Difficulty in Identifying Factors Responsible for Pressure Ulcer Healing in Veterans With Spinal Cord Injury

Accepted Manuscript The Difficulty in Identifying Factors Responsible for Pressure Ulcer Healing in Veterans with Spinal Cord Injury Marylou Guihan, PhD, Min-Woong Sohn, PhD, William A. Bauman, MD, Ann M. Spungen, EdD, Gail M. Powell-Cope, PhD, ARNP, FAAN, Susan S. Thomason, DNP, RN DNP, RN, ACNS-BC, CWCN, CRRN, Joseph F. Collins, PhD, Barbara M. BatesJensen, PhD, RN PII:

S0003-9993(16)30267-2

DOI:

10.1016/j.apmr.2016.05.025

Reference:

YAPMR 56590

To appear in:

ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION

Received Date: 29 December 2015 Revised Date:

29 April 2016

Accepted Date: 26 May 2016

Please cite this article as: Guihan M, Sohn M-W, Bauman WA, Spungen AM, Powell-Cope GM, Thomason SS, Collins JF, Bates-Jensen BM, The Difficulty in Identifying Factors Responsible for Pressure Ulcer Healing in Veterans with Spinal Cord Injury, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2016), doi: 10.1016/j.apmr.2016.05.025. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Running Head: Difficulty Identifying PrU Healing factors in SCI

The Difficulty in Identifying Factors Responsible for Pressure Ulcer Healing in Veterans

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with Spinal Cord Injury Marylou Guihan, PhD; Spinal Cord Injury Quality Enhancement Research Initiative (SCI QUERI) & Edward Hines Jr. VA Hospital, Hines, Il 60141 and Department of Physical

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Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University, Chicago,

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IL. [email protected]

Min-Woong Sohn, PhD; Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, VA. [email protected]

William A Bauman, MD; VA RR&D National Center for the Medical Consequences of Spinal

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Cord Injury, James J. Peters VA Medical Center, Bronx, NY and Department of Medicine and Rehabilitation Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY. [email protected]

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Ann M Spungen, EdD; VA RR&D National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY and Department of Medicine and

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Rehabilitation Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY. [email protected]

Gail M Powell-Cope, PhD, ARNP, FAAN Center of Innovation for Disability and Rehabilitation Research (CINDRR), Tampa, FL. University of South Florida, School of Nursing, Tampa, FL. [email protected] Susan S Thomason, DNP, RN DNP, RN, ACNS-BC, CWCN, CRRN; Center of Innovation for 1

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Disability and Rehabilitation Research (CINDRR), Tampa, FL. [email protected]

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Joseph F Collins, PhD; Cooperative Studies Program Coordinating Center, Perry Point VAMC, Maryland. [email protected]

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Barbara M. Bates-Jensen, PhD, RN; SCI QUERI and University of California at Los Angeles (UCLA), School of Nursing & David Geffen School of Medicine, Los Angeles, CA [email protected]

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This study was funded by the Department of Veterans Affairs, Office of Research and

Development, Health Services Research and Development Service, Quality Enhancement

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Research Initiative (RRP-11-376). The views expressed in this presentation are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the US government.

Corresponding author contact information: Marylou Guihan, PhD, Edward Hines, Jr. VA

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Hospital (151-H), Box 5000, 5000 S. 5th Avenue, Hines, IL 60141-3030 ph: 708.202.5870

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email: [email protected]

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The Difficulty in Identifying Factors Responsible for Pressure Ulcer Healing in Veterans with

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Spinal Cord Injury

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Abstract:

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Objective: To identify characteristics associated with pressure ulcer (PrU) healing for individuals with spinal cord injury (SCI)

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Design: Secondary analysis of a large clinical trial data for healing PrUs in individuals with SCI; Prospective Delphi process was conducted with SCI and/or PrU experts.

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Setting: US Department of Veterans Affairs Spinal Cord Injury Centers

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Participants: 629 screening and 162 treatment participants; 185 SCI clinicians/national PrU/wound care experts participated in the Delphi process.

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Interventions: None

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Main Outcome Measure(s): 50% and 100% PrU healing at Weeks 4 and 12

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Results: Screening participants were 57±11 years, non-Hispanic white (61%), with complete motor paraplegia and more than a college education (55%). Baseline PrU size was 15.3 ± 19.0 cm2 and located on the ischium or perineum (48%).

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Poisson regression models using the top Delphi-recommended factors found that baseline ulcer size and ulcer severity (Stage IV) did not significantly predict 50% or 100% healing at Weeks 4 or 12. Ischial/perineal location was associated with 33% higher likelihood of 50% healing at Week 4. Patient non-compliance with treatment recommendations, the top-ranked Delphi factor, did not predict 50% or 100% healing at Week 12. At Week 4, baseline PrU size, PrU stage IV, multiple PrUs, PrU pain, and ASIA A significantly predicted 100% healing. At Week 12, only PrU stage (IV) significantly predicted 100% healing. Significant predictors of 50% healing at Week 12 included PrU duration and paraplegia. SCI center identifiers consistently showed two to five-fold variation in 50% PrU healing.

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Conclusions: Delphi panel-recommended factors such as patient compliance did not predict PrU healing. Reducing center-level variability in wound healing by learning from best practices should be a health system goal. PrU healing in SCI is still poorly understood and future studies should focus on as yet unidentified or under-appreciated factors.

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Key Words: pressure ulcer, spinal cord injury, Veterans, healing

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Pressure ulcers (PrUs) are a frequent complication in people with spinal cord injury (SCI) due to loss of sensation below the level of lesion, motor denervation and resultant immobility.1,2,

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Approximately 36-50% of all persons with SCI will develop a new or recurrent ulcer within the first

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year after SCI4 and most will develop at least one severe PrU (stage III/IV) during their lifetime.5,6

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Recurrence is common, with up to 40% of PrUs recurring among those living in the community.5,7,7,8,

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The impact of PrUs in individuals with SCI and on the health care system is substantial.

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Individuals with SCI and PrUs have significantly greater deficits in activities of daily living and

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participate in fewer community activities.13 Unemployment rates in individuals with SCI and PrUs are

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twice as high as those without PrUs.14 PrUs (and recurrences) are among the most frequent reasons for

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hospitalization in Veterans with SCI. PrUs in SCI are costly. The annual adjusted total healthcare costs

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in Veterans with SCI and a PrU are significantly higher than those without a PrU ($91,341 vs. $13,754;

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P<0.05). 15

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As longevity in people with SCI advances, PrU incidence is expected to rise in parallel with

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other functional impairments. However, despite the enormous disability and cost burden that PrUs exact

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on patients, and the health care system, there is little evidence on specific predictors of PrU healing. PrU

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treatment in persons with SCI is multi-faceted and may include moist dressings, debridement, infection

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management, nutritional supplementation, pressure redistribution strategies and equipment, adjunctive

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therapies, and/or reconstructive surgery.16 SCI clinicians are challenged to manage non-healing PrUs in

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persons with SCI. While PrU clinical practice guidelines provide general recommendations for standard

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wound care, evidence is not documented on which patient should receive surgical versus medical

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treatment. Identifying clinical predictors of PrU healing would likely allow for more effective treatment

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and potentially shorter healing times. Therefore, the objective of this study was to identify

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characteristics of PrU healing from prospective clinical trial data collected from individuals with PrUs

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and SCI.

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Methods

The Methods section is organized so that the relevant information for each section is presented for the parent study first, followed by the Delphi process.

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Research Design and Study Sample

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Parent study sample and design. Factors related to PrU healing were examined as a secondary analysis of the largest known prospective randomized clinical trial (RCT) for healing PrUs among

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individuals with SCI (i.e., “parent study”).17, 18 Detailed information on recruitment into the parent study

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is available in the primary manuscript (Figure 1: Study Flow Diagram) and on the clinicaltrials.gov

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website.19, 20 Briefly, eligibility for participating in the parent study included the following: SCI/D, of

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either gender, receiving inpatient treatment at one of the 16 VA SCI Centers which involved in the VA

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Cooperative Study for at least one Stage III/or IV pelvic PrU <260cm2. Patients with a “difficult-to-

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heal” PrU, defined as “failing to decrease by at least 30% over the 28-day “screening phase”, were

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eligible to participate in the “treatment phase”. A total of 1900 inpatients were initially evaluated

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(reasons for exclusion are in Figure 1 of the “parent” study), 779 participated in the “screening phase”

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(reasons for not continuing to the treatment phase are in Figure 1 of the “parent” study), and 212 were

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randomly assigned to placebo/drug treatment.

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During the 28-day “screening phase”, participants received standard PrU care (e.g., debridement,

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wound cleansing, moist dressings, off-loading, pressure reduction strategies) (“screening sample”,

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n=629). Participants whose PrU demonstrated <30% surface area (length x width) reduction during 4

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screening were eligible to participate in the “treatment phase” (24 weeks). Screening participants were

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followed for 4 weeks or until PrU healing occurred (i.e., complete epithelialization for 72 hours),

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whichever came first. Treatment participants were followed for 24 weeks or until PrU healing occurred

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(as above). The treatment sample (n=162) was a subset of the screening sample (n=629). During the

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treatment phase in addition to standard care, patients received oxandrolone or placebo in the treatment or

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control arms. Secondary data analyses of factors related to PrU healing were examined for both

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screening and treatment participants.

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Week 4 analyses included all participants with PrU area > 0 cm2 at the first screening visit (including those with healed PrUs between Weeks 0-4). Week 12 analyses included all treatment

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participants with PrU surface area >0 cm2 at Week 4 with complete data through Week 12 (including

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those with healed PrUs between Weeks 4-12). Participants with missing PrU size measurements for

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Weeks 4 or 12 were excluded from the Week 12 analyses because healing status could not be

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determined.

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Delphi Panel sample and design. To identify variables collected in the parent study for inclusion in predictive models, a modified Delphi panel was conducted with experts in SCI and/or PrUs. An

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explanatory email with survey links was sent to members of the VA’s national wound care email list; the

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Boards of Directors for the Wound Healing Society, Association for Advancement of Wound Care, and

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the National Pressure Ulcer Advisory Panel, and other national experts (defined as having published a

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paper on PrUs within the last five years).

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This study was approved by the institutional review board of the Hines VA Hospital, Hines, IL.

Study Outcomes and Measures Parent study outcomes and measures. Baseline data collected in the parent study included participant demographics (e.g., age, race/ethnicity, education, height, weight, smoking status and/or 5

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alcohol use); SCI characteristics (e.g., etiology, injury level/duration, American Spinal Injury

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Association [ASIA] score) and weekly serial measures of PrU characteristics (e.g., area, number,

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anatomic location, stage, duration, tunneling, undermining, and odor). Key variables in the parent study were defined as follows. Location included sacral, ischial,

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perineal or trochanteric. Patient non-compliance, defined as affirmation of inappropriate pressure to the

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target PrU, trauma to the PrU site, refusing dressing changes and/or general non-compliance was

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assessed by study clinicians weekly during the treatment phase. Receipt of adjunctive therapies defined

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as documented use of electrical stimulation, hyperbaric oxygen, light (infrared, ultraviolet, low-energy

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laser), ultrasound, sub-atmospheric pressure, topical growth factors, electro-magnetic, and/or radiowave

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therapies were permitted only during the screening phase.

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Target PrUs were measured in a systematic manner by an individual who was trained to use a digital camera with a software package which calculated total wound area. In this way, these

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measurement procedures were rigidly standardized across all study sites.

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For this study, “Complete (100%) PrU healing” was defined as PrU surface area = 0 cm2 and

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“50% PrU healing” as >50% decrease in PrU area at Week 4 or 12. The rationale for selecting these

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timepoints for assessing healing is as follows. Week 4 marked the end of the screening period for the

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parent study. The SCI PrU guideline recommends that treatment should be modified if the ulcer shows

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no evidence of healing within 2-4 weeks. Weeks 4 and 12 are commonly used endpoints in studies of

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other chronic wounds (e.g., venous leg ulcers [VLU], diabetic foot ulcers [DFU]).19, 20, 21, 22

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Both outcomes were calculated using baseline PrU surface area and serial measurements

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documented each subsequent week. PrUs were continuously treated over time but once complete healing

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was achieved, no further measurements were obtained. PrU healing status was defined as cumulative

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over the study by carrying forward the last PrU area measure for any PrU achieving complete healing

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between Weeks 0-4 for the Week 4 analyses and between Weeks 5-12 for the Week 12 analyses. The 50% 6

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and 100% PrU healing rates were determined for all 212 treatment participants over the course of the

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entire study.

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Delphi Survey outcomes and measures. The parent study collected a large amount of baseline

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and weekly assessments, so a modified Delphi process was used to develop a more parsimonious set of

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variables for analysis. Delphi panelists were asked to rank 29 variables collected for the parent study in

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terms of their importance for PrU healing. Participants received an email with an Internet link to the

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survey (see Supplemental material) with four weeks to respond. Electronic reminders were sent out in

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the second and third weeks. The second round of the survey was sent to all round 1 respondents 2 weeks

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after the first survey closed and included aggregate results of the first survey. Participants in the second

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round of the Delphi process were asked to rank order characteristics rated highest in the first survey. The

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Delphi panel’s responses were ranked according to proportion of panelists who classified a characteristic

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within their top 10 factors for PrU healing. These characteristics were used in a multivariable regression

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model to predict PrU healing.

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Statistical Analysis

Parent study analyses. Descriptive statistics were calculated to compare demographic, SCI and PrU characteristics of screening, and treatment participants.

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Multivariable analyses. A Poisson regression was used for multivariable analyses and corrected

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for SCI center-level clustering using Huber-White sandwich estimators for both 50% and 100% PrU

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healing models. Models for 50% and 100% PrU healing were performed at Weeks 4 and 12. Week 4

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marked the end of screening and Week 12 was chosen based on use as an endpoint in many wound

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healing studies. Two models were estimated for each outcome. The first model included as covariates

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the top six Delphi-recommended factors. The second expanded model included the Delphi factors and 7

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baseline PrU characteristics (tunneling or undermining, foul odor, pain, signs of infection, multiple

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PrUs), BMI, adjunctive therapy received, ASIA score, paraplegia, educational status and race/ethnicity. In the Poisson regression models, SCI center identifiers (to which the authors were blinded)

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proved to be the most important predictors of 50% PrU healing. Due to small number of participants

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achieving 100% healing (n=31), the models for 100% healing which included center identifiers did not

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converge. Therefore, models for 100% healing without center identifiers are presented. Pearson χ2

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goodness-of-fit tests showed that all models fit the data well. Power analysis shows that the minimum

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incidence rate ratios that our treatment sample (N = 162) can sensitively detect ranged between 1.4 and

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1.6, depending on the predictors.

descriptive statistics.

Analyses were conducted using STATA SE 14.23

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Results

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Delphi survey analyses. Data from the two rounds of the Delphi survey were analyzed using

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Delphi results. The Delphi survey link was emailed to 451 SCI clinicians and national PrU/wound care experts with response rates of 41% (n=185) and 27% (n=132) for the first and second

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rounds respectively. As shown in Table 1, respondents were mostly female, nurses, >45 years old, with a

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mean of 13.5 ± 10 years of wound care experience. A third of respondents described themselves as

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working primarily with PrUs in patients with SCI. Most described themselves as being employed in a

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VA medical center, an SCI center or a nursing home.

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As shown in Table 2, Delphi respondents identified characteristics related to the patient, PrU and

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treatment as important for PrU healing. Highest rated patient characteristics (n=11 plus two SCI

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characteristics) included compliance with treatment recommendations, smoking status, weight, high or

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low BMI, education, level of SCI injury and ASIA score. PrU characteristics (n=15) rated highly 8

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included PrU number, baseline PrU size, history, stage, location, tunneling, infection, and pain. Top

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treatment characteristics included inpatient treatment and use of adjunctive therapies.

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Sample description for Week 4 and 12 analyses

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As shown in Table 3, 629 screening phase participants and 162 treatment phase participants met inclusion criteria for the Week 4 and 12 analyses. Most of those screened were male (99%), non-

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Hispanic white (61%), with more than a college education (55%) and a mean age of 57±11 years. Over

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50% of the sample had complete motor paraplegia.

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PrU characteristics

PrUs were most frequently located on the ischium or perineum (48%/39.5%) and sacrum (37%/

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44.4%) among screening and treatment participants respectively. The average PrU size at baseline was

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15.3 ± 19.0 cm2 (median = 8.8 cm2; interquartile range [IQR] = 3.5 – 19.9 cm2) for screening

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participants (Week 4) and 16.5 ± 16.4 cm2 (median = 11.2; IQR = 4.5 – 24.1 cm2) for treatment

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participants (Week 12). Among screening and treatment participants at baseline, mean PrU duration was

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33.3 ± 54.8 weeks (median = 18; IQR, 12 – 32), tunneling or undermining was present in 63%, signs of

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infection in 54%, and foul odor in 17%. A quarter of participants received at least one adjunctive

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therapy during screening and 23% of treatment participants were “non-compliant to treatment

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recommendations” at least once during 24 weeks of treatment.

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PrU healing during the treatment phase

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Figure 1 presents the 50% and 100% PrU healing rates for 212 treatment phase participants over

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the course of the entire study. Complete healing was achieved in 13% at Week 12 and 32% at Week 24.

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Fifty percent healing was achieved in 25% at baseline (Week 4), 74% at Week 12, and 86% (n = 140) at

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Week 24.

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Delphi models Poisson regression models were conducted to predict 50% and 100% healing at Weeks 4 and 12

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using only the top six Delphi panel recommended factors (Table 4). Only ulcer severity (Stage IV)

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significantly predicted failure to achieve 50% or 100% healing at Weeks 4 and 12. In addition, ischial or

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perineal location was associated with 33% higher likelihood of 50% healing at Week 4 (Incidence Rate

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Ratio [IRR] = 1.33; 95% CI, 1.11 – 1.59). Notably, participant compliance, which was the top ranked

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Delphi factor, was not a significant predictor of 50% or 100% healing at Week 12 (IRR = 0.892; 95% CI,

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0.347 – 2.293; IRR = 0.832; 95% CI, 0.618 – 1.121, respectively).

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Expanded Models

The results for 100% PrU healing at Weeks 4 and 12 from the second expanded models are

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shown in Table 5. At Week 4, significant predictors of 100% PrU healing included baseline PrU size,

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PrU stage , multiple PrUs, PrU pain, and ASIA Score (A vs. B-E). At 12 Weeks, only PrU stage (IV)

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was significant in predicting 100% healing.

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The results predicting 50% PrU healing at Weeks 4 and 12 from the expanded models (which included SCI center identifiers) are shown in Table 6. Except for center identifiers, baseline PrU size,

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PrU stage IV, ischial or perineal location, BMI > 30 kg/m2, foul odor, and signs of infection

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significantly predicted 50% PrU healing at 4 weeks. None of these factors significantly predicted 50%

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PrU healing at Week 12. Significant predictors of 50% healing at Week 12 were PrU duration and

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paraplegia. Participant compliance was not significant.

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Variation in PrU healing by SCI centers 10

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For the Weeks 4 and 12 analyses (Table 6), SCI center identifiers consistently showed the

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strongest associations with PrU healing. Compared to Center 7 (which had the worst 50% healing rate at

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Week 12), Center 11 had about three times higher 50% healing (IRR = 2.879; 95% CI, 2.496 – 3.319) at

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Week 4, while Center 2 had three times higher 50% PrU healing at Week 12 (IRR = 3.300; 95% CI,

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2.137 – 5.096).

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Discussion

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The study results found that SCI center identifiers were the strongest predictors of PrU healing, consistently showing two- to five-fold variation in 50% PrU healing. Because our analyses controlled

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for differences in SCI Center sample size, these differences may reflect unmeasured variations in PrU

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management strategies. Of the PrU healing predictors examined, only five variables were significantly

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associated with 50% healing at Weeks 4 or 12, including smoking (Week 12), PrU location,

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tunneling/undermining and nutritional status (all in Week 4). Of the Delphi-endorsed factors, three

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variables significantly predicted PrU healing: 1) smoking, 2) tunneling and 3) undermining. Ischial or

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perineal PrUs were most likely to heal.

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observed took place before Week 12.The diabetic foot ulcer (DFU) literature has consistently found rate

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of surface area decrease within 4 weeks to be a predictor of wound healing.24,25 This does not appear to

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be the case for PrUs in SCI, perhaps because they are larger and more complex. Our results suggest

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some factors, which may provide insight into which PrUs might heal at certain time points, but this

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appears to change over time.

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For example, the role of PrU onset and duration in predicting healing in SCI is not well-

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understood.26,27,28,29,30,31, 32 Existing studies of wound healing provide limited detail in describing ulcer

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onset or duration and no uniform definition of PrU duration exists. Foot ulcer duration ranges from 15 11

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days33 to 2 months post onset.34 We have previously described a mean duration of severe PrUs in people

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with SCI of more than a year prior to the index hospitalization.35,36 Identifying ulcer duration may be

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more complicated than in other populations because people with SCI may be unaware of PrU onset due

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to lack of sensation or a specific preceding event. For those with limited mobility, visualizing anatomic

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locations susceptible to PrUs can be challenging. People with SCI may lack awareness of the early signs

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and symptoms signaling PrU onset in the able-bodied. Patients with SCI may fail to recognize the

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severity of what may initially present as a minor problem (e.g., redness over area or abrasion). Finally,

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patients with SCI may perceive disincentives for early reporting of PrU onset (e.g., long hospitalizations

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for PrU healing). Considerable research shows that males are more reluctant to seek help for medical as

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well as mental health problems.37,38 Future research should examine how factors such as PrU onset, PrU

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duration and gender are defined and/or understood by providers and patients.

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It is worth noting that while Delphi participants in both rounds ranked “patient compliance” as the most important factor for predicting PrU healing, in our analyses, it did not predict 50% or 100%

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PrU healing at any time point. Evidence supporting patient non-compliance as a major factor in

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predicting PrU healing is lacking. How patients’ behavior influences non-healing PrUs remains poorly

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understood in part because: 1) most studies collect no data on patient compliance, or 2) if collected,

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they use non-specific measures that may not reflect the patient’s contribution (or lack thereof) to PrU

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healing. In the parent study, non-compliance was based on clinical judgment and data was collected only

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during the treatment phase. Reasons for patient non-compliance to PrU treatments were not collected in

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the parent study. It’s also possible that situations that providers label as “non-compliance” may actually

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reflect the patient’s lack of understanding of how their behavior adversely affects PrU healing. The

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parent study’s definition of patient non-compliance may have been insufficiently specific or sensitive to

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predict healing in this population. More research is needed to identify the patient- and provider-based

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reasons for non-compliance and how best to address them to better support patients and providers to

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achieve the goal of PrU healing. Based on the strong relationship that providers posit between patient

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non-compliance and healing, the types and frequency of non-compliance that impedes PrU healing

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should be more comprehensively addressed in future studies to assess and mediate its potential impact

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on PrU healing.

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SCI Center identifiers were the strong predictors of healing in every regression and the

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magnitude of the odds ratios indicates that it is necessary to better understand what might explain these

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differences. Our analyses comparing use of adjunctive therapies found no significant differences by site

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during the screening phase. Center-level variation in healing outcomes may also reflect differences in

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patient casemix, patient/treatment selection approaches, availability and intensity of treatment prior to

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admission to the SCI center, as well as several other ill-defined factors. Because PrU etiology, as well as

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its treatment, are appreciated to be highly complex and multi-factorial, questions raised by these

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considerations should be addressed in future clinical trials. Future studies should also examine other

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factors that might explain these site-level differences (e.g., availability of plastic surgery and wound

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debridement) that were not collected for the parent study.

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Just as PrU risk assessment is necessary for allocating limited resources and guiding clinical decision-making related to PrU prevention, so is identifying factors that successfully predict PrU healing

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in Veterans with SCI. Over 200 PrU risk factors in SCI have been described in the published literature,39

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but few address factors that predict PrU healing in SCI.24 Across populations, guidelines recommend

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that treatment plans be modified if the ulcer shows no evidence of healing within 2 to 4 weeks.40, 41

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The purpose of this study was to identify factors associated with PrU healing in data derived

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from a large, prospective clinical trial. Even when appropriately managed, many PrUs in SCI do not heal

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in a timely fashion. Non-healing PrUs are costly to the health care system as well as to persons with SCI,

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who may be required to put their lives on hold for months at a time in order to heal the ulcer. At present, 13

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SCI providers must rely on good clinical judgment and personal experience in deciding when to use

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more aggressive or more expensive technologies and interventions. Therefore, understanding partial and

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complete PrU healing over time provides information and enhances the decision-making tools available

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to assist clinicians in developing the most appropriate treatment plans for patients with non-healing PrUs.

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Furthermore, validated predictors of PrU healing could also serve as proxy endpoints in evaluating new

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treatments and/or in improving design of future clinical trials.

Evaluating PrU healing progress in SCI has been challenging, due in part to the many different

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tools used by SCI clinicians to assess PrU healing. In turn, the lack of uniformity in tools used to assess

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PrU healing has made assessing treatment effectiveness difficult. The stringent methods used to measure

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wounds in the parent study are not generally available for and would be very challenging to implement

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in routine clinical care. However, to address this problem, VA researchers and clinicians developed the

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SCI Pressure Ulcer Monitoring Tool (SCI-PUMT) to assess PrU healing in persons with SCI.42, 43 The

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full implementation of the SCI-PUMT at all 24 VA SCI centers may greatly facilitate identification of

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factors that affect PrU healing in SCI.44

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Limitations

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Strengths of this study included a large sample size of persons with SCI with PrUs,

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systematically observed wound characteristics, patient compliance, physiological measures, and

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progression of wound healing over the course of 24 weeks. Limitations included the decreasing sample

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sizes which limited analyses of complete PrU healing and the low rates of complete PrU healing overall,

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limiting more robust analyses. Furthermore, the analysis may not be adequately powered for some

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variables in the treatment sample (e.g., patient non-compliance and smoking). These results may not

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generalize to non-Veterans or to women with SCI.

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We found that the Delphi panel recommended factors, including patient compliance, were not generally predictive of PrU healing. Instead, SCI center identifiers were the most significant factors,

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suggesting that modeling PrU care after the centers with the best healing rates and thus reducing inter-

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center variability should be a health system goal. Our findings also suggest that PrUs that fail to heal

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after being treated for 24 weeks may have as yet unidentified factors that continue to be persistently

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present which continue to impede wound healing. If these factors can be identified and appropriately

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treated, improved wound healing would undoubtedly result. However, our findings also suggest that

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there may continue to be that one or more extremely potent factors are still not being clinically

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appreciated, or, if recognized, are not being adequately treated.

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References 1

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Gélis A, Dupeyron A, Legros P, Benaïm C, Pelissier J, Fattal C. Pressure ulcer risk factors in persons with spinal cord injury part 2: the chronic stage. Spinal Cord. 2009 Sep;47(9):651-61 2

Byrne DW, Salzberg CA. Major risk factors for pressure ulcers in the spinal cord disabled: a literature review. Spinal Cord. 1996 May;34(5):255-63 3

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Fuhrer MJ, Garber SL, Rintala DH, et al. (1993) Pressure ulcers in community-resident persons with spinal cord injury: Prevalence and risk factors. Arch Phys Med Rehabil; 74:1172-1177. 4

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Chen D, Apple DF, Hudson MF, Bode R. (1999) Medical complications during acute rehabilitation following spinal cord injury. Arch Phys Med Rehabil;80:1397-1401.

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Charlifue S, Jha A, Lammertse D. Aging with spinal cord injury. Phys Med Rehabil Clin N Am 2010; 21: 383–402.

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Chen Y, Devivo MJ, Jackson AB. Pressure ulcer prevalence in people with spinal cord injury: ageperiod-duration effects. Arch Phys Med Rehabil 2005; 86: 1208–1213. Young JS, Burns PE. Pressure sores and the spinal cord injured: part II. SCI Digest 1981;3:11-26, 48.

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Carlson CE, King RB, Kirk PM, Temple R, Heinemann A. Incidence and correlates of pressure ulcer development after spinal cord injury. J Rehabil Nurs Res 1992;1:34-40. 9

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Fuhrer MJ, Garber SL, Rintala DH, Clearman R, Hart K. Pressure ulcers in community-resident persons with spinal cord injury: Prevalence and risk factors. Arch Phys Med Rehabil 1993; 74:11721177. Niazi ZB, Salzberg CA, Byrne DW, Viehbeck M. Recurrence of initial pressure ulcer in persons with spinal cord injuries. Adv Wound Care 1997; 10:38-42. 11

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Holmes SA, Rintala D, Garber SL, Friedman JD. Prevention of recurrent pressure ulcers after myocutaneous flap. Journal of Spinal Cord Medicine, 2002, 25 (Supplement 1), S23. 12

Goodman CM, Cohen V, Armenta A, Thornby J, Netscher DT. Evaluation of results and treatment variables for pressure ulcers in 48 veteran spinal cord-injured patients. Ann Plast Surg 1999;43:572574. 13

Lala D, Dumont FS, Leblond J, Houghton PE, Noreau L. Impact of pressure ulcers on individuals living with a spinal cord injury.Arch Phys Med Rehabil. 2014 Dec;95(12):2312-9.

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Krause JS. Skin sores after spinal cord injury: relationship to life adjustment. Spinal Cord 1998;36:5156. 15

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Stroupe KT, Manheim, LL, Evans CT, Guihan M, Ho CC, Li K, Cowper-Ripley D, Hogan T, St. Andre JR, Huo J, and Smith BM. (2011) Cost of Treating Pressure Ulcers for Veterans with Spinal Cord Injury. Top Spinal Cord Inj Rehabil;16(4):62–73.

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Kruger EA, Pires M, Ngann Y, Sterling M, Rubayi S. Comprehensive management of pressure ulcers in spinal cord injury: Current concepts and future trends. JCSM. 2013;36(6):572-585.

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Bauman WA, Spungen AM, Collins JF, Raisch DW, Ho C, Deitrick GA, Nemchausky BA, Goetz LL, Park JS, Schwartz M, Merritt JL, Jayawardena V, Sandford P, Sabharwal S, Holmes SA, Nasar F, Sasaki R, Punj V, Zachow KF, Chua WC, Thomas MD, Trincher RC. The effect of oxandrolone on the healing of chronic pressure ulcers in persons with spinal cord injury: a randomized trial. Ann Intern Med. 2013 May 21;158(10):718-726. https://clinicaltrials.gov/ct2/show/NCT00101361

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Sheehan P, Jones P, Caselli A, Giurini J, Veves A. Percent change in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12-week prospective trial. Diabetes Care. 2003;26(6):1879–1882. 20

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Margolis D, Gelfand J, Hoffstand O, Berlin J. Surrogate endpoints for the treatment of diabetic neuropathic foot ulcers. Diabetes Care, 2003: 26: 1696-700. Cardinal, M, Eisenbud, DE, Phillips, T, Harding, K. Early healing rates and wound area measurements are reliable predictors of later complete wound closure. Wound Repair Regen, 2008; 16: 19-22. 22

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Stata Statistical Software: Release 14. College Station, TX: StataCorp LP.

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Hill, DP, Poore, S, Wilson, RGN, Robson, MC, Cherry, GW. Initial healing rates of venous ulcers: are they useful as predictors of healing? Am J Surg, 2004; 188 (Suppl): 22S-25S.

Robson, M, Hill, D, Woodske, M, Steed, D. Wound healing trajectories as predictors of effectiveness of therapeutic agents. Arch Dermatol, 2000; 135: 773-7. 25

Cardinal, M, Eisenbud, DE, Phillips, T, Harding, K. Early healing rates and wound area measurements are reliable predictors of later complete wound closure. Wound Repair Regen, 2008; 16: 19-22. 26

Margolis DJ, Allen-Taylor L, Hoffstad O, Berlin JA (2002) Diabetic neuropathic foot wounds: the association of wound size, wound duration, and wound grade on healing. Diabetes Care 5:1835–1839.

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Margolis DJ, Kantor J, Santanna J, Strom BL, Berlin JA. (2000) Risk factors for delayed healing of neuropathic diabetic foot ulcers: a pooled analysis. Arch Dermatol 136:1531–1535 28

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Hill DP, Poore S, Wilson RG, Robson MC, Cherry GW. Initial healing rates of venous ulcers: are they useful as predictors of healing? Am J Surg, 2004; 188 (Suppl): 22S-25S.

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Margolis, D, Gelfand, J, Hoffstand, O, Berlin, J. Surrogate endpoints for the treatment of diabetic neuropathic foot ulcers. Diabetes Care, 2003: 26: 1696-700. 30

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Tallman, P, Muscare, E, Carson, P, Eaglstein, WH, Falanga, V. Initial rate of healing predicts complete healing of venous leg ulcers. Arch Dermatol, 1997; 133: 1231-324. 31

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Sheehan P, Jones P, Caselli A, Giurini J, Veves A. Percent change in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12-week prospective trial. Diabetes Care. 2003;26(6):1879–1882. 32

Gelfand JM, Hoffstad O, Margolis DJ. Surrogate endpoints for the treatment of venous leg ulcers. J Invest Dermatol. 2002 Dec;119(6):1420-5 33

Ince P, Game FL, Jeffcoate WJ (2007) Rate of healing of neuropathic ulcers of the foot in diabetes and its relationship to ulcer duration and ulcer area. Diabetes Care. 2007 Mar;30(3):660-3.

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Margolis DJ, Allen-Taylor L, Hoffstad O, Berlin JA. (2003) Diabetic neuropathic foot ulcers: predicting which ones will not heal. Am J Med 115:627–631,

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Guihan M, Garber SL, Bombardier CH, Durazo-Arizu R, Goldstein B, Holmes SA. (2007) Lessons learned while conducting research on prevention of pressure ulcers in veterans with spinal cord injury. Arch Phys Med Rehabil. Jul;88(7):858-61.

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Guihan M, Bombardier CH, Ehde DM, Rapacki LM, Rogers TJ, Bates-Jensen B, Thomas FP, Parachuri R, Holmes SA. (2014) Comparing multicomponent interventions to improve skin care behaviors and prevent recurrence in veterans hospitalized for severe pressure ulcers. Arch Phys Med Rehabil. Jul;95(7): 1246-1253. Mackenzie CS, Gekoski WL, Knox VJ. Age, gender, and the underutilization of mental health services: the influence of help-seeking attitudes. Aging Ment Health. 2006 Nov;10(6):574-82.

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Yousaf O, Grunfeld EA, Hunter MS. A systematic review of the factors associated with delays in medical and psychological help-seeking among men. Health Psychol Rev. 2015;9(2):264-76 39

Byrne DW and Salzberg CA. Major risk factors for pressure ulcers in the spinal cord disabled: a literature review. Spinal Cord. 1996 34, 255–263.

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Consortium for Spinal Cord Medicine. Pressure ulcer prevention and treatment following spinal cord injury: a clinical practice guideline for health-care professionals 2000. Paralyzed Veterans of America, Washington DC. 41

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Consortium for Spinal Cord Medicine. Pressure Ulcer Prevention and Treatment Following Injury: A Clinical Practice Guideline for Health-Care Providers (2nd edition). 2014. Paralyzed Veterans of America, Washington DC.

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Thomason SS, Luther SL, Powell-Cope GM, Harrow JJ, Palacios P. Validity and reliability of a pressure ulcer monitoring tool for persons with SCI. J Spinal Cord Med. 2014 May;37(3):317-27.

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http://www.queri.research.va.gov/tools/sci-pumt/default.cfm

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Thomason SS, Graves BA, Madaris L. A pilot study to evaluate the role of the SCI-PUMT in clinical decisions for pressure ulcer treatment. Ostomy Wound Manage. 2014 Dec;60(12):28-36.

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Table 1. Delphi Panel Participant Demographics

82 (46.1%) 96 (53.9%) 50 (32) 16 (17) 10 (21) 20 (25) 4 (12)

63 (51.6%) 59 (48.4%) 51 (31) 17 (16) 10 (21) 19 (23) 4 (13)

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Gender

Some College College Graduate Master's Degree PhD Professional Degree Female Male 25-34 35-44 45-54 55-64 65-74 Non Wound Nurse Wound Nurse MD Other SCI Wound Care Geriatrics Surgery Other VA Medical Center VA SCI Center Nursing Home VA SCI Outpatient Clinic University University Medical Center Community Hospital Other

Round 2 n=123 1 (0.8%) 37 (30.1%) 52 (42.3%) 10 (8.1%) 23 (18.7%) 98 (81.7%) 22 (18.3%) 11 (9.2%) 16 (13.4%) 33 (27.7%) 50 (42.0%) 9 (7.6%) 43 (35.2%) 50 (41.0%) 12 (9.8%) 17 (14.0%) 19 (16.5%) 70 (60.9%) 10 (8.7%) 1 (0.9%) 15 (13.0%) 50 (40.7%) 41 (33.3%) 8 (6.5%) 6 (4.9%) 2 (1.6%) 7 (5.7%) 21 (17.1%) 13 (9)

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Round 1 n=185 4 (2.2%) 55 (30.1%) 71 (38.8%) 20 (10.9%) 33 (18.0%) 146 (79.3%) 38 (20.7%) 17 (9.2%) 27 (14.7%) 57 (31.0%) 70 (38.0%) 13 (7.1%) 79 (42.7%) 58 (31.4%) 17 (9.2%) 31 (16.7%) 44 (26.8%) 34 (20.7%) 23 (14.0%) 15 (9.1%) 48 (29.3%) 71 (38.4%) 57 (30.8%) 15 (8.1%) 11 (5.9%) 9 (4.9%) 8 (4.3%) 2 (1.1%) 26 (15.4%) 14 (10)

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Number of Years Working with Wounds, mean (sd) Academic Affiliation Percentage of time devoted to, mean (sd)

Yes No Direct Patient Care Teaching Research Administration Other

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Table 2. Delphi panel rankings of factors associated with PrU healing Round 2 (% endorsing in their top 10)

90.8 87.0 81.1 75.5 68.6 63.2 62.2 62.2 62.2 61.1 60.0 59.5 58.9 56.2 55.1 52.4 52.4 51.9 51.4 51.4 49.7 49.7 49.2 48.6 47.0 0 0 0 0

72.4 56.9 59.3 52.8 57.7 49.6 47.2 -

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Round 1 (% endorsing in their top 10)

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Patient noncompliance Current smoker PrU history PrU size Level of injury History of PrU flap(s) PrU duration PrU location (sacral) PrU severity PrU odor Multiple PrUs PrU stage PrU location (ischial/perineal) PrU tunneling Patient weight ASIA score Number current PrUs Receipt of adjunctive therapy High BMI (> 30 kg/m2) Low BMI (< 25 kg/m2) Education Inpatient treatment PrU pain PrU infection Smoking history Body Mass Index (BMI) Race PrU color (necrotic tissue) PrU undermining

Type of factor patient patient PrU PrU SCI patient PrU PrU PrU PrU PrU PrU PrU PrU patient SCI PrU treatment patient patient patient treatment PrU PrU patient patient patient PrU PrU

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BMI= body mass index, ASIA Score: American Spinal Injury Association score

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Table 3. Demographic, SCI and PrU characteristics for participants in Weeks 4 and 12 analyses Patient, SCI and PrU Characteristics

Screening Sample Treatment Sample N (%) N (%) 629 162

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N Demographic Characteristics Mean age, years (sd) 57.3 (11.3) 58.0 (10.5) Male sex 624 (99.2) 160 (98.8) White race 382 (60.7) 105 (64.8) College or higher 348 (55.3) 79 (48.8) Body Mass Index, kg/m2 Normal (< 25) or Unknown 343 (54.5) 96 (59.3) Overweight (25 - 29.9) 190 (30.2) 45 (27.8) Obese (≥ 30) 96 (15.3) 21 (13.0) Current smoker 145 (23.1) 43 (26.5) SCI Characteristics Injury level Tetraplegia 289 (45.9) 75 (46.3) Paraplegia 340 (54.1) 87 (53.7) ASIA Score A 445 (70.7) 112 (69.1) B - E or Unknown 184 (29.3) 50 (30.9) Pressure Ulcer Characteristics Area (width x length), cm2, mean (sd) 15.3 (19.0) 16.5 (16.4) Study PrU Location Sacral 234 (37.2) 72 (44.4) Ischial or perineal 304 (48.3) 64 (39.5) Trochanteric 91 (14.5) 26 (16.1) Study PrU Stage III 161 (25.6) 32 (19.8) IV 468 (74.4) 130 (80.3) Multiple PrUs Stage II or higher 225 (35.8) 69 (42.6) First PrU 164 (26.1) 47 (29.0) PrU duration, weeks, mean (sd) 33.3 (54.8) 31.3 (40.6) Sign of infection 339 (53.9) 70 (43.2) Pain 95 (15.1) 25 (15.4) Tunneling or undermining 395 (62.8) 114 (70.4) Foul odor 109 (17.3) 19 (11.7) Treatment Adjunctive therapies, any 152 (24.2) 24 (14.8) Not compliant 37 (22.8) PrU Healing Outcomes 100% 29 (4.6) 31 (19.1) 50% 118 (18.8) 95 (58.6) * All patient and PrU characteristics except treatment variables are from the baseline measures.

Treatment characteristics reflect the last measure prior to Week 4 (for adjunctive therapies, which were only allowed during the screening phase) or Week 12 (for non-compliance, which was only collected during the trial). .

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Table 4. Poisson regressions predicting 50% and 100% healing at Weeks 4 and 12 using top 5 Delphi panel factors1 50% Healing 100% Healing Week 4 (N = 629) Week 12 (N = 162) Week 4 (N = 629) Week 12 (N = 162) IRR (95% CI) P-Value IRR (95% CI) P-Value IRR (95% CI) P-Value IRR (95% CI) P-Value Non-compliance 0.803 (0.326 - 1.982) 0.635 0.919 (0.757 - 1.116) 0.395 Current smoker 1.010 (0.753 - 1.202) 0.132 0.906 (0.445 - 1.844) 0.785 1.010 (0.753 - 1.355) 0.946 0.942 (0.762 - 1.165) 0.585 First PrU 0.962 (0.788 - 2.845) 0.552 0.688 (0.294 - 1.606) 0.387 0.962 (0.788 - 1.175) 0.704 1.013 (0.820 - 1.250) 0.908 PrU Duration in Weeks† 0.914 (0.795 - 2.377) 0.283 1.016 (0.588 - 1.754) 0.955 0.914 (0.795 - 1.052) 0.212 0.978 (0.896 - 1.067) 0.617 PrU Location [vs Sacral] Ischial or Perineal 1.329 (1.111 - 2.006) 0.562 0.815 (0.432 - 1.539) 0.529 1.329 (1.111 - 1.589) 0.002* 1.018 (0.854 - 1.214) 0.840 Trochanteric 0.798 (0.566 - 2.873) 0.854 0.323 (0.070 - 1.483) 0.146 0.798 (0.566 - 1.125) 0.197 0.895 (0.680 - 1.177) 0.427 Stage IV [vs III] 0.631 (0.524 - 0.438) < 0.001* 0.437 (0.223 - 0.859) 0.016* 0.631 (0.524 - 0.758) < 0.001* 0.835 (0.707 - 0.986) 0.034*

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Reference category in brackets. † PrU duration in natural logarithmic scale. * p<0.002

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Table 5. Poisson regression predicting 100% PrU healing at Week 4 and 12 Week 4 (N = 629) IRR (95% CI) P-Value

Variables

Week 12 (N = 162) IRR (95% CI) P-Value 0.892 (0.347 - 2.293) 0.812 0.640 (0.218 - 1.875) 0.415 0.655 (0.312 - 1.378) 0.265 0.999 (0.991 - 1.007) 0.756

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Non-compliant Current smoker 1.662 (0.789 - 3.500) 0.182 First PrU 1.014 (0.498 - 2.063) 0.969 PrU Duration in Weeks† 1.001 (0.997 - 1.006) 0.601 PrU Location [vs Sacral] Ischial or Perineal 0.832 (0.493 - 1.403) 0.490 0.710 (0.372 - 1.354) 0.298 Trochanteric 0.849 (0.379 - 1.903) 0.692 0.281 (0.044 - 1.804) 0.181 Stage IV (vs III) 0.370 (0.180 - 0.759) 0.007* 0.553 (0.323 - 0.949) 0.031* PrU size at Week 1 0.867 (0.787 - 0.954) 0.003* 0.994 (0.972 - 1.016) 0.561 Multiple PrUs 0.347 (0.158 - 0.763) 0.008 0.975 (0.565 - 1.680) 0.927 BMI (vs < 25 kg/m2) 25 - 30 kg/m2 0.920 (0.503 - 1.684) 0.787 1.440 (0.441 - 4.705) 0.546 > 30 kg/m2 1.218 (0.416 - 3.569) 0.719 0.433 (0.091 - 2.051) 0.292 Adjunctive therapy received 0.630 (0.233 - 1.705) 0.363 1.629 (0.774 - 3.431) 0.199 PrU pain 0.282 (0.120 - 0.661) 0.004* 1.306 (0.747 - 2.284) 0.350 Paraplegia [vs tetraplegia] 1.065 (0.712 - 1.592) 0.761 1.444 (0.705 - 2.960) 0.315 ASIA score = A [vs B – E] 0.565 (0.361 - 0.884) 0.013* 1.241 (0.783 - 1.967) 0.358 Foul odor 0.859 (0.317 - 2.328) 0.765 2.096 (0.707 - 6.210) 0.182 Tunneling or undermining 0.613 (0.227 - 1.661) 0.336 0.665 (0.302 - 1.462) 0.310 Sign of infection 1.149 (0.544 - 2.428) 0.716 0.990 (0.440 - 2.226) 0.981 College or higher education 1.229 (0.564 - 2.676) 0.604 0.713 (0.372 - 1.367) 0.308 White race 1.023 (0.394 - 2.658) 0.962 0.904 (0.464 - 1.763) 0.768 Reference category in brackets. NH = Non-Hispanic; BMI = body mass index; ASIA = American Spinal Injury Association; PrU = pressure ulcer. † PrU Duration in natural logarithmic scale. ** p<0.05

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Table 6 Poisson regressions predicting 50% PrU healing at Week 4 and 122

1.304 (1.086 - 1.566) 0.938 (0.690 - 1.276) 0.833 (0.650 - 1.068)

0.004* 0.684 0.150

1.032 (0.873 - 1.221) 0.963 (0.705 - 1.316) 0.947 (0.763 - 1.175)

1.183 1.262 0.971 1.224 1.076 0.904 1.366 0.884 0.646 0.914 0.938

(0.995 - 1.407) (1.049 - 1.518) (0.767 - 1.229) (0.729 - 2.054) (0.900 - 1.287) (0.760 - 1.075) (1.056 - 1.768) (0.734 - 1.066) (0.491 - 0.850) (0.777 - 1.075) (0.792 - 1.113)

0.057 0.014* 0.807 0.444 0.422 0.253 0.018* 0.197 0.002* 0.276 0.464

1.035 0.939 0.899 1.230 1.400 0.940 1.113 0.968 0.905 1.046 1.020

(0.763 - 1.405) (0.649 - 1.357) (0.605 - 1.334) (0.696 - 2.175) (1.018 - 1.925) (0.763 - 1.159) (0.698 - 1.775) (0.808 - 1.160) (0.696 - 1.178) (0.873 - 1.254) (0.810 - 1.283)

0.824 0.737 0.596 0.477 0.039* 0.565 0.653 0.725 0.459 0.627 0.868

2.645 0.972 1.220 2.226 1.900 2.127 1.653 2.244 2.269 2.879 1.932 1.234 0.897 0.941 1.965

(2.279 - 3.070) (0.785 - 1.203) (0.996 - 1.493) (1.679 - 2.950) (1.529 - 2.361) (1.683 - 2.688) (1.117 - 2.447) (1.967 - 2.560) (1.843 - 2.794) (2.496 - 3.319) (1.478 - 2.525) (0.944 - 1.613) (0.713 - 1.129) (0.640 - 1.383) (1.519 - 2.542)

< 0.001* 0.793 0.054 < 0.001* < 0.001* < 0.001* 0.012* < 0.001* < 0.001* < 0.001* < 0.001* 0.123 0.355 0.756 < 0.001*

1.715 3.300 1.803 1.982 2.051 2.002 1.296 1.698 1.968 2.282 1.842 2.040 0.944 1.512 1.678

(1.192 - 2.468) (2.137 - 5.096) (1.459 - 2.228) (1.599 - 2.457) (1.562 - 2.693) (1.464 - 2.739) (0.699 - 2.401) (1.213 - 2.376) (1.450 - 2.672) (1.912 - 2.724) (1.377 - 2.465) (1.570 - 2.650) (0.769 - 1.159) (0.965 - 2.369) (1.255 - 2.243)

0.004* < 0.001* < 0.001* < 0.001* < 0.001* < 0.001* 0.411 0.002* < 0.001* < 0.001* < 0.001* < 0.001* 0.581 0.071 < 0.001*

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12 Weeks (N = 162) IRR (95% CI) P-Value 0.832 (0.618 - 1.121) 0.226 0.783 (0.610 - 1.005) 0.054 1.001 (1.000 - 1.001) 0.017* 0.992 (0.984 - 1.000) 0.051 1.008 (0.824 - 1.233) 0.940 0.863 (0.696 - 1.072) 0.183

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Non-compliant Current smoker PrU Duration in Weeks† PrU size at Week 1 First PrU Stage IV [vs III] PrU Location [vs Sacral] Ischial or Perineal Trochanteric Multiple PrUs BMI [vs < 25 kg/m2] 25 - 30 kg/m2 > 30 kg/m2 Adjunctive therapy received PrU pain Paraplegia (vs tetraplegia) ASIA score = A [vs B – E] Foul odor Tunneling or undermining Sign of infection College or higher education White race SCI Center [vs 7] 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16

4 Weeks (N = 629) IRR (95% CI) P-Value 1.003 (0.730 - 1.379) 0.983 0.999 (0.997 - 1.001) 0.557 0.988 (0.979 - 0.997) 0.008* 0.897 (0.750 - 1.074) 0.238 0.665 (0.546 - 0.809) 0.000*

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0.712 0.815 0.620

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Figure 1. Cumulative percentages of participants who achieved 50% and 100% healing of study PrU during the treatment phase (N = 212)*

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*Total number of participants (N = 212) include 162 treatment group participants shown in Tables 3 and 4 and 50 participants who were excluded from Week 12 regression analyses because they lacked PrU size measurements between Weeks 4 and 12.

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RESEARCH ON FACTORS ASSOCIATED WITH PRESSURE ULCER WOUND HEALING

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Thank you for helping with this survey. Results from this study will provide valuable information on factors associated with pressure ulcer healing. Please note that the survey is hosted by SurveyMonkey.com and consequently survey responses will not be stored behind the VA firewall. If you have difficulties with completing the survey, please email: [email protected] To begin, please indicate what type of position you hold at your institution:

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Physician Physician Assistant (PA) Nurse Nurse Practitioner (NP) Wound Certified Nurse Researcher Other:

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Potential factors associated with wound healing: Please select the top 5 variables you believe may be associated with pressure ulcer healing (1 – Most likely to be associated: 5 – Least likely to be associated) Rank DEMOGRAPHIC FACTORS Weight BMI Low BMI High BMI Smoking History Race/Ethnicity Educational Level If spinal cord injured Level of SCI injury ASIA Level LABORATORY VALUES Elevated serum glucose Elevated hemoglobin A1c Decreased prealbumin Elevated white blood cell count Decreased red blood cell count WOUND HISTORY History of flap surgery at the same anatomic location History of pressure ulcer(s) at the same anatomic location Presence of concurrent pressure ulcer(s) Number of current stage 2 pressure ulcers Number of current stage 3 pressure ulcers Number of current stage 4 pressure ulcers Use of adjunctive therapies to treat the ulcer (i.e. negative pressure wound therapy, hyperbaric oxygen) Noncompliance with treatment regimen Treatment for pressure ulcer in the inpatient setting WOUND CHARACTERISTICS Location of current pressure ulcer Duration of current pressure ulcer Stage of pressure ulcer Size of current pressure ulcer Total surface area of pressure ulcer Signs and symptoms of infection at the ulcer site Pressure ulcer has odor Tunneling present Undermining present Pain associated with the pressure ulcer Ulcer bed color Ulcer exudate

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Are there any other factors not listed that affect to wound healing:

DEMOGRAPHIC DATA

□ Yes □ No

SC

2. Are you affiliated with an academic institution?

RI PT

1. Please indicate where you are employed: [check all that apply] □ VA SCI Center □ VA SCI Outpatient Center □ VA non-SCI Center □ SCI Model systems □ Private Rehab hospital □ Community hospital □ Nursing Home/Skilled Nursing Facility □ University □ Other [specify]:

3. How long have you been working in wound care/SCI/research?

M AN U

4. How long have you been working with SCI patients, if at all?

years years

TE D

5. What is your primary health care specialty? [select one] □ Physical Medicine and Rehabilitation □ Internal Medicine □ Neurology □ Urology □ Orthopedics □ General surgery □ Neurosurgery □ Infectious Disease □ Geriatrics □ Spinal Cord Injury □ Not applicable □ Other [specify]:

□ Female

AC C

7. Gender □ Male

EP

6. Please allocate the percentage of your professional time across the following activities: Direct patient care Teaching Research Administration Other [Please specify]

8. Educational Level: [select highest level] □ High School □ College Graduate □ Graduate Degree (PhD)

□ Some College □ Graduate Degree (Masters) □ Professional Degree

9. Age □ 18 to 25 years old □ 36 to 45 years old □ 56 to 65 years old

□ 26 to 35 years old □ 46 to 55 years old □ 66 or older

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