-100) mm and median infrarenal aortic neck length was 6 (range 0-13) mm. Customized fenestrated Zenith stent-grafts were employed in all procedures, incorporating fenestrations to preserve flow into renal (80), superior mesenteric (35) and coeliac (two) arteries. Eighty-two target vessels were stented (61 bare metal, 21 covered). RESULTS: All aneurysms were isolated successfully, with preservation of the target vessels. One accessory renal artery was lost. One patient died after 5 days from myocardial infarction, and another at 3 months from multiorgan failure secondary to atheroembolism. At median follow-up of 24 (range 1-48) months, all aneurysms were stable or shrinking, with no late ruptures or graft-related endoleaks. Six patients required a secondary intervention. The primary vessel patency rate was 96.6 per cent. There were four late deaths, unrelated to the aneurysm. CONCLUSION: F-EVAR enabled successful treatment of juxtarenal aortic aneurysm with a low complication rate.

Endovascular management of isolated infrarenal aortic occlusive disease is safe and effective in selected patients.

OBJECTIVE: To examine the safety and efficacy of endovascular management of isolated infrarenal aortic occlusive disease within our centre. DESIGN AND METHODS: Retrospective analysis of all patients who underwent endovascular treatment of occlusive disease that is confined to the infrarenal aorta between September 1993 and November 2004. RESULTS: Primary aortic stenting was carried out in 16 women and five men using self-expanding (12 patients) and balloon expanding stents to treat both occlusions (six) and stenoses (15). Indications included intermittent claudication (13), critical limb ischaemia (six), and distal embolisation (three). Significant postoperative complications within 30 days were noted in three, including one death. Fifteen patients completed 1-year follow-up with primary patency in 14 and secondary patency in the remaining patient. Clinical improvement was documented in all patients. CONCLUSION: Primary stenting for occlusive disease isolated in the infrarenal aorta is relatively safe in selected patients with encouraging early follow-up results.

Rupture of infra-renal aortic aneurysm after endovascular repair: a series from EUROSTAR registry.

OBJECTIVES: Although small, the risk of rupture after EVAR remains a major concern. The aim of this study was to identify mechanisms of late aneurysm rupture after endovascular repair. METHODS: Patients who suffered a proven aneurysm rupture after EVAR were identified from the EUROSTAR (European Collaborators on Stent-graft Techniques for Abdominal Aortic Aneurysm Repair) registry. Complications preceding rupture were studied to identify common patterns and possible mechanisms of late rupture. RESULTS: A rupture was documented in 34 patients resulting in death of 21 (62%). Adverse events documented during previous follow-up in these patients included endoleak (30%), migration (18%), limb occlusion (12%) and kinking (12%). The findings at time of rupture were documented in 24 patients and including endoleak: Type III (10), Type I (9), Type II (1); stent-graft disintegration (2) and migration (3). Aneurysm diameter changes could be ascertained in 24 patients and had increased in only seven. CONCLUSION: The importance of graft-related endoleak, stent-graft disintegration and migration in the causation of aneurysm rupture was confirmed. Poor compliance with follow-up schedule was also identified as a common feature. However, the absence of complications in some patients, who attended regularly for follow-up, highlights the difficulty of predicting rupture after EVAR.

Aortic side branch perfusion alone does not account for high intra-sac pressure after endovascular repair (EVAR) in the absence of graft-related endoleak.

OBJECTIVE: to examine the effect of stent-graft deployment on pressure within an aneurysm sac and to investigate the potential sources of intra-sac pressure. MATERIAL AND METHODS: intra-sac pressure was monitored during and immediately after endovascular repair via an indwelling catheter. Intra-sac pressure was also monitored during conventional open repair and was compared with the pressure measured within patent lumbar and inferior mesenteric side-branches, both before and after restoration of iliac arterial blood flow. Intra-sac and side-branch pressures were recorded and expressed as ratios of simultaneously measured radial artery pressure. RESULTS: in the absence of a graft-related endoleak (23/25 patients), endovascular repair resulted in a significant reduction in intra-sac pulse pressure (median ratio 0.31 IQR 0.10-0.46). There was no corresponding reduction in mean intra-sac pressure (median ratio 0.91; IQR 0.83-1.00). Application of clamps at conventional open repair resulted in a fall in both intra-sac pressure (median ratio 0.39, IQR 0.32-0.64) and pressure within side-branches (median ratio 0.45, IQR 0.33-0.64). Restoration of iliac blood flow resulted in a modest recovery of the side-branch pressure (median ratio 0.63, IQR 0.57-0.81), which nonetheless remained significantly less than the intra-sac pressure recorded after EVAR (p=0.01). CONCLUSION: reperfusion of the aneurysm sac through patent side-branches seems insufficient to account for persistent pressurisation of the aneurysm after endovascular repair. This finding supports the hypothesis that pressure may be transmitted directly through stent-graft fabric.

Perianeurysmal fibrosis: a relative contra-indication to endovascular repair.

OBJECTIVE: Perianeurysmal fibrosis (PAF) with involvement of neighbouring viscera can render open repair of inflammatory aneurysms technically difficult and therefore hazardous. For this reason, endovascular repair (EVAR) has been advocated as the preferred approach for this condition. EVAR is known to induce a systemic inflammatory response in patients but the nature of the local response remains unknown. If significant, such a response could exacerbate rather than ameliorate PAF. The aim of the study was to examine the incidence, course and consequences of perianeurysmal fibrosis detected by computerised tomography (CT) before and after EVAR. MATERIAL AND METHODS: The clinical records of patients treated by EVAR and followed for at least 6 months were reviewed. Pre and post-operative CT images were independently graded for PAF by three radiologists according to a standard protocol. RESULTS: PAF was documented preoperatively in six out of a total of 61 patients. In two of these PAF worsened after EVAR resulting in ureteric obstruction and hydronephrosis requiring ureteric stents. In the remaining 4 patients PAF did not reduce postoperatively. PAF of low grade developed postoperatively in 10 out of 55 patients (18%) in whom there was no evidence of PAF on preoperative imaging. Median follow-up was 18 months (range 6-36 months). The development of periaortic fibrosis de novopostoperatively was statistically significant (McNemar's test p=0.002). CONCLUSION: EVAR does not seem to reverse PAF if this is present preoperatively and it induces this condition in approximately one sixth of patients without evidence of preoperative PAF. The potential for this adverse inflammatory local response should be taken into account when considering EVAR for treatment of aneurysms with perianeurysmal fibrosis and must be weighed against the perceived benefits of this approach.

Lessons learnt from the EUROSTAR registry on endovascular repair of abdominal aortic aneurysm repair.

OBJECTIVE: The EUROSTAR project is a multicentred database of the outcome of endovascular repair of infra-renal aortic aneurysms. To date 92 European centres of vascular surgery have contributed. The purpose of the article here is to review the medium term (up to 4 years) results of endovascular aneurysm repair as reported to Eurostar. PATIENTS AND METHODS: Patients intended for endovascular aneurysm repair were notified to the EUROSTAR Data Registry Centre before treatment in order to eliminate bias due to selective reporting. The following data was collected on all patients: (1) their demographic details and the anatomical characteristics of their aneurysms, (2) details of the endovascular device used, (3) procedural complications and the immediate outcome, (4) results of contrast enhanced CT imaging at 3, 6, 12 and 18 months after operation and at yearly intervals thereafter, (5) all adverse events. Life table analysis was performed to determine the cumulative rates of: (1) death from all causes, (2) secondary intervention. Risk factors for rupture and late conversion were identified by regression analysis. RESULTS: By July 2000, 2862 patients had been registered and their median duration of follow-up was 12 mo (range 0-72). Successful deployment was achieved in 2812 patients with a perioperative (30 day) mortality of 2.9%. In 2464 patients enrolled by March 2000 late rupture of the aneurysm occurred in 14 patients for an annual cumulative rate of 1%. The significant factors were proximal type I endoleak (P=0.001), midgraft (type III) endoleak (P=0.001), graft migration (P=0.001) and post-operative kinking of the endograft (P=0.001). Forty-one patients had late conversion to open repair for an annual cumulative rate (risk) of approximately 2.1%. Risk factors (indications) for late conversion were: proximal type I endoleak (P=0.001), midgraft (type III) endoleak (P=0.001), type II endoleak (P=0.003), graft migration (P=0.001), graft kinking (P=0.001) and distal type I endoleak (P=0.001). CONCLUSIONS: Endovascular repair of infra-renal aortic aneurysms using the first and second-generation devices that predominated in this study was associated with a risk of late failure of 3% per year, based upon an analysis of observed primary endpoints of rupture and conversion. Eurostar continues to provide responsible evaluation of the technique for the benefit of both physicians and the industry.

Incidence and risk factors of late rupture, conversion, and death after endovascular repair of infrarenal aortic aneurysms: the EUROSTAR experience. European Collaborators on Stent/graft techniques for aortic aneurysm repair.

OBJECTIVE: The EUROSTAR (European Collaborators on Stent/graft techniques for aortic aneurysm repair) Registry was established in 1996 to collect data on the outcome of treatment of patients with infrarenal aortic aneurysms with endovascular repair. To date, 88 European centers of vascular surgery have contributed. The purpose of the study was to evaluate the results of this treatment in the medium term (up to 4 years) according to the analysis of "hard" or primary end points of rupture, late conversion, and death. PATIENTS AND METHODS: Patients with aortic aneurysms suitable for endovascular aneurysm repair were notified to the EUROSTAR Data Registry Centre before treatment to eliminate bias due to selective reporting. The following information was collected on all patients: (1) demographic details and the anatomic characteristics of their aneurysms, (2) details of the endovascular device used, (3) complications encountered during the procedure and the immediate outcome, (4) results of contrast enhanced computed tomographic imaging at 3, 6, 12, and 18 months after operation and at yearly intervals thereafter, and (5) all adverse events. Life table analysis was performed to determine the cumulative rates of (1) death from all causes, (2) rupture, and (3) late conversion to open repair. Risk factors for rupture and late conversion were identified through regression analysis. RESULTS: By March 2000, 2464 patients had been registered, and their mean duration of follow-up was 12.19 months (SD, 12.3 months). There were 14 patients with confirmed rupture of their aneurysms. The cumulative rate (risk) of rupture was approximately 1% per year. Emergency surgery was undertaken in 12 (86%) patients, of whom five (41.6%) survived. Two patients who were not treated surgically also died, which resulted in an overall death rate of 64.5% (9/14) of the patients. Significant risk factors for rupture were proximal type I endoleak (P =.001), midgraft (type III) endoleak (P =.001), graft migration (P =.001), and postoperative kinking of the endograft (P =.001). Forty-one patients underwent late conversion to open repair with a perioperative mortality rate of 24.4% (10/41). The cumulative rate (risk) of late conversion was approximately 2.1% per year. Risk factors (indications) for late conversion were proximal type I endoleak (P =. 001), midgraft (type III) endoleak (P =.001), type II endoleak (P =. 003), graft migration (P =.001), graft kinking (P =.001), and distal type I endoleak (P =.001). CONCLUSIONS: Endovascular repair of infrarenal aortic aneurysms with the first- and second-generation devices that predominated in this study was associated with a risk of late failure, according to an analysis of observed hard end points of 3% per year. Action taken to address the risk factors identified by the study may improve results in the future.