Clinical Review & Education Clinical Challenges in Otolaryngology
ARTICLE INFORMATION Author Affiliations: Division of Rhinology and Sinus Surgery, Department of Otolaryngology–Head and Neck Surgery, Medical University of South Carolina, Charleston. Corresponding Author: Rodney J. Schlosser, MD, Division of Rhinology and Sinus Surgery, Department of Otolaryngology–Head and Neck Surgery, Medical University of South Carolina, 171 Ashley Ave, Charleston, SC 29425 ([email protected]). Section Editor: Marion Boyd Gillespie, MD, MSc. Submitted for Publication: July 20, 2012; final revision received March 27, 2013; accepted September 15, 2013. Published Online: October 31, 2013. doi:10.1001/jamaoto.2013.5439. Author Contributions: Drs Soler and Schlosser had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Both authors. Acquisition of data: Soler. Analysis and interpretation of data: Soler. Drafting of the manuscript: Both authors. Critical revision of the manuscript for important intellectual content: Both authors. Statistical analysis: Soler. Study supervision: Schlosser. Conflict of Interest Disclosures: None reported. REFERENCES 1. Stevens RW. Nasal packing; the rubber pneumatic pack. AMA Arch Otolaryngol. 1951;54(2):191-194. 2. Weitzel EK, Wormald PJ. A scientific review of middle meatal packing/stents. Am J Rhinol. 2008;22(3):302-307. 3. Valentine R, Wormald PJ. Nasal dressings after endoscopic sinus surgery: what and why? Curr Opin Otolaryngol Head Neck Surg. 2010;18(1):44-48. 4. McCoul ED, Smith TL, Mace JC, et al. Interrater agreement of nasal endoscopy in patients with a
Clinical Review & Education
prior history of endoscopic sinus surgery. Int Forum Allergy Rhinol. 2012;2(6):453-459. 5. Lee JM, Grewal A. Middle meatal spacers for the prevention of synechiae following endoscopic sinus surgery: a systematic review and meta-analysis of randomized controlled trials. Int Forum Allergy Rhinol. 2012;2(6):477-486. 6. Frenkiel S, Desrosiers MY, Nachtigal D. Use of hylan B gel as a wound dressing after endoscopic sinus surgery. J Otolaryngol. 2002;31(Suppl 1): S41-S44. 7. Kimmelman CP, Edelstein DR, Cheng HJ. Sepragel sinus (hylan B) as a postsurgical dressing for endoscopic sinus surgery. Otolaryngol Head Neck Surg. 2001;125(6):603-608. 8. Wormald PJ, Boustred RN, Le T, Hawke L, Sacks R. A prospective single-blind randomized controlled study of use of hyaluronic acid nasal packs in patients after endoscopic sinus surgery. Am J Rhinol. 2006;20(1):7-10. 9. Jameson M, Gross CW, Kountakis SE. FloSeal use in endoscopic sinus surgery: effect on postoperative bleeding and synechiae formation. Am J Otolaryngol. 2006;27(2):86-90. 10. Kastl KG, Betz CS, Siedek V, Leunig A. Control of bleeding following functional endoscopic sinus surgery using carboxy-methylated cellulose packing. Eur Arch Otorhinolaryngol. 2009;266(8):1239-1243. 11. Kastl KG, Betz CS, Siedek V, Leunig A. Effect of carboxymethylcellulose nasal packing on wound healing after functional endoscopic sinus surgery. Am J Rhinol Allergy. 2009;23(1):80-84. 12. Valentine R, Athanasiadis T, Moratti S, Hanton L, Robinson S, Wormald PJ. The efficacy of a novel chitosan gel on hemostasis and wound healing after endoscopic sinus surgery. Am J Rhinol Allergy. 2010;24(1):70-75. 13. Bugten V, Nordgård S, Skogvoll E, Steinsvåg S. Effects of nonabsorbable packing in middle meatus after sinus surgery. Laryngoscope. 2006;116(1):83-88.
increase synechiae after sinus surgery: randomized controlled study. Am J Rhinol Allergy. 2011;25(4): 268-271. 15. Antisdel JL, West-Denning JL, Sindwani R. Effect of microporous polysaccharide hemospheres (MPH) on bleeding after endoscopic sinus surgery: randomized controlled study. Otolaryngol Head Neck Surg. 2009;141(3):353-357. 16. Woodworth BA, Chandra RK, Hoy MJ, Lee FS, Schlosser RJ, Gillespie MB. Randomized controlled trial of hyaluronic acid/carboxymethylcellulose dressing after endoscopic sinus surgery. ORL J Otorhinolaryngol Relat Spec. 2010;72(2):101-105. 17. Tom LW, Palasti S, Potsic WP, Handler SD, Wetmore RF. The effects of gelatin film stents in the middle meatus. Am J Rhinol. 1997;11(3):229-232. 18. Wee JH, Lee CH, Rhee CS, Kim JW. Comparison between Gelfoam packing and no packing after endoscopic sinus surgery in the same patients. Eur Arch Otorhinolaryngol. 2012;269(3):897-903. 19. Metson RB, Platt MP. Complications of endoscopic sinus surgery: Prevention and management. In: Kennedy DW, Hwang PH, eds. Rhinology: Diseases of the Nose, Sinuses, and Skull Base. New York, NY: Thieme; 2012. 20. Musy PY, Kountakis SE. Anatomic findings in patients undergoing revision endoscopic sinus surgery. Am J Otolaryngol. 2004;25(6):418-422. 21. Mus L, Hermans R, Jorissen M. Long-term effects of cutting versus non-cutting instruments in FESS. Rhinology. 2012;50(1):56-66. 22. Ramakrishnan VR, Kingdom TT, Nayak JV, Hwang PH, Orlandi RR. Nationwide incidence of major complications in endoscopic sinus surgery. Int Forum Allergy Rhinol. 2012;2(1):34-39. 23. Orlandi RR, Lanza DC. Is nasal packing necessary following endoscopic sinus surgery? Laryngoscope. 2004;114(9):1541-1544.
14. Antisdel JL, Matijasec JL, Ting JY, Sindwani R. Microporous polysaccharide hemospheres do not
Invited Commentary CLINICAL CHALLENGES IN OTOLARYNGOLOGY
The Role of Middle Meatal Dressings in Endoscopic Sinus Surgery Andrew P. Lane, MD
Outcomes in endoscopic sinus surgery are determined by an interplay of numerous factors, some intrinsic to the patient and others related to management decisions and actions taken by the surgeon before, during, and after surgery. Related article page 1351 There is great variety in the specific perioperative medical regimens and surgical techniques that sinus surgeons employ. This is in part necessitated by the heterogeneity of sinus disease but mainly reflects individual practice prefer1354
ences derived from training, experience, and interpretation of expert recommendations. A relatively small number of these interventions have a strong evidence basis in randomized clinical trials. In formulating treatment plans, we all strive to use our informed clinical judgment to achieve the best results for our patients. One of the numerous decisions faced along the way in the surgical management of sinusitis is the placement of a postsurgical middle meatal dressing. The article by Soler and Schlosser 1 in this issue cogently reviews the current evidence regarding the pros and cons of
JAMA Otolaryngology–Head & Neck Surgery December 2013 Volume 139, Number 12
Copyright 2013 American Medical Association. All rights reserved.
Downloaded From: http://archotol.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/23/2015
jamaotolaryngology.com
Clinical Review & Education
Clinical Challenges in Otolaryngology Clinical Review & Education
this practice. Interestingly, despite the widespread use of middle meatal dressings and the number of products on the market, Soler and Schlosser1 conclude, as others have in the past,2-4 that insufficient evidence exists to demonstrate a necessity for dressings in most endoscopic sinus surgery procedures. Middle meatal packing was long considered a routine part of sinus surgery. At the time of my training, virtually every patient received a nonabsorbable dressing at the end of the procedure. With rapid advancements in endoscopic techniques, biomaterial technology, and understanding of sinusitis pathophysiology, the value of nasal packing has been reconsidered. Soler and Schlosser1 cite evidence that the main concerns driving use of middle meatal dressings— hemostasis and the prevention of scarring—may be clinically insignificant and/or greatly ameliorated by attention to preoperative preparation and the use of mucosal-sparing surgical techniques. While there is evidence that the risks of synechiae and middle turbinate lateralization can be effectively addressed with certain middle meatal dressings, the authors argue that other preventive means are also available, such as turbinate pexy maneuvers and meticulous surgical dissection and postoperative debridements. In short, if critical aspects of the perioperative management are optimized, the placement of dressings to control bleeding and promote ethmoid patency is unwarranted. This is a position with which I personally agree and act upon in my current practice. However, I would hasten to add that despite our best efforts, we will encounter suboptimal circumstances from time to time, and in these cases, the pros of middle meatal dressings should be recognized, as outlined in the review. The current frontier in middle meatal dressings is the topical delivery of pharmaceutical agents to promote healing and/or limit inflammation. In concept, this is a highly desirable goal. Continued inflammation and infection after sinus surgery can lead to surgical failure, and thus any treatment that limits early disease recurrence or persistence is a welcome addition to the surgeon’s armamentarium. Insomuch as inflammation contributes to postoperative bleeding and scarring, its control with
topical drugs may enhance the short-term benefits of dressings. Soler and Schlosser1 highlight the absence of evidence for a long-term impact of drug-delivering middle meatal dressings on disease outcomes. While such an effect beyond the initial healing phase would certainly add value, this may not be a reasonable expectation for materials that are removed or degraded within days or weeks of surgery. Are there any specific maneuvers applied in endoscopic sinus surgery that are proven to have an independent long-term benefit? Given that the surgical goals in chronic rhinosinusitis have shifted to more strongly emphasize access for drug delivery as a primary objective, perhaps the evolution of the middle meatal dressing will eventually extend beyond the immediate postsurgical period. I foresee a time when otolaryngologists in the office setting will periodically implant dressinglike drug delivery vehicles into sinuses previously operated on, to more effectively address chronic inflammatory sinus disease. In principle, most would agree that placebo-controlled evidence of improvement in clinically meaningful outcomes should be the standard for the therapies we give our patients. The reality is that current management of patients with sinusitis is an amalgamation of diverse practices, most of which are not validated with clinical trials. In the case of middle meatal dressings, the evidence-based recommendation from Soler and Schlosser1 is that surgeons should employ dressings selectively and only in patients deemed to be at risk for bleeding or scarring. This perhaps suggests a need for future research to clarify risk factors that would prospectively identify those patients likely to benefit. Until then, like so many decisions made in the medical and surgical management of sinusitis, it remains up to the clinical judgment of the individual surgeon whether a specific patient meets criteria. The report by Soler and Schlosser1 should further challenge those who continue to use middle meatal dressings routinely and automatically at the conclusion of every endoscopic sinus surgery procedure. We are reminded that many factors contribute to surgical outcomes, and that ultimately there is no dressing that can substitute for meticulous perioperative management and attention to technical detail.
ARTICLE INFORMATION
Conflict of Interest Disclosures: None reported.
Author Affiliation: Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
REFERENCES
3. Weber RK. Nasal packing after FESS—time is over? [in German]. Laryngorhinootologie. 2009;88(6):379-384.
1. Soler ZM, Schlosser RJ. Post-FESS middle meatal dressings: avoiding the inevitable? [published online October 31, 2013]. JAMA Otolaryngol Head Neck Surg. doi:10.1001/jamaoto.2013.5439.
4. Valentine R, Wormald PJ. Are routine dissolvable nasal dressings necessary following endoscopic sinus surgery? Laryngoscope. 2010;120(10): 1920-1921.
Corresponding Author: Andrew P. Lane, MD, Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins Outpatient Center, 601 N Caroline St, Sixth Floor, JHOC 6250, Baltimore, MD 21287-0910 ([email protected]). Published Online: October 31, 2013. doi:10.1001/jamaoto.2013.5475.
jamaotolaryngology.com
2. Eliashar R, Gross M, Wohlgelernter J, Sichel JY. Packing in endoscopic sinus surgery: is it really required? Otolaryngol Head Neck Surg. 2006;134(2):276-279.
JAMA Otolaryngology–Head & Neck Surgery December 2013 Volume 139, Number 12
Copyright 2013 American Medical Association. All rights reserved.
Downloaded From: http://archotol.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/23/2015
1355
ARTICLE INFORMATION Author Affiliations: Division of Rhinology and Sinus Surgery, Department of Otolaryngology–Head and Neck Surgery, Medical University of South Carolina, Charleston. Corresponding Author: Rodney J. Schlosser, MD, Division of Rhinology and Sinus Surgery, Department of Otolaryngology–Head and Neck Surgery, Medical University of South Carolina, 171 Ashley Ave, Charleston, SC 29425 ([email protected]). Section Editor: Marion Boyd Gillespie, MD, MSc. Submitted for Publication: July 20, 2012; final revision received March 27, 2013; accepted September 15, 2013. Published Online: October 31, 2013. doi:10.1001/jamaoto.2013.5439. Author Contributions: Drs Soler and Schlosser had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Both authors. Acquisition of data: Soler. Analysis and interpretation of data: Soler. Drafting of the manuscript: Both authors. Critical revision of the manuscript for important intellectual content: Both authors. Statistical analysis: Soler. Study supervision: Schlosser. Conflict of Interest Disclosures: None reported. REFERENCES 1. Stevens RW. Nasal packing; the rubber pneumatic pack. AMA Arch Otolaryngol. 1951;54(2):191-194. 2. Weitzel EK, Wormald PJ. A scientific review of middle meatal packing/stents. Am J Rhinol. 2008;22(3):302-307. 3. Valentine R, Wormald PJ. Nasal dressings after endoscopic sinus surgery: what and why? Curr Opin Otolaryngol Head Neck Surg. 2010;18(1):44-48. 4. McCoul ED, Smith TL, Mace JC, et al. Interrater agreement of nasal endoscopy in patients with a
Clinical Review & Education
prior history of endoscopic sinus surgery. Int Forum Allergy Rhinol. 2012;2(6):453-459. 5. Lee JM, Grewal A. Middle meatal spacers for the prevention of synechiae following endoscopic sinus surgery: a systematic review and meta-analysis of randomized controlled trials. Int Forum Allergy Rhinol. 2012;2(6):477-486. 6. Frenkiel S, Desrosiers MY, Nachtigal D. Use of hylan B gel as a wound dressing after endoscopic sinus surgery. J Otolaryngol. 2002;31(Suppl 1): S41-S44. 7. Kimmelman CP, Edelstein DR, Cheng HJ. Sepragel sinus (hylan B) as a postsurgical dressing for endoscopic sinus surgery. Otolaryngol Head Neck Surg. 2001;125(6):603-608. 8. Wormald PJ, Boustred RN, Le T, Hawke L, Sacks R. A prospective single-blind randomized controlled study of use of hyaluronic acid nasal packs in patients after endoscopic sinus surgery. Am J Rhinol. 2006;20(1):7-10. 9. Jameson M, Gross CW, Kountakis SE. FloSeal use in endoscopic sinus surgery: effect on postoperative bleeding and synechiae formation. Am J Otolaryngol. 2006;27(2):86-90. 10. Kastl KG, Betz CS, Siedek V, Leunig A. Control of bleeding following functional endoscopic sinus surgery using carboxy-methylated cellulose packing. Eur Arch Otorhinolaryngol. 2009;266(8):1239-1243. 11. Kastl KG, Betz CS, Siedek V, Leunig A. Effect of carboxymethylcellulose nasal packing on wound healing after functional endoscopic sinus surgery. Am J Rhinol Allergy. 2009;23(1):80-84. 12. Valentine R, Athanasiadis T, Moratti S, Hanton L, Robinson S, Wormald PJ. The efficacy of a novel chitosan gel on hemostasis and wound healing after endoscopic sinus surgery. Am J Rhinol Allergy. 2010;24(1):70-75. 13. Bugten V, Nordgård S, Skogvoll E, Steinsvåg S. Effects of nonabsorbable packing in middle meatus after sinus surgery. Laryngoscope. 2006;116(1):83-88.
increase synechiae after sinus surgery: randomized controlled study. Am J Rhinol Allergy. 2011;25(4): 268-271. 15. Antisdel JL, West-Denning JL, Sindwani R. Effect of microporous polysaccharide hemospheres (MPH) on bleeding after endoscopic sinus surgery: randomized controlled study. Otolaryngol Head Neck Surg. 2009;141(3):353-357. 16. Woodworth BA, Chandra RK, Hoy MJ, Lee FS, Schlosser RJ, Gillespie MB. Randomized controlled trial of hyaluronic acid/carboxymethylcellulose dressing after endoscopic sinus surgery. ORL J Otorhinolaryngol Relat Spec. 2010;72(2):101-105. 17. Tom LW, Palasti S, Potsic WP, Handler SD, Wetmore RF. The effects of gelatin film stents in the middle meatus. Am J Rhinol. 1997;11(3):229-232. 18. Wee JH, Lee CH, Rhee CS, Kim JW. Comparison between Gelfoam packing and no packing after endoscopic sinus surgery in the same patients. Eur Arch Otorhinolaryngol. 2012;269(3):897-903. 19. Metson RB, Platt MP. Complications of endoscopic sinus surgery: Prevention and management. In: Kennedy DW, Hwang PH, eds. Rhinology: Diseases of the Nose, Sinuses, and Skull Base. New York, NY: Thieme; 2012. 20. Musy PY, Kountakis SE. Anatomic findings in patients undergoing revision endoscopic sinus surgery. Am J Otolaryngol. 2004;25(6):418-422. 21. Mus L, Hermans R, Jorissen M. Long-term effects of cutting versus non-cutting instruments in FESS. Rhinology. 2012;50(1):56-66. 22. Ramakrishnan VR, Kingdom TT, Nayak JV, Hwang PH, Orlandi RR. Nationwide incidence of major complications in endoscopic sinus surgery. Int Forum Allergy Rhinol. 2012;2(1):34-39. 23. Orlandi RR, Lanza DC. Is nasal packing necessary following endoscopic sinus surgery? Laryngoscope. 2004;114(9):1541-1544.
14. Antisdel JL, Matijasec JL, Ting JY, Sindwani R. Microporous polysaccharide hemospheres do not
Invited Commentary CLINICAL CHALLENGES IN OTOLARYNGOLOGY
The Role of Middle Meatal Dressings in Endoscopic Sinus Surgery Andrew P. Lane, MD
Outcomes in endoscopic sinus surgery are determined by an interplay of numerous factors, some intrinsic to the patient and others related to management decisions and actions taken by the surgeon before, during, and after surgery. Related article page 1351 There is great variety in the specific perioperative medical regimens and surgical techniques that sinus surgeons employ. This is in part necessitated by the heterogeneity of sinus disease but mainly reflects individual practice prefer1354
ences derived from training, experience, and interpretation of expert recommendations. A relatively small number of these interventions have a strong evidence basis in randomized clinical trials. In formulating treatment plans, we all strive to use our informed clinical judgment to achieve the best results for our patients. One of the numerous decisions faced along the way in the surgical management of sinusitis is the placement of a postsurgical middle meatal dressing. The article by Soler and Schlosser 1 in this issue cogently reviews the current evidence regarding the pros and cons of
JAMA Otolaryngology–Head & Neck Surgery December 2013 Volume 139, Number 12
Copyright 2013 American Medical Association. All rights reserved.
Downloaded From: http://archotol.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/23/2015
jamaotolaryngology.com
Clinical Review & Education
Clinical Challenges in Otolaryngology Clinical Review & Education
this practice. Interestingly, despite the widespread use of middle meatal dressings and the number of products on the market, Soler and Schlosser1 conclude, as others have in the past,2-4 that insufficient evidence exists to demonstrate a necessity for dressings in most endoscopic sinus surgery procedures. Middle meatal packing was long considered a routine part of sinus surgery. At the time of my training, virtually every patient received a nonabsorbable dressing at the end of the procedure. With rapid advancements in endoscopic techniques, biomaterial technology, and understanding of sinusitis pathophysiology, the value of nasal packing has been reconsidered. Soler and Schlosser1 cite evidence that the main concerns driving use of middle meatal dressings— hemostasis and the prevention of scarring—may be clinically insignificant and/or greatly ameliorated by attention to preoperative preparation and the use of mucosal-sparing surgical techniques. While there is evidence that the risks of synechiae and middle turbinate lateralization can be effectively addressed with certain middle meatal dressings, the authors argue that other preventive means are also available, such as turbinate pexy maneuvers and meticulous surgical dissection and postoperative debridements. In short, if critical aspects of the perioperative management are optimized, the placement of dressings to control bleeding and promote ethmoid patency is unwarranted. This is a position with which I personally agree and act upon in my current practice. However, I would hasten to add that despite our best efforts, we will encounter suboptimal circumstances from time to time, and in these cases, the pros of middle meatal dressings should be recognized, as outlined in the review. The current frontier in middle meatal dressings is the topical delivery of pharmaceutical agents to promote healing and/or limit inflammation. In concept, this is a highly desirable goal. Continued inflammation and infection after sinus surgery can lead to surgical failure, and thus any treatment that limits early disease recurrence or persistence is a welcome addition to the surgeon’s armamentarium. Insomuch as inflammation contributes to postoperative bleeding and scarring, its control with
topical drugs may enhance the short-term benefits of dressings. Soler and Schlosser1 highlight the absence of evidence for a long-term impact of drug-delivering middle meatal dressings on disease outcomes. While such an effect beyond the initial healing phase would certainly add value, this may not be a reasonable expectation for materials that are removed or degraded within days or weeks of surgery. Are there any specific maneuvers applied in endoscopic sinus surgery that are proven to have an independent long-term benefit? Given that the surgical goals in chronic rhinosinusitis have shifted to more strongly emphasize access for drug delivery as a primary objective, perhaps the evolution of the middle meatal dressing will eventually extend beyond the immediate postsurgical period. I foresee a time when otolaryngologists in the office setting will periodically implant dressinglike drug delivery vehicles into sinuses previously operated on, to more effectively address chronic inflammatory sinus disease. In principle, most would agree that placebo-controlled evidence of improvement in clinically meaningful outcomes should be the standard for the therapies we give our patients. The reality is that current management of patients with sinusitis is an amalgamation of diverse practices, most of which are not validated with clinical trials. In the case of middle meatal dressings, the evidence-based recommendation from Soler and Schlosser1 is that surgeons should employ dressings selectively and only in patients deemed to be at risk for bleeding or scarring. This perhaps suggests a need for future research to clarify risk factors that would prospectively identify those patients likely to benefit. Until then, like so many decisions made in the medical and surgical management of sinusitis, it remains up to the clinical judgment of the individual surgeon whether a specific patient meets criteria. The report by Soler and Schlosser1 should further challenge those who continue to use middle meatal dressings routinely and automatically at the conclusion of every endoscopic sinus surgery procedure. We are reminded that many factors contribute to surgical outcomes, and that ultimately there is no dressing that can substitute for meticulous perioperative management and attention to technical detail.
ARTICLE INFORMATION
Conflict of Interest Disclosures: None reported.
Author Affiliation: Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
REFERENCES
3. Weber RK. Nasal packing after FESS—time is over? [in German]. Laryngorhinootologie. 2009;88(6):379-384.
1. Soler ZM, Schlosser RJ. Post-FESS middle meatal dressings: avoiding the inevitable? [published online October 31, 2013]. JAMA Otolaryngol Head Neck Surg. doi:10.1001/jamaoto.2013.5439.
4. Valentine R, Wormald PJ. Are routine dissolvable nasal dressings necessary following endoscopic sinus surgery? Laryngoscope. 2010;120(10): 1920-1921.
Corresponding Author: Andrew P. Lane, MD, Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins Outpatient Center, 601 N Caroline St, Sixth Floor, JHOC 6250, Baltimore, MD 21287-0910 ([email protected]). Published Online: October 31, 2013. doi:10.1001/jamaoto.2013.5475.
jamaotolaryngology.com
2. Eliashar R, Gross M, Wohlgelernter J, Sichel JY. Packing in endoscopic sinus surgery: is it really required? Otolaryngol Head Neck Surg. 2006;134(2):276-279.
JAMA Otolaryngology–Head & Neck Surgery December 2013 Volume 139, Number 12
Copyright 2013 American Medical Association. All rights reserved.
Downloaded From: http://archotol.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/23/2015
1355
