Pilot Testing Prehabilitation Services Aimed at Improving Outcomes of Frail Veterans Following Major Abdominal Surgery
Phase: NA
Conditions: Frailty
Sponsor: VA Office of Research and Development

 
 
 
 
 
 
 
 
Pilot Testing Prehabilitation services aimed at improving outcomes 
among frail Veterans following major abdominal surgery. 
NCT03040336 
4/3/2019 

 
 
 
* Study Name: 
Pilot Testing Prehabilitation services aimed at improving outcomes among frail Veterans following 
major abdominal surgery 
 
 
* Brief Description (using layman's terms) - 500 words or less: 
Frail Veterans are at increased risk for poor surgical outcomes, and as the Veteran population 
grows older and more frail, there is a critical need to identify effective strategies for reducing 
surgical risks for these patients. Prior research shows that inter-disciplinary rehabilitation 
strategies deployed after surgery enhance recovery and improve outcomes by building strength 
and improving nutrition. We believe that similar improvements may be obtained by using similar 
interventions before surgery to “prehabilitate” patients’ capacity to tolerate the stress of surgery. 
The proposed research will examine the feasibility of a new, prehabilitation intervention aimed at 
improving postoperative surgical outcomes through preoperative exercise training and nutritional 
supplementation. Findings from the study will inform the design of a larger randomized controlled 
trial of the prehabilitation intervention. If proven effective, prehabilitation could benefit as many 
as 42,000 frail Veterans who are scheduled for major elective surgery each year. 
 
 
* Abstract. Please provide a brief description of the study. 
Background: Frail Veterans are at increased risk for poor surgical outcomes. Although surgeons 
operate safely on even the oldest old, if the elder is also frail, the stress of surgery can result in 
significant mortality, morbidity, and institutionalization. Frailty is a clinical syndrome marked by 
muscle atrophy, diminished strength, decreased physical activity, and exhaustion. It is 
independent of any specific disease, but it increases with age, and is a more powerful predictor of 
increased perioperative mortality, morbidity, length of stay, and cost than predictions based on 
age or comorbidity alone. As the Veteran and US populations grow older and more frail, it is 
critically important to identify effective strategies for improving the surgical outcomes of these 
patients. 
“Prehabilitation” has the potential to improve surgical outcomes among the frail. Prior 
research demonstrates that inter-disciplinary rehabilitation strategies deployed after surgery 
enhance recovery and improve outcomes by building strength, improving nutrition, and optimizing 
home supports. Based on this success, there is growing interest in deploying similar interventions 
before surgery in what some call “prehabilitation.” By modifying physiological and environmental 
risks, prehabilitation aims to augment patients’ capacity to compensate for the stress of both 
surgery and recovery. Frail patients will likely benefit disproportionately from prehabilitation 
because they have the most diminished capacity to adapt to the stress of surgery. However, 
prehabilitation has not yet been studied in either Veteran or specifically frail populations. 
Objectives: We will examine the feasibility of a novel, multifaceted pre-habilitation intervention 
aimed at improving postoperative outcomes for frail Veterans undergoing major abdominal 
surgery. Specific aims are to: 
(1) Estimate rates of recruitment, randomization, retention, and compliance with the 
prehabilitation intervention; 
(2) Measure (a) physical performance, (b) pulmonary function, and (c) nutrition at baseline and 
2-week intervals to estimate changes over time and explore the optimal duration of 
prehabilitation (2 vs. 4 vs. 6 weeks); and 
(3) Estimate overall and treatment-specific summary statistics for postoperative outcomes in 
terms of 30- and 90-day (a) mortality, (b) major complications, (c) length of hospital stay, (d) 
health-related quality of life, (e) quality of surgical care, and (f) change in level of independent 
living. 
Methods: This randomized pilot study will enroll a consecutive cohort of up to 50 Veterans 
identified as frail using a standardized frailty assessment and scheduled for major abdominal 
surgery on the general or urological surgery services at the VA Pittsburgh Healthcare System. We 
will randomize participants 1:1 to receive either: (1) standard preoperative optimization by the 
Interdisciplinary Medical Preoperative Assessment Consultation & Treatment Clinic (IMPACT), or 
(2) prehabilitation + standard IMPACT optimization. The 6-week long prehabilitation intervention 

 
 
will include (1) strength and balance training; (2) inspiratory muscle training; and (3) nutritional 
coaching and supplementation. Assessments will include standard postoperative outcomes as well 
as the Short Physical Performance Battery to measure physical performance, Maximal Inspiratory 
Pressure to measure pulmonary function, and both prealbumin and the 7-point Subjective Global 
Assessment to measure nutrition. Outcomes will be assessed 30 or 90 days after surgery. 
Compliance with the prehabilitation regimen will be assessed through patient logs and 
pedometers. Analyses will inform the development of a larger randomized controlled trial testing 
the prehabilitation intervention. Findings will be relevant for the as many as 42,000 frail Veterans 
scheduled for major elective surgery each year. 
 
 * Describe the study objectives. Please include primary aim and hypothesis, if applicable 
any secondary aims and hypotheses. 
We will examine the feasibility of a novel, multifaceted pre-habilitation intervention aimed at 
improving postoperative outcomes for frail Veterans undergoing major abdominal surgery. Specific 
aims are to: 
(1) Estimate rates of recruitment, randomization, retention, and compliance with the 
prehabilitation intervention; 
(2) Measure (a) physical performance, (b) pulmonary function, and (c) nutrition at baseline and 
2-week intervals to estimate changes over time and explore the optimal duration of 
prehabilitation (2 vs. 4 vs. 6 weeks); and 
(3) Estimate overall and treatment-specific summary statistics for postoperative outcomes in 
terms of 30- and 90-day (a) mortality, (b) major complications, (c) length of hospital stay, (d) 
health-related quality of life, (e) quality of surgical care, and (f) change in level of independent 
living. 
 
 
* Provide a summary of the background of the study and explain how this research will 
contribute to existing knowledge. Describe previous studies that provides a basis to 
show that the proposed research can be carried out without undue risk to human 
subjects. 
A.1. What is frailty? Although frailty can be defined in many ways, an international panel of 
experts convened in 2011 agreed that it is a multidimensional construct consisting of 6 domains 
(physical performance, gait speed, mobility, nutritional status, mental health and cognition) that 
together indicate increased risk of death, disability and institutionalization.30 Frailty goes beyond 
organ-specific comorbidities to characterize a broader state of global health that extends to both 
physical and cognitive attributes.31-34 Frailty increases with age, but the elderly are not necessarily 
frail, and the young are not necessarily robust. As such, frailty can be conceptualized as a 
measure of “physiologic reserve,” defined as the critical threshold at which external stressors 
overwhelm the human body’s multiple mechanisms for adaptation, resulting in decompensation 
(i.e., acute illness or injury).1 Frailty is the consequence of a process whereby small deficits 
accumulate in multiple adaptive systems, any one of which might be clinically insignificant, but 
together they produce significant vulnerability to stress that can lead to catastrophic 
decompensation. Thus, a robust 80 year old might survive an operation that a frail 60 year old 
might not. 
A.2. Frailty will increase as the US and Veteran populations age, constituting a growing 
vulnerable population. By 2040, the population over age 65 is expected to double and continue 
expanding thereafter.35 Many aging Veterans will develop decreased physical and cognitive 
capacities,36-38 making them vulnerable to impaired decision making,39 loss of independence,40 
polypharmacy41 and elder abuse.42 The VA’s Strategic Plan for 2014-2020 recognizes that 
“geriatric care will continue to be a significant portion of VA’s health care,”43 and the VA Office of 
Geriatrics and Extended Care includes treatment of the frail in its mandate.44 

 
 
A.3. Frail Veterans frequently undergo major surgery with dramatically increased 
morbidity and mortality. Some form of frailty is present in half of all Veterans undergoing 
colorectal and cardiac surgery,5 and one third of the US population is expected to undergo a major 
surgical procedure within the last year of life.45 Some frail patients clearly benefit from surgery 
through improved symptom management and extended life. However, the high rate of surgical 
morbidity and mortality among the frail suggests that for many, surgery confers significant 
burdens for patients, families, and society at large.4-9 For example, compared to robust patients, 
frail surgical patients are less likely to be discharged to home,8 more likely to be readmitted within 
30 days,5,9 and have substantially increased rates of perioperative mortality and 
complications.4,6,7,9 In fact, our preliminary analysis demonstrates similar patterns across 1,632 
major abdominal operations performed at VAPHS from 2010 to 2014 where 192 (11.8%) Veterans 
with differing degrees of frailty suffered dramatically increased mortality, morbidity and length of 
stay. Even in the mildly frail, 30-day postoperative mortality was 10 times greater than among the 
robust (4% vs. 0.4%, p<.001), and increased dramatically with increasing frailty. However, little 
is known about how to improve the surgical outcomes of frail patients. 
A.4. A recent expert panel of VA surgeons identified several potential targets for 
improving surgical care of Veterans before, during, and after surgery.46 Targets included 
improved preoperative decision-making, optimized intraoperative anesthetic management, and 
postoperative prevention of frailty-associated complications like delirium. For example, the panel 
hypothesized that if patients and surgeons were accurately informed of frailty-associated risks, 
many would choose less invasive procedures or even non-surgical therapies, thereby avoiding 
predictable complications. In fact, our previous work provides preliminary support for this 
hypothesis: In one of the only prospective attempts to improve the surgical care of the frail, we 
demonstrated that pre-operative, palliative care consultation ordered by a surgeon to inform and 
clarify surgical decision-making was associated with a markedly reduced odds of dying, even after 
controlling for age, frailty, and whether or not Veterans had surgery (OR=0.27; 95% CI 
0.11-0.68, p=.006).47 Some of these Veterans opted out of surgery, but most proceeded to the 
operating room, thus demonstrating the critically important need to identify effective strategies for 
mitigating frailty-associated risks of those choosing surgery. 
A.5. Prehabilitation is a promising, yet largely untested, strategy for mitigating surgical 
risk. The concept of prehabilitation before surgery is rooted in the demonstrated success of 
cardiac rehabilitation to advance activity, modify cardiac risk factors, and foster healthful lifestyles 
after surgery through a standardized, structured, exercise-educational-behavioral strategy.10 The 
orientation of cardiac rehabilitation to surgical recovery evolved from its original function to first 
mobilize and then advance activity for patients who had survived what was usually a devastating 
myocardial infarction and/or who had undergone what was usually a severely debilitating coronary 
artery bypass procedure.48 As demonstrated by several systematic reviews, similar strategies have 
proven successful not only for cardiac surgery,10 but also for orthopedic,11,13 lung,14,49 and 
abdominal surgery.12 However, rather than waiting until after the surgery to initiate these proven 
strategies, there is growing interest in deploying similar exercise-educational-behavioral strategies 
before surgery to mitigate perioperative risks by increasing patients’ capacity to respond to 
intraoperative stress and accelerate postoperative recovery.12,19,50 Several cohort and small 
randomized controlled trials (RCTs) have explored the feasibility and impact of prehabilitation for 
cardiac, orthopedic, and major abdominal operations.16-18,20,21 However, these studies focused on 
relatively high-functioning patients, and thus both the feasibility and effectiveness of 
prehabilitation among specifically frail populations remains uncertain. 

 
 
A.6. Prehabilitation is most promising among the frail. Although prehabilitation may benefit 
everyone, frail patients likely have the most to gain because they have the greatest deficits in 
physiologic reserve, and thus even modest improvements in strength, balance, and nutrition may 
prevent the physiologic decompensation that leads to poor outcomes.51,52 However, it remains 
unclear if frail patients can fully comply with intensive physical therapy (PT), and even if they do, 
it is not clear if they will build strength, muscle mass, aerobic capacity, and nutrition 
demonstrated in more robust populations.53 A recent review demonstrates preliminary feasibility, 
safety and effectiveness of PT programs focused on frail populations,54 but because the most 
effective interventions lasted ≥5 months, it remains uncertain if clinically significant benefits can 
be achieved in the 4-6 weeks that typically elapse between diagnosis and surgery. To begin 
examining these questions, researchers in Canada are conducting a multi-site RCT of 
prehabilitation for cardiac surgery.55 However, further research is needed to demonstrate the 
feasibility and effectiveness of frailty-focused prehabilitation in the non-cardiac surgery that 
accounts for the majority of surgery conducted in US Veteran populations. 
A.7. We therefore developed a multifaceted prehabilitation intervention for frail patients 
scheduled for major abdominal surgery. We will leverage the existing standard of care at 
VAPHS through which all patients scheduled for surgery are routinely evaluated for frailty as part 
of a standard preoperative risk assessment (but not risk mitigation). For those identified as frail, 
we will offer prehabilitation focused on increasing physiological reserve through (a) strength and 
balance training to support the improved outcomes associated with early mobilization after 
abdominal surgery,56 (b) inspiratory muscle training to reduce postoperative pulmonary 
complications57 and (c) nutritional coaching and supplementation to enhance physical 
performance58 and wound healing.59 We will also arrange occupational and physical therapy 
consults to identify and supply needed durable medical equipment. 
A.8. Conceptual model for prehabilitation. Our approach to prehabilitation is informed by a 
conceptual model adapted from Hoogeboom and colleagues12 to illustrate how prehabilitation 
might improve postoperative outcomes by increasing physiological reserve at the time of surgery. 
As indicated by the solid lines, the decreased physiological reserves of frailty limit capacity to 
adapt to the stress of surgery, leading to worse outcomes. Prehabilitation aims to increase 
physiological reserve at the time of surgery by increasing physical and pulmonary function along 
with improved nutrition, thereby increasing adaptive capacity and improving outcomes including 
decreased mortality, complications length of stay and improved quality of life. 
PRELIMINARY STUDIES 
B.1. Our interdisciplinary research team has the expertise to accomplish this study. Dr. 
Hall is a general surgeon and former recipient of an HSR&D Career Development Award focused on 
improving the process of surgical informed consent. In 2014, he began collaborating with Dr. 
Johanning (Co-I) to validate the Risk Analysis Index (RAI) of frailty used in this study (B.2). He is 
a consultant on several quality improvement (QI) projects related to surgical frailty at the Omaha, 
Atlanta, Nashville and Pittsburgh VAMCs and the University of Pittsburgh. Dr. Forman is a 
geriatrician and cardiologist who directs the VAPHS Cardiac Rehabilitation Center. He has 
extensive experience with exercise physiology trials (B.3), including an ongoing RR&D I01 
(F0834-R) aimed at understanding the effects of different types of exercise training on the 
functional capacity of heart failure patients. Dr. Johanning is a vascular surgeon and health system 
administrator with geriatric training who implemented the Frailty Screening Initiative at the 
Omaha VAMC (B.4), collaborated with Dr. Hall to validate the RAI, and serves as a consultant with 
similar initiatives at several VA and non-VA centers. Dr. Wilson, the Chief of Surgery at VAPHS, 
has expertise in surgical QI. With Dr. Hall, he implemented procedures at VAPHS to systematically 

 
 
screen all preoperative patients for frailty, and will work closely with the team to implement the 
prehabilitation procedures proposed here. Dr. Cahalin brings key expertise as a leader in the field 
of inspiratory muscle training (IMT),60-65 having developed a convenient and effect regimen for 
IMT (B.5). He is collaborating on Dr. Forman’s RR&D I01 (B.3), and he will guide the IMT 
component of the present study. 
B.2. Development, validation, and implementation of the Risk Analysis Index (RAI) of 
frailty. None of the existing tools for measuring frailty have proved suitable for widespread, 
prospective clinical screening. To fill this gap, Drs. Hall and Johanning developed, validated and 
refined the RAI that can be calculated retrospectively from VA Surgical Quality Improvement 
Program (VASQIP) data or prospectively from a 2-minute 14-item survey. Both versions of the RAI 
yield a continuous score that captures a full range of frailty from robust (0-15) to mild (16-25), 
moderate (26-35) and severe frailty (≥36). From July 2011 to September 2015, they used the 14- 
item survey to assess frailty in a consecutive cohort of 6,905 patients scheduled for surgery at the 
Omaha VAMC. In this cohort, the RAI has strong predictive power for 6-month mortality 
(c-statistic=0.772).66 At a cutoff of ≥16, the RAI survey classified 12.5% of the cohort as frail with 
a sensitivity of 0.50 and specificity of 0.90. By linking this cohort to VASQIP data, they compared 
the RAI to the previously validated, retrospectively calculated modified Frailty Index (mFI)67 in a 
sub-sample of 1,024 patients where the RAI survey (c=.797) performed on par with the mFI 
(c=.811), thus establishing preliminary convergent validity with the advantage of prospective 
assessment that can inform real-time clinical decisions. Based on these data, the RAI 
questionnaire was implemented as standard of care for pre-surgical risk stratification at the 
Omaha, Pittsburgh, Atlanta, Nashville and Phoenix VAMCs. 
B.3. Effective implementation of exercise training programs in frail heart failure patients 
and recruiting subjects into training trials. Dr. Forman was Site PI for both the NHLBI aerobic 
training trial HF-ACTION68 and the NCCAM Tai Chi Mind-Body Movement Therapy for Patients with 
Chronic Heart Failure.69 He is skilled in the prehabilitation techniques planned for this 
investigation, reliably achieving both training effects and endpoints. For example, in a trial of older 
female patients, those randomized to a strength training program similar to that proposed here 
had significantly increased strength (43.4±8.8% vs.-1.7± 2.8% in controls, p= 0.001) and 
endurance (299±66% vs. 1±3%, p= 0.001).70 Dr. Forman’s RR&D I01 is currently randomizing 
200 heart failure patients to regimens similar to those proposed here that focus on strength 
training and IMT. 
B.4. The Omaha Frailty Screening Initiative (FSI) is the first feasible and effective 
facility-level intervention to improve postoperative survival among frail Veterans. While 
Chief of Surgery at the Omaha VA, Dr. Johanning began using the RAI to screen pre-surgical 
patients for frailty. Those identified as frail were subjected to an administrative review aimed at 
clarifying surgical decision-making through informal discussions with surgeons, anesthesiologists 
and palliative care physicians focused on each patient’s frailty and frailty-associated risk.47,71-73 By 
comparing outcomes after FSI implementation to historical controls, he and Dr. Hall found that 
180-day survival among frail patients improved 7-fold after implementing the FSI (OR 7.50, 95% 
CI 4.08-13.79), reflecting a drop in 180-day mortality from 23.9% to 4.5% (p<.001).74 
B.5. IMT improves pulmonary function in as little as 2 weeks. Dr. Cahalin’s study of IMT in 
advanced heart failure patients found that dyspnea symptoms improved when maximal inspiratory 
pressure increased 24% (51±21 to 63±23 cm H20, p=.0001) only 2 weeks after initiating an IMT 
regimen that was far more convenient and efficient than others which had been studied at that 
time.62 A subsequent study also in heart failure patients showed that IMT significantly improved 

 
 
 
 
gait speed and quality of life.63 This experience informs both the methods presented here, as well 
those of Dr. Forman’s RR&D I01. 
 
 
* Describe the overall significance of the research in terms of the problem to be studied 
and potential findings, as well as its relevance to the care of veterans, the VAPHS, and 
the VHA: 
C.1. The proposed research has potentially high impact because it addresses the needs 
of as many as 42,000 frail Veterans scheduled for major elective surgery each year.29 
These patients experience disproportionately poor outcomes and accrue markedly higher costs, 
thus representing a highly significant opportunity to improve the processes of surgical care 
through prehabilitation strategies to yield a practical, preventative strategy for improving both 
quality and quantity of life for vulnerable, frail Veterans. 
C.2. Prehabilitation for the frail is innovative because it shifts established rehabilitation 
strategies to the preoperative period and focuses those strategies on the frail Veterans 
most likely to benefit. As such, it addresses a critical gap in the science of frailty research, and 
does so with a focused strategy to direct preventative resources to the limited population at 
greatest risk and thus most likely to benefit. 
C.3. The proposed research is directly aligned with VA’s operational imperatives. Our 
study “advances healthcare innovation” (Theme 3 of the VA’s Strategic Plan75) by developing an 
innovative, preventative healthcare intervention that “anticipates and meets the unique needs of… 
[the] most vulnerable Veterans” (Blueprint Strategy 1). It also aligns with HSR&D Priority Areas A 
(access for vulnerable Veteran populations) and B (health equity) along with the Office of 
Geriatrics and Extended Care Service’s focus on “optimizing the health and well-being of Veterans 
with multiple chronic conditions, life-limiting illness…and frailty.”44 Letters of support demonstrate 
that Assistant Deputy Under Secretary of Health for Clinical Operations and Management, Dr. 
Thomas Lynch, as well as the Director of Geriatrics and Extended Care Operations, Dr. Thomas 
Edes, are enthusiastic partners in the proposed research and are prepared to use study findings to 
guide future, system-wide initiatives to improve the quality of patient-centered surgical care 
throughout VHA. There is also significant interest from CMS Deputy Chief Medical Officer, Dr. Shari 
Ling, indicating that the VA can again lead the nation in developing high-value medical care. 
 
 
Research study methods 
Research Study Methods 
 
Describe all study related procedures following enrollment of a subject in this study. 
 
 
* Research Procedures/Interventions: 
D.1. Overview. We will conduct a randomized pilot study of a prehabilitation intervention in a 
consecutive sample of up to 50 frail patients scheduled for elective major abdominal surgery at 
the VAPHS. Participants will be recruited from the mandatory preoperative IMPACT clinic where 
all patients are routinely screened for frailty. Frail patients agreeing to participate will be 
randomized 1:1 to (a) standard preoperative optimization by the IMPACT clinic or (b) 
prehabilitation + standard IMPACT optimization. The prehabilitation intervention will deploy 
existing cardiac rehabilitation resources to provide (a) strength and balance training, (b) 
respiratory muscle training, and (c) nutritional coaching and supplementation. Using physical 
performance tests, biomarkers, chart review, survey instruments, and patient logs, we will 
assess the feasibility of the recruitment, randomization, retention and assessment procedures, 
compensating patients for their time. 
D.4. Eligibility criteria. We will include all patients with RAI>16 scheduled for major 
abdominal surgery on the general or urological surgery services. Major surgery is defined 
according to VASQIP criteria to include cases requiring general, epidural, or spinal anesthesia. 

 
 
 
 
For general and urological surgery, it includes 270 standard, 356 intermediate, and 34 complex 
procedures, but excludes 291 low risk, “minor” surgical procedures with limited morbidity (e.g., 
abscess drainage, lipomas, or hemorrhoids). From these major surgeries, we will include those 
abdominal procedures that deliberately violate the peritoneal or retroperitoneal spaces. For 
example, from the general surgery service we will include all bowel resections, biliary 
procedures, and abdominal wall reconstructions, but exclude open, anterior inguinal hernia 
repair. The list of included CPT codes (see Appendix) represents 56% and 35% of the general 
and urological surgery volume at VAPHS, respectively (Table 2 below). Given the burden of 
comorbidity among the frail, we anticipate that many eligible Veterans will have concurrent 
cognitive impairment or dependent living situations. These limitations need not preclude 
inclusion so long as the patient can provide first-person informed consent and participate in the 
prehabilitation regimen described below (D.6). No other exclusions are planned. 
D.5. Randomization procedures and their rationale. Some patients may be reluctant to 
accept the possibility of randomization to control conditions, and if so, recruitment rates of a 
randomized trial would be diminished. We will therefore use the randomization feature in 
REDCap to randomize participants in a 1:1 ratio. As each patient enrolls, REDCap will assign 
the patient to intervention or control conditions as specified by a fixed allocation table. If 
patients refuse participation based on the risk of randomization, we will note this fact, but offer 
the opportunity to participate in the preferred arm (intervention or control). This approach will 
permit accurate estimates of randomization while accruing the largest possible sample size. 
D.6. Prehabilitation Procedures. 
(a) Overview. Prehabilitation will include hospital- and home-based components within 
an integrated intervention led by Dr. Forman. The hospital-based component will occur 
at the VAPHS Cardiac Rehabilitation facility and focus on supervised strength and 
balance training. One-hour sessions will be scheduled twice weekly for at least 4, but no 
more than 6 weeks before the operation. The home-based component will entail walking 
or seated pedaling on a home exerciser, as well as Respiratory Muscle Training (RMT), 
both of which are feasible and safe to do in a non-supervised setting. Nutritional 
supplementation will be linked to the composite training protocol. Compliance will be 
measured with exercise log books (See Appendix) and pedometers given to each 
participant. With the consent of the surgeon, operative dates will be scheduled to 
accommodate prehabilitation. 
(b) Hospital-based Training will be scheduled twice weekly and include strength and 
balance training. All sessions will begin with an assessment of the subject’s vital signs and a 
review of their progress with home-based training. Based on evaluation of the exercise log 
books and pedometer data, the exercise physiologist will reinforce the goals and techniques of 
the home-based regimen as needed. After the assessment phase, subjects will complete 5 
minutes of warm-up with low-intensity walking or seated pedaling. Seated pedaling can be 
used to exercise the upper extremities in cases of lower extremity disability. Mode of exercise 
will depend on patient preference and safety, but the same mode of exercise will be used in 
both the hospital- and home-based regimens (see below). Subjects will then complete 10 
minutes of balance training tailored to each subject’s capacities and progressing as tolerated. 
Regimens will uniformly include elements of static, tandem and one-foot stands, weight shifts, 
side steps, crossovers, grape vines, backward walking, and stepping over objects. Balance 
training will be coupled with an additional 10 minutes of transitional movement training to 
enable and strengthen the proper form of movements required after surgery such as lying-to- 
sitting and sitting-to-standing. Next, subjects will complete 25 minutes of strength training (2 
sets with 8-12 repetitions) focused on a spectrum of antagonist muscles for the core abdominal 
muscles impacted by surgery, including hip flexors and extensors, obliques, rhomboids, erectus 
spinous, and latissimus dorsi. In addition, to optimize mobility and daily function, we will target 
other muscle groups in the legs, arms, and hands (quads, hamstrings, calf, biceps, triceps, and 
hand groups). The hospital-based session will finish with full body stretching and reassessment 
of vital signs. During each session, the exercise physiologist will use a log book (Appendix) to 

 
 
 
 
record completion of each component along with details about the duration and intensity of the 
aerobic training, balance, and weight training. Regimens such as this have been shown to be 
both safe and effective among the frail elderly,76 and the improvements in strength and 
balance will likely facilitate early mobilization after surgery—an intervention shown to improve 
outcomes after surgery.56 
(c) Home-based Training: Patients will be coached to complete home-based training at least 
2-3 days a week and more as tolerated. Exercise will start with a 5 minute warm-up (i.e., slow 
paced walking or seated pedaling, consistent with the mode of exercise used in the hospital). 
The same exercise modality will then extend for an additional 30 minute aerobic training 
session. This phase will entail efforts at a comfortable speed with increasing duration. We will 
coach patients to reach 30 minutes of continuous, moderate exertion of 11-13 on the Borg 
Rating of Perceived Exertion (RPE) scale,77 but it is expected that initially many subjects may 
only tolerate shorter intervals. In that case, 5-10 minute intervals of less intense (slower) 
walking or pedaling may then be combined with periods of rest, with the goal of repeating and 
elongating them as tolerated until 30 continuous minutes are achieved. If/when 30 minutes of 
continuous exercise is achieved (at RPE 11-13), the next step will be to progress the intensity 
(speed) with short periods of relatively greater speed (RPE 13-15) for 1-2 minutes, and 
alternate with slower intensity (speed) at RPE 11-13. Patients will record the duration and 
exertion of training in their log books along with step counts from their pedometer affixed to 
either the patient’s waist (walking) or wrist/ankle (pedaling). Family members or other 
caregivers can assist patients in completing the log books if needed. After aerobic activity, 
home-based exercise will continue with 30 minutes of progressive RMT using a Threshold RMT 
device (RespironicsTM). Threshold RMT requires that subjects inspire and exhale through a 
mouthpiece at a comfortable rate using diaphragmatic breathing techniques. The Threshold 
IMT device prohibits the subject from inhaling or exhaling until a set negative pressure is 
achieved and overcome. This is accomplished through the use of weighted plungers or spring-
loaded valves. It is inexpensive, convenient, and easy to administer at home. We will set each 
patient’s threshold to 40% of maximal inspiratory and expiratory pressures (MIP & 
MEP) as measured by the Test of Incremental Respiratory Endurance (TIRE)60 device, a 
breathing assessment tool that links a pneumotachometer to a computer tablet and can be 
used gauge inspiratory pressures. MIP & MEP are the peak pressures generated by respiratory 
muscles when patients forcibly inhale or exhale against resistance. It is analogous to a 
maximum weight lifted in the gym but measures the strength of the diaphragm and accessory 
breathing muscles. MIP & MEP will be defined as the average of 3 assessment breaths on a 
TIRE device. MIP & MEP will be measured at the first hospital-based session and bi-weekly 
thereafter, adjusting the Threshold RMT device to maintain a workload at 40% of MIP & MEP as 
respiratory muscle conditioning improves. Patients will again record the threshold and number 
of breaths completed in the 30-minute session in log books. Family members or other 
caregivers can assist patients in completing the log books if needed. Regimens such as this 
have been shown to increase MIP (15 cm H20, 95% CI 9-21) and halve the risk of 
postoperative pulmonary complications following abdominal surgery (relative risk 0.48, 95% CI 
0.26 to 0.8).78 
(d) Nutritional Counseling. Malnutrition at hospital admission increases length of stay,79 and 
nutritional supplementation has been shown to enhance both wound healing59 and exercise- 
induced improvements in physical performance.58 Based on patient preference and 
convenience, we will arrange for a standard consult with VAPHS Nutrition Services to coincide 
either with the initial IMPACT clinic visit or the first scheduled visit to the Cardiac Rehabilitation 
facility. Staff nutritionists (see letter) will administer the standardized Subjective Global 
Assessment (SGA) of nutrition (Appendix) to identify nutritional needs and classify the patient 
as either normal or mildly, moderately or severely malnourished. All patients will receive best 
practice nutritional counseling focused on lean, high protein foods in preparation for surgery. 

 
 
 
 
Cardiac rehabilitation personnel will be trained to assess and reinforce progress on these 
dietary practices. In addition, standard of care nutritional supplementation will be prescribed to 
malnourished patients, including Impact® Advanced Recovery, an immunomodulating formula 
shown to improve outcomes after major surgery.80 Supplements will be delivered to patient’s 
homes. Patients will also record their meals and supplements in log books (Appendix), and 
cardiac rehab personnel will be trained to monitor and encourage consumption of the 
supplements as prescribed during the hospital-based coaching sessions. Family members or 
other caregivers can assist patients in completing the log books if needed. Although the 
evidence is somewhat equivocal, approaches such as this have been shown to reduce 
postoperative complications (relative risk 0.67, 95% CI 0.53-0.84).81 
(e) Occupational and Physical Therapy (OT/PT). We will arrange for a standard OT/PT 
consult to coincide with either the initial IMPACT clinic visit or the first scheduled visit to the 
Cardiac Rehabilitation facility. Staff therapists (see letter) will perform routine, standardized 
assessments of the patient’s home, environment and mobility, prescribing and supplying 
indicated durable medical equipment to aid mobility, exercise, and safe transition to 
independent living at home after the proposed surgery. As per their usual protocol, the PT/OT 
consult will consult with the Social Work services to adequately assess the home environment 
and supports in anticipation of postoperative discharge planning. 
D.7. Assessment Schedule. As shown in Table 1, research staff will collect baseline data at 
the time of recruitment regarding demographics, physical performance, and nutrition. We will 
monitor physical performance, nutrition and compliance every other week during in-hospital 
prehabilitation and on the day of surgery. Postoperative outcomes will be assessed 30 or 90 
days after the surgery. Patient Survey Instruments will be administered either face to face, by 
telephone or by mail, depending on patient preference. Responses will be entered directly into 
REDCap using a project utility distinct from the RAI measurement tool. For patients electing 
surveys by mail, we will send printed copies of the Redcap forms with a self-addressed, 
stamped envelope for return. Responses on returned surveys will be keyed into Redcap before 
storing the paper surveys in locked cabinets. Instruments assessing living location, quality of 
life, quality of surgical care, and decision quality are described in D.8. and in the Appendix. 
Chart reviews will be completed by the research assistant to determine details of the surgical 
procedure, including postoperative mortality, length of stay, and major complications. Physical 
Performance Tests will be administered by the exercise physiologist in the Cardiac 
Rehabilitation facility, located near the IMPACT clinic, and thus convenient for patients to visit 
on both the days of recruitment and surgery. Nutrition assessments include serum prealbumin 
and Body Mass Index (BMI) collected biweekly by hospital phlebotomists, and the 7-point 
Subjective Global Assessment (SGA-7)28 administered by hospital nutritionists at baseline and 
again on the day of surgery. Patient Logs will assess patient compliance with the home-based 
prehabilitation regimen and document progress with aerobic training, IMT and nutritional 
supplementation. They will be collected weekly and on the day of surgery. Those randomized 
to control conditions will not complete the patient logs or the weekly in-hospital assessments, 
but they will complete all other assessments. 
 
Assessments will end after the assessment planned for 90 days after the surgery. Ideally, 
patients will return to the hospital for this final visit to conduct measures of physical 
performance and nutrition along with the survey instruments. However, if they are unable to 
make the visit, we will conduct the surveys over the phone. 
 
Table 1: Assessment Schedule 

 
 
 
 
Baseline 
Every other 
Week 
In-hospital 
Day of 
surgery 
30 Days 
post-op 
90 Days 
post-op 
Demographics 
Age, sex, race, ethnicity, etc 
X 
Procedure-related variables 
X 
X 
Living Location 
X 
X 
X 
X 
Physical Performance 
SPPB 
X 
X 
X 
x 
MIP & MEP 
X 
X 
X 
x 
6 Minute Walk Test 
X 
X 
X 
X 
Frailty (multiple measures) 
X 
X 
X 
x 
 
Nutrition 
Prealbumin (biweekly) 
X 
X 
X 
x 
BMI 
X 
X 
X 
x 
Subjective Global 
Assessment 
X 
X 
x 
Compliance 
Patient Logs 
X 
X 
Outcomes 
Mortality 
X 
X 
Length of Stay 
X 
Major Complications (30 day) 
X 
Quality of Life 
X 
X 
X 
Quality of Surgical Care (Pre) 
X 
Quality of Surgical Care 
(Post) 
X 
Measures of Decision Quality 
x 
x 
X 
x 
 
 
 
Minimizing the Burden of Assessments: Some participants in this study will be concurrently 
enrolled in a related study of frailty and preoperative palliative care consultation 
(Pro1840). Some of the outcome assessments planned for Pro1754 are identical to those 
planned here. When a participant is enrolled in both studies (Pro1840 and Pro1754) the study 

 
 
 
 
coordinators will work together to ensure that participants do not have to complete identical 
assessments twice. At any given time point when potentially duplicative assessments could 
occur, study staff will record the participant's singular response to a duplicative question 
simultaneously into the case report forms (CRFs) of each separate study. This could be 
accomplished by having a two separate study staff on the phone or in the room as the patient 
is interviewed. It could also be accomplished by having a single cross-listed staff member 
(e.g., listed on the staff form of both studies) administer the assessment and record the 
responses into the separate CRFs of each study at the same sitting. Additionally, some 
participants may be concurrently enrolled in a minimal risk study (PI James Ibinson MD; 
Pro1843) that has similar inclusion criteria. However, participation in Pro1843 will not impact 
the outcomes of this protocol (1754). 
D.8. Variables Assessed. 
 
▪ Age, sex, race, ethnicity and socioeconomic status will be assessed by direct patient 
survey or chart review. 
▪ Procedure-related variables will include the CPT codes of the initially planned 
operation as well as the operation actually performed. We will also abstract from the 
chart the type of anesthesia, the duration of the procedure, and the disposition of the 
patient at the end of surgery (e.g., discharge v. admission) 
▪ Living Location is the environment where patients are living before and after the index 
operation (i.e., home, nursing home, etc). It will be assessed by direct patient survey or 
chart review and followed as an outcome. 
▪ Short Physical Performance Battery (SPPB) is a test of balance, gait, strength, and 
endurance that combines gait speed, repeated chair stands and balance tests that 
together take less than 5 minutes to complete. Each of the 3 tests are scored on a scale 
from 0-4 with a combined score ranging from 0-12 with lower scores indicating worse 
performance.26 Scores below 8 or 10 are interpreted as poor performance.82 The SPPB 
accurately predicts adverse outcomes such as disability, hospitalization, nursing home 
admission, frailty and mortality, and is becoming the reference standard in rehabilitation 
literature.82-86 
▪ 6 Minute Walk Test is a standard measure of physical performance that measures the 
total distance traversed in 6 minutes, measured in meters. Clinically significant 
differences can be quantified in as little as 30 meters. This is an exploratory measure 
that will only be administered if time allows. As a pilot study, we aim to determine what 
kinds of assessments are feasible in this group. 
▪ Maximal Inspiratory & Expiratory Pressures (MIP & MEP) are the standard metrics of 
respiratory muscle strength27 and will be measured using the TIRE device described 
above (D.6c). It has been shown that changes as small as 15 cm H20 can significantly 
reduce postoperative pulmonary complications and length of stay.78 
▪ Frailty will be assessed through several measures because no single measure of frailty 
captures the breadth of the syndrome. In addition to the RAI described above, we will 
quantify the Hopkins & Edmonton Frail Scales and independently analyze the gait speed 
and handgrip strength that is part of the Hopkins Frail Scale. We recently developed a 
streamlined approach to measuring all of these metrics simultaneously in a parsimonious 
exercise that takes <5 minutes to administer.87 
▪ Hopkins Frail Scale encompasses slowness, weakness, weight loss, low physical 
activity, and exhaustion with ≥3/5 criteria required to distinguish frailty.31,32 It is 
the most frequently cited tool shown to predict mortality and disability in large 
cohorts of community-dwelling elders and surgical patients. 
▪ Edmonton Frail Scale is an 11-item survey that assesses 8 dimensions of frailty. 
Each item is scored 0, 1, or 2 with higher scores indicating greater frailty. The 
total score ranges from 0-17 with good inter-rater reliability (k = 0.77), moderate 
internal consistency (alpha=0.62), and strong correlation with a geriatrician’s 
assessment of frailty (r=.64, p<.001).88 
▪ Gait speed is one key measure of frailty76,97,98 that has excellent inter-rater 
reliability (intraclass coefficient 0.88-0.96) and test-retest reliability (intraclass 
coefficient 0.86-0.91). 
▪ Handgrip Strength has also been demonstrated to have key utility as an index of 
frailty.32,89 A grip dynamometer will be used, averaging 2 serial assessments from 
the dominant hand. 
▪ Prealbumin will be measured with standard serological testing. Changes can be detected 
in days, and it is the best available biomarker of nutrition.90,91 However, because 

 
 
 
 
prealbumin can function as an acute phase reactant, we will also concurrently measure 
c-reactive protein as a measure of inflammation and interpret prealbumin as proposed 
by Jensen, et al.92,93 
▪ Body Mass Index (BMI) will be calculated from height and weight assessed each week at 
the Cardiac Rehab facility, and is considered the most suitable, objective anthropometric 
indicator of nutritional status,94 and changes in BMI have been shown to predict survival 
in the elderly.95 
▪ Subjective Global Assessment of Nutrition (SGA) is the standard approach to nutritional 
assessment.96 It evaluates multiple domains of nutrition and reliably categorizes patients 
into 1 of 4 categories: normal, mild-, moderate- and severely malnourished. We will use 
the 7-point SGA (See Appendix) because it is sensitive to 1-point changes in as little as 
1 month and has excellent inter-rater reliability (k=.726).28 
▪ Compliance with Prehabilitation. Each patient will receive a prehabilitation log book in 
which they will record details about their home-based regimen, including the date of 
training, duration and intensity of exercise, IMT repetitions and threshold pressures, 
nutritional supplements consumed, dietary intake, and pedometer data (e.g., step 
counts at the beginning and end of each training session). They will be coached in the 
use of this log at each hospital session. Data from the logbook will be collected from 
patients weekly and entered into the database for analysis. In addition, because the 
pedometer stores 7 days of data, and the exercise physiologists will record daily step 
counts as a measure of overall activity at each hospital session. 
▪ Health-Related Quality of Life will be measured with the Assessment of Quality of Life 
(AQoL-6D) that includes 20 items on a Guttman scale assessing 6 domains: independent 
living, mental health, relationships, senses, pain and coping.97 The utility score ranges 
from -.04 (state worse than death) to 1.0 (full health). It is sensitive to change with a 
minimum clinically important difference (MCID) of 0.06.98 
▪ Quality of Surgical Care will be measured with the Surgical Care Survey (SCS) that 
includes subscales for quality of pre-surgical care (11 items), day of surgery (6 items), 
and postoperative care (12 items).99 
▪ Measures of Decision Quality include Decision Regret (5 items), Patient Centeredness of 
Care (12 items), Satisfaction with the Process of Decision Making (14 items), 
Satisfaction with the IMPACT clinic (8 items), Satisfaction with the frailty diagnosis (8 
items), satisfaction with the palliative care consult (8 items), and Satisfaction with the 
surgeon (8 items). 
▪ Mortality. Patients completing the 30- and 90-day surveys will be confirmed alive. For all 
others, chart review including telephone contact with identified surrogates will confirm 
vital status and date of death (if deceased). 
▪ Length of Stay will be calculated from the date of surgery to the date of discharge or 
transfer from the hospital. We will also record the time spent in the intensive care unit. 
Intervals will be calculated in days. 
▪ Major Complications will be abstracted from the chart according to VASQIP coding rules 
(Appendix). The presence or absence of each complication will be recorded separately, 
but analysis will focus on a dichotomous outcome indicating the occurrence of serious, 
Clavien-Dindo level IV complications.100 These include deep wound infections, organ 
space infections, wound disruption, pneumonia, unplanned intubation, pulmonary 
embolism, mechanical ventilation for >48 hours, progressive renal insufficiency, acute 
renal failure, stroke, coma, cardiac arrest, myocardial infarction, bleeding in excess of 4 
units, deep vein thrombosis, sepsis and C. difficile colitis. This approach to analyzing 
complications has been shown to correlate with frailty.6 Co-I and Chief of Surgery Mark 
Wilson (see letter) has authorized the VASQIP nurse abstractor to use standard VASQIP 
procedures to code the charts of participating patients. 
 
Incidental Findings: If any of these tests generate an incidental finding of sufficient clinical 
significance to warrant review by the patient's primary care physician (PCP), we send the test 
results to the PCP and follow up with an encrypted email. We will also telephone the patient 
within a week to inform the patient of the finding and the planned PCP follow-up. 
 
 
 
 
Research study methods: analysis Plan 
 
* Please describe the analysis plan for the study (it is acceptable to refer to the 

 
 
 
 
sponsor/multi-site protocol for section if applicable): 
D.10. Data Analysis. 
(a) General approach for quantitative data. We will first explore the data using descriptive 
statistics (e.g., means, standard deviations, percentiles, ranges) and graphical techniques 
(e.g., histograms, scatter plots) to examine key variables to assess distributional assumptions, 
the existence of outliers and data sparseness. For categorical variables, we will generate 
frequency and percentage distributions to identify data sparseness. In the event of data 
sparseness, categories with small frequencies will be merged when meaningful and 
appropriate. Continuous variables will be categorized into meaningful groups if the distributions 
are skewed. All analyses will be performed using Stata statistical software (StataCorp, 2013). 
(b) Missing Data Strategies. We will attempt to minimize the amount of missing due to 
dropouts (withdrawals, lost to follow-up, or deaths) or individuals who missed at least one of 
the follow-up assessments (intermittent missing). In the event of missing data, we will use 
multiple imputation to impute the missing values. 
(c) Estimate rates of recruitment, randomization, retention, and compliance with the 
prehabilitation intervention [Aim 1]. To assess the feasibility of recruitment, 
randomization, and retention, we will summarize the total number of eligible patients 
approached, recruited, randomized to intervention and control conditions, and retained through 
the completion of study procedures 90 days postoperatively, estimating rates as well as 
associated confidence intervals.25 For those lost to follow up, we will estimate the proportion of 
planned in-hospital prehabilitation sessions completed before dropping out along with rates of 
30-day outcome assessment (if available). For those randomized to the intervention condition, 
compliance with the hospital-based regimen will be measured as the number of scheduled 
sessions completed. If patients are able to comply with only a portion of the training regimen, 
this will be noted and the patient will be categorized as partially compliant. Compliance with 
the home-based regimen will be measured as the number of assigned activities documented in 
the patient logs. Overall compliance rates with confidence intervals (CIs) will be estimated for 
the home, hospital, and combined intervention. We will also compute rates (and CIs) of partial 
compliance as well as rates (and CIs) of intervention-specific task compliance. 
(d) Measure (a) physical performance with the SPPB, (b) pulmonary function with 
MIP, and (c) nutrition with the SGA-7 and prealbumin at baseline and 2-week 
intervals to estimate changes over time and explore the optimal duration of 
prehabilitation (2 vs. 4 vs. 6 weeks) [Aim 2]. We will use graphical analyses to assess 
simple change in physical performance, pulmonary function and nutrition over the 
prehabilitation period. We will also use simple mixed models to explore changes over the 
multiple time points (baseline and 2, 4, and 6 weeks). Separate models for each outcome will 
assess the rate of change, including a fixed effect for time and a random effect for subject. The 
type of mixed model used will be dependent on the data type of the outcome with linear mixed 
model for continuous variables (SPPB, MIP, prealbumin, BMI and RAI) and generalized mixed 
models for categorical/ dichotomous (SGA). To the extent possible, the modelling of the rate of 
change in the outcomes over time will include an assessment of the shape of this relationship 
utilizing simple piecewise linear functions to explore any indication of the optimal duration of 
therapy. We anticipate that improvements in the outcome will grow logarithmically over time, 
and that the majority of the growth will be achieved between 3-6 weeks. 
(e) Estimate overall and treatment-specific summary statistics for postoperative 
outcomes in terms of 30- and 90-day (a) mortality, (b) major complications, (c) 
length of hospital stay, (d) health-related quality of life, (e) quality of surgical care, 
and (f) change in level of independent living [Aim 3]. We will summarize separately the 
total number of deaths and major complications at 30 and 90 days for all patients, estimating 
rates (overall and by treatment-group) as well as associated CIs. Rates will be computed as 
the number of specific events (deaths or major complication), divided by the total accrued 

 
 
 
 
person-time where person-time is defined as the amount of time a patient is followed from 
study start to either the end of study, death or loss to follow-up (whichever occurs first). We 
will also compute summary statistics (mean, median, standard deviation, range) for length of 
hospital stay, health-related quality of life, quality of surgical care and recovery to independent 
living. We will make assessments overall and by treatment group. While our emphasis is to 
assess feasibility, we will also attempt to assess if differences exist between the intervention 
and control conditions with regards to these post-operative measures. 
D.11. Justification of Pilot sample size. Based on the historical surgical volume at VAPHS, 
the participating surgical services will treat 54 eligible patients who meet our inclusion criteria 
during a 7 month recruitment window (Table 3). We are not estimating the effect size between 
intervention and control conditions. Although there is a tradition of using pilot studies to do so, 
there is growing consensus that this approach is ill-founded because the small samples result 
in imprecision that makes power estimates unreliable.23 Therefore, based on recruitment and 
retention rates estimated here (Aim 1), we will power our subsequent study based on 
“minimum clinically meaningful differences” defined for each outcome a priori.24 
 
 
Table 3: Sample Size Estimates 
General 
Urology 
Total 
Total Surgical Cases/year 
1488 
610 
2098 
VASQIP Eligible Cases/year 
748 
298 
1046 
Proportion Abdominal 
56.2% 
35.3% 
x̄=50.2% 
Proportion Frail 
12.0% 
10.3% 
x̄=11.5% 
Eligible Cases/year 
70.9 
21.5 
92.4 
Eligible Cases/7 month recruitment 
41.4 
12.5 
53.9 

 
 
 
 
 
 
 
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