Evidence-based Medicine and Clinical Trials in Pediatric Orthopaedics Kishore Mulpuri, MBBS, MS(ortho), MHSc (Epi)* and Brian K. Brighton, MD, MPHw
Key Words: evidence-based medicine, clinical trials, practice guidelines (J Pediatr Orthop 2014;34:S71–S73)
T
he purpose of the evidence-based medicine and clinical trial symposium was to focus on the current state of evidence-based medicine, the application of clinical practice guidelines (CPGs), and to provide an update on clinical trials within pediatric orthopaedics. Evidencebased medicine has been quoted as “the integration of best research evidence with our clinical expertise and our patient’s unique values and circumstances.”1 The application of evidence-based medicine in our practice is an approach to patient care that emphasizes knowledge of the current and best clinical evidence available for making treatment decisions with our patients.2 However, in the absence of solid evidence, clinicians must often make decisions in the dark. Equally as important as searching for and applying best evidence is recognizing and dealing with the systematic errors inherent in our thinking.3,4 The presenters in the opening portion of our symposium discussed the question: Where are we with evidence today? In 2012, a total of 5 prospective and/or randomized trials about or including pediatric orthopaedic surgical patients were identified through a hand search of clinical journals. Three of these trials reported on treatment,5–7 and 2 reported on perioperative management, adding to the evidence within pediatric orthopaedics.8,9 The concept of the evidence cycle was introduced and starts with evidence analysis (Fig. 1).10 Through review and evaluation of the existing literature with regard to a particular clinical question, evidence analysis begins with examination of the available levels of evidence, and the availability of systematic reviews and independent meta-analyses and the quality and applicability of that
From the *Department of Orthopaedic Surgery, BC Children’s Hospital/University of British Columbia, Vancouver, BC, Canada; and wDepartment of Orthopaedic Surgery, Levine Children’s Hospital/ Carolinas Medical Center, Charlotte, NC. The authors declare no conflicts of interest. Reprints: Kishore Mulpuri, MBBS, MS(ortho), MHSc (Epi), Department of Orthopaedic Surgery, BC Children’s Hospital/University of British Columbia, 4480 Oak Street A230, Vancouver, BC, Canada V6H 3V4. E-mail: [email protected]. Copyright r 2014 by Lippincott Williams & Wilkins
J Pediatr Orthop
evidence.10 Once the evidence is analyzed it can guide the development of evidence-based guidelines. Evidencebased guidelines then give rise to a number of patientcentered “derivative work products” including process safety checklists, appropriate use criteria, performance measures, shared decision-making tools, performance improvement modules, and clinical pathways. Each of these then focuses on patient outcomes. Defined outcomes from any of these process or practice measures can lead to clinical research through meaningful comparative effectiveness research, patient-centered outcomes research, clinical registries, and research-specific focus groups. In addition, this becomes a platform for developing a research agenda as well as the opportunity to evaluate quality performance and improvement around clinical pathway and patient safety checklist effectiveness. Outcome measures effectively drive future research, education, and policy, which lead to higher-quality evidence within the evidence cycle (Fig. 1).10 The second half of the program featured leaders in our society who are actively involved in national/international study groups with particular focus on pediatric spinal deformity, pediatric and adolescent hip conditions, and sports medicine. Members from each group presented an overview and structure of their study group, their research activities, and also discussed key points that make their study groups successful and the challenges they face going forward.
POSNA CLINICAL TRIALS PLANNING GRANT AND ITS IMPACT ON CLINICAL TRIALS POSNA introduced a clinical trials planning competition in 2011. This generated interest and became the impetus of surgeons coming forward and creating groups to plan multicenter clinical trials. One successful example of this is the International Perthes’ Study Group (IPSG). Since receiving the award, IPSG has had 3 successful meetings in Dallas, TX, as well as meetings on the sidelines of POSNA and AAOS. As a result, these meetings have initiated multicentered, international studies focusing on determining best clinical practice for a disease with many remaining questions.
NEED FOR PROSPECTIVE STUDY GROUPS AND CLINICAL TRIALS IN PEDIATRIC ORTHOPAEDICS There has been increased interest in determining the level of evidence of publications within pediatric
Volume 34, Number 1 Supplement, October/November 2014
www.pedorthopaedics.com |
S71
Mulpuri and Brighton
J Pediatr Orthop
Volume 34, Number 1 Supplement, October/November 2014
FIGURE 1. The evidence cycle.10
orthopaedics. Levels of evidence are used to inform the reader of the study quality and the relative significance. Studies have been conducted to determine whether, with our increased knowledge, these levels of evidence have improved over time. One study looked at abstracts presented at POSNA for years 2001, 2002, 2007, and 2008.11 The majority of abstracts were rated as level IV for both the earlier and later time points. A similar study was conducted on articles published in the Journal of Pediatric Orthopaedics A and Journal of Pediatric Orthopaedics B for years 2001, 2002, 2007, 2008 and Journal of Children’s Orthopaedics for years 2007 and 2008.12 The results were similar, wherein the majority of articles obtained a level of IV for both prepublications and postpublications, with a slight increase in the number of articles with a level of III. These results are significant as there could be an increase in level I and II publications by fostering study groups and clinical trials. A shift toward this mentality will only improve research methodology and research outcomes for pediatric orthopaedics. Evidence-based CPGs provide the foundation for all quality initiatives as well as an opportunity to expose gaps in our knowledge around a particular disease, diagnosis, or condition. CPG’s are essentially the language of the evidence. Within pediatric orthopaedics there are currently 3 published evidence-based CPGs developed from a systematic, transparent, and nonbiased examination of the highestquality evidence in peer-reviewed published literature.13–15 These guidelines have been published by AAOS on pediatric diaphyseal femur fractures, osteochondritis dessicans of the knee, and pediatric supracondylar humerus fractures. Within the evidence-based CPGs the quality of the recommendation is driven by the strength of the evidence. Although a majority of the recommendations were weak or inconclusive, with only 1 of 44 recommendations receiving a rating of
S72 | www.pedorthopaedics.com
“strong,” the gaps in knowledge exposed by CPGs can give rise to a research agenda. Publications seen in these areas are often retrospective in nature with no comparative groups. We have a need for prospective, comparative data, which can be generated by study groups. An example of this is seen by the ROCK (Research on Osteochondritis Dessicans of the Knee) study group. This group focuses on osteochondritis dessicans and has been able to publish prospective data on this condition within a few years after forming the group.16
STUDY GROUPS IN PEDIATRIC ORTHOPAEDICS Harms Study Group of the Setting Scoliosis Straight Foundation.17 Spinal Deformity Study Group. ROCK Study Group.16 International Perthes’ Study Group.18 International Hip Dysplasia Institute.19 Chest Wall and Spinal Deformity Research Foundation/ Study Group.20 Growing Spine Study Group. The groups that presented shared information about study coordination, data sharing, and their methodology to determine authorship. Of the study groups that presented at the EBM/Clinical Trials Symposium, the Harms Study Group has the most established infrastructure for a conducting prospective research with very organized, central coordination run by a masterslevel graduate in Kinesiology and Biomechanics. These presentations also highlighted some of the issues these study groups are facing, such as: funding, patient recruitment, follow-up, data quality monitoring, and study coordination. Funding for these groups ranged from surgeon contributions, grants, industry partnership, r
2014 Lippincott Williams & Wilkins
J Pediatr Orthop
Volume 34, Number 1 Supplement, October/November 2014
and philanthropy. There is growing concern regarding sustainability of funding for these study groups as well as ongoing maintenance of the study databases. There was discussion around whether POSNA could play a role around creating a template for initiating these study groups or clinical trial planning. This may involve manuals, standard operating procedures, and database setup and maintenance.
POSNA CLINICAL TRIALS SURVEY In early 2013, POSNA sent out a Clinical Trials Survey to its members and received 153 responses. Of those that responded, 49.3% participate in clinical trials, 55.9% of which were multicenter studies. However, 83.6% of these trials were not registered with NIH or ClinicalTrials.gov. It is important for us to disseminate the knowledge that trials that are registered are received in higher esteem by journals for publication as well as by funding sources. Currently, funding has been seen from a variety of sources like NIH, OREF, or industry sponsors. Of the 153 responses, 83.1% are interested in learning more about clinical trials and 89% would like to participate in clinical trials. Of those that responded, 96.6% believed that POSNA could play a role in informing members of current clinical trials. It is promising that so many POSNA members have an interest and see the benefit of using clinical trials to improve orthopaedic research and, in turn, clinical practice. It is indeed an exciting time for all of us as POSNA continues to strive for advancement through ongoing research and provide the most relevant information on pediatric musculoskeletal health-related conditions. ACKNOWLEDGMENTS The authors would like to thank James Sanders, MD, Colin Moseley, MD, Andrew Howard, MD, Michael Goldberg, MD, Peter O. Newton, MD, Daniel J. Sucato, MD, Kevin Shea, MD, Behrooz Akbarnia, MD, Harry Kim, MD, Michael Vitale, MD, Michelle C. Marks, PT, MA, Burt Yaszay, MD, Norman Otsuka, MD, and Paul Sponseller, MD, MBA. REFERENCES 1. Staus SE, Richardson WS, Glasziou P, et al. Evidence-based Medicine: How to Practice and Teach EBM. 3rd ed. Edinburgh: Churchill Livingstone; 2005.
r
2014 Lippincott Williams & Wilkins
Evidence-based Medicine and Clinical Trials
2. Wright JG, Kocher MS, Sanders JO. Evidence-based pediatric orthopaedics: an introduction, part I. J Pediatr Orthop. 2012;32(suppl 2): S83–S90. 3. Moseley C. Evidence-based medicine: the dark side: POSNA 2008 presidential guest lecture. J Pediatr Orthop. 2009;29:839–843. 4. Moseley CF. Evidence-based medicine: not a slam dunk. J Pediatr Orthop. 2012;32(suppl 2):S111–S113. 5. Larson AN, Sucato DJ, Herring JA, et al. A prospective multicenter study of Legg-Calve-Perthes disease: functional and radiographic outcomes of nonoperative treatment at a mean follow-up of twenty years. J Bone Joint Surg Am. 2012;94:584–592. 6. Leu D, Sargent MC, Ain MC, et al. Spica casting for pediatric femoral fractures: a prospective, randomized controlled study of single-leg versus double-leg spica casts. J Bone Joint Surg Am. 2012; 94:1259–1264. 7. Silva M, Eagan MJ, Wong MA, et al. A comparison of two approaches for the closed treatment of low-energy tibial fractures in children. J Bone Joint Surg Am. 2012;94:1853–1860. 8. Georgopoulos G, Carry P, Pan Z, et al. The efficacy of intraarticular injections for pain control following the closed reduction and percutaneous pinning of pediatric supracondylar humeral fractures: a randomized controlled trial. J Bone Joint Surg Am. 2012; 94:1633–1642. 9. Thakkar SC, Mears SC. Visibility of surgical site marking: a prospective randomized trial of two skin preparation solutions. J Bone Joint Surg Am. 2012;94:97–102. 10. Wright JG, Tolo VT. JBJS and evidence-based orthopaedics. J Pediatr Orthop. 2012;32(suppl 2):S101–S103. 11. Kelley SP, Cashin MS, Douziech JR, et al. Levels of evidence at the Pediatric Orthopaedic Society of North America annual meetings. J Pediatr Orthop. 2010;30:612–616. 12. Cashin MS, Kelley SP, Douziech JR, et al. The levels of evidence in pediatric orthopaedic journals: where are we now? J Pediatr Orthop. 2011;31:721–725. 13. Chambers HG, Shea KG, Carey JL. AAOS Clinical Practice Guideline: diagnosis and treatment of osteochondritis dissecans. J Am Acad Orthop Surg. 2011;19:307–309. 14. Kocher MS, Sink EL, Blasier RD, et al. American Academy of Orthopaedic, Surgeons. American Academy of Orthopaedic Surgeons clinical practice guideline on treatment of pediatric diaphyseal femur fracture. J Bone Joint Surg Am. 2010;92:1790–1792. 15. Mulpuri K, Hosalkar H, Howard A. AAOS clinical practice guideline: the treatment of pediatric supracondylar humerus fractures. J Am Acad Orthop Surg. 2012;20:328–330. 16. ROCK Study Group. Available at: http://kneeocd.org/. Accessed November 7, 2013. 17. HARMS Study Group. Available at: http://www.hsg.settingscoliosis straight.org/. Accessed November 7, 2013. 18. International Perthes Study Group. Available at: http://community. tsrhc.org/IPSG. Accessed November 7, 2013. 19. International Hip Dysplasia Institute. Available at: http://www.hip dysplasia.org/. Accessed November 7, 2013. 20. Chest wall and Spinal Deformity Research Foundation/Study Group. Available at: http://www.chestandspine.org. Accessed November 8, 2013.
www.pedorthopaedics.com |
S73
Key Words: evidence-based medicine, clinical trials, practice guidelines (J Pediatr Orthop 2014;34:S71–S73)
T
he purpose of the evidence-based medicine and clinical trial symposium was to focus on the current state of evidence-based medicine, the application of clinical practice guidelines (CPGs), and to provide an update on clinical trials within pediatric orthopaedics. Evidencebased medicine has been quoted as “the integration of best research evidence with our clinical expertise and our patient’s unique values and circumstances.”1 The application of evidence-based medicine in our practice is an approach to patient care that emphasizes knowledge of the current and best clinical evidence available for making treatment decisions with our patients.2 However, in the absence of solid evidence, clinicians must often make decisions in the dark. Equally as important as searching for and applying best evidence is recognizing and dealing with the systematic errors inherent in our thinking.3,4 The presenters in the opening portion of our symposium discussed the question: Where are we with evidence today? In 2012, a total of 5 prospective and/or randomized trials about or including pediatric orthopaedic surgical patients were identified through a hand search of clinical journals. Three of these trials reported on treatment,5–7 and 2 reported on perioperative management, adding to the evidence within pediatric orthopaedics.8,9 The concept of the evidence cycle was introduced and starts with evidence analysis (Fig. 1).10 Through review and evaluation of the existing literature with regard to a particular clinical question, evidence analysis begins with examination of the available levels of evidence, and the availability of systematic reviews and independent meta-analyses and the quality and applicability of that
From the *Department of Orthopaedic Surgery, BC Children’s Hospital/University of British Columbia, Vancouver, BC, Canada; and wDepartment of Orthopaedic Surgery, Levine Children’s Hospital/ Carolinas Medical Center, Charlotte, NC. The authors declare no conflicts of interest. Reprints: Kishore Mulpuri, MBBS, MS(ortho), MHSc (Epi), Department of Orthopaedic Surgery, BC Children’s Hospital/University of British Columbia, 4480 Oak Street A230, Vancouver, BC, Canada V6H 3V4. E-mail: [email protected]. Copyright r 2014 by Lippincott Williams & Wilkins
J Pediatr Orthop
evidence.10 Once the evidence is analyzed it can guide the development of evidence-based guidelines. Evidencebased guidelines then give rise to a number of patientcentered “derivative work products” including process safety checklists, appropriate use criteria, performance measures, shared decision-making tools, performance improvement modules, and clinical pathways. Each of these then focuses on patient outcomes. Defined outcomes from any of these process or practice measures can lead to clinical research through meaningful comparative effectiveness research, patient-centered outcomes research, clinical registries, and research-specific focus groups. In addition, this becomes a platform for developing a research agenda as well as the opportunity to evaluate quality performance and improvement around clinical pathway and patient safety checklist effectiveness. Outcome measures effectively drive future research, education, and policy, which lead to higher-quality evidence within the evidence cycle (Fig. 1).10 The second half of the program featured leaders in our society who are actively involved in national/international study groups with particular focus on pediatric spinal deformity, pediatric and adolescent hip conditions, and sports medicine. Members from each group presented an overview and structure of their study group, their research activities, and also discussed key points that make their study groups successful and the challenges they face going forward.
POSNA CLINICAL TRIALS PLANNING GRANT AND ITS IMPACT ON CLINICAL TRIALS POSNA introduced a clinical trials planning competition in 2011. This generated interest and became the impetus of surgeons coming forward and creating groups to plan multicenter clinical trials. One successful example of this is the International Perthes’ Study Group (IPSG). Since receiving the award, IPSG has had 3 successful meetings in Dallas, TX, as well as meetings on the sidelines of POSNA and AAOS. As a result, these meetings have initiated multicentered, international studies focusing on determining best clinical practice for a disease with many remaining questions.
NEED FOR PROSPECTIVE STUDY GROUPS AND CLINICAL TRIALS IN PEDIATRIC ORTHOPAEDICS There has been increased interest in determining the level of evidence of publications within pediatric
Volume 34, Number 1 Supplement, October/November 2014
www.pedorthopaedics.com |
S71
Mulpuri and Brighton
J Pediatr Orthop
Volume 34, Number 1 Supplement, October/November 2014
FIGURE 1. The evidence cycle.10
orthopaedics. Levels of evidence are used to inform the reader of the study quality and the relative significance. Studies have been conducted to determine whether, with our increased knowledge, these levels of evidence have improved over time. One study looked at abstracts presented at POSNA for years 2001, 2002, 2007, and 2008.11 The majority of abstracts were rated as level IV for both the earlier and later time points. A similar study was conducted on articles published in the Journal of Pediatric Orthopaedics A and Journal of Pediatric Orthopaedics B for years 2001, 2002, 2007, 2008 and Journal of Children’s Orthopaedics for years 2007 and 2008.12 The results were similar, wherein the majority of articles obtained a level of IV for both prepublications and postpublications, with a slight increase in the number of articles with a level of III. These results are significant as there could be an increase in level I and II publications by fostering study groups and clinical trials. A shift toward this mentality will only improve research methodology and research outcomes for pediatric orthopaedics. Evidence-based CPGs provide the foundation for all quality initiatives as well as an opportunity to expose gaps in our knowledge around a particular disease, diagnosis, or condition. CPG’s are essentially the language of the evidence. Within pediatric orthopaedics there are currently 3 published evidence-based CPGs developed from a systematic, transparent, and nonbiased examination of the highestquality evidence in peer-reviewed published literature.13–15 These guidelines have been published by AAOS on pediatric diaphyseal femur fractures, osteochondritis dessicans of the knee, and pediatric supracondylar humerus fractures. Within the evidence-based CPGs the quality of the recommendation is driven by the strength of the evidence. Although a majority of the recommendations were weak or inconclusive, with only 1 of 44 recommendations receiving a rating of
S72 | www.pedorthopaedics.com
“strong,” the gaps in knowledge exposed by CPGs can give rise to a research agenda. Publications seen in these areas are often retrospective in nature with no comparative groups. We have a need for prospective, comparative data, which can be generated by study groups. An example of this is seen by the ROCK (Research on Osteochondritis Dessicans of the Knee) study group. This group focuses on osteochondritis dessicans and has been able to publish prospective data on this condition within a few years after forming the group.16
STUDY GROUPS IN PEDIATRIC ORTHOPAEDICS Harms Study Group of the Setting Scoliosis Straight Foundation.17 Spinal Deformity Study Group. ROCK Study Group.16 International Perthes’ Study Group.18 International Hip Dysplasia Institute.19 Chest Wall and Spinal Deformity Research Foundation/ Study Group.20 Growing Spine Study Group. The groups that presented shared information about study coordination, data sharing, and their methodology to determine authorship. Of the study groups that presented at the EBM/Clinical Trials Symposium, the Harms Study Group has the most established infrastructure for a conducting prospective research with very organized, central coordination run by a masterslevel graduate in Kinesiology and Biomechanics. These presentations also highlighted some of the issues these study groups are facing, such as: funding, patient recruitment, follow-up, data quality monitoring, and study coordination. Funding for these groups ranged from surgeon contributions, grants, industry partnership, r
2014 Lippincott Williams & Wilkins
J Pediatr Orthop
Volume 34, Number 1 Supplement, October/November 2014
and philanthropy. There is growing concern regarding sustainability of funding for these study groups as well as ongoing maintenance of the study databases. There was discussion around whether POSNA could play a role around creating a template for initiating these study groups or clinical trial planning. This may involve manuals, standard operating procedures, and database setup and maintenance.
POSNA CLINICAL TRIALS SURVEY In early 2013, POSNA sent out a Clinical Trials Survey to its members and received 153 responses. Of those that responded, 49.3% participate in clinical trials, 55.9% of which were multicenter studies. However, 83.6% of these trials were not registered with NIH or ClinicalTrials.gov. It is important for us to disseminate the knowledge that trials that are registered are received in higher esteem by journals for publication as well as by funding sources. Currently, funding has been seen from a variety of sources like NIH, OREF, or industry sponsors. Of the 153 responses, 83.1% are interested in learning more about clinical trials and 89% would like to participate in clinical trials. Of those that responded, 96.6% believed that POSNA could play a role in informing members of current clinical trials. It is promising that so many POSNA members have an interest and see the benefit of using clinical trials to improve orthopaedic research and, in turn, clinical practice. It is indeed an exciting time for all of us as POSNA continues to strive for advancement through ongoing research and provide the most relevant information on pediatric musculoskeletal health-related conditions. ACKNOWLEDGMENTS The authors would like to thank James Sanders, MD, Colin Moseley, MD, Andrew Howard, MD, Michael Goldberg, MD, Peter O. Newton, MD, Daniel J. Sucato, MD, Kevin Shea, MD, Behrooz Akbarnia, MD, Harry Kim, MD, Michael Vitale, MD, Michelle C. Marks, PT, MA, Burt Yaszay, MD, Norman Otsuka, MD, and Paul Sponseller, MD, MBA. REFERENCES 1. Staus SE, Richardson WS, Glasziou P, et al. Evidence-based Medicine: How to Practice and Teach EBM. 3rd ed. Edinburgh: Churchill Livingstone; 2005.
r
2014 Lippincott Williams & Wilkins
Evidence-based Medicine and Clinical Trials
2. Wright JG, Kocher MS, Sanders JO. Evidence-based pediatric orthopaedics: an introduction, part I. J Pediatr Orthop. 2012;32(suppl 2): S83–S90. 3. Moseley C. Evidence-based medicine: the dark side: POSNA 2008 presidential guest lecture. J Pediatr Orthop. 2009;29:839–843. 4. Moseley CF. Evidence-based medicine: not a slam dunk. J Pediatr Orthop. 2012;32(suppl 2):S111–S113. 5. Larson AN, Sucato DJ, Herring JA, et al. A prospective multicenter study of Legg-Calve-Perthes disease: functional and radiographic outcomes of nonoperative treatment at a mean follow-up of twenty years. J Bone Joint Surg Am. 2012;94:584–592. 6. Leu D, Sargent MC, Ain MC, et al. Spica casting for pediatric femoral fractures: a prospective, randomized controlled study of single-leg versus double-leg spica casts. J Bone Joint Surg Am. 2012; 94:1259–1264. 7. Silva M, Eagan MJ, Wong MA, et al. A comparison of two approaches for the closed treatment of low-energy tibial fractures in children. J Bone Joint Surg Am. 2012;94:1853–1860. 8. Georgopoulos G, Carry P, Pan Z, et al. The efficacy of intraarticular injections for pain control following the closed reduction and percutaneous pinning of pediatric supracondylar humeral fractures: a randomized controlled trial. J Bone Joint Surg Am. 2012; 94:1633–1642. 9. Thakkar SC, Mears SC. Visibility of surgical site marking: a prospective randomized trial of two skin preparation solutions. J Bone Joint Surg Am. 2012;94:97–102. 10. Wright JG, Tolo VT. JBJS and evidence-based orthopaedics. J Pediatr Orthop. 2012;32(suppl 2):S101–S103. 11. Kelley SP, Cashin MS, Douziech JR, et al. Levels of evidence at the Pediatric Orthopaedic Society of North America annual meetings. J Pediatr Orthop. 2010;30:612–616. 12. Cashin MS, Kelley SP, Douziech JR, et al. The levels of evidence in pediatric orthopaedic journals: where are we now? J Pediatr Orthop. 2011;31:721–725. 13. Chambers HG, Shea KG, Carey JL. AAOS Clinical Practice Guideline: diagnosis and treatment of osteochondritis dissecans. J Am Acad Orthop Surg. 2011;19:307–309. 14. Kocher MS, Sink EL, Blasier RD, et al. American Academy of Orthopaedic, Surgeons. American Academy of Orthopaedic Surgeons clinical practice guideline on treatment of pediatric diaphyseal femur fracture. J Bone Joint Surg Am. 2010;92:1790–1792. 15. Mulpuri K, Hosalkar H, Howard A. AAOS clinical practice guideline: the treatment of pediatric supracondylar humerus fractures. J Am Acad Orthop Surg. 2012;20:328–330. 16. ROCK Study Group. Available at: http://kneeocd.org/. Accessed November 7, 2013. 17. HARMS Study Group. Available at: http://www.hsg.settingscoliosis straight.org/. Accessed November 7, 2013. 18. International Perthes Study Group. Available at: http://community. tsrhc.org/IPSG. Accessed November 7, 2013. 19. International Hip Dysplasia Institute. Available at: http://www.hip dysplasia.org/. Accessed November 7, 2013. 20. Chest wall and Spinal Deformity Research Foundation/Study Group. Available at: http://www.chestandspine.org. Accessed November 8, 2013.
www.pedorthopaedics.com |
S73
