{'fraction_non_alphanumeric': 0.026743398781313474, 'fraction_numerical': 0.008598510494245091, 'mean_word_length': 5.521412803532009, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Patient-reported Outcome Instruments in Lower Extremity Trauma: A Systematic Review of the Literature

Background: Advances in fracture fixation and soft tissue coverage continue to improve the care of patients after limb-threatening lower extremity (LE) trauma. However, debate continues regarding which treatment option—reconstruction or amputation—is most appropriate. Many authors have attempted to quantify the patient experience in this treatment paradigm; however, they have not used patient-reported outcome (PRO) instruments specific to this population. Our aim was to identify and evaluate PRO instruments developed specifically for LE trauma, applicable to reconstruction and amputation, using established PRO instrument development and validation guidelines. Methods: A multidisciplinary team used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method to query PubMed, Medline Ovid, EMBASE, Cochrane, Medline Web of Science, and Psych Info databases from inception to November 2016. Publications were included that described the development and/or validation of a PRO instrument assessing satisfaction and/or quality of life in LE trauma, applicable to both amputation and reconstruction. Two authors independently reviewed each full-text citation. Results: After removing duplicates, 6,290 abstracts were identified via the database query. Following a preliminary title and abstract screen, 657 full-text citations were reviewed. Of these references, none satisfied the previously established inclusion criteria. Conclusions: No studies were identified that described a PRO instrument developed to assess outcomes in LE trauma patients applicable to both reconstruction and amputation. There is thus a need for a PRO instrument designed specifically for patients who have sustained limb-threatening LE trauma to guide treatment decisions.


INTRODUCTION
Severe lower extremity (LE) traumatic injuries are life-changing events. Treatment options include early amputation, limb reconstruction, or delayed amputation after reconstructive attempts; however, there is a no consensus regarding the best treatment modality. [1][2][3][4][5][6][7] Successful reconstruction may involve numerous operations with a high rate of complications and long-term disability. 3,8 However, amputation has its own limitations, including life-long reliance on a prosthesis for ambulation. In the setting of modern reconstructive microsurgery and orthopedic trauma care, the optimal treatment has not yet been established.
The impact of severe LE trauma is multidimensional. Traditional metrics including infection rates, postoperative complications, and pure functional assessments only capture a small portion of the experience borne by this patient population, neglecting outcomes such as return to work status, social integration, and substance abuse. A thorough assessment of the utility of amputation versus reconstruction must therefore be more comprehensive than the approach we have applied in the past to other surgical conditions, and therefore requires the development and application of a meaningful, appropriate patient-reported outcome (PRO) instrument.
PRO instruments are broadly categorized into 2 groups: generic and disease specific. Generic instruments evaluate concepts of interest (COI) across a broad range of patient populations, allowing for a general comparison of health and well-being. Disease-specific PRO instruments capture COI relevant to the disease process and allow an assessment of change within these COI domains. 11 Both types of PRO instruments are in contrast to ad hoc measures, which are a nonvalidated compilation of questions felt to be important by the research team and/or clinician.
Current PRO research in LE trauma has relied heavily upon generic measures, such as the SF-36 and Sickness Impact Profile. Disease-specific PRO instruments designed for populations other than LE trauma patients, such as the Prosthesis Evaluation Questionnaire (designed for amputees) and the Musculoskeletal (MSK) Tumor Society Scoring System (designed for MSK oncology) have also been used, along with ad hoc instruments. [12][13][14][15] Although these instruments may offer some insight into LE trauma patient experiences, none have been rigorously developed for, or validated in, the LE trauma population. Therefore, these instruments lack the content validity required to fully capture all COI relevant to these patients.
Given the stakes of LE trauma decision-making-the significant length of time, use of resources, and potential morbidity associated with salvage, and the permanence of amputation-a disease-specific, valid, reliable instrument allowing comparison between these treatment conditions is essential. To identify and evaluate available options, we conducted a systematic review of the literature. Our primary aim was to identify PRO instruments developed specifically for LE trauma patients, applicable to both reconstruction and amputation patient cohorts. Our secondary aim was to evaluate any identified instruments based on established guidelines for PRO instrument development and validation. 16

Search Strategy
A comprehensive search was designed with the assistance of a medical librarian using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify PRO instruments assessing quality of life and/or satisfaction for patients with LE traumatic injuries, applicable to both patients undergoing reconstruction and/or amputation. 17 The search was conducted in PubMed, Medline Ovid, EMBASE, Cochrane, Medline Web of Science, and Psych Info, from inception to November 2016. Search terms were developed for LE trauma and outcome instruments, as listed in Table 1. The search terms were searched as text words and mapped to medical subject headings when applicable. Terms within each search category were combined with the Boolean operator OR, and the 3 categories were combined with AND.

Selection Criteria
Publications were included if they were published in English and if they described the development and/or validation of a PRO instrument designed to measure satisfaction and/or quality of life in LE trauma patients, applicable to both amputation and reconstruction cohorts. Conference abstracts, theses, letters to the editor, editorials, and review articles were excluded. Secondary searching, including a citation review of applicable publications, was performed to identify additional instruments. Corresponding authors were contacted to obtain additional information if necessary.

Data Extraction
One author (L.R.M.) reviewed all titles and abstracts. All potentially applicable publications were reviewed as full-text by 2 authors (A.J.G. and L.R.M.). Any disagreements between A.J.G. and L.R.M. were resolved by consensus with the senior author (M.J.G.). All publications utilizing a PRO instrument that was not applicable to both amputation and reconstruction patients were excluded. Excluded citations were sorted into the following categories: ad hoc instruments, non-MSK PRO instruments, MSK PRO instruments not developed for LE trauma, MSK PRO instruments assessing functional outcomes only, PRO instruments specific to amputation patients only, LE PRO instruments specific to reconstruction only, and trauma PRO instruments not specific to the LE. Utilization frequencies of each PRO instrument in each category were also recorded.

RESULTS
The results of the electronic search are shown in Figure 1. There were 9,113 publications identified in the search, with 6,290 publications after removal of duplications. After the initial title and abstract screen, there were 657 articles remaining, all of which were reviewed in full text and assessed for eligibility. There were no articles meeting inclusion criteria; none described a PRO instrument assessing outcomes in LE trauma patients that were applicable to both reconstruction patients and amputation patients. There were no additional articles added via secondary searching. Table 2 reports the most frequently utilized PRO instruments that are used to assess outcomes in LE trauma patients. The majority of studies utilized multiple PRO measures, with a combination of ad hoc measures, generic PRO instruments, and disease-specific PRO instruments. These instruments were most commonly designed for nontrauma MSK injuries and/or disease processes. Table 3 lists the proposed domains for a novel PRO instrument for LE trauma patients, based on the topics covered in the instruments listed here and expert opinion.

DISCUSSION
The decision to pursue reconstruction or amputation in the setting of limb-threatening LE trauma represents a significant challenge to both surgeons and patients. These injuries are often the result of high-energy mechanisms and patients present with extensive soft tissue loss, periosteal stripping, concomitant damage to neurovascular structures, and varying degrees of contamination. 18 Early initiation of broad-spectrum antibiotic therapy, wound debridement, rigid fracture stabilization, and soft tissue coverage has revolutionized the treatment of these injuries and led to increased rates of limb salvage. 2,19,20 However, debate continues concerning who should undergo reconstruction versus amputation. Although each treatment group faces unique challenges, both groups have worse clinical and functional outcomes compared with the general population due to persistent wounds, multiple procedures, depression, pain, posttraumatic stress disorder, and, in the setting of amputees, difficulties with prostheses. [21][22][23][24][25] The LE Assessment Project (LEAP) is the most comprehensive civilian study to date. This study attempted to determine whether amputated or salvaged patients had superior clinical, functional, and health-related quality of life outcomes using the Sickness Impact Profile. 22,23,26 This prospective observational trial of 601 patients enrolled from 1994 to 1997 found no difference in clinical and  from the musculoskeletal function assessment (32) 3 *Included only in the WHOQOL-100, not the WHOQOL-BREF. †A version of a scale within the Prosthetic Profile of the Amputee that is used independently. ‡Domains listed for PRO portion, also a clinician portion. functional outcomes or with health-related quality of life, patient satisfaction with treatment, or rates of returning to work. Worse outcomes, based on the Sickness Impact Profile, were alternatively correlated with patient and environmental factors independent of treatment pathway, including lower socioeconomic status, non-white race, tobacco use, using the legal system for injury compensation, and low levels of self-efficacy. The Military Extremity Trauma Amputation/Limb Salvage (METALS) study attempted to answer the same question in a military population. 24 A retrospective cohort study from 2003 to 2007 was performed on 324 service members who served in either Afghanistan or Iraq and who had suffered limb-threatening trauma to the LE. In addition to outcome measures for depression, posttraumatic stress disorder, chronic pain, and daily activities, general MSK PROs were evaluated with the Short Musculoskeletal Function Assessment (SMFA). 27 In contrast to the LEAP study, amputees had higher SMFA scores and engagement in vigorous sports in comparison to reconstruction patients. Amputation patients also had lower rates of posttraumatic stress disorder, although both groups had equivalent rates of employment and depression. These findings reflected the higher levels of intensive postinjury rehabilitation services and access to prostheses and support devices provided to the military amputees, in comparison with both civilian amputees and military reconstruction patients.
The LEAP and METALS studies have improved our understanding of treatment outcomes in high-energy LE trauma patients, but a major limitation to the above studies is the use of the Sickness Impact Profile, a generic PRO instrument, and the SMFA, a general MSK PRO instrument. These measures are appropriate tools to compare outcomes between LE trauma patients and either the general population or patients with various MSK diseases besides LE trauma. However, they do not have the sensitivity to evaluate LE trauma-specific COI that is critical to make comprehensive inferences about LE trauma treatment outcomes. Qualitative interviews of LE trauma patients have identified numerous COI that are of importance to this population, which are not captured in the above measures. Physical function and symptoms, appearance, psychosocial and sexual well-being, social support, impact on family, perceptions of recovery, coping, self-efficacy, medical decision-making, the impact on work and education, and impact on finances have all been identified as COI in qualitative research of LE trauma patients. [28][29][30] Although many of these COI may be addressed in various other PRO instruments or ad hoc measures, no instru-ment was found that comprehensively evaluates all COI relevant to LE trauma patients to allow for reproducible, rigorous comparisons between treatment outcomes. The most frequently observed paradigm was the use of a non-MSK-specific PRO instrument on patients with LE trauma (n = 266). It was also observed that authors often utilized an ad hoc instrument either alone (n = 61), or in addition to another PRO instrument (n = 44), in an attempt to describe the outcomes of their cohort. The frequency with which ad hoc instruments were employed further reinforces that there is a need for a metric capable of capturing and reporting severe LE trauma-relevant domains that are not adequately reflected in any of the currently available instruments.
With regards to study limitations, the results of this systematic review are dictated by the reliance upon the reviewed studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to design our search query to reduce our risk of inadvertently omitting any studies that may be applicable to our hypothesis. However, missed relevant texts are possible. For those studies captured, the use of 2 separate reviewers reduced the possibility of selection bias from one reviewer.

CONSLUSIONS
The results of this systematic review highlight the need for a rigorously developed, reliable, and well-validated outcome instrument to better understand those with limb-threatening LE trauma. This tool would allow for the collection of more specific outcomes to this population. Additionally, it would provide a better understanding of the domains that are most important to limb-threatened patients and focus our clinical efforts to provide a greater impact on their outcomes.