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Is Use of Bone-Morphogenetic Proteins for Spine Fusion Surgery Cost-effective?

Is Use of Bone-Morphogenetic Proteins for Spine Fusion Surgery Cost-effective? Abstract JAMA Prevalence, Complications, and Hospital Charges Associated With Use of Bone-Morphogenetic Proteins in Spinal Fusion Procedures Kevin S. Cahill, MD, PhD, MPH; John H. Chi, MD, MPH; Arthur Day, MD; Elizabeth B. Claus, MD, PhD Context: No national data exist to examine use of bone-morphogenetic proteins (BMPs) in spinal fusion surgery. Objective:  To determine the patterns of use and rates of complications and financial charges associated with BMP use in spinal fusion nationally. Design, Setting, and Patients:  Retrospective cohort study of 328 468 patients undergoing spinal fusion procedures from 2002-2006 identified from the Nationwide Inpatient Sample database, a 20% sample of US community hospitals. Main Outcome Measures:  The rates of use of BMP among patients undergoing spinal fusion procedures are examined along with complications, length of stay, and hospital charges associated with use of this fusion adjunct. Results:  The nationwide usage of BMP has increased from 0.69% of all fusions in 2002 to 24.89% of all fusions in 2006. Use of BMP varied by patient sex, race, and primary payer with increased use seen in women (56.26% with BMP vs 53.35% without BMP; odds ratio [OR], 1.12; 95% confidence interval, [CI], 1.09-1.16) and Medicare patients (29.62% with BMP vs 27.16% without BMP; OR, 1.43; 95% CI, 1.31-1.56) and decreased use in nonwhite patients (8.69% with BMP vs 10.23% without BMP; OR, 0.80; 95% CI, 0.75-0.85). When comparing immediate postoperative, in-hospital rates of complications for the year 2006 among patients undergoing spinal fusion by BMP use status, no differences were seen for lumbar, thoracic, or posterior cervical procedures. On univariate analysis and after multivariable adjustment, the use of BMP in anterior cervical fusion procedures was associated with a higher rate of complication occurrence (7.09% with BMP vs 4.68% without BMP; adjusted OR, 1.43; 95% CI, 1.12-1.70) with the primary increases seen in wound-related complications (1.22% with BMP vs 0.65% without BMP; adjusted OR, 1.67; 95% CI, 1.10- 2.53) and dysphagia or hoarseness (4.35% with BMP vs 2.45% without BMP; adjusted OR, 1.63; 95% CI, 1.30-2.05). Bone-morphogenetic protein use was associated with greater inpatient hospital charges across all categories of fusion. Increases between 11% and 41% of total hospital charges were reported, with the greatest percentage increase seen for anterior cervical fusion. Conclusion:  Bone-morphogenetic protein was used in approximately 25% of all spinal fusions nationally in 2006, with use associated with more frequent complications for anterior cervical fusions and with greater hospital charges for all categories of fusions. JAMA. 2009;302(1):58-66.. Undergoing a spine arthrodesis can be problematic, even when the most experienced spine surgeons perform them. Twenty years ago, the introduction of segmental spine fixation greatly reduced pseudarthrosis rates. However, despite the wide incorporation of segmental fixation, pseudarthrosis is still reported to be high within the cervical and thoracolumbar spine.1-7 In addition, the procurement of bone graft is associated with high donor site morbidities and chronic pain.8,9 Over the past decade, spine biologics have played an important role in decreasing the risk of pseudarthrosis and eliminating autograft morbidity. In 1965, the family of growth factors known as bone morphogenetic proteins (BMPs) were discovered by Urist.10 Currently, recombinant human BMP-2 (Infuse, Medtronic, Memphis, Tennessee) and BMP-7 (OP-1; Stryker, Kalamazoo, Michigan) have been approved by the Food and Drug Administration (FDA) for use within the spine. In 2002, Infuse was approved for use within adult anterior lumbar interbody fusions and in 2003, OP-1 received a humanitarian use device approval for revision intertransverse lumbar fusions.11,12 Since FDA approval, both Infuse and OP-1 have been used off label in spine fusions. The study by Cahill et al is a retrospective cohort study of patients from the Nationwide Inpatient Sample database who underwent spinal fusion procedures from 2002 to 2006. The authors report on the rate of BMP use in spine fusions and their association with complications, length of stay, and hospital charges. They report an increase in BMP use from 0.7% in 2002 to 24.3% in 2006. This increase is expected given the FDA approvals in 2002 and 2003 for BMP-2 and BMP-7, respectively. In addition, the authors report that by 2006, at least 20% of BMP use was off label (16% cervical and 4% thoracic). This reported value is likely underestimated given that there is no clear breakdown of the lumbosacral fusions into anterior or posterior groups or whether FDA guidelines where followed. The authors found that female and white patients were more likely to receive BMP. Although not mentioned, an explanation may be that these patients may have been more likely to be osteoporotic, a known risk factor for pseudarthrosis.13-15 As well, the authors noted that patients with more significant spinal pathology (eg, multilevel fusion, revision surgery, and deformity correction) were likely to receive BMP. In all 3 situations, the risk of pseudarthrosis can be substantially higher and may warrant BMP use.2 Unfortunately, one of the major weaknesses of this study is its lack of patient follow-up. Thus, it is impossible to identify the true cost savings that BMP use could provide over the long-term in patients at higher risk of pseudarthrosis. Regarding complications associated with BMP use, Medtronic released a safety alert with regards to the off- label use of recombinant human BMP-2 in anterior cervical spine fusions in 2004.16 Postoperative complications have been reported to occur in as much as 28% of patients,17,18 and this current study reports a complication rate of 7.1%. Complications such as edema, dysphagia, respiratory distress, hematomas, and reoperation appear to be dose dependent.19 Therefore, a lower dose may obviate a greater risk of complication and still maintain the clinical benefits. Regardless, BMP use in the anterior cervical spine must be done with caution and possibly be avoided until a more appropriate dose can be studied. Notably, use of the Nationwide Inpatient Sample Database has allowed these authors to accrue data from many patients (328 468), thus potentially making any findings more significant. However, such administrative databases have been shown to be inaccurate with respect to multiple patient characteristics, most notably diagnosis and treatment received, thus making any conclusions potentially invalid.20 Furthermore, using this database, the authors could not qualify or quantify the actual inpatient costs associated with the direct use of BMP. Although there is no doubt that BMP use adds to hospital costs, it is not clear from this study whether sicker patients were more costly regardless of BMP use. In this way, without patient follow-up and without delineating the actual costs associated with inpatient hospital care, the study fails to provide insight on the most important question regarding use of BMP: Is use of BMP in the spine cost-effective? Nonetheless, the authors should be commended on presenting the trends of BMP use in the United States over the last several years and highlighting procedures associated with potentially increased risk (eg, anterior cervical fusion). More rigorous cost analysis studies coupled with patient outcomes may eventually allow for more specific recommendations for BMP use, which may improve both treatment efficacy and cost efficiency for the patient. Correspondence: Dr Sciubba, Johns Hopkins Medical Institutions, 600 N Wolfe St, Meyer 7-109, Baltimore, MD 21287 (dsciubb1@jhmi.edu). Author Contributions:Study concept and design: Cardoso and Sciubba. Analysis and interpretation of data: Cardoso and Sciubba. Drafting of the manuscript: Cardoso and Sciubba. Critical revision of the manuscript for important intellectual content: Cardoso and Sciubba. Statistical analysis: Sciubba. Study supervision: Sciubba. Financial Disclosure: The Spinal Oncology Study Group, of which Dr Sciubba is a member, is supported by Medtronic. Dr Sciubba has received honorarium for a talk from DePuy Spine. References 1. Bridwell KHSedgewick TAO'Brien MFLenke LGBaldus C The role of fusion and instrumentation in the treatment of degenerative spondylolisthesis with spinal stenosis. J Spinal Disord 1993;6 (6) 461- 472PubMedGoogle ScholarCrossref 2. Kim YJBridwell KHLenke LGRhim SCheh G Pseudarthrosis in long adult spinal deformity instrumentation and fusion to the sacrum: prevalence and risk factor analysis of 144 cases. Spine (Phila Pa 1976) 2006;31 (20) 2329- 2336PubMedGoogle ScholarCrossref 3. McGuire RAAmundson GM The use of primary internal fixation in spondylolisthesis. Spine (Phila Pa 1976) 1993;18 (12) 1662- 1672PubMedGoogle ScholarCrossref 4. Wang JC McDonough PWEndow KKanim LEDelamarter RB The effect of cervical plating on single-level anterior cervical discectomy and fusion. J Spinal Disord 1999;12 (6) 467- 471PubMedGoogle ScholarCrossref 5. Wang JC McDonough PWEndow KKDelamarter RB Increased fusion rates with cervical plating for two-level anterior cervical discectomy and fusion. Spine (Phila Pa 1976) 2000;25 (1) 41- 45PubMedGoogle ScholarCrossref 6. Wang JC McDonough PWKanim LEEndow KKDelamarter RB Increased fusion rates with cervical plating for three-level anterior cervical discectomy and fusion. Spine (Phila Pa 1976) 2001;26 (6) 643- 647PubMedGoogle ScholarCrossref 7. West JL IIIBradford DSOgilvie JW Results of spinal arthrodesis with pedicle screw-plate fixation. J Bone Joint Surg Am 1991;73 (8) 1179- 1184PubMedGoogle Scholar 8. Banwart JCAsher MAHassanein RS Iliac crest bone graft harvest donor site morbidity: a statistical evaluation. Spine (Phila Pa 1976) 1995;20 (9) 1055- 1060PubMedGoogle ScholarCrossref 9. Silber JSAnderson DGDaffner SD et al. Donor site morbidity after anterior iliac crest bone harvest for single-level anterior cervical discectomy and fusion. Spine (Phila Pa 1976) 2003;28 (2) 134- 139PubMedGoogle ScholarCrossref 10. Urist MR Bone: formation by autoinduction. Science 1965;150 (698) 893- 899PubMedGoogle ScholarCrossref 11. Burkus JKTransfeldt EEKitchel SHWatkins RGBalderston RA Clinical and radiographic outcomes of anterior lumbar interbody fusion using recombinant human bone morphogenetic protein-2. Spine (Phila Pa 1976) 2002;27 (21) 2396- 2408PubMedGoogle ScholarCrossref 12. Vaccaro ARPatel TFischgrund J et al. A pilot safety and efficacy study of OP-1 putty (rhBMP-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions. Eur Spine J 2003;12 (5) 495- 500PubMedGoogle ScholarCrossref 13. Cummings SRKelsey JLNevitt MCO’Dowd KJ Epidemiology of osteoporosis and osteoporotic fractures. Epidemiol Rev 1985;7178- 208PubMedGoogle Scholar 14. Melton LJ IIIKan SHFrye MAWahner HWO’Fallon WMRiggs BL Epidemiology of vertebral fractures in women. Am J Epidemiol 1989;129 (5) 1000- 1011PubMedGoogle Scholar 15. Stephen ABWallace WA The management of osteoporosis. J Bone Joint Surg Br 2001;83 (3) 316- 323PubMedGoogle ScholarCrossref 16. Safety Alert RWT INFUSE Bone Graft. Memphis, TN Medtronic Sofamor Danek2004; 17. Shields LBRaque GHGlassman SD et al. Adverse effects associated with high-dose recombinant human bone morphogenetic protein-2 use in anterior cervical spine fusion. Spine (Phila Pa 1976) 2006;31 (5) 542- 547PubMedGoogle ScholarCrossref 18. Smucker JDRhee JMSingh KYoon STHeller JG Increased swelling complications associated with off-label usage of rhBMP-2 in the anterior cervical spine. Spine (Phila Pa 1976) 2006;31 (24) 2813- 2819PubMedGoogle ScholarCrossref 19. Baskin DSRyan PSonntag VWestmark RWidmayer MA A prospective, randomized, controlled cervical fusion study using recombinant human bone morphogenetic protein-2 with the CORNERSTONE-SR allograft ring and the ATLANTIS anterior cervical plate. Spine (Phila Pa 1976) 2003;28 (12) 1219- 1225PubMedGoogle Scholar 20. Woodworth GFBaird CJGarces-Ambrossi GTonascia JTamargo RJ Inaccuracy of the administrative database: comparative analysis of two databases for the diagnosis and treatment of intracranial aneurysms. Neurosurgery 2009;65 (2) 251- 257PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Surgery American Medical Association

Is Use of Bone-Morphogenetic Proteins for Spine Fusion Surgery Cost-effective?

Cardoso, Mario J.; Sciubba, Daniel M.
Archives of Surgery , Volume 144 (11) – Nov 16, 2009
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References (19)

Publisher
American Medical Association
Copyright
Copyright © 2009 American Medical Association. All Rights Reserved.
ISSN
0004-0010
eISSN
1538-3644
DOI
10.1001/archsurg.2009.185
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Abstract

Abstract JAMA Prevalence, Complications, and Hospital Charges Associated With Use of Bone-Morphogenetic Proteins in Spinal Fusion Procedures Kevin S. Cahill, MD, PhD, MPH; John H. Chi, MD, MPH; Arthur Day, MD; Elizabeth B. Claus, MD, PhD Context: No national data exist to examine use of bone-morphogenetic proteins (BMPs) in spinal fusion surgery. Objective:  To determine the patterns of use and rates of complications and financial charges associated with BMP use in spinal fusion nationally. Design, Setting, and Patients:  Retrospective cohort study of 328 468 patients undergoing spinal fusion procedures from 2002-2006 identified from the Nationwide Inpatient Sample database, a 20% sample of US community hospitals. Main Outcome Measures:  The rates of use of BMP among patients undergoing spinal fusion procedures are examined along with complications, length of stay, and hospital charges associated with use of this fusion adjunct. Results:  The nationwide usage of BMP has increased from 0.69% of all fusions in 2002 to 24.89% of all fusions in 2006. Use of BMP varied by patient sex, race, and primary payer with increased use seen in women (56.26% with BMP vs 53.35% without BMP; odds ratio [OR], 1.12; 95% confidence interval, [CI], 1.09-1.16) and Medicare patients (29.62% with BMP vs 27.16% without BMP; OR, 1.43; 95% CI, 1.31-1.56) and decreased use in nonwhite patients (8.69% with BMP vs 10.23% without BMP; OR, 0.80; 95% CI, 0.75-0.85). When comparing immediate postoperative, in-hospital rates of complications for the year 2006 among patients undergoing spinal fusion by BMP use status, no differences were seen for lumbar, thoracic, or posterior cervical procedures. On univariate analysis and after multivariable adjustment, the use of BMP in anterior cervical fusion procedures was associated with a higher rate of complication occurrence (7.09% with BMP vs 4.68% without BMP; adjusted OR, 1.43; 95% CI, 1.12-1.70) with the primary increases seen in wound-related complications (1.22% with BMP vs 0.65% without BMP; adjusted OR, 1.67; 95% CI, 1.10- 2.53) and dysphagia or hoarseness (4.35% with BMP vs 2.45% without BMP; adjusted OR, 1.63; 95% CI, 1.30-2.05). Bone-morphogenetic protein use was associated with greater inpatient hospital charges across all categories of fusion. Increases between 11% and 41% of total hospital charges were reported, with the greatest percentage increase seen for anterior cervical fusion. Conclusion:  Bone-morphogenetic protein was used in approximately 25% of all spinal fusions nationally in 2006, with use associated with more frequent complications for anterior cervical fusions and with greater hospital charges for all categories of fusions. JAMA. 2009;302(1):58-66.. Undergoing a spine arthrodesis can be problematic, even when the most experienced spine surgeons perform them. Twenty years ago, the introduction of segmental spine fixation greatly reduced pseudarthrosis rates. However, despite the wide incorporation of segmental fixation, pseudarthrosis is still reported to be high within the cervical and thoracolumbar spine.1-7 In addition, the procurement of bone graft is associated with high donor site morbidities and chronic pain.8,9 Over the past decade, spine biologics have played an important role in decreasing the risk of pseudarthrosis and eliminating autograft morbidity. In 1965, the family of growth factors known as bone morphogenetic proteins (BMPs) were discovered by Urist.10 Currently, recombinant human BMP-2 (Infuse, Medtronic, Memphis, Tennessee) and BMP-7 (OP-1; Stryker, Kalamazoo, Michigan) have been approved by the Food and Drug Administration (FDA) for use within the spine. In 2002, Infuse was approved for use within adult anterior lumbar interbody fusions and in 2003, OP-1 received a humanitarian use device approval for revision intertransverse lumbar fusions.11,12 Since FDA approval, both Infuse and OP-1 have been used off label in spine fusions. The study by Cahill et al is a retrospective cohort study of patients from the Nationwide Inpatient Sample database who underwent spinal fusion procedures from 2002 to 2006. The authors report on the rate of BMP use in spine fusions and their association with complications, length of stay, and hospital charges. They report an increase in BMP use from 0.7% in 2002 to 24.3% in 2006. This increase is expected given the FDA approvals in 2002 and 2003 for BMP-2 and BMP-7, respectively. In addition, the authors report that by 2006, at least 20% of BMP use was off label (16% cervical and 4% thoracic). This reported value is likely underestimated given that there is no clear breakdown of the lumbosacral fusions into anterior or posterior groups or whether FDA guidelines where followed. The authors found that female and white patients were more likely to receive BMP. Although not mentioned, an explanation may be that these patients may have been more likely to be osteoporotic, a known risk factor for pseudarthrosis.13-15 As well, the authors noted that patients with more significant spinal pathology (eg, multilevel fusion, revision surgery, and deformity correction) were likely to receive BMP. In all 3 situations, the risk of pseudarthrosis can be substantially higher and may warrant BMP use.2 Unfortunately, one of the major weaknesses of this study is its lack of patient follow-up. Thus, it is impossible to identify the true cost savings that BMP use could provide over the long-term in patients at higher risk of pseudarthrosis. Regarding complications associated with BMP use, Medtronic released a safety alert with regards to the off- label use of recombinant human BMP-2 in anterior cervical spine fusions in 2004.16 Postoperative complications have been reported to occur in as much as 28% of patients,17,18 and this current study reports a complication rate of 7.1%. Complications such as edema, dysphagia, respiratory distress, hematomas, and reoperation appear to be dose dependent.19 Therefore, a lower dose may obviate a greater risk of complication and still maintain the clinical benefits. Regardless, BMP use in the anterior cervical spine must be done with caution and possibly be avoided until a more appropriate dose can be studied. Notably, use of the Nationwide Inpatient Sample Database has allowed these authors to accrue data from many patients (328 468), thus potentially making any findings more significant. However, such administrative databases have been shown to be inaccurate with respect to multiple patient characteristics, most notably diagnosis and treatment received, thus making any conclusions potentially invalid.20 Furthermore, using this database, the authors could not qualify or quantify the actual inpatient costs associated with the direct use of BMP. Although there is no doubt that BMP use adds to hospital costs, it is not clear from this study whether sicker patients were more costly regardless of BMP use. In this way, without patient follow-up and without delineating the actual costs associated with inpatient hospital care, the study fails to provide insight on the most important question regarding use of BMP: Is use of BMP in the spine cost-effective? Nonetheless, the authors should be commended on presenting the trends of BMP use in the United States over the last several years and highlighting procedures associated with potentially increased risk (eg, anterior cervical fusion). More rigorous cost analysis studies coupled with patient outcomes may eventually allow for more specific recommendations for BMP use, which may improve both treatment efficacy and cost efficiency for the patient. Correspondence: Dr Sciubba, Johns Hopkins Medical Institutions, 600 N Wolfe St, Meyer 7-109, Baltimore, MD 21287 (dsciubb1@jhmi.edu). Author Contributions:Study concept and design: Cardoso and Sciubba. Analysis and interpretation of data: Cardoso and Sciubba. Drafting of the manuscript: Cardoso and Sciubba. Critical revision of the manuscript for important intellectual content: Cardoso and Sciubba. Statistical analysis: Sciubba. Study supervision: Sciubba. Financial Disclosure: The Spinal Oncology Study Group, of which Dr Sciubba is a member, is supported by Medtronic. Dr Sciubba has received honorarium for a talk from DePuy Spine. References 1. Bridwell KHSedgewick TAO'Brien MFLenke LGBaldus C The role of fusion and instrumentation in the treatment of degenerative spondylolisthesis with spinal stenosis. J Spinal Disord 1993;6 (6) 461- 472PubMedGoogle ScholarCrossref 2. Kim YJBridwell KHLenke LGRhim SCheh G Pseudarthrosis in long adult spinal deformity instrumentation and fusion to the sacrum: prevalence and risk factor analysis of 144 cases. Spine (Phila Pa 1976) 2006;31 (20) 2329- 2336PubMedGoogle ScholarCrossref 3. McGuire RAAmundson GM The use of primary internal fixation in spondylolisthesis. Spine (Phila Pa 1976) 1993;18 (12) 1662- 1672PubMedGoogle ScholarCrossref 4. Wang JC McDonough PWEndow KKanim LEDelamarter RB The effect of cervical plating on single-level anterior cervical discectomy and fusion. J Spinal Disord 1999;12 (6) 467- 471PubMedGoogle ScholarCrossref 5. Wang JC McDonough PWEndow KKDelamarter RB Increased fusion rates with cervical plating for two-level anterior cervical discectomy and fusion. Spine (Phila Pa 1976) 2000;25 (1) 41- 45PubMedGoogle ScholarCrossref 6. Wang JC McDonough PWKanim LEEndow KKDelamarter RB Increased fusion rates with cervical plating for three-level anterior cervical discectomy and fusion. Spine (Phila Pa 1976) 2001;26 (6) 643- 647PubMedGoogle ScholarCrossref 7. West JL IIIBradford DSOgilvie JW Results of spinal arthrodesis with pedicle screw-plate fixation. J Bone Joint Surg Am 1991;73 (8) 1179- 1184PubMedGoogle Scholar 8. Banwart JCAsher MAHassanein RS Iliac crest bone graft harvest donor site morbidity: a statistical evaluation. Spine (Phila Pa 1976) 1995;20 (9) 1055- 1060PubMedGoogle ScholarCrossref 9. Silber JSAnderson DGDaffner SD et al. Donor site morbidity after anterior iliac crest bone harvest for single-level anterior cervical discectomy and fusion. Spine (Phila Pa 1976) 2003;28 (2) 134- 139PubMedGoogle ScholarCrossref 10. Urist MR Bone: formation by autoinduction. Science 1965;150 (698) 893- 899PubMedGoogle ScholarCrossref 11. Burkus JKTransfeldt EEKitchel SHWatkins RGBalderston RA Clinical and radiographic outcomes of anterior lumbar interbody fusion using recombinant human bone morphogenetic protein-2. Spine (Phila Pa 1976) 2002;27 (21) 2396- 2408PubMedGoogle ScholarCrossref 12. Vaccaro ARPatel TFischgrund J et al. A pilot safety and efficacy study of OP-1 putty (rhBMP-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions. Eur Spine J 2003;12 (5) 495- 500PubMedGoogle ScholarCrossref 13. Cummings SRKelsey JLNevitt MCO’Dowd KJ Epidemiology of osteoporosis and osteoporotic fractures. Epidemiol Rev 1985;7178- 208PubMedGoogle Scholar 14. Melton LJ IIIKan SHFrye MAWahner HWO’Fallon WMRiggs BL Epidemiology of vertebral fractures in women. Am J Epidemiol 1989;129 (5) 1000- 1011PubMedGoogle Scholar 15. Stephen ABWallace WA The management of osteoporosis. J Bone Joint Surg Br 2001;83 (3) 316- 323PubMedGoogle ScholarCrossref 16. Safety Alert RWT INFUSE Bone Graft. Memphis, TN Medtronic Sofamor Danek2004; 17. Shields LBRaque GHGlassman SD et al. Adverse effects associated with high-dose recombinant human bone morphogenetic protein-2 use in anterior cervical spine fusion. Spine (Phila Pa 1976) 2006;31 (5) 542- 547PubMedGoogle ScholarCrossref 18. Smucker JDRhee JMSingh KYoon STHeller JG Increased swelling complications associated with off-label usage of rhBMP-2 in the anterior cervical spine. Spine (Phila Pa 1976) 2006;31 (24) 2813- 2819PubMedGoogle ScholarCrossref 19. Baskin DSRyan PSonntag VWestmark RWidmayer MA A prospective, randomized, controlled cervical fusion study using recombinant human bone morphogenetic protein-2 with the CORNERSTONE-SR allograft ring and the ATLANTIS anterior cervical plate. Spine (Phila Pa 1976) 2003;28 (12) 1219- 1225PubMedGoogle Scholar 20. Woodworth GFBaird CJGarces-Ambrossi GTonascia JTamargo RJ Inaccuracy of the administrative database: comparative analysis of two databases for the diagnosis and treatment of intracranial aneurysms. Neurosurgery 2009;65 (2) 251- 257PubMedGoogle ScholarCrossref

Journal

Archives of Surgery – American Medical Association

Published: Nov 16, 2009

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