Technology & Innovation Volume 18, Numbers 2-3 by National Academy of Inventors

ISSN 1949-8241 â&#x20AC;˘ E-ISSN 1949-825X

Volume 18, Numbers 2-3

Outcomes and Advances in Assistive Technologies for Rehabilitation

Transtibial Economic Evaluations

Review of Amputee Gait Training

Residual Limb Ulcer Management for Leg Amputees

115

EDITORS-IN-CHIEF PAUL R. SANBERG University of South Florida Tampa, FL

ERIC R. FOSSUM Dartmouth College Hanover, NH

SENIOR EDITORS HOWARD J. FEDEROFF University of California, Irvine Irvine, CA

NASSER ARSHADI University of Missouri – Saint Louis St. Louis, MO

EDITORIAL STAFF Judy Lowry, Managing Editor

Kimberly Macuare, Assistant Editor

EDITORIAL BOARD Shantikumar Nair, Amrita University, India

Steven J. Kubisen, The George Washington University

Sethuraman Panchanathan, Arizona State University

Jarett Rieger, H. Lee Moffitt Cancer Center & Research Institute

David Winwood, Association of University Technology Managers

Christopher Fasel, Idaho State University

Jay Gogue, Auburn University

Sharon Heise, Institute for Human & Machine Cognition

Rivka Carmi, Ben-Gurion University of the Negev, Israel

A. Alan Moghissi, Institute for Regulatory Science

Ernest B. Izevbigie, Benson Idahosa University, Nigeria

Cama McNamara, Inventor’s Digest

Mark Rudin, Boise State University

Ken S. Lee, Jackson State University

Gloria Waters, Boston University

Christy Wyskiel, Johns Hopkins University

Farnam Jahanian, Carnegie Mellon University

Solomon H. Snyder, Johns Hopkins University

Joseph Jankowski, Case Western Reserve University

Mary Rezac, Kansas State University

Shinn-Zong (John) Lin, China Medical University, Taiwan

Paul DiCorleto, Kent State University

Todd Headley, Colorado State University

Norman R. Augustine, Lockheed Martin Corporation

Scot Hamilton, Columbia University

Kalliat T. Valsaraj, Louisiana State University

Alice Li, Cornell University

Richard Kordal, Louisiana Tech University

Donna M. DeCarolis, Drexel University

Robert S. Langer, Massachusetts Institute of Technology

Marti Van Scott, East Carolina University

Rebecca Mahurin, Montana State University

Todd Sherer, Emory University

Vimal Chaitanya, New Mexico State University

John W. Newcomer, Florida Atlantic University

Kurt H. Becker, New York University

Tachung (T.C.) Yih, Florida Gulf Coast University

Lesley Rigg, Northern Illinois University

Tristan J. Fiedler, Florida Institute of Technology

James G. Conley, Northwestern University

Andres G. Gil, Florida International University

Arlene A. Garrison, Oak Ridge Associated Universities

Lawrence O. Gostin, Georgetown University Law Center

Lonnie G. Thompson, The Ohio State University

John J. Kopchick, Ohio University

Karen J.L. Burg, University of Georgia

Steven Price, Oklahoma State University

Derek E. Eberhart, University of Georgia

Neil A. Sharkey, The Pennsylvania State University

Richard C. Willson, University of Houston

Curtis R. Carlson, The Practice of Innovation

Lesley Millar-Nicholson, University of Illinois at Urbana-Champaign

Kenneth J. Blank, Rowan University S. David Kimball, Rutgers, The State University of New Jersey

Taunya Phillips Walker, University of Kentucky Mary Shire, University of Limerick, Ireland

Raymond C. Tait, Saint Louis University

William M. Pierce, Jr., University of Louisville

Arthur Molella, Smithsonian Lemelson Center

Patrick O’Shea, University of Maryland

Arthur J. Tipton, Southern Research Institute

Louis A. Carpino, University of Massachusetts – Amherst

Christos Christodoulatos, Stevens Institute of Technology

James P. McNamara, University of Massachusetts Medical School

Robert V. Duncan, Texas Tech University Stephen Klasko, Thomas Jefferson University Richard A. Houghten, Torrey Pines Institute for Molecular Studies Woody Maggard, University at Buffalo – State University of New York Stephen Z. Cheng, The University of Akron Richard P. Swatloski, The University of Alabama Richard B. Marchase, The University of Alabama at Birmingham Frederic Zenhausern, The University of Arizona Jim Rankin, University of Arkansas Linda P. B. Katehi, University of California, Davis M. J. Soileau, University of Central Florida Patrick A. Limbach, University of Cincinnati Inge Wefes, University of Colorado – Denver/AMC Jeff Seemann, University of Connecticut Mathew Willenbrink, University of Dayton David S. Weir, University of Delaware Paula Heldt, University of Evansville David P. Norton, University of Florida

Kenneth J. Nisbet, University of Michigan Henry C. Foley, University of Missouri – Columbia Lawrence Dreyfus, University of Missouri – Kansas City Prem S. Paul, University of Nebraska-Lincoln Zachary Miles, The University of Nevada, Las Vegas Kumi Nagamoto-Combs, The University of North Dakota John Kantner, University of North Florida Thomas McCoy, University of North Texas James H. Bratton, The University of Oklahoma Lynne U. Chronister, The University of South Alabama Judy Genshaft, University of South Florida Gordon C. Cannon, University of Southern Mississippi T. Taylor Eighmy, The University of Tennessee, Knoxville Thomas Parks, The University of Utah William Barker, University of Wisconsin – Madison H. Holden Thorp, Washington University in St. Louis Keith H. Pickus, Wichita State University Robert E. W. Fyffe, Wright State University T. Kyle Vanderlick, Yale University

National Academy of Inventors. Technology and Innovation, University of South Florida Research Park, 3702 Spectrum Boulevard, Suite 165, Tampa, FL 33612-9445 USA. Tel: +1-813-974-1347; Fax: +1-813-974-4962; tijournal@academyofinventors.org; www. academyofinventors.org.

PUBLISHING INFORMATION Technology and Innovation, Journal of the National Academy of Inventors (ISSN: 1949-8241) is published by the National Academy of Inventors, University of South Florida Research Park, 3702 Spectrum Boulevard, Suite 165, Tampa, FL 33612-9445 USA. Tel: +1-813-974-1347; Fax: +1-813-974-4962; tijournal@ academyofinventors.org; www.academyofinventors.org. Subscriptions: Technology and Innovation (T&I) is published 4 times a year. For subscription information, please visit our website or contact tijournal@academyofinventors.org. Advertisement: T&I will accept advertisements. All advertisements are subject to approval by the editors. For details and rates, please contact tijournal@academyofinventors.org. Disclaimer: While every effort is made by the publisher, editors, and editorial board to see that no inaccurate or misleading data, opinion, or statement appears in T&I, they wish to make it clear that the data and opinions appearing in the articles and advertisements contained herein are the sole responsibility of the contributor or advertiser concerned. Therefore, the publisher, editors, editorial board, their respective employees, officers, and agents accept no responsibility or liability whatsoever for the effect of any such inaccurate or misleading opinion, data, or statement. Copyright Notice: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. By submitting a manuscript, the authors agree that the copyright for their article is transferred to the publisher if and when the article is accepted for publication. However, assignment of copyright is not required from authors who work for organizations that do not permit such assignment. The copyright covers the exclusive rights to reproduce and distribute the article, including reprints, photographic reproductions, microform, or any other reproductions of similar nature and translations. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, electrostatic, magnetic type, mechanical, photocopying, recording, or otherwise, without permission in writing from the copyright holder. Photocopying information for users in the USA: For permission to reuse copyrighted content from T&I, please access www.copyright.com or contact Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923, telephone +1-855-239-3415 (Monday-Friday, 3 AM to 6 PM Eastern Time), fax +1-978-6468600. Copyright Clearance Center is a not-for-profit organization that provides copyright licensing on behalf of the National Academy of Inventors. The copyright owner’s consent does not extend to copying for general distribution, for promotion, for creating new works, or for resale. Specific written permission must be obtained from the publisher for such copying. In case of doubt, please contact T&I at tijournal@ academyofinventors.org. Copyright © 2016 National Academy of Inventors® Printed in the USA

Cover Photo: Eric Schroeder | Thinkstock.com

Volume 18, Numbers 2-3, 2016

Pages 83 –225

ISSN 1949-8241 E-ISSN 1949-825X

CONTENTS SPECIAL TOPIC ISSUE: OUTCOMES AND ADVANCES IN ASSISTIVE TECHNOLOGIES FOR REHABILITATION Outcomes and Advances in Assistive Technologies for Rehabilitation: Special Topic Edition 83 Overview M. Jason Highsmith Economic Evaluations of Interventions for Transtibial Amputees: A Scoping Review of 85 Comparative Studies M. Jason Highsmith, Jason T. Kahle, Amanda Lewandowski, Tyler D. Klenow, John J. Orriola, Rebecca M. Miro, Owen T. Hill, Sylvia Ursula Raschke, Michael. S. Orendurff, James T. Highsmith, and Bryce S. Sutton Gait Training Interventions for Lower Extremity Amputees: A Systematic Literature Review 99 M. Jason Highsmith, Casey R. Andrews, Claire Millman, Ashley Fuller, Jason T. Kahle, Tyler D. Klenow, Katherine L. Lewis, Rachel C. Bradley, and John J. Orriola Interventions to Manage Residual Limb Ulceration Due to Prosthetic Use in Individuals with Lower Extremity Amputation: A Systematic Review of the Literature M. Jason Highsmith, Jason T. Kahle, Tyler D. Klenow, Casey R. Andrews, Katherine L. Lewis, Rachel C. Bradley, Jessica M. Ward, John J. Orriola, and James T. Highsmith

115

Predicting Walking Ability Following Lower Limb Amputation: An Updated Systematic 125 Literature Review Jason T. Kahle, M. Jason Highsmith, Hans Schaepper, Anton Johannesson, Michael S. Orendurff, and Kenton Kaufman Effects of the Genium Knee System on Functional Level, Stair Ambulation, Perceptive and Economic Outcomes in Transfemoral Amputees M. Jason Highsmith, Jason T. Kahle, Matthew M. Wernke, Stephanie L. Carey, Rebecca M. Miro, Derek J. Lura, and Bryce S. Sutton

139

Effects of the Genium Microprocessor Knee System on Knee Moment Symmetry during Hill Walking M. Jason Highsmith, Tyler D. Klenow, Jason T. Kahle, Matthew M. Werke, Stephanie L. Carey, Rebecca M. Miro, and Derek J. Lura

151

Bioenergetic Differences during Walking and Running in Transfemoral Amputee Runners Using Articulating and Non-Articulating Knee Prostheses M. Jason Highsmith, Jason T. Kahle, Rebecca M. Miro, and Larry J. Mengelkoch

159

The Effect of Transfemoral Interface Design on Gait Speed and Risk of Falls Jason T. Kahle, Tyler D. Klenow, William J. Sampson, and M. Jason Highsmith

167

Comparative Effectiveness of an Adjustable Transfemoral Prosthetic Interface Accomodating Volume Fluctuation: Case Study Jason T. Kahle, Tyler D. Klenow, and M. Jason Highsmith

175

Concurrent Validity of the Continuous Scale-Physical Functional Performance-10 (CS-PFP-10) Test in Transfemoral Amputees M. Jason Highsmith, Jason T. Kahle, Rebecca M. Miro, M. Elaine Cress, William S. Quillen, Stephanie L. Carey, Rajiv V. Dubey, and Larry J. Mengelkoch

185

Psychometric Evaluation of the Hill Assessment Index (HAI) and Stair Assessment Index (SAI) in High-Functioning Transfemoral Amputees M. Jason Highsmith, Jason T. Kahle, Brain Kaluf, Rebecca M. Miro, Larry J. Mengelkoch, and Tyler D. Klenow

193

Biopsy 1-2-3 in Dermatologic Surgery: Improving Smartphone Use to Avoid Wrong-Site 203 Surgery James T. Highsmith, David A. Weinstein, M. Jason Highsmith, and Jeremy R. Etzkorn

PLAY Hands Protective Gloves: Technical Note on Design and Concept 207 Michele Houston-Hicks, Derek J. Lura, and M. Jason Highsmith Radiographic Assessment of Extremity Osseointegration for the Amputee Munjed Al Muderis, Belinda A. Bosley, Anthony V. Florschutz, Paul A. Lunseth, Tyler D. Klenow, M. Jason Highsmith, and Jason T. Kahle

211

REGULAR FEATURES Taking Aim at Cancer James Higgins and Alex Camarota

217

The NAI Profile: An Interview with Dr. Robert S. Langer Robert S. Langer and Kimberly A. Macuare

219

Aims and Scopes

Preparation of Manuscripts

Ethics Statement

ii www.technologyandinnovation.org

ISSN 1949-8241 • E-ISSN 1949-825X http://dx.doi.org/10.21300/18.2-3.2016.83 www.technologyandinnovation.org

OUTCOMES AND ADVANCES IN ASSISTIVE TECHNOLOGIES FOR REHABILITATION: SPECIAL TOPIC EDITION OVERVIEW M. Jason Highsmith1-3 1 School of Physical Therapy & Rehabilitation Sciences, University of South Florida, Tampa, FL, USA Extremity Trauma & Amputation Center of Excellence (EACE), U.S. Department of Veterans Affairs, Tampa, FL, USA 3 319th Minimal Care Detachment, U.S. Army Reserves, Pinellas Park, FL, USA

Once again, the National Academy of Inventors (www.academyofinventors.org), a nonprofit organization recognizing and encouraging creativity and invention, is pleased to present scientific findings in the areas of prosthetics, orthotics, and assistive technologies from researchers representing the University of South Florida’s (USF) School of Physical Therapy & Rehabilitation Sciences (SPTRS), the Extremity Trauma & Amputation Center of Excellence (EACE), and numerous colleagues and collaborators in the U.S. and abroad. The NAI continues to grow its reach with new national and international academic and institutional partnerships. This special topic edition of Technology and Innovation, Journal of the National Academy of Inventors will predominantly feature prosthetic and amputee rehabilitation related topics. It also includes other assistive technology, therapeutic, and surgical topics with high clinical relevance from clinician scientists. This edition is timely in the wake of recent significant challenges with health care reimbursement. Specifically, third-party payors of health care services, citing limited quality and quantity of evidence regarding interventions provided by rehabilitation clinicians who care for patients with limb loss who use prostheses, have attempted to restructure reimbursement practices and policies. As a result, professional organizations within the prosthetic and orthotic professions, including the American Academy of Orthotists and Prosthetists and the American Orthotic & Prosthetic Association among others, formulated a multi-pronged response to defend the merit of the interventions provided by these professionals. Domains represented in the responses from these organizations included advocacy and research. Some of the products of these efforts are contained within this edition. Specific study designs contained in this issue represent a considerable portion of the evidence pyramid, including systematic reviews, clinical research, case reports, outcomes research, and technical notes. From a funding perspective, numerous sponsors deserve acknowledgment for facilitating production of this research and the associated knowledge products. For instance, the USF SPTRS, the state of Florida, industry sponsors, professional organizations, and the National Institutes of Health, by way of a Scholars in Patient Oriented Research (SPOR) grant, were among the research sponsors. Highlights from a content perspective include an economic analysis of transtibial interventions and systematic reviews on dermatologic issues, gait training, and walking function in persons with lower limb amputation. Additionally, several intervention pieces evaluate comparative efficacy of prosthetic socket and knee interven_____________________ Accepted July 1, 2016. Address correspondence to M. Jason Highsmith, Extremity Trauma & Amputation Center of Excellence (EACE), 8900 Grand Oak Circle (151R), Tampa, FL 33637-1022, USA. Tel: +1 (813) 558-3936; Fax: +1 (813) 558-3990; E-mail: michael.highsmith@va.gov

HIGHSMITH

tions. New concepts are considered in select assistive technologies and surgical domains. Finally, much needed psychometric work is presented in clinical outcome measures used in the evaluation of those using artificial limb technologies. Those who contributed to the science and dissemination of this research hope that consumers, payors, clinicians, academicians, and, above all, patients will benefit from the findings contained in this edition of Technology and Innovation. It is hoped that the findings will continue to build the body of knowledge within the rehabilitation sciences, including prosthetics and orthotics. It is further hoped that this science will assist in the reimbursement arena with clinical decision making and that others will build on and expand on these findings to continue to push the boundaries of what can be achieved for those who use assistive technologies.

ISSN 1949-8241 • E-ISSN 1949-825X http://dx.doi.org/10.21300/18.2-3.2016.85 www.technologyandinnovation.org

ECONOMIC EVALUATIONS OF INTERVENTIONS FOR TRANSTIBIAL AMPUTEES: A SCOPING REVIEW OF COMPARATIVE STUDIES M. Jason Highsmith1-3, Jason T. Kahle4,5, Amanda Lewandowski6, Tyler D. Klenow7, John J. Orriola8, Rebecca M. Miro1, Owen T. Hill9, Sylvia Ursula Raschke10, Michael S. Orendurff11, James T. Highsmith12,13, and Bryce S. Sutton14 1 School of Physical Therapy & Rehabilitation Sciences, University of South Florida, Tampa, FL, USA Extremity Trauma & Amputation Center of Excellence (EACE), U.S. Department of Veterans Affairs, Tampa, FL, USA 3 319th Minimal Care Detachment, U.S. Army Reserves, Pinellas Park, FL, USA 4 OP Solutions, Tampa, FL, USA 5 Prosthetic Design + Research, Tampa, FL, USA 6 Select Physical Therapy, Brandon, FL, USA 7 Prosthetics and Sensory Aids Service, James A. Haley Veterans’ Hospital, Tampa, FL, USA 8 Shimberg Health Sciences Library, University of South Florida, Tampa, FL, USA 9 Extremity Trauma & Amputation Center of Excellence (EACE), San Antonio Medical Center, Fort Sam Houston, TX, USA 10 Center for Rehabilitation Engineering and Technology that Enables (CREATE), BCIT Technology Centre, Burnaby, Canada 11 Motion & Sports Performance Laboratory, Lucile Packard Children’s Hospital Stanford, Palo Alto, CA, USA 12 Dermatology Service, James A. Haley Veterans’ Hospital, Tampa, FL, USA 13 Dermatology Surgery Institute, Lutz, FL, USA 14 Center of Innovation on Disability and Rehabilitation Research (CINDRR-TPA), James A. Haley Veterans’ Hospital, Tampa, FL, USA 2

Transtibial amputation (TTA) is life-altering emotionally, functionally, and economically. The economic impact to all stakeholders is largely unknown, as is the cost-effectiveness of prosthetic intervention. This scoping report’s purpose was to determine if there is sufficient evidence to conduct a formal systematic review or meta-analysis in any particular prosthetic intervention area and to determine if any evidence statements could be synthesized relative to economic evaluation of interventions provided to patients with TTA. The scoping review revealed six articles representing three topical areas of transtibial care: Care Models, Prosthetic Treatment, and Prosthetic Sockets. All six articles were cost-identification or cost-consequence design and included a total of 704 subjects. Presently, it can be concluded with moderate confidence that specific weight-bearing and total-contact sockets for transtibial amputees are functionally and economically equivalent in the short term when costs, delivery time, and all stakeholder perspectives are considered. Long-term socket outcomes are relatively unexplored. Further primary research is needed beyond this to determine cost-effectiveness for other areas of transtibial prosthetic care although clinical outcomes are somewhat established through systematic review and meta-analysis in other areas of care. Conversely, evaluation of narrative economic reports relative to transtibial care may be sufficient to warrant further analysis. Guidance from the profession may also be useful in devising a strategy for how to assure economic analyses are a routine element of future prosthetic science. Key words: Cost-benefit; Cost-consequence; Cost-effectiveness; Cost utility; Cost identification; Health economics; Prosthetic socket _____________________ Accepted July 1, 2016. Address correspondence to M. Jason Highsmith, Extremity Trauma & Amputation Center of Excellence (EACE), 8900 Grand Oak Circle (151R), Tampa, FL 33637-1022, USA. Tel: +1 (813) 558-3936; Fax: +1 (813) 558-3990; E-mail: michael.highsmith@va.gov

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INTRODUCTION Persons with transtibial amputation (TTA) commonly use prostheses to ambulate. Prosthetic provision is a considerable health care expense over the lifetime for TTA patients. Estimated lifetime prosthetic costs for an individual with unilateral lower limb amputation could range from $0.5 to $1.8 million depending on many factors, such as the number and type of prostheses in service at a given time (1). Collectively, care for the amputee of dysvascular etiology has societal costs (U.S.) of an estimated $4.3 billion, and Medicare reimbursed $655 million worth of lower limb prosthetic services in 2009 (2,3). Given the numerous intervention options and costs associated with amputee rehabilitation and prosthetic provision, it is problematic that the literature’s ability to guide clinical practice, reimbursement, or health care policy is limited. For example, prominent reviews on the subjects of foot prescription (4) and post-operative management (5) indicate that no clinical recommendations can be made due to a lack of evidence. Within the prosthetic profession, this is problematic given the 2012 report by the U.S. Office of the Inspector General indicating ≈$4.7 million worth of Medicare billings were inappropriate (2). Moreover, some insurers impose a one-limb-per-lifetime reimbursement limit, further substantiating the need for economic data related to TTA prosthetic care (6). Another consideration is that TTA patients develop secondary conditions related to sound limb overuse, prosthetic malalignment, and other factors, including degenerative joint disease, osteopenia, postural issues, low back pain, and others (7). Each of these secondary complications has health care utilization and cost implications that are unexplored with regard to this population. Nevertheless, many TTA patients lead functional lifestyles (8), at times participating in sport and athletic pursuits (9). Incorporation of a prosthesis is routinely part of the rehabilitation and reintegration plan (10). A 2013 analysis of Medicare beneficiaries (2008 Jan 1 to 2009 Jun 30) with recent lower limb amputation reported that, compared to non-prosthetic users, those who received prostheses had comparable Medicare episode payments (including prosthetic costs: $68,040 vs. $67,312; p > 0.05) and superior

outcomes (i.e., fewer emergency room admissions 1.6 vs. 2.1; p < 0.05) (11). Prosthetic users were more likely to receive outpatient therapy compared with non-prosthetic users (27.2 more visits; p < 0.05). Physical therapy participation was associated with fewer acute care hospitalizations and less facility-based care (p < 0.05), which offsets the initial high cost associated with prosthetic provision. In other words, the higher initial costs decrease the burden on the health care system by decreasing utilization and adverse events. This cost savings provides insight into costs not paid (i.e., resources saved) as a result of proper rehabilitative care including prosthetic provision. This savings might be considered value. These data (11) further suggest the prosthesis was nearly amortized at 12 months, and users may experience higher quality of life and increased independence compared to non-prosthetic users. Given the recent reimbursement challenges based on a lack of clinical and economic evidence, there is a need to understand and document the cost-effectiveness of prosthetic rehabilitation for TTA patients. Therefore, this project’s purpose was to conduct a systematic scoping review of the literature to determine if clinical sub-topics had sufficient evidence for further systematic review and meta-analysis. Additionally, the review sought to formulate evidence statements related to prosthetic interventions for persons with TTA from an economic evaluation perspective based solely on comparative studies. METHODS On the assumption that economic evaluations for TTA prosthetic interventions would be limited, investigators opted for an inclusive search considering any element of the prosthesis (foot, ankle, pylon, socket, liner, suspension) as well as complete prosthetic care. On November 18, 2015, three databases—MEDLINE (Pubmed), The Cumulative Index to Nursing and Allied Health Literature (CINAHL) (Ovid), and the Cochrane Database of Systematic Reviews—were systematically searched for combinations of the following primary search terms:

TRANSTIBIAL ECONOMIC EVALUATIONS

(prosthe* OR “Prostheses and Implants” OR prosthesis OR prostheses OR preprosthe* OR pre-prosthe*) AND (((transtibial OR trans-tibial OR trans tibial OR below knee OR bka OR tta OR Leg[Mesh] OR leg OR legs OR lower limb OR lower limbs OR lower extremity OR lower extremit* OR “Lower Extremity”[Mesh])))

for classification as: 1) pertinent, 2) not pertinent, or 3) uncertain pertinence. Full-text articles were reviewed for citations classified as pertinent or uncertain pertinence. Disagreement regarding citations of uncertain pertinence were resolved by discussion with a third rater. Review of full-text articles and associated discussion led to group consensus and ultimate inclusion/exclusion. The following inclusion criteria were applied to studies (12):

Primary search terms were combined systematically with the following secondary search terms:

1. Included a clinical intervention comparison for patients with TTA 2. Included any one of the following types of economic evaluation: a. Cost-consequence analysis (CCA), involving a way of reporting cost and an array of outcomes in a separate and disaggregated way so that no incremental ratios are involved b. Cost-effectiveness analysis (CEA), involving incremental analysis between the calculated differences in costs and outcomes c. Cost-benefit analysis (CBA), which values both measured health and non-health outcomes in monetary units d. Cost-utility analysis (CUA), involving utilities, quality-adjusted life years (QALY), or their variants as the measured outcomes e. Cost-identification analysis (CIA), in which a cost comparison is made without the inclusion of a comparison of health outcomes 3. Published within the aforementioned timeline

Cost OR Econ* OR Efficacy OR “Cost Benefit” OR “Cost Effectiveness” OR “Cost Utility” OR “Healthcare Econ*” The following date limits were implemented as part of the database search parameters: 1997 Jan 1 through 2015 Nov 15. Article Screening Resulting references were exported to EndNote (vX6, Thompson, CA, USA) reference management software, where Stage 1 screening was applied. Stage 1 screening, including a title and abstract review and the elimination of duplicate references, was applied. Remaining economic evaluation articles were sorted by topic. Exclusion criteria were applied starting at Stage 1 to eliminate studies that merely describe costs but otherwise lack cost comparison. Foreign language articles were eliminated because of prohibitive translation fees. Economic evaluation articles from developing nations were excluded due to an inability to apply their findings to the U.S. health care market. Articles were screened for exclusion using the following criteria within EndNote: 1. Foreign language (i.e., non-English language) 2. Developing countries 3. Any study lacking an economic evaluation or cost-comparison analysis 4. Retrospective studies 5. Case studies Following Stage 1 screening, Stage 2 screening was applied as outlined here. Remaining economic evaluation articles were reviewed by two raters and screened independently to verify inclusion/exclusion and

Data Extraction Data were extracted and categorized according to country origin, economic evaluation analysis design (trial- or modeling-design), economic evaluation type (CCA, CEA, CBA, CUA, or CIA as defined above), perspective, time horizon, intervention and follow-up period, study population, alternatives compared, costs, and outcomes. Reported costs were converted to U.S. dollars by dividing the local currency unit with the purchasing power parity rates for the mentioned price year and subsequently inflated to 2016 year dollars as defined by the World Bank Group (13,14). If the price-year was not stated in the study, the publication year was used. Final costs displayed

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were rounded to the nearest whole number. If possible, data were evaluated as appropriate for pooled analyses. Sorting by Topic Following screening for eligibility determination and data extraction, articles were sorted for pertinence into available intervention topical areas. Quality Assessment Economic Evaluation Quality Each manuscript was assessed for its economic evaluation quality by two reviewers using the Quality of Health Economic Studies (QHES) instrument and the per-item scores averaged (15). In its original form, QHES has 16 weighted criteria scored (scaled 1 to 100). Full weight is awarded for a ‘yes’ and no weight for a ‘no’ response per criterion. Weights are relative to the per-criterion importance. This better discriminates between poor and good quality economic evaluations and is suitable for both trial- and modeling-based evaluation (16). QHES has good reliability (17) and construct validity (18) and is a commonly used tool (16,17,19). Its major limitation is its multi-topic items in a single criterion (i.e., multiple items within a single item share a single weight). For this review, the QHES scoring system was modified without changing the original weights to overcome this drawback in accordance with previous use (12). Multi-topic questions were assigned sub-weights per item but still summed to the original weight. Items 12 and 13 were modified to rate both trial- and modeling-based economic evaluation. Item 6 was modified to enable the ability to rate CBA evaluations; however, it was still not applicable to CCA. Thus, the total base score was 94 for CCA evaluations. The score of item 4 did not count when it was not applicable, but the total score remained 100 since its weight was small and only negligibly affected the overall score. After determining the total scores and converting to a percentage, a total QHES score of 75 to 100 indicated “high quality,” 50 to 74 indicated “fair quality,” 25 to 49 indicated “poor quality,” and 0 to 24 indicated “extremely poor quality” (12). Following the rating for economic evaluation with QHES, methodological

quality of included studies was rated as described below. Evaluation of Internal and External Validity Methodological quality of included publications was independently assessed by two reviewers according to the American Academy of Orthotists and Prosthetists (AAOP) State-of-the-Science Evidence Report Guidelines protocol (20). The AAOP Study Design Classification Scale was used to describe the design type of the included studies (20). The State of the Science Conference (SSC) Quality Assessment Form was used to rate the methodological quality of studies classified as experimental (E1 to E5) or observational (O1 to O6) (20). The form identifies 18 potential threats to internal validity, with the first four threats not applicable for study classifications E3 to E5 and the first five threats not applicable for classifications O1 to O6. Threats were evaluated and tabulated. The internal and external validity of each study was then subjectively rated as “high,” “moderate,” or “low” based on the quantity and importance of threats present. For internal validity, 0 to 3 threats was rated “high,” 4 to 6 threats as “moderate,” and 7 to 13 or 14 threats as “low.” For external validity, the form identifies eight threats. For this study, 0 to 2 threats to external validity was rated “high,” 3 to 5 threats as “moderate,” and 6 to 8 threats as “low.” Each study was then given an overall quality of evidence of “high,” “moderate,” and “low” outlined by the AAOP State-of-the-Science Evidence Report Guidelines (20). The overall ratings from the QHES and from the AAOP State-of-the-Science Evidence Report Guidelines were used in assigning confidence to the developed empirical evidence statements described in following section. Empirical Evidence Statements Based on results from the included publications, empirical evidence statements (EES) were developed that compared TTA interventions economically. Reviewers rated the level of confidence of each EES as “high,” “moderate,” “low,” or “insufficient” based on the number of publications contributing to the statement, the methodological quality of those studies,

TRANSTIBIAL ECONOMIC EVALUATIONS

Included Eligibility Screening Identification

Figure 1. Flow diagram. Articles identified through database searching: PubMed, CINAHL, Google Scholar (n =292)

Articles potentially avaialble for classification of pertinence (n =29)

Articles deemed appropriate for Soring & Evaluation (n =6)

Care Models (n =1)

Prosthetic Treatment (n =2)

and whether the contributing findings were confirmatory or conflicting as similarly outlined by others (21). RESULTS Literature Search The search yielded 292 manuscripts (Figure 1). Stage 1 screening eliminated 263 manuscripts and stage 2 screening an additional 23 manuscripts, leaving six articles meeting eligibility criteria. The six remaining articles, published from 2004 to 2011, were divided into the following three topical areas: 1. Care Models (n = 1) (22) 2. Prosthetic Treatment (n = 2) (23,24) 3. Prosthetic Sockets (n = 3) (25-27) Three of the articles were published in Prosthetics and Orthotics International. The remaining three papers were published in other journals. From an economic evaluation type, all six papers were trial-design (as opposed to modeling). Five were cost-consequence evaluations and one was a cost-identification design (Table 1). Funding Four of the six manuscripts included a statement disclosing whether or not the study was funded. Of

Articles Eliminated Stage 1 Screening (n =263)

Articles Eliminated Stage 2 Screening (n =23)

Prosthetic Sockets (n =3)

these, only two of the studies were funded, one by multiple sources (professional association, governmental, educational) (23) and the other by an insurer (26). Study Demographics, Interventions, and Outcome Measures Articles in this review included a total of 704 patients. Among them, 460 were undergoing limb salvage, whereas the remaining 244 had TTA of mixed etiology. The median (range) sample size was n = 43 (20 to 484). See Table 1 for extracted study data, including specific characteristics of the subjects and studies. The reviewed studies were classified into three of the 15 potential study designs (controlled trial, randomized controlled trial, and case-control designs) described by the AAOP Study Design Classification Scale (20). All three of the socket manuscripts represented experimental study designs, while the remaining three utilized observational designs. Clinical outcome measures reported in the reviewed publications included duration of care, perceived function, prosthetic satisfaction, clinical gait outcomes, time to prosthetic delivery, and number of visits. Economic outcomes reported in the reviewed publications included cost of prosthetic fabrication, prosthetic maintenance, prosthetic provision,

Gordon et al. Australia

Mackenzie et al. U.S.

Gil et al. U.S.

Datta et al. England

Selles et al. Netherlands

Normann et al. Sweden

Care Models. 2010

Prosthetic Treatment. 2007‡

Prosthetic Treatment. 2010

Prosthetic Sockets. 2004

Prosthetic Sockets. 2005

Prosthetic Sockets. 2011

76 CF; 17 TTA

384 LS; 100 TTA

66 y; 69 y

68 y; 58 y

14 PVD; 11 Trauma; 1 Cancer

12 PVD; 7 Trauma; 1 Infection

52 y

≈55 y

DM + Obese + CF vs. TTA 7 PVD; 10 Trauma; 4 other

2045 y*

Age†

Trauma

78% PVD, 22% other

Etiology

Plaster Casted Socket: $585 Direct Manufactured Socket: $858

PTB socket: $1,045 TSB socket: $1,743

PTB socket: $477 HSD socket: $1,232

TTA + Care (including prosthesis): $147,375 LS + Associated Care: $247,589

TTA + Care (including prosthesis): $90,875 LS + Associated Care: $85,682

Avg Labor Cost/Patient Public Sector: $1,466 Private Sector: $2,020

Interventions & Costs§ (Standard vs. Comparator)

17 d (Plaster); 1 d (Direct mfg)

3 mos

6 wks

1 yB

Hospitalization: 17.9 d (LS) vs. 17.4d (TTA)A

Interim to definitive fit (d): 112 vs. 119 (p = 0.6)A

Follow-up Period

Direct mfg'd socket provision costs higher (p < 0.01; 32%), delivered faster (p < 0.01; 58%) & fewer visits (1 vs. 2.5) vs. plaster casting.

PTB socket material provision cost 60% of TSB. Subjects preferred new socket regardless of type. More provision time & visits for PTB socket (p < 0.05) vs TSB.

LS + care (surgery thru 1 y + hospitalizations, device provision, therapy) $97,076 more vs. TTA. PTB socket provision cost 60% less than HSD. PTB provision time 3x that of HSD.

TTA + care (surgery-2 y followup including prosthesis) $4,928 more costly vs. LS.

Public sector patients perceived function & prosthetic satisfaction increased & labor costs 10-29% lower (p < 0.05).

Outcomes

§Costs are converted to U.S. Dollars and inflated to 2015 from the publication year as outlined in the methods. Regarding time horizon, A is a 2 y horizon and B is a 40 mos horizon otherwise, time horizon was not reported. *age data for 72% of the sample. †Age(y). ‡Mackenzie et al. used a cost-identification design whereas all others used a cost-consequence design. CF is Charcot Foot. HSD is hydrostatic design socket. PTB is patella tendon bearing socket. TSB is total surface bearing socket. LS is limb salvage.

Author. Country

Topic. Year

Table 1.Data Extracted Data Table 1. Extracted

90 HIGHSMITH ET AL.

QHES QHESisisQuality QualityofofHealth HealthEconomic EconomicStudies. Studies.‡Mackenzie ‡Mackenzieetetal. al.used usedaacost-identification cost-identificationdesign designwhereas whereasallallothers othersused usedaacost-consequence cost-consequence design. design.

64.0 64.0(Fair (FairQuality) Quality) 77.0 77.0(High (HighQuality) Quality) 62.5 62.5(Fair (FairQuality) Quality) 69.0 69.0(Fair (FairQuality) Quality) 57.5 57.5(Fair (FairQuality) Quality) 65.5 65.5(Fair (FairQuality) Quality) 2010 Gordon 2010 Gordonetetal.(22) al.(22) 2007 2007 Mackenzie Mackenzieetetal.al.(23) (23) 2010 Gil 2010 Giletetal. al.(24) (24) 2004 Datta 2004 Dattaetetal. al.(25) (25) 2005 Selles 2005 Sellesetetal. al.(26) (26) 2011 2011 Normann Normannetetal. al.(27) (27) Care CareModels Models Prosthetic ProstheticTreatment Treatment Prosthetic ProstheticTreatment Treatment Prosthetic ProstheticSockets Sockets Prosthetic ProstheticSockets Sockets Prosthetic ProstheticSockets Sockets

Year Year Topic Topic

Table 2.2. Study Quality Ratings Table2. Study Quality Ratings Table Study Quality Ratings

Author Author

Study StudyDesign Design

Internal Internal Validity Validity Case High CaseControl Control High Case Low CaseControl‡ Control‡ Low Case Low CaseControl Control Low Randomized Mod RandomizedControlled ControlledTrial Trial Mod Randomized Mod RandomizedControlled ControlledTrial Trial Mod Controlled Mod ControlledTrial Trial Mod

External External Validity Validity High High High High High High High High High High High High

QHES QHESRating Rating

TRANSTIBIAL ECONOMIC EVALUATIONS

amputation or limb reconstruction surgical costs, and total care costs. Economic Study Quality All six studies were trial designs, so there were no modeling designs. All included studies represented the perspective of the provider, facility, and system with only the exception of the Datta et al. (25) study, which included elements from the patient perspective (e.g., travel considerations). Time horizon was reported in the Care Model (two years) and Prosthetic Treatment papers (40 months to two years). No time horizon was reported in the Prosthetic Socket papers. Conversely, follow-up periods were reported or discernable in every case. Criteria 5 (statistical and sensitivity analyses) and 6 (incremental cost comparison) were the least included criteria of the involved studies. Normann et al. (27) was the only study that included methods to address uncertainty, which was not addressed in any of the other studies. The conduct of incremental analyses between alternative interventions was not done in any of the included studies (i.e., all were cost-identification or cost-consequence trial designs). Generally, positive attributes of the studies included clear and measurable presentation of objectives, use of detailed methodology for data extraction, and appropriate utilization of primary outcome measures. Other positive attributes of the included studies included the use of reliable and well justified measures, the measurement of appropriate costs, the inclusion of descriptions of assumptions and study limitations, and conclusions that were generally based on study results. Overall, five of the studies were rated as fair quality. The remaining paper, Mackenzie et al. (23), was rated as high quality according to the QHES (Table 2). Internal and External Validity Threats to internal validity included lack of blinding, not addressing fatigue and learning, and not reporting effect size. Areas needing improvement for internal validity were issues with attrition and statistical analyses. Use of robust outcome measures was among the stronger criteria bolstering internal validity. Two studies had low, three had moderate level, and one study had high internal validity. Conversely,

HIGHSMITH ET AL.

all of the studies had high external validity according to the AAOP rating tool. Bias risk from a research funding perspective was low given the majority of studies were unfunded. Economic Data Key cost comparisons and outcomes are extracted into Table 1. Regarding Care Models, the average labor cost per patient was 27% less costly in the public sector and was coupled with an improvement (p < 0.001) in patient satisfaction relative to the private sector care model. For Prosthetic Treatment, when limb salvage was the comparator, two different studies yielded mixed results. Mackenzie et al. reported no practical difference in length of hospital stay between all average limb salvage scenarios (17.9 days) and TTA (17.4 days). However, their analysis concluded that twoyear costs were 6% higher ($4,928) for TTA versus limb salvage. Importantly, the nature of the limb trauma and type of limb salvage procedure are factors, and, in some limb salvage situations, two-year costs may be as much as 5% higher than TTA. In a study of those with Charcot foot and other comorbidities, one-year total care costs (i.e., hospitalization, device) were compared between those undergoing limb salvage versus TTA. In this specific population, the limb salvage surgery and the total cost of care, including hospitalization, device provision, therapy, etc., were reportedly more costly with limb salvage than TTA. The average cost increase for limb salvage was $7,461 or a 13% increase even with the added expense of the prosthesis for the TTA cases. Three studies supported the Prosthetic Socket topic. Two of the studies compared specific weightbearing (PTB) sockets with forms of total-contact sockets (hydrostatic design (HSD) and total surface bearing (TSB)). Both studies conclude that provision costs of PTB sockets are 60% (p < 0.01) of those of total-contact alternatives. The tradeoff for the reduced provision costs associated with PTB sockets are increased provision time (three-fold increase; p < 0.05) and more visits (p < 0.05) necessary to achieve a proper fit. Clinical outcomes were similar between socket designs and preference was for the

newer socket regardless of which design it was. Also within the Prosthetic Socket Topic was a comparison of a direct fabrication technique compared with traditional plaster casting methods. The direct manufacturing method was associated with 32% higher provision costs (p < 0.01) but had the benefit of 58% faster delivery (p < 0.01) and 1.5 fewer visits. Evidence Statements Five EESs (Table 3) were synthesized from the results within the three topical areas previously identified. Four of the statements were supported by a single study resulting in an insufficient level of confidence. One statement from the Prosthetic Socket topical area had two studies with moderate and fair quality, respectively, from their validity and economic assessment, resulting in moderate confidence in the statement from both the clinical science and economic perspectives. DISCUSSION One purpose of this scoping review was to formulate evidence statements and determine cost efficacy using economic evaluations of interventions provided to patients with TTA. Three topical areas, Care Models, Prosthetic Treatment, and Prosthetic Sockets, were identified, yielding synthesis of five evidence statements. The first statement addresses public versus private care models at the point in care when an interim prosthesis is utilized by patients (22). Under the public model, a prosthetist was employed to provide prostheses, whereas patients were referred out to external private practice prosthetists for artificial limb provision under the private care model. Briefly, clinical outcomes were determined to be similar between the models, yet patient satisfaction was higher and costs were approximately 29% lower per patient when care was received from the public sector compared with the private sector care model. In this case, payors received the added value of cost savings in addition to higher patient satisfaction with comparable clinical outcomes. The evidence statement is supported by a single study that has high internal and external validity and fair quality as rated by the QHES (Tables 2 and 3), thus providing high

TRANSTIBIAL ECONOMIC EVALUATIONS

Table 3. Empirical Evidence Statements

Category

Care Models

Prosthetic Treatment

Prosthetic Sockets

Empirical Evidence Statement (EES) (EES 1) In socialized healthcare systems, patients with unilateral transtibial amputation may experience similar clinical outcomes from the interim to definitive prosthetic stages of rehabilitation with lower average per-patient labor costs and higher satisfaction when managed in a public sector care model compared with a private sector care model. (EES 2) Patients having experienced lower limb trauma requiring limb salvage or transtibial amputation will likely experience similar hospitalization duration regardless of the choice of surgical procedure. However, the two-year costs, on average, will be approximately 6% higher for TTA versus limb salvage. In some situations, the limb trauma and type of limb salvage procedure can necessitate up to 5% higher costs compared with TTA. (EES 3) Patients with Charcot foot arthropathy and multiple comorbidities will likely experience up to 13% increased one-year costs (including hospitalization, device provision, therapy) if limb salvage is selected as opposed to transtibial amputation. (EES 4) Provision of patella tendon bearing (PTB) sockets for patients with transtibial amputation costs 40% less than total contact socket alternatives however PTB sockets require up to three-times longer to achieve a proper fit with no clinical performance differences between the alternatives. (EES 5) Compared with traditional plaster casting fabrication, the direct manufacturing method of providing prosthetic sockets for patients with transtibial amputation have 32% higher provision costs but are delivered to patients up to 58% faster and in fewer visits.

Supporting Studies

High/Fair(22)

Moderate/High (23)

Moderate/Fair (24)

Moderate/Fair Two studies (25,26)

Moderate/Fair (27)

Supporting Studies rated by AAOP tool/QHES. The Level of Confidence for EESs 1-3 and 5 is Insufficient based on limited evidence (i.e. a single study per topic). The fourth statement (EES 4) is supported by sufficient evidence to support a Moderate level of confidence in the statement.

HIGHSMITH ET AL.

confidence in the clinical outcomes and moderate confidence in the economic analysis. However, despite generally favorable scientific and economic quality ratings from a single study, this is insufficient to support the statement until further studies can confirm the findings. Another consideration for this statement is that the study represents the single country of Australia. While other countries have socialized medical models, various nationsâ&#x20AC;&#x2122; approaches to the provision of socialized health care differ considerably. For comparison, the Veterans Affairs Amputation System of Care (VA ASoC) is a U.S. government (i.e., public) sector health care system charged with providing care for the unique population of military service Veterans with limb loss (28). The VA ASoCâ&#x20AC;&#x2122;s mission differs considerably from socialized models charged with care provision for an entire countryâ&#x20AC;&#x2122;s population, and there is no clear private sector alternative to compare outcomes within the U.S. Therefore, further study is needed to determine if results of this study (22) are repeatable in other nations or sectors. The second topical area was Prosthetic Treatment. This topical area yielded two EESs. Both statements compared limb salvage with TTA. Factors included were surgical costs, device provision, and associated costs. The first statement involved patients who experienced lower limb trauma requiring either limb salvage or TTA. Their hospitalization times were similar regardless of the choice of surgical procedure. However, the average two-year costs were 6% higher for those undergoing TTA compared to those undergoing limb salvage. This higher cost of TTA with associated care is not always the case. For instance, in some limb salvage situations, the extent of the limb trauma and type of limb salvage procedure can necessitate up to 5% higher costs compared with TTA (23). This EES is supported by a single study that has low internal and high external validity and high quality as rated by the QHES, thus providing moderate confidence in the clinical outcomes and high confidence in the economic analysis. Nevertheless, the single study supporting this statement has disagreement within it about costs relative to the specific levels of amputation and certain types of limb salvage procedures. Therefore, additional evidence is needed to support this EES given that only a single study supports the

statement and the fact that costs differ depending upon so many factors. Further, both amputation and limb salvage result in neuromusculoskeletal deficit, which can lead to pain and loss of strength, power generation, range of motion, and sensation. These impairments can impact function and quality of life. Clinical outcomes following amputation have been compared to those following limb salvage (29). A definitive advantage to either has not been identified (30-33). This further confirms the autonomy that practitioners must have when discussing options with patients facing this decision due to an inability to empirically identify clear functional or economic advantages related to either decision given currently available data. Also within the Prosthetic Treatment topic, EES 3, which addresses patients with Charcot foot arthropathy and multiple comorbidities such as diabetes and obesity, was synthesized. In this study, patients reportedly experienced up to 13% increased one-year costs (including hospitalization, device provision, and therapy) if limb salvage was selected as opposed to TTA. This is a different clinical situation than that described in EES 2 due to the etiology and comorbidities of the respective patients. The statement is supported by a single study that has low internal and high external validity and fair quality as rated by the QHES. Clinical outcomes were not reported. Therefore, evidence supporting this statement is also insufficient due to a lack of data to confirm support. Unlike the previous scenario, in which trauma drives the decision to surgically salvage or amputate, authors in this study unanimously report increased cost associated with limb salvage in the obese diabetic patient with Charcot arthropathy. This warrants further consideration, as obesity has not been shown to significantly impair ambulation or prognosis with a prosthesis (34). Prosthetic Sockets represent the third topical area in the review. This topic also resulted in the synthesis of two evidence statements. The first statement in this topic (EES 4) states that provision of specific weight-bearing PTB sockets for patients with TTA cost 40% less than total-contact socket alternatives. However, PTB sockets require up to three times longer to achieve a proper fit with no clinical performance

TRANSTIBIAL ECONOMIC EVALUATIONS differences among the alternatives. Therefore, according to the included studies (25,26), there is no cost reduction or clinical performance difference between the interventions. Although the PTB sockets have a lower initial cost, the additional clinic visits, which require increased time commitments and travel costs as well as the risk of potential complications, ultimately increase latent costs. Conversely, provision of the more costly (initial cost) total-contact alternative sockets results in fewer of these additional expenses and visits. Thus, the interventions appear to be economically equivalent when viewed from all stakeholder perspectives in the short term. This fourth EES is supported by two studies, both with moderate internal validity and high external validity (25,26). Both are rated as fair quality studies according to the QHES. This evidentiary support provides moderate confidence in the clinical outcomes and fair confidence in the economic analysis. In contrast to these studies, a recent systematic review suggests that use of gel-lined sockets, as opposed to traditional PTB sockets, results in numerous clinical benefits, including decreased walk aid dependence, improved suspension options, improved load distribution, decreased pain, and increased comfort (35). This systematic review of clinical studies suggests gel-lined sockets offer clinical improvements relative to PTB sockets and is supported by Level 1 evidence. Thus, if clinical outcomes are improved with total-contact sockets, users may realize greater value through their use relative to PTB alternatives. This particular topic and EES also point out the importance of considering all perspectives in an economic analysis. A limitation of this EES is the time horizon. It is unclear if there are potential functional or cost differences over the long term between specific weight-bearing and total-contact socket alternatives. The second statement (EES 5) within the Prosthetic Socket topic addresses traditional plaster casting fabrication with direct manufacturing methods of providing prosthetic sockets for patients with TTA. Direct fabrication methods of socket delivery reportedly have 32% higher initial provision costs but are delivered to patients up to 58% faster and in fewer visits. This EES is supported by a single study with moderate internal validity and high external validity.

It is rated as fair quality according to the QHES. This evidentiary support provides moderate confidence in the clinical outcomes and fair confidence in the economic analysis. Again, further studies are needed to strengthen confidence in EES 5. Additionally, authors were unable to locate data to support widespread adoption of direct manufacturing techniques for TTA socket provision. A second purpose of this scoping review was to determine if further review and analysis is indicated based on the current state of the economic science relative to care for the patient with TTA. It seems that further analysis of economic comparison studies is less of an issue compared with the need for further primary economic comparison research, input, and guidance from the profession relative to a strategy to further develop this area of research. Additionally, multiple manuscripts were excluded from this analysis of economic comparisons that alternatively provide descriptive economic information relative to care for persons with TTA. These excluded narrative economic papers merit further review and analysis and are currently being evaluated by the authors. Limitations Many subjects in this report were patients of limb salvage procedures selected for comparison to TTA cases. Unfortunately, many individual aspects of transtibial prosthetic intervention are not represented or are under-represented in the health care economic literature. Currently, economic evaluations in any area of transtibial patient care are limited. There were no cost-benefit, cost-effectiveness, or cost-utility analyses identified in this search, as all available studies were cost-identification or cost-consequence studies. No economic modeling was identified. Further, described services and interventions were not quantifiably connected directly to health measures. Therefore, more sophisticated and comprehensive economic evaluations are needed with regard to transtibial interventions to better understand the potential value of certain interventions for the patient with TTA. One possible solution is to incorporate outcomes conducive to economic analysis and modeling as part of prosthetic oriented clinical trials (35). While total

HIGHSMITH ET AL.

prosthetic care has some representation, discrete topics of interest to the prosthetic clinical community were not represented, including topics such as prosthetic suspension, feet, newer socket designs (i.e., elevated vacuum), and others. Finally, this body of literature is biased to include predominantly the perspective of the care provider, their practice facility, or a care system. These are limited because cost burden to society, the patient, or the payor are not accounted for. CONCLUSIONS The comparative economic literature in transtibial prosthetics is presently insufficient for further review, conclusion, and policy guidance. Six cost-identification or cost-consequence articles were eligible for scoring in three topical areas: Care Models, Prosthetic Treatment, and Prosthetic Sockets. From these, five evidence statements were synthesized, with one supported by sufficient evidence to provide moderate confidence regarding comparable cost between totalcontact and specific weight-bearing socket designs when clinic visits, adjustments, and initial costs are considered in the short term. Further and more sophisticated economic analyses of transtibial prosthetic interventions are needed in order to determine value related to device provision and maintenance, outcomes, and health. Where further primary comparative economic analyses of TTA prosthetic care are needed, analyses of narrative economic reports relative to TTA care may be sufficient to warrant further review. Finally, guidance from the profession may be useful in devising a strategy for how to assure economic analyses are a routine element of prosthetic science in the future. ACKNOWLEDGMENTS Contents of this manuscript represent the opinions of the authors and not necessarily those of the U.S. Department of Defense, U.S. Department of the Army, U.S. Department of Veterans Affairs, or any academic or health care institution. Authors declare no conflicts of interest. This project was funded by the

American Orthotics and Prosthetics Association, the American Academy of Orthotists & Prosthetists, and the National Institutes of Health Scholars in Patient Oriented Research (SPOR) grant (1K30RR22270). REFERENCES 1.

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20. Hafner B. State of the science evidence report guidelines. Washington (DC): American Academy of Orthotists & Prosthetists; 2008. 21. Carey SL, Lura DJ, Highsmith MJ. Differences in myoelectric and body-powered upper-limb prostheses: systematic literature review. J Rehabil Res Dev. 2015;52(3):247-262. 22. Gordon R, Magee C, Frazer A, Evans C, McCosker K. An interim prosthesis program for lower limb amputees: comparison of public and private models of service. Prosthet Orthot Int. 2010;34(2):175-183. 23. MacKenzie EJ, Jones AS, Bosse MJ, Castillo RC, Pollak AN, Webb LX, Swiontkowski MF, Kellam JF, Smith DG, Sanders RW, Jones AL, Starr AJ, McAndrew MP, Patterson BM, Burgess AR. Health-care costs associated with amputation or reconstruction of a limb-threatening injury. J Bone Joint Surg Am. 2007;89A(8):1685-1692. 24. Gil J, Schiff AP, Pinzur MS. Cost comparison: limb salvage versus amputation in diabetic patients with charcot foot. Foot Ankle Int. 2013;34(8):1097-1099. 25. Datta D, Harris I, Heller B, Howitt J, Martin R. Gait, cost and time implications for changing from PTB to ICEX (R) sockets. Prosthet Orthot Int. 2004;28(2):115-120. 26. Selles RW, Janssens PJ, Jongenengel CD, Bussmann JB. A randomized controlled trial comparing functional outcome and cost efficiency of a total surface-bearing socket versus a conventional patellar tendon-bearing socket in transtibial amputees. Arch Phys Med Rehabil. 2005;86(1):154-161; quiz 180. 27. Normann E, Olsson A, Brodtkorb TH. Modular socket system versus traditionally laminated socket: a cost analysis. Prosthet Orthot Int. 2011;35(1):76-80. 28. Webster JB, Poorman CE, Cifu DX. Guest editorial: Department of Veterans Affairs amputations system of care: 5 years of accomplishments and outcomes. J Rehabil Res Dev. 2014;51(4):vii-xvi. 29. MacKenzie EJ, Bosse MJ, Pollak AN, Webb LX, Swiontkowski MF, Kellam JF, Smith DG, Sanders RW, Jones AL, Starr AJ, McAndrew MP, Patterson BM, Burgess AR, Castillo RC. Long-term per-

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lower-extremity trauma. J Bone Joint Surg Am. 2013;95(2):138-145. 33. Busse JW, Jacobs CL, Swiontkowski MF, Bosse MJ, Bhandari M, Evidence-Based Orthopaedic Trauma Working G. Complex limb salvage or early amputation for severe lower-limb injury: a meta-analysis of observational studies. J Orthop Trauma. 2007;21(1):70-76. 34. Kalbaugh CA, Taylor SM, Kalbaugh BA, Halliday M, Daniel G, Cass AL, Blackhurst DW, Cull DL, Langan EM 3rd, Carsten CG, York JW, Snyder BA, Youkey JR. Does obesity predict functional outcome in the dysvascular amputee? Am Surg. 2006;72(8):707-712; discussion 712-703. 35. Highsmith MJ, Kahle JT, Miro RM, Orendurff MS, Lewandowski AL, Orriola JJ, Sutton B, Ertl JP. Prosthetic Interventions for people with transtibial amputation: systematic review and meta-analysis of high-quality prospective literature and systematic reviews. J Rehabil Res Dev. 2016;53(2):157-84.

ISSN 1949-8241 • E-ISSN 1949-825X http://dx.doi.org/10.21300/18.2-3.2016.99 www.technologyandinnovation.org

GAIT TRAINING INTERVENTIONS FOR LOWER EXTREMITY AMPUTEES: A SYSTEMATIC LITERATURE REVIEW M. Jason Highsmith1-3, Casey R. Andrews1,4, Claire Millman1, Ashley Fuller1, Jason T. Kahle5,6, Tyler D. Klenow7, Katherine L. Lewis1, Rachel C. Bradley4, and John J. Orriola8 2

1 School of Physical Therapy & Rehabilitation Sciences, University of South Florida, Tampa, FL, USA Extremity Trauma & Amputation Center of Excellence (EACE), U.S. Department of Veterans Affairs, Tampa, FL, USA 3 319th Minimal Care Detachment, U.S. Army Reserves, Pinellas Park, FL, USA 4 Physical Medicine & Rehabilitation Service, James A. Haley Veterans’ Hospital, Tampa, FL, USA 5 OP Solutions, Tampa, FL, USA 6 Prosthetic Design + Research, Tampa, FL, USA 7 Prosthetics and Sensory Aids Service, James A. Haley Veterans’ Hospital, Tampa, FL, USA 8 Shimberg Health Sciences Library, University of South Florida, Tampa, FL, USA

Lower extremity (LE) amputation patients who use prostheses have gait asymmetries and altered limb loading and movement strategies when ambulating. Subsequent secondary conditions are believed to be associated with gait deviations and lead to long-term complications that impact function and quality of life as a result. The purpose of this study was to systematically review the literature to determine the strength of evidence supporting gait training interventions and to formulate evidence statements to guide practice and research related to therapeutic gait training for lower extremity amputees. A systematic review of three databases was conducted followed by evaluation of evidence and synthesis of empirical evidence statements (EES). Eighteen manuscripts were included in the review, which covered two areas of gait training interventions: 1) overground and 2) treadmill-based. Eight EESs were synthesized. Four addressed overground gait training, one covered treadmill training, and three statements addressed both forms of therapy. Due to the gait asymmetries, altered biomechanics, and related secondary consequences associated with LE amputation, gait training interventions are needed along with study of their efficacy. Overground training with verbal or other auditory, manual, and psychological awareness interventions was found to be effective at improving gait. Similarly, treadmill-based training was found to be effective: 1) as a supplement to overground training; 2) independently when augmented with visual feedback and/or body weight support; or 3) as part of a home exercise plan. Gait training approaches studied improved multiple areas of gait, including sagittal and coronal biomechanics, spatiotemporal measures, and distance walked. Key words: Amputee; Physical therapy; Prosthesis; Rehabilitation; Therapeutic exercise; Transfemoral; Transtibial; Treadmill

_____________________ Accepted July 1, 2016. Address correspondence to M. Jason Highsmith, Extremity Trauma & Amputation Center of Excellence (EACE), 8900 Grand Oak Circle (151R), Tampa, FL 33637-1022, USA. Tel: +1 (813) 558-3936; Fax: +1 (813) 558-3990; E-mail: michael.highsmith@va.gov

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INTRODUCTION In 2005, there were 1.6 million Americans with limb amputation(s) (1-3). Annually, 185,000 people experience upper or lower extremity (LE) limb loss for many reasons, including diabetic and vascular complications, trauma, and malignancy (1). Lower limb amputations represent â&#x2030;&#x2C6;86% of all limb amputations, and â&#x2030;&#x2C6;357,000 individuals experienced amputation at the transfemoral level (2). Ninety-five percent of transfemoral amputations (TFA) are attributable to vascular disease, and the remaining five percent are due to trauma, malignancy, and congenital limb deficiencies (2). Further, non-white males, specifically African Americans, Hispanics, and Native Americans, have increased risk of LE amputation (1,3). From 1979 to 1996, there were reportedly 70% more TFA patients and 46% more transtibial amputations (TTA) in males than females (4). Moreover, those older than 65 years of age experience 6.5 and 2.7 times the number of TFAs and TTAs, respectively, compared to those younger than 65 (4). By 2050, the number of Americans with amputations is expected to increase from 1.6 million to 3.6 million (1,3). An individual with LE amputation may face increased mortality and morbidity rates, decreased quality of life, and impaired function (5). Impaired function may include gait problems such as movement asymmetry (6). Amputee gait impairments have been objectively documented in multiple domains, including spatiotemporal and biomechanical parameters as well as in terms of bioenergetics (7-9). Gait parameters potentially altered in LE amputees include changes in magnitude and symmetry of forces and joint moments, event duration, and others (6). These deviations may contribute to decreased balance and increased metabolic costs as well as more insidious chronic issues, potentially including degenerative joint disease for example (6). TFA patients are impaired relative to non-amputees due to the lack of muscles controlling their knees. TFA patients depend on a prosthetic knee joint that, despite technological advancements and functional improvements, limits function to some degree (10). The TFA gait pattern is described as having shorter stance and longer swing phases on the prosthetic side. Additionally, their gait speed and ability to change speed are also

impaired (7,11). Gait patterns of LE amputees may also include lateral trunk flexion toward the prosthetic side secondary to weak hip abductors or decreased balance caused by socket instability and discomfort. Moreover, the TFA gait pattern may also include vaulting to assure prosthetic limb clearance during swing phase. The abnormalities of lateral trunk flexion and forces from vaulting may be contributing factors in the development of back pain, osteoarthritis, or other chronic overuse conditions (5,6,12,13). As previously mentioned, LE amputee gait impairments also include significantly increased ambulatory energy requirements, which may impact overall activity and participation (8,12,14). Interventions to mitigate gait deviations and improve quality of life for LE amputees include prescribing the proper componentry and participating in physical therapy for gait training. For example, to manage TFA patients with gait deviations, an appropriate prosthesis needs to be prescribed. This includes the choice of socket type (15); knee type, such as non-microprocessor or microprocessor knee systems (MPK); and foot type to maximally benefit user lifestyle, budget, function, and quality of life. If patients frequently ascend and descend stairs in their homes and at work for instance, then perhaps an MPK that facilitates stair ambulation should be considered (16-18). There are numerous factors to consider when formulating the prosthetic prescription, including patient age, medical history, activity level, goals (e.g., functional, occupational, recreational, etc.), amputation length and level, strength, environments (e.g. home, work, recreational, etc.), aesthetic preference, and more. In addition to proper componentry, participation in physical therapy, including therapeutic exercise, neuromuscular re-education, and gait training, is beneficial for LE amputees to improve function and quality of life. Specifically, gait training reportedly improves spatiotemporal parameters, joint kinematics, and bioenergetic efficiency during gait for LE amputees (16,17,19). The purpose of this study was to systematically review the literature to determine the strength of evidence supporting gait training interventions and to formulate evidence statements to guide practice and research related to therapeutic gait training for LE amputees.

REVIEW OF AMPUTEE GAIT TRAINING

METHODS A multidisciplinary review team planned methodology in accordance with that used previously in prosthetic research (8) in addition to standards established by the Prisma Statement (20,21). Reviewers had graduate education or professional healthcare training in physical therapy or prosthetics. The team met on three occasions and outlined search methodology to include multiple databases and key search terms (primary and secondary) that would assure identification of available evidence to address gait training interventions for those with LE amputation. Search methodology was based upon a broad view of LE amputations with regard to gait training intervention. Preliminary test searches were conducted and outcomes previewed at pre-search meetings to assure adequate inclusion of key articles in terms of both quantity and quality within the topic of interest. The search statement was planned to be sensitive to include patients with LE amputation and gait training interventions. The search term sets sought to combine all levels of LE amputation with all forms of clinical gait training. Complete search term sets are listed in Table 1. On December 15, 2014, the following databases were searched: 1.) MEDLINE (Pubmed), 2.) the Cumulative Index to Nursing and Allied Health Literature (CINAHL)(Ovid), and 3.) Web of Science. The following date limits were implemented as part of the database search parameters: 2000 Jan 1 to 2014 Dec 14. One month after the initial search, the search was repeated by a pair of separate information scientists. Article Screening Resulting references were exported to EndNote (vX6, Thompson, CA, USA) reference management software. Duplicate references were eliminated. Remaining articles were preliminarily sorted by article type. Exclusion criteria were selected to eliminate manuscripts that did not include gait training for adults with LE amputation who used prostheses. Foreign language articles were eliminated relative to prohibitive costs associated with translation. Manuscripts were screened for exclusion using the

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following initial criteria within EndNote: 1. Foreign language (i.e., non-English language) 2. Non-human subject (i.e., materials science, finite element studies) 3. Pediatric studies Following the EndNote search using the aforementioned exclusion criteria, remaining intervention articles were divided up equally between reviewers. Each article was assigned a primary and secondary reviewer. The reviewers independently screened references according to inclusion/exclusion criteria and classified them as either: 1) pertinent, 2) not pertinent or 3) uncertain pertinence. Full-text articles were reviewed for all citations classified as pertinent or uncertain pertinence. Disagreement regarding citations of uncertain pertinence were resolved by discussion at weekly follow-up meetings with the two other reviewers. Review of full-text articles and associated discussion led to group consensus and ultimate inclusion/exclusion. Exclusion criteria applied during the EndNote search were applied at this stage of screening. Inclusion criteria applied were: 1. Peer-reviewed manuscript 2. Gait training intervention for LE Amputees 3. Published within the aforementioned timeline Quality Assessment Evaluation of Internal and External Validity Methodological quality of included publications was independently assessed by two reviewers according to the American Academy of Orthotists and Prosthetists (AAOP) State-of-the-Science Evidence Report Guidelines protocol (22). The AAOP Study Design Classification Scale was used to describe the design type of included studies (22). The State of the Science Conference (SSC) Quality Assessment Form was used to rate the methodological quality of studies classified as experimental (E1 to E5) or observational (O1 to O6) (22). The form identifies 18 potential threats to internal validity, with the first four threats not applicable for study classifications E3 to E5 and the first five threats not applicable for classifications

MEDLINE Gait[mesh] OR gait[tiab] OR gait[ot] OR stride[tiab] OR stride[ot] OR treadmill* OR walk*[tiab] OR running OR step[tiab]OR steps[tiab] OR stair* OR ramp[tiab] OR ambulat* OR balance[tiab] OR balance[ot] OR climb* OR slope OR "functional training"

((((("Lower Extremity"[Mesh] OR lower extrem*[TIAB] OR lower extrem*[OT] OR lower limb*[TIAB] OR lower limb*[OT] OR leg[TIAB] OR leg[OT] OR legs[TIAB] OR legs[OT] OR hip[TIAB] OR hip[OT] OR hips[TIAB] OR hips[OT] OR thigh*[TIAB] OR thigh*[OT] OR foot[TIAB] OR foot[OT] OR feet[TIAB] OR feet[OT] OR "Knee Joint"[Mesh] OR knee[TIAB] OR knee[OT] OR knees[TIAB] OR knees[OT] OR "Ankle Joint"[Mesh] OR ankle*[TIAB] OR ankle*[OT] OR "Femur"[Mesh] OR femur*[TIAB] OR femur*[OT] OR transfemoral[TIAB] OR transfemoral[OT] OR trans-femoral[TIAB] OR transfemoral[OT] OR "Tibia"[Mesh] OR tibia*[TIAB] OR tibia*[OT] OR transtibial[TIAB] OR transtibial[OT] OR trans-tibial[TIAB] OR trans-tibial[OT] OR transpelvic[TIAB] OR transpelvic[OT] OR transpelvic[TIAB] OR trans-pelvic[OT] OR syme's[TIAB] OR syme's[OT] OR symes[TIAB] OR symes[OT]))) AND (("Amputation"[Mesh] OR amput*[TIAB] OR amput*[OT] OR disarticulat*[TIAB] OR disarticulat*[OT] OR hemipelvectom*[TIAB] OR hemipelvectom*[OT] OR "Amputees"[Mesh] OR "Amputation Stumps"[Mesh] OR "Artificial Limbs"[Mesh] OR artificial limb*[TIAB] OR artificial limb*[OT] OR "Amputation, Traumatic"[Mesh] OR "Prostheses and Implants"[Mesh:noexp] OR residual limb*[TIAB] OR residual limb*[OT] OR limb loss*[TIAB] OR limb loss*[OT] OR prosthe*[TIAB] OR prosthe*[OT] OR stump*[TIAB] OR stump*[OT]))))

Database General Search Term Set

Amput* String

Table Search Sets and Databases Table 1.1. Search TermTerm Sets and Databases

((MH "Lower Extremity+") OR (TI lower extrem* OR AB lower extrem*) OR (TI lower limb* OR AB lower limb*) OR (TI leg OR AB leg) OR (TI legs OR AB legs) OR (TI hip OR AB hip) OR (TI hips OR AB hips) OR (TI foot OR AB foot) OR (TI feet OR AB feet) OR (MH "Knee Joint+") OR (TI knee OR AB knee) OR (TI knees OR AB knees) OR (MH "Ankle Joint") OR (TI ankle* OR AB ankle*) OR (MH "Femur+") OR (TI femur* OR AB femur*) OR (TI transfemoral OR AB transfemoral) OR (TI transfemoral OR AB trans-femoral) OR (MH "Tibia") OR (TI tibia* OR AB tibia*) OR (TI transtibial OR AB transtibial) OR (TI trans-tibial OR AB trans-tibial) OR (TI transpelvic OR AB transpelvic) OR (TI transpelvic OR AB trans-pelvic) OR (TI syme's OR AB syme's) OR (TI symes OR AB symes) OR (TI thigh* OR AB thigh*)) AND ((MH "Amputation+") OR (TI amput* OR AB amput*) OR (TI disarticulat* OR AB disarticulat*) OR (TI hemipelvectom* OR AB hemipelvectom*) OR (MH "Amputees") OR (MH "Amputation, Traumatic") OR (MH "Limb Prosthesis") OR (TI prosthe* OR AB prosthe*) OR (TI artificial limb* OR AB artificial limb*) OR (TI limb loss OR AB limb loss) OR (TI residual limb* OR AB residual limb*) OR (TI stump* OR AB stump*) OR (MH "Prostheses and Implants"))

CINAHL (MH "Walking+") OR gait OR step OR walk OR running OR stair* OR (MH "Stair Climbing") OR ramp OR ambulat* OR balance OR climb* OR slope OR (MH "Functional Training")

Web of Science Gait OR stride OR treadmill* OR walk* OR running OR step OR steps OR stair*OR ramp OR ambulat* OR balance OR climb* OR slope OR "functional training" (Lower AND (extremit* OR limb*)) OR leg OR legs OR hip OR hips OR foot OR feet OR thigh* OR knee OR knees OR ankle* OR femur OR transfemoral OR trans-femoral OR tibia* OR transtibial OR trans-tibial OR transpelvic OR transpelvic OR syme's OR symes AND amput* OR disarticulat* OR hemipelvectom* OR artificial Limb* OR residual limb* OR prosthe* OR stump*

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O1 to O6. Threats to validity were evaluated and tabulated. The internal and external validity of each study was then subjectively rated as “high,” “moderate,” or “low” based on the quantity and importance of threats present. For internal validity, 0 to 3 threats was rated “high,” 4 to 6 threats as “moderate,” and 7 to 13 or 14 threats as “low.” For external validity, the form identifies eight threats. For this study, 0 to 2 threats to external validity was rated “high,” 3 to 5 threats as “moderate,” and 6 to 8 threats as “low.” Each study was then given an overall quality of evidence of “high,” “moderate,” or “low” as outlined by the AAOP State-of-the-Science Evidence Report Guidelines (22). Following the quality assessment of each study, key data (e.g., demographic, anthropometric, outcomes, etc.) were extracted to assist in describing the studied subjects, interventions, and their relative effects. Overall ratings from the AAOP State-of-the-Science Evidence Report Guidelines were used to assign the level of confidence for the developed empirical evidence statements (EES) described in the following section.

RESULTS

Empirical Evidence Statements Based on results from the included publications, EESs were developed that described study findings related to gait training interventions for LE amputees. Reviewers rated the level of confidence of each EES as “high,” “moderate,” “low,” or “insufficient” based on the number of publications contributing to the statement, the methodological quality of those studies, and whether the contributing findings were confirmatory or conflicting as similarly outlined by others (23). These levels of evidence were somewhat adjustable in accordance with study quality, effect size, and other factors.

Funding Eight of the 18 included studies (40%) were unfunded. Local government supported four (20%) of the studies. Industry and the U.S. National Institutes of Health each funded 10% of this research. The remaining studies were sponsored by a university, a hospital system, a non-profit organization, or the U.S. Department of Defense. Bias risk from a research funding perspective was considered low given that

Analysis Data pooling (i.e., meta-analyses) was conducted when homogeneous data were available. When data pooling was possible, mean difference with 95% confidence interval was calculated and significance determined a priori to be p ≤ 0.05 (24). Sorting by Topic Following procedures for screening and eligibility determination, full-text articles were sorted by reviewers into sub-topical areas.

Literature Search, Sub-topics, and Study Designs The search yielded 11,118 total manuscripts (Figure 1). Following screening, 11,100 manuscripts were eliminated, leaving 18 articles that met eligibility criteria. The 18 remaining articles, published from 2001 to 2014, were divided into two topical areas: 1. Overground Training (n = 13) (6,11,16,17,19,2532) 2. Treadmill Training (n = 5) (12,33-36) The two most represented journals were Prosthetics and Orthotics International (six publications) and the Journal of Prosthetics and Orthotics (three publications). All other journals had a single publication, and the group included a dissertation. In terms of study design (22), the case study was most represented (n = 5). There were 11 experimental studies and two expert opinion manuscripts (Table 2). None of the included studies had an economic analytic component.

2. Distribution of Included Studies Study Design TableTable 2. Distribution of Included Studies by Studyby Design Study Design Meta-Analysis (S1) Systematic Review (S2) Randomized Control Trial (E1) Controlled Trial (E2) Interrupted Time Series Trial (E3) Single Subject Trial (E4) Controlled Before and After Trial (E5) Cohort Study (O1) Case-Control Study (O2) Cross Sectional Study (O3) Qualitative Study (O4) Case Series (O5) Case Study (O6) Group Consensus (X1) Expert Opinion (X2) Total

Number of Publications 0 0 3 1 3 0 4 0 0 0 0 0 5 0 2 18

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Figure 1. Study flow diagram.

only 10% of the research was funded by industry, with the majority being either unfunded or government sponsored. Study Demographics, Interventions, and Outcome Measures Conclusions from this systematic review are drawn from 229 subjects (Table 3). Some subjects represent single projects in multiple manuscripts (11,27,28). A total of 145 persons with lower limb amputation served as experimental subjects. Their mean (interquartile range (IQR), range) age, height, and mass were: 48.2 years (29.5, 31 to 85), 1.7 m (0.04, 1.7 to 1.8), and 80.6 kg (10.3, 67.4 to 99.3). There were 66 amputees who served as control subjects. Their mean (IQR, range) age, height, and body mass were: 48.7 years (27.8, 28 to 66), 1.7 m (0.03, 1.7 to 1.76), and 73.2 kg (5.4, 68 to 82). Eighteen lower limb amputee subjects served as their own controls in cross-over design studies. Finally, an additional 18 non-amputees served as controls with a mean age of 35.8 years, height of 1.7 m, and mass of 72.5 kg. The etiology for

amputation was comparable between traumatic and dysvascular cases and included some malignancy cases. In terms of level of amputation, 57% of the sample had TFA level amputation, 21% had TTA, 21% were mixed lower extremity samples, and 1% were bilaterally involved. Time since amputation was 5.9 years (9.2, 0.3 to 25.5). The median (mean, IQR, range) sample size was n = 9 (14, 20, 1 to 50). Outcome measures assessed included symmetry of external work, spatiotemporal measures, biomechanical and bioenergetic outcomes, level of assist with functional tasks (i.e., sit to stand, stair climbing ability), walking test performance, ambulatory weight bearing, clinical performance measures (i.e., timed up and go test), perceptive measures (i.e., Activities-specific Balance Confidence Scale, general self-efficacy scale), and performance against patient goals. Due to the varied levels of amputation, methods of data collection, training, and other factors, aggregation of data and meta-analysis were not possible.

REVIEW OF AMPUTEE GAIT TRAINING Internal and External Validity Threats to internal validity included lack of intervention blinding, inadequate reporting of eligibility criteria, and failure to include statistical analyses (i.e., expert opinions, editorials) (Table 4). Ten studies had low, six had moderate, and two had high internal validity. Conversely, sixteen studies had high and two had moderate external validity according to the AAOP rating tool (Table 5). Evidence Statements Eight EESs were synthesized from the results within the two topical areas previously identified (Table 6). One of the statements was supported by a single study, resulting in an insufficient level of confidence. Four statements had two to four studies supporting their synthesis, resulting in low confidence. One statement was supported by four studies, yielding moderate confidence, and two statements were supported by sufficient evidence to provide high confidence. Four statements address overground gait training exclusively, one statement addresses treadmill gait training exclusively, and three statements address both overground and treadmill gait training. DISCUSSION The purpose of this study was to systematically review the literature to determine the current strength of evidence regarding different gait training methods for lower limb amputees and to formulate evidence statements to guide current practice and future research related to gait training for persons with lower limb amputation. This search revealed limited literature on the subject, which is consistent with a recently published systematic review that identified eight studies investigating the effectiveness of exercise programs to improve gait performance in lower limb amputees (37). The difference in the number of studies may be due to the other review (37) limiting included articles to one-group cohort, pre- to post-test studies, two-group case-control trials, and control trials, whereas this review included all publications, including expert opinions. Though publications are limited, our literature review supported our hypothesis that multiple gait training modalities are effective to improve overall gait quality in lower limb amputees. Generally, gait training was described

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in two major categories: traditional overground and treadmill-based training. Beyond this, the evidence supports general themes with regard to benefits of therapeutic gait training. Funding, Subjects, and Outcomes A high number of these studies were unfunded. This is not surprising, as it is less common for commercial parties to have an interest in sponsoring the development or study of new gait therapies. This is likely because gait training therapies commonly represent services rather than products. Therefore, packaging gait training services for a profit is difficult. The highest amount of funding in this review was from local government, which may likely be connected to academia by way of investigatorsâ&#x20AC;&#x2122; academic affiliations. This is especially surprising given that federal sponsors, such as the U.S. National Institutes of Health, have a mission to apply knowledge to enhance health, lengthen life, and reduce disability. This body of work demonstrates that gait training reduces disability. Clearly, more federal funding is needed to further enhance this body of gait training research in lower limb amputees. Subjects in the included studies tended to be community ambulators of approximately 48 years of age who had lost their limbs to either trauma or vascular disease. Additionally, the cohort had a higher presence of transfemoral limb loss than other levels. These characteristics are a bit different than commonly cited epidemiologic studies, which describe most U.S. amputees as considerably older than 40 years and having lost their limbs to vascular disease, most likely at the transtibial level (1,38). These differences are not surprising given that transfemoral amputees may have greater impairment than more distal levels of amputation thus justifying heightened interest in gait training. Further, given that most subjects were community ambulators, it is feasible that the age and etiology would shift lower and toward trauma, respectively. In terms of outcome measures, spatiotemporal, biomechanical, and bioenergetic measures are common and logical assessments to determine objectively if gait is improving following therapy. Problematically, these tend to be more research laboratory tools and less clinically oriented. Therefore, inclusion of obser-

Cole et al. (2003)

Faucher et al. (2005) Highsmith et al. (2012)

Yigiter et al. (2002) Highsmith et al. (2014)

12 x 30 min sessions; 3x/wk

PNF; Traditional training Genium knee stair ascent/ramp training

In-shoe audio feedback device Typical gait training pgm w/ verbal tactile cues, varying surfaces WB & amb on post-op day 1 Reciprocal stair descent training for stance yielding knees Grps: Impairment vs. Task Oriented

Psychological awareness training & PT

TM training maximizing walk time improved function years post-amputation regardless of training mode. Anti-gravity TM useful for TTA rehab. Combined psychological & PT improved TFA gait. Training improved gait speed, pattern, symmetry. Intact knee flex/loading differed from reference side. Pts w/ >2 y prosthetic use improved gait (emphasized prox. muscle strength & stability; balance & coord. LEAFS improved trunk sway & gait symmetry. Gait training improves functional independence & community integration. Trauma teams should remain aware of this option. Training may improve stumble recovery, STS & loading response. Both strategies equally improve TTA mobility. Function improved in 10 d protocol. PNF improved LEA balance, weight acceptance & gait. Ramp/stair training may improve overall function & safety.

12 x 30 min sessions x 3 wks

Visual feedback via CAREN VR system & verbal PT feedback In-shoe BW measurement w/ audio feedback; PT feedback for FWB BWSTT (30% BWS), gradually ↓ by 5% intervals; TM w/out support Anti-gravity TM training

30 min/d x10 sessions NR

10 d

10 d NR

6 x 30 min sessions x 3 wks 12 sessions

1x/wk x 10 mos (range 7-14)

20-40 min; 3x/wk x 2 wks

4 x 30 min sessions x 14 d

Conclusions SEW improved in K2 amputees trained to use K3 prosthetic feet. Gait adaptation occurred w/ functional prosthesis. Unclear benefit at d/c after using either EWA. Partial BWSTT improved speed & gait pattern. Home TM training improved TFA gait. Consider use after initial rehab. 12 sessions w/ real-time feedback improved TFA gait. Clinically important changes in biomechanics & VO2. Pts improved WB thru PL w/ auditory feedback device.

Treatment Duration 1-4 h x 10-14 d accommodation period/ foot Individual need; Rehab duration 78.1 ± 25.3 (40–126 ) d 2x/wk x 8 sessions x 4.5 wks 3x/wk x 8 wks

Treatment (Independent Variables) SACH, SAFE, Talux, Proprio; Foot type specific training Pneumatic Post-Amputation Aid; Amputee Mobility Aide 50-60% BWSTT at 1.0-1.6mph 30 min home-based TM training

selected walking speed. STS: sit to stand. TTA: transtibial amputee.

*High overall qualityscore. score. other studies were Moderate quality.‡Denotes a treadmill training study. other studies used overground training. BWSTT: *High overall quality AllAll other studies were Moderate quality.‡Denotes a treadmill training study. All All other studies used overground gait gait training. BWSTT: body weight supported body weight supported treadmill training. BWS: bodyEWA: weight. NR:walk not aid. reported. early bearing. walk aid.LEA: FWB: full weight bearing. LEA: treadmill training. BWS: body weight support. BW: body body weight weight.support. NR: not BW: reported. early FWB:EWA: full weight lower extremity amputee. MPH: miles/hour. TM: lower extremity miles/hour. TM: environment. treadmill. CAREN: computer assisted rehabilitation environment. WB: weight bearing. physical therapy. Amb: Grp: group. PNF: treadmill. CAREN:amputee. computerMPH: assisted rehabilitation WB: weight bearing. PT: physical therapy. Amb: ambulation. LEAFs: lower PT: extremity feedback system. ambulation. LEAFs: lower extremity feedback system. Grp: group. PNF: proprioceptive neuromuscular facilitation. SEW: symmetry of external work. SSWS: selfproprioceptive neuromuscular facilitation. SEW: symmetry of external work. SSWS: self-selected walking speed. STS: sit to stand. TTA: transtibial amputee.

Hyland et al. (2009)*

Yang et al. (2012)

Isakov et al. (2006)

Sjodahl et al. (2003)

Darter et al. (2011)‡

Darter et al. (2013)‡

Sjodahl et al. (2002)

Black et al. (2006)‡

1 9

Barnett et al. (2009)

Agrawal et al. (2013)

Lamberg et al. (2014)*‡ Mikami et al. (2014)‡ Sjodahl et al. (2001)

Author (Yr)

Table 3. Extracted StudyStudy Data Data Table 3. Extracted

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8 5 4 4 7 7 9 1 5 2 7 11 11 3 4 2 6 1

Overall assessment

Total # threats

Free from conflicts of interest

Statistical power adequate

Statistical significance

Effect size reported

Proper statistical analysis

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Outcome measures reliable

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Attrition equal

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Attrition explained & <20%

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Accommodation & washout

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Addresses fatigue & learning

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Exclusion criteria appropriate

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Inclusion criteria appropriate

Interventions blinded

Comparison Group appropriate

Similar group treatment

Groups comparable at baseline

E5 E5 E1 E5 O6 O6 O6 E1 E3 E1 O6 E5 X2 E3 E3 E2 O6 X2

Randomization

Author Sjodahl et al. Sjodahl et al. Yigiter et al. Sjodahl et al. Cole et al. Faucher et al. Black et al. Isakov et al. Barnett et al. Hyland et al. Darter et al. Yang et al. Highsmith et al. Agrawal et al. Darter et al. Lamberg et al. Mikami et al. Highsmith et al.

Control group used

Year 2001 2002 2002 2003 2003 2005 2006 2006 2009 2009 2011 2012 2012 2013 2013 2014 2014 2014

Study Classification

Table Table4. 4.Internal Internal Validity Validity Assessment AssessmentofofIncluded IncludedManuscripts Manuscripts

Low Mod Mod Mod Low Low Low Low Mod High Low Low Low Mod Mod High Low Low

Boxesthat thatare areblacked blackedout outare arenot notapplicable applicablefor forthe thespecific specificstudy studydesign design and thus not count threats validity. Boxes and thus dodo not count asas threats to to validity. A dot in the box A dot in the indicates the criteria identified by reviewers whereas a blank box represents a criteria not indicates thebox criteria was identified by was reviewers whereas a blank box represents a criteria not identified. identified.

vational gait scales and perceptive and functional measures may facilitate improved translation into the clinical setting. Overground Gait Training Of the articles included in this review, 13 included some form of overground gait training. Multiple therapeutic gait interventions, including in-shoe auditory feedback (6,26), verbal and tactile cues (16,17,25,29,31), PNF (19), component specific training (16,17,25), early weight-bearing (30), early walking aids (32), part or whole task training (31), and combined PT and psychological awareness training (11,27,28), were identified in our literature review. Sufficient evidence provided moderate confidence

that gait training focused on practicing components of gait, while utilizing verbal and manual cues, prior to initiating the task as a whole was an effective strategy to improve overground ambulation and stair negotiation. Superiority of part task versus whole task training has long been debated (39-41). Here, it seems there is merit in both approaches. For instance, Highsmith et al. advocated one scenario where breaking down the subparts of a complex skill (i.e., stair ascent) enabled whole task mastery (17). Conversely, adding treadmill training as part of a home exercise plan incorporates whole task training that has also proved effective (33). This evidence statement is based on one randomized control trial (31), one case study (29), and two expert opinions (16,17).

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HIGHSMITH ET AL. Table 5. External Validity Assessment of Included Manuscripts

2014



E3 E3 E2 O6

   



     

         

          

    

   

          

2 0 0 0 3 2 2 1 2 0 2 2



   

0 0 0 1

Conclusion placed in literary context

   

Findings clinically significant

   

Intervention adequately described

Outcomes valid for the study

    

         

Outcomes adequately described

Sample representative

     

Number of Threats

2013 2013 2014 2014

E5 E5 E1 E5 O6 O6 O6 E1 E3 E1 O6 E5

Findings support conclusions

2012

Sample adequately described

Year 2001 2002 2002 2003 2003 2005 2006 2006 2009 2009 2011 2012

Study Classification

Table 5. External Validity Assessment of Included Manuscripts

    



All manuscripts had high external validity except those noted with (*) which had moderate external All manuscripts had high external validity except those noted with (*) which had moderate external validity. The three manuscripts by Sjodahl et al. represent a single project and are thus counted as a validity. The three manuscripts by Sjodahl et al. represent a single project and are thus counted as a single “manuscript” for the purposes of this review and analysis. A dot in the box indicates the criteria single “manuscript” forwhereas the purposes ofrepresents this review and not analysis. A dot in the box indicates the criteria was was identified by reviewers a blank box a criteria identified.

identified by reviewers whereas a blank box represents a criteria not identified.

Treadmill-Based Gait Training Improved bioenergetic efficiency was the most prevalent finding for treadmill-based gait training that differed from traditional overground gait training (12,33,36). Lower limb amputees demonstrate a less efficient gait pattern as observed by higher O2 cost, which becomes more pronounced with higher level of amputation or bilateral involvement (42). This can lead to other gait implications, such as reduced

self-selected walking speed, reliance on an assistive device, or gait deviations, as the amputee attempts to reduce energy expenditure while ambulating, therefore emphasizing the importance of improving bioenergetic efficiency for this population. Our findings support a low level of evidence that demonstrates improved bioenergetic efficiency was observed following a supervised treadmill training program that included a structured home exercise program,

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Table Evidence Statements, Levels of Evidence, andConfidence Overall Confidence Table 6.6.Evidence Statements, Levels of Evidence and Overall Evidence Statement 1.†

2.†

3.†‡

4.‡

5.†‡

6.†

7.†

8.†‡

Level of Evidence

Integration of psychological awareness training with a typical gait training program is effective at improving frontal and sagittal plane joint kinematics in unilateral transfemoral amputees.

Moderate (x2*)11,28

Integration of an in-shoe, auditory feedback device into a typical gait training program is effective at improving involved-side loading in lower limb amputees. Therapeutic overground or treadmill based gait training under skilled supervision is effective to improve spatiotemporal gait parameters in transfemoral and transtibial amputees.

Low (x2)6,26

Following lower extremity amputation, bioenergetic efficiency of gait may be improved with treadmill based gait training augmented either by reduced loading, real-time visual feedback, or a structured home-based program. Lower limb amputee gait training protocols including typical gait and prosthetic training procedures with verbal and tactile cues, ambulation on post-op day 1, and treadmill training with body weight unloading are effective to increase ambulatory distance with reduced assistance. Gait training utilizing verbal and manual cues to practice gait components prior to whole task initiation is an effective strategy to improve overground ambulation and stair negotiation in lower limb amputees. Combining prosthetic component specific gait training with appropriate prosthetic foot prescription can promote higher external work symmetry in limited and unlimited community ambulating unilateral transtibial amputees.

Low (x2), Moderate (x1)12,33,36

Therapeutic gait training programs under skilled supervision, that maximize time spent performing ambulatory activities beyond current functional daily walking, are safe and effective at improving walking function in lower limb amputees.

Low (x10), Moderate (x6), High (x2)6,11,12,16,17,19,26-37

Low

Low Low (x5), Moderate (x3), High (x2)6,11,12,26,27,31-35 High

Low

Low (x4)29,30,34,36 Low

Low (x3), High (X1)16,17,29,31 Moderate Moderate (x1)37 Insufficient

†Denotes overground gait training. ‡ Denotes treadmill gait training. *Same study. overground gait training. ‡ Denotes treadmill gait training. *Same study.

†Denotes

Overall Confidence

High

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anti-gravity training system, or a virtual reality system that provides real-time visual feedback. Two out of the three articles to support this statement were case studies (12,36), making current evidence to support this statement low. Also, the finding that treadmill training is the superior gait training modality to improve bioenergetic efficiency is misleading, as none of the studies that included traditional overground gait training methods measured energy consumption or expenditure as a primary outcome measure. This is most likely explained by the convenience of measuring O2 consumption and gas exchange while participants are relatively fixed on a treadmill versus collecting this data while they ambulate over ground. Even so, it is unable to be determined at this time if improved bioenergetics can also be achieved with overground training methods or if this finding is limited to treadmill training. Therefore, future research is recommended. Lamberg et al. compared the effects of bodyweight support treadmill training versus treadmill training without body-weight support (35). They found that treadmill training with and without bodyweight support is effective to improve six-minute walk test distance and timed up and go test time; increase treadmill speed; and improve spatiotemporal parameters for lower limb amputees with no significant differences found between groups. This study reflects similar findings in patients post-stroke as published in a recent Cochrane review, which concluded that treadmill training with or without body weight support is effective to improve walking speed and endurance (43). These findings have also been demonstrated in patients with Parkinson’s disease (44), traumatic brain injury (45), and in some patients following orthopedic surgery (46). All of these studies demonstrated carryover to overground training. Beyond providing activity repetitions, the effectiveness of treadmill training may be partially attributed to the patients’ ability to practice walking in a safe environment, especially when utilizing a harness system with or without body-weight support to minimize risk for falls, which improves the patients’ confidence when attempting to ambulate at increased speeds.

General Statements Due to the high variability of gait training methods identified in the literature, a clear pattern of the most beneficial method of gait training was not able to be identified. Conversely, the literature revealed a high level of evidence to support that any of the therapeutic gait training programs administered under skilled supervision that increases time spent performing ambulatory activities beyond the patient’s current functional daily ambulation was effective at improving walking function in lower limb amputees (6,11,12,16,17,19,25-36). Most studies assessed spatiotemporal, joint kinematics, bioenergetic efficiency, outcome measures, level of assistance, or a combination of these to demonstrate improvements in gait. Subsequently, evidence statements were able to be formed. It is also important to note that adverse or safety issues were not reported in connection with the gait training methods studied. Spatiotemporal Gait Parameters Current literature supports a high level of evidence that therapeutic gait training methods, including early ambulation with a walking aid (32); in-shoe auditory feedback devices (6,26); psychological awareness training (11); or treadmill training with or without body-weight support (34,35), or as a part of a structured home exercise plan, are effective to reduce spatiotemporal gait deviations. Lower limb amputees demonstrate impaired spatiotemporal gait parameters, including decreased prosthetic limb stance phase duration, decreased intact limb step length, decreased cadence, and decreased self-selected walking speed compared to a healthy population (7,47). Changes in spatiotemporal gait parameters can lead to reduced energy efficiency (42) and increased joint stress of intact limb and trunk. Ephraim et al. reported that approximately 63% and 49% of amputees experienced back pain or pain of their intact limb, respectively (48). Also, reduced self-selected walking can make participation in functional and recreational activities difficult and lead to reduced safety when ambulating in the community, such as being able to cross the street in an appropriate amount of time (37). This reinforces the importance of reducing spatiotemporal gait impairments to improve functional mobility,

REVIEW OF AMPUTEE GAIT TRAINING increase safety, and increase amputeesâ&#x20AC;&#x2122; ability to participate in their typical functional and recreational activities. Joint Kinematics and Loading Two studies were identified, resulting in low level confidence to support improved frontal and sagittal plane joint kinematics when psychological awareness training was integrated into a typical gait training program (11,28). Two additional studies supported use of an auditory feedback device to improve involved side loading (6,26). In patients with lower limb amputation, joint loading in gait and in functional activities is known to be altered and possibly connected with long term secondary consequences (13,49). Therefore, gait training interventions to mitigate these sequelae are needed. Limitations Aggregation of data and meta-analyses were not possible due to the high variability in interventions administered and studied, levels of amputation, etiologies, and selection of outcome measures. Numerous text resources provide gait training intervention concepts; however, they are not peer-reviewed and therefore were not included in this review. CONCLUSION Due to the gait asymmetries, altered biomechanics, and related secondary consequences associated with lower extremity amputation, gait training interventions are needed. Eight evidence statements were synthesized over two general areas of gait training therapy: overground and treadmill training. Overground training with verbal or other auditory, manual, and psychological awareness interventions was found to be effective at improving gait. Similarly, treadmill-based training was found to be effective: 1) as a supplement to overground training; 2) independently when augmented with visual feedback and/or body weight support; or 3) as one part of a home exercise plan. Gait training approaches studied improved multiple areas of gait, including sagittal and coronal biomechanics, spatiotemporal measures, and distance walked. No adverse or safety events were reported in connection with the studied interventions.

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ACKNOWLEDGMENTS Contents of this manuscript represent the opinions of the authors and not necessarily those of the U.S. Department of Defense, U.S. Department of the Army, U.S. Department of Veterans Affairs, or any academic or health care institution. Authors declare no conflicts of interest. This project was partially funded by the National Institutes of Health Scholars in Patient Oriented Research (SPOR) grant (1K30RR22270). REFERENCES 1. Zeigler-Graham K, Mackenzie EJ, Ephraim PL, Travison TG, Brookmeyer R. Estimating the prevalence of limb loss in the United States: 2005 to 2050. Arch Phys Med Rehabil. 2008;89:422-9. 2. Dillingham TR, Pezzin LE, Mackenzie EJ. Limb amputation and limb deficiency: epidemiology and recent trends in the United States. South Med J. 2002;95:875-83. 3. Varma P, Stineman MG, Dillingham TR. Epidemiology of limb loss. Phys Med Rehabil Clin N Am. 2014;25:1-8. 4. Feinglass J, Brown JL, LoSasso A. Rates of lower-extremity amputation and arterial reconstruction in the United States, 1979 to 1996. Am J Public Health. 1999;89:1222-7. 5. Sauter CN, Pezzin LE, Dillingham TR. Functional outcomes of persons who underwent dysvascular lower extremity amputations. Am J Phys Med Rehabil. 2013;92:287-96. 6. Yang L, Dyer PS, Carson RJ, Webster JB, Bo Foreman K, Bamberg SJM. Utilization of a lower extremity ambulatory feedback system to reduce gait asymmetry in transtibial amputation gait. Gait Posture. 2012;36:631-4. 7. Highsmith MJ, Schulz BW, Hart-Hughes S, Latlief GA, Phillips SL. Differences in the spatiotemporal parameters of transtibial and transfemoral amputee gait. J Prosthet Orthot. 2010;22:26-30. 8. Highsmith MJ, Kahle JT, Bongiorni DR, Sutton BS, Groer S, Kaufman KR. Safety, energy efficiency, and cost efficacy of the C-Leg for transfemoral amputees: a review of the literature. Prosthet Orthot Int. 2010;34:362-77.

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HIGHSMITH ET AL. Lura DJ, Wernke MM, Carey SL, Kahle JT, Miro RM, Highsmith MJ. Differences in knee flexion between the Genium and C-Leg microprocessor knees while walking on level ground and ramps. Clin Biomech (Bristol, Avon). 2015;30:175-81. Highsmith MJ, Kahle JT, Lura DJ, Dubey RV, Carey SL, Quillen WS, Mengelkoch, LJ. Short and mid-distance walking and posturography with a novel microprocessor knee. Technol Innov. 2014;15:359-68. Sjodahl C, Jarnlo GB, Soderberg B, Persson BM. Kinematic and kinetic gait analysis in the sagittal plane of transfemoral amputees before and after special gait re-education. Prosthet Orthot Int. 2002;26:101-12. Darter BJ, Wilken JM. Gait training with virtual reality-based real-time feedback: improving gait performance following transfemoral amputation. Phys Ther. 2011;91:1385-94. Gailey R, Allen K, Castles J, Kucharik J, Roeder M. Review of secondary physical conditions associated with lower-limb amputation and long-term prosthesis use. J Rehabil Res Dev. 2008;45:15-29. Mengelkoch LJ, Kahle JT, Highsmith MJ. Energy costs & performance of transtibial amputees & non-amputees during walking & running. Int J Sports Med. 2014;35:1223-8. Kahle JT, Highsmith MJ. Transfemoral interfaces with vacuum assisted suspension comparison of gait, balance, and subjective analysis: ischial containment versus brimless. Gait Posture. 2014;40:315-20. Highsmith MJ, Kahle JT, Lewandowski AL, Kim SH, Mengelkoch LJ. A method for training stepover-step stair descent gait with stance yielding prosthetic knees. J Prosthet Orthot. 2012;24:10-5. Highsmith MJ, Kahle JT, Lura DJ, Lewandowski AL, Quillen WS, Kim SH. Stair ascent and ramp gait training with the Genium knee. Technol Innov. 2014;15:349-58. Bellmann M, Schmalz T, Ludwigs E, Blumentritt S. Stair ascent with an innovative microprocessor-controlled exoprosthetic knee joint. Biomed Tech. 2012;57:435-44. Yiğiter K, Sener G, Erbahçeci F, Bayar K, Ulger

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OG, Akdoğan S. A comparison of traditional prosthetic training versus proprioceptive neuromuscular facilitation resistive gait training with trans-femoral amputees. Prosthet Orthot Int. 2002;31:258-70. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535. Hafner B. State of the Science Evidence Report Guidelines. Washington (DC): American Academy of Orthotists & Prosthetists; 2008. Carey SL, Lura DJ, Highsmith MJ. Differences in myoelectric and body-powered upper-limb prostheses: systematic literature review. J Rehabil Res Dev. 2015;52:247-62. Neyeloff JL, Fuchs SC, Moreira LB. Meta-analyses and Forest plots using a microsoft excel spreadsheet: step-by-step guide focusing on descriptive data analysis. BMC Res Notes. 2012;5:52. Agrawal V, Gailey R, O’Toole C, Gaunaurd I, Finnieston A. Influence of gait training and prosthetic foot category on external work symmetry during unilateral transtibial amputee gait. Prosthet Orthot Int. 2013;37(5):396-403. Isakov E. Gait rehabilitation: a new biofeedback device for monitoring and enhancing weight-bearing over the affected lower limb. Eura Medicophys. 2007;43:21-6. Sjodahl C, Jarnlo GB, Persson BM. Gait improvement in unilateral transfemoral amputees by a combined psychological and physiotherapeutic treatment. J. Rehabil Med. 2001;33:114-8. Sjodahl C, Jarnlo GB, Soderberg B, Persson BM. Pelvic motion in trans-femoral amputees in the frontal and transverse plane before and after special gait re-education. Prosthet Orthot Int. 2003;27:227-37. Cole ES. Training elders with transfemoral ampu-

REVIEW OF AMPUTEE GAIT TRAINING tations. Top Geriatr Rehabil. 2003;19(3):183-190. 30. Faucher LD, Shurr DG. Ambulation on postoperative day 1 after bilateral transtibial amputations: a case report and literature review. J Prosthet Orthot. 2005;17:47-9. 31. Hyland NW. A comparative analysis of two gait training approaches for individuals with transtibial amputation [dissertation]. [South Orange, (NJ)]: Seton Hall University; 2009. 32. Barnett C, Vanicek N, Polman RC, Hancock A, Brown B, Smith L, Chetter I. Kinematic gait adaptations in unilateral transtibial amputees during rehabilitation. Prosthet Orthot Int. 2009;33:135-47. 33. Darter BJ, Nielsen DH, Yack HJ, Janz KF. Home-based treadmill training to improve gait performance in persons with a chronic transfemoral amputation. Arch Phys Med Rehabil. 2013;94:2440-7. 34. Black M, Seale J. Prosthetic gait training following bilateral transfemoral amputation using body weight supported treadmill training. A case report. J Neurol Phys Ther. 2006;30:215-6. 35. Lamberg EM, Muratori LM, Streb R, Werner M, Penna J. Harness-supported versus conventional treadmill training for people with lower-limb amputation: a preliminary report. J Prosthet Orthot. 2014;26:93-8. 36. Mikami Y, Fukuhara K, Kawae T, Kimura H, Ochi M. The effect of anti-gravity treadmill training for prosthetic rehabilitation of a case with below-knee amputation. Prosthet Orthot Int. 2015;39:502-6. 37. Wong CK, Ehrlich JE, Ersing JC, Maroldi NJ, Stevenson CE, Varca MJ. Exercise programs to improve gait performance in people with lower limb amputation: a systematic review. Prosthet Orthot Int. 2016;40:8-17. 38. Ephraim PL, Dillingham TR, Sector M, Pezzin LE, Mackenzie EJ. Epidemiology of limb loss and congenital limb deficiency: a review of the literature. Arch Phys Med Rehabil. 2003;84:74761. 39. Cunningham D. Task analysis and part versus whole learning methods. ETR & D. 1971;19:36598.

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40. Gopher D, Weil M, Siegel D. Practice under changing priorities: an approach to the training of complex skills. Acta Psychol (Amst). 1989;71:147-77. 41. Naylor JC, Briggs GE. Effects of task complexity and task organization on the relative efficiency of part and whole training methods. J Exp Psychol. 1963;65:217–24. 42. Waters RL, Mulroy S. The energy expenditure of normal and pathologic gait. Gait Posture. 1999;9:207-31. 43. Mehrholz J, Pohl M, Elsner B. Treadmill training and body weight support for walking after stroke. Cochrane Database Syst Rev. 2014:CD002840. 44. Miyai I, Fujimoto Y, Yamamoto H, Ueda Y, Saito T, Nozaki S, Kang J. Long-term effect of body weight-supported treadmill training in Parkinson’s disease: a randomized controlled trial. Arch Phys Med Rehabil. 2002;83:1370-3. 45. Brown TH, Mount J, Rouland BL, Kautz KA, Barnes RM, Kim J. Body weight-supported treadmill training versus conventional gait training for people with chronic traumatic brain injury. J Head Trauma Rehabil. 2005;20:402-15. 46. Hesse S, Werner C, Seibel H, von Frankenberg S, Kappel EM, Kirker S, Käding M. Treadmill training with partial body-weight support after total hip arthroplasty: a randomized controlled trial. Arch Phys Med Rehabil. 2003;84:1767-73. 47. Skinner HB, Effeney DJ. Gait analysis in amputees. Am J Phys Med. 1985;64:82-9. 48. Ephraim PL, Wegener ST, MacKenzie EJ, Dillingham TR, Pezzin LE. Phantom pain, residual limb pain, and back pain in amputees: results of a national survey. Arch Phys Med Rehabil. 2005;86:1910-9. 49. Highsmith MJ, Kahle JT, Carey SL, Lura DJ, Dubey RV, Csavina KR, Quillen WS. Kinetic asymmetry in transfemoral amputees while performing sit to stand and stand to sit movements. Gait Posture. 2011;34:86-91.

ISSN 1949-8241 • E-ISSN 1949-825X http://dx.doi.org/10.21300/18.2-3.2016.115 www.technologyandinnovation.org

INTERVENTIONS TO MANAGE RESIDUAL LIMB ULCERATION DUE TO PROSTHETIC USE IN INDIVIDUALS WITH LOWER EXTREMITY AMPUTATION: A SYSTEMATIC REVIEW OF THE LITERATURE M. Jason Highsmith1-3, Jason T. Kahle4,5, Tyler D. Klenow6, Casey R. Andrews1,7, Katherine L. Lewis1, Rachel C. Bradley7, Jessica M. Ward8, John J. Orriola9, and James T. Highsmith10,11 2

1 School of Physical Therapy & Rehabilitation Sciences, University of South Florida, Tampa, FL, USA Extremity Trauma & Amputation Center of Excellence (EACE), U.S. Department of Veterans Affairs, Tampa, FL, USA 3 319th Minimal Care Detachment, U.S. Army Reserves, Pinellas Park, FL, USA 4 OP Solutions, Tampa, FL, USA 5 Prosthetic Design + Research, Tampa, FL, USA 6 Prosthetics and Sensory Aids Service, James A. Haley Veterans’ Hospital, Tampa, FL, USA 7 Physical Medicine & Rehabilitation Service, James A. Haley Veterans’ Hospital, Tampa, FL, USA 8 Department of Chemistry, University of South Florida, Tampa, FL, USA 9 Shimberg Health Sciences Library, University of South Florida, Tampa, FL, USA 10 Dermatology Service, James A. Haley Veterans’ Hospital, Tampa, FL, USA 11 Dermatology Surgery Institute, Lutz, FL, USA

Patients with lower extremity amputation (LEA) experience 65% more dermatologic issues than non-amputees, and skin problems are experienced by ≈75% of LEA patients who use prostheses. Continuously referring LEA patients to a dermatologist for every stump related skin condition may be impractical. Thus, physical rehabilitation professionals should be prepared to recognize and manage common non-emergent skin conditions in this population. The purpose of this study was to determine the quantity, quality, and strength of available evidence supporting treatment methods for prosthesis-related residual limb (RL) ulcers. Systematic literature review with evidence grading and synthesis of empirical evidence statements (EES) was employed. Three EESs were formulated describing ulcer etiology, conditions in which prosthetic continuance is practical, circumstances likely requiring prosthetic discontinuance, and the consideration of additional medical or surgical interventions. Continued prosthetic use is a viable option to manage minor or early-stage ulcerated residual limbs in compliant patients lacking multiple comorbidities. Prosthetic discontinuance is also a viable method of residual limb ulcer healing and may be favored in the presence of severe acute ulcerations, chronic heavy smoking, intractable pain, rapid volume and weight change, history of chronic ulceration, systemic infections, or advanced dysvascular etiology. Surgery or other interventions may also be necessary in such cases to achieve restored prosthetic ambulation. A short bout of prosthetic discontinuance with a staged re-introduction plan is another viable option that may be warranted in patients with ulceration due to poor RL volume management. High-quality prospective research with larger samples is needed to determine the most appropriate course of treatment when a person with LEA develops an RL ulcer that is associated with prosthetic use. Key words: Decubitus ulcer; Dermatopathology; Hot spot; Prosthesis; Rehabilitation; Skin _____________________ Accepted July 1, 2016. Address correspondence to M. Jason Highsmith, Extremity Trauma & Amputation Center of Excellence (EACE), 8900 Grand Oak Circle (151R), Tampa, FL 33637-1022, USA. Tel: +1 (813) 558-3936; Fax: +1 (813) 558-3990; E-mail: michael.highsmith@va.gov

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INTRODUCTION Rehabilitation for persons with lower extremity amputation (LEA) is complex and requires an interprofessional healthcare team. Members of the multidisciplinary healthcare team for individuals with LEA may include orthopedic and vascular surgeons, physiatrists, prosthetists, physical therapists, dermatologists, mental health professionals, and others. Patients with amputation spend considerable time with physical rehabilitation professionals to learn selfcare with their new prostheses. During this period, rehabilitation professionals frequently encounter skin ulceration of the patient’s residual limb (RL) related to prosthetic use. Continuously referring patients to a dermatologist for every skin condition may not be practical. Therefore, it is important that physical rehabilitation professionals are prepared to recognize and manage common non-emergent skin conditions in this population. Proper management should be recommended and may include teaching self-care strategies to the patient as well as recognition of conditions requiring referral. Currently, more than 80% of amputations in the U.S. are the result of complications from vascular disease and diabetes (1,2). Less than 10% of LEA results from trauma (3,4). People with amputation experience nearly 65% more dermatologic issues than the general population. Skin problems are experienced by approximately 75% of patients with LEA who use lower limb prostheses (5). With LEA, the normal pressure-distributing anatomy is missing or altered. Therefore, the RL is exposed to several atypical conditions with prosthetic use. These include elevated shear forces, stress risers, increased humidity, and prolonged moist contact within the prosthesis, which can macerate tissue and contribute to ulceration. Ulcers or pressure sores, among the more common skin conditions in prosthetic users, may be mitigated with minor prosthetic adjustments to redistribute pressure (6). However, the size of areas over which pressures are applied and their magnitude can be considerable and may require recovery time out of the prosthesis or even a new socket to be fit (5). Prosthetic disuse can have many adverse consequences for the patient. These may include weakness, decreased flexibility, reduction of ambulatory ability, functional decline, decreased

physical activity, difficulty performing activities of daily living and occupational tasks, increased fall risk, decreased exercise tolerance, weight gain, financial hardship, and psychological implications. Alteration to RL shape and volume are common, with fluctuation, daily and over the lifespan, contributing to mismatch between prosthetic socket and RL. Socket to RL volume mismatch is a common problem often contributing to skin ulceration. Patients can have a high level of influence on this situation, for example, by adding socks. Therefore, monitoring fit and comfort along with other self-management techniques are vital to minimize a breakdown of skin integrity and function. This project’s aim was to review the intervention and management of RL ulcers in persons with LEA who use prostheses. The purpose of this literature review was specifically to determine the quantity, quality, and strength of available evidence to formulate evidence statements supporting treatment methods for prosthesis-related RL ulcers. Methods An interprofessional team was recruited to design the search term set that would best capture manuscripts to address the project’s aim and purpose. The team included the following disciplines: prosthetics, physical therapy, physiatry, dermatology, and information science. The PICO (Participants, Interventions, Comparison, Outcome) framework was used to identify key terms relevant to the project’s aim and purpose (7). On the assumption that available evidence regarding the treatment of pressure ulcers in lower extremity prosthetic users would be limited, PICO related search terms were selected, tested, and kept non-specific to identify as many potential manuscripts as possible. On November 1, 2014, the following search terms, Medical Subject Headings (MESH) terms, and Boolean Operators were agreed upon and utilized to search the MEDLINE (Pubmed), The Cumulative Index to Nursing and Allied Health Literature (CINAHL)(Ovid) and Embase databases: ((((((((((((((((((((((lower extremity OR lower extremit*)) OR (lower limb OR lower limb*)) OR leg) OR hip) OR foot) OR knee) OR ankle) OR (above knee OR AK)) OR (below knee OR BK)) OR (transfemoral OR “trans-femoral”))

RESIDUAL LIMB ULCER MANAGEMENT IN LEG AMPUTEES OR (transtibial OR “trans-tibial”)) OR (transpelvic OR “trans-pelvic”)) OR (syme’s OR symes))) AND ((((“Amputation”[Mesh]) OR amput*) OR disarticulation) OR (hemipelvectomy OR “hemi-pelvectomy”)))) OR stump)) NOT ((((((((pirogoff) OR chopart) OR lisfranc) OR (transmetatarsal OR “trans-metatarsal”)) OR “ray resection”) OR “ray resections”) OR “ray amputation”) OR “ray amputations”))) AND (ulcer OR ulcerat* OR pressure sore OR pressure ulcer OR decubit* OR breakdown)) AND (intervention OR treatment OR management OR non-use OR dressing OR negative pressure OR wound vacuum). Inclusion criteria were based on the definition of prosthesis-related ulcer and LEA as defined by the authors. Prosthesis-related ulceration, as defined by the authors, referred to an uninfected wound on the RL of a patient with an LEA that occurred from excessive pressure associated with prosthetic use. In this review, LEA referred to any Syme’s, transtibial, knee disarticulation, transfemoral, hip disarticulation, or hemipelvectomy amputation of any etiology. Foot and toe amputations were excluded. To be included, manuscripts were required to: 1. Include subjects with a lower extremity amputation and a prosthesis-related ulcer on their residual limb(s) 2. Be published after 1990 3. Study interventions, treatments, or management of wounds or ulcers in the amputated residual limb(s) of a person with lower extremity amputation who has used or uses a prosthesis Manuscripts were excluded if they were: 1. Studies involving animals, cadavers, or computational modeling (i.e., non-human) 2. Published before January 1, 1990 3. Not written in English Search results were exported into Endnote reference management software (V7, Thompson, CA, USA). Once imported, reference titles and then abstracts were screened for inclusion. Full text articles were then obtained for review of remaining articles that

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were not included initially through title and abstract screening. Articles not meeting inclusion criteria were eliminated. Included articles were then evaluated using the American Academy of Orthotists and Prosthetists’ (AAOP) evidence rating tool because of its content and population specificity (8). This rating tool was also selected because it permits evaluation of the full range of manuscripts and study designs (i.e., editorials to meta-analyses). The AAOP rating tool identifies 18 potential threats to internal validity and eight potential threats to external validity of the included experimental, quasi-experimental, and observational research articles reviewed (Table 1). Following review and rating, internal and external validity were then classified as “high,” “moderate,” or “low.” Articles were classified as having high internal or external validity if they met >80% of the tool’s criteria, moderate internal or external validity if they met 60% to 80% of criteria, and low internal or external validity if they met <60% of the criteria (Table 2). RESULTS The search identified 3,024 peer-reviewed articles (Figure 1). Studies involving animal, cadaver, or modeling; written before January 1, 1990; and/or not written in English were excluded. Additionally, articles were eliminated based on title when the title failed to reasonably support manuscript inclusion. Table 1. Distribution Distribution Included Studies by Study Design Table 1. of of Included Studies by Study Design Study Design

Number of Publications

Meta-Analysis (S1)

Systematic Review

Randomized Control Trial (E1)

Controlled Trial (E2)

Interrupted Time Series Trial (E3)

Single-Subject Trial (E4)

Controlled Before and After Trial (E5)

Cohort Study (O1)

Case-Control Study (O2)

Cross-Sectional Study (O3)

Qualitative Study (O4)

Case Series (O5)

Case Study (O6)

Group Consensus (X1)

Expert Opinion (X2)

Total

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Table Internal andand External Validity of Included Studies Studies Table2.2. Internal External Validity of Included

Study Bruno & Kirby (2009) Karakos (2006) Highsmith & Highsmith (2007) Salawu et al. (2006) Trabellesi et al. (2012)

Study Design

Internal Validity 1011 12 13 14 15



TOTAL



Mod



High



Low



High



Mod



High



High



High



High



High



External Validity 18 TOTAL

NA available criteria for thefor indicated study type. Blank spaces indicate the criteria was not whereas NA isisnot notanan available criteria the indicated study type. Blank spaces indicate the identified criteria was not “•” indicates the criteria was observed. Mod is moderate.

identified whereas “” indicates the criteria was observed. Mod is moderate.

Included

Eligibility

Screening

Identification

Figure 1. Study flow diagram and elimination process.

Articles identified through database searching: (n =3,024)

Articles potentially available for classification of pertinence (n =68)

Articles deemed appropriate for Full Evaluation (n =22)

Articles Included (n =5)

Articles Eliminated from Title Screening (n =2,956)

Articles Eliminated from Abstract Screening (n =46)

Articles Eliminated from Full Review (n =17)

RESIDUAL LIMB ULCER MANAGEMENT IN LEG AMPUTEES These two steps resulted in the elimination of 2,956 articles. A further 46 articles were excluded following abstract review. Full text articles were obtained and reviewed for the remaining 22 references. Of these, 17 were excluded based on eligibility criteria. The remaining five articles (Table 3) were included in the evaluation and synthesis. All studies were clinically oriented, including one randomized-control trial (9), one observational cohort study (10), one case series (5), and two case studies (11,12). None of the included studies incorporated blinding nor reported effect size. All studies addressed accommodation and washout and were free of conflicts of interest. Also, attrition was addressed in all studies and was <20%; however, attrition rates were not equal among groups due to the inclusion of case studies. Only valid and reliable outcome measures were used in the included studies. One study addressed the AAOP instrument’s fatigue and learning criteria. Statistical analysis was appropriate, adequately powered, and reported in two of the five studies. Additionally, exclusion criteria were not discussed in three of the five included studies. Finally, since all articles had high external validity, total confidence in the synthesized evidence statements were predominantly in accordance with the internal validity ratings. In total, conclusions from this report were made from 117 subjects with a mean (interquartile) age

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of 61.8 years (range: 44 to 80 years) who completed their respective studies. Eight subjects did not complete their studies, so attrition was 6% when all five studies were considered. The majority of subjects were male (74%) and unilaterally involved at the transtibial level. Only four subjects were bilaterally involved. Most subjects sustained their amputation as a result of peripheral vascular disease. At least three comorbid diagnoses, but as many as eight comorbidities, were reported in some cases. Most ulcers were classified as stage II level (13), and the leading diagnostic methodology was history and physical examination. In some cases, the physical examination was augmented with either wound measurement or Duplex imaging. Two dependent variables—time to wound healing and wound size (or area)—have the promise of aggregation and synthesis. Unfortunately, due to reporting at an apparently preset follow-up date, rather than at the date of complete healing, wounds were in various stages of healing upon follow-up. Therefore, time to healing data could not be aggregated. Time to healing or time to follow-up were widely varied, with a range from two to 20 weeks. Regarding wound size, the wounds in the Traballesi et al. study (9) were nearly two times the size of those reported in the Salawu et al. study (10). Traballesi et al. reported mean initial wound areas of 7 cm2 (Vacuum Assisted Suction Suspension (VASS) group)

Table 3. Study design, Intervention (Use vs. Disuse), Demographics, Outcome Measures, and Evidence Quality

Table 3. Study Design, Intervention (Use versus Disuse), Demographics, Outcome Measures, Evidence Quality Study

Study Design*

Intervention Use/Disuse

Sample Size

Mean Age (y)

Outcome Measures

Overall Quality of Evidence

Bruno & Kirby (2009)

Use, 6 hours per day proper use of silicone liners otherwise they will lead to pressure sores. Ulcer healed 4 months d/c

FIM, Ulcer measurements, Silicone use/disuse for ulcer prevention

Moderate

Karakos (2006)

Disuse. additional interventions: surgery (Angioplasty) 6 months due to pain and ulceration

Duplex scan

Moderate

Highsmith & Highsmith (2007)

Case 1: Use, 4 hours per day Case 2: Disuse, 1 month + Case 3: Use, with frequent adjustments Case 4: Disuse 1 week Case 5: Use with wound protection

Returned to independent ambulation and function

Moderate

Salawu et al. (2006)

Use of prosthetic device with healing ulceration

102

Changes in surface area of ulcers and photographs, wound cultures

High

Trabellesi et al. (2012)

Use of prosthetic device, VAS vs Suction socket system following ulcers/wounds healing. 12 weeks

demographics, locomotor capability index, visual analogue scale

High

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and 6.3 cm2 (control/suction socket group) compared with mean initial wound areas of 3.6 cm2 in established prosthesis users and 3.1 cm2 in new prosthesis users reported by Salawu et al. (9,10). Further, these wound area measures were made using vastly different methodologies. For instance, there were manual measurements (10) and scaled on-screen measurements taken in software (9). These differences in wound area measurement methodologies further complicate the ability to aggregate data for meta-analyses. Ultimately, prosthetic continuance or prosthetic discontinuance were the predominant intervention options available to manage RL ulcers related to prosthetic use. Multiple adjuvant interventions were included within the themes of prosthetic continuance (i.e., use) or discontinuance (i.e., disuse). These adjunct interventions included: 1. 2. 3. 4.

Prosthetic modification or adjustment Planned progressive prosthetic re-introduction Patient education Continued prosthetic use (VASS, suction, or usual suspension) with wound care (during disuse periods or scheduled)

Finally, three evidence statements were synthesized from the results. The topics addressed were 1) ulcer etiology, 2) continued prosthetic use, and 3) cessation of prosthetic use (Table 4).

DISCUSSION The purpose of this review was to determine the quantity, quality, and consistency of available evidence to formulate evidence statements supporting treatment methods for prosthesis-related RL ulcers. The review identified five articles (Table 3) that described the treatment of RL ulceration in 117 amputee subjects. With the exception of four bilaterally involved individuals, subjects had a history of unilateral transtibial amputation of vascular or unknown etiologies. The subjects were mostly elderly and had multiple comorbidities, including Type 2 Diabetes Mellitus, coronary artery disease, hypertension, hyperlipidemia, chronic venous insufficiency, neuropathy, anemia, post-herpetic neuralgia, pruritus, and chronic smoking. All subjects received modification of prosthetic use, including restriction and disuse, as an intervention. The first empirical evidence statement (EES) addressed development of an ulcer relative to improper volume management and utilization of interface components (Table 4). Scenarios that can contribute to ulceration include weight gain or loss, changes in activity, medication and physiologic changes, componentry damage, patient compliance issues, and improper patient education. Confidence in this statement was moderate. It is standard practice

Table EvidenceStatements Statements Table 4. 4. Empirical Empirical Evidence Empirical Evidence Statement

Supporting Studies

Improper volume management and utilization of interface components can result in ulceration to the skin of the residual limb.

Bruno & Kirby (2009) [Moderate] Highsmith & Highsmith (2007) [Moderate]

Following development of an ulcer, in the absence of comorbidities that delay healing and impair cognition, patient education and modified prosthetic use with or without elevated vacuum suspension is safe, can reduce ulcer size, and result in limited but continued function during healing.

Bruno & Kirby (2009) [Moderate] Highsmith & Highsmith (2007) [Moderate] Salawu et al. (2006) [High] Trabellesi et al. (2012) [High]

Prosthetic disuse and/or alternative interventions such as surgery or systemic antibiotics, may be indicated in the case of residual limbs that ulcerate in the presence of chronic heavy smoking, intractable pain, rapid volume and weight change, history of chronic ulceration, systemic infections, or dysvascular etiology.

Karakos (2006) [Moderate] Highsmith & Highsmith (2007) [Moderate]

Level of Confidence

Category

Moderate

Ulcer etiology

Moderate

Continued prosthetic use

Moderate

Cessation of prosthetic use

RESIDUAL LIMB ULCER MANAGEMENT IN LEG AMPUTEES for prosthetists to educate patients regarding the risk of developing an ulcer as well as numerous methods of preventing and managing them should they arise, including proper device utilization and volume management. Specifically, skin ulcers reportedly develop in nearly 27% of diagnosed skin problems in prosthetic users (14). The responsibility for preventing and managing ulcers in the residual limbs of prosthetic users is shared between the prosthetist, who provides a properly fit device and educates the patient, and the patient, who should practice diligent self-care and compliance. Controversy exists as to whether continued prosthetic use is indicated for amputees with RL ulcerations because ambulation has many physiological benefits that improve wound healing (15), such as increased circulation (16), tissue oxygenation (16,17), and fluid filtration (17). Prolonged inactivity, which is often associated with prosthetic disuse, is associated with several deleterious effects on health, including reduced functional capacity, respiratory function, skin integrity, and oxygen transportation (17) as well as muscle atrophy (18). This list is not inclusive of negative psychological effects of inactivity, such as depression, anxiety, and psychosomatic fatigue (19). In the event that an ulcer develops, there are numerous management options, including prosthetic use or disuse. EES 2 (Table 4) indicates that, in the absence of comorbidities that may delay healing and impair cognition, patient education and modified prosthetic use with or without elevated vacuum suspension is safe, can reduce ulcer size, and result in limited but continued function during healing. Conversely, EES 3 (Table 4) indicates that prosthetic disuse with or without alternative interventions such as surgery or systemic antibiotics may be indicated in the case of residual limbs that ulcerate in the presence of chronic heavy smoking, intractable pain, rapid volume and weight change, history of chronic ulceration, systemic infections, or advanced dysvascular etiology. The confidence in both statements is moderate based on available evidence. An additional case series, published after conducting this review, reported on continued prosthetic use in ulcerative care. Hoskins et al. described six (n = 6)

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unilateral transtibial patients (five male, one female, mean age = 66.5 years, mean weight = 94.6 kg) of vascular (n = 5) and traumatic (n = 1) etiology prescribed VASS prostheses upon presentation with an open RL wound (20). Subjects had several comorbidities, including Diabetes Mellitus Type 1 and 2, peripheral vascular disease, Charcot joint disease, retinopathy, hearing impairment, dermatillomania, and history of chronic alcohol and tobacco use. All subjects received physiatrist-prescribed wound care and were instructed to continue prosthetic use “as much as possible given any pain they may experience and not to limit their activities” (20). Vacuum pump and prosthetic foot type were not controlled. Wound size (determined by software analysis of ulcer photographs) and time to complete wound closure were primary outcome measures. Wound surface area was 2.17 ± 0.65 cm2 (initially) and mean time to wound closure was 117 ± 113 d (range: 40 to 380 d). During that period, one subject was non-compliant with proper use protocols for a short time (≈20 d), another had a hole in the sealing sleeve that required repair (at ≈100 d), and a third subject suffered a fall requiring surgery and rehabilitation (at ≈30 d). Authors concluded VASS prostheses may be used while managing RL wounds in transtibial amputation patients. Results further suggest a well-fitting VASS socket does not preclude RL wound healing and closure in compliant users even without activity limitation (20). This recently published data supports EES 2 and suggests that continued prosthetic use without activity restrictions may be possible in the presence of common diabetic-related complications when VASS is utilized. It further suggests that, on a per-case basis, comorbidities do not preclude continued prosthetic use in the presence of a residual limb ulcer. Limitations Though most included articles demonstrated moderate to high internal validity and high external validity, only one randomized control trial was included. This indicates substantial need for more high-quality research including more randomized control trials to determine the optimal treatment methods to reduce wound healing time and increase

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overall function for patients with a prosthesis-related RL ulcer. Meta-analyses were not possible due to a lack of standardized wound assessment scales and measures. Additionally, subjects in the included studies ranged in age from 44 to 80 years and had predominantly stage II ulcers, so it is unclear if results will generalize to younger subjects with ulcers in different stages. CONCLUSION This systematic review indicates that continued prosthetic use is a viable option to manage a residual limb with minor early stage ulceration in the compliant patient lacking comorbidities that would likely delay healing. Conversely, prosthetic discontinuance is also a viable method of residual limb ulcer healing in the presence of multiple comorbidities that delay healing, such as chronic heavy smoking, intractable pain, rapid volume and weight change, history of chronic and complex ulceration, systemic infections, or advanced dysvascular etiology. Surgery, physical rehabilitation, or other interventions may also be necessary in such cases to achieve restored prosthetic ambulation. Evidence suggests that continued use of specific sockets (i.e., VASS) in select compliant patients, even with comorbidities that could delay wound healing (i.e., diabetes), may not be detrimental to wound healing under some circumstances. The results of this review show that a short bout of prosthetic discontinuance with a staged re-introduction plan is also viable and may be warranted in patients with ulceration due to poor residual limb volume management. Ultimately, the majority of amputees studied returned to prosthetic use and ambulation upon conclusion. Finally, high-quality prospective research with larger samples is needed to determine the most appropriate course of treatment when the residual limb of a person with amputation develops an ulcer associated with prosthetic use. ACKNOWLEDGMENTS Contents of this manuscript represent the opinions of the authors and not necessarily those of the U.S. Department of Defense, U.S. Department of the Army, U.S. Department of Veterans Affairs, or any academic or health care institution. Authors

declare no conflicts of interest. This project was partially funded by the National Institutes of Health Scholars in Patient Oriented Research (SPOR) grant (1K30RR22270). REFERENCES 1. Turney BW, Kent SJ, Walker RT, Loftus IM. Amputations: no longer the end of the road. J R Coll Surg Edinb. 2001;46:271-3. 2. Taylor SM, Kalbaugh CA, Blackhurst DW, Hamontree SE, Cull DL, Messich HS, Robertson RT, Langan EM 3rd, York JW, Carsetn CG 3rd, Snyder BA, Jackson MR, Youkey JR. Preoperative clinical factors predict postoperative functional outcomes after major lower limb amputation: an analysis of 553 consecutive patients. J Vasc Surg. 2005;42:227-35. 3. Smith DG, Bowker J, Michael J, editors. Atlas of amputations and limb deficiencies: surgical, prosthetic and rehabilitation principles. 3rd ed. Rosemont (IL): American Academy of Orthopaedic Surgeons; 2004. 4. Zeigler-Graham K, Mackenzie EJ, Ephraim PL, Travison TG, Brookmeyer R. Estimating the prevalence of limb loss in the United States: 2005 to 2050. Arch Phys Med Rehabil. 2008;89:422-9. 5. Highsmith JT, Highsmith MJ. Common skin pathology in LE prosthesis users. JAAPA : official journal of the American Academy of Physician Assistants. 2007;20:33-6, 47. 6. Meulenbelt HE, Geertzen JH, Jonkman MF, Dijkstra PU. Skin problems of the stump in lower limb amputees: 1. A clinical study. Acta Derm Venereol. 2011;91:173-7. 7. Richardson WS, Wilson MC, Nishikawa J, Hayward RS. The well-built clinical question: a key to evidence-based decisions. ACP J Club. 1995;123:A12-3. 8. Hafner B. State of the Science Evidence Report Guidelines. Washington (DC): American Academy of Orthotists & Prosthetists; 2008. 9. Traballesi M, Delussu AS, Fusco A, Iosa M, Averna T, Pellegrini R, Brunelli S. Residual limb wounds or ulcers heal in transtibial amputees using an active suction socket system. A randomized controlled study. Eur J Phys Rehabil

RESIDUAL LIMB ULCER MANAGEMENT IN LEG AMPUTEES Med. 2012;48:613-23. 10. Salawu A, Middleton C, Gilbertson A, Kodavali K, Neumann V. Stump ulcers and continued prosthetic limb use. Prosthet Orthot Int. 2006;30:279-85. 11. Bruno TR, Kirby RL. Improper use of a transtibial prosthesis silicone liner causing pressure ulceration. Am J Phys Med Rehabil. 2009;88:264-6. 12. Karkos CD, Bright E, Bolia A, London NJ. Subintimal recanalization of the femoropopliteal segment to promote healing of an ulcerated below-knee amputation stump. J Endovasc Ther. 2006;13:420-3. 13. Sussman CB, Bates-Jensen BM. Wound care: a collaborative practice manual for health professionals. 4th ed. Philadelphia (PA): Wolters Kluwer Health/Lippincott Williams & Wilkins; 2012. 14. Dudek NL, Marks MB, Marshall SC, Chardon JP. Dermatologic conditions associated with use of a lower-extremity prosthesis. Arch Phys Med Rehabil. 2005;86:659-63. 15. Eisenbud DE. Oxygen in wound healing: nutrient, antibiotic, signaling molecule, and therapeutic agent. Clin Plast Surg. 2012;39:293-310.

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16. Genc A, Ozyurek S, Koca U, Gunerli A. Respiratory and hemodynamic responses to mobilization of critically ill obese patients. Cardiopulm Phys Ther J. 2012;23:14-8. 17. Wani I, Sangeen S, Khan Q, Wani M, Shah Z, Baneerje A, Balsaree D. Study to compare the effect of supine lying position along with mobilization over half lying position head up 45 degree in patients following open heart surgery. Int J Thoracic Cardiovasc Surg. 2009;13:9. 18. Siu AL, Penrod JD, Boockvar KS, Koval K, Strauss E, Morrison RS. Early ambulation after hip fracture: effects on function and mortality. Arch Intern Med. 2006;166:766-71. 19. Berlin AA, Kop WJ, Deuster PA. Depressive mood symptoms and fatigue after exercise withdrawal: the potential role of decreased fitness. Psychosom Med. 2006;68:224-30. 20. Hoskins RD, Sutton EE, Kinor D, Schaeffer JM, Fatone S. Using vacuum-assisted suspension to manage residual limb wounds in persons with transtibial amputation: a case series. Prosthet Orthot Int. 2014;38:68-74.

ISSN 1949-8241 • E-ISSN 1949-825X http://dx.doi.org/10.21300/18.2-3.2016.125 www.technologyandinnovation.org

PREDICTING WALKING ABILITY FOLLOWING LOWER LIMB AMPUTATION: AN UPDATED SYSTEMATIC LITERATURE REVIEW Jason T. Kahle1,2, M. Jason Highsmith3-5, Hans Schaepper6, Anton Johannesson7, Michael S. Orendurff8, and Kenton Kaufman9 OP Solutions, Tampa, FL, USA Prosthetic Design + Research, Tampa, FL, USA 3 School of Physical Therapy & Rehabilitation Sciences, University of South Florida, Tampa, FL, USA 4 Extremity Trauma & Amputation Center of Excellence (EACE), U.S. Department of Veterans Affairs, Tampa, FL, USA 5 319th Minimal Care Detachment, U.S. Army Reserves, Pinellas Park, FL, USA 6 Orthotics and Prosthetics Department, Loma Linda University, Loma Linda, CA, USA 7 Össur Nordic, Stockholm, Sweden 8 Motion & Sports Performance Laboratory, Lucile Packard Children’s Hospital Stanford, Palo Alto, CA, USA 9 Motion Analysis Laboratory, Mayo Clinic, Rochester, MN, USA 1

There is not a clear clinical recommendation for the determination of prosthetic candidacy. Guidelines do not delineate which member(s) of the multidisciplinary team are responsible for prosthetic candidacy decisions and which factors will best predict a positive outcome. Also not clearly addressed is a patient-centered decision-making role. In a previous systematic review (SR), Sansam et al. reported on the prediction of walking ability following lower limb amputation using literature up to 2007. The search strategy was designed from the previous Sansam SR as an update of previously valuable predictive factors of prosthetic candidacy. An electronic literature search was executed from August 8, 2007, to December 31, 2015, using MEDLINE (Pubmed), Embase, The Cumulative Index to Nursing and Allied Health Literature (CINAHL) (Ovid), and Cochrane. A total of 319 studies were identified through the electronic search. Of these, 298 were eliminated, leaving a total of 21 for full evaluation. Conclusions from this updated study are drawn from a total recruited sample (n) of 15,207 subjects. A total of 12,410 subjects completed the respective studies (18% attrition). This updated study increases the size of the original Sansam et al. report by including 137% more subjects for a total of 21,490 between the two articles Etiology, physical fitness, pre-amputation living status, amputation level, age, physical fitness, and comorbidities are included as moderate to strongly supported predictive factors of prosthetic candidacy. These factors are supported in an earlier literature review and should be strongly considered in a complete history and physical examination by a multidisciplinary team. Predictive factors should be part of the patient’s healthcare record. Key words: Amputee; Physical therapy; Prosthesis; Rehabilitation; Functional level; Prosthetic candidacy

_____________________ Accepted July 1, 2016. Address correspondence to Jason T. Kahle, OP Solutions, 12206 Bruce B. Downs Blvd., Tampa, FL 33612, USA. Tel: +1 (813) 971-1100; Fax: +1 (813) 9719300; E-mail: Jason@opsolutions.us

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INTRODUCTION Guidelines for amputee rehabilitation are available nationally and internationally (1-4). However, there is not a clear clinical recommendation for the determination of prosthetic candidacy. Moreover, while multidisciplinary decision support is recognized in the aforementioned guidelines, the guidelines do not delineate which member(s) of the multidisciplinary team are responsible for prosthetic candidacy decisions nor which factors will best predict a positive outcome. Also not clearly addressed is a patient-centered decision-making role, which is crucial to any clinical decision process. In a systematic review (SR), Sansam et al. reported on the prediction of walking ability following lower extremity amputation (LEA) (5). Conclusions of that SR were that adequately powered prospective studies reporting predictive ability of factors measured before the onset of rehabilitation could accurately estimate an individual’s walking potential (5). Prospective reports could establish clinic practice guidelines (CPG) for predicting prosthetic candidacy and functional level. Further, predictive factors that are modifiable through preemptive therapies could be explored further to establish whether targeting these factors would lead to improvements in walking outcome. Lastly, Sansam et al. reported there was mixed heterogeneity of methods and outcome measures used in comparing predictive factors (5). Investigation of predictive factors is needed to estimate walking potential more accurately, targeting modifiable factors to optimize outcome after LEA. Ultimately, this would help establish much needed CPGs (5). All factors should be considered when determining walking capacity, as not walking following amputation could lead to physical deterioration and comorbidities and be detrimental to overall health (6,7). The quality of rehabilitation studies has improved in the last decade (8). Sansam et al.’s SR included literature up to August 2007. There have been many changes and proposed changes to health care regarding LEA, particularly in the U.S. These changes may have initiated more contemporary reports of predicting walking ability. Therefore, the purpose of this SR is to establish factors to predict walking ability with a prosthesis following LEA. This review is an extension

and update using similar methods from a previous SR to help establish a wider, more current base of evidence regarding walking ability following lower limb amputation. METHODS Search Strategy for Extension of Previous Sansam et al. Systematic Review An electronic literature search was executed from August 1, 2007, to December 31, 2015, using MEDLINE (Pubmed), Embase, The Cumulative Index to Nursing and Allied Health Literature (CINAHL) (Ovid), and Cochrane and using the following keywords in the title or abstract: Amput* AND ambulat* OR mobil* OR walk* AND predict* OR prognos* OR probability Manuscripts were selected or eliminated based on the following criteria: Inclusion criteria: • Adult subjects with unilateral or bilateral lower limb amputation • Published after August 1, 2007 • Examined the relationship between predictive variables recorded prior to amputee rehabilitation and measures of walking ability following rehabilitation • Studies using health outcomes with a mobility component, such as the Functional Independence Measure • English language • Observational, retrospective studies if predictor variables were available • Randomized clinical trials Exclusion criteria: • Non-adult • Prosthetic device or rehabilitation interventions studies • Animal studies • Case reports and series • Letters, editorials, conference proceedings • Manuscripts from developing nations Two authors independently assessed selected papers for content, quality, and critical appraisal.

RESULTS Number of Identified Studies A total of 319 unique studies were identified through the electronic search. Of these, 298 were eliminated, leaving a total of 21 for full evaluation (Figure 1). Description of Sample The original SR from Sansam et al. included a total (n) of 9,080 subjects (5). Conclusions from this updated study are drawn from a total recruited sample (n) of 15,207 subjects. A total of 12,410 subjects completed the respective studies (18% attrition). There was incomplete and inconsistent reporting of anthropometric, demographic, and etiologic data; of those studies sufficiently reporting this information, the lower extremity limb loss had the following distribution: 37% peripheral vascular disease (PVD), 27% trauma, 17% diabetic, 12% cancer, 6% infection, and 2% congenital. Three sub-groups of subjects were included: an experimental group of subjects with LEA, a control group of subjects with LEA, and another control group of otherwise healthy non-amputee controls. Within the experimental group of LEA patients, the subjects described had a mean age of 57.3 years (median 60.9 (interquartile range (IQR): 8.5); range: 48.1 to 69.8 years) and a mean body mass index

Screening Eligibility Included

Similar to the original Sansam et al. SR, a standardized checklist was used to extract each report’s methods, population, outcome measures, and predictive factors (5). Additionally, the UK National Service Framework for Long-term Conditions (3,9) was used to assess the quality of each study, as it allows assessment of quality in non-randomized cohort studies. The reports and data extracted were verified by at least two independent authors who agreed on final scoring and data extraction. The International Classification of Functioning, Disability and Health (4) was used to present the predictive factors identified from these studies. Following study evaluation and data extraction, factors predictive of walking ability following LEA were aggregated and compared narratively with the findings of the original Sansam et al. SR.

Identification

PREDICTING WALKING ABILITY AFTER AMPUTATION

PubMed (n = 107)

Embase (n = 130)

Cochrane (n = 23)

127

CINAHL (n = 216)

Records retrieved from searches (n = 476) Records retrieved from searches (n = 476)

Duplicates removed (n = 157)

Articles’ titles and abstracts screened (n = 319)

Records excluded (n = 220)

Full-text articles assessed for eligibility (n = 99)

Full-text articles excluded, after full article review (n = 78)

Studies included in quantitative synthesis (meta-analysis) (n = 21)

Figure 1. PRISMA 2009 flow diagram. Reprinted with permission from PLoS Medicine (Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred Reporting tems for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med. 2009;6(7):e1000097), copyright 2009. For more information, visit www.prisma-statement.org.

(BMI) of 30.2 kg/m2 (median: 31.3 (IQR: 4); range: 27.6 to 31.6 kg/m2). Within the described control group of subjects with LEA, the reported etiology was typically PVD with comorbid diabetes mellitus. Their mean age was 61.8 years (median 66.7 (IQR: 11.8); range: 46.0 to 67.7 years) and mean BMI was 29.6 kg/ m2 ± 6.3. Age and BMI were not different (p > 0.05) between experimental and control subjects with LEA. Finally, there was a smaller group of non-amputee, otherwise healthy control subjects described whose mean age was 49.0 years (median 59.2 years (IQR: 35.6); range: 26.1 to 61.7 years) and mean BMI was 25.7 kg/m2 (Table 1). Settings, Study Designs, and Independent Variables The predominant setting for these studies was the rehabilitation center. These were in varied organizations, including university medical centers, Veterans Administration hospitals, private sector hospitals, and skilled nursing facilities. In addition to these, data were also collected from military treatment

160

PVD

PVD, DM, T

Erjavec (11)

Erjavec (33)

4727

4357

PVD, NR

PVD, T, CA

T, NR

PVD, DM, T

PVD, I, DM

Hamamura (17)

Landry (26)

O’Neil (25)

Raya (32)

Stineman (22) Stineman (21)

PVD, DM

Linberg (12)

Webster (18)

215

118

Charlson comorbidity index, VA Large Health Survey, AUDIT-C, MSSS, PHQ-9, Phantom limb/stump pain, daily prosthetic use/ambulation, TAPES

6MWT

CHAMP

PEQ, LCI, TUG

Ambulate w/ "success" at 1 y, Pre-op blood labs, Am Soc. Anesthes. status, Pedal pulses

ECG, BP, oxygen uptake, HR

Oxygen uptake

SIGAM-WAP, TUG

Ambulating independently or w/ assistance & living at home at follow up. Assessed at DC & 1y

FIM

1 y survival, Discharged home

6MWT

Frequency of prosthetic use, ability at DC

Modified Houghton Scale, 2 groups: unlimited walking capacity (score=20) & incapacity to walk, regardless of severity (score <20) Patients who could walk ≥ 100 m w/ at most 1 cane = “successful prosthetic users”; otherwise, “failed users” TMA healing, ambulation, living status, survival

Healing, mortality, 2MWT, TUG, Step activity

Arm Ergometer

FIM, 6MWT, Stress

AMP, etiology

Oxygen uptake

Walking Ability Measures

Most individuals achieve successful prosthetic fitting by 1 y following a first major dysvascular LLA, TFAs were significantly less likely to achieve prosthetic fitting success at 1 y. TFA, increased age, major depressive episode, and history of dialysis were associated with significantly less prosthetic ambulation. Higher social support was associated with greater prosthetic ambulation.

Characteristics such as age, height, weight, and waist circumference moderately affected 6MWT.

Older adults amputated because of vascular deficiency had a lower aerobic capacity compared with able-bodied controls and traumatic amputees. Level of amputation not associated with VO2 peak. Vascular LEA patients had lower walking ability vs traumatic LEA patients, which were similar to controls in oxygen uptake during exercise. TTA success rate 74%, w/ mortality rate 21% w/in 6 mos. 50% attained prosthetic mobility after 1 y. Infection & poor vascularity (i.e., popliteal pulse absence & low ABI) associated w/ poor clinical outcome. Functional use of a prosthesis 1y after TTA is related to RL quality. Tibial length of 12–15cm from the knee is correlated w/better functional outcomes than shorter tibial lengths. Surgical technique and RL length important for good functional outcome after TTA. Salvage the knee joint whenever possible. Intact knee joints increase the possibility of returning to high-level mobility activities following rehab. Rehab-related factors such as lower limb strength, standing and dynamic balance, and ability to displace the CoM over the base of support were all significantly related to ability to perform high-level mobility activities.

LEAs receiving specialized rehab can achieve 8.0 pt FIM motor increase vs. those receiving consultative rehab. One pt. FIM increase associated w/ avg decreased care from a 2nd person of 2.2-5.0min/d. LEA functional outcomes after LEB directly influenced by amp level. Possible to ID amps likely to achieve good functional outcomes based on pre-op patient characteristics. Can risk-stratify pts at time of LEB least likely to achieve good functional outcome when faced w/ subsequent LEA. Elderly patients referred to SNF for rehab have high probability of prosthetic use after TTA, w/out phantom pain; prosthetic candidates.

Receiving inpatient rehab in 1 y of LEA associated w/ increased likelihood of 1 y survival & hospital discharge to home.

Strong hip abduction strength strong predictor of; 6MWT score, ability to STS & cross obstacles.

Memory & FAS verbal fluency correlate w/ more frequent prosthetic use.

TMA healing predicts subsequent ambulatory status & should be pursued in patients with good rehab potential.

Minimal comorbidities, walking motivation & sound limb SLS ability are valuable factors contributing to successful prosthetic ambulation in geriatric LEA patients. Also, ≥50% VO2max is a valid initial guideline for physical fitness level required for successful prosthetic rehab.

2MWT proposed as first-line clinical test. FRT indicated for specific assessment of balance disorders.

Evidence supporting prognosis for prosthetic & non-prosthetic elderly mobility currently unavailable.

High

Medium

High

Medium

High

Medium

High

Medium

High

Medium

Older HDAs in good health & w/ low comorbidity prevalence able to successfully walk w/prosthesis in a community. Physical fitness of ≈60% VO2max necessary for older HAD patients to successfully walk. Rehab in CIRU improved mobility success for Veterans undergoing LEA for PVD or DM. No relation to differences in baseline mobility, demographic, psychosocial factors, or # rehab visits. Better exercise test performance relates to increased # patients fitted with prosthesis. Exercise test is good predictor of prosthetic fitting. TFA patients who reach the level of 30W or more in the exercise test with an arm ergometer are likely to be able to complete the 6MWT using a prosthesis. Simple ergometry may be useful for screening before prosthetic fitting.

Quality

Results

Summary of studies included in literature review. Using the UK National Service Framework for Long-term Conditions.(3, 4, 9) Articles were scored out of 10, with up to 2 points awarded for each of the following 5 items: Are the research question/aims and design clearly stated? Is the research design appropriate for the aims and objectives of the research? Are the methods clearly described? Is the data adequate to support the authors’ interpretations/conclusions? Are the results generalizable? Quality grade; ≤3 =poor, 4-6 = medium, ≥7= high quality. Factors considered important for predicting prosthetic use are supported by ≤3 references.

Gaunard (31)

PVD

Artwert (29)

151

T, PVD

Wong (19)

T, PVD

PVD, DM, CA, I

van Eijk (20)

Wezenberg (28) Wezenberg (14)

3691

PVD

Sukow (23)

Gremeaux (24)

831

PVD, NR

PVD, T, I, CA, CONG

Fortington (30)

199

PVD, DM

Czerniecki (27)

Total n

CA, I

Population

Chin (10)

First Author

Table 1. Diabetes Mellitus (DM), Cancer (CA), Infection (I), Peripheral Vascular Disease (PVD), Trauma (T), Congenital (CONG)

128 KAHLE ET AL.

PREDICTING WALKING ABILITY AFTER AMPUTATION facilities, trauma centers, private sector prosthetic practices, and university laboratories. Fifty percent of the included studies were prospective, 38% were retrospective, and 3% were SRs. Cohort and cross-sectional designs were the most common designs, and only two experimental studies were included. The predominant independent variable was LEA. In addition to this, prosthetic rehabilitation was commonly included as treatment. Since the original Sansam et al. article, the following factors were each supported by a single reference: BMI, motivation, social support, smoking, and phantom limb condition. The following predictive factors were moderately supported (i.e., two references): independence in activities of daily living (ADL), time to rehabilitation, race, and vascular intervention. The following predictive factors were more strongly supported (i.e., three to five references): ability to stand on one leg, cognition and mood disturbance, gender, pre-amputation living status, and cause of amputation. Race, vascular intervention, and pre-amputation living status were newly identified in this report and not identified in the original Sansam et al. article. The most strongly supported factors (i.e., â&#x2030;Ľ6 references) emerging from the search when considering prosthetic candidacy were: amputation level, physical fitness, age, and comorbidities. There is increasing agreement that these identified predictive factors are important when contemplating prosthetic candidacy and walking ability. Meta-analysis was not possible, as the studies of like outcome measures did not observe the same homogeneous patient characteristics; mainly, level, etiology, and mean ages were heterogeneous among these studies (10-14). DISCUSSION The purpose of this study was to extend the body of knowledgeâ&#x20AC;&#x201D;using the same search strategy originally completed in the Sansam et al. articleâ&#x20AC;&#x201D;of predicting walking ability following lower limb amputation. This SR identifies predictive factors of walking ability and updates the findings to include current literature. We hypothesized that most factors previously identified as important or predictive in determining prosthetic candidacy and walking ability would be reinforced

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and that new factors would potentially emerge as important in candidacy determinations. This hypothesis was confirmed, as all but five of the previous predictive factors were reported in the updated articles, with 15 of the same predictive characteristics from the original Sansam article recurring. Three new predictive factors were identified in this review that were not previously identified in the original Sansam review (Table 2). This literature review spans the seven years (20072015, 21 studies) following the original Sansam et al. article, whereas the original search included 57 years of literature (1950-2007, 57 studies). This updated study increases the size of the original Sansam et al. report by including 137% more subjects for a total of 21,490 between the two articles. However, the authors caution that, due to poor reporting, it is not clear at times if patients are repeat counted in multiple publications. Nevertheless, in terms of prosthetic studies, this is a considerably large study relative to other SRs, which tend to include much smaller samples. For example, a recent comprehensive SR of microprocessor knees based conclusions on 625 subjects (15). The patients in this SR had predominantly lost their lower extremities due to PVD, which is consistent with epidemiologic data (16). Therefore, it is plausible that the results of this SR would have high generalizability to clinical practice. Given the predominant setting was the rehabilitation center or major medical centers, results may be particularly relevant within these types of settings. Predictive Factors in a Single Study in This Literature Review BMI Linberg et al. found demographics (i.e., height, weight) did not affect the six-minute walk test (6MWT) (12). This is consistent with previous reports in finding that, when adjusting for medical comorbidities, age, and sex, BMI was not a significant predictor of walking ability (5). Motivation Hamamura et al., in a high quality study, found significance in motivation as a predictive factor for successful prosthetic ambulation among geriatric subjects (17). This is consistent with a previous report

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Table 2. Predictive Factors Investigated by Included Studies

Vascular intervention/ disease

Race

Pre-morbid living status

Smoking

Time to rehabilitation

Social support

Gender (sex)

Comorbidities

Age

IADLs

Ability to Stand on 1 Leg (SLS)

Motivation

Physical Fitness

BMI -Height, weight

Cognition/ Mood Disturbance

Stump factors and pain

Amputation Level

First Author Chin (10) Czerniecki (27) Erjavec (11) Erjavec (33) Fortington (30) Gremeaux (24) Hamamura (17) Landry (26) O'Neil (25) Raya (32) Stineman (22) Stineman (21) Suckow (23) van Eijk( 20) Wezenberg (28) Wezenberg (14) Wong (19) Artwert (29) Gaunard (31) Linberg (12) Webster (18) Total

Cause of amputation (Etiology)

Table 2. Predictive Factors Investigated by Included Studies

1 1 1 1 1 1

1 1

1 1 1

1 1 1 1

1 1

1 1 1 3

1 1 1

1 1 1 1

1 4

Predictive factors in common with Sansam et al, and this systematic review are grey color filled. Predictive factors identified in studies in the Sansam et al. article, but not found in studies included in this extension are: pre-rehab motor function, employment and sport, Predictive factors in common with Sansam et al., and this systematic review are grey color filled. hemiparesis, psychological factors, and self-efficacy.(5) Predictive factors exclusive to this review are white color filled.

Predictive factors identified in studies in the Sansam et al. article, but not found in studies included in this extension are: pre-rehab motor function, employment and sport, hemiparesis, psychological factors, and self-efficacy (5). Predictive factors exclusive to this review are white color filled.

PREDICTING WALKING ABILITY AFTER AMPUTATION finding a statistically significant association between patient â&#x20AC;&#x153;motivationâ&#x20AC;? and the ability to learn to walk with a prosthesis (5). Social Support Webster et al. identified greater levels of baseline social support were associated with more hours of prosthetic walking and identified a need to build in social support structures for patients that have limitations in this regard (18). Greater perceived social support as a predictor of higher mobility was not a well-supported predictive factor in previous studies (5). Smoking Wong et al. reported smoking was associated with significantly poorer outcomes in diabetic transtibial amputation (TTA) patients (19). Czerniecki et al. reported smoking status and reported a likely relationship between smoking and a more proximal level amputation, which is discussed later. Although smoking is implicated in the etiology of many amputations, Sansam et al. reported that it is unlikely to have a significant impact on mobility outcome (5). Stump Factors and Pain van Eijk et al., in a medium quality article, reported that the presence of phantom pain was significantly associated with the ability to use a prosthesis (20). Phantom limb pain specifically was not reported as a predictive factor outcome measure in previous studies. Predictive Factors Supported with Two References in This Literature Review Independence in Activities of Daily Living van Eijk et al., in a medium quality article, reported preoperative Barthel Index (BI) as a measure of oneâ&#x20AC;&#x2122;s ability to perform basic ADLs. It is reported as evaluation of the functional status at baseline. In addition, the preoperative BI was estimated based on history taking and was significantly positively associated with prosthetic use (20). Further, BI was a significant indicator of the ability to complete the Timed Up and Go (TUG) test. However, Wong et al., in a high quality study, found no correlation between independence in ADLs and outcome in TTA patients (19). This is inconsistent with the previous report of dependency for self-care prior to amputation as an

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independent negative predictor of walking ability up to 18 years after surgery. A significant association between post-operative ADLs and walking ability after rehabilitation with a prosthesis has also been described (5). Therefore, it seems the preponderance of evidence suggests that independence in completion of ADLs is a factor worth considering when determining prosthetic candidacy. Time to Rehabilitation Stineman et al., in two separate high quality studies, reported that patients who had early rehabilitation initially made higher motor gains than those individuals who had later rehabilitation (21). Additionally, patients who received acute postoperative inpatient rehabilitation, compared to those with no evidence of inpatient rehabilitation, had an increased likelihood of one-year survival and home discharge. Prosthetic limb procurement did not differ significantly between groups (22). Sansam et al. found a shorter time interval between surgery and admission for rehabilitation is related to better walking potential. Similarly, the length of time taken from surgery to fitting for a prosthesis is significantly associated with outcome, with those waiting longer having poorer walking ability at one year (5). Race In two high quality studies, race was reported as not significant in affecting the outcome of TTA patients or being a predictive factor (18,19). Race was not reported as a predictive factor outcome measure in previous studies. Vascular Intervention In a high quality study, Suckow et al. reported it is possible, based on preoperative patient characteristics, to identify patients undergoing lower extremity bypass surgery who are most or least likely to achieve good functional outcomes even if a major amputation is ultimately required. These findings may assist in patient education and surgical decision making in patients who are poor candidates for lower extremity bypass (23). Wong et al. found indicators of poor vascularity, such as absence of popliteal pulse and low Ankle Brachial Index (ABI), were significantly associated with poor clinical outcomes (19). Vascular intervention was not reported as a predictive factor outcome measure in previous studies.

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Predictive Factors Supported with Three to Five References in This Literature Review Ability to Stand on One Leg In a medium quality study, Grameaux et al. identified the one-leg balance test as appropriate for early evaluation in the immediate follow-up of the amputation in order to establish a prognosis for success in prosthetic ambulation (24). Hamamura et al., in a high quality study, identified the patient’s ability to stand on one leg on the non-amputated limb as one of the most valuable factors contributing to successful prosthetic ambulation in geriatric amputees, reporting significance in successful prosthetic walkers (17). van Eijk et al., in a medium quality article, reported that one-leg balance was significantly positively associated with prosthetic use (20). These reports are consistent with previous reports identifying the ability to stand on one leg as indicative of better walking potential after unilateral lower limb amputation (5). Cognition and Mood Disturbance Webster et al. reported, in a study of high quality, that management of depression and promotion of social support may have a positive effect on prosthetic use (18). O’Neill et al., in a report of medium quality, concluded that identified cognitive deficits may indicate augmented rehabilitation or provision of alternative mobility rehabilitation (25). Stineman et al. reported ADL function and mobility (physical functioning) using gains in motor FIM™ scores achieved by rehabilitation discharge. Psychosis was associated with lower motor FIM™ gains, but no direct correlation between psychosis and prosthetic candidacy was reported (21). In the previous Sansam et al. article, cognitive ability was consistently found to be a significant predictor of walking ability following rehabilitation, with a superior outcome reported in those with better cognitive ability (5). Gender Four high quality studies found no association between gender and walking ability following lower limb amputation, suggesting it is not a predictive determinant (19-22). Previous studies also found no consistent association with gender (5).

Pre-Amputation Living Status Several reports in this literature review collected data on factors related to living status, such as marital status and independence. However, none of them reported correlations on living status being a predictive characteristic of walking ability following lower extremity amputation (18,21,22,26). Cause of Amputation Some authors reported cause of amputation as a factor in prosthetic candidacy; however, there was no association of cause as a predictive characteristic of walking candidacy (11,21,27). Hamamura et al. reported on cause of amputation, yet no significant difference between the two groups (successful and unsuccessful ambulators) was observed (17). Wezenberg et al. found that the presence of an amputation as a result of vascular deficiency was significantly associated with a lower VO2 peak of 29.1%, whereas a traumatic amputation was not significantly associated with a difference in VO2 peak compared with controls. Having a vascular amputation was associated with a 26.4% decrease in VO2 peak compared with having an amputation because of trauma (28). In a second later article, Wezenberg et al. found traumatic amputees walked at the same VO2 as able-bodied controls but did so at a lower walking speed. Vascular amputees walked at an even slower speed with a substantially higher VO2. Both amputee groups chose a walking speed that was lower than the most efficient walking speed. Consideration of peak aerobic capacity is an important factor when aiming to improve walking ability in amputees (14). Finally, peak aerobic capacity is an important determinant for walking ability. Sansam et al. also reported an association between the cause of amputation and walking potential in five studies, with subjects undergoing an amputation for dysvascularity achieving a poorer outcome than those due to trauma or other non-vascular causes (5). Predictive Factors Previously Reported Supported With Six or More References in This Literature Review Amputation Level Artwert et al., in a high quality article, reported that functional use of a prosthesis in TTA patients

PREDICTING WALKING ABILITY AFTER AMPUTATION is related to residual-limb quality in general as well as for specific bony aspects of the residual limb. A tibial length of 12 to 15 cm from the knee joint line correlated with a better functional outcome than shorter tibial lengths. Surgical technique and attention to the residual limb length ensures a more likely good functional outcome after TTA (29). In a high quality article, Suckow et al. reported TTA and transfemoral amputee (TFA) patients were equally likely to ambulate independently or with assistance (within groups) at hospital discharge. Between groups, however, there were significant differences based on level of amputation. Patients who underwent a minor amputation were more likely to ambulate with or without assistance but less so than patients who did not have an amputation after lower extremity bypass (23). Linberg et al., in a high quality article, reported a significant difference in 6MWT performance between bilateral TTA patients and TFA patients, with bilateral TTA patients walking further (12). Chin et al. reported, in a medium quality study, solely on the hip disarticulation amputee (HDA), where older HDA patients in good physical condition and with a low prevalence of comorbidities were able to successfully walk with a prosthesis in a community setting (10). Czerniecki et al. reported the rates of success were similar: 35%, 31%, and 33% of amputees with transmetatarsal (TM), TTA, and TFA, respectively, achieved mobility success when seen in a comprehensive inpatient rehabilitation unit (27). Fortington et al. reported poorer performance by people with a TFA versus TTA. Slower five-meter walk tests and fewer steps taken per day were reported one year after amputation. One year after discharge, people with TFA or TTA increased the number of steps taken per day from 570 steps at discharge to 1314 steps and were able to maintain this level in the second year (30). Grameaux et al. did not find a statistically significant worse result in bioenergetic efficiency after TFA but did find a reduction in walking speed. Only when age was taken into account in a multiple regression model did the impact of the level of amputation become statistically significant (24). Hamamura et al. reported, in a high quality study, no significant difference between the successful and unsuccessful ambulator groups when considering amputation level (17). Guanard et al., in a high quality article, reported on the importance of an

133

intact knee joint for providing the TTA patient with the ability to return to high-level mobility activities following rehabilitation (31). Stineman et al. reported ADLs and mobility (physical functioning) using gains in motor FIMâ&#x201E;˘ scores achieved by rehabilitation discharge. TFA was associated with lower motor FIMâ&#x201E;˘ gains, but no direct correlation between amputation level and prosthetic candidacy was reported. There was no statistically significant difference in prosthetic limb procurement for the group who received impatient rehabilitation compared to the group who did not (21). van Eijk et al., in a medium quality article, reported amputation level (low versus high) was significantly positively associated with prosthetic use (20). Further, van Eijk et al. found level as a predictor for ability to complete the TUG test. Webster et al., in a high quality article, reported TFA patients were significantly less likely to achieve prosthetic fitting success at one year (18). Wezenberg et al. reported that the level of amputation was not associated with VO2 peak (28). Sansam et al. previously found that the majority of studies reported better walking ability and greater ability to achieve ADLs after distal and unilateral amputations compared with more proximal or bilateral amputations. At this time, it seems the preponderance of evidence suggests that level of amputation is a factor in determining prosthetic ability but not a preclusion from candidacy. Finally, having more intact joints (i.e., having an intact knee compared with not having it) is consistent with a higher potential level of function in TTA patients. Moreover, the longer the transtibial residual limb, the greater potential there is for increased functional level. It is noteworthy, however, that having a long TTA is not requisite for achieving community ambulation, as those with HDA can achieve community ambulation as well. Physical Fitness Raya et al., in a high quality article, reported hip strength and balance were significant factors impacting 6MWT scores in individuals with LLA. The 6MWT can identify impairments of the musculoskeletal system that can affect ambulation ability such as weakness in the muscles that support ambulation (32). Chin et al. reported that when older HDA patients are in good physical condition, they

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are successfully able to walk with a prosthesis in a community setting (10). Hamamura et al. found, in a high quality article, that the successful ambulatory group had a significantly higher VO2 max compared with the failure group (17). van Eijk et al., in a medium quality article, reported that functional ambulation (Functional Ambulation Catagories (FAC) score, which measures the independency of gait) was significantly positively associated with prosthetic use (20). Guanard et al., in a high quality article, reported rehabilitation-related factors, such as lower limb strength, standing and dynamic balance, and ability to displace the center of mass over the base of support, were all significantly related to ability to perform high-level mobility activities (31.) Sansam et al. previously reported that two medium to high quality studies with the same first author have looked at physical fitness and its relationship to walking ability following unilateral above knee amputation. Both studies concluded that a %VO2 max of at least 50% could be regarded as a guideline value for the level of fitness required for successful ambulation with an above-knee prosthesis. This provides agreement that fitness parameters, particularly cardiorespiratory fitness, can be an important factor in determining prosthetic candidacy and success. Age Erjavec et al. found that age was a key determining predictive factor in combination with the results of the exercise stress test, a 6MWT at admission, the FIMâ&#x201E;˘ at admission, and consideration of gender, allowing the successful discrimination between patients who were fit with a prosthesis and those who were not (11). Grameaux et al. reported a statistically significant worse result in bioenergetic efficiency related to age when taken into account with amputation level (24). Hamamura et al. reported, in a high quality study, no significant difference between the successful and unsuccessful ambulator groups when considering age (17). Webster et al., in a high quality article, reported that increased age was associated with significantly less prosthetic ambulation (18). Stineman et al. reported ADL function and mobility (physical functioning) using gains in motor FIMâ&#x201E;˘ scores achieved by rehabilitation discharge. Advanced

age was associated with lower motor FIMâ&#x201E;˘ gains, but no direct correlation between age and prosthetic candidacy was reported (21). Wong et al., in a high quality article, reported that age was not a significant predictive factor in affecting the outcome in TTA patients (19). van Eijk et al., in a medium quality article, reported that age was not significantly associated with prosthetic use (20). Sansam et al. previously reported that, in most studies, older age at the time of amputation had an adverse effect on walking potential, with six studies reporting a much stronger dependence of walking ability on age than on comorbidity. There is disagreement on the extent to which age is a factor in determining prosthetic candidacy or success. The majority of the studies, including the higher quality evidence, suggests that age does have a role in prosthetic and functional determinations but that it should not restrict candidacy. Comorbidities Chin et al. reported that, when there is a low prevalence of commodities, older HDA patients were able to successfully walk with a prosthesis in a community setting (10). Hamamura et al. reported a significant difference between the successful and unsuccessful ambulator groups in the number of comorbidities, with fewer comorbidities having a positive effect (17). Webster et al., in a high quality article, reported that a history of dialysis was associated with significantly less prosthetic ambulation (18). Wong et al., in a high quality article, reported that amputation due to diabetes, high total white count, erythrocyte sedimentation rate, C-reactive protein, urea, creatinine, neutrophils, absence of pulses, low ABI, and Toe Brachial Index were significantly associated with poor clinical outcomes in TTA patients (19). van Eijk et al., in a medium quality article, reported multimorbidity was not significantly associated with prosthetic use (20). Sansam et al. previously reported that the effect of comorbid conditions on walking outcome is not clear. In the majority of studies investigating the role of comorbidities, the conclusions have been drawn from secondary analyses or in conjunction with other factors. At this time, the majority of the evidence is

PREDICTING WALKING ABILITY AFTER AMPUTATION unclear on the extent to which multiple comorbidities impacts prosthetic candidacy and use. However, some studies clearly demonstrate a negative effect of comorbidities on successful outcomes and a positive effect of fewer comorbidities on successful outcomes. Moreover, no studies have shown positive outcomes associated with the presence of comorbidities. Limitations Several publications in this review were written by the same or similar author teams. Further, the study topics are also commonly related. The study samples vary slightly at times among these seemingly related publications, making it difficult to be able to sum total number of subjects. Caution is advised related to the interpretation of the results of total sample size. CONCLUSION In this literature review, body mass index, motivation, gender, and smoking are among the factors with minimal support to assist in determining candidacy for a prosthesis. Moderately supported factors for prosthetic candidacy included cognition/mood disturbance, etiology, physical fitness, ability to stand on one leg, and pre-amputation living status. The most strongly supported factors for considering prosthetic candidacy were amputation level, age, physical fitness, and comorbidities. These factors are mostly supported in an earlier literature review and should be strongly considered in a complete history and physical examination by a multidisciplinary team. Predictive factor data is likely available in a complete patient health record. Prosthetic candidacy and functional level determinations could be predicted prior to prosthetic prescription based on a comprehensive review of the aforementioned factors. Additionally, these factors seem to remain important later in rehabilitation when determining the appropriate prosthetic prescription and functional level potential. Prosthetic over-prescription is preferred to under-prescription because the cost of a less active and less healthy patient, limited by technologies and therapies that adversely impacts their function and mobility, far outweighs the cost of a higher level prosthesis.

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ACKNOWLEDGMENTS Authors would like to acknowledge Tyler Klenow, MSOP, CPT-ACSM, for his contributions to the project. Contents of this manuscript represent the opinions of the authors and not necessarily those of the U.S. Department of Defense, U.S. Department of the Army, U.S. Department of Veterans Affairs, or any academic or health care institution. Authors declare no conflicts of interest. This project was funded by the AOPA RFP 04012015 and the National Institutes of Health Scholars in Patient Oriented Research (SPOR) grant 1K30RR22270. REFERENCES 1.

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KAHLE ET AL. Cunningham BP, Harmsen S, Kweon C, Patterson J, Waldrop R, McLaren A, McLemore R. Have levels of evidence improved the quality of orthopaedic research? Clin Orthop Relat Res. 2013;471(11):3679-86. Department of Health Long-term Conditions NSF Team. The national service framework for long-term conditions. London (UK): Department of Health; 2005. Annex 2 research and evidence; p. 88. Chin T, Kuroda R, Akisue T, Iguchi T, Kurosaka M. Energy consumption during prosthetic walking and physical fitness in older hip disarticulation amputees. J Rehabil Res Dev. 2012;49(8):1255-60. Erjavec T, Presern-Strukelj M, Burger H. The diagnostic importance of exercise testing in developing appropriate rehabilitation programmes for patients following transfemoral amputation. Eur J Phys Rehabil Med. 2008;44(2):133-9. Linberg AA, Roach KE, Campbell SM, Stoneman PD, Gaunaurd IA, Raya MA, Gomez-Orozco C, Gailey RS. Comparison of 6-minute walk test performance between male Active Duty soldiers and servicemembers with and without traumatic lower-limb loss. J Rehabil Res Dev. 2013;50(7):931-40. Raya MA, Gailey RS, Fiebert IM, Roach KE. Impairment variables predicting activity limitation in individuals with lower limb amputation. Prosthet Orthot Int. 2010;34(1):73-84. Wezenberg D, van der Woude LH, Faber WX, de Haan A, Houdijk H. Relation between aerobic capacity and walking ability in older adults with a lower-limb amputation. Arch Phys Med Rehabil. 2013;94(9):1714-20. Highsmith MJ, Kahle JT, Bongiorni DR, Sutton BS, Groer S, Kaufman KR. Safety, energy efficiency, and cost efficacy of the C-Leg for transfemoral amputees: a review of the literature. Prosthet Orthot Int. 2010;34(4):362-77. Ziegler-Graham K, MacKenzie EJ, Ephraim PL, Travison TG, Brookmeyer R. Estimating the prevalence of limb loss in the United States: 2005 to 2050. Arch Phys Med Rehabil. 2008;89(3):4229.

17. Hamamura S, Chin T, Kuroda R, Akisue T, Iguchi T, Kohno H, Kitagawa A, Tsumura N, Kurosaka M. Factors affecting prosthetic rehabilitation outcomes in amputees of age 60 years and over. J Int Med Res. 2009;37(6):1921-7. 18. Webster JB, Hakimi KN, Williams RM, Turner AP, Norvell DC, Czerniecki JM. Prosthetic fitting, use, and satisfaction following lower-limb amputation: a prospective study. J Rehabil Res Dev. 2012;49(10):1493-504. 19. Wong KL, Nather A, Liang S, Chang Z, Wong TT, Lim CT. Clinical outcomes of below knee amputations in diabetic foot patients. Ann Acad Med Singapore. 2013;42(8):388-94. 20. van Eijk MS, van der Linde H, Buijck B, Geurts A, Zuidema S, Koopmans R. Predicting prosthetic use in elderly patients after major lower limb amputation. Prosthet Orthot Int. 2012;36(1):4552. 21. Stineman MG, Kwong PL, Xie D, Kurichi JE, Ripley DC, Brooks DM, Bidelspach DE, Bates BE. Prognostic differences for functional recovery after major lower limb amputation: effects of the timing and type of inpatient rehabilitation services in the Veterans Health Administration. PM R. 2010;2(4):232-43. 22. Stineman MG, Kwong PL, Kurichi JE, PrvuBettger JA, Vogel WB, Maislin G, Bates BE, Reker DM. The effectiveness of inpatient rehabilitation in the acute postoperative phase of care after transtibial or transfemoral amputation: study of an integrated health care delivery system. ArchPhys Med Rehabil. 2008;89(10):1863-72. 23. Suckow BD, Goodney PP, Cambria RA, Bertges DJ, Eldrup-Jorgensen J, Indes JE, Schanzer A, Stone DH, Kraiss LW, Cronenwett JL, Vascular Study Group of New England. Predicting functional status following amputation after lower extremity bypass. Ann Vasc Surg. 2012;26(1):6778. 24. Gremeaux V, Damak S, Troisgros O, Feki A, Laroche D, Perennou D, Benaim C, Casillas JM. Selecting a test for the clinical assessment of balance and walking capacity at the definitive fitting state after unilateral amputation: a comparative study. Prosthet Orthot Int. 2012;36(4):415-22.

PREDICTING WALKING ABILITY AFTER AMPUTATION 25. Oâ&#x20AC;&#x2122;Neill BF, Evans JJ. Memory and executive function predict mobility rehabilitation outcome after lower-limb amputation. Disabil Rehabil. 2009;31(13):1083-91. 26. Landry GJ, Silverman DA, Liem TK, Mitchell EL, Moneta GL. Predictors of healing and functional outcome following transmetatarsal amputations. Arch Surg. 2011;146(9):1005-9. 27. Czerniecki JM, Turner AP, Williams RM, Hakimi KN, Norvell DC. The effect of rehabilitation in a comprehensive inpatient rehabilitation unit on mobility outcome after dysvascular lower extremity amputation. Arch Phys Med Rehabil. 2012;93(8):1384-91. 28. Wezenberg D, de Haan A, Faber WX, Slootman HJ, van der Woude LH, Houdijk H. Peak oxygen consumption in older adults with a lower limb amputation. Arch Phys Med Rehabil. 2012;93(11):1924-9. 29. Arwert HJ, van Doorn-Loogman MH, Koning J, Terburg M, Rol M, Roebroeck ME. Residuallimb quality and functional mobility 1 year after transtibial amputation caused by vascular insuf-

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ficiency. J Rehabil Res Dev. 2007;44(5):717-22. Fortington LV, Rommers GM, Geertzen JH, Postema K, Dijkstra PU. Mobility in elderly people with a lower limb amputation: a systematic review. JAm Med Dir Assoc. 2012;13(4):319-25. Gaunaurd IA, Roach KE, Raya MA, Hooper R, Linberg AA, Laferrier JZ, Campbell SM, Scoville C, Gailey RS. Factors related to highlevel mobility in male servicemembers with traumatic lower-limb loss. J Rehabil Res Dev. 2013;50(7):969-84. Raya MA, Gailey RS, Gaunaurd IA, Ganyard H, Knapp-Wood J, McDonough K, Palmisano T. Amputee mobility predictor-bilateral: a performance-based measure of mobility for people with bilateral lower-limb loss. J Rehabil Res Dev. 2013;50(7):961-8. Erjavec T, Vidmar G, Burger H. Exercise testing as a screening measure for ability to walk with a prosthesis after transfemoral amputation due to peripheral vascular disease. Disabil Rehabil. 2014;36:1148-55.

ISSN 1949-8241 •• E-ISSN 1949-825X http://dx.doi.org/10.21300/18.1.2016.5 http://dx.doi.org/10.21300/18.2-3.2016.139 www.technologyandinnovation.org

EFFECTS OF THE GENIUM KNEE SYSTEM ON FUNCTIONAL LEVEL, STAIR AMBULATION, PERCEPTIVE AND ECONOMIC OUTCOMES IN TRANSFEMORAL AMPUTEES M. Jason Highsmith1-3, Jason T. Kahle4,5, Matthew M. Wernke6, Stephanie L. Carey7, Rebecca M. Miro1, Derek J. Lura8, and Bryce S. Sutton9 1 School of Physical Therapy & Rehabilitation Sciences, University of South Florida, Tampa, FL, USA Extremity Trauma & Amputation Center of Excellence (EACE), U.S. Department of Veterans Affairs, Tampa, FL, USA 3 319th Minimal Care Detachment, U.S. Army Reserves, Pinellas Park, FL, USA 4 OP Solutions, Inc., Tampa, FL, USA 5 Prosthetic Design + Research, Tampa, FL, USA 6 WillowWood, Mt. Sterling, OH, USA 7 Department of Mechanical Engineering, University of South Florida, Tampa, FL, USA 8 Department of Bioengineering and Software Engineering, Florida Gulf Coast University, Ft. Myers, FL, USA 9 Center of Innovation on Disability and Rehabilitation Research (CINDRR-TPA), James A. Haley Veterans’ Hospital, Tampa, FL, USA 2

Compared to non-microprocessor knees, the C-Leg microprocessor knee (MPK) is bioenergentically and economically more efficient and safer for transfemoral amputation (TFA) patients. The Genium MPK has demonstrated improvements in perceived function, knee kinematics, and physical functional performance compared to C-Leg. Clinical and health economic analyses have not been conducted with the Genium knee system. The purpose of this study was to determine if laboratory determined benefits of Genium are detectable using common clinical assessments and if there are economic benefits associated with its use. This study utilized a randomized AB crossover study with 60 d follow-up including cost-effectiveness analysis. Twenty TFA patients tested with both knees in mobility and preference measures. Incremental cost-effectiveness ratios (ICER) were calculated based on performance measures. Stair Assessment Index scores improved with Genium. Mean stair completion times and descent stepping rate were not different between knees. Stair ascent stepping rate for C-Leg was greater compared with Genium (p = 0.04). Genium use decreased Four square step test completion time and increased functional level and step activity (p ≤ 0.05). Further, Genium use improved (p ≤ 0.05) function and safety in three out of five Activities of Daily Living (ADL) survey domains. Finally, more subjects preferred Genium following testing. Functional measures were used to calculate ICERs. ICER values for Genium fall within established likely-to-accept value ranges. Compared with C-Leg, Genium use improved stair walking performance, multi-directional stepping, functional level, and perceived function. In this group of community ambulators with TFA, Genium was preferred, and, while more costly, it may be worth funding due to significant improvements in functional performance with ADLs. Key words: Amputee mobility predictor; Four square step test; Gait; Incremental cost-effectiveness ratio; Physical therapy; Preference; Rehabilitation; Stair assessment index; StepWatch _____________________ Accepted July 1, 2016. Address correspondence to M. Jason Highsmith, Extremity Trauma & Amputation Center of Excellence (EACE), 8900 Grand Oak Circle (151R), Tampa, FL 33637-1022, USA. Tel: +1 (813) 558-3936; Fax: +1 (813) 558-3990; E-mail: michael.highsmith@va.gov

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INTRODUCTION Compared to non-microprocessor prosthetic knee systems (NMPK), the C-Leg microprocessor knee system (MPK; Otto Bock Healthcare, Duderstadt, Germany) is more efficient in terms of gait bioenergentics and health-economic measures as well as safer for persons with transfemoral amputation (TFA) (1). Recently, the Genium MPK system has demonstrated improvements in perceived functional measures (2), knee kinematics (3), and physical functional performance (4) compared to C-Leg. Clinimetric assessment and health economic analysis have not yet been conducted. Therefore, the purpose of this study was to determine if laboratory determined benefits of the Genium are detectable using common clinical outcome assessments. A second purpose was to determine if there are health-economic benefits associated with use of the Genium knee system. METHODS The study was approved by the University of South Florida’s Institutional Review Board and listed in a federal clinical trial registry. Subjects gave informed consent prior to participation in the study. Study Design Overview A randomized experimental crossover design, where TFA patients used Genium and C-Leg MPK systems, was used. Subjects tested on both knee systems in random order separated by an accommodation period of >2 weeks to <3 months, depending upon when they determined their readiness to test. Subjects were assessed in a university clinical laboratory setting using common clinical outcome measures as described below. Randomization, Eligibility, and Interventions Subjects had to be unilateral TFA patients from any etiology and not have impairments that adversely impacted their gait beyond their amputations (e.g., cardiopulmonary, orthopedic impairments). Additionally, subjects had to be C-Leg users for ≥1 year prior to enrollment. An electronic random number generator was used to assign subjects (off site) to either continue with the C-Leg or be fit with a Genium MPK at recruitment. The study prosthetist was noti-

fied of each subject’s assigned condition via telephone on the day of the subject’s knee fitting. All fittings and adjustments were performed by the same study prosthetist, who was state-licensed and certified by the American Board for Certification in Orthotics, Prosthetics, and Pedorthics as well as by Ottobock Healthcare for fitting both C-Leg and Genium MPK systems. Subjects’ prosthetic sockets and suspension systems were not changed for the experiment’s duration to reduce confounding effects from fitting and acclimation issues. Subjects were fit with an Ottobock Trias (standard height) or Axtion (low profile) prosthetic foot, based on limb length, for use over the study duration. Manufacturer specifications were used to set componentry alignment and were verified using the LASAR (Ottobock, Duderstadt, Germany) alignment system. Fitting and Accommodation Periods After enrollment, anthropometric and demographic data and the study foot were recorded. Knee fittings and alignment were conducted and settings recorded. Subjects were invited to return to the study prosthetist or physical therapist for adjustment, alignment, and training as many times as they wished to optimize fit, comfort, and function and to mirror real clinical practice and component prescription. Visits were counted and reasons for each visit recorded. All subjects, regardless of the knee system with which they began the study, received an initial training session from the study physical therapist for each knee system for training in transitional movements, obstacle crossing, ramps, stairs, speed variation, and variable surfaces. Portions of the study’s training techniques have been previously published (5,6). The minimum accommodation period was two weeks. After this, subjects were contacted weekly to determine their ability to walk without personal assistance on 1) level ground, 2) inclines, 3) declines, 4) up & down stairs, and 5) on uneven ground. Subjects could contact investigators at any time after the two-week minimum to declare their readiness to physically demonstrate they had accommodated to their currently assigned knee and study foot. Subjects were considered accommodated after verbally

GENIUM KNEE: MOBILITY & ECONOMIC OUTCOMES acknowledging and physically demonstrating their ability to ambulate independently on all five of the previous terrains (7,8). Following accommodation, subjects were scheduled for initial data collection (phase A testing). Following initial testing, knee units were switched and the process repeated for the second data collection (phase B testing). Following the second data collection (phase B test), subjects were switched back into their C-Leg (original, pre-study knee). At this time, a third and final data collection (phase C testing) was administered 60 d following the second data collection. The third data collection (i.e., the 60 d follow-up) was administered via U.S. mail to subjects at their home addresses. Return of this survey marked the formal conclusion of subjects’ involvement in the study. Testing and Outcomes Objective Measures Stair Assessment Index (SAI) Subjects were asked to ascend and descend stairs compliant with the Americans with Disabilities Act (9) (four steps 17cm high x 28cm long x 91cm wide leading up to a platform with railing on both sides). Three trials ascending and three trials descending at a self-selected speed were timed using a stopwatch and video recorded. Stair assessment index (SAI) scores were determined later by two independent reviewers viewing the video recording using criteria outlined previously (7). The SAI is a stair gait evaluation instrument using a 13-point scale to determine gross motor pattern implementation of the subject and use of assistive devices (7,10). The SAI was found to have excellent inter-rater and intra-rater reliability for assessing both stair ascent and descent (11). Time to complete the test was recorded at data collection and SAI scores obtained from video review. Stepping rate was calculated by dividing the number of steps completed by time to complete the test. Four Square Step Test (4SST) The four square step test is a timed assessment of multi-directional stepping. Subjects step forward, backward, and to each side while stepping over canes oriented in a cross configuration to create four

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squares on the floor. In older adults, scores of ≥12 s are associated with fall risk, whereas in unilateral TTA patients, ≥24 s are associated with fall risk (12,13). Instructions were consistent with previous applications. Briefly, subjects were instructed to complete the test as quickly as possible but not to hop or jump over the canes. Three repeated trials were conducted and averaged to represent the subject’s final score. If a subject’s foot touched a cane, the trial was stopped and repeated until three successful trials were completed. Amputee Mobility Predictor (AMP) The AMP is a 21-item test of functional mobility used to determine a lower limb amputee’s ability to ambulate. AMP was shown to have moderate to strong concurrent validity with the six-minute walk test and the Amputee Activity Survey (14). Specific details of each item and test administration of the AMP have been described previously (14). The following is a synopsis of the mobility functions assessed by the AMP (14). Items 1 and 2 test the ability to maintain sitting balance. Items 3 through 7 test the ability to maintain balance while performing tasks of transferring from chair to chair and standing unchallenged. Items 8 through 13 test more challenging standing balance activities. Items 14 through 20 evaluate quality of gait and the ability to negotiate specific obstacles. Item 21 accounts for the use of particular assistive devices. Most AMP items offer three scoring choices: 0 indicates inability to perform the task, 1 indicates minimal level of achievement or that some assistance was required in completing the task, and 2 indicates complete independence or task mastery. The AMP test requires approximately 10 to15 min to administer and was administered by the study’s licensed physical therapist a single time at each data collection. Step Activity Derived Functional Level (SAD-FL) The Galileo cloud was accessed at https://galileo. orthocareinnovations.com (Orthocare Innovations, Mountlake Terrace, WA, USA), and subjects were registered in the cloud and the StepWatch device was programmed to start recording step activity. Subjects wore the StepWatch on the prosthetic limb’s lateral side just proximal to the approximate location of the anatomical ankle. The StepWatch recorded subjects’

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step activity for a two-week period immediately prior to laboratory data collections. At the end of the two-week recording period, StepWatch data was uploaded into the Galileo cloud server. At the point of data upload, each subject’s body mass and the study physical therapist’s opinion of the subject’s functional level (i.e., Medicare K-level) was also entered into the Galileo software. Following upload, a report of step activity and functional level is generated. The report provides an estimated K-level (i.e., functional level) based on multiple factors, including cadence variability, potential to ambulate, ambulation requirement, and the clinician’s observation of functional level. Cadence variability includes the proportion of steps taken at low, medium, and high cadence rates. Potential to ambulate relates to the intensity of walking during minutes of activity with the highest number of steps taken. Ambulation requirement considers the energy exerted during walking. Additionally, the clinically observed K-level is included and all of these K-levels are averaged into an overall K-level that has one-tenth level precision. The report’s K-level was intended to be rounded to achieve the final K-level. Perceptive Measures The significance of patient input on prosthetic prescription, knee selection, and fabrication and its influence on successful outcomes is established (15). To circumvent some of the pitfalls associated with subjective data collection yet still include it because of the value of capturing participant input and preference, two methods were considered. The first was to use a functional survey previously deployed in this population (16). The second method was to directly query participants regarding their component preference, a method which has previously been described as having the ability to strengthen or refute other study findings (15). Finally, these subjective measures were administered at a 60 d follow-up after subjects were returned to their pre-study knee, which was the C-Leg, and followed the initial two data collections (one for each knee for the crossover). This is particularly important given that, historically, MPK studies have not offered a follow-up assessment.

Activities of Daily Living Survey A questionnaire developed for a previous study (16) was used to survey subjects in activities of daily living (ADL) tasks (45 total items) divided into five activity categories: Personal Care and Dressing (four activities), Family and Social Roles, Leisure Time Activities (12 activities), Mobility and Transportation (19 activities), Health-related Exercise (four activities), and Other Activities (six activities). The individual ADL items are listed elsewhere (16). The survey has a portion for each comparative MPK system where subjects first rate the importance of ADLs and then rate the perceived difficulty and safety with the respective knee system. This was asked for each MPK at the respective test sessions for each knee. Finally, there is a third portion of the survey in which subjects are asked to subjectively compare the perceived difficulty and safety of performing the same 45 ADLs between the comparative MPK systems. This comparative survey was administered at a 60 d follow-up after the second (phase B) data collection. In this analysis, only the comparison of difficulty and safety were evaluated using an ordinal scale and non-parametric analysis consistent with survey’s authors (16). This provided insight into the difference in both functional ADL performance and safety between the two MPK systems from the patients’ perspective. Preference In order to capture true patient preference and exclude potential novelty effects or glitz bias (15), at the study’s conclusion (phase C test), subjects were asked which knee mechanism they preferred and would actually wish to continue using following the study’s conclusion. This measure was used to identify true subject preference regardless of the performance data. Subjects were asked four questions conducive to completing a 2 × 2 contingency table. Questions were: “Do you prefer and would you like to keep the C-Leg?” and “Do you reject and wish to stop using the C-Leg?” These were repeated for the Genium. Asked this way, subjects could ultimately choose to keep or reject either or both MPKs. Finally, subjects were asked, “If you could only keep either the Genium

GENIUM KNEE: MOBILITY & ECONOMIC OUTCOMES or the C-Leg, which would you prefer to keep as a permanent part of your prosthesis?” Cost-Effectiveness A previous report of the current randomized control trial analyzed function in activities of daily living using the Continuous Scale-Physical Functional Performance-10 assessment (CS-PFP-10), a measure shown to be valid, reliable, and sensitive to change in multiple diagnostic populations, including TFA patients (4,17-19). Incremental cost effectiveness ratios (ICER) were calculated using differences in scores for each of three domains (balance & coordination (BAL), upper body flexibility (UBF), and endurance (END)) that were significantly improved (p ≤ 0.05) when subjects used Genium compared with C-Leg on the CS-PFP-10 as source data for effects (denominator). Calculations for ICERs were conducted using the following equation:

The payor’s perspective was taken in order to understand if Genium use (new strategy) is cost-effective compared to the C-Leg (current practice) given the recent challenges with the reimbursement of advanced microprocessor prosthetic technologies. Private and federal sector prosthetic practitioners (i.e., expert opinion) were queried in terms of the differences reimbursed between the two study interventions. Because private sector practitioners commonly accept healthcare reimbursement from multiple payors, a considerable range of cost resulted. The range of differences in cost used for calculations was $30,000 and $55,000. ICERs were calculated in $5,000 increments across this range of reimbursement differences where the Genium is the more costly strategy. Assumptions used for ICER calculations included generalizability of the reported reimbursement across the U.S. given that practitioners were only queried from Florida. Another assumption is that discounting is built into the range of cost differences. An example is that some practitioners within the private sector receive volume

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purchasing discounts based on the size of their practice, and, further, federal sector practitioners may also receive discounted component costs. Uncertainty with the difference in performance was addressed by only using the domain score differences that were both improved and statistically significant from our previously published work (4). This was important given that Genium improved all domains of the CS-PFP-10, but not all domains were significantly improved. In terms of time horizon, ICERs were calculated based on the findings of the randomized clinical trial from which patients accommodated over a period <90 d. Therefore, ICER values were then projected over five years to project value over a common life expectancy for an MPK then amortized across this five-year period. Statistical Analyses Statistical analyses were performed with IBM SPSS (v21, Armonk, NY, USA). Data were compiled into a database, assessed for completeness, and descriptive analyses were performed (i.e., frequency, central tendency, variance). The Shapiro-Wilk test was used to determine if data were normally distributed. Betweenknee comparisons were made for each dependent variable. Normally distributed continuous data were assessed using dependent samples t tests (i.e., 4SST times). For ordinal data or data that were not normally distributed, a Related-Sample Wilcoxon Signed Rank test was used. This test evaluates the distribution of the difference between related samples rather than the difference between means. The a priori level of significance was p ≤ 0.05. Cohen’s d was then calculated to represent the magnitude of effect size between knee conditions for continuously scaled data when statistically significant differences were present. Cohen’s d was interpreted as d = 0.2 representing a small effect, 0.5 representing a medium effect, and 0.8 representing a large effect (20). Investigators adopted the “last observation carried forward” or “next observation carried backward” methods as the study’s a priori intention-to-treat plan (21,22). To determine if there were significant differences for preference, chi-squares/Fishers exact tests were used (i.e., categorical variables (prefer/not prefer, accept/ reject)).

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RESULTS Subject Demographics Twenty TFA subjects (n = 20) participated and completed all study tasks with complete data from both MPK systems. Most subjects were male (80%) with a mean (SD) age of 46.5 years (14.2) and BMI of 26.4 kg/m2 (4.2). The majority were employed (55%), 25% were governmentally classified as “disabled,” and the remaining 20% were students or retired. All subjects were independent, unlimited community ambulators (Medicare functional classification level 3). Mean time since amputation was 17.7 years (15.6), and amputation etiology was predominantly traumatic (70%) followed by malignancy (20%) and peripheral vascular disease (10%). Mean relative residual limb length (SD) was 70% (30%) of the sound side femur, and the mean hip flexion contracture was 12.8° (7.7) as measured with a manual goniometer in the Thomas test position. A variety of prosthetic sockets (e.g. ischial ramus containment, ischial support, subischial, quadrilateral) and suspension systems (e.g. locking liners, suction, elevated vacuum) were used. Sagittal knee alignment was not different (p > 0.05) between knee systems.

descent using C-Leg were 3.8 (1.1), 3.8 (1.0), and 3.7 (1.0) for trials one, two, and three, respectively. Corresponding times, in seconds, for Genium were 3.8 (1.0), 3.7 (0.8) and 3.6 (0.8). Mean differences for completion times were not significantly different. With C-Leg, subjects ascended stairs at a mean (SD) rate of 1.1 steps/s (0.5) compared to a mean rate of 0.8 steps/s (0.2) with Genium. The stepping rate was significantly increased when using C-Leg (p = 0.04; medium effect size). For descent, the mean (SD) stepping rate with C-Leg was 1.2 steps/s (0.4) compared to 1.1 steps/s (0.2) when using Genium. The stepping rate for descent was not significantly different between knee systems. 4SST, AMP, SAD-FL Results for the 4SST, AMP, and SAD-FL are shown in Table 1. Use of the Genium decreased time to complete the 4SST by 1.1 s. Functional performance increased by two points with Genium use as measured by the AMP and also by 0.2 points as measured by step activity derived functional level. These differences were all significantly improved (p ≤ 0.05) following accommodation and use of the Genium MPK.

SAI Table 1. Objective Measures: 4SST, AMP, and SAD-FL Table 1. Objective Measures: 4SST, AMP, and SAD-FL Mean and median SAI scores for trials one, two, and three using C-Leg during stair ascent were 5.6, C-Leg Genium 6.0, and 6.3 and 5, 6, and 6, respectively. Corresponding scores for Genium during stair ascent were 9.7, Test p value Central Central 9.9, and 10.1 with a median score of 11 for all trials. Variance Variance These results were significantly different (p = 0.001) Tendency Tendency between knee systems. Mean and median SAI scores for trials one, two, and three using C-Leg during stair 4SST 12.2 3.3 11.1 3.4 0.04 descent were 11.0, 10.3, and 11.2 with a median of 11 for all trials. Corresponding scores for Genium AMP 42 33 to 45 44 39 to 46 ≤0.001 during stair descent were 12, 11.7, and 11.8 with a median score of 11 for all trials. These results were SAD-FL 3.4 1.8 to 4.0 3.6 2.0 to 4.3 0.01 also significantly different between interventions (p = 0.04). Mean (SD) times, in seconds, for stair ascent using 4SST is a 4 square step test. AMP is amputee mobility predictor. C-Leg were 4.4 (1.5), 4.4 (1.4), and 4.5 (1.5) for triSAD-FL activitymobility derivedpredictor. functionalSAD-FL level. Central 4SST is 4 square step test. AMPisisstep amputee is stepTenactivity derived f als one, two, and three, respectively. Corresponding is mean for 4SST is median(range) (range)for forall allother other tests. Statistic level. Central Tendencydency is mean (SD)(SD) for 4SST andand is median times, in seconds, for Genium were 5.0Significance (1.0), 5.2 (1.6), Statistical is p small ≤0.05.(dEffect size for the 4SST is p ≤ 0.05.tests. Effect size for Significance the 4SST was = 0.33). was small (d = 0.33). and 4.7 (1.3). Mean (SD) times, in seconds for stair

GENIUM KNEE: MOBILITY & ECONOMIC OUTCOMES

Activities of Daily Living Survey Results for the ADL survey are in Table 2. Genium use resulted in improvements (p < 0.05) in perceived function and safety in three of five of the domains queried in the ADL survey. Improved domains included: 1) Family and Social Roles, Leisure Time Activities, 2) Mobility and Transportation, and 3) Other Activities. No differences were identified in the remaining two domains of the ADL survey: Personal Care and Dressing and Health-related Exercise. Preference There was a significant difference (p < 0.001; Fisher’s Exact Test given cell counts <5) between those who selected accept Genium (80.0% responses or 16/20 vs. 4/20 C-Leg accept) and those who selected reject C-Leg (65% or 13/20 vs. 1/20 who replied reject Genium). Some subjects seemed to be undecided or had some preference for both devices. Cost-Effectiveness Subjects achieved significantly higher (p < 0.05) function with Genium use (4). Using these measures of function, incremental cost-effectiveness of Genium vs. C-Leg ranged from $6,000 to $6,522 per unit increase in function (END & UBF and BAL

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respectively) assuming a $30,000 difference in cost (Figure 1). Using these same measures of function, incremental cost-effectiveness of Genium vs. C-Leg ranged from $11,000 to $11,957 per unit increase in function (END & UBF and BAL respectively) assuming a $55,000 difference in cost. If these costs were divided across five equal annual payments (i.e., five-year service life), the annual cost per increase in function is $1,200 to $1,304 (assuming $30,000 increased cost) or up to $2,200 to $2,391. The total one-time reimbursed difference in cost divided into five equal annual payments (i.e., one payment per year for 5 years with no interest) is $6,000/year ($30,000 cost difference) or $11,000/year ($55,000 cost difference). These costs are not adjusted for inflation or discounting and are expressed in 2016 U.S. dollars. These costs also presume that each unit of functional increase occurs in isolation. However, this is not the case, as each of these units of functional gain occurred simultaneously (4), thereby increasing value. DISCUSSION This study’s hypothesis was that laboratory determined benefits of Genium use previously identified (2,3,23-25) would translate into measurable improve-

Table 2. Activities of Daily Living Survey

Domain

Functional Improvement

Safety

Personal Care and Dressing

Family and Social Roles, Leisure Time

Genium

Mobility and Transportation

Genium

Health-related Exercise

Other Activities

Genium

Activities

ND is not different between MPK systems. When an MPK is listed (Genium or C-Leg), it was identified by subjects to be either a functional improvement or safer when used with the activities of daily living in the respective ND is not different between MPK systems. When an MPK is listed (Genium or C-Leg), it was identified by domain (p ≤ 0.05).

subjects to be either a functional improvement or safer when used with the activities of daily living in the respective domain (p ≤ 0.05).

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HIGHSMITH ET AL. Figure 1. Incremental cost effectiveness ratios for differences in cost between microprocessor knees based on functional improvements.

Incremental cost effectiveness ratios were determined based on the difference in cost of the interventions (Y axis), as a function of the ratio of the relative cost per unit of functional increase in three respective domains: balance (BAL), upper body flexibility (UBF), and endurance (END).

ments in common clinical outcome assessments as well. A second hypothesis was that, due to the increased functional benefits associated with Genium use, the technology could meet established thresholds acceptable to merit third-party reimbursement. SAI, 4SST, AMP, and SAD-FL Genium use resulted in significantly improved SAI scores and decreased stepping rate (medium effect size) while ascending stairs in a similar time. Further, Genium use improved SAI scores for stair descent with similar descent times and stepping rate. With Geniumâ&#x20AC;&#x2122;s stair ascent mode, most subjects were able to use a step-over-step pattern as opposed to a skipping step pattern and were able to decrease handrail usage. The step-over-step pattern is more symmetrical and utilizes kinematic patterns more like those of non-amputees. Typical stair climbing patterns have demonstrated improved physiological costs relative to alternative stair gait patterns (26). Reduced energy demand resulting from an improved stair gait pattern is potentially corroborated by the significant reduction in stepping rate with use of the Genium. The reduction in handrail use is also clinically relevant, as it was used in recent Medicare/

Medicaid Local Coverage Determination verbiage as a suggested factor in functional level determination with the use of a cane limiting a prosthetic user to the K2 level, which does not allow for reimbursement of MPK components (27). Although median SAI scores were identical between knees for stair descent, Genium allowed all subjects to perform a step-over-step descent without assistive device use. The maximum score for C-Leg was 11 during descent with a minimum score of three. This range of scores likely contributed to the statistical difference between knees but suggests improved consistency with the Genium system. Although there was no aggregate difference in time or stepping rate for descent between MPK systems, the gross motor pattern implemented (i.e., SAI scores) and decreased assistive device use with Genium further suggests that engineering advancements included in the Genium allowed for increased stability and balance compared to C-Leg as has been previously identified in other functional activities. The decreased time to complete the 4SST (small effect size), a test of multi-directional stepping, is also consistent with the notion of improved balance suggested here by improved stair climbing abilities

GENIUM KNEE: MOBILITY & ECONOMIC OUTCOMES resulting from Genium use. Beyond this, previous tests of function in ADLs demonstrated improvements in multi-directional stepping (4). Most notably, rearward directed steps and small steps were improved (4,25). In a previous test involving moving laundry from a washer to a dryer, a task involving small side steps and rearward steps, significant improvements were observed (4), which are consistent with the 9% improvement in 4SST times recorded in this study. Two means were used to assess functional level in this study. One was the AMP test, a test of transitional movement, stepping and balance (14) and the second was a functional level based on step activity. Tasks improved on the AMP test associated with Genium use included stair gait, obstacle crossing, and variable cadence. Conversely, most subjects were unable to achieve single-limb balance on the prosthesis regardless of which MPK they were using. The 2.0 point increase observed with Genium use in this study did not reach the minimal detectable change (MDC) value of 3.4 points for the AMP reported by Resnik and Borgia (28). Because the difference in AMP scores did not reach the MDC, it could be argued that true change may not have occurred relative to this specific test. However, Resnik and Borgiaâ&#x20AC;&#x2122;s sample was of mixed amputation level. Further, AMP scores were statistically significantly different, and key functions were improved with Genium use (e.g., stair gait, variable cadence, and obstacle crossing). Additional issues worthy of consideration include the testâ&#x20AC;&#x2122;s use of interval level data and the wide range of task difficulty. Previous study has shown that TFA patients tend to not alter their usual living patterns and step activity based solely on receipt of a new knee system (29). However, in this study, there was a significant increase in functional performance based on step activity. These changes in activity took place while participants were in their community or home environments, as lab steps were not counted. Thus, subjects had sufficiently increased steps, steps/bout, or step intensity to elevate their step activity derived functional levels. It is possible that subjects took these additional steps or changed their stepping routine in part due to participation in the study while attempting to accommodate with the study knee. From an activity perspective, this

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is desirable and yielded positive changes in function as previously noted in stair and multi-directional stepping function. Further supporting true change is the fact that the AMP test also measured a significant increase in functional level using parameters other than step activity. While this was true for both functional level measurements, neither functional measure changed to a higher functional level. Instead, subjectsâ&#x20AC;&#x2122; function increased significantly within their respective functional level. For instance, the group did not change from limited community to unlimited community ambulation. ADL Survey and Preference In addition to the objective functional measures described above, perceptive measures were increased or unchanged. Subjectively, there were no decreased functional measures or decreased perceptions of safety associated with use of the Genium. It is noteworthy that Genium increased safety and function in areas requiring community engagement (e.g., family, social and leisure roles, mobility and transportation) because this is consistent with the type of subject enrolled in the study who was (on average) in their mid-forties and active in the community. The fact that there was no difference in self-care suggests C-Leg may be meeting many of these needs. Conversely, the lack of difference in exercise function could be that both components still leave room for improvement. Interestingly, there was a significant difference in preference among this group of unlimited community ambulators. The magnitude of difference was comparable to that previously observed when a more functionally diverse subject group was asked their preference between NMPKs and the C-Leg (15). It is unclear if preference would be so strong in more functionally diverse patient groups or patients more homogeneously located at higher or lower ends of the functional spectrum. Cost-Effectiveness In this study, using functional measures, the ICER for reimbursing Genium vs. C-Leg ranged from $6,000 to $6,522 per unit of functional increase assuming a $30,000 intervention cost difference. Assuming the component would not require replacement for five

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years, this cost would likely amortize over the fiveyear service period (i.e., five equal annual payments with no interest). Thus, the estimated annual cost for this functional increase is $1,200 to $1,304. Alternatively, depending upon discounting and other factors, if the cost difference between the interventions is higher, at $55,000, the ICER for reimbursing Genium vs. C-Leg ranges from $11,000 to $11,957 per unit of functional increase. Again this amortizes to $2,200 to $2,391 annually over a five-year service period. When the C-Leg was initially introduced as an alternative to NMPKs, the initial cost was notably higher. In time, it was proven that while C-Leg was more expensive, it was worth funding for numerous reasons, including reducing falls, reducing lost time for prosthetic maintenance, and others (1). In the case of the Genium, in higher-functioning patients, it is clear that higher function in ADLs, quality of life, and functional level are all domains that realize gains that are above what the C-Leg can provide (2-4,16,24,25). In this sense, our estimates of incremental cost-effectiveness may be conservative, as our ICERs are expressed in terms of a single functional measure. Limitations This study lacked blinding, which is difficult to incorporate in rehabilitation research for safety and ethical reasons. The findings are based upon the experiences and performance of patients who may not be representative of the entire TFA population, as these subjects were unlimited community ambulators who lost their limbs predominantly due to trauma and malignancy. Regarding the cost effectiveness portion of the study, the patient and societal perspectives were not considered in the economic analysis. Future studies need to carefully consider the impact of improvement in functional measures on productivity. Our cost-effectiveness analysis only considered improvement in specific functional measures individually and not improvement simultaneously in these measures, which likely yielded conservative estimates. Future studies will need to consider overall health-related quality of life and quality-adjusted life years.

CONCLUSION Accommodation and use of the Genium knee system compared with C-Leg improved stair walking performance, multi-directional stepping, functional level, and perceived function. Genium was also preferred compared to C-Leg in this group of highfunctioning community ambulators with unilateral transfemoral amputation. Finally, Genium is a more costly microprocessor knee system but, in this group of patients, is worth funding due to significant differences in functional performance with activities of daily living. ACKNOWLEDGMENTS Contents of this manuscript represent the opinions of the authors and not necessarily those of the U.S. Department of Defense, U.S. Department of the Army, U.S. Department of Veterans Affairs, or any academic or health care institution. Authors declare no conflicts of interest. This project was funded by: 1. The Florida High Tech Corridor/USF Connect (Grant #FHT 10-26). 2. Otto Bock Healthcare (USF Grant #6140101200). 3. The National Institutes of Health Scholars in Patient Oriented Research (SPOR) grant (1K30RR22270). REFERENCES 1.

Highsmith MJ, Kahle JT, Bongiorni DR, Sutton BS, Groer S, Kaufman KR. Safety, energy efficiency, and cost efficacy of the C-Leg for transfemoral amputees: a review of the literature. Prosthet Orthot Int. 2010;34:362-77. Highsmith MJ, Kahle JT, Miro RM, Mengelkoch, LJ. Perceived differences between the Genium and the C-Leg microprocessor prosthetic knees in prosthetic-related function and quality of life. Technol Innov 2014;15(4):369-75. Lura DJ, Wernke MM, Carey SL, Kahle JT, Miro RM, Highsmith MJ. Differences in knee flexion between the Genium and C-Leg microprocessor knees while walking on level ground and ramps. Clin Biomech (Bristol, Avon). 2015;30:175-81.

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Highsmith MJ, Kahle JT, Miro RM, Cress ME, Lura DJ, Quillen WS, Carey SL, Dubey RV, Mengelkoch LJ. Functional performance differences between the Genium and C-Leg prosthetic knees and non-Amputees. J Rehabil Res Dev. Forthcoming. Highsmith MJ, Kahle JT, Lewandowski AL, Kim SH, Mengelkoch LJ. A method for training stepover-step stair descent gait with stance yielding prosthetic knees. J Prosthet Orthot. 2012;24:10-5. Highsmith MJ, Kahle JT, Lura DJ, Lewandowski AL, Quillen WS, Kim SH. Stair ascent and ramp gait training with the Genium knee. Technol Innov. 2014;15(4):349-58. Hafner BJ, Willingham LL, Buell NC, Allyn KJ, Smith DG. Evaluation of function, performance, and preference as transfemoral amputees transition from mechanical to microprocessor control of the prosthetic knee. Arch Phys Med Rehabil. 2007;88:207-17. Highsmith MJ. Microprocessor knees: considerations for accommodation and training. J Prosthet Orthot. 2013;25:60-4. US Department of Justice. ADA standards for accessible design. Washington (DC): US Department of Justice; 2010. Buell NC, Willingham LL, Allyn KJ, Hafner BJ, Smith DG. Evaluation of gait style to ascend and descend stairs for lower limb amputees. In: Boone D, editor. Proceedings of the 11th World Congress of the International Society of Prosthetics and Orthotics; 2004 Aug 1-6 Hong Kong. Hong Kong: Hong Kong National Society of the International Society for Prosthetics and Orthotics; 2004. p 367. Highsmith MJ, Kahle JT, Kaluf B, Miro RM, Mengelkoch LJ, Klenow TD. Psychometric evaluation of the HAI and SAI in transfemoral amputees using a microprocessor knee system. Technol Innov. Forthcoming 2016 Aug. Dite W, Connor HJ, Curtis HC. Clinical identification of multiple fall risk early after unilateral transtibial amputation. Arch Phys Med Rehabil. 2007;88:109-14. Dite W, Temple VA. A clinical test of stepping and change of direction to identify multiple

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falling older adults. Arch Phys Med Rehabil. 2002;83:1566-71. Gailey RS, Roach KE, Applegate EB, Cho B, Cunniffe B, Licht S, Maguire, Nash MS. The amputee mobility predictor: an instrument to assess determinants of the lower-limb amputeeâ&#x20AC;&#x2122;s ability to ambulate. Arch Phys Med Rehabil. 2002;83:613-27. Kahle JT, Highsmith MJ, Hubbard SL. Comparison of nonmicroprocessor knee mechanism versus C-Leg on Prosthesis Evaluation Questionnaire, stumbles, falls, walking tests, stair descent, and knee preference. J Rehabil Res Dev. 2008;45:1-14. Kannenberg A, Zacharias B, Mileusnic M, Seyr M. Activities of daily living: Genium bionic prosthetic knee compared with C-Leg. J Prosthet Orthot. 2013;25:110-7. Cress ME, Buchner DM, Questad KA, Esselman PC, deLateur BJ, Schwartz RS. Continuous-scale physical functional performance in healthy older adults: a validation study. Arch Phys Med Rehabil. 1996;77:1243-50. Cress ME, Petrella JK, Moore TL, Schenkman ML. Continuous-scale physical functional performance test: validity, reliability, and sensitivity of data for the short version. Phys Ther. 2005;85:323-35. Highsmith MJ, Kahle JT, Miro RM, Cress ME, Quillen WS, Carey SL, Dubey RV, Mengelkoch LJ. Concurrent validity of the continuous scale physical functional performance-10 (CS-PFP-10) test in transfemoral amputees. Technol Innov. Forthcoming 2016 Aug. Cohen J, editor. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale (NJ): Erlbaum; 1988. Buhi ER, Goodson P, Neilands TB. Out of sight, not out of mind: strategies for handling missing data. Am J Health Behav. 2008;32:83-92. Kenward MG, Molenberghs G. Last observation carried forward: a crystal ball? J Biopharm Stat. 2009;19:872-88. Highsmith MJ, Kahle JT, Lura DJ, Dubey RV, Carey SL, Quillen WS, Mengelkoch LJ. Short and mid-distance walking and posturography

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HIGHSMITH ET AL. with a novel microprocessor knee. Technol Innov 2014;15(4):359-68. Bellmann M, Schmalz T, Ludwigs E, Blumentritt S. Stair ascent with an innovative microprocessor-controlled exoprosthetic knee joint. Biomed Tech. 2012;57:435-44. Bellmann M, Schmalz T, Ludwigs E, Blumentritt S. Immediate effects of a new microprocessor-controlled prosthetic knee joint: a comparative biomechanical evaluation. Arch Phys Med Rehabil. 2012;93:541-9. Shiomi T. Effects of different patterns of stairclimbing on physiological cost and motor efficiency. J Hum Ergol. 1994;23:111-20. NHIC, Corp. A CMS Contractor. Proposed/Draft

Local Coverage Determination (LCD): Lower limb prostheses (DL33787). Hingham (MA): NHIC, Corp; 2015. Contract #16003. [accessed 2016 Aug 12]. http://www.amputee-coalition.org/ content/documents/medicare-alert-2015/doc_ LLP_Draft_LCD_071615.pdf. 28. Resnik L, Borgia M. Reliability of outcome measures for people with lower-limb amputations: distinguishing true change from statistical error. Phys Ther. 2011;91:555-65. 29. Klute GK, Berge JS, Orendurff MS, Williams RM, Czerniecki JM. Prosthetic intervention effects on activity of lower-extremity amputees. Arch Phys Med Rehabil. 2006;87:717-22.

ISSN 1949-8241 • E-ISSN 1949-825X http://dx.doi.org/10.21300/18.2-3.2016.151 www.technologyandinnovation.org

EFFECTS OF THE GENIUM MICROPROCESSOR KNEE SYSTEM ON KNEE MOMENT SYMMETRY DURING HILL WALKING M. Jason Highsmith1-3, Tyler D. Klenow4, Jason T. Kahle5,6, Matthew M. Wernke7, Stephanie L. Carey8, Rebecca M. Miro1, and Derek J. Lura9 2

1 School of Physical Therapy & Rehabilitation Sciences, University of South Florida, Tampa, FL, USA Extremity Trauma & Amputation Center of Excellence (EACE), U.S. Department of Veterans Affairs, Tampa, FL, USA 3 319th Minimal Care Detachment, U.S. Army Reserves, Pinellas Park, FL, USA 4 Prosthetics and Sensory Aids Service, James A. Haley Veterans’ Hospital, Tampa, FL, USA 5 OP Solutions, Inc., Tampa, FL, USA 6 Prosthetic Design and Research, Tampa, FL, USA 7 WillowWood, Mt. Sterling, OH, USA 8 Department of Mechanical Engineering, University of South Florida, Tampa, FL, USA 9 Department of Bioengineering and Software Engineering, Florida Gulf Coast University, Ft. Myers, FL, USA

Use of the Genium microprocessor knee (MPK) system reportedly improves knee kinematics during walking and other functional tasks compared to other MPK systems. This improved kinematic pattern was observed when walking on different hill conditions and at different speeds. Given the improved kinematics associated with hill walking while using the Genium, a similar improvement in the symmetry of knee kinetics is also feasible. The purpose of this study was to determine if Genium MPK use would reduce the degree of asymmetry (DoA) of peak stance knee flexion moment compared to the C-Leg MPK in transfemoral amputation (TFA) patients. This study used a randomized experimental crossover of TFA patients using Genium and C-Leg MPKs (n = 20). Biomechanical gait analysis by 3D motion tracking with floor mounted force plates of TFA patients ambulating at different speeds on 5° ramps was completed. Knee moment DoA was significantly different between MPK conditions in the slow and fast uphill as well as the slow and self-selected downhill conditions.In a sample of high-functioning TFA patients, Genium knee system accommodation and use improved knee moment symmetry in slow speed walking up and down a five degree ramp compared with C-Leg. Additionally, the Genium improved knee moment symmetry when walking downhill at comfortable speed. These results likely have application in other patients who could benefit from more consistent knee function, such as older patients and others who have slower walking speeds. Key words: Amputee; Biomechanics; Gait; Knee kinetics; Physical therapy; Ramps; Rehabilitation; Slope; Transfemoral

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INTRODUCTION The Genium microprocessor knee (MPK) system (Ottobock Healthcare, Duderstadt, Germany) reportedly implements several engineering advancements over previously manufactured MPK systems (1-5). Study of these advancements has resulted in a recent body of literature showing improved performance of the Genium even when compared to the C-Leg (Ottobock Healthcare, Duderstadt, Germany), the most studied commercially available MPK system (1-5). Compared to C-Leg, Genium use resulted in improved symmetry in peak knee flexion angles during stance and swing when ascending and descending ramps in a sample of transfemoral amputation (TFA) patients (6). This improved kinematic pattern was more similar to non-amputee controls when walking on different hill conditions and at different speeds. Given the improved kinematics associated with hill walking while using the Genium, a similar improvement in the symmetry of knee kinetics is also feasible. Due to the increased kinematic symmetry of the knee previously reported following Genium accommodation and use, the hypothesis of this study was that the Genium MPK system would increase symmetry in peak knee flexion moment during ramp gait. Thus, the study’s purpose was to determine if use of the Genium MPK would reduce the degree of asymmetry (DoA) of peak stance knee flexion moment compared to the C-Leg MPK in persons with transfemoral amputation.

reflective markers and an 8-camera Vicon (Oxford, United Kingdom) motion analysis system. Subjects walked up and down 5° ramps at slow, normal, and fast walking speeds. The task variations (walking speeds, ascent/descent) were intended to evaluate knee component performance under diverse gait conditions seen during community ambulation.

METHODS The study was approved by the University of South Florida’s Institutional Review Board and listed on clinicaltrials.gov (#NCT01473992). Subjects gave informed consent prior to participation in the study.

Fitting and Accommodation Periods After enrollment, anthropometric data, randomization order, and the study foot were recorded. Knee fittings and alignment were conducted and recorded. All subjects were invited to return to the study prosthetist or physical therapist for adjustment, alignment, and training as many times as they wished to optimize their fit, comfort, and function and to mirror real clinical practice and component prescription. Visits were counted, and reasons for each visit were recorded. All subjects, regardless of which knee system they began the study with, received an initial training session from the study physical therapist for each knee system for training in transitional movements, obstacle

Study Design Overview This study was a randomized experimental crossover of TFA patients using Genium and C-Leg MPKs. Each subject tested on both knee conditions in a random order separated by an accommodation period of >2 weeks to <3 months, depending upon when subjects determined their readiness to test. Subjects’ gait patterns were recorded using passive

Randomization and Interventions All subjects entering the study were C-Leg users for ≥1 year prior to enrollment. An electronic random number generator was used to assign subjects (off site) to either continue with their C-Leg or to be fit with a Genium knee system at recruitment. The study prosthetist was notified of the subject’s assigned condition via telephone on the day of the subject’s knee fitting. All fittings and adjustments were performed by the study prosthetist, who was state-licensed and certified by the American Board for Certification in Orthotics, Prosthetics, and Pedorthics as well as by Ottobock Healthcare for fitting both C-Leg and Genium MPK systems. The subjects’ prosthetic sockets and suspension systems were not changed for the duration of the experiment to reduce the confounding effects from fit and acclimation issues. All subjects were fit with an Ottobock Trias (standard height) or Axtion (low profile) prosthetic foot, based on limb length, for use over the study duration. Manufacturer specifications were used to set componentry alignment and were verified using the LASAR (Ottobock, Duderstadt, Germany) alignment system.

KNEE MOMENT SYMMETRY DURING HILL WALKING crossing, ramps, stairs, speed variation, and variable surfaces. Portions of the training techniques used in this protocol have been previously published (1,7). The minimum accommodation period was two weeks. After this, subjects were contacted weekly to determine their ability to walk without personal assistance on 1) level ground, 2) inclines, 3) declines, 4) up & down stairs, and 5) on uneven ground. Subjects could contact investigators at any time after the two-week minimum to declare their readiness to physically demonstrate they had accommodated to their currently assigned knee and study foot. Subjects were considered accommodated after verbally acknowledging and physically demonstrating their ability to ambulate independently on all five of the previous terrains. This study accommodation test was adapted from Hafner et al. (8,9). Following accommodation, subjects were scheduled for initial testing. Following initial testing, knee units were switched, and the process was repeated for follow-up testing. Testing Passive marker-based 3D motion tracking was selected to record and analyze knee movements because it is valid, reliable, and considered to be the gold standard measurement technique for gait analysis (10). Specifically, an 8-camera Vicon motion analysis system was used to collect knee kinematic data of subjects performing hill gait tasks. Passive reflective markers were attached to subjects using neoprene straps and double side adhesive collars as previously described (6). Force platforms (AMTI, Watertown, MA, USA) were embedded in the gait platform and ramps and used to record ground reaction forces and to time events. For instance, heel strike and toe off were identified with force plate data; however, the subsequent heel strike was recorded with kinematic approximation (11). In accordance with manufacturer specifications and recommendations, the Vicon cameras were calibrated and force platforms zeroed before each session and after adjusting the ramp to the slope condition. All subjects completed the hill walking tasks in the same order: 1) normal speed on 5° ramp uphill, 2) normal speed on 5° ramp downhill, 3) slow speed (i.e., casual) on 5° ramp uphill, 4) slow speed on 5°

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ramp downhill, 5) fast speed (i.e., hurried, late for appointment) on 5° ramp uphill, and 6) fast speed on 5° ramp downhill. Subjects were given the opportunity to rest between tests. A total of six different trial types were assessed, and each type was completed twice to record data over the force platform for both the prosthetic and anatomical leg. Data Processing Tracking segments were defined using the surface markers, and redundancy was included in the marker set to compensate for marker drop out and to increase data consistency and reliability. Frames were tracked by least squares minimization of the in-segment marker reconstruction error (12). A combination of anatomical markers and calculated joint centers were then used to define anatomical segments. Segment axes definitions were based on the recommendations of the International Society of Biomechanics (13). Joint angles were calculated from Euler angle transformations of anatomical segments. Although the marker set used enabled tracking of the entire lower body, knee flexion moment was the measure of interest that addressed the a priori hypotheses, and therefore was the only measure included in this report. The gait cycle was defined from heel strike to heel strike of the involved foot. Peak knee flexion moment was defined as the maximum knee flexion moment from 0% to 30% of the gait cycle to assure peak stance flexion in the loading response. The remainder of the gait cycle (30% to 100%) was considered swing phase and was not included in this report. These definitions were used to prevent subjects who used the ‘ride-down’ strategy on the ramp descent from inflating the stance flexion angles after the loading response and further increasing deviations in subject moment data. Vertical ground reaction forces (GRF) were determined from the force plates. A 2D kinematic model was written in Vicon Bodybuilder software to determine joint angles, forces, and moments of the knee in the sagittal plane. DoA between sound and prosthetic side knee flexion moments of the same trial type was calculated using the following equation:

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In this equation, “S” represents the sound side knee peak stance flexion moment and “P” represents the prosthetic side knee peak stance flexion moment. As a result of this calculation, a positive value would indicate a greater moment on the sound side, a negative value would indicate a greater moment of the prosthetic side, and a value of zero would indicate perfect symmetry between the two sides. Statistical Analyses Statistical analyses were performed with IBM SPSS (v21, Armonk, NY, USA). Data were compiled into a database, assessed for completeness, and descriptive analyses were performed (i.e., central tendency). The Shapiro-Wilk test was used to determine if data were normally distributed. Normally distributed data were assessed using dependent samples t tests for both peak stance and swing flexion moment by knee type per walking condition. For data that were not normally distributed, a Related-Sample Wilcoxon Signed Rank test was used. This test evaluates the distribution of the difference between related samples rather than the difference between means. The a priori level of significance was p ≤ 0.05. Cohen’s d was then calculated to represent the magnitude of effect size between knee conditions with regard to DoA of peak knee flexion moment. Cohen’s d was interpreted as d = 0.2 representing a small effect, 0.5 representing a medium effect, and 0.8 representing a large effect (14). Investigators adopted the “last observation carried forward” or “next observation carried backward” methods as the study’s a priori intention-to-treat plan (15,16). RESULTS Subject Demographics Twenty TFA subjects (n = 20) participated and completed all study tasks with complete data from both MPK systems. The majority of subjects were male (80%) with a mean (SD) age of 46.5 years (14.2) and BMI of 26.4 kg/m2 (4.2). The majority were employed (55%), 25% were governmentally classified as “disabled,” and the remaining 20% were students

or retired. All subjects were independent, unlimited community ambulators (Medicare functional classification level 3). The mean time since amputation was 17.7 years (15.6), and amputation etiology was predominantly traumatic (70%) followed by malignancy (20%) and peripheral vascular disease (10%). Mean relative residual limb length (SD) was 70% (±30%) of the sound side femur, and the mean hip flexion contracture was 12.8° (7.7) as measured with a manual goniometer in the Thomas test position. A variety of prosthetic sockets (i.e., ischial ramus containment, ischial support, subischial, quadrilateral) and suspension systems (i.e., locking liners, suction, elevated vacuum) were utilized by these subjects. Overall Knee moment DoA was statistically different between MPK conditions in the slow and fast uphill as well as the slow and self-selected downhill conditions (Table 1). The Genium improved knee moment DoA in all of these conditions except in the fast uphill condition, where there was no mean difference. In the latter condition, however, the increased variance, as shown with the increased SD of C-Leg compared with Genium, resulted in the statistical difference. Effect size within uphill conditions was medium for slow walking speed and small for the fast walking speed. Effect size within the downhill condition was small for the slow speed and large for the self-selected walking speed. The Genium MPK also displayed lower variance in peak knee stance flexion moment symmetry, as shown by SD, in all walking speeds in the uphill conditions and the self-selected downhill condition. The C-Leg displayed less variance than the Genium in the slow and fast downhill conditions. DISCUSSION Due to engineering advancements incorporated into the Genium MPK, including a sagittal knee moment sensor, angle sensor, and gyroscope, we hypothesized Genium use would increase symmetry in peak stance knee flexion moment in TFA patients compared to the C-Leg. This hypothesis was supported, as a majority (3 of 4) of the significant differences resulted in improved knee moment

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Table Degree of Asymmetry for Knee during Hill Walking Table1.1. Degree of Asymmetry for Moment Knee Moment during Hill Walking Walking Speed

Hill Condition Uphill Downhill

Slow

Self-selected

Fast

Measurement Parameter DoA (mn ± sd)

C-Leg

Genium

C-Leg

Genium

C-Leg

0.03 (0.15)

0.00 (0.04)*M

0.01 (0.23)

-0.01 (0.07) NA

0.00 (0.11)

0.00 (0.00)*S

DoA (mn ± sd)

0.03 (0.06)

0.01 (0.10)*S

0.07 (0.10)

0.00 (0.01)*L

0.03 (0.04)

0.08 (0.29)NA

Genium

DoA is degree of Asymmetry. *significantly different from C-Leg (p ≤ 0.05). When differences are significant, effect sizes are S for small, M for medium and L for large. When differences are not significant, effect size is NA (not available).

cant finding yielded no mean difference but, rather, decreased variance in knee moment with Genium use, which was a common trend in the results when compared to C-Leg. These findings indicate accommodation and use of the Genium MPK enabled increased prosthetic gait control as reflected by more favorable DoA values and variability in knee flexion moment in stance phase during ramp ascent and descent for unilateral TFA patients capable of unlimited community ambulation. Previous work has shown improved stability and knee flexion with C-Leg use compared to non-MPK (17,18) and MPK systems alike (19). Use of the Genium MPK has been shown to provide a more consistent stance flexion knee angle in a variety of walking speeds and terrains compared with C-Leg (6). The results of the present study corroborate the previously identified kinematic symmetry, as maximum stance flexion moments were markedly symmetrical and minimally varied with Genium MPK use compared with C-Leg use in this sample of high-functioning persons with TFA. Although these findings were derived from generally young, healthy, and highly-active amputees, clinical application exists for elderly amputees who may display high variation in gait parameters, which leads to falls (20). Prosthetic components that reduce biomechanical gait variability may be an effective means to facilitate independence for amputees at increased fall risk (21-23). A notable finding from this work is the improved knee moment symmetry and reduced variance in knee kinetics at slow walking conditions among MPKs. Older individuals are consistently found to have reduced gait speed relative to those in other age

a fear of falling, which could be intensified in amputees, thus contributing to notably reduced walking speed (21-23,25). Results of this work suggest that the Genium MPK system may be a desirable intervention for patients with transfemoral limb loss who range in function from high-functioning community ambulators to older amputees who walk slower and require more consistent knee performance. Current U.S. healthcare regulations mandate the ability to vary cadence in order to be considered for MPK eligibility. Elderly persons with TFA are thus at risk of denial of MPK consideration due to this requirement. However, limited community ambulators have been shown to gain as many (or more) of the benefits of MPK technology than their unlimited community ambulating peers (26). CONCLUSION Accommodation and use of the Genium knee system, compared with C-Leg, improved knee moment symmetry in slow speed walking up and down a five degree ramp. Additionally, the Genium improved knee moment symmetry when walking downhill at comfortable speed. At fast walking speed, variance in knee moment symmetry was lower when using Genium. These results were found in a sample of high functioning persons with unilateral transfemoral amputation; however, the results likely have application in other patients who could benefit from more consistent knee function, such as older patients and others who have slower walking speeds. ACKNOWLEDGMENTS Contents of this manuscript represent the opinions of the authors and not necessarily those of the

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U.S. Department of Defense, U.S. Department of the Army, U.S. Department of Veterans Affairs, or any academic or health care institution. Authors declare no conflicts of interest. This project was funded by: 1. The Florida High Tech Corridor/USF CONNECT (USF Grant #FHT 10-26). 2. Otto Bock Healthcare (USF Grant #6140101200). 3. The National Institutes of Health Scholars in Patient Oriented Research (SPOR) grant (1K30RR22270). REFERENCES 1. Highsmith MJ, Kahle JT, Lura DJ, Lewandowski AL, Quillen WS, Kim SH. Stair ascent and ramp gait training with the Genium knee. Technol Innov. 2014;15(4):349-58. 2. Highsmith MJ, Kahle JT, Lura DJ, Dubey RV, Carey SL, Quillen WS, Mengelkoch LJ. Short and mid-distance walking and posturography with a novel microprocessor knee. Technol Innov. 2014;15(4):359-68. 3. Highsmith MJ, Kahle JT, Miro RM, Lura D, Dubey RV, Carey SL, Quillen WS, Mengelkoch LJ. Perceived differences between the Genium and the C-Leg microprocessor prosthetic knees in prosthetic-related function and quality of life. Technol Innov. 2014;15(4):369-75. 4. Bellmann M, Schmalz T, Ludwigs E, Blumentritt S. Stair ascent with an innovative microprocessor-controlled exoprosthetic knee joint. Biomed Tech. 2012;57:435-44. 5. Bellmann M, Schmalz T, Ludwigs E, Blumentritt S. Immediate effects of a new microprocessor-controlled prosthetic knee joint: a comparative biomechanical evaluation. Arch Phys Med Rehabil. 2012;93:541-9. 6. Lura DJ, Wernke MM, Carey SL, Kahle JT, Miro RM, Highsmith MJ. Differences in knee flexion between the Genium and C-Leg microprocessor knees whil walking on level ground and ramps. Clinical Biomech (Bristol, Avon). 2015;30:17581. 7. Highsmith MJ, Kahle JT, Lewandowski AL, Kim SH, Mengelkoch LJ. A method for training stepover-step stair descent gait with stance yielding

9. 10.

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12.

13.

14. 15. 16. 17.

prosthetic knees. J Prosthet Orthot. 2012;24:10-5. Hafner BJ, Willingham LL, Buell NC, Allyn KJ, Smith DG. Evaluation of function, performance, and preference as transfemoral amputees transition from mechanical to microprocessor control of the prosthetic knee. Arch Phys Med Rehabil. 2007;88:207-17. Highsmith MJ. Microprocessor knees: considerations for accommodation and training. J Prosthet Orthot. 2013;25:60-4. Hillman SJ, Donald SC, Herman J, McCurrach E, McGarry A, Richardson AM, Robb JE. Repeatability of a new observational gait score for unilateral lower limb amputees. Gait Posture. 2010;32:39-45. O’Connor CM, Thorpe SK, O’Malley MJ, Vaughan CL. Automatic detection of gait events using kinematic data. Gait Posture. 2007;25:46974. Cappozzo A, Cappello A, Della Croce U, Pensalfini F. Surface-marker cluster design criteria for 3-D bone movement reconstruction. IEEE Trans Biomed Eng. 1997;44:1165-74. Wu G, Siegler S, Allard P, Kirtley C, Leardini A, Rosenbaum D, Whittle M, D’Lima DD, Cristofolini L, Witte H, Schmid O, Stokes I, Standardization and Terminology Committee of the International Society of Biomechanics. ISB recommendation on definitions of joint coordinate system of various joints for the reporting of human joint motion--part I: ankle, hip, and spine. International Society of Biomechanics. J Biomech. 2002;35:543-8. Cohen J, editor. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale(NJ): Erlbaum; 1988. Buhi ER, Goodson P, Neilands TB. Out of sight, not out of mind: strategies for handling missing data. Am J Health Behav. 2008;32:83-92. Kenward MG, Molenberghs G. Last observation carried forward: a crystal ball? J Biopharm Stat. 2009;19:872-88. Kaufman KR, Levine JA, Brey RH, Iverson BK, McCrady SK, Padgett DJ, Joyner MJ. Gait and balance of transfemoral amputees using passive mechanical and microprocessor-controlled

KNEE MOMENT SYMMETRY DURING HILL WALKING prosthetic knees. Gait Posture. 2007;26:489-93. 18. Segal AD, Orendurff MS, Klute GK, McDowell ML, Pecoraro JA, Shofer J, Czerniecki JM. Kinematic and kinetic comparisons of transfemoral amputee gait using C-Leg and Mauch SNS prosthetic knees. J Rehabil Res Dev. 2006;43:85770. 19. Thiele J, Westebbe B, Bellmann M, Kraft M. Designs and performance of microprocessor-controlled knee joints. Biomed Tech (Berl). 2014;59:65-77. 20. Hollman JH, McDade EM, Petersen RC. Normative spatiotemporal gait parameters in older adults. Gait Posture. 2011;34:111-8. 21. Miller WC, Deathe AB, Speechley M, Koval J. The influence of falling, fear of falling, and balance confidence on prosthetic mobility and social activity among individuals with a lower extremity amputation. Arch Phys Med Rehabil. 2001;82:1238-44.

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22. Miller WC, Speechley M, Deathe B. The prevalence and risk factors of falling and fear of falling among lower extremity amputees. Arch Phys Med Rehabil. 2001;82:1031-7. 23. Miller WC, Speechley M, Deathe AB. Balance confidence among people with lower-limb amputations. Phys Ther. 2002;82:856-65. 24. Bohannon RW. Comfortable and maximum walking speed of adults aged 20-79 years: reference values and determinants. Age Ageing. 1997;26:15-9. 25. Miller WC, Deathe AB. A prospective study examining balance confidence among individuals with lower limb amputation. Disabil Rehabil. 2004;26:875-81. 26. Kannenberg A, Zacharias B, Probsting E. Benefits of microprocessor-controlled prosthetic knees to limited community ambulators: systematic review. J Rehabil Res Dev. 2014;51:1469-96.

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BIOENERGETIC DIFFERENCES DURING WALKING AND RUNNING IN TRANSFEMORAL AMPUTEE RUNNERS USING ARTICULATING AND NON-ARTICULATING KNEE PROSTHESES M. Jason Highsmith1-3, Jason T. Kahle4,5, Rebecca M. Miro1, and Larry J. Mengelkoch6 School of Physical Therapy & Rehabilitation Sciences, University of South Florida, Tampa, FL, USA Extremity Trauma & Amputation Center of Excellence (EACE), U. S. Department of Veterans Affairs, Tampa, FL, USA 3 319th Minimal Care Detachment, U.S. Army Reserves, Pinellas Park, FL, USA 4 OP Solutions, Inc., Tampa, FL, USA 5 Prosthetic Design + Research, Tampa, FL, USA 6 Doctor of Physical Therapy Program, University of St. Augustine for Health Sciences, St. Augustine, FL, USA 1

Transfemoral amputation (TFA) patients require considerably more energy to walk and run than non-amputees. The purpose of this study was to examine potential bioenergetic differences (oxygen uptake (VO2), heart rate (HR), and ratings of perceived exertion (RPE)) for TFA patients utilizing a conventional running prosthesis with an articulating knee mechanism versus a running prosthesis with a non-articulating knee joint. Four trained TFA runners (n = 4) were accommodated to and tested with both conditions. VO2 and HR were significantly lower (p ≤ 0.05) in five of eight fixed walking and running speeds for the prosthesis with an articulating knee mechanism. TFA demonstrated a trend for lower RPE at six of eight walking speeds using the prosthesis with the articulated knee condition. A trend was observed for self-selected walking speed, self-selected running speed, and maximal speed to be faster for TFA subjects using the prosthesis with the articulated knee condition. Finally, all four TFA participants subjectively preferred running with the prosthesis with the articulated knee condition. These findings suggest that, for trained TFA runners, a running prosthesis with an articulating knee prosthesis reduces ambulatory energy costs and enhances subjective perceptive measures compared to using a non-articulating knee prosthesis. Key words: Above-knee amputee; Energy costs; No-knee running prosthesis; Oxygen uptake; Physical therapy; Rehabilitation

improve energy costs and ambulatory performance would be functionally important to persons with TFA. Mengelkoch et al. (2) recently reported on the effects of prosthetic foot components on energy costs and ambulatory performance for TFA patients during walking and running. In this study, all TFA subjects were tested using three prosthetic feet conditions: a conventional solid ankle cushioned heel (SACH) foot; a general-purpose energy storing and return (ESAR)

INTRODUCTION Transfemoral amputation (TFA) patients require considerably more energy to ambulate than non-amputees. Studies by Genin at al. (1) and Mengelkoch et al. (2) have reported that the energy costs (oxygen uptake (VO2)) during walking for TFA patients are 30% to 78% greater than for non-amputee control subjects. Thus, any prosthetic component that could

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Accepted July 1, 2016. Address correspondence to M. Jason Highsmith, Extremity Trauma & Amputation Center of Excellence (EACE), 8900 Grand Oak Circle (151R), Tampa, FL 33637-1022, USA. Tel: +1 (813) 558-3936; Fax: +1 (813) 558-3990; E-mail: michael.highsmith@va.gov

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foot, which utilized a carbon fiber keel and ankle; and a running-specific ESAR foot, which utilized a carbon fiber C-shaped keel but was heelless. During walking for TFA, at both fixed speeds and self-selected walking speeds (SSWS), no significant differences were observed for energy costs (VO2, gait economy, gait efficiency (GE)) among the three prosthetic feet conditions. However, at SSWS, TFA patients demonstrated significantly improved speed with the general-purpose ESAR foot and running-specific ESAR foot compared to the SACH foot (7% and 9% respectively). Studies reporting the effects of prosthetic foot components on energy costs and ambulatory performance for TFA patients during running are very limited. In their study, Mengelkoch et al. (2) reported that TFA patients were not safely able to utilize the SACH foot during running. They observed that TFA participants were able to run at speeds up to their self-selected running speeds (SSRS) using the general purpose ESAR foot and the running-specific ESAR foot. At SSRS, the speed deemed comfortable for sustained distance running, GE was similar for TFA subjects using the general-purpose ESAR foot and the running-specific ESAR foot. However, a functional difference was that SSRS was significantly slower using the general-purpose ESAR foot (13%) compared to the running-specific ESAR foot. Another important observation from this study was that TFA participants were only able to run at speeds greater than SSRS using the running-specific ESAR foot. These researchers recommended that clinicians should recommend and prescribe a running-specific ESAR foot for TFA runners interested in performing more vigorous distance-type running (i.e., for exercise and running competition). It has been observed that some TFA distance runners prefer to run with a prosthesis that has a non-articulating knee joint (i.e., a no-knee condition, in which a straight pylon attaches to the prosthetic socket and foot components). Anecdotally, it has been suggested that, during running, increased energy may be required for TFA patients to control the prosthetic articulating knee to prevent it from buckling, compared to a prosthesis with a non-articulating knee joint (3). Previously, a preliminary

study compared VO2 peak attained during running for two TFA runners utilizing both a conventional running prosthesis with an articulating knee mechanism and a prosthesis that had a non-articulating knee joint (3). Results were mixed in that VO2 peak was higher for one subject using the prosthesis with an articulating knee mechanism and one subject using the prosthesis that had the non-articulating knee joint. However, both subjects were able to run longer and attained faster speeds using the prosthesis that had the non-articulating knee joint. Based on their results, these researchers suggested that a prosthesis with a non-articulating knee joint may be more energy efficient for TFA runners. However, this study had several limitations. It utilized only two subjects, did not specify an accommodation period for TFA patients to utilize each type of prosthesis, performed the maximal exercise tests for both prostheses with only a 30 min rest between tests, and did not include information concerning ratings of perceived exertion during testing or subjective preference for running with each type of running prosthesis. Given the limitations in the study by Wening et al. (3), the purpose of this study was to further examine potential bioenergetic differences for TFA patients utilizing a conventional running prosthesis with an articulating knee mechanism versus a running prosthesis that has a non-articulating knee joint. METHODS Subjects Two male and two female (n = 4) unilateral TFA runners with amputation due to non-vascular causes were recruited (Table 1). Participants were healthy recreational runners (K4, Medicare Functional Classification Level), age ≤45 years, who performed run training 3 to 5 d·week-1 for ≤30 min·d-1 for ≥1 year. The study was conducted in accordance with ethical standards recommended by the Belmont Report (4). The study protocol was approved by the University of South Florida’s Institutional Review Board, and each study participant provided written informed consent.

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Table 1. Physical Characteristics of Transfemoral Amputee were then given a one-month accommodation period Table 1. Physical Characteristics of Transfemoral Amputee Participants Participants to train and exercise with the non-articulating knee Gender Age (y) Height (cm) Weight (kg) 2-1 Body Mass Index kg*m

n = 2 male, n = 2 female 28.5 ± 4.2 173.6 ± 6.2 68.5 ± 23.4 22.5 ± 7.0

All amputees were non-dysvascular.

Study design Figure 1. Running prostheses: (a) articulated knee prosthesis and (b) non-articulated knee prosthesis.

The study utilized a two-period repeated measures crossover experimental design. Each TFA participant was tested with two prosthetic knee conditions (Figure 1). Condition 1: The participant’s usual running prosthesis was used with an articulating knee mechanism. All TFA runners utilized the same articulating knee mechanism, and all TFA participants utilized a running-specific ESAR foot, but the manufacturer differed among subjects (Table 2). Condition 2: The participant’s usual running prosthesis fitted with a pylon (non-articulating knee condition, also called no-knee condition) of sufficient length to replace their preferred articulating knee mechanism. Subjects

condition prior to assessment. To ensure the assignment of the order of testing for the two prosthetic knee conditions was balanced and randomized, a block randomization method was used (5,6). Subjects acclimated to both conditions then tested with each prosthetic configuration on separate days in random order.

Exercise Testing Procedures For exercise testing, participants reported to the laboratory in the morning following a minimum 8 h fasting period and having refrained from exercise for approximately 48 h. Participants performed peak effort exercise testing for each test condition using an incremental treadmill (Quinton TM65™, Cardiac Science, Waukesha, WI, USA) walking and running protocol. Testing began at 0.67 m·s-1 at a 0% grade. Speed increased every 2 min by 0.233 m·s-1. Approximately 48 to 72 h prior to testing, participants came to the laboratory for a treadmill familiarization session. At familiarization, individual SSWS & SSRS were determined for the given prosthetic knee condition and programmed into the subjects’ respective exercise tests. Measurements Heart rate (HR) and VO2 were measured continuously by telemetry and breath-by-breath gas exchange analysis (COSMED K4b2 ™, Rome, Italy). Calibration was performed immediately prior to testing according to manufacturer specifications. Flow volume measures were calibrated using a 3 L syringe and gas analyzers were calibrated to known gas mixtures. Body weight measurements without prosthesis were used for VO2 (ml O2·kg-1·min-1) measurements relative to body weight. During each minute of exercise testing and at peak exercise, participants rated perceived exertion (RPE) using the Borg scale (6 to 20) (7). Upon concluding exercise testing with both prosthetic knee conditions, participants were asked to subjectively rank the two prosthetic conditions by which was most preferred.

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Table 2. Characteristics ofTypes the Two Types of Running Prostheses Table 2. Characteristics of the Two of Running Prostheses Socket Suspension Knee Foot

Weight of Prosthesis (kg)

Articulated Knee n = 2, ischial containment; n = 2, sub-ischial. n = 2, elevated vacuum; n = 2, suction. n = 4, Total Knee 2000® (Ossur, Reykjavek, Iceland)

Non-Articulated Knee n = 2, ischial containment; n = 2, sub-ischial. n = 2, elevated vacuum; n = 2, suction. n = 4, Pylon

n = 2, Flex Run® (Ossur, Reykjavek, Iceland); n = 2, Nitro® (Freedom Innovations, Irvine, CA, USA) 3.65 ± 0.40

n = 2, Flex Run® (Ossur, Reykjavek, Iceland); n = 2, Nitro® (Freedom Innovations, Irvine, CA, USA) 3.05 ± 0.40

a. The Total Knee 2000 utilizes a mechanical hydraulic knee system. b. The Flex Run and Nitro prosthetic feet are running-specific, energy storing and return feet. a. The Total Knee 2000 utilizes a mechanical hydraulic knee system. c. No significant difference in the weight of the articulated knee prosthesis vs. the non-articulated knee prosthesis.

b. The Flex Run and Nitro prosthetic feet are running-specific, energy storing and return feet. c. No significant difference in the weight of the articulated knee prosthesis vs. the non-articulated Data Analysis indicating the non-articulating knee condition cost knee prosthesis.

Data were verified for accuracy, completeness, and normality. Parametric tests were selected and applied when appropriate; otherwise, non-parametric equivalent tests were used to compare responses between the two prosthetic knee conditions. It was expected that, during running, TFA participants would have variable speed/stage end-points of exercise tolerance for each prosthetic knee condition. Thus, some missing data for the TFA participants for the two prosthetic knee conditions was anticipated. We selected, a priori, the “last observation carried forward” method as our intention-to-treat strategy for imputation of missing data (8). Statistical analyses were performed using IBM SPSS software (v22, Armonk, NY, USA). For all procedures, statistical significance was p < 0.05. Values are reported as means ± standard deviation (SD).

more energy to use at most speeds. Mean RPE was not significantly different between the two prosthetic knee conditions. However, as seen in Figure 4, there was a trend in which RPE was higher for the non-articulating knee condition at six of eight speeds, which suggests more effort was needed at most speeds with the non-articulating knee condition. Differences in gait speeds between the two prosthetic knee conditions are shown in Figure 5. There were no significant differences between the two prosthetic knee conditions for SSWS, SSRS, or maximal speed attained. However, a trend emerged whereby use of the articulating knee condition resulted in faster SSWS, SSRS, and maximal speed. All four TFA participants subjectively ranked the prosthesis with the articulated knee condition as their most preferred running prosthesis.

RESULTS Mean VO2 for five of eight speeds, represented as the shaded region (speeds 1.12 to 2.01 m·sec-1) in Figure 2, were significantly greater (p ≤ 0.05) for the non-articulating knee (no-knee) condition, indicating the non-articulating knee condition cost more energy to use at these speeds. Mean HR for five of eight speeds, represented as the shaded region (speeds 1.34 to 2.24 m·sec-1) in Figure 3, were significantly greater for the non-articulating knee condition, also

DISCUSSION The results in this study differ from those reported by Wening et al. (3). In that study, they tested two TFA runners and reported only on their end of exercise data. They reported VO2 peak was higher for one subject using the prosthesis with an articulating knee mechanism and one subject using the prosthesis that had the non-articulating knee joint. However, both subjects were able to run longer and attained faster speeds using the prosthesis that had the non-articu-

KNEE VS. NO-KNEE TRANSFEMORAL RUNNING Figure 2. Differences in oxygen uptake (VO2) during walking & running for TFA using a non-articulated knee prosthesis (no-knee) & an articulated knee prosthesis (knee).

Transfemoral amputees (TFA). VO2 at speeds 1.12 – 2.01 m·sec-1 (shaded region), were significantly greater (p < 0.05) for the non-articulating knee (no-knee) condition.

Figure 3. Differences in heart rate during walking & running for TFA using a non-articulated knee prosthesis (no-knee) & an articulated knee prosthesis (knee).

Transfemoral amputees (TFA). Heart rate at speeds 1.34 – 2.24 m·sec-1 (shaded region), were significantly greater (p < 0.05) for the non-articulating knee (no-knee) condition.

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HIGHSMITH ET AL. Figure 4. Differences in rating of perceived exertion (RPE) during walking & running for TFA using a non-articulated knee prosthesis (no-knee) & an articulated knee prosthesis (knee).

Transfemoral amputees (TFA). No significant differences in RPE between knee conditions.

Figure 5. Differences in self-selected walking speeds (SSWS), self-selected running speeds (SSRS), & maximal speeds (MAX) attained for TFA using a non-articulated knee prosthesis (noknee) & an articulated knee prosthesis (knee).

Transfemoral amputees (TFA). No significant differences in SSWS, SSRS and MAX between knee conditions.

KNEE VS. NO-KNEE TRANSFEMORAL RUNNING lating knee joint. In the current study, we compared VO2, HR, and RPE data at eight fixed ambulation speeds (walking & running) and SSWS and SSRS. We observed significant differences at most fixed speeds for VO2 and HR, suggesting that energy costs were lower using the prosthesis with the articulated knee condition. For RPE, we observed a trend wherein, at most fixed speeds, RPE was lower using the prosthesis with the articulated knee condition, suggesting that less effort was required using that prosthesis. We also observed that there was a trend for SSWS, SSRS, and maximal speed attained to be faster for TFA subjects using the prosthesis with the articulated knee condition. Finally, all four TFA participants preferred ambulating with the prosthesis with the articulated knee condition. The primary limitation of this study was the small sample size and thus the generalizability; these findings may be limited to TFA runners with similar characteristics. Moreover, more thorough demographic (i.e., time since amputation), anthropometric (i.e., limb length), and history (i.e., exercise history) data could be gathered to facilitate better understanding regarding to whom the results would apply. CONCLUSION These findings suggest that, for trained TFA runners, a running prosthesis with an articulating knee prosthesis reduces ambulatory energy costs and enhances subjective perceptive measures compared to using a non-articulating knee prosthesis. ACKNOWLEDGMENTS Contents of this manuscript represent the opinions of the authors and not necessarily those of the U.S. Department of Defense, U.S. Department of the Army, U.S. Department of Veterans Affairs, or any academic or health care institution. Authors declare no conflicts of interest. This project was funded by the National Institutes of Health Scholars in Patient Oriented Research (SPOR) grant (1K30RR22270).

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Genin JJ, Bastien GJ, Franck B, Detrembleur C, Willems PA. Effect of speed on the energy cost of walking in unilateral traumatic lower limb amputees. Eur J Appl Physiol. 2008;103(6):655-63. Mengelkoch LJ, Kahle JT, Highsmith MJ. Energy costs & performance of transfemoral amputees & non-amputees during walking & running: a pilot study. Prosthet Orthot Int. Forthcoming. Wening J, Stockwell M. Oxygen consumption and prosthetic moments for two transfemoral amputees running with and without a knee. Paper presented at: AAOP 2012. American Academy of Orthotists & Prosthetists 38th Academy Annual Meeting and Scientific Symposium; 2012 Mar 21-24; Atlanta, GA.US Department of Health. HCFA Common Procedure Coding System (HCPCS) 2001. Springfield (VA): US Department of Commerce, National Technical Information Service; 2001. US Department of Health, Education, and Welfare. The Belmont report: ethical principles and guidelines for the protection of human subjects of research. Washington (DC): US Government Printing Office; 1979 [accessed 2016 Jul 7]. http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html. Kang M, Ragan BG, Park JH. Issues in outcomes research: an overview of randomization techniques for clinical trials. J Athl Train. 2008;43: 215-221. Doig GS, Simpson F. Randomization and allocation concealment: a practical guide for researchers. J Crit Care. 2005;20:187-191. Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc. 1982;14(5):377-81. Kenward MG, Molenberghs G. Last observation carried forward: a crystal ball? J Biopharm Stat. 2009;19(5):872-8

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THE EFFECT OF TRANSFEMORAL INTERFACE DESIGN ON GAIT SPEED AND RISK OF FALLS Jason T. Kahle1,2, Tyler D. Klenow3, William J. Sampson4, M. Jason Highsmith5-7 OP Solutions, Tampa, FL, USA Prosthetic Design + Research, Tampa, FL, USA 3 Prosthetics and Sensory Aids Service, James A. Haley Veterans’ Hospital, Tampa, FL, USA 4 Sampson’s Prosthetic & Orthotic Laboratories, Schenectady, NY, USA 5 School of Physical Therapy & Rehabilitation Sciences, University of South Florida, Tampa, FL, USA 6 Extremity Trauma & Amputation Center of Excellence (EACE), U.S. Department of Veterans Affairs, Tampa, FL, USA 7 319th Minimal Care Detachment, U.S. Army Reserves, Pinellas Park, FL, USA 1

Falls and diminished walking capacity are impairments common in persons with transfemoral amputation (TFA). Reducing falls and optimizing walking capacity through such means as achieving a more normal gait speed and community ambulation should be considered when formulating the prosthetic prescription. Because walking capacity and balance confidence are compromised with TFA, these outcomes should be considered when evaluating interfaces for transfemoral prosthetic users. The purpose of this study was to compare the effect of TFA interface design on walking capacity and balance confidence A retrospective cohort design was utilized involving unilateral TFA patients who used ischial ramus containment (IRC) and High-Fidelity (HiFi) interfaces (independent variables). Dependent variables included the Activity-specific Balance Scale (ABC) and the two-minute walk test (2MWT). Complete records were available for 13 patients (n = 13). The age range was 26 to 58 years. Three patients functioned at the K4 activity level, whereas all others functioned at the K3 level. Mean ABC scores were significantly different (p ≤ 0.05) at 77.2 (±16.8; 35.6 to 96.9) for IRC and 90.7 (±5.7; 77.5 to 98.7) for HiFi. The mean distance walked on the 2MWT was 91.8 m (±22.0, 58.3 to 124.7) for IRC compared to 110.4 m (±28.7; 64.7 to 171.1) for the HiFi socket (p ≤ 0.05). Alternative transfemoral interface design, such as the HiFi socket, can improve walking capacity and balance confidence in higher-functioning TFA patients. Key words: Above the knee amputee; Activity balance confidence; Compression release socket; High-fidelity interface; Ischial containment; Prosthetic socket; Walking tests

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INTRODUCTION Falling is prevalent among the amputee population particularly when comorbidities exist. Developing and studying fall prevention is a priority for reducing adverse effects and costs. Falls cost $23.3 billion annually. Their mean cost ranges from $3,476 per faller to $10,749 per injurious fall to $26,483 per fall requiring hospitalization. Approximately 20% of falls require medical attention (1,2). Annually, 52.4% of lower limb amputees report falling, whereas 49.2% report fear of falling (3,4). Falling and fear of falling are common among patients with transfemoral amputation (TFA), who have yearly fall rates as high as 66% (5,6). Further studies are required to characterize the mechanisms of falling and to develop appropriate prevention strategies (7). Rehabilitation of amputee Service Members, Veterans, and civilians using prosthetic devices is a priority of the Department of Defense (DoD), the Veterans Health Administration (VA), and Centers for Medicare and Medicaid Services (CMS), respectively. Fall prevention programs have been established and evaluated, including exercise programs designed to improve function and balance (1,2). However, the role of the prosthetic interface in maximizing balance confidence is poorly studied. Exploring interventions, including prosthetic interfaces that may prevent falls and reduce healthcare costs, is a priority in amputee care (8,9). In addition to reducing falls, walking capacity is another important factor in determining function for TFA patients (10). Poor walking capacity, as evidenced by lower gait speed, is associated with increased comorbidity, falls, and mortality (11). Optimizing walking capacity through such means as achieving a more normal gait speed and community ambulation should be considered when formulating the prosthetic prescription. Because walking capacity and balance confidence are compromised with TFA, these outcomes should be considered when evaluating interfaces for transfemoral prosthetic users. Therefore, the purpose of this study was to compare the effect of TFA interface design on walking capacity and balance confidence.

METHODS A retrospective cohort design was utilized. All data were collected in accordance with the Declaration of Helsinki. In order to be included in the record review, subjects had to meet the following eligibility criteria: 1. 2. 3. 4.

Unilateral TFA 18 to 60 years of age K2 or higher activity level History of prosthetic ambulation without an assistive device â&#x2030;Ľ2 years 5. No other comorbidities 6. History of use of both socket conditions of interest 7. Complete outcome assessment for both socket conditions Subjects were excluded if they did not meet all inclusion criteria. Independent Variable: Interfaces The Standard of Care (SOC) interface is the ischial ramus containment (IRC). The experimental interface is the High-Fidelity Interfaceâ&#x201E;˘ (HiFi, biodesigns, inc., Westlake Village, CA,USA) TFA interface design (12) (Figure 1).

Figure 1. Subischial transfemoral TransfemoralHiFi HiFiinterface. Interface.

TRANSFEMORAL SOCKET IMPACT ON GAIT & FALLS

Dependent Variables: Outcome Measures The following outcome measures were routinely utilized during clinical evaluation of new prosthetic fittings: The Activity-specific Balance Confidence Scale (ABC): The ABC Scale is a 16-item self-report measure of balance confidence in performing various activities of daily living (ADL) without falling. Items are scored on a rating scale from 0 to 100, with higher scores reflecting higher levels of balance confidence. An average score is calculated by adding all item scores and dividing by the total number of items. The ABC can be administered in 10 to 20 min and is appropriate for use in the clinical environment (13). Two-Minute Walk Test (2MWT): The 2MWT was used to determine walking capacity. The six-minute walk test (6MWT) is highly regarded in clinical care; however, Reid et al. determined the 2MWT is as predictive as the 6MWT in determining an amputee’s ability to ambulate in the community. The 2MWT was used given its comparable performance to the 6MWT and because it takes less time to administer within the clinical environment (14).

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Data Collection Timeline Patients included in the review were initially fit into an IRC interface and assessed following at least 30 d of accommodation. All data were documented in the clinical prosthetic progress notes. Following eventual rejection or failure, patients were subsequently fit with a HiFi interface. Again, following at least 30 d accommodation, patients were assessed and results recorded in their prosthetic clinic records. Statistical Analyses Data were entered into a database and evaluated for completeness and accuracy. Central tendency and variance were calculated. Parametric tests were used when appropriate considering data dependency and normality; otherwise, equivalent non-parametric tests were used. Statistical significance was set a priori at p ≤ 0.05. IBM SPSS (v21, Armonk, NY, USA) was used for statistical analysis. RESULTS Complete records were available for eleven males and two females (n = 13). The age range was 26 to 58 years. Three patients functioned at the K4 activity level and the remaining 10 at the K3 level. Mean body mass was 85.2 kg (57.7 to 137.7). Subjects’ mean

Table 1. Sociodemographic Data

Subject 1 2 3 4 5 6 7 8 9 10 11 12 13Table 1.

Prosthetic History (y) 3 13 5 5 6 20 16 33 40 8 25 3 10

Gender

Amputated Side

Activity Level

Height (Ft. In)

Weight (lbs.)

M M M M M M M F M M M M F

L L R R R L L L L L L L R

K3 K3 K3 K3 K3 K4 K3 K4 K3 K3 K3 K3 K4

5.5 5.9 5.1 5.9 5.8 5.9 5.9 5.3 5.7 5.9 5.9 6 5.7

190 222 165 187 303 185 168 127 180 156 145 220 190

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Figure 2. Activity-specific Balance Confidence Scale. Subjects’ mean ABC score was 77.2 (±16.8; 35.6 to 96.9) for the IRC and 90.7(±5.7; 77.5 to 98.7) for the HiFi. The difference was statistically significant (p = 0.02).

Figure 3. Two-Minute Walk Test. The aggregated mean distance walked on the 2MWT was 91.8 m (±22.0, 58.3 to 124.7) on the IRC compared to 110.4 m (±28.7; 64.7 to 171.1) for the HiFi socket (p = 0.0001).

TRANSFEMORAL SOCKET IMPACT ON GAIT & FALLS prosthetic use was 14.4 years (3 to 40) (Table 1). Subjects’ mean ABC score was 77.2 (±16.8; 35.6 to 96.9) for the IRC and 90.7 (±5.7; 77.5 to 98.7) for the HiFi. The difference was statistically significant (p = 0.02) (Figure 2). The aggregated mean distance walked on the 2MWT was 91.8 m (±22.0, 58.3 to 124.7) on the IRC compared to 110.4 m (±28.7; 64.7 to 171.1) for the HiFi socket (p = 0.0001) (Figure 3). DISCUSSION We hypothesized that the less cumbersome walls and subischial trimlines afforded by the HiFi, compared with SOC interfaces, would offer improved freedom of movement. This freedom of movement may enable improved walking capacity and improved prosthetic control as evidenced by improved ABC scores. The minimum detectable change (MDC) for the 2MWT has been previously reported as 34.3 m (15). This threshold was not reached in this study. However, in three previous studies comparing lower extremity amputees using the 2MWT, distances walked reached up to 140 m (14). The majority of amputees tested in these studies had transtibial level amputation. In this study, only transfemoral level amputees were evaluated. TFA patients using the HiFi socket achieved distances similar to transtibial amputees in previous studies. Patients’ walking capacity was significantly improved with use of the HiFi interface relative to the SOC alternative, supporting this portion of the hypothesis. Reduced gait speed, an indicator of walking capacity, has been associated with falling (16). This is of particular relevance in the TFA population. Maintaining optimal walking capacity, including normal or near normal gait speed, should be of primary concern in prosthetic design. Prosthetic elements, including the socket, must be considered as potential factors in assisting a patient to achieve variable cadence and faster gait speeds. In this study, the HiFi interface design was determined to have a significant effect on improving walking capacity. Deathe et al. assessed 17 outcome measures used in amputee clinical trials to assess mobility (17). The ABC scale was recognized as being valid and widely used. The MDC for the ABC has been previously reported as 11 and 13 in studies of other pathologies.

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MDC has not been established in the TFA population. In this study, the mean difference was a 23.5 point improvement (p = 0.02) for the users of the HiFi (90.7) versus the IRC (77.2) sockets. An ABC score of 68 is associated with falling post-stroke (18). In this study, both groups were above this fall risk threshold. Our hypothesis that the improved prosthetic control would yield increased ABC scores was supported. Further, the HiFi group reported ABC scores higher than other patient populations, such as those suffering from Parkinson’s or stroke and the elderly. Conversely, when using the IRC socket, ABC scores tended to be similar to scores in these populations (18-20). The socket has been identified as the most important prosthetic element; however, TFA prosthetic socket fit is problematic using SOC IRC prosthetic socket interface. A subischial compression and tissue release design such as the HiFi may improve comfort and increase user control by utilizing femoral control. This could lead to improved walking capacity and confidence, which could reduce falls. Discomfort and lack of control have been associated with poor socket fit. This reduces function of the prosthesis for the amputee. Although common, the SOC IRC interface design has potential limitations, such as limiting range of motion, decreasing comfort, and interfering with urogenital function, and potential fitting complications affecting overall quality of life (21,22). Benefits of a novel TFA interface such as the HiFi could potentially address areas identified as problematic and lead to alternative interface designs that improve quality of life among TFA patients. A common conclusion among the aforementioned studies is that falls in amputees can be mitigated with training programs and alternative interventions. To begin a strength and walking program, the use of an effective prosthesis is imperative. Collectively, prior authors also agreed that ongoing research is required to develop appropriate intervention strategies to ameliorate fall risk (6,23-25). Such interventions should consider alternative prosthetic interfaces. Limitations A limitation of this study was the small patient population exposed to both socket designs. Socket

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studies are expensive, and it can be difficult to control attrition. Interface studies are particularly challenging due to the socket being an intimate part of the prosthesis that can require weeks of accommodation prior to effective use. A paucity of funding has created a void in the understanding of a prosthetic socket interface’s role in affecting falls and walking capacity (26). CONCLUSION Prosthetic clinical documentation and outcome measure implementation can be effective means of demonstrating changes and improvements in clinical interventions. The Activity-specific Balance Confidence Scale and two-minute walk test are valid measures that can be used to determine differences among intervenions in the transfemoral amputee population. Alternative transfemoral interface design, such as the HiFi socket, can improve walking capacity and balance confidence in higher functioning patients with transfemoral amputation. ACKNOWLEDGMENTS Contents of this manuscript represent the opinions of the authors and not necessarily those of the U.S. Department of Defense, U.S. Department of the Army, U.S. Department of Veterans Affairs, or any academic or health care institution. Authors declare no conflicts of interest. This project was partially supported by the National Institutes of Health Scholars in Patient Oriented Research (SPOR) grant (1K30RR22270). REFERENCES 1. Gillespie LD, Robertson MC, Gillespie WJ, Lamb SE, Gates S, Cumming RG, Rowe BH. Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev. 2012 [accessed 2016 Jul 30]. http://onlinelibrary. wiley.com/doi/10.1002/14651858.CD007146. pub2/abstract;jsessionid=BA68AD47531BF7024E46E7B7A696A558.f04t03 2. Tinetti ME, Mendes de Leon CF, Doucette JT, Baker DI. Fear of falling and fall-related efficacy in relationship to functioning among community-living elders. J Gerontol. 1994;49(3):M140-7.

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Miller WC, Speechley M, Deathe B. The prevalence and risk factors of falling and fear of falling among lower extremity amputees. Arch Phys Med Rehabil. 2001;82(8):1031-7. Miller WC, Speechley M, Deathe AB. Balance confidence among people with lower-limb amputations. Phys Ther. 2002;82(9):856-65. Gooday HM, Hunter J. Preventing falls and stump injuries in lower limb amputees during inpatient rehabilitation: completion of the audit cycle. Clin Rehabil. 2004;18(4):379-90. Pauley T, Devlin M, Heslin K. Falls sustained during inpatient rehabilitation after lower limb amputation: prevalence and predictors. Am J Phys Med Rehabil. 2006;85(6):521-32. Yu WY, Hwang HF, Hu MH, Chen CY, Lin MR. Effects of fall injury type and discharge placement on mortality, hospitalization, falls, and ADL changes among older people in Taiwan. Accid Anal Prev. 2013;50:887-94. Davis JC, Donaldson MG, Ashe MC, Khan KM. The role of balance and agility training in fall reduction. A comprehensive review. Eura Medicophys. 2004;40(3):211-21. Dyer D, Bouman B, Davey M, Ismond KP. An intervention program to reduce falls for adult in-patients following major lower limb amputation. Healthc Q. 2008;11(3 Spec No.):117-21. [CMS] Centers for Medicare and Medicaid Services. Healthcare Common Procedure Coding System. Springfield (VA): U.S. Department of Commerce, National Technical Information Service; 2007. Fritz S, Lusardi M. White paper: “walking speed: the sixth vital sign”. J Geriatr Phys Ther. 2009;32(2):46-9. Alley RD, Walley, Albuquerque MJ, Altobelli DE. Prosthetic sockets stabilized by alternating areas of tissue compression and release. J Rehabil. Res. Dev. 2011;48(6):679-96. Powell LE, Myers AM. The activities-specific balance confidence (ABC) scale. J Gerontol A Biol Med Sci. 1995;50A(1):M28-34. Reid L, Thomson P, Besemann M, Dudek N. Going places: does the two-minute walk test predict the six-minute walk test in lower extremity

TRANSFEMORAL SOCKET IMPACT ON GAIT & FALLS amputees? J Rehabil Med. 2015;47(3):256-61. 15. Resnik L, Borgia M. Reliability of outcome measures for people with lower-limb amputations: distinguishing true change from statistical error. Phys Ther. 2011;91(4):555-65. 16. Montero-Odasso M, Schapira M, Soriano ER, Varela M, Kaplan R, Camera LA, Mayorga LM. Gait velocity as a single predictor of adverse events in healthy seniors aged 75 years and older. J Gerontol A Biol Med Sci. 2005;60(10):1304-9. 17. Deathe AB, Wolfe DL, Devlin M, Hebert JS, Miller WC, Pallaveshi L. Selection of outcome measures in lower extremity amputation rehabilitation: ICF activities. Disabil Rehabil. 2009;31(18):1-19. 18. Botner EM, Miller WC, Eng JJ. Measurement properties of the Activities-specific Balance Confidence Scale among individuals with stroke. Disabil Rehabil. 2005;27(4):156-63. 19. Huang TT, Wang WS. Comparison of three established measures of fear of falling in community-dwelling older adults: psychometric testing. Int J Nurs Stud. 2009;46(10):1313-9. 20. Mak MK, Pang MY, Mok V. Gait difficulty, postural instability, and muscle weakness are associated with fear of falling in people with Parkinsonâ&#x20AC;&#x2122;s disease. Parkinsons Dis. 2012 [accessed 2016 Jul 30]. doi: 10.1155/2012/901721. 21. Kahle JT, Highsmith MJ. Transfemoral sockets

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with vacuum-assisted suspension comparison of hip kinematics, socket position, contact pressure, and preference: ischial containment versus brimless. J Rehabil Res Dev. 2013;50(9):1241-52. Kahle JT, Highsmith MJ. Transfemoral interfaces with vacuum assisted suspension comparison of gait, balance, and subjective analysis: ischial containment versus brimless. Gait Posture. 2014;40(2):315-20. Vrieling AH, van Keeken HG, Schoppen T, Hof AL, Otten B, Halbertsma JP, Postema K. Gait adjustments in obstacle crossing, gait initiation and gait termination after a recent lower limb amputation. Clin Rehabil. 2009;23(7):659-71. Vanicek N, Strike S, McNaughton L, Polman R. Postural responses to dynamic perturbations in amputee fallers versus nonfallers: a comparative study with able-bodied subjects. Arch Phys Med Rehabil. 2009;90(6):1018-25. Vanicek N, Strike S, McNaughton L, Polman R. Gait patterns in transtibial amputee fallers vs. non-fallers: biomechanical differences during level walking. Gait Posture 2009;29(3):415-20. Highsmith MJ, Kahle JT, Miro RM, Orendurff MS, Lewandowski AL, Oriolla JJ, Sutton B, Ertl JP. Prosthetic interventions for transtibial amputees: a systematic review and meta-analysis of high-quality prospective literature and systematic reviews. J Rehabil Res Dev. 2016;53(2):157-84.

ISSN 1949-8241 • E-ISSN 1949-825X http://dx.doi.org/10.21300/18.2-3.2016.175 www.technologyandinnovation.org

COMPARATIVE EFFECTIVENESS OF AN ADJUSTABLE TRANSFEMORAL PROSTHETIC INTERFACE ACCOMMODATING VOLUME FLUCTUATION: CASE STUDY Jason T. Kahle1,2, Tyler D. Klenow3, M. Jason Highsmith4-6 OP Solutions, Tampa, FL, USA Prosthetic Design + Research, Tampa, FL, USA 3 Prosthetics and Sensory Aids Service, James A. Haley Veterans’ Hospital, Tampa, FL, USA 4 School of Physical Therapy & Rehabilitation Sciences, University of South Florida, Tampa, FL, USA 5 Extremity Trauma & Amputation Center of Excellence (EACE), U.S. Department of Veterans Affairs, Tampa, FL, USA 6 319th Minimal Care Detachment, U.S. Army Reserves, Pinellas Park, FL, USA 1

The socket-limb interface is vital for functionality and provides stability and mobility for the amputee. Volume fluctuation can lead to compromised fit and function. Current socket technology does not accommodate for volume fluctuation. An adjustable interface may improve function and comfort by filling this technology gap. The purpose of this study was to compare the effectiveness of the standard of care (SOC) ischial ramus containment to an adjustable transfemoral prosthetic interface socket in the accommodation of volume fluctuation. A prospective experimental case study using repeated measures of subjective and performance outcome measures between socket conditions was employed. In the baseline volume condition, the adjustable socket improved subjective and performance measures 19% to 37% over SOC, whereas the two-minute walk test demonstrated equivalence. In the volume loss condition, the adjustable socket improved all subjective and performance measures 22% to 93%. All aggregated data improved 16% to 50% compared with the SOC. In simulated volume gain, the SOC socket failed, while the subject was able to complete the protocol using the adjustable socket. In this case study, the SOC socket was inferior to the comparative adjustable transfemoral amputation interface in subjective and performance outcomes. There is a lack of clinical trials and evidence comparing socket functional outcomes related to volume fluctuation. Key words: Amputee; Ischial containment; Lower extremity amputee; Limb loss; Rehabilitation; Socket

_____________________ Accepted July 1, 2016. Address correspondence to: Jason T. Kahle, OP Solutions, 12206 Bruce B. Downs Blvd., Tampa, FL 33612, USA. Tel: (813) 971-1100; Fax: (813) 971-9300; E-mail: Jason@opsolutions.us

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INTRODUCTION In the U.S., approximately two million people live with limb loss (1). It is estimated that by 2050, nearly 3.6 million Americans will be living with lower extremity (LE) limb loss (1). Of the two million American amputees, approximately 86% are individuals living with lower limb loss and 18.5% have transfemoral amputation (TFA) (2). In spite of this increasing amputee population, there is limited prosthetic research, resulting in healthcare service gaps, excess hospital utilization, and increased cost to patients and payors (3). Addressing these issues is of critical importance since rehabilitation care, fitting of prostheses, and adjustment of devices alone were the fifteenth most expensive condition treated in U.S. hospitals in 2011, with a total cost of more than $5.4 billion (4). The socket-limb interface is vital for functionality and provides stability and mobility for the amputee. An inadequate fit may lead to skin breakdown, thereby limiting mobility and requiring additional clinician time, replacement components, and a possible remaking of the prosthesis altogether (5). As a result, Medicare data shows that 45% of the overall $750 million in Medicare expenditures on prosthetic technology each year were for socket-related codes. Successful socket fitting reduces this economic burden and increases prosthetic usage. Amputees encounter multiple challenges during their recovery, rehabilitation, and reintegration into their homes and communities. Learning and adopting new strategies for basic mobility, personal hygiene, and activities of daily living with a prosthesis is difficult (6). Complicating this process, the residual limb (RL) naturally goes through a period of volume fluctuation post amputation that impacts fit (7). Newly amputated limbs commonly undergo reduction in size, shape, and volume (7,8). This progression occurs in two phases: 1) rapid, acute shrinkage immediately following amputation and 2) progressive stabilization of volume one year post amputation. These changes are dependent on individual lifestyle, activity level, and weight. Moreover, amputees experience daily volume fluctuations influenced by multiple factors, including diet, environment, and weather conditions. These

fluctuations require an iterative process involving numerous trips to the prosthetist for socket adjustments. Poor fit can lead to prosthetic abandonment (9). RL volume management is a common issue for prosthetic users, especially during the intermediate recovery stage of amputee rehabilitation when the most rapid volume fluctuation occurs (7). It has been shown that limb volume decreases 17% to 35% over the first 160 d post amputation, 7% to 10% in the 12-month post-operative period and approximately 2% on a daily basis thereafter, thus requiring patient-provider coordination (7,10). In addition, chronic volume change may continue for up to 12 to 18 months post amputation due to tissue atrophy and indefinite diurnal volume fluctuations. Poor volume management can result in a variety of secondary adverse effects of prosthetic use, including ulcers, verrucous hyperplasia, and osteomyelitis (7). These effects may lead to further amputation and re-hospitalization, which contributes to the annual $8 billion expenditure on amputee hospital care (11). Traditional rigid sockets do not accommodate volume fluctuations. Poor fit can cause skin ulcerations and infection and may lead to revision amputation (12). Furthermore, socket discomfort is common among LE amputees and may delay prosthetic use, prevent return to normal function, compromise patient outcomes, and increase healthcare costs. The primary cause for failure of amputee prostheses is user dissatisfaction associated with poor socket fit and comfort (9,12-14). In addition to the unmet need in addressing comfort, there is a considerable technology gap in the area of socket fabrication and access. Therefore, the objective of this prospective experimental clinical case study is to compare the effectiveness of the standard of care (SOC) ischial ramus containment (IRC) to an adjustable transfemoral prosthetic interface socket in the accommodation of volume fluctuation by observing both functional and subjective outcomes. METHODS Methods were in accordance with the Declaration of Helsinki, and the subjects provided informed consent.

ADJUSTABLE ABOVE-KNEE PROSTHETIC INTERFACE

Subject Subject inclusion was unilateral TFA, either gender, any ethnicity, between 18 and 65 years of age, and <113.4 kg. Exclusion criteria included non-TFA level, <18 and >65 years of age, and >113.4 kg. The subject identified had the following characteristics: male, 24 years old, right unilateral TFA, 1.7 m, 70.3 kg, and a BMI of 24 kg/m2. The subject elected for limb amputation at age 19, secondary to osteosarcoma. His activity level was K4 per his medical record. No other known injuries were present. Subject exhibited upper and LE active range of motion within normal limits. His current prosthesis included a pin-lock gel liner, Infinite Socketâ&#x201E;˘ (LIM Innovations, San Francisco, CA, USA), Genium knee, and Triton foot (Otto

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Bock Healthcare, Duderstadt, Germany). The subject was physically capable of completing the functional testing protocol. The subject had normal cognitive ability and was able to provide informed consent and socket fitting feedback to investigators. Interventions Tested 1. IRC. This design is characterized by a high (proximal) brim that medially contains the ischiopubic ramus and is the SOC. The socket consisted of a rigid thermoplastic material. This was suspended with a gel pin-locking liner. The subject was casted and fit into a custom SOC socket over the same liner he had been using to eliminate confounding and the potential introduction of dermatologic issues.

Figure 1. Interventions tested. Pictured left is the standard of care socket with the 5-ply sock and the pin system. Pictured right is the Infinite adjustable socket.

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2. Adjustable TFA Interface. The Infinite Socket™ is a custom-molded four-strut design combined with a textile brim and tensioner to contain and control the pelvis and femur and soft tissues across a varying volume. Adjustments can be made by both clinicians and patients to manage long-term and daily fluctuations. The pivoting and sliding connection between the struts and base provides additional flexibility in adjustability as well as shock absorption and energy response. The dynamic frame of the Infinite socket™ has a textile interface that is reportedly low in friction, anti-microbial, durable, and washable. The Infinite Socket™ achieves control and pressure distribution through multiple custom components, which include an ischial seat, proximal brim, four struts, and a flexible inner distal cup. Study Design To simulate the same volume fluctuations an amputee would experience, three conditions were tested. First, to establish a baseline (BASE), the subject was casted over his Otto Bock 6Y87 3D TF pin-locking liner (Otto Bock Healthcare, Duderstadt, Germany) and a five-ply sock. Both the SOC and Infinite™ sockets were fabricated from this cast. The sockets were then fit and adjusted to this configuration to ensure an equal baseline. Second, to simulate volume loss (VLOSS), the five-ply sock was removed from the RL and liner, and then the subject was tested in this condition. This constituted a 2 cm circumferential volume change (VLOSS) less than the BASE circumference. Third, to simulate volume gain (VGAIN), the five-ply sock plus an eight-ply sock was added to the RL and liner for a total of 13-ply. This constituted a 2 cm circumferential volume change (VGAIN) more than the BASE circumference. An experimental case study design was utilized for this project. An independent researcher randomized

six study conditions across three repeated independent utilization periods, each followed by an outcome assessment. The study design controlled for all prosthetic variables (Table 1), as the subject utilized his usual prosthetic components with only the exception of the socket (independent variable) throughout the study. The order of testing was randomized using an offsite computer randomized number generator to improve methodological quality and minimize bias risk. Further, raters and the study statistician were blinded to the independent variables. Data collection was completed over three sequential days. Each data collection period began at the same time of day. The subject was instructed to maintain fluid, salt intake, and diet over the study period. Weight was recorded each day, in addition to RL circumference measurements, to help ensure volume consistency. A ten-minute rest period between conditions was provided between tests to mitigate confounding from fatigue. Blood pressure and heart rate were monitored before each test to ensure normalization prior to re-testing. Outcome Measures Physical performance measures were selected to assess functional capability and safety differences between the two socket conditions. For instance, speed of movement and walking are valuable clinical tests of functionality and provide good identification of multiple-falls risk (15-17). Slower gait has also been shown to be an indication of fall risk (18). Thus, the following tests were selected: a. L-Test: a short walking test with transitional movements and multiple turns b. Four Square Step Test (4SST): a brief assessment of multi-directional stepping (15) c. Two-Minute Walk Test (2MWT): a test to pro-

Table 1. Table of Variables

 

Independent SOC- IRC TFA Interface LIM -Adjustable TFA Interface

   

Dependent Subjective Response (i.e., Comfort, Pain) Mobility, i.e., 4SST Function, i.e., AMP Gait Speed, L-Test, 2MWT

   

Controlled Accommodation Clinical Schedule Environment Knee, Foot, Liner, Suspension

ADJUSTABLE ABOVE-KNEE PROSTHETIC INTERFACE vide insight into cardiorespiratory and functional capacity and determine walking speed d. The Amputee Mobility Predictor (AMP): an instrument used to determine mobility and ambulatory status for amputees e. Socket Comfort Score (SCS): a valid, reliable, and sensitive assessment between practitioner and patient that indicates comfort and the need for interface adjustments (19) f. Pain Scale: a valid and reliable tool for determining the severity of specific types of pain Data Analyses Data were entered into a database and analyzed for normality and completeness. Central tendency, variance, and percent differences were calculated where possible. The analysis included a two-part

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approach. Repeated measures assessment was selected to determine differences across assessment sessions and between conditions. Additionally, differences were assessed at individual volume points (i.e., dependent, between-group comparison tests) as well as cumulatively across conditions. Parametric tests were used when possible (i.e., normal distribution); otherwise, non-parametric equivalent tests were selected. Statistical significance was set a priori at p â&#x2030;¤ 0.05. It must be noted that the use of statistical analysis with case studies is not novel, but it is also not a commonly accepted practice. However, at times, data generation from case studies may be mathematically conducive to analyses that may provide insight into a magnitutde of effect that could be useful for power and sample estimates for future expanded research with the intervention (20).

Figure 2. Results for: Socket Comfort Score (SCS), 2-Minute Walk Test (2MWT), 4 Square Step Test (4SST), and L Test. *Statistical significance p â&#x2030;¤ 0.05, NT = not tested due to missing data.

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RESULTS In the BASE condition, SCS in the Infinite socket improved 37% over SOC, L-Test improved 21%, FSST improved 19%, whereas 2MWT demonstrated equivalence. In the VLOSS condition, SCS improved 93%, L-Test improved 22%, FSST improved 25%, and 2MWT improved 26% with the Infinite socket compared with the SOC. The VGAIN condition could not be analyzed across all three data collections, as the patient was unable to don the prosthesis on the second and third collection due to pain and the inability to don the SOC prosthesis. All aggregated data (BASE, VLOSS, VGAIN), SCS improved 50%, L-Test improved 18%, 2MWT improved 21%, and 4SST improved 16% using the Infinite socket compared with SOC (Figure 2). DISCUSSION In this study, we simulated minimum volume fluctuations that have been reported to occur commonly among amputees during the acute and intermediate stage of rehabilitation. Generally, improvements with the Infinite socket were shown in the outcomes of SCS, mobility, and gait speed. These functional outcomes are predictive of falling. SCS, mobility, and gait speed should be a focus of interventions used in rehabilitation of the amputee. Preventing falls during the acute and intermediate stages of amputation rehabilitation should be a priority in minimizing adverse effects. Curtze et al. reported the annual fall incidence in lower limb amputees as approximately 50% (21,22). Injuries are sustained in 61% of falls, necessitating fall prevention strategies, such as improved socket interfaces, for the LE amputee (23). Falls in amputees can be mitigated with strength and gait training programs. However, to begin a strength and walking program, the use of an effective well-fit socket interface is imperative. A prosthetic socket interface that accommodates an amputeeâ&#x20AC;&#x2122;s volume fluctuation, known to occur in the acute and intermediate stage of rehabilitation, could improve clinical outcomes and function. For instance, Schon et al. reported on the use of an ambulatory immediate post-operative prosthesis (IPOP) and found that none of the 19 patients had falls while wearing the IPOP. However, in the non-IPOP group, 12 of 23 patients

had a total of 34 falls. Further, there were no revisions in the IPOP group, but eight patients in the non-IPOP group required 10 revisions to a higher amputation level, four of which were related to falls (24). Others have noted that interventions that could prevent secondary effects of falling in amputee rehabilitation would be beneficial, including prosthetic devices that better accommodate the acute phase when volume fluctuation is most prevalent (25-27). Evidence is not available comparing the efficacy of interventions addressing issues related to poor socket fit during the intermediate stage of rehabilitation in TFA patients. An adjustable TFA socket interface that better addresses the known problems of the SOC IRC socket interface could improve functional outcomes. Additional research is required to develop appropriate intervention strategies to ameliorate the risk of falling during amputee rehabilitation (28-31). This case study compared the efficacy of an alternative TFA intervention for volume fluctuation. The socket is the most important element of the prosthesis. However, prosthetic fit in the TFA during volume fluctuations is problematic using the current SOC prosthetic socket interface. As the socket loses its fit quality, the user loses control and comfort, which eventually leads to pain, compromised function, reduction in use, and potentially prosthetic abandonment. The current SOC clinical procedure for volume management is the addition and subtraction of prosthetic socks of various ply to fill the void between RL and socket. Although common, this method is sub-optimal. An adjustable prosthetic socket is advantageous in assisting prosthetic users in managing common volume fluctuations. A socket with instant adjustability could be a valuable alternative to common volume management strategies and may help reduce adverse effects of prosthetic use due to poor volume management and socket fit (7,32-36). Limitations Case studies could provide insight into important variables that should be considered in a larger clinical trial, and their conclusions merit consideration in the development of future clinical trials. The outcome measures selected in this case showed a difference between the socket conditions. However, the strategy

ADJUSTABLE ABOVE-KNEE PROSTHETIC INTERFACE for simulating volume change and then comparing the different sockets may require reconsideration. In this case, the VLOSS condition was designed to simulate a situation where an amputee may not know, or have the option, to add a sock in a SOC socket. In the VGAIN condition, the subject was unable to don the SOC socket. The absence of these data points did not allow for comparison between sockets under this condition. In a larger funded clinical trial, using liners of different thickness to simulate volume gain and loss should be considered. Finally, as previously mentioned, the use of statistical analysis in case studies, while not novel, is also not widely accepted. Statistical significance in case reports should be interpreted with caution, as the findings of case reports are commonly regarded as non-generalizable. CONCLUSION A well-fit prosthetic socket interface is the most important aspect of a prosthesis. Volume fluctuation is a pervasive problem in a lower extremity amputee. This fluctuation can contribute to socket fitting issues and compromised function. The standard of care socket interface does not offer inherent adjustability. In this case study, the standard of care socket was inferior to the comparative adjustable TFA interface in subjective and performance outcomes. This case study demonstrates the need for a well-designed clinical trial using outcome measures comparing the efficacy of an adjustable prosthetic socket interface to the standard of care. There is a lack of clinical trials and evidence comparing socket functional outcomes related to volume fluctuation. ACKNOWLEDGMENTS Contents of this manuscript represent the opinions of the authors and not necessarily those of the U.S. Department of Defense, U.S. Department of the Army, U.S. Department of Veterans Affairs, or any academic or health care institution. This project was partially funded by National Institutes of Health Scholars in Patient Oriented Research (SPOR) grant (1K30RR22270). Authors declare no conflicts of interest.

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Limb Loss Statistics. Manassas (VA): Amputee Coalition. [accessed 8 Aug 2016]. http://www. amputee-coalition.org/fact_sheets/amp_stats_ cause.pdf. 3. Highsmith MJ Kahle JT, Miro R, Orendurff MS, Lewandowski A, Oriolla JJ, Sutton B, Ertl JP. Prosthetic interventions for transtibial amputees: a systematic review and meta-analysis of high quality, prospective literature and systematic reviews. J Rehabil Res Dev. 2016;53(2):157-184. 4. Torio CM, Andrews RM. National inpatient hospital costs: the most expensive conditions by payer, 2011. Rockville (MD): Healthcare Cost and Utilization Project; 2013. Statistical Brief #160. [accessed 8 Aug 2016]. http://www. hcup-us.ahrq.gov/reports/statbriefs/sb160.pdf. 5. Raichle KA, Hanley MA, Molton I, Kadel NJ, Campbell K, Phelps E, Ehde D, Smith DG. Prosthesis use in persons with lower- and upper-limb amputation. J Rehabil Res Dev. 2008;45(7):961-72. 6. Pasquina CP, Carvalho AJ, Sheehan TP. Ethics in rehabilitation: access to prosthetics and quality care following amputation. AMA J Ethics. 2015;17(6):535-46. 7. Sanders JE, Fatone S. Residual limb volume change: systematic review of measurement and management. J Rehabil Res Dev. 2011;48(8):94986. 8. Fernie GR, Holliday PJ. Volume fluctuations in the residual limbs of lower limb amputees. Arch Phys Med Rehabil. 1982;63(4):162-5. 9. Roffman CE, Buchanan J, Allison GT. Predictors of non-use of prostheses by people with lower limb amputation after discharge from rehabilitation: development and validation of clinical prediction rules. J Physiother. 2014;60(4):224-31. 10. Mosadeghrad AM. Factors influencing healthcare service quality. Int J Health Policy Manag. 2014;3(2):77-89.

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11. Limb Loss Task Force/Amputee Coalition. Roadmap for preventing limb loss in America: recommendations from the 2012 Limb Loss Task Force. Knoxville (TN): Amputee Coalition; 2012. [accessed 8 Aug 2016]. http://www.amputee-coalition.org/wp-content/uploads/2014/09/ Isp_Roadmap-for-limb-loss-Prevention-andAmputee-Care-Improvement_241014-092312. pdf. 12. Reiber GE, McFarland LV, Hubbard S, Maynard C, Blough DK, Gambel JM, Smith DG. Servicemembers and veterans with major traumatic limb loss from Vietnam war and OIF/ OEF conflicts: survey methods, participants, and summary findings. J Rehabil Res Dev. 2010;47(4):275-97. 13. Moore TJ, Barron J, Hutchinson F 3rd, Golden C, Ellis C, Humphries D. Prosthetic usage following major lower extremity amputation. Clin Orthop Relat Res. 1989;(238):219-24. 14. Gailey RS, McFarland LV, Cooper RA, Czerniecki J, Gambel JM, Hubbard S, Maynard C, Smith DG, Raya M, Reiber GE. Unilateral lower-limb loss: prosthetic device use and functional outcomes in servicemembers from Vietnam war and OIF/ OEF conflicts. J Rehabil Res Dev. 2010;47(4):31731. 15. Whitney SL, Marchetti GF, Morris LO, Sparto PJ. The reliability and validity of the Four Square Step Test for people with balance deficits secondary to a vestibular disorder. Arch Phys Med Rehab. 2007;88(1):99-104. 16. Dite W, Connor HJ, Curtis HC. Clinical identification of multiple fall risk early after unilateral transtibial amputation. Arch Phys Med Rehabil. 2007;88(1):109-14. 17. Dite W, Temple VA. Development of a clinical measure of turning for older adults. Am J Phys Med Rehabil. 2002;81(11):857-66; quiz 67-8. 18. Montero-Odasso M, Schapira M, Soriano ER, Varela M, Kaplan R, Camera LA, Mayorga LM. Gait velocity as a single predictor of adverse events in healthy seniors aged 75 years and older. J Gerontol A Biol Sci Med Sci. 2005;60(10):13049. 19. Hanspal RS, Fisher K, Nieveen R. Prosthetic

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socket fit comfort score. Disabil Rehabil. 2003;25(22):1278-80. Carson R, Stevens PM, Webster JB, Foreman KB. Using clinically relevant outcome measures to assess the ambulatory efficiency, balance confidence, and overall function associated with â&#x20AC;&#x153;stubbyâ&#x20AC;? prostheses and C-Leg prostheses for a patient with bilateral transfemoral prostheses. J Prosthet Orthot. 2010;22:140-144. Curtze C, Hof AL, Otten B, Postema K. Balance recovery after an evoked forward fall in unilateral transtibial amputees. Gait Posture. 2010;32(3):336-41. Curtze C, Hof AL, Postema K, Otten B. The relative contributions of the prosthetic and sound limb to balance control in unilateral transtibial amputees. Gait Posture. 2012;36(2):276-81. Yu WY, Hwang HF, Hu MH, Chen CY, Lin MR. Effects of fall injury type and discharge placement on mortality, hospitalization, falls, and ADL changes among older people in Taiwan. Accid Anal Prev. 2013;50:887-94. Schon LC, Short KW, Soupiou O, Noll K, Rheinstein J. Benefits of early prosthetic management of transtibial amputees: a prospective clinical study of a prefabricated prosthesis. Foot Anlke Int. 2002;23(6):509-14. Gardner LA, Bray PJ, Finley E, Sterner C, Ignudo TL 3rd, Stauffer CL, Kincaid SA, Marella WM. Standardizing falls reporting: using data from adverse event reporting to drive quality improvement. J Patient Saf. 2015. Gardner MM, Buchner DM, Robertson MC, Campbell AJ. Practical implementation of an exercise-based falls prevention programme. Age Ageing. 2001;30(1):77-83. Gardner MM, Robertson MC, Campbell AJ. Exercise in preventing falls and fall related injuries in older people: a review of randomised controlled trials. Br J Sports Med. 2000;34(1):717. Pauley T, Devlin M, Heslin K. Falls sustained during inpatient rehabilitation after lower limb amputation: prevalence and predictors. Am J Phys Med Rehabil. 2006;85(6):521-32. Vrieling AH, van Keeken HG, Schoppen T,

ADJUSTABLE ABOVE-KNEE PROSTHETIC INTERFACE Postema K. Gait adjustments in obstacle crossing, gait initiation and gait termination after a recent lower limb amputation. Clinical Rehabil. 2009;23(7):659-71. 30. Vanicek N, Strike S, McNaughton L, Polman R. Postural responses to dynamic perturbations in amputee fallers versus nonfallers: a comparative study with able-bodied subjects. Arch Phys Med Rehabil. 2009;90(6):1018-25. 31. Vanicek N, Strike S, McNaughton L, Polman R. Gait patterns in transtibial amputee fallers vs. non-fallers: biomechanical differences during level walking. Gait Posture. 2009;29(3):415-20. 32. Sanders JE, Rogers EL, Abrahamson DC. Assessment of residual-limb volume change using bioimpedence. J Rehabil Res Dev. 2007;44(4):525-35.

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CONCURRENT VALIDITY OF THE CONTINUOUS SCALE-PHYSICAL FUNCTIONAL PEFORMANCE-10 (CS-PFP-10) TEST IN TRANSFEMORAL AMPUTEES M. Jason Highsmith1-3, Jason T. Kahle4,5, Rebecca M. Miro1, M. Elaine Cress6, William S. Quillen1, Stephanie L. Carey7, Rajiv V. Dubey7, and Larry J. Mengelkoch8 2

1 School of Physical Therapy & Rehabilitation Sciences, University of South Florida, Tampa, FL, USA Extremity Trauma & Amputation Center of Excellence (EACE), U.S. Department of Veterans Affairs, Tampa, FL, USA 3 319th Minimal Care Detachment, U.S. Army Reserves, Pinellas Park, FL, USA 4 OP Solutions, Tampa, FL, USA 5 Prosthetic Design + Research, Tampa, FL, USA 6 Department of Kinesiology, University of Georgia, Athens, GA, USA 7 Department of Mechanical Engineering, University of South Florida, Tampa, FL, USA 8 Doctor of Physical Therapy Program, University of St. Augustine for Health Sciences, St. Augustine, FL, USA

The Continuous Scale-Physical Functional Performance-10 (CS-PFP-10) test consists of 10 standardized daily living tasks that evaluate overall physical functional performance and performance in five individual functional domains: upper body strength (UBS), upper body flexibility (UBF), lower body strength (LBS), balance and coordination (BAL), and endurance (END). This study sought to determine the concurrent validity of the CS-PFP-10 test and its functional domains that involve the lower extremities (LBS, BAL, or END) in comparison to measures that have established validity for use in persons with transfemoral amputation (TFA). Ten TFA patients functioning at K3 or higher (Medicare Functional Classification Level) completed the study. Participants were assessed performing the CS-PFP-10, Amputee Mobility Predictor (AMP), 75 m self-selected walking speed (75 m SSWS) test, timed down stair walking (DN stair time), and the limits of stability (LOS) balance test. Concurrent validity was assessed using correlation analysis. The AMP, 75 m SSWS, LOS, and the DN stair time tests were strongly correlated (r = ± 0.76 to 0.86) with their paired CS-PFP-10 domain score (LBS, BAL, or END) and CS-PFP-10 total score. These findings indicate that the lower limb and balance domains of the CS-PFP-10 are valid measures to assess the physical functional performance of TFA patients. Key words: Activities of daily living; Lower extremity amputees; Outcome measures; Physical therapy; Psychometric testing

INTRODUCTION There are approximately two million persons presently living with limb loss in the U.S. Of these, approximately 350,000 have transfemoral amputation (TFA) (1). For clinicians, it is often challenging to select appropriate outcome measures to evaluate physical functional performance for persons with lower extremity amputation (LEA). An important

consideration for using any outcome measure is to have evidence that the measure has strong psychometric properties for its target population. Psychometric properties include the level of measurement of the outcome data, the validity and reliability of the test, and the test’s sensitivity to detect change among different interventions.

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The Amputee Mobility Predictor (AMP) is a 21-item test of functional mobility used to predict an LEA patient’s ability to ambulate. The AMP was shown to have moderate to strong concurrent validity with the six-minute walk test (6MWT) (r = 0.69 to 0.82) and the Amputee Activity Survey (r = 0.67 to 0.77) (2). It was also found to have strong test-retest and inter-rater reliability (intraclass correlation coefficients (ICC) = 0.86 to 0.98) (2). Recently, Resnik and Borgia (3) reported a minimal detectable change of 3.4 points for the AMP. This population-specific test is designed to require minimal equipment and approximately 10 to 15 min to administer. While these are all positive attributes, there are limitations to the AMP. For instance, at the item level, the AMP is scored with ordinal ranking. Arguably, this necessitates non-parametric analysis. Additionally, some assessment items on the AMP may be inordinately difficult or easy for different amputees. For example, maintaining singlelimb balance for persons with higher level amputation (i.e., hip disarticulation, transfemoral) may be quite difficult, while maintaining seated balance for amputees who function as community ambulators may be quite easy. The AMP is ultimately a test of mobility that includes walking. However, walking distance is actually quite limited within the AMP test (24 to 48 feet). Furthermore, the AMP does not assess activities of daily living (ADL) function, and there is no way to compare amputee values from the AMP test with other diagnostic groups or with non-amputees. The Continuous Scale-Physical Functional Performance-10 (CS-PFP-10) test measures physical function across a wide range of functional abilities (4). The CS-PFP-10 consists of 10 standardized ADL tasks that evaluate overall physical functional performance and performance in five individual physiologic functional domains: upper body strength (UBS), upper body flexibility (UBF), lower body strength (LBS), balance and coordination (BAL), and endurance (END). A key difference in measuring physical performance in this way is that the test’s activities are familiar to participants in terms of their usual activities as opposed to isolated tests that may have seemingly little relevance to participants. Raw data (time, distance, mass) from each task are converted, via an algorithm within licensed scoring software, into a continuously scaled score (0 to 100) for a singular overall performance

score and five individual domain scores. The continuous scaling (ratio level data) allows the use of more precise parametric statistical analyses and provides sensitivity to discriminate small differences with a small number of participants. In a study with healthy elderly, the CS-PFP-10 demonstrated strong psychometric properties (ratio level data/parametric statistical analyses, convergent validity, test-retest reliability, and sensitivity to change) (4). Thus, the CS-PFP-10 meets requirements to recommend its use in clinical and research applications. Furthermore, the CS-PFP-10 has been utilized in multiple diagnostic groups, including frail elderly (4, 5); wheelchair users (6); persons with stroke (7), cardiac disorders (8, 9), and Parkinson’s disease (10); and others (1115). Therefore, performance comparisons against different populations are possible. Recently, the CS-PFP-10 was utilized to determine significant change differences in functional performance with TFA patients using two different microprocessor knee systems (Genium™ and C-Leg™) (16). This study reported that Genium use significantly improved UBF, BAL, and END domain scores (change difference 7% to 8.4%; effect size 0.28 to 0.45) compared to C-Leg use (16). However, in order to generally recommend use of the CS-PFP-10 as the preferred outcome measure for testing functional performance in TFA patients, additional testing of psychometric properties in this specific population is warranted. This study sought to determine the concurrent validity of the CS-PFP-10 and its domains that involved the lower extremities (LBS, BAL, or END) in comparison to measures of comparable ADL tasks or physiologic measures that have established validity for use in persons with TFA. METHODS Subjects Adult individuals with unilateral TFA were considered for enrollment if they met the following inclusion criteria: had used a microprocessor prosthetic knee (MPK) system for ≥1 year; had no skin impairments on lower extremities for the previous 90 d; performed ADL tasks independently; and were able to ambulate independently within the home and community at K3 or higher (Medicare Functional Classification

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Table 1. Description of CS-PFP-10 Tasks

Functional Domains

Task Difficulty Low Difficulty Moderate Difficulty

Task 1. 2. 3. 4. 5. 6. 7.

High Difficulty

8. 9. 10.

Pot carry 1 m Don/Doff jacket Vertical reach Pick up scarves from floor Floor sweep Laundry: a) transfer clothes washer to dryer, b) dryer to basket Transfer from standing to long-sit on floor and back to standing Stair ascent/descent Carry groceries 70 m 6-minute walk test

UBS

LBS

Mass Time Time Time

Mass

UBF Time Distance

BAL

END

Time Time Time Time

Time

Time Mass

Time Time

Distance

Balance and coordination (BAL), endurance (END), lower body strength (LBS), upper body flexibility (UBF), and upper body strength (UBS).

Balance and coordination (BAL), endurance (END), lower body strength (LBS), upper body flexibility

Level) TFA subjects used their preferred pros(UBF),(17). and upper body strength (UBS). theses with an MPK system and an energy storing and return prosthetic foot. Each participant had their prosthesis evaluated for proper fit, alignment, and function by the study’s licensed prosthetist. The study protocol was approved by the University of South Florida’s Institutional Review Board, and each study participant provided written informed consent. Study Design

This was a cross-sectional study to determine concurrent validity (the extent of statistical correlation) of the CS-PFP-10 and its specific physiologic domains that involved the lower extremities (LBS, BAL, or END) in comparison to measures of comparable ADL tasks or physiologic measures that have established validity for use in persons with TFA. Participants were assessed performing the CS-PFP-10, AMP, 75 m self-selected walking speed test (75 m SSWS), down stair walking time (DN stair time), and the limits of stability (LOS) balance test. CS-PFP-10 The CS-PFP-10 was administered using standardized procedures (i.e., certified test site and test administrators, script dialogue; all reported elsewhere) (4,18). The CS-PFP-10 consists of 10 ADL tasks performed at maximal effort within the person’s

judgement of safety and comfort. Tasks are performed serially from low to high difficulty. The CS-PFP-10 tasks use time, distance, and weight to evaluate overall physical functional performance and performance in five physiologic functional domains: UBS, UBF, LBS, BAL, and END. Raw data (time, distance, mass) are converted, via an algorithm within licensed scoring software, into a continuously scaled score (0 to 100) for a singular overall total performance score and five individual domain scores. The CS-PFP-10 requires approximately 30 to 40 min to complete. Table 1 provides a description of CS-PFP-10 tasks.

Amputee Mobility Predictor (AMP) The AMP is a 21-item test of functional mobility used to predict an LEA patient’s ability to ambulate and was shown to have moderate to strong concurrent validity with the 6MWT and the Amputee Activity Survey (2). Specific details of each item and test administration of the AMP have been described previously (2). The following is a synopsis of the mobility functions assessed by the AMP (2). Items 1 and 2 test the ability to maintain sitting balance. Items 3 through 7 test the ability to maintain balance while performing tasks of transferring from chair to chair and standing unchallenged. Items 8 through 13 test more challenging standing balance activities. Items

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14 through 20 evaluate quality of gait and the ability to negotiate specific obstacles. Item 21 accounts for the use of particular assistive devices. Most AMP items offer three scoring choices: 0 indicates inability to perform the task, 1 indicates minimal level of achievement or that some assistance was required in completing the task, and 2 indicates complete independence or mastery of the task. The AMP test requires approximately 10 to 15 min to administer. The AMP test was administered by the study’s licensed physical therapist. The AMP score was used to test for correlations with the CS-PFP-10 total score and the END score. 75 m Self-Selected Walking Speed (75 m SSWS) Test Walking tests, including the 75 m SSWS test, are accepted measures of ambulatory function for TFA patients using both mechanical and microprocessor knee systems (19). In this study, timed performance data were collected using a manual stopwatch for a distance-based walking test of 75 m on even terrain. The test included a turnaround at 37.5 m. Participants were instructed to walk at their preferred self-selected walking speed (SSWS). The average of three trials was the participant’s representative time. The 75 m SSWS test was used to test for correlations with the CS-PFP-10 total score and the END score. Down Stair Walking (DN Stair Time) Stair descent is recognized as an important measure of functional independence for LEA patients (1921). Participants walked down stairs from a bilaterally railed, four-step stair platform. Subjects were asked to walk down the stairs in the manner and speed that represents their usual technique if they were in their homes or out in public. Subjects were asked to begin at the platform, facing down the stairs. They were asked to walk down following the command, “ready, set, go.” A handheld stopwatch was used to record the time between the “go” command and the instant when both feet were in contact with the floor. The average of three trials was the subject’s representative time. DN stair time was used to test for correlation with the LBS score.

Limits of Stability (LOS) For individuals to safely engage in functional activities while standing, they need to effectively maintain balance by positioning their center of mass (COM) within the limits of their base of support. The LOS balance test represents the maximal inclination from the vertical position that an individual can achieve without taking a step or falling (i.e., without changing their base of support) (22,23). The LOS test using computer posturography has validated that LEA patients have decreased LOS compared to non-amputee controls (22). The Biodex Balance SD system™ (Biodex Medical Systems, Shirley, NY, USA) was used to measure LOS. The Biodex Balance SD system™ incorporates a hemispherical suspended force platform that can tilt any direction up to 20˚ from horizontal (23). The platform includes gridlines for test-retest positioning reliability and a screen to provide COM data in real time to the patient visually. LOS were assessed in eight directions: forward, backward, right, left, forward-right, forward-left, backward-right, and backward-left. Poor directional control is scored by large variance (unitless). Subjects had to maintain the COM in the middle of a concentric circle that appeared on a screen positioned in front of them at a comfortable height. The LOS assessment consisted of three trials of 20 s duration each with 25 s rest periods between trials. The Biodex SD tests LOS by displaying an onscreen target placed in front of the subject. The target appears randomly in eight different directions only once, indicated when the respective target blinks in an alternating color (yellow to red) onscreen. Subjects are instructed to move their COM toward the target without changing foot position. The system permits three difficulty levels for this task (100%, 50%, and 25%) depending on the degree of ankle motion required to reach the target. Pilot testing with two TFA patients (not study subjects) was used to select the appropriate level at which the targets could be reached safely without loss of balance. For safety reasons following pilot data assessment, we selected the 25% difficulty level, which required platform tilt of 2° anteriorly, 1° posteriorly, 2° towards right, and 2° towards left. Sway required to reach each target from the center by the perfect shortest vertical or horizontal path is recorded by the instrument and

CS-PFP-10 VALIDITY IN TRANSFEMORAL AMPUTEES scored. A score of 100 is the maximal achievable score in any direction. In each LOS test, the system computes the eight directional LOS scores and an overall LOS score as a percentage of the maximal score, which is 100. A lower score indicates greater sway. The system also calculates the time it takes for the subject to reach all eight directional targets, thus completing the assessment. The overall LOS score was used to test for correlation with the BAL score. Statistical Analysis The extent of statistical correlation was examined to determine concurrent validity. Data were entered into a database and examined for normality. For normally distributed data, Pearson product moment correlation coefficients (r) were calculated for each test pair (i.e., respective PFP total or domain score compared to a test with established validity for use with TFA). If data were abnormally distributed, Spearman rank correlation coefficients (rs) were calculated. Strength of correlation values were categorized as 0 to ± 0.29 very weak, ± 0.30 to 0.49 weak, ± 0.50 to 0.69 moderate, and ± 0.70 to 1.00 strong (24). Statistical significance for test pairs was also assessed with a critical α of p < 0.05. Statistical analyses were performed using IBM SPSS (v21, Armonk, NY, USA). RESULTS Ten persons (eight males, two females) aged 24 to 75 years with unilateral TFA were recruited. See Table 2 for TFA participants’ physical characteristics. Correlations for Concurrent Validity All four selected comparison tests, representing mobility, walking speed, balance, and stair walking capacity (i.e., the AMP test, 75 m SSWS test, LOS test, and the DN stair time test), strongly correlated (i.e., r = ± 0.76 to 0.86) with their matched CS-PFP-10 domain score or total score. For example, the CS-PFP-10 domain score for LBS strongly correlated (r = -0 .79) with stair descent time (DN stair time) as a concurrent measure of strength. Furthermore, all of the paired tests’ correlations were statistically significant at p ≤ 0.01 (Table 3).

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DISCUSSION To recommend the general use of an outcome measure, evidence is necessary that the measure has strong psychometric properties for the target population. Psychometric properties include the level of measurement of the outcome data, validity and reliability, and the test’s sensitivity to detect change following intervention. Since the CS-PFP-10 provides ratio level outcome data, it allows for more precise parametric statistical analyses. Previous work by Highsmith et al. (16) has shown that the CS-PFP-10 was able to determine significant change differences in functional performance with TFA patients using two different interventions (i.e., microprocessor knee systems). The primary findings of this study were that the CS-PFP-10 and its specific physiologic functional domains that involve the lower extremities (LBS, BAL, or END) demonstrated high concurrent validity (i.e., statistically significant, strong correlations) with measures of comparable ADL tasks or physiologic

Table2.2. Physical Characteristics of Transfemoral Table Physical Characteristics of Transfemoral AmputeeAmputee (TFA) Participants (TFA)

Gender Etiology of Amputation

Male Female

Cancer Peripheral Vascular Disease Trauma

Age (y) Time since Amputation (y) Residual Limb Ratio (Residual limb length ÷ Intact limb length * 100%) Height (cm) Weight (kg)

n=8 n=2 n=3 n=1 n=6 41.3 ± 15.5 9.6 ± 10.8 76% ± 19 % 176.5 ± 5.2 78.8 ± 16.5

Table 3. Correlations for Concurrent Validity Table 3. Correlations for Concurrent Validity CS-PFP-10 Total Score or Specific Domain Score Total Score Total Score BAL Domain END Domain END Domain LBS Domain

Comparative Test AMP 75m SSWS LOS AMP 75m SSWS DN stair time

Pearson Correlation Coefficient (r) 0.80 -0.86 0.76 0.76 -0.81 -0.79

Balance and coordination (BAL), endurance (END), lower body strength (LBS). Amputee Mobility Predictor (AMP), 75m self-seBalance and coordination (BAL), endurance (END), lower body strength (LBS). A lected walking speed (75m SSWS), down stair walking time (DN Predictor (AMP), 75m self-selected walking speed (75m SSWS), down stair walk stair limits of stability (LOS). All paired tests’ limits time), of stability (LOS). All paired tests’ correlations were correlations statistically significant a were statistically significant at p ≤ 0.01.

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measures that have established validity for use with TFA patients. Our findings of the correlation between the END domain (i.e., 6MWT) and AMP (r = 0.76) agree well with the correlation between the AMP and 6MWT reported by Gailey et al. (r = 0.69 to 0.82) (2). Additionally, the CS-PFP-10 total score correlates strongly with the AMP (r = 0.80). We suggest that it may be more advantageous to use the CS-PFP-10 rather than the AMP with TFA patients as a measure of general physical functional performance, as the CS-PFP-10 involves usual ADL tasks, including more functional walking tasks (i.e., carrying groceries 70 m, 6MWT, and manipulating clothing and cookware). Furthermore, use of the CS-PFP-10 allows for performance comparisons to other populations. CONCLUSION These findings, combined with the results reported by Highsmith et al. (16), indicate that the CS-PFP-10 has strong psychometric properties. These include the ability to detect change in a small sample clinical trial and concurrent validity in high functioning persons with TFA. To further increase confidence with use of the CS-PFP-10 in TFA cases, additional psychometric properties should be determined, such as test-retest reliability. ACKNOWLEDGMENTS This project was funded by: 1. The Center for Prosthetic Orthotic Learning. (USF Grant #6140103000) 2. National Institutes of Health Scholars in Patient Oriented Research (SPOR) grant (1K30RR22270) Contents of this manuscript represent the opinions of the authors and not necessarily those of the U.S. Department of Defense, U.S. Department of the Army, U.S. Department of Veterans Affairs, or any academic or health care institution. The authors declare no conflicts of interest.

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PSYCHOMETRIC EVALUATION OF THE HILL ASSESSMENT INDEX (HAI) AND STAIR ASSESSMENT INDEX (SAI) IN HIGH-FUNCTIONING TRANSFEMORAL AMPUTEES M. Jason Highsmith1-3, Jason T. Kahle4,5, Brian Kaluf6, Rebecca M. Miro1, Larry J. Mengelkoch7, and Tyler D. Klenow8 School of Physical Therapy & Rehabilitation Sciences, University of South Florida, Tampa, FL, USA Extremity Trauma & Amputation Center of Excellence (EACE), U.S. Department of Veterans Affairs, Tampa, FL, USA 3 319th Minimal Care Detachment, U.S. Army Reserves, Pinellas Park, FL, USA 4 OP Solutions, Tampa, FL, USA 5 Prosthetic Design + Research, Tampa, FL, USA 6 Ability Prosthetics and Orthotics, Greenville, SC, USA 7 Doctor of Physical Therapy Program, University of St. Augustine for Health Sciences, St. Augustine, FL, USA 8 Prosthetics and Sensory Aids Service, James A. Haley Veterans’ Hospital, Tampa, FL, USA 1

The hill assessment index (HAI) and stair assessment index (SAI) were developed to objectively evaluate ramp and stair gait. This study’s purpose was to determine the validity and reliability of these tests in a sample of persons with unilateral transfemoral amputation (TFA) using microprocessor prosthetic knee systems. All subjects were fit with a microprocessor knee system. After accommodation, subjects performed three trials ascending and descending a 5° ramp and a flight of stairs while being recorded on video. Sensitivity and specificity for the HAI was calculated against degree of asymmetry in step length using Dartfish video analysis software. Reliability was assessed using intraclass correlational coefficients calculated using Spearman’s Rho (rs). A priori significance level was set at p ≤ 0.05. Twenty (n = 20) individuals with TFA completed the study protocol. Sensitivity and specificity of the HAI were calculated at 88.0% and 75.0% during ascending conditions and 94.0% and 67.0% during descending conditions, respectively. Significant correlations for the HAI included rs = 0.87 and rs = 0.73 within raters uphill and downhill, respectively. Corresponding coefficients of rs = 0.80 and rs = 0.67 were calculated between raters. For the SAI, significant correlations included rs = 1.00 for both comparisons within raters and in the comparison between raters in the ascending condition. A correlation of rs = 0.89 was calculated for the between-rater comparison in the descending condition. The HAI showed moderate to excellent sensitivity and specificity but good to adequate reliability. The SAI showed excellent to good reliability. Key words: Gait evaluation; Observational gait assessment; Outcome measures; Physical therapy; Ramps; Rehabilitation; Step

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INTRODUCTION Observational gait analysis (OGA) serves an integral role in many rehabilitation fields and is a current clinical assessment standard for prosthetics. However, while OGA has been found to have approximately 60% to 85% reliability (1), it has been infrequently investigated on ramps and stairs (2). Further, few clinically useful outcome measures to objectively evaluate gait on ramps and stairs have been introduced. The hill assessment index (HAI) and stair assessment index (SAI) were developed for this reason (3,4). These assessments utilize an 11and 13-point ordinal scale, respectively, to describe gross motor pattern implementation, degree of step length symmetry, and use of assistive devices. The inter-rater and intra-rater reliability of the HAI was found to be excellent in hill descent tasks for a sample of unilateral transfemoral amputation (TFA) patients using mechanical and C-Leg microprocessor knee (MPK) systems (2). However, no further evidence of psychometric properties for either outcome measure is available. Video motion analysis has been used to determine criterion validity for other observational and functional outcome measures in the past and may allow for establishing evidence of the validity of the HAI and SAI (5-7). Therefore, the purpose of this study was to determine the criterion validity and interrater and intra-rater reliability of the HAI and SAI in a sample of persons with unilateral TFA using a prosthetic MPK system. METHODS All procedures were reviewed and approved by the University of South Florida’s Institutional Review Board, and subjects gave informed consent prior to study participation. Subjects were considered for study inclusion if they met the following criteria: • Unilateral transfemoral or knee disarticulation amputation • Use of a prosthesis with MPK for at least one year • Independent level of community ambulation without use of an assistive device

• Ability to ascend and descend a ramp without human support • Ability to ascend and descend stairs without human support Subjects who met the inclusion criteria were enrolled in the study and evaluated by the study prosthetist to assure proper fit and function. The study prosthetist was state-licensed and certified by the American Board for Certification in Orthotics, Prosthetics, and Pedorthics. Subjects’ prosthetic sockets and suspension systems were not changed for the duration of the experiment to reduce confounding from fit and acclimation issues. All subjects were fit with the same model energy-storing prosthetic foot for use over the study duration. Manufacturer specifications were used to set componentry alignment and were verified using the LASAR alignment system (Ottobock Healthcare, Duderstadt, Germany). Each subject received training from the study physical therapist on the functions of the MPK and study foot for transitional movements, obstacle crossing, ramps, stairs, speed variation, and variable surfaces. Training techniques were used from prior publications (8,9). Subjects then accommodated with the new foot components until they reported and demonstrated confidence in walking unassisted on level ground, inclines, declines, and up and down stairs. Following this accommodation, subjects were scheduled for testing. Subjects were asked to ascend and descend an Americans with Disabilities Act-compliant cement Figure 1. Hill Assessment Index (HAI).

HILL & STAIR ASSESSMENT IN ABOVE-KNEE AMPUTEES ramp, which was 0.9 m in width, 4.9 m in length, and sloped at an angle of 5°. Each subject completed three trials up and three trials down at a self-selected walking speed using handrails as they deemed necessary. These trials were timed using a stopwatch and recorded (sagitally) on video. The recordings were scored by two independent raters who reviewed the video recordings to determine the appropriate HAI value based on the criteria outlined in Figure 1 (3,4). The recordings were then assessed using Dartfish™ 2D (v7, Dartfish USA, Inc. Alpharetta, GA,USA) gait analysis software to determine prosthetic and sound side step length. Step length was measured relative to a 1.0 m reference object captured in the video background and measured using reflective markers placed on subjects’ heels and toes. A previous investigation found inconsequential differences in marker movement tracked by 3D motion capture and Dartfish software on the order of ≤5 mm (10). Further, this program was previously found to be a valid (PCC ≥ 0.95; p < 0.05) and reliable (ICC ≥ 0.93; p < 0.05) motion analysis tool (11). Degree of asymmetry (DoA) was then calculated for step length using the following equation: Degree of Asymmetry =

Sound Step Length – Prostethetic Step Length Sound Step Length + Prostethetic Step Length

Subjects then repeated the protocol on a flight of Americans with Disabilities Act-compliant stairs (12). The three trials ascending and three trials descending at a self-selected speed were timed using a handheld stopwatch and sagittaly recorded on video. These recordings were again scored by two independent raters, this time using the criteria outlined in Figure 2 to determine the appropriate SAI score (3,4). Subjects repeated the study protocol on the ramp and stairs 90 d after initial testing to assess intra-rater reliability. The HAI is scored on an ordinal scale from 0 to 11. In this sample, however, all subjects received a score of 10 or 11, resulting in a dichotomous data set. This allowed for step length, specifically DoA of step length (13), to become the reference standard for an assessment of sensitivity and specificity of the instrument at its higher scoring levels. The HAI indicates that a perfect score of 11 is an even step length without an assistive device determined visually by the

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Figure 2. Stair Assessment Index (SAI).

rater. Asymmetrical movements in function and gait between 5% and 10% have previously been described as typical (13,14). A perfect DoA score of 0, providing allowances for normal asymmetrical movement, can then be assumed to equate to a perfect HAI score. Therefore, absolute DoA values of ≤±0.1 were determined to be representative of a symmetric step length and thus eligible for an HAI rating of 11/11. This was used to establish the reference standard and those participants with absolute DoA values >±0.1 from the video motion analysis were determined to have an asymmetric step length and scored 10/11 on the HAI in this dichotomous set. Sensitivity and specificity are statistical measures of the validity of an outcome measure (15). Sensitivity is the proportion of subjects who test positive for a condition to all those who truly have the condition. Specificity is the proportion of subjects who test negative for a condition to all those who truly do not have the condition. In this case, sensitivity and specificity of the HAI in identifying subjects who do and do not exhibit step length symmetry during ramp gait was assessed. These variables were calculated using a twoby-two configuration of HAI score and step length symmetry determined by the Dartfish software and the calculation of DoA in step length. Sensitivity and specificity were calculated as:

Sensitivity = (nHAI score 10/n|DoA|>0.1) * 100 Specificity = (nHAI score 11/n|DoA|≤0.1) * 100

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In the above equation for sensitivity, nHAI score 10 represents the number of subjects who scored 10 on the HAI because the rater found them to have an asymmetrical step length, and n|DoA|>0.1 represents the number of subjects who truly exhibited asymmetrical steps as assessed with video motion analysis and the DoA equation for step length symmetry. In the above equation for specificity, nHAI score 11 represents the number of subjects who scored 11 on the HAI because the rater found them to have symmetrical step length, and n|DoA|≤0.1 represents the number of subjects who truly did exhibit symmetrical steps as assessed with video motion analysis and the DoA equation for step length symmetry. Higher levels of sensitivity and specificity provide evidence to support the validity of the HAI to assess step length symmetry walking on ramps. To evaluate levels of sensitivity and specificity, we interpreted scores from 90% to 100% as excellent, 75% to 89% as good, 50% to 74% as adequate, and below 50% as poor sensitivity and specificity for the HAI uphill and downhill. Positive and negative likelihood ratios can be calculated from the sensitivity and specificity values. A positive likelihood ratio indicates how many times more likely a positive test will be seen in those with more symmetric step lengths than in those with less symmetric step lengths (15). Interpretation of likelihood ratios vary (16,17). We interpreted a positive likelihood ratio of 10 or more as large, 5 to 9.94 as moderate, 2 to 4.94 as small, and 1 to 1.94 as very small positive likelihood. These positive likelihood ratios were used to determine if the HAI was a very useful, often useful, sometimes useful, or rarely useful test, respectively. A negative likelihood ratio, then, indicated how many times more likely a negative test will be seen in those with more step length symmetry compared to those with less step length symmetry (15). A negative likelihood ratio of less than 0.1 was interpreted as large, 0.11 to 0.2 as moderate, 0.21 to 0.5 as small, and 0.51 to 1.0 as very small negative likelihood. These negative likelihood ratios were used to determine if the HAI was a very useful, often useful, sometimes useful, or rarely useful test, respectively. Comparisons between rater one and rater two at initial testing and rater one at the repeat evaluation were made to assess inter- and intra-rater reliability

of each instrument, respectively. Data were compared for both tests for ascending and descending conditions. Intraclass correlation coefficients (ICC) were determined using Spearman’s Rho. Definitions for correlation strength also vary (15,18-20). We interpreted 0.9 to 1.0 as an excellent correlation, 0.75 to 0.89 a good correlation, 0.5 to 0.74 an adequate correlation, and below 0.5 a poor correlation. The level for statistical significance was determined a priori to be p ≤ 0.05. RESULTS Twenty (n = 20) individuals with TFA completed the study. The sample was 80% male with etiology of trauma (70%), tumor (20%), or vascular disease (10%). Mean (SD) age was 46.5 years of age (±14.2). All subjects were unlimited community ambulators. Sensitivity of the HAI was calculated at 88.0% for uphill and 94.0% for downhill conditions. These results correspond to positive likelihood ratios of 3.5 and 2.8, respectively. Specificity for the instrument was determined to be 75.0% for uphill and 67.0% for downhill. These results correspond to negative likelihood ratios of 0.17 and 0.10, respectively. These results are summarized in Table 1. For the HAI, Spearman Rho ICCs of rs = 0.80 (p < 0.001) for uphill and 0.67 (p = 0.001) for downhill conditions between rater one and rater two were found. ICCs of rs = 0.87 (p < 0.001) and 0.73 (p < 0.001) were calculated between initial and repeat testing scores for uphill and downhill conditions, respectively (Table 2). Mean (SD) uphill times (Table 3), in seconds, for trials one, two, and three were 4.71 (0.86), 4.71 (0.99), and 4.72 (1.03), respectively, resulting in a mean percent difference of 0.11% among trials. Mean and median scores were 10.8 and 11 for all trials. Mean downhill times, in seconds, for trials one, two, and three were 4.80 (1.14), 4.74 (1.19), and 4.78 (1.40), respectively, resulting in a mean percent difference of 1.1% among trials. Mean and median downhill scores were 10.9 and 11 for all trials. For the SAI, ICCs of rs = 1.00 (p < 0.001) and 0.89 (p < 0.001) were found between raters one and two for ascending and descending conditions, respectively. ICCs of rs = 1.00(p < 0.001) were calculated for both

HILL & STAIR ASSESSMENT IN ABOVE-KNEE AMPUTEES

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Table 1. Sensitivity, Specificity, and Likelihood Ratios 12.0, 11.7, and 11.8, with a constant median of 11. Times and scores for the HAI and SAI are shown in Condition Uphill Downhill Table 3.

Table 1. Sensitivity, Specificity, Likelihood Ratios

Sensitivity

88.0%

94.0%

DISCUSSION The results of this study provide evidence of the Specificity 75.0% 67.0% validity and reliability of the HAI and SAI in a sample of persons with unilateral TFA using an MPK system + Likelihood Ratio' 3.50 2.80 and ambulating at an unlimited-community level. The sensitivity of the HAI was determined to be - Likelihood Ratio' 0.17 0.10 good for uphill and excellent for downhill evaluations in this sample of community ambulating transfemoral amputees. The good sensitivity for uphill and excellent ascending and descending conditions between inisensitivity for downhill evaluations resulted because tial and repeat testing (Table 2). Mean (SD) ascent the raters on the HAI correctly identified those who times (Table 3), in seconds, for trials one, two, and walked with step length DoA above the 0.1 reference three were 4.95 (1.01), 5.15 (1.62), and 4.68 (1.33), standard. Especially on hill descent, the excellent respectively, resulting in a mean percent difference of sensitivity shows that the HAI will have a low rate of 6.7% among trials. Corresponding mean trial scores false negatives, meaning that if a subject is identified were 9.7, 9.9, and 10.1, with a constant median of 11. by the rater as having asymmetrical step length, it is Mean descent times, in seconds, for trials one, two, highly likely that they actually do have asymmetrical and three were 3.82 (0.97), 3.72 (0.80), and 3.61 (0.80), step length. Both positive likelihood ratios indicate respectively, resulting in a mean percent difference of the HAI is a â&#x20AC;&#x153;sometimes usefulâ&#x20AC;? test for uphill and 2.76%. Corresponding mean descending scores were downhill assessments of hill gait in higher functioning Table 2. HAI/SAI Inter/Intra-Rater CorrelationsTFA subjects. Table 2. HAI/SAI Inter/Intra-Rater Correlations

Hill Assessment Index

Inter-rater

Variable

Uphill

Downhill

Uphill

Downhill

Spearman's Rho (rs)

0.80

0.67

0.87

0.73

ICC significance

p < 0.001

p = 0.001

p < 0.001

Intra-rater

Stair Assessment Index

Inter-rater

Variable

Ascent

Descent

Ascent

Descent

Spearman's Rho (rs)

1.00

0.89

1.00

ICC significance

p < 0.001

Intra-rater

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HIGHSMITH ET AL. Table 3. Mean/Median Stair Performance Table 3. Mean/Median Stair Performance

Instrument

HAI

Condition

Uphill

SAI Downhill

Ascent

Descent

Time (sec)

mean

Trial 1

4.71

0.86

4.80

1.14

4.95

1.01

3.82

0.97

Trial 2

4.71

0.99

4.74

1.19

5.15

1.62

3.72

0.80

Trial 3

4.72

1.03

4.78

1.40

4.68

1.33

3.61

0.80

% diff

0.11%

1.07%

6.72%

2.76%

Score

mean

median

mean

median

mean

median

mean

median

Trial 1

10.8

11.0

10.9

11.0

9.7

11.0

12.0

11.0

Trial 2

10.8

11.0

10.9

11.0

9.9

11.0

11.7

11.0

Trial 3

10.8

11.0

10.9

11.0

10.1

11.0

11.8

11.0

The specificity of the HAI was determined to be good for uphill and adequate for downhill assessment. The lower specificity on ramp descent was a result of some subjects being scored by the raters as having asymmetrical step length although they actually had symmetrical step lengths based on having step length DoA below 0.1. This could mean that identifying step length symmetry during ramp descent may be more difficult and there is the potential for an increased rate of false positives (i.e., giving a lower HAI score for step symmetry). The negative likelihood ratios confirm that the HAI is a “sometimes useful” test for both uphill and downhill assessments of hill gait. In summary, the HAI was found to be an adequate to excellent assessment tool of step length symmetry during uphill and downhill gait of subjects in this sample. The assessment was found to be more sensitive for downhill assessment and more specific for uphill in high-functioning persons with unilateral TFA. Due to the lower specificity in ramp descent, low scores may be vulnerable to false results in this population. However, due to the good and excellent sensitivity of the HAI, lower scores should truly identify those with less symmetrical step length during ramp gait.

Assessment of intra-rater reliability for the HAI was found to be good for uphill but adequate for downhill gait in this sample based on the strength of correlation (Spearman’s Rho). These results were identical to the inter-rater reliability in this sample, with uphill being found as good and downhill being found as adequate. The downhill inter-rater reliability assessment was adequate. These results differ slightly from the results of previous work, which found excellent inter-rater reliability in a more heterogeneous sample of TFA subjects utilizing C-Leg MPKs (2). The modest differences could be multi-factorial and potentially include sample heterogeneity, rater experience and background, a lack of scoring instructions for the instrument, slight performance interpretation differences, and other factors. The consistency of HAI times, with a percent change in time of 0.1% and 1.1% for ascent and descent, respectively, and the reliability of uphill HAI scores among trials provide some evidence of the instrument’s stability on repeat testing within a single visit. Based on the negligible differences in time to ambulate on the ramp and HAI scores, no learning or fatigue effects were noted in this sample. This internal consistency commonly suggests no benefit between

HILL & STAIR ASSESSMENT IN ABOVE-KNEE AMPUTEES a single or repeated testing protocol. Thus, in the interest of valuable clinical time, it seems feasible that a single administration of the test may be sufficient to determine the patientâ&#x20AC;&#x2122;s ability to ambulate ramps. Repeated testing of high-functioning TFA patients within a single clinic visit seems unlikely to yield different scores provided conditions (e.g., components, physical status) are not changed. The SAI was found to be a very reliable assessment tool for high-functioning transfemoral prosthetic users. Inter-rater reliability was excellent for ascending and good for downhill conditions based on the strength of correlation. Excellent intra-rater reliability was found for both ascending and descending assessments. The percent differences among trial times was higher than the HAI, but the mean differences remain adequately low to preliminarily declare the instrument as stable in comparable samples. No clear trend in time or scoring for the SAI was found among trials, further suggesting no learning or fatigue effect. The results of this work also show no benefit or detriment to performing the test once or multiple times. For clinical simplicity, the test may only require a single administration to determine a high-functioning TFA subjectâ&#x20AC;&#x2122;s true stair ascent or descent capability. As with the HAI, this is provided that the subject has been trained and is confident in using the specific functional features (e.g., stair ascent mode) of the MPK. The SAI may provide more obvious differentiation between scores relative to the HAI, as there is less opportunity for subjectivity in the construct. The HAI requires the rater to determine step length ratios, which may have large variability between subjects, whereas the SAI requires identification of more discretely discernable stepping patterns. Future research should attempt to establish validity for the SAI, as this study demonstrated strong evidence of the inter-rater and intra-rater reliability for the SAI as a measure of stair ascent and descent. Replication research is needed to confirm the recommendation for a single test in comparable samples but also in TFA patients using mechanical knees or other types of knees and in those who ambulate at lower functional levels.

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Limitations This study utilized a group of high-functioning subjects with unilateral TFA who ambulated with MPKs. Therefore, results may not be applicable to individuals of differing amputation level(s), those with bilateral or upper extremity involvement, amputees of lower functional levels, or individuals of other diagnostic groups. Further, the dichotomous results of the HAI allowed for sensitivity and specificity calculation but prevented evaluation of the entire ordinal scale (i.e., at the lower end of the functional spectrum). A lack of low scores was also observed in SAI scores, resulting in left skewed data. Also, the reference standard adopted for this study, DoA in step length, while a more objective measure of step length symmetry than observational gait analysis, has not been thoroughly evaluated. The DoA cut-off score of Âą0.1 was chosen based on the assumption that 5% to 10% asymmetry in movement is typical in gait and other functional movement patterns (13,14). For this reason, it is difficult to make definitive conclusions of the reliability and validity of the entirety of the HAI and SAI. Further research is needed to confirm the results of this work in other amputation populations, including lower-functioning patients who would score lower in the range of the HAI and SAI measures. CONCLUSION The results of this work established validity and reliability of the upper end of the HAI and SAI in a population of high-functioning subjects with unilateral TFA using microprocessor knee systems. The HAI showed moderate sensitivity and specificity. Intra-rater reliability of the HAI was good for uphill and adequate for downhill assessment. Inter-rater reliability was found to be good for uphill and adequate for downhill assessment. Since other ramp gait assessment tools are scarce, the HAI was shown to be a viable assessment tool. The SAI showed excellent and good inter-rater reliability for ascending and descending conditions, respectively, and excellent intra-rater reliability for both. Both HAI and SAI were shown to be stable instruments for both ascending and descending assessments, resulting in a recom-

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mendation for one trial as a true assessment of hill and stair gait. More research is needed to determine validity of the SAI and to confirm all of these results in other amputation populations. ACKNOWLEDGMENTS The authors declare no conflicts of interest and are solely responsible for the content of this manuscript. Contents of this manuscript represent the opinions of the authors and not necessarily those of the U.S. Department of Defense, U.S. Department of the Army, U.S. Department of Veterans Affairs, or any academic or health care institution.

This project was funded by: 1. The Florida High Tech Corridor/USF Connect. (Grant # FHT 10-26) 2. National Institutes of Health Scholars in Patient Oriented Research (SPOR) grant (1K30RR22270) REFERENCES 1. 2.

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ISSN 1949-8241 • E-ISSN 1949-825X http://dx.doi.org/10.21300/18.2-3.2016.203 www.technologyandinnovation.org

BIOPSY 1-2-3 IN DERMATOLOGIC SURGERY: IMPROVING SMARTPHONE USE TO AVOID WRONG-SITE SURGERY James T. Highsmith1,2, David A. Weinstein3, M. Jason Highsmith4-6, Jeremy R. Etzkorn7 Dermatology Service, James A. Haley Veterans’ Hospital, Tampa, FL, USA 2 Dermatology Surgery Institute, Lutz, FL, USA 3 Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL, USA 4 School of Physical Therapy & Rehabilitation Sciences, University of South Florida, Tampa, FL, USA 5 Extremity Trauma & Amputation Center of Excellence (EACE), U.S. Department of Veterans Affairs, Tampa, FL, USA 6 319th Minimal Care Detachment, U.S. Army Reserves, Pinellas Park, FL, USA 7 Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA 1

The smartphone has become a ubiquitous tool in modern culture. Given the current high quality of smartphone cameras, they should be considered a valuable tool for the dermatologic surgeon in the pre-operative consultation. The purpose of this technical note is to describe a methodology using smartphone camera technology to improve the process for capturing biopsy site photographs and including those photos in decision making to maximize cutaneous surgical outcomes. This technical note describes a three-step procedure (BIOPSY 1-2-3) to simplify and standardize the protocol for capturing a biopsy site photograph using the patient’s own smartphone. The steps are also intended to improve the resolution and value of the image. A case example is provided. Using the steps of BIOPSY 1-2-3, the case example biopsy site image is clearly identified compared to a less structured image. Using BIOPSY 1-2-3, biopsy site images taken by patient-owned smartphone cameras can empower and involve patients in their care, improve image quality, and reduce medical errors. Key words: Cutaneous surgery; Digital photography; Mohs micrographic surgery; Skin cancer; Surgical site; Wrong-site surgery

taken, calorie intake, and exercise. Healthcare professionals use smartphones to replace pagers, assist in gait evaluation, and monitor medications (2). Additionally, they may be used to monitor ulcers in amputees or reduce the incidence of wrong-site surgeries in dermatologic surgery (1,3,4). With the current high quality of smartphone cameras, they

INTRODUCTION The smartphone has become a ubiquitous tool in modern culture. In 2011, 83% of Americans were estimated to have cellular phones (1). These devices have applications to entertain, assist in navigation, and receive electronic messages; they can also monitor health by logging sleep duration, heart rate, steps _____________________

Accepted July 1, 2016. Address correspondence to James T. Highsmith, James A. Haley Veterans’ Administration Hospital, Dermatology Service, 13000 Bruce B Downs Blvd, Tampa, Florida 33612, USA. Tel +1 (813) 457-0153; Fax +1 (813) 631-3228; E-mail: James.Highsmith@va.gov

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Figure 1. Patient presented for MMS for a biopsy-proven squamous cell carcinoma on his “right temple” that healed well and is difficult to locate. He initially refused treatment but eventually rescheduled, and the lesion was excised using MMS. Note the biopsy site is difficult to confidently locate because of background solar damage, rhytids, and scarring.

should be considered a valuable tool for the dermatologic surgeon in the pre-operative consultation. Wrong-site surgery has been identified as one of the most common adverse events (13.1%) reported by The Joint Commission (TJC) (4). To reduce these errors, TJC has implemented a “Universal Protocol,” thereby mandating pre-procedure verification, surgical site marking, and a “time out” to prevent surgical errors (5). Wrong-site surgeries are also a common cause of medical malpractice lawsuits affecting fellowship-trained Mohs surgeons (14.3%) (6). Identifying the correct biopsy site is complicated by background sun damage, adjacent skin conditions, biopsy technique (e.g., deep scallop versus superficial shave), and the amount of time between the biopsy and planned curative procedure (7). Biopsy sites often heal very well and can be difficult to locate, leading many patients to refuse an excision or at least question the need for another procedure as in the case example in Figure 1. An estimated 25% of patients presenting for Mohs Micrographic Surgery (MMS) could not correctly identify their biopsy sites (8). While a pre-operative biopsy may result in complete tumor removal in 15% to 42% of cases, identification of the correct surgical site is imperative to ensure definitive treatment of most cutaneous neoplasms (9,10). Given the previously identified value of patient involvement and the ease of access to smartphone technology and digital photography, the purpose of this project was to describe a methodology to improve the process for capturing biopsy site photographs and including those photos in decision making to maximize cutaneous surgical outcomes.

METHODS Many of the problems encountered with a biopsy site selfie (BSS) may be overcome by using a key strategy we have named BIOPSY 1-2-3. The three steps of the technique are as follows: 1. First, it is optimal to have one other person take the photo. 2. Next, make sure there are two anatomical land marks in the image. 3. Finally, verify there are three photos of each site. With each biopsy site, have one person who is not the patient take the photograph to avoid problems inherent with a BSS. This is recommended because often the secondary self-facing camera on the smartphone device is typically inferior to the primary camera, which results in lower quality photographs. Also, BSSs tend to be excessively zoomed in and out of focus. Having someone else take the picture with the patient’s device allows the picture to be taken with the primary camera at an adequate distance. The pictures can be taken at home by the patient’s family member or even at the office by the patient’s nurse at the time of their visit. Always mark the area that was, or is about to be, biopsied, as in Figure 2 of the case example. Use a dark pen, highlighter, or marker to circle the lesion to distinguish between two nearby dyspigmented patches at a later date. Next, have two body parts (e.g., ear and nose) or two joints (e.g., elbow and wrist) visualized in at least two of the pictures. Lastly, have at least three pictures of every site. It is best if each photograph is taken from a different vantage

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Figure 2. Smartphone photograph of the planned biopsy site taken prior to shave removal. Note that the lesion is circled and at least two anatomic landmarks are present.

point to ensure the site can be isolated from nearby lesions or background skin changes. Always zoom in to review each photograph. Delete the photo(s) and re-take them if they are out of focus or otherwise unsatisfactory. Consider repeating the technique with each biopsy site on the day of biopsy or at any time within the first week after the biopsy, which will still provide tremendous benefit at follow-up. RESULTS AND DISCUSSION The outlined steps (Figure 3) are simple and should improve biopsy site photography to facilitate improved outcomes and reduce medical errors. The case example highlights the value in a systematic approach for this process. Photography has become the gold standard in the pre-operative evaluation of dermatologic surgery and has been shown to reduce wrong-site surgeries. Furthermore, pre-operative photography has been shown to facilitate patient confidence in the treatment of the appropriate surgical site (7). Given the popular nature of smartphones today, patients may be encouraged to participate in their own care by using their own cell phone cameras to document the biopsy site and assist in the identification of the appropriate surgical site. Nijhawan et al. found the use of BSSs was crucial in correctly locating the surgical site in 21% of referred cases. This study also noted that the use of BSSs empowered patients to be active participants in their own care. Moreover, delaying surgery to confirm the correct biopsy site was minimized, and unnec-

essary re-biopsies were avoided (8). However, the BSS has several limitations. For example, a biopsy site on the scalp or back may be difficult to self-photograph, or the patient may have difficulty using a smartphone due to arthritis or lack of hand dexterity. There are also problems with the photos themselves. For instance, photos may be out of focus or excessively zoomed in, resulting in too few anatomical landmarks to facilitate location. Finally, patients may be resistant to taking a BSS picture. Figure 3. BIOPSY 1-2-3 steps.

BIOPSY 1-2-3 Biopsy: mark every biopsy site with a pen, marker, or highlighter. 1. One other person take your biopsy site pictures 2. Two joints or two body parts in at least two of the pictures 3. Three total pictures (different distances or angles)

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CONCLUSION Although dedicated high-resolution cameras would be ideal for biopsy site photography, many referring physicians do not send pictures with their consultations. Some physicians may not integrate photography into their practice, and others simply have the printed photographs on a paper chart and have not converted to electronic medical record systems (EMRs). Whether the referring and consulting physician has adopted EMRs or not, another obstacle is that EMRs are not universal and do not link or synchronize data. Even if all EMRs were fully integrated, there would still be a potential to violate the Health Insurance Portability and Accountability Act (HIPAA) if the photos were released. Therefore, the only truly universal form of photography that would not violate HIPAA and could go to every patient visit would come from the patient’s own smartphone device. Smartphones may one day provide a real-time, universal, and fully integrated EMR platform between clinicians and patients. However, until a more reliable system is in place, BIOPSY 1-2-3 serves as a simple solution to a common problem in dermatologic surgery today. ACKNOWLEDGMENTS This work was partially funded by the National Institutes of Health Scholars in Patient Oriented Research (SPOR) grant (1K30RR22270). Contents of this manuscript represent the opinions of the authors and not necessarily those of the U.S. Department of Defense, U.S. Department of the Army, U.S. Department of Veterans Affairs, or any academic or health care institution. REFERENCES 1. Lichtman MK, Countryman NB. Cell phone assisted identification of surgery site. Dermatol Surg. 2013;39(3 Pt 1):491-2. 2. Ginis P, Nieuwboer A, Dorfman M, Ferrari A, Gazit E, Canning CG, Rocchi L, Chiari L,

Hausdorff JM, Mirelman A. Feasibility and effects of home-based smartphone-delivered automated feedback training for gait in people with Parkinson’s disease: a pilot randomized controlled trial. Parkinsonism Relat Disord. 2016; 22:28-34. 3. Foltynski P, Ladyzynski P, Wojcicki JM. A new smartphone-based method for wound area measurement. Artif Organs. 2014;38(4):346-52. 4. Ke M, Moul D, Camouse M, Avram M, Carranza D, Soriano T, Lask G. Where is it? The utility of biopsy-site photography. Dermatol Surg. 2010;36(2):198-202. 5. The Joint Commission Universal Protocol [poster]. [accessed 2016 Mar 2]. http://www. jointcommission.org/assets/1/18/up_poster1. pdf. 6. Perlis CS, Campbell RM, Perlis RH, Malik M, Dufresne RG Jr. Incidence of and risk factors for medical malpractice lawsuits among Mohs surgeons. Dermatol Surg. 2006;32(1):79-83. 7. Zhang J, Rosen A, Orenstein L, Van Voorhees A, Miller CJ, Sobanko JF, Shin TM, Etzkorn JR. Factors associated with biopsy site identification, postponement of surgery, and patient confidence in a dermatologic surgery practice. J Am Acad Dermatol. 2016; Epub ahead of print. 8. Nijhawan RI, Lee EH, Nehal KS. Biopsy site selfies—a quality improvement pilot study to assist with correct surgical site identification. Dermatol Surg. 2015;41(4):499–504. 9. Gurunluoglu R, Kubek E, Arton J, Olsen A, Bronsert M. No residual basal cell carcinoma after excision for biopsy-proven tumor: clinical and medicolegal implications. Plast Reconstr Surg Glob Open. 2014;1(9):e87. 10. Stewart CM, Garlick J, Mcmullin J, Siddiqi F, Crombie C, Rockwell WB, Gociman B. Surgical excision of non-melanoma skin cancer in an elderly Veteran’s Affairs population. Plast Reconstr Surg Glob Open. 2015;2(12):e277.

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PLAY HANDS PROTECTIVE GLOVES: TECHNICAL NOTE ON DESIGN AND CONCEPT Michele Houston-Hicks1, Derek J. Lura2, and M. Jason Highsmith3-5 1 Physical Therapy Center, University of South Florida Morsani College of Medicine, Tampa, FL, USA Department of Bioengineering and Software Engineering, Florida Gulf Coast University, Ft. Myers, FL, USA 3 School of Physical Therapy & Rehabilitation Sciences, University of South Florida, Tampa, FL, USA 4 Extremity Trauma & Amputation Center of Excellence (EACE), U.S. Department of Veterans Affairs, Tampa, FL, USA 5 319th Minimal Care Detachment, U.S. Army Reserves, Pinellas Park, FL, USA 2

Cerebral Palsy (CP) is the leading cause of childhood motor disability, with a global incidence of 1.6 to 2.5/1,000 live births. Approximately 23% of children with CP are dependent upon assistive technologies. Some children with developmental disabilities have self-injurious behaviors such as finger biting but also have therapeutic needs. The purpose of this technical note is to describe design considerations for a protective glove and finger covering that maintains finger dexterity for children who exhibit finger and hand chewing (dermatophagia) and require therapeutic range of motion and may benefit from sensory stimulation resulting from constant contact between glove and skin. Protecting Little and Adolescent Youth (PLAY) Hands are protective gloves for children with developmental disorders such as CP who injure themselves by biting their hands due to pain or sensory issues. PLAY Hands will be cosmetically appealing gloves that provide therapeutic warmth, tactile sensory feedback, range of motion for donning/ doffing, and protection to maximize function and quality of life for families of children with developmental disorders. The technology is either a per-finger protective orthosis or an entire glove solution designed from durable 3D-printed biodegradable/bioabsorbable materials such as thermoplastics. PLAY Hands represent a series of protective hand wear interventions in the areas of self-mutilating behavior, kinematics, and sensation. They will be made available in a range of protective iterations from single- or multi-digit finger orthoses to a basic glove design to a more structurally robust and protective iteration. To improve the quality of life for patients and caregivers, they are conceptualized to be cosmetically appealing, protective, and therapeutic. Key words: Cerebral Palsy; Developmental delay; Finger biting; Physical therapy; Rehabilitation; Self-mutilation

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INTRODUCTION Annually in the U.S., approximately 10,000 infants are born with cerebral palsy (CP) (1). The worldwide incidence of CP is 1.6 to 2.5/1,000 live births, placing CP as the leading cause of childhood motor disability (1,2). Approximately 23% of children with CP are dependent upon assistive technologies (3). Use of these assistive technologies includes functional uses such as walking aids and orthoses but may also include protective roles. Protective roles may be aimed at limiting injury during function but may also be necessary in the case of self-injury caused by behaviors such as finger biting. Currently, technologies to facilitate the dual role of therapeutics and protection of the hand and finger in populations such as these are limited. The purpose of this technical note is to describe potential needs and design considerations for a protective glove and/or finger covering that maintains dexterity of the finger for children with diagnoses such as cerebral palsy, Lesch-Nyhan syndrome, and dermatophagia who exhibit finger/hand chewing, require therapeutic range of motion, and may benefit from sensory stimulation from constant contact. CONCEPT Protecting Little and Adolescent Hands (PLAY) Hands Gloves are protective gloves for children with developmental disorders such as CP who injure themselves by biting their hands due to pain or sensory issues. At times, these self-mutilating behaviors result in wounds, pain, loss of function, and increased dependence or self-care. PLAY Hands are conceived to be cosmetically appealing gloves that provide therapeutic warmth, tactile sensory feedback, range of motion for donning/doffing, and protection to maximize function and quality of life for families of children with developmental disorders. DESIGN PLAY Hands are gloves with protective finger pad material reinforcement to prevent young persons with CP, or other diagnoses contributing to self-mutilating behaviors, from biting and traumatizing their fingers. The gloves will be reinforced with protective materials to cover the finger pads where these individuals

attempt to bite and traumatize the fingers, leading to pain, wounds, and difficulties with subsequent selfcare tasks and play. The reinforcing material will be non-toxic but durable to minimize the risk of ingesting harmful materials. The gloves would ideally appeal to children by being adorned with popular cartoon characters, pending licensing agreements. The gloves will facilitate higher quality of life for patients and caregivers by mitigating complications associated with finger biting. An additional benefit of PLAY Hands is that many people affected by CP and other neurologic disorders may have contractures of the joints of the hands and fingers. The act of donning/ doffing PLAY Hands will require a range of motion activity for the hands, offering a therapeutic effect in addition to protection. Finally, wearing a glove offers a sensory experience from both tactile and thermal perspectives that may be beneficial for some users. The wearable finger protection design is dependent upon the desired device utilization. A solution is presented that is either an entire glove or independent for each finger, allowing either targeted intervention on digits that are more prone to chewing or protection for the entire hand when used in combination. For this construction, use of high molecular weight poly(lactic acid) PLA or high to ultra-high molecular weight polyethylene (UHMWPE) should be considered in the design of a bite protection device. Both materials are commonly used in food packaging materials, are non-toxic, and can be used in implantable devices with proper processing. “PLA is a thermoplastic, high-strength, high-modulus polymer that can be made from annually renewable resources to yield articles for use in … biocompatible/bioabsorbable medical device market” according to Garlotta (4). PLA is a thermoplastic material with a melting point of approximately 180 °C, a tensile strength typically in the range of 50 MPa (depending upon processing and origin), and an elastic modulus of 3500 MPa. PLA also has a glass transition temperature of 60 to 65 °C, which allows for easy at-home thermofitting around the patient’s finger to ensure a tight yet comfortable fit. Figure 1 presents a sample prototype showing fitting of a basic protective frame using 3D-printed PLA. The second thermoplastic under consideration for the proposed design is UHMWPE. Although it

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Figure 1. 3D-printed prototype showing a simple thermo-molded protective frame with compliant hinges. A) Original 3D-printed device, B) device after molding to the userâ&#x20AC;&#x2122;s finger, C) device attached to the finger in an extended position, and D) device attached to the finger in a flexed position. These images are a basic orthotic framework for only the single digit and lack the cosmetic/protective outer covering. Further, the concept is envisioned for use either as single- or multi-digit finger covering(s) or as a whole hand glove.

typically has a lower tensile strength than PLA (~25 MPa), it is also considerably softer (elastic modulus 500 to 800 MPa) and has a longer elongation range prior to failure (5). These characteristics would make the final product less prone to breakage but more likely to bend and thus less likely to damage teeth. This product would not be formable to the user; therefore, it would require more complex molds to produce the finished product, and careful attention would have to be used when selecting sizes. Protective plates could also be added to textile gloves for pressure distribution in patients where a rigid frame is not needed (low force chewing). Ultimate selection of materials depends on a variety of desired specifications for the final product, including weight, strength, and stiffness as well as cost and production volume. Initial prototyping in PLA is advisable, as it can be 3D printed readily by fuse deposition modeling or fused filament fabrication. Custom gloves and inserts should be tested along with traditional protective hand wear, such as hockey

and motocross gloves, to assure wear and failure commensurate with other established protective wear for hands. CONCLUSION PLAY Hands represent a series of protective hand wear interventions that offer solutions in the areas of self-mutilating behavior, kinematics, and sensation. They will be made available in a range of protective iterations, from a basic glove design to a more structurally robust and protective iteration. They are conceptualized to be cosmetically appealing, protective, and therapeutic and to ultimately improve the quality of life for patients and caregivers. ACKNOWLEDGMENTS Contents of this manuscript represent the opinions of the authors and not necessarily those of the U.S. Department of Defense, U.S. Department of the Army, U.S. Department of Veterans Affairs, or any academic or health care institution. Authors declare no conflicts

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of interest. This project was partially supported by the National Institutes of Health Scholars in Patient Oriented Research (SPOR) grant (1K30RR22270).

REFERENCES 1.

Ashwal S, Russman BS, Blasco PA, Miller G, Sandler A, Shevell M, Stevenson R, Quality Standards Subcommittee of the American Academy of Neurology, Practice Committee of the Child Neurology Society. Practice parameter: diagnostic assessment of the child with cerebral palsy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology

3. 4. 5.

Society. Neurology. 2004;62(6):851-863. Odding E, Roebroeck ME, Stam HJ. The epidemiology of cerebral palsy: incidence, impairments and risk factors. Disabil Rehabil. 2006;28(4):183191. Beckung E, Hagberg G, Uldall P, Cans C. Probability of walking in children with cerebral palsy in Europe. Pediatrics. 2008;121(1):e187-192. Garlotta D. A literature review of poly(lactic acid). J. Polym. Environ. 2001;9(2):63-84. Kurtz SM. UHMWPE biomaterials handbook: ultra high molecular weight polyethylene in total joint replacement and medical devices. 2nd ed. Cambridge (MA): Academic Press; 2009.

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RADIOGRAPHIC ASSESSMENT OF EXTREMITY OSSEOINTEGRATION FOR THE AMPUTEE Munjed Al Muderis1-3, Belinda A. Bosley3, Anthony V. Florschutz4, Paul A. Lunseth4, Tyler D. Klenow5, M. Jason Highsmith6-8, and Jason T. Kahle9,10 The Australian School of Advanced Medicine, Macquarie University, Macquarie, Australia 2 School of Medicine, University of Notre Dame Australia, Auburn, Australia 3 Norwest Private Hospital, Bella Vista, Australia 4 BayCare Medical Group, Tampa, FL, USA 5 Prosthetics and Sensory Aids Service, James A. Haley Veterans’ Hospital, Tampa, FL, USA 6 School of Physical Therapy & Rehabilitation Sciences, University of South Florida, Tampa, FL, USA 7 Extremity Trauma & Amputation Center of Excellence (EACE), U.S. Department of Veterans Affairs, Tampa, FL, USA 8 319th Minimal Care Detachment, U.S. Army Reserves, Pinellas Park, FL, USA 9 OP Solutions, Tampa, FL, USA 10 Prosthetic Design + Research, Tampa, FL, USA 1

Osseointegration (OI) is a bone-anchoring procedure that allows the direct skeletal attachment of a prosthesis through the use of an implant. Transcutaneous OI implants are similar to subcutaneous intramedullary joint implants with some exceptions. Particularly, OI implants are inserted at the distal aspect of the femur, while intramedullary implants are inserted at the proximal aspect of the femur. In this report, an additional adaptation of the radiographic zonal analysis used for intramedullary implants, known as Gruen zones, is introduced to include OI implants of extremity prosthetics. Radiographic zonal analyses and interpretations are proposed. Gruen zones are used for intramedullary implants, which are generally inserted from the proximal aspect of the bone. OI extremity implants are inserted from the distal end of the bone. Therefore, the zonal analysis is inverted. A radiographic zonal analysis has been introduced by the Osseointegration Group of Australia (OGA). This analysis is needed specifically for the clinical evaluation of extremity OI, as significant changes to the bone and OI implant have been reported and need to be clinically described. A classification technique is necessary for establishing treatment guidelines for the extremity osseointegrated implant. The OGA Zonal analysis addresses this need by adapting a common reference standard to osseointegration of the extremity amputee. Key words: Amputation surgery; Implant; Interface; Socket; Prosthesis; Transfemoral amputation

_____________________ Accepted July 1, 2016. Address correspondence to: Jason T. Kahle, OP Solutions, 12206 Bruce B. Downs Blvd., Tampa, FL 33612, USA. Tel: +1 (813) 971-1100; Fax: +1 (813) 971-9300; E-mail: Jason@opsolutions.us

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INTRODUCTION The current standard of care for a person living with limb loss who uses an artificial limb is a socket attached to the prosthetic limb components. Examples of prosthetic components for the lower extremity amputee would be the knee, foot, and pylon, and, for the upper extremity amputee, they would be the elbow and hand. The prosthetic socket interface is the aspect of the prosthesis that attaches the components to the residual limb, or the remaining part of the amputated arm or leg. The socket interface has two primary functions: 1) to suspend the prosthesis to the human body during periods of unweighting and 2) to support the body weight of user during periods of weight bearing (1). A socket interface is designed to support the weight through the sidewalls, as walking on the distal end would cause excessive pain and discomfort. To achieve this and give the user control, the socket interface must be tightly fit and must enclose the majority of the residual limb. This can be uncomfortable, evidenced by more than 30% of lower extremity users noting problems with their socket interfaces, including skin breakdown, excessive heat and subsequent perspiration, limited range of motion, interference with urogenital function, quality of life, and function (2,3). Socket interface problems lead to more than 30 percent of amputees reducing their prosthetic use and having diminished quality of life and some choosing not to wear a prosthesis at all (4,5). Osseointegration (OI) is a bone-anchoring procedure that allows direct skeletal attachment of a prosthesis through the use of an implant (6-8). Increasing in popularity, OI is now used routinely in maxillofacial prosthetics and dentistry and, more recently, is gaining support for use in attaching lower and upper extremity prosthetics. In an extremity OI, the implant is an intramedullary attachment similar to a total hip arthrhroplasty (THA) or hip joint replacement. Extremity OI is transcutaneous, whereas other joint replacements are contained beneath the skin and underlying soft anatomy (subcutaneous) (6,7). Modern intramedullary joints report high rates of success (9); however, when first introduced, failure rates were near 20% (10,11). There are several techniques to subcutaneous intramedullary joint replacement, and all

techniques do not perform equally. Additionally, there are several types of failures that can occur. Because of the popularity of joint replacement and the prevalence of failure at the time, Gruen et al. reported on the modes of failure and a technique to radiographically identify the area, or zone, of failure (10,12). The stability of the joint replacement is graded using this zonal analysis, or Gruen zones. Gruen zones and modes of failure are the standard for evaluating the condition of a subcutaneous intramedullary joint replacement (Figure 1). Figure 1. Gruen zones compared to OGA Zones. The zones are simply inverted to properly place the exit of the OI extremity implant from the bone distal.

OI for the extremity amputee is only offered in a limited number of countries. In those countries, however, OI is beginning to gain popularity similar to the way subcutaneous joint replacement did nearly 50 years ago, and a protocol for zonal analysis must be similarly implemented. Recently, OI for the extremity amputee cleared Food and Drug Administration (FDA) approval with an Investigational Device Exemption for limited inclusion criteria in the U.S. Given the high incidence of amputees with socket interface problems, it is likely that OI for the extremity amputee will garner a significant patient population seeking solutions, similar to those with

RADIOGRAPHIC ASSESSMENT OF OSSEOINTEGRATION pain associated with joints over 50 years ago. As with joint replacement, there are many OI techniques. Different modes and types of failures associated with these techniques have been reported and can be anticipated as these techniques are studied over time. A system for radiographically analyzing transcutaneous extremity OI, similar to a traditional intramedullary implant, would be beneficial for future analysis of OI extremity implants. Therefore, the purpose of this report is to introduce a radiological zonal analysis for the use of the extremity OI transcutaneous implants. METHODS While Gruen et al. originally reported on using an analysis for intramedullary implants, there is precedence for modifying the protocol (10). In a later report, Gruen et al. changed the seven zones to include uncemented stems with porous coatings. Ten years after the original report, Johnston et al. described a more comprehensive approach to include extensive clinical parameters, such as demographics, pain levels, and activities of daily living. Additionally, they expanded the radiographic approach to include sagittal (M/L) zonal analysis, adding Zones 8 to 14. Further, an algorithmic scoring system was added to provide an overall rating (12). Amstutz et al. also added three zones to include the short metaphyseal stem of a metal hip joint (13). Ultimately, Santori and Santori modified this approach to five zones for the proximal-loading short femoral stem (14). In this report, an additional adaptation of the Gruen zones technique is introduced to include OI implants of extremity prosthetics. Gruen zones are used for intramedullary implants, which are generally inserted from the proximal aspect of the bone. OI extremity implants are inserted from the distal end of the bone. Therefore, the zonal analysis is inverted. This extremity OI zonal analysis technique, first reported by the Osseointegration Group of Australia (OGA) as the OGA Zones, would simply invert the zones to properly correspond with the aspects to the uncemented portion of the implant (9,15). Adaptation is necessary to transpose the spatial terms because extremity OI terminates proximal into the bone, whereas the traditional implant terminates distal into the bone. Therefore, to stay consistent with

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using Zones 1 and 7 to describe the coated area, where the implant exits the bone, the zones must be inverted. ZONES Gruen originally divided the femur into seven zones using the coronal (A/P) radiograph view (Figure 2a). While Johnston et al. added the sagittal (ML) view zones, OGA Zones are divided into seven zones and radiographically measured on the coronal (A/P) view only. These include three equally divided zones on each side of the radiograph and a zone (Zone 4) at the proximal aspect of the implant (Figure 1). Zone 1 is the most distolateral aspect of the bone implant interface opposite to Zone 7, which is the most vital, on the medial aspect on the radiograph. Zone 2 is mid-lateral portion opposite to zone 6 medially, and Zone 3 is at the lateral proximal aspect of the implant bone interface opposite to Zone 5 medially (Figure 2). IMPLANT DESIGN CHANGES AND THE EFFECT ON BONE The initial design of the Integral Leg Prosthesis (ILP; Orthdynamic GmbH, LuĚ&#x2C6;beck, Germany) was made from a Chrome cobalt alloy with a surface coating having a spongy metal macroporous structure of 300 to 1500 um in pore diameter with titanium coating (press fit cementless implant; Figure 3) . The area of the implant that has this macroporous structure covers most of the implant with the exception of the distal 1.5 cm at Zones 1 and 7 and at the proximal portion of the implant at Zone 4, where the surface is smooth. The observation first reported by OGA was that the cortical bone remodels over time and follow-up radiographs demonstrate bone resorption at the area where the implant portion is smooth (Zones 1 and 7), with the resorption stopping at the beginning of the spongy metal structure (Figures 2a and 2b). Conversely, the area of Zones 3 and 5 shows significant cortical bone thickening. These observations led to fundamental changes in the implant design of the Osseointegrated Prosthetic Limb (OPL; Permedica s.p.a, Milan, Italy) (Figure 3). First, the material was changed to titanium, which has a modulus of elasticity closer to bone of 110 GPa (bone modulus of elasticity is 17 GPa), while chrome cobalt alloy modulus of

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Figure 2. Two separate subjects with an ILP OI implant with distal bone resorption or the femur in Zones 1 and 7 (a and b); Two separate subjects with an OPL OI implant with distal cortical bone thickening in Zones 1 and 7 (c and d).

elasticity is 190 GPa. Second, the implant shape was changed, making a proximal 80 mm smooth surface with multiple longitudinal sharp splines of 1 mm high to cut through the cortical bone during implantation to provide initial rotational stability. Third, the distal 80 mm of the implant is fully coated with microporous plasma spray particles to provide potential bony ingrowth and has a similar collar to the ILP to provide initial axial stability against subsidence. The design changes have led to recent observations of distal stress shielding and proximal cortical bone thickening over time (Figures 2c and 2d) (9,15). DISCUSSION Clinical trials of OI have not yet been extensively reported. OI for the extremity amputee is relatively early in the cycle of product, procedure, and technique development. Currently it is only offered in a few countries and has only recently been introduced in the U.S. There is an opportunity for amputees to potentially benefit from this technology. However, potential side effects must also be understood. As the health care community observes changes and results of OI use, the evolution of OI implant design and technique can progress. Bone resorption, growth, and problems may be associated with the extremity OI at different locations than traditional intramedullary implants. Muderis et al. first reported these changes

using the OGA Zonal analysis and has noted changes particularly in the distal aspects of the implant, or Zones 1 and 7 (9,15). Implementation of the OGA Zones allows determination of location of radiographic changes, such as resorption, overgrowth, extremity OI implant changes, description, and consistency in clinical reporting. The OGA Zonal analysis will allow a practitioner to accurately track changes that occur over a timeframe to allow evidence-based decision making regarding OI extremity implants. CONCLUSION Radiographic zonal analysis is used in orthopedic intramedullary implant evaluation to clinically assess the location of changes as a result of the implant. OI using an intramedullary implant for the extremity amputee may yield similar changes. A classification technique is necessary for establishing treatment guidelines. The OGA Zonal analysis addresses this need by adapting a common reference standard to OI of the extremity amputee. ACKNOWLEDGMENTS Contents of this manuscript represent the opinions of the authors and not necessarily those of the U.S. Department of Defense, U.S. Department of the Army, U.S. Department of Veterans Affairs, or any academic or health care institution. Authors declare no conflicts

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Figure 3. Design changes in the OPL implant (bottom) compared to the IPL (top): 1) Titanium material, 2) proximal 80 mm smooth surface with multiple longitudinal sharp splines of 1 mm high to cut through the cortical bone, and 3) distal 80 mm of the implant is fully coated with microporous plasma spray particles.

of interest. This project was partially supported by the National Institutes of Health Scholars in Patient Oriented Research (SPOR) grant (1K30RR22270). REFERENCES 1.

Smith DG, Bowker J, Michael J, editors. Atlas of amputations and limb deficiencies: surgical, prosthetic and rehabilitation principles. 3rd ed. Rosemont (IL): American Academy of Orthopaedic Surgeons; 2004. Kahle JT, Highsmith MJ. Transfemoral sockets with vacuum-assisted suspension comparison of hip kinematics, socket position, contact pressure, and preference: ischial containment versus brimless. J Rehabil Res Dev. 2013;50:1241-52. Kahle JT, Highsmith MJ. Transfemoral interfaces with vacuum assisted suspension comparison of gait, balance, and subjective analysis: ischial containment versus brimless. Gait Posture. 2014;40:315-20. Dillingham TR, Pezzin LE, MacKenzie EJ, Burgess AR. Use and satisfaction with prosthetic devices among persons with trauma-related amputations: a long-term outcome study. Am J Phys MedRehabil. 2001;80:563-71. Lyon CC, Kulkarni J, Zimerson E, Van Ross E, Beck MH. Skin disorders in amputees. J Am

Acad Dermatol. 2000;42:501-7. Branemark R, Berlin O, Hagberg K, Bergh P, Gunterberg B, Rydevik B. A novel osseointegrated percutaneous prosthetic system for the treatment of patients with transfemoral amputation: a prospective study of 51 patients. Bone Joint J. 2014;96-B:106-13. 7. Branemark R, Branemark PI, Rydevik B, Myers RR. Osseointegration in skeletal reconstruction and rehabilitation: a review. J Rehabil Res Dev. 2001;38:175-81. 8. Hagberg K, Branemark R. One hundred patients treated with osseointegrated transfemoral amputation prostheses--rehabilitation perspective. J Rehabil Res Dev. 2009;46:331-44. 9. Al Muderis M, Bosley B, Tungusova A. Post limb reconstruction strategy for post traumatic amputees (OGAAP-2). Paper presented at: First World Congress on Innovations in Amputation Surgery and Prosthetic Technologies; 2016 May 12-13; Chicago, IL. 10. Gruen TA, McNeice GM, Amstutz HC. â&#x20AC;&#x153;Modes of failureâ&#x20AC;? of cemented stem-type femoral components: a radiographic analysis of loosening. Clin Orthop Relat Res. 1979:17-27. 11. Banaszkiewicz PA, Kader DF, editors. Classic papers in orthopaedics. London (UK): Springer6.

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Verlag; 2014. 12. Johnston RC, Fitzgerald RH Jr, Harris WH, Poss R, Muller ME, Sledge CB. Clinical and radiographic evaluation of total hip replacement. A standard system of terminology for reporting results. J Bone Joint Surg.1990;72:161-8. 13. Amstutz HC, Beaule PE, Dorey FJ, Le Duff MJ, Campbell PA, Gruen TA. Metal-on-metal hybrid surface arthroplasty: two to six-year follow-up study. J Bone Joint Surg. 2004;86-A:28-39. 14. Santori FS, Santori N. Mid-term results of a

custom-made short proximal loading femoral component. J Bone Joint Surg. 2010;92:1231-7. 15. Tetsworth K, Al Muderis, M, Khemka, A, Wilmot, S, Bosley, B, Lord, S, Glatt, V. The Osseointegration Group of Australia Accelerated Protocol (OGAAPâ&#x20AC;?1) for Twoâ&#x20AC;?stage osseointegrated reconstruction of amputees. Paper presented at: First World Congress on Innovations in Amputation Surgery and Prosthetic Technologies; 2016 May 12-13; Chicago, IL.

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TAKING AIM AT CANCER James Higgins and Alex Camarota Office of Innovation Development, United States Patent and Trademark Office, Alexandria, VA, USA

In his final State of the Union Address, President Obama announced the “Cancer Moonshot,” an effort to greatly accelerate the rate of progress in cancer treatment development over the next five years. To support this effort, the USPTO is launching several initiatives that leverage the role patents play in catalyzing life-saving medical treatments. Key words: Patents; Innovation; Immunotherapy; Cancer; Cancer moonshot; USPTO

Fostering American innovation has always been a central mission of the United States Patent and Trademark Office (USPTO), inseparable from our role in protecting it. Although the process for receiving that protection in the form of a patent can be lengthy, the USPTO strives to ensure that it is thorough and fair. Patents must be issued while the technology is still relevant in order to provide a benefit in the marketplace. The patenting process has been especially critical in the medical field, as it protects and monetizes the investment in research and development that is poured into life-saving technologies. Indeed, the patent system has spurred life-changing technological innovation around the world. In that same spirit of progress and improvement, President Obama used his final State of the Union address to challenge the United States to make ten years’ worth of progress toward finding a cure for cancer in just five. Federal and state agencies, nonprofits, businesses, and citizens must collectively contribute

for this goal to be realized. The USPTO has a particular call to action in this “moonshot moment.” The president’s plan leverages the USPTO’s mission as an important catalyst for research and development by freeing trapped data, resolving applications that are without a final decision, and increasing patient access to treatment and clinical studies. The goal is to halve the average examination time of patents pertaining to certain medical technologies and thereby reduce the time it takes for that technology to reach a patient. To meet the president’s expectations, we must also tap into the resources of several different agencies. The USPTO will launch two new programs to accomplish these tasks. First, the USPTO established a “Fast Track” review pilot program for certain treatment-related patents in order for medicines and technologies to reach patients more quickly. This pilot program, “Patents 4 Patients,” more formally known as the “Cancer Immunotherapy Pilot Program,” will cut the time it takes to

_____________________ Accepted July 1, 2016. Address correspondence to: Alex Camarota, Office of Innovation Development, U.S. Patent and Trademark Office, 600 Dulany Street, Alexandria, VA 22314, USA. E-mail: alexander.camarota@uspto.gov

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review patent applications for cancer immunotherapy in half (final decisions achieved in less than twelve months). This “Fast Track” review will be open to new application filings from any applicant, including early-stage bio-tech companies, universities, and large pharmaceutical firms alike. Entities who have products already in Food and Drug Administration (FDA) clinical trials will also be able to opt in to the acceleration program in applications already on file. With approximately 900 cancer immunotherapy applications received by the USPTO annually from around the world, this program aims to move innovative new treatments from conception through patent approval, helping to swiftly reach the patient’s bedside. To be eligible for the “Patents 4 Patients” program, an application must contain one or more claims to a method of treating a cancer using immunotherapy. There are several other requirements, which can be found on the USPTO website. There is no additional fee to participate in the program. Second, the agency aims to stimulate innovation and improve economic competitiveness by unlocking the potential in expansive data sets. The USPTO’s new “IP Horizon-Scanning Tool” will sift through data products contained in the USPTO’s Developer Hub data and will use applied data science to unveil trend lines based on successful and failed immunology and cancer-related product development and treatments. Users will be able to build rich visualizations of intellectual property data as a way to locate meaningful research and development at an earlier stage. Combined with economic, funding, and litigation data, the

tool will enable users to make more informed policy and investment decisions. It has the potential to help inform Securities and Exchange Commission filings, FDA reporting, National Science Foundation grant applications and approvals, and philanthropic and venture capital investments, achieving maximum impact across a spectrum of innovation incubators. Following the release of the IP Horizon Scanning Tool, the USPTO’s Office of the Chief Economist will host public workshops that bring together cancer experts, policymakers, and data scientists to discuss how combinations of data sets can improve cancer research. The goal will be to find the most efficient way to connect various agencies’ data and grasp the insights contained within them. The USPTO’s new programs will provide the same protection to inventors more quickly while also connecting federal agencies and research teams with each other. While it is true that the Cancer Moonshot comes in the twilight of the Obama Administration, the goal is to cultivate a host of programs and efforts that can be seamlessly packaged and passed along to the next administration. The productive competition of businesses and inventors, aided by the resources of government and the research prowess of academia, promises to accelerate our march towards curing a disease that has left virtually no American untouched. For the health of the nation and the world, these collective efforts must come to fruition. They remind us that when the various components of America’s innovation ecosystem work together, no challenge is insurmountable.

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THE NAI FELLOW PROFILE: AN INTERVIEW WITH DR. ROBERT S. LANGER Robert S. Langer1 and Kimberly A. Macuare2 1

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA 2 National Academy of Inventors, Tampa, FL, USA

In a recent interview with T&I, inventor and professor Dr. Robert S. Langer discusses his most recent work and weighs in on the symbiotic relationship between universities and companies in the tech transfer arena, the importance of teaching students to ask good questions as well as to give good answers, and the ongoing motivation that impels him to excellence.

INTRODUCTION In our continuing series of profiles, which honor academic invention and inventors, Technology and Innovation (T&I) is pleased to present Dr. Robert S. Langer—biotechnologist, chemical engineer, and serial entrepreneur—as the subject of this issue’s NAI Fellow Profile. Langer is one of thirteen Institute Professors at MIT, the highest honor awarded to faculty, and the head of Langer Lab at the Massachusetts Institute of Technology (MIT), one of the largest academic biomedical engineering labs in the world. Langer holds a B.S. in chemical engineering from Cornell University and a Sc.D. in chemical engineering from MIT. At a time when chemical engineers rarely did crossover work in medicine, he took a postdoctoral position with Dr. Judah Folkman, a medical researcher who was working on tumor angiogenesis. This allowed Langer to forgo the multiple job offers he received in the petroleum industry, a much more traditional chemical engineering arena, to focus on his passion: helping others. From that beginning sprung a career in biomedical engineering that has spanned five decades and led to important breakthroughs in drug delivery, tissue engineering,

(photo courtesy of Robert Langer)

_____________________ Accepted July 1, 2016. Address correspondence to:

Robert S. Langer, PhD, Langer Lab, 77 Massachusetts Avenue, Room 76-661, Cambridge, MA 02139-4307, USA. Kimberly A. Macuare, PhD, Assistant Editor, Technology and Innovation, Journal of the National Academy of Inventors®, USF Research Park, 3702 Spectrum Boulevard, Suite 165, Tampa, FL 33612, USA. Tel +1 (813) 974-1347; E-mail: tijournal@academyofinventors.org

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and nanotechnology. As the author of over 1350 articles; the inventor on over 1,100 U.S. and foreign patents; and the mastermind behind over 30 companies, Langer’s innovation output calls for an adjective beyond prolific. As if his own work weren’t impressive enough, his accolades are legion. He is the recipient of over 220 prestigious awards, including the National Medal of Science, the National Medal of Technology and Innovation, the Charles Stark Draper Prize, the Millennium Prize, the Kyoto Prize, and the Queen Elizabeth Prize for Engineering. He is also one of the select group who has been elected to the U.S. National Academies of Science, Engineering, and Medicine and elected a fellow of the National Academy of Inventors, the American Association for the Advancement of Science, and the American Academy of Arts and Sciences. Langer’s work is inveterately transdisciplinary, leveraging the fundamentals of materials science to create advanced biotechnological products and applications. A large part of that work has centered on drug delivery systems, where Langer has engineered polymers that allow drugs to be delivered at controlled rates for specific and often prolonged time spans. These advances offer the potential for better treatment of disease, advances in gene therapy, and improved vaccines among other areas. In addition, Langer’s lab has been active in the field of artificial tissue and organs, investigating the use of polymers for improved tissue engineering. Dr. Langer graciously agreed to an interview with T&I, discussing his most recent work and weighing in on various topics, including the symbiotic relationship between universities and companies in the tech transfer arena, the importance of teaching students to ask good questions as well as give good answers, and the ongoing motivation that impels him to excellence. INTERVIEW T&I: In her recent book Grit, Angela Duckworth, a psychology professor at U Penn, suggests that “grit”—a combination of resilience to failure and sustained passion for your core interests—is key to success. To what extent do you think this is true in your case, especially given the early years of your career when your scientific work was not well received? What kind of traits allowed you to persevere during the 28

years between your first publication on angiogenesis and the approval of the first cancer drug based on your work? Langer: I would say that [the idea of grit as a key to success] is true. I think that’s exactly right what she said. And, as to what kind of traits [allowed me to persevere], I guess that would be stubbornness, a strong belief in wanting to do good for the world, and perseverance, things like that. That’s a very good question; people have asked that before, and I don’t really know 100%. But, I think it’s those kinds of things. T&I: Where does that strong core of self-belief come from? Langer: Well, I don’t know if it’s a strong core of self-belief. I mean there are lots of times that I’ve had a lot of doubts. You know, I think most things come from your family. I mean my mom and dad. My mom was the type of person who was very nice and helped people, and my dad got me interested in more intellectual stuff, like he’d play math games with me. They got me these Gilbert chemistry sets and gifts like that. T&I: When you consider that time gap from your and Judah Folkman’s discovery of the first angiogenesis inhibitor (1976) to the first angiogenesis inhibitor being approved by the FDA (2004), 28 years is a long time. Langer: Well, it is, but medicine takes a long time. There have been longer times for people to go from discovery to FDA approval, but that’s a long time, I agree. T&I: You read Outliers, a book analyzing exceptional performers by Malcolm Gladwell. Do you see yourself as an outlier? Langer: Probably I am in different ways. I think that’s probably right. All of these people you are talking to [NAI Fellows] are outliers in different ways. T&I: You have been and remain a leader in invention and translational technology and a champion for companies and the role they play in getting technology to consumers. As someone who was involved in academic start-ups before they were in vogue, what do you see as being the ideal relationship between universities and start-up companies? What roles do

THE NAI PROFILE they play in making sure that research has a real and measurable impact? Langer: I think that what MIT does and Stanford does is close to ideal. In other words, I think that research goes on in the universities, but when research gets past a certain point, when it gets to be more development, when a lot of the things involve manufacturing issues, clinical trial issues in our case, I think then it does make sense to have a company, and I think it’s also been a great career for the people in the lab who have spent a lot of their graduate student or postdoctoral lives working on these things. So, it’s kind of like a hand-off. And yet, I don’t think the things that the company does are what you’d want to see done in the university or vice versa. I think that what happens in Kendall Square and what happens in Silicon Valley is terrific. T&I: How is that hand-off connected to the mission of each type of entity? That is, why isn’t the university the ideal place to develop businesses? Langer: Well, I think that the university can do it, but the problem is that it is not really something that the university is skilled at, and it’s not really something the professors are skilled at either, or the students. I mean, we can help, but I think it’s a business kind of thing—it’s really production, development, clinical trials, so I think that it is not a classical skill of the university. Could it be some day? I suppose it could be. I mean, I think that would be a big change, but that’s not impossible. But I think people would be also concerned about conflicts of interest and things like that if that were to happen. I think people already are concerned about some conflicts of interest. My feeling is that what we and Stanford are doing gives you the best of both worlds. It gives you the opportunity to do research and yet not just the opportunity to do research but the opportunity to see that research benefit mankind and even benefit the economy too. So I think that’s good. T&I: Moving beyond your research, you have a clear dedication to service. From your early work writing a math and science curriculum for inner city students to your current projects with the Bill & Melinda Gates Foundation to your daily meetings, phone calls, and emails to offer advice and help to students, colleagues, and business associates, you are a man on a mission

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to help others. What motivates that? Did you have any early experiences or role models that ignited your passion for service? Langer: I don’t know if I’m on a mission, but I’ve always gotten a lot of satisfaction out of teaching, out of helping people get educated. It’s just who I am. Why I am that way? I don’t know. I think again those things probably come down to your parents. You asked about people, and I’d say a couple of people made a big impact on me. My mom and dad were probably the biggest influences, but there was also Judah Folkman, who was my postdoctoral mentor. He was a terrific scientist, he was a surgeon, and he definitely wanted to do a lot of good for the world and did do a lot of good. Also, he was the kind of person who had all kinds of far-reaching ideas and was criticized for them. And yet, he persevered, and he certainly was a great role model in a lot of ways. And the other person I would say is George Scheele. I was his teaching assistant at Cornell when I was a senior, and I loved that. That was a great experience for me to teach young students. In that case, it was heat and mass transfer. I really enjoyed the experience, and I think that got me excited about teaching. So, those would be some of the people who made an impact on me.

(photo courtesy of Robert Langer)

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T&I: You are a dedicated teacher and mentor as well as researcher. Do you still love teaching? Langer: I do. I still love giving lectures. I don’t teach a formal class right now. I have at different points in time. When you are an Institute Professor, which is the title I have at MIT, you can pretty much do what you feel like, but I do like teaching. I enjoy it very much. And I like teaching in different ways, and this gets to part of the next question. I like teaching classes, but I also like being a part of my students’ and postdocs’ lives and teaching them research and seeing them do well in the lab and later on. I like all of that. T&I: One intriguing comment you made about your teaching was that instead of teaching students to give good answers, you want to teach them to ask good questions. How would you describe the pedagogical process by which you achieve this? Langer: I think it’s individualized, and it’s not something that you can really do in a class very well. But it is something that you can do for postdoctoral fellows and for graduate students. It’s trying to be a bit of a guide but not too much of a guide. In other words, if somebody is doing a research project, you want to try to get them to think. You want to give them a bit of guidance but not tell them what to do. Let me use an airplane view analogy: Maybe I would give students a 50,000- to 100,000-foot view of what I want them to do to get started, but, ultimately, they are going to figure out the 30,000-foot view, the 10,000-foot view. They are going to ultimately figure it all out. But I try to help them if they run into problems. I don’t think it is that structured, but it’s really with the intent that you want to see what they’re interested in, you put them on the course to do something that you and they feel is important, but how they get there is going to be mostly up to them. And, of course, you help them if they get lost a bit. T&I: Do you model that process for them? Langer: No, not really. I don’t think I model it. I think that it’s very individualized. Everybody is different, and some people want more guidance than others, and so I adjust what I do for each student. I never want to give too much, or too little, guidance. You want people to stretch a little bit, but you don’t want them to have to stretch too much.

T&I: How would you assess your success as a teacher? Langer: I think it’s pretty good. I don’t know if it’s just me; I’ve been very lucky to have had really good people in my lab. There’s different metrics you could use. One metric you could use is to ask how many are in the National Academy of Inventors. I think there are 21. I know there are 14 who are in the National Academy of Engineering, 9 in the National Academy of Medicine, 36 in the Technology Review, and there are nearly 300 or so who are professors. A whole bunch who have started companies. I don’t want to brag. If I look back at what I’ve done, I’m very proud of the research, but the thing I’m always proudest of is how well my students have done. This year, we will have people become professors at places like Stanford, Harvard, and MIT, and that’s great. I’m delighted about that. T&I: I’ve read that your work has impacted two billion lives. What does that mean to you? Langer: I guess that was my dream. Not two billion but the fact that our research could do good for the world. When I was a young person, I didn’t have a very clear idea of what I wanted to do, but I definitely wanted to help people, and I’m thrilled that what I’ve done as a scientist and an educator has hopefully helped people. That was my dream, so I feel very happy about that. T&I: How does it relate to your perception of your own success? It seems like a lot of your perception of your success is connected to your ability to help people. Langer: Helping people is what I wanted to do, so success ultimately relates back to that. Not that I had a very clear sense of goals, but if you set some goals and you are able to get there, then you feel like you’ve done ok. It’s nice to see that a lot of the therapies have gotten out to the world. That’s one of the things I wanted to see happen. I think the companies have helped that, and I think the students have done that. It’s a team effort. T&I: How do you sustain such a high level of engagement and commitment? Langer: It’s the students and the postdocs and the things that we’re doing. I think the projects we’re

THE NAI PROFILE working on will do even more good, so I want them —both in terms of the research itself and the training—to be successful. And I have just a fantastic group of people in the lab, and I just love that, so I think it kind of [sustains itself] automatically. It’s the people and the mission of being an educator and trying to do research that I really enjoy and that can do more good. T&I: Thinking about the people and the research, tell us about some of the current projects your lab is working on. Langer: One of the things we are doing a lot with is the Gates Foundation. This is great because they want to help developing countries, and I do too. One big area we’re involved in is drug delivery systems, so I’ll give you a few examples of some of the new things we’re doing there. One is the idea that you could make a pill that can last anywhere from—not just a day, which is the longest they last now— a week to a month to a year. The reason for that is that patient compliance in developing countries is very poor. They’ve done calculations at the Gates Foundation that if someone could keep a blood level of a certain drug—say over six nanograms per ml for two weeks—it could treat malaria, but people don’t keep taking their drugs. So we are working on a pill that could literally last any length of time, and it’s looking quite promising. Similarly with vaccines, people don’t come back for second or third injections. Some years ago, there were statistics from the World Health Organization indicating that around half a million babies die of tetanus every year because their mothers don’t come back for a second tetanus shot. So we’re creating a vaccine that allows you to give a single injection of any vaccine that is actually many injections in one. Basically, we have little microspheres that release their compounds not only at time zero but also at one month, six months, and one year. We are also working on nanotechnology, ways of delivering new drugs like siRNA (these are gene therapy agents), CRISPR, and messenger RNA. One of the big challenges of many of these genetic therapies is getting it to the right cells, so we have been doing a lot of work on nanoparticles that are specially designed to do that. The other big area is tissue engineering. We’ve done a lot on trying to come up with new strategies

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using materials and cells to create new tissues and organs, and that’s already led to artificial skin for burn victims. We’re in clinical trials helping people who are paralyzed with spinal cord repair. Some of the newer things we’re doing are new treatments for diabetes. We published a couple of papers in Nature Journals earlier this year on new methods and new materials for encapsulating islet cells that could create an artificial pancreas that you could put in the body and hopefully someday even be a cure for diabetes. There are a lot of different things along those lines, like more basic work on understanding how materials could affect drug behavior and different disease treatments. Those are a few things that we’re doing. There are a lot of areas where we could potentially do a lot of good. The Gates Foundation has been great to work with. They have been big supporters of a number of different things that we’ve done. We’re also doing stuff with NIH and with different foundations. Some of the work with the nanoparticles is aimed at cancer, so we’re working on a lot of different things that I hope will help people in the long run. T&I: This last question is a little off the wall, but let’s talk about your work with Living Proof, the hair care company. Given your work in the medical field, it might seem like a departure in some way from your other ventures. However, it’s often the fact that two things which seem to be contrary are actually fundamentally similar. How is your work with Living Proof connected to your other work? Langer: This is really a two-part question. The first part is: why do we do it? The reason I did it is because the investors, some of whom are my former students, had been nice enough to invest in the companies that have spun out of our lab. One day, they said they wanted to do a hair company and asked if I would help them, and they have been so good to me in terms of putting money into the companies that we’ve done in medicine that I felt it was the least that I could do to help them. Then, secondly, when I looked into it, it was exactly what you just said. Basically, some of the major products really came from looking at fundamentals of materials. In the case of the anti-frizz product, what happened is the same thing I saw in medicine.

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People were taking off-the-shelf materials and applying them to every single hair care product and with very little scientific fundamentals. Every single product for anti-frizz has silicone as the main ingredient, and that doesn’t work that well. It doesn’t keep moisture out that well, and that’s the issue with frizz. We just took a more fundamental look and asked what would you really want from a material to keep moisture out, and we examined the fundamentals and came up with one specific material, and that’s how we solved that problem. Another example that relates to what you said is a product to give hair more body. Dan Anderson, one of my former postdocs who is a professor now at MIT, and I designed this library of polymers for gene therapy agents. There are literally thousands and thousands of polymers in that library, and we have composition of matter patents on them so that you could fish one out for gene therapy, but you could also fish others out for other things. We picked one out that gave hair a lot more body, and so this built off some of the other things we were already doing and had already done in the lab. CONCLUSION As if to reaffirm his prodigious productive capacities, in the brief interval between the interview and the write-up, Langer has been named as a finalist for another major prize, the 2016 European Inventor Award (he subsequently received that award); has published a paper in Nature Materials on a “second skin” technology that was picked up by every major news outlet in the country; and has taken yet another company, Selecta Biosciences, public. Taken in the context of his CV, which in the complete version occupies some 70-odd pages, one understands that this is par for the course for Langer. His level of output is all the more incredible when you consider that Langer is well-known for devoting a large number of his waking hours to advising others— from undergraduates to fellow researchers to biotech entrepreneurs—both in person and by phone. It is not just an apocryphal tale that Langer will respond to requests at lightning speed; it’s factual, with rarely more than a few minutes elapsing between his receipt of a message and his response.

When reviewing Langer’s career and hearing the sincerity of his sentiments when discussing his work, you realize that his productiveness and intellectual generosity are quite simply products of who he is: a genuinely nice person with a passion for service. His dream was always to help people, and he lives that dream every day. FURTHER READING 1. Langer R, Brem H, Falterman K, Klein M, Folkman J. Isolation of a cartilage factor that inhibits tumor neovascularization. Science. 1976;193:70-72. 2. Langer R. Controlled release: a new approach to drug delivery, Tech Rev. 1981;83:26-34. 3. Langer R. New methods of drug delivery. Science. 1990;249:1527-1533. 4. Langer R, Vacanti J. Tissue engineering. Science. 1993;260:920-926. 5. Gref R, Minamitake Y, Peracchia M, Trubetskoy V, Torchillin V, Langer R. Biodegradable long-circulating polymeric nanospheres. Science. 1994;263:1600-1603. 6. Langer R, Vacanti J. Artificial organs. Sci Am. 1995;273:100-103. 7. Langer R. Drug delivery and targeting. Nature. 1998;392(Supp):5-10. 8. Langer R, Tirrell D. Designing materials for biology and medicine. Nature. 2004;428:487-492. 9. Khademhosseini A, Vacanti J, Borenstein J, Langer R. Microscale technologies for tissue engineering and biology. PNAS. 2006;103:24802487. 10. Peer D, Karp J, Hong S, Farokhzad O, Margalit R, Langer R. Nanocarriers: emerging platforms for cancer therapy. , Nat Nanotechnol. 2007;2:751760. 11. Langer R. Biomaterials and biotechnology: from the discovery of the first angiogenesis inhibitors to the development of controlled drug delivery systems and the foundation of tissue engineering, J Biomed Mater Res. 2013;101A:2449-2455. 12. Langer R, Fuller J, Levin M. Entrepreneurship in Biomaterials. In: Ratner D, Hoffman S, Schoen F, editors. Biomaterials science. 3rd ed. Oxford

THE NAI PROFILE (UK): Academic Press; 2013. pp. 1459-1472. 13. Dang T, Thai A, Cohen J, Slosberg J, Siniakowicz D, Doloff J, Ma M, Hollister-Lock J, Tang K, Gu Z, Cheng H, Weir G, Langer R, Anderson D. Enhanced function of immune-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug, Biomaterials. 2013;34:5792-5801. 14. Dahlman J, Kauffman K, Langer R, Anderson D. Nanotechnology for in vivo targeted siRNA delivery. Adv Genet. 2014;88:37-69. 15. Yu B, Kang S, Akthakul A, Ramadurai N, Pilkenton M, Sakamoto F, Gilchrest B, Anderson R, Langer R. An elastic second skin. Nat Mater. 2016 [accessed 15 Jul 2016]. http://www. nature.com/nmat/journal/vaop/ncurrent/full/ nmat4635.html.

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Aims and Scope The journal Technology and Innovation, Journal of the National Academy of Inventors (T&I) is a forum for presentation of information encompassing essentially the entire field of applied sciences, with a focus on transformative technology and academic innovation. Owing to the broad nature of the applied sciences, authors should be guided by the interest of the readers who are likely to be knowledgeable non-specialist scholars. Contributions containing the following information will be considered for publication: • Description of advances in transformative technology and translational science • Critical assessments of a segment of science, engi neering, medicine, or other technologies • Economics of a technology, governmental and policy action, and innovation as related to intellectual prop erty • Environmental (including human health) impact of various technologies • Articles on historical, societal, ethical, and related aspects of science,engineering, medicine, or technol ogy, provided they are written for the scientific com munity and in a style compatible with a scientific journal • Articles should have a discussion on the process of innovation and invention Because T&I serves a multidisciplinary audience, authors are urged to avoid writing for specialists. In particular, they are discouraged from using expressions that are understandable only to a select audience of specialists. For example, mathematical expressions should be explained in words to assure their appreciation by nonmathematicians. All contributions will be subjected to peer review and will be evaluated on the basis of their general usefulness for the readers, including scientific quality, originality, and compliance with the style and format of the journal. The following categories of contributions will be considered for publication: Articles: Most articles will be review format with no minimum or maximum length. The journal subscribes to the concept that the length of an article is determined by its content. However, a preference will be given for articles that are between 7 and 15 published pages. Commentaries and Discussions: (Letters to the editor, editorials, and similar contributions also fall into this category.) These are subjected to peer review and are required to follow T&I format and style and must be consistent with the requirements of a scholarly journal. The discussion of contested areas of science where a consensus is lacking is included in this category. Commentaries are shorter than regular manuscripts and must contain information that is likely to invoke scientific discussion with the objective of

promoting the development of a consensus. Patent Reviews: New patents of interest to the readers of T&I are included in this category. Book Reviews on Innovation and Technology: Solicited or unsolicited short reviews of relevant books and issued patents are considered for publication in this category.

Preparation of Manuscripts Submissions to Technology and Innovation must be in English, in an editable Microsoft Word-compatible electronic file, typed, 12-point font, double-spaced, formatted for 22 × 28 cm (8.5 × 11 in) with a margin of 2.5-3 cm (1 in) at the top, sides, and bottom of each page. Tables should be placed on separate page(s) sequentially at the end of the manuscript (after the ‘Reference’ section). Figures should be submitted separately from text. Title page: Each paper should include a title page with the title of the paper, submission type, name(s) of author(s), and complete affiliation(s). Provide a short title to be used as running head. Indicate the author to whom correspondence and proofs should be addressed (i.e. ‘corresponding author’), and provide a complete physical mailing address, phone, fax, and email address. Title: The title should be as short as possible but fully descriptive. Submission Type: The author should indicate the type of submission that best describes their manuscript (Article, Commentary, Editorial, or Patent Review). Abstract and key words: The abstract should contain a summary of the article, including its results in 250 words or less. Because many abstracting services use the abstract without reference to the content, the authors are urged to succinctly provide the essence of the paper in the (up to) 250 words allocated. Additionally, provide 3 to 6 key words after the abstract. Tables and figures: Tables and figures should be understandable without excessive reference to the text; particularly, units and quantities should be clearly identified. In general, material should be presented in tables or figures but not in both. Avoid very wide or long figures and tables that would not fit on a printed page. By default, tables and figures will appear in B&W. If color figures are necessary or desired, there is a charge for their reproduction. Figures should be submitted at the highest resolution possible, preferably 300dpi at 7 inches (width or height). Low-resolution files that appear pixilated when printed will NOT be accepted for publication. Tables: Present each table on a separate page at the end of the manuscript (i.e., not within the body of the text). Provide a short title for each table. Cite all tables sequentially

ii in the text and provide publishing staff with a cue for where they should approximately appear in the manuscript (e.g., ‘INSERT TABLE 1’) when published. Tables should be in an editable format.

time and carefully check all editorial changes within 48 hours of receipt. Corrections at this stage should be limited to printer’s errors and minor changes. No major changes or rewrites are allowed.

Figures: Figures should be submitted separately from the text. Cite all figures sequentially in the text and provide publishing staff with a cue for where they should approximately appear in the manuscript (e.g., ‘INSERT FIGURE 1’) when published. All figures must be high-quality art work in electronic format. Lettering should be large enough to be readable when reduced to fit page or column size. Avoid light lettering and gray shading. SPECIAL NOTE: Figures in accepted submissions are printed for free in black & white. If you wish to have your figures reproduced in color, there is an additional fee for this service. All legends for figures should be included on a separate page at the end of the manuscript.

Open Access: To help authors reach maximum exposure for manuscripts published in Technology and Innovation, T&I utilizes Open Access publishing. Fees are billed when a manuscript is accepted for publication.

Equations: All equations should be typewritten. Mathematical notations should be simple and suitable for a multidisciplinary audience. For example, fractions within fractions and subscripts within subscripts should be avoided. Where possible, incorporate equations into the text rather than as a separate figure. Units, quantities, and abbreviations: Use SI (metric) units and international quantities and abbreviations. Equivalent values in other systems may be used, provided their metric equivalents are included in every case. Note that percent, ppm, and ppb are not metric units. Footnotes: Avoid text footnotes. Footnote material should be incorporated into the text for the benefit of the readers, editors, and printers. Financial Disclosure: The authors should indicate any financial or other relationships connected with the information in the article. Acknowledgment: If an acknowledgment is included, it should not contain lengthy descriptions of the reason for the acknowledgement. References: For references, please follow CSE citation-sequence style. Information about CSE citation format can be found at http://www.scientificstyleandformat.org/Tools/ SSF-Citation-Quick-Guide.html. If you have additional questions about references or other formatting issues, please contact T&I at tijournal@academyofinventors.org. The designated corresponding author will receive a proof of their article in PDF format via email before publication. The corresponding author should answer all queries at this

Open Access Fee Rates Standard Single Submission: ...................................$1,000 NAI Fellow Contributed Single Submission: ...........$800 If you are interested in publishing with T&I but believe you will be unable to meet the Open Access fees, please contact T&I at tijournal@academyofinventors.org or (813) 974-1347. Copyright: If data from any source other than the authors is used in tables or figures, it is the responsibility of the authors to obtain permission to reproduce such material. Editorial staff may ask authors to provide proof that permission has been granted from the original publisher and indicate the source when signing our copyright forms. For any questions relating to the formatting or submitting of manuscripts, please contact T&I at tijournal@ academyofinventors.org or (813) 974-1347.

Ethics Statement The publishers and editorial board of Technology and Innovation have adopted the publication ethics and malpractice statements of the Committee on Publication Ethics (COPE) (http://publicationethics.org/resources/guidelines). These guidelines highlight what is expected of authors and what they can expect from the reviewers and editorial board in return. They also provide details of how problems will be handled. Briefly: Author Responsibilities: Authors listed on a manuscript must have made a significant contribution to the study and/ or writing of the manuscript. During revisions, authors cannot be removed without their permission and that of the other authors. All authors must also agree to the addition of new authors. It is the responsibility of the corresponding author to ensure that this occurs. Financial support and conflicts of interest for all authors must be declared. Further information on this can be obtained from the International Committee for Medical Journal Editors (http://www.icmje.org/).

iii The reported research must be novel and authentic and the authors should confirm that the same data has not been and is not going to be submitted to another journal (unless already rejected). Statements made in the introduction and discussion should be supported by appropriate references, and sufficient experimental detail should be provided to allow for repetition of the study by another group. Plagiarism of the text/data will not be tolerated and could result in retraction of an accepted article. Any text or figures reproduced for another source require the permission of the original copyright holders (normally the publishers). Any manipulation of figures should be equally applied and described in the text (including pseudocoloring) and must not change the meaning of the figure. When humans, animals, or tissue derived from them have been used, then mention of the appropriate ethical approval must be included in the manuscript. Reviewer responsibilities: Reviewers are expected to not possess any conflicts of interest with the authors and research. They should review the science objectively and provide recommendations for improvements where necessary. When aware of relevant published work not being cited, the reviewers should recommend inclusion of these references. If the reviewer feels that they would be unable to repeat the study as described, then additional methodological details should be requested. Any unpublished information read by a reviewer should be treated as confidential. Editorial responsibilities: The editors will select an appropriate number of reviewers for the manuscript so that they can make an informed decision about whether to reject/ accept a manuscript. Their decision must be based only on the paperâ&#x20AC;&#x2122;s importance, originality, clarity, and suitability for the journal. They must not have a conflict of interest with the authors or work described. The anonymity of the reviewers must be maintained. Should problems come to light after acceptance, then the editors agree to promote the publication of corrections and/or retractions as deemed necessary. Publishing responsibilities: The publisher agrees to ensure that, to the best of their abilities, the information that they publish is genuine and ethically sound. If publishing ethics issues come to light, not limited to accusations of fraudulent data or plagiarism, during or after the publication process, they will be investigated by the editorial board, including contact with the authorâ&#x20AC;&#x2122;s institution if necessary

so that a decision on the appropriate corrections, clarifications, or retractions can be made. The publisher agrees to publish this as necessary so as to maintain the integrity of the academic record. Protection for Research Participants These policies are in accordance with the recommendations of The International Committee of Medical Journal Editors (ICMJE) n

Humans

1. If experiments or research reported in the article in volve human subjects, the authors must indicate if their procedures were approved by an Institutional Review Board, ethics committee, or similar reg ulatory oversight committee. If a review board or committee is not available, the authors should indicate that their procedures are in accor dance with the Helsinki Declaration as revised in 2013. 3. Manuscripts must be accompanied by a statement that the informed consent of research participants was obtained prior to participation or that documen tation of informed consent was waived by the Insti tutional Review Board, ethics committee, or similar regulatory oversight committee. If images or other identifying information is included in the manuscript, explicit written informed consent of the individual/patient must be obtained and included with your submission. Measures to protect the confidentiality of the individual(s) should also be employed. If consent cannot be obtained, you are encouraged to contact the editor for further guidance. n

Animals

If experiments or research reported in the article involve animals, the authors must indicate if their procedures were performed in accordance with the U.S. Public Health Serviceâ&#x20AC;&#x2122;s (PHS) Policy on Human Care and Use of Laboratory Animals and the Guide for the Care and Use of Laboratory Animals and were approved by appropriate institutional review committee(s). Editors reserve the right to reject manuscripts if there is doubt that appropriate ethical standards have not been met in research involving human and animal subjects or if there is reason to suspect research misconduct.

MICHAEL BASS, University of Central Florida ISSA BATARSEH, University of Central Florida RAYMOND J. BERGERON, University of Florida SHEKHAR BHANSALI, Florida International University ROBERT H. BYRNE, University of South Florida SELIM A. CHACOUR, University of South Florida WILLIAM J. CLANCEY, Institute for Human & Machine Cognition ROY CURTISS III, University of Florida WILLIAM S. DALTON, H. Lee Moffitt Cancer & Research Institute PETER J. DELFYETT, University of Central Florida DONN M. DENNIS, University of Florida DAVID M. EDDY, University of South Florida GREGG B. FIELDS, Florida Atlantic University KENNETH M. FORD, Institute for Human & Machine Cognition MICHAEL W. FOUNTAIN, University of South Florida RICHARD D. GITLIN, University of South Florida LEONID B. GLEBOV, University of Central Florida D. YOGI GOSWAMI, University of South Florida CLIFFORD M. GROSS, University of South Florida BARBARA C. HANSEN, University of South Florida RICHARD A. HOUGHTEN, Torrey Pines Institute for Molecular Studies LONNIE O. INGRAM, University of Florida S. SITHARAMA IYENGAR, Florida International University RICHARD JOVE, Nova Southeastern University SAKHRAT KHIZROEV, Florida Internatitonal University DAVID C. LARBALESTIER, Florida State University C. DOUGLAS LETSON, H. Lee Moffitt Cancer & Research Institute GUIFANG LI, University of Central Florida STEPHEN B. LIGGETT, University of South Florida ALAN F. LIST, H. Lee Moffitt Cancer & Research Institute DEAN F. MARTIN, University of South Florida THOMAS O. MENSAH, Florida State University SHYAM MOHAPATRA, University of South Florida BRIJ M. MOUDGIL, University of Florida

INNOVATION CAN BE DIFFICULT TO CREATE and more difficult to sustain. For the past 6 years, the National Academy of Inventors has sustained and grown as an organization that recognizes and encourages invention.

DAVID P. NORTON, University of Florida VICTOR L. POIRIER, University of South Florida ANN PROGULSKE-FOX, University of Florida ALAIN T. RAPPAPORT, Institute for Human & Machine Cognition PAUL R. SANBERG, University of South Florida W. GREGORY SAWYER, University of Florida ANDREW V. SCHALLY, University of Miami SUDIPTA SEAL, University of Central Florida

CONGRATULATIONS TO THE NAI FOR 6 YEARS OF GROWTH and to these Florida inventors honored to be called NAI Fellows.

SAID M. SEBTI, H. Lee Moffitt Cancer & Research Institute MARWAN A. SIMAAN, University of Central Florida FRANKY SO, University of Florida M. J. SOILEAU, University of Central Florida NAN-YAO SU, University of Florida HERBERT WEISSBACH, Florida Atlantic University

proud to partner with the

SHIN-TSON WU, University of Central Florida JAMES J. WYNNE, University of South Florida JANET K. YAMAMOTO, University of Florida JIANPING (JIM) P. ZHENG, Florida State University