comparing the effectiveness of nonsurgical treatments for … · 2019. 2. 26. · 1 comparing the...

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Comparing the Effectiveness of Nonsurgical Treatments for Lumbar Spinal Stenosis in Reducing Pain and Increasing Walking Ability

Michael J. Schneider, DC, PhD1,2, Carlo Ammendolia3, Donald Murphy4,5, Ronald Glick6, Sara Piva1, Elizabeth Hile7, Dana Tudorascu8 , Sally C Morton9

1 Associate Professor, Department of Physical Therapy, University of Pittsburgh, Pittsburgh, Pennsylvania 2 Associate Professor, Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania

3 Assistant Professor, Institute of Health Policy, Management and Evaluation, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada 4 Director of Primary Spine Care Services, Care New England Health System, Providence, Rhode Island 5 Clinical Assistant Professor, Department of Family Medicine, Alpert Medical School of Brown University, Providence, Rhode Island 6 Assistant Professor, Departments of Psychiatry and Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, Pennsylvania 7 Assistant Professor, College of Allied Health, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 8 Assistant Professor, Department of Internal Medicine and Geriatric Psychiatry Neuroimaging Lab, University of Pittsburgh, Pittsburgh, Pennsylvania 9 Dean of Science, Virginia Tech, Blacksburg, Virginia

Original Project Title: A Comparison of Non‐Surgical Treatment Methods for Patients with Lumbar Spinal StenosisPCORI ID: 587 HSRProj ID: 20142228 ClinicalTrials.gov ID: NCT01943435

_______________________________ To cite this document, please use: Schneider M, Ammendolia C, Murphy D,et al. 2019. Comparing the Effectiveness of Nonsurgical Treatments for Lumbar Spinal Stenosis in Reducing Pain and Increasing Walking Ability. Washington, DC: Patient‐Centered Outcomes Research Institute (PCORI). https://doi.org/10.25302/2.2019.CER.587

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Table of Contents

ABBREVIATIONS ..................................................................................................................... 3

ABSTRACT ................................................................................................................................ 4

BACKGROUND ......................................................................................................................... 5

PARTICIPATION OF STAKEHOLDERS IN RESEARCH STUDY DESIGN .......................................... 7

METHODS .............................................................................................................................. 11

Study Design .................................................................................................................................. 11 Sample Size ................................................................................................................................... 11

Inclusion/Exclusion Criteria ........................................................................................................... 12

Recruitment .................................................................................................................................. 13

Randomization .............................................................................................................................. 14

Interventions .................................................................................................................................. 15

Study Outcome Measures ............................................................................................................. 17

Blinding ......................................................................................................................................... 21

Study Setting .................................................................................................................................. 21

Follow-up ...................................................................................................................................... 22

Missing Data .................................................................................................................................. 25

Ancillary Qualitative Study ............................................................................................................ 25

RESULTS ................................................................................................................................ 26

Participant Flow ............................................................................................................................ 26

Baseline Data ................................................................................................................................ 28

Results of Primary Analyses of Primary and Secondary Aims (Linear Mixed Models) ................. 48

Results of Analyses for Exploratory Aim 1 ..................................................................................... 43

Results of Analyses for Exploratory Aim 2 (Heterogeneity of Treatment Effect ........................... 48

Patient Global Index of Change and Satisfaction ........................................................................... 52

DISCUSION ............................................................................................................................ 62

Context for Study Results in Context ............................................................................................. 62

Uptake of Study Results and Generalizability of Findings ............................................................. 66

Subpopulation Considerations ...................................................................................................... 69

Study Limitations .......................................................................................................................... 69

Future Research ............................................................................................................................ 71

CONCLUSION ......................................................................................................................... 72

REFERENCES .......................................................................................................................... 74

APPENDIX ............................................................................................................................. 79

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Abbreviations

LSS Lumbar Spinal Stenosis MC Medical Care GE Group Exercise MTE Manual Therapy and Individualized Exercise SSS Swiss Spinal Stenosis Questionnaire SPWT Self-paced Walking Test ESI Epidural Steroid Injection NASS North American Spine Society UPMC University of Pittsburgh Medical Center PGIC Patient Global Index of Change ABI Ankle Brachial Index PCORI Patient-centered Outcomes Research Institute MET Metabolic Equivalent IMMPACT Initiative on Methods, Measurement and Pain

Assessment in Clinical Trials CI Confidence Interval OR Odds Ratio SAT Patient Satisfaction PCP Primary Care Practitioner OA Osteoarthritis BMI Body Mass Index MCDI Modified Co-morbidity Disease Index TSK Tampa Scale for Kinesiophobia ABC Activities Specific Balance Confidence Scale RAND GH General Health RAND P Pain RAND SF Social Functioning RAND EF Energy/Fatigue RAND EW Emotional Well-being RAND PF Physical Functioning RAND RLE Role Limitations due to Emotional Problems RAND RLP Role Limitations due to Physical Health SW SenseWear FU Follow-up PROMIS Patient Reported Outcomes Measurement

Information System SPPB Short Physical Performance Battery CEQ Credibility/Expectancy Questionnaire MRI Magnetic resonance Imaging CT Computed Tomograph PT Physical Therapy RCT Randomized Clinical Trial

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ABSTRACT Background: Lumbar spinal stenosis (LSS) is a highly prevalent condition among older adults and the

most frequent indication for spinal surgery in patients older than the age of 65. In this past decade the

fastest growth in lumbar surgery in the United States has occurred in older adults with LSS, and the rate

of complex fusion procedures has significantly increased. These operations are associated with

significant health care costs, risks, complications, and rehospitalization rates. Yet, evidence is lacking for

the effectiveness of the various nonsurgical treatment options offered to patients with LSS. This study

was designed to help bridge this evidence gap.

Objective: Compare the clinical effectiveness of 3 common nonsurgical approaches to the

management of patients with LSS: (1) medical care (MC) provided by a physiatrist; (2) nonspecific group

exercise classes (GE) provided by certified exercise instructors; or (3) a combination of manual therapy

and individualized exercises (MTE) provided by chiropractors and physical therapists.

Methods: Randomized controlled clinical trial of 259 patients with LSS. Patients were

community-dwelling older adults (≥ 60 years of age) recruited from the Pittsburgh metro area. We

confirmed diagnosis of LSS by both diagnostic imaging (MRI or CT) and symptoms of neurogenic

claudication. Participants were randomized into 1 of the 3 groups described above and treated for a

total of 6 weeks. Participants in the GE and MTE groups had a total of 12 treatment sessions; those in

the MC group had a total of 3 treatment sessions. The primary outcome measures were self-reported

pain/function measured by the Swiss Spinal Stenosis (SSS) questionnaire and walking performance

measured by the Self-paced Walking Test (SPWT). The secondary outcome measure was daily physical

activity measured by accelerometry. We took outcome measures at baseline as well as 2 months and 6

months from baseline. The primary end point was at 2 months. The primary analysis used linear mixed

models to compare changes in each outcome measure between the groups. The secondary analysis was

a comparison of the proportion of responders (≥ 30% change) in each outcome measure by group, using

the chi-square test.

Results: No serious adverse events were reported in any of the groups. At 2 months, there was a

statistically significantly greater reduction in adjusted mean SSS score (range = 12-55) in the MTE group

compared with MC (2.1; 95% CI, 0.3-3.9) or GE (2.4; 95% CI, 0.6-4.3). The minimum clinically important

difference (MCID) for the SSS is 3.02 points; therefore the between-group SSS differences were not

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clinically significant. The adjusted mean differences in SPWT scores at 2 months favored MTE compared

with MC (135.1; 95% CI, –17.2-287.4) or GE (46.2; 95% CI, –110.9-203.4), but these between-group

SPWT differences were not statistically significant. GE showed significantly greater improvement in

adjusted mean physical activity at 2 months compared with MC (30.5; 95% CI, 3.1-57.9), but clinical

significance is unknown due to the lack of an established MCID for physical activity. The MTE group had

significantly more SSS (20%) and SPWT (65.3%) responders at 2 months compared with MC (7.6%;

48.7%) or GE (3%; 46.2%) (P = 0.002 and P = 0.04, respectively). We prespecified responders as those

participants who showed ≥ 30% improvement from baseline on the measured outcome. At 6 months,

there were no longer significant between-group differences on any outcome measures. There was a

general trend toward short-term improvement in SSS and physical activity that was not sustained over

time; however, all groups maintained their improvements in walking performance (SPWT) at 6 months.

Study Limitations: There were a greater of proportion of GE dropouts immediately after randomization

and a potential attention bias due to the greater amount of individualized attention given to the MTE

group.

Conclusion: The combination of manual therapy and individualized exercise led to

significantly greater improvement in SSS and SPWT at 2 months, whereas group exercise led

to significantly greater improvement in physical activity at 2 months. The clinical significance of

these short-term improvements is unknown.

BACKGROUND Lumbar spinal stenosis (LSS) is a highly prevalent condition among older adults. Radiographic and clinical

data from the Framingham cross-sectional study report a 30% prevalence of degenerative LSS in this

population.1 A degenerative disease of the spine, LSS is often associated with significant functional

limitation of walking and disability.2 LSS has an associated risk of falling that is comparable to that found

in patients with severe knee osteoarthritis.3,4

A review of the literature reveals that the bulk of previous published clinical trials for LSS have

focused on 2 main areas of research: (1) comparisons of epidural injections, and (2) comparisons of

spine surgery with nonsurgical treatments such as physical therapy. The literature on these 2 topic areas

has generated conflicting results, which can be confusing to patients and providers. The largest epidural

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steroid injection (ESI) study to date involved the randomization of 400 patients with central LSS to

receive ESI with glucocorticoids plus lidocaine, or ESI with lidocaine alone.5 The results showed no

additional benefit in the glucocorticoid injection group in short-term reduction of physical disability or

leg pain.5 A systematic review and meta-analysis was published about the use of ESI for radiculopathy

and spinal stenosis.6 This review concluded that ESI for radiculopathy was associated with immediate

reductions in pain and function, but the effect sizes were small and not sustained. Limited evidence

suggested that there was little or no effectiveness of ESI for LSS.

The North American Spine Society (NASS) has published a clinical guideline for the diagnosis

and treatment of degenerative LSS.7 The only 2 interventions recommended as evidence

based and effective were ESI and surgical decompression. The NASS guideline concluded that

there was insufficient evidence to make a recommendation for or against the use of these

commonly utilized nonsurgical treatments for LSS: pharmacological treatments, physical therapy,

exercise, or spinal manipulation. Yet the favorable recommendation by NASS for ESI is

contradicted by recently published reviews concluding that the body of evidence for the

effectiveness of ESI is of low quality.8,9

Most of the clinical trials about LSS to date have focused on comparing patients who undergo

spine surgery with those who do not. Several randomized trials have concluded that patients

with severe LSS do better with surgical decompression, compared with nonsurgical

treatments.10-13 However, these surgical procedures are associated with significant costs, risks,

and complications as well as high rehospitalization rates.14-16 The largest clinical trial to date

compared surgical versus nonsurgical care, and concluded that patients with LSS treated

surgically had greater improvement in pain and function.17 However, the results from this same

trial also showed that about a third of the patients in the nonsurgical group had significant

improvements in pain and function lasting up to 4 years.18 A more recently published trial

randomized patients with LSS to surgical decompression or physical therapy treatment, finding

that both groups showed the same amount of improvement in physical function at 2

years.19

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Many large gaps in evidence remain about the effectiveness of nonsurgical treatment

options for the management of LSS. Several published systematic reviews of the LSS literature

highlight the gaps in evidence about nonsurgical treatments for LSS.12,20-26

A Cochrane systematic review of multiple nonsurgical treatment options for LSS identified

21 randomized clinical trials; however, the authors were unable to find moderate- or high-

quality evidence for any specific treatment option.21 The most recent Cochrane systematic

review on surgical versus nonsurgical treatments for LSS found a severe lack of high-quality

research performed to date.20 This led the authors to conclude, “We have very little

confidence to conclude whether surgical treatment or a conservative approach is better for

lumbar spinal stenosis. . . . We can provide no new recommendations to guide clinical

practice.”20

To help bridge this evidence gap, we designed a randomized trial to explore the comparative

clinical effectiveness of 3 common nonsurgical management approaches for patients with LSS:

(1) medical care provided by a physiatrist; (2) community-based group exercises provided by

fitness instructors; and (3) manual therapy/individualized exercises provided by chiropractors

and physical therapists. The primary aim was comparing the safety and effectiveness of these 3

interventions on pain and physical function, measured by a self-reported outcome and a

performance-based outcome. The secondary aim was to compare the changes in physical

activity between these 3 groups, measured by accelerometry.

PARTICIPATION OF STAKEHOLDERS IN RESEARCH STUDY DESIGN In formulating our original research questions, we started by identifying gaps in the current

evidence. The principal investigator (MS) and coinvestigator (CA) previously published 2

systematic reviews of the literature, which revealed large gaps in the evidence for many of the

commonly used conservative nonsurgical treatment methods used for patients with LSS.21,22

As noted previously, the evidence gap is very clear: The clinical guidelines for treatment of

LSS published by the North American Spine Society find inconclusive evidence for the

effectiveness of physical therapy, medications, exercise, and manipulation.10 Yet these are

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commonly utilized nonsurgical treatments for LSS—and are actually mandated by the local

University of Pittsburgh Medical Center (UPMC) Health Plan before spine surgery can be

authorized.27

We designed this trial to provide clinically relevant evidence to help fill this gap and to inform

the choices confronting clinicians and patients with LSS when faced with the decision about

nonsurgical treatment. There is also a paucity of evidence that takes into account which clinical

outcomes are important to patients. This is consistent with the goal of all patient-centered

outcomes research to determine which treatment works best, for whom, and under what

circumstances.28

We designed this study with input from a variety of stakeholders, including patients

with LSS, community senior center directors, clinicians who treat patients with LSS, and a

medical director from our local UPMC Health Plan. We developed a formal study protocol and

research design only after taking into consideration input we received from our stakeholders.

We developed the medical care protocol with input from physician stakeholders, and the

manual therapy/exercise protocol with input from physical therapists and

chiropractors.

We conducted group discussions at local community senior centers and asked patients with LSS

for their perspectives about which clinical outcomes were most important to them. Most

patients told us that living with a chronic degenerative condition that caused daily pain caused

many challenges. However, most patients told us that their biggest concern was the inability to

walk for any prolonged distance. They related stories about how their walking impairment

affected their ability to perform normal activities of daily living, such as shopping or walking to or

from a bus stop. This information helped us to decide on our use of outcome measures for our

study. We decided to include the self-paced walking test as an objective measure of walking

performance, in addition to our primary outcome of a self- reported measure of pain and

function.

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We also learned from our focus group participants that many of them were using community

senior centers as an alternative to receiving physical therapy or chiropractic care associated

with attending 2 to 3 physical therapy or chiropractic sessions per week for several weeks. They

were essentially substituting group exercise at community centers for individualized exercise at

chiropractic or physical therapy clinics, chiefly because they could not afford the cost of the

multiple copays associated with clinic-based care.

We also met with the directors of 2 large community centers who confirmed these patients’

perspectives. The fitness instructors had told them that many older adults in their group

exercise classes said that they were attending the classes as a substitution for physical therapy

and chiropractic care. This was concerning to center directors, because the purpose of these

group exercise classes was to promote general fitness; they were not intended for therapeutic

purposes. These directors also brought up the importance of knowing whether patients with

LSS could safely participate in the group exercise setting.

The research team had originally envisioned a 2-arm trial comparing medical care with a

combination of manual therapy and clinic-based individualized exercises; however, after

listening to our patient and community center stakeholders, we expanded the study design into

a 3-arm trial that included community-based exercise as an additional comparator arm. This

aligns well with the PCORI methodological standard RQ-5, which recommends the comparator

treatments be chosen to reflect viable treatment options for patients and avoiding the use of a

“no treatment” control group. We feel confident that each of our 3 comparator arms represents

a “real-world” management option that is commonly used by patients with LSS, which should

enhance the generalizability of our findings. We have published a summary of our research

protocol in an open-access peer reviewed journal.29

SPECIFIC AIMS (as presented in the original research application) The study was a pragmatic comparative effectiveness trial designed as a 3-group randomized

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clinical trial. The main goal of this study was to provide research evidence that could better

inform the choices between these 3 types of nonsurgical treatment options for patients

with LSS. The 3 comparison groups in this trial were the following:

• Group 1: Usual medical care*

• Group 2: Community-based group exercise classes

• Group 3: Clinic-based manual therapy and individualized exercise

*Note: In the design phase of this study, we interviewed primary care physicians and asked them

about how they managed patients with LSS. They told us that they commonly followed a 2-step approach:

Step 1: oral medications and advice to stay active; Step 2: referral for epidural injection. Therefore,

we considered this 2-step approach to be reflective of “usual medical care.” However, the

physician providing the medical care in our trial was board certified in physical medicine and

rehabilitation. Although we basically followed the same 2-step approach, we allowed him to

follow a more pragmatic and tailored approach (described in more detail later). This led to the

recognition that the words “usual medical care” were no longer the best terminology to describe

this intervention group. Therefore, we decided to delete the adjective “usual” and simply use

the term medical care in this report and future publications.

Primary Aim: To compare the clinical outcomes between these 3 interventions using 2

validated primary outcome measures of pain and physical function: Swiss Spinal Stenosis (SSS)

questionnaire (self-report measure) and Shuttle Walk Test* (performance-based measure).

• Hypothesis: LSS subjects in Groups 1 and 2 will demonstrate greater improvement in

self-reported pain/function and walking performance compared with Group 3.

*Note: We substituted the Self-paced Walking Test (SPWT) for the Shuttle Walk Test and notified

PCORI of this change before we began recruitment. This change in our choice of walking

performance measure occurred for 2 reasons. First, the developer of the SPWT consulted with

us about our research design and presented evidence about the reliability and accuracy of the

SPWT. Secondly, feedback from focus groups with stenosis patients indicated that the SPWT was

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a more patient-centered outcome that replicated real-life walking performance.

Secondary Aim: To compare changes in physical activity between these 3 treatment groups

using the SenseWear Armband (real-time activity measure).

•Hypothesis: Subjects in Groups 1 and 2 will demonstrate a greater change in physical

activity compared with Group 3.

Exploratory Aim 1: To explore relationships between 6-month attrition rates, number of

adverse events, adherence rates, number of falls, and cointerventions across treatment groups.

• Hypothesis: For all 3 treatment groups there will be a low incidence of adverse events and

similar treatment adherence rates. The 6-month attrition rate, number of falls, and

cointerventions will be lower in Groups 1 and 2 compared with Group 3.

Exploratory Aim 2: To explore treatment effects and responses by subgroup.

• Hypothesis: A group of baseline physical, psychosocial, and demographic measures

will be associated with treatment response and nonresponse in each group.

METHODS Methodological Standards Study Design This was a 3-arm, randomized controlled trial that compared the clinical effectiveness of group

exercise with manual therapy/individualized exercise, and each of these interventions with

medical care. The study was approved by the University of Pittsburgh Institutional Review

Board (PRO 12120422) and registered on ClinicalTrials.gov (NCT 01943435).

Sample Size

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We based sample-size estimation on hypothesized changes in our primary outcome

measure, the SSS questionnaire. We originally calculated a total sample size of 180 subjects with

an anticipated dropout rate of 15%, which would give us a final sample size of N = 150. This

would give us 80% power to detect a difference as small as 3.6 points (with a SD of 6.1) on the

total 12-item SSS score (30). In addition, this sample size also yields sufficient power to fit a

regression model that detects a statistical difference in the proportion of variability explained.

More specifically, a sample size of 150 achieves 81% power to detect an R-square of 5%

attributed to 2 independent variables (representing treatment) and assuming the control

variables account for an additional 20% of the variability. Due to an early unanticipated success

in enrollment and supplemental PCORI funding, we were able to continue recruitment for an

additional 6 months and achieve a larger final sample size (N = 259). We performed no interim

data analysis after reaching our original sample size of N = 180; we conducted only a single final

data analysis using data from the final sample size of N = 259.

Inclusion/Exclusion Criteria Participants were required to have been previously diagnosed with LSS by a physician and to

supply an MRI or CT report in which the radiologist confirmed the presence of anatomical

narrowing of the central canal, lateral recess, and/or foramen. We also confirmed the presence

of the following clinical signs of LSS: leg symptoms worsened by walking/relieved by sitting,

symptoms worsened by lumbar extension/relieved by flexion, and leaning forward on a

shopping cart while walking to relieve leg pain. To be eligible for the study, participants were

also required to (1) be aged 60 or older, (2) be able to read and write English, (3) be able to

walk at least 50 feet without an assistive device, (4) have a limitation of walking due to LSS, (5)

be able to engage in mild exercise, and (6) be willing to be randomized.

We excluded patients who (1) had a history of metastatic cancer, (2) had previous surgery for LSS

or lumbar fusion, (3) had cauda equina symptoms, (4) had a known history of severe peripheral

artery disease or exhibited an Ankle-Brachial index of < 0.8, (5) were told by a physician that they

should not engage in physical exercise, (6) had severe hypertension (systolic > 200 or diastolic >

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110), (7) could not complete a self-paced walking test for any reason other than symptoms

related to LSS, or (8) had a history of a neurological or neurodegenerative disease other than LSS

that affected their ability to walk.

Recruitment We used several strategies to recruit potentially eligible research participants from the general

population of older adults in the Pittsburgh metro area. The principle investigatorand research

coordinator set up informational booths and attended local community health fairs that were

targeted to older adults. Trifold informational brochures were produced and placed in the

waiting rooms of many primary care clinics affiliated with UPMC. We also produced a full-page

advertisement that we ran regularly in the Pittsburgh Senior News, a free monthly newspaper

with a circulation of 20 000 that is available in public venues such as major supermarkets in the

Pittsburgh region.

Our 2 most productive recruitment methods were the use of the University of Pittsburgh

Clinical and Translational Science Institute (CTSI) research registry and a series of direct

postcard mailings to the general public. The CTSI research registry is a voluntary database of

more than 100 000 patients who consented to be contacted for potential participation in

research studies. We also produced an oversize color postcard with information about our

study, an conducted a targeted direct mailing to Pittsburgh residents ≥ 60 years of age, living

within a 5- mile radius of our research facilities. Appendix B is a list of our direct mailings by ZIP

code and number of residents, which totaled more than 60 000 mailings over a period of 2

years.

Our recruitment strategies were extremely successful; we achieved our goal of enrolling 180

research participants about 6 months ahead of schedule—by June 1, 2015. Because of this

unanticipated early recruitment success, our program officer strongly suggested that we

continue recruitment for as long as possible to increase our total sample size. We were

subsequently awarded supplemental funding by PCORI, which allowed us to increase our final

sample size from N = 180 to N = 259 subjects. We achieved this new recruitment milestone by

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the end of November 2015. In order maintain statistical integrity, we did not conduct any

interim data analysis after reaching our original recruitment goal of N = 180 subjects. We

conducted all analyses only after reaching the final total of N = 259 subjects.

We conducted a 2-phase screening process with those patients who contacted us expressing

interest in our research study (n = 710). The first phase consisted of a telephone screening

designed to filter out patients who clearly did not meet our inclusion criteria—for

example those who were younger than the age of 60 years or did not have MRI evidence of LSS.

Only those patients who passed the phone screening process (n = 298) were scheduled for the

second phase, a baseline physical examination at our research clinic. We designed this

examination to further screen out patients who had physical problems that could not be

established with a phone screen, including abnormal ankle brachial index, abnormally high blood

pressure, inability to walk 50 feet without an assistive device, or stopping the self-paced walking

test for reasons other than LSS (eg, chest pain, shortness of breath).

Randomization Randomization occurred immediately after the baseline screening examination confirmed that

the patient was eligible to participate in the trial. We used a computerized adaptive allocation

randomization algorithm to balance the 3 groups on 3 important baseline variables: (1)

SSS score, (2) SPWT score, and (3) age. We based the randomization scheme

on a minimization algorithm proposed by Stigsby and Taves.30 The approach is to use a rank-

based method to balance on multiple baseline prognostic factors.

All self-report questionnaires were converted into electronic format and completed by patients

on iPads. Research staff entered data from the baseline physical examination into iPads . All data

entered into the iPads were encrypted and transferred wirelessly to a secure central database,

where the randomization algorithm automatically processed the data and created the group

assignment. Within a few minutes of completing the baseline examination and self-report

questionnaires, our research assistant received an email from the research coordinator with the

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group assignment. Each participant was informed about which intervention they would be

receiving, and the research assistant scheduled his or her first appointment. This electronic

system of randomization automated the concealment of allocation sequence and eliminated the

need for double data entry.

Interventions The medical care arm of the study involved 3 visits to a physical medicine physician over 6

weeks—1 initial evaluation and 2 follow-up office visits. We designed a pragmatic treatment

protocol that was based chiefly on prescription of oral medications and epidural injections.

The physician reviewed each patient’s currently prescribed medications for LSS and was

permitted to modify/prescribe any of the following oral medications:

Nonsteroidal antiinflammatories: ibuprofen, celecoxib, diclofenac, or misoprostol

• Adjunctive analgesics: acetaminophen or gabapentin

• Antidepressant agents: nortriptyline, duloxetine, sertraline, trazodone, or mirtazapine

In addition to prescribing any of the above oral medications, the physician had the option of

referring participants for epidural steroid injections (ESIs) at 2 cooperating pain clinics in

Pittsburgh. Indications for ESI referral included inadequate pain relief with oral medications,

severe neurogenic claudication, or positive nerve tension signs. The clinical protocol was

pragmatic; the physician was allowed to tailor his recommendations to each patient’s individual

needs while staying within the parameters of the medications listed above, with the option of

recommending ESI when considered appropriate. The principle of shared-decision making was

used for all suggested medications and ESIs; in other words, research participants had an open

discussion with the physician about his recommendations and were not coerced into receiving

any prespecified regime of medications or injections. In addition to oral medications and/or

spinal injections, all subjects were given advice to stay active and to perform 2 home exercises:

hip-flexor stretching and prone, lumbar-extension stretching (yoga cobra pose). In addition, they

were encouraged to walk as much as possible despite their walking limitations.

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The community-based group exercise arm of our trial involved attendance by the research

participants in supervised group exercise classes for older adults. These classes were held at 2

local senior community centers in Pittsburgh. Participants could choose to attend exercise

classes at either community center, based on convenience of location. The centers were

responsible for setting up the participants’ memberships, enrolling them in the group exercise

classes, and providing the approved schedule of classes for the study.

Participants were asked to attend 2 exercise classes per week for 6 weeks, for a total of 12

exercise classes. Each class was about 45 minutes in length and was taught by certified fitness

instructors who were experienced with supervising exercise classes for older adults. The

intensity and difficulty level of the exercise classes ranged from very easy to medium. The

pragmatic nature of our trial allowed for participants to self-select the level of exercise

class based on their perception of their fitness level. Community center staff monitored

attendance at each class, compiled this information into monthly spreadsheets, and sent them

to our research team. Although the reports were sent monthly, they had details about daily

class attendance.

The clinic-based manual therapy/individualized exercise arm of the trial involved treatment

provided by chiropractors and physical therapists at the Physical Therapy Clinical and

Translational Research Center at the University of Pittsburgh. Participants were

treated 2 times per week for 6 weeks; each treatment session lasted about 45 minutes. The

clinicians followed a pragmatic treatment protocol that consisted of 3 basic interventions:

(1) warm-up procedure using a stationary bicycle; (2) manual therapy procedures that included

lumbar distraction mobilization, hip-joint mobilization, side-posture lumbar and/or sacroiliac-

joint mobilization, and sciatic/femoral nerve mobilization; and (3) individualized exercise

procedures with instruction in spinal-stabilization exercises and stretching exercises to be

completed at home. Each subject was assessed by physical examination for which specific

muscles required stretching and which other muscles required strengthening. The treating

chiropractor or physical therapist then developed an individualized program of

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stretching/strengthening exercises for each patient; this was in contrast with the nonspecific

nature of the group exercise classes and general exercise instructions given to all patients by

the physician. Appendix A provides a detailed list of all the manual therapy and therapeutic

exercise procedures utilized in our treatment protocol for this arm of the study.

Study Outcome Measures Our primary subjective outcome measure of self-reported pain/function was the SSS

questionnaire,31 which is a validated patient self-report of pain and physical function. We used

the 12-item version of this form, which has 2 subscales; a 7-item Symptom Severity subscale

and a 5-item Physical Function subscale. The SSS has been shown to possess adequate

psychometric properties for use with LSS patients, with a minimal clinically important

difference (MCID) of 3.02 points for the total 12-item SSS score, which is 0.36 and 0.10 points

per item for the Symptom Severity and Physical Function subscales, respectively.32 The primary

objective outcome measure of walking performance was the distance walked (meters) during

the SPWT, which is a validated measure of walking performance in patients with LSS.33 The

SPWT has been shown to be highly reproducible with a test–retest intraclass correlation

coefficient (ICC) of 0.98 34. No MCID has been established for the SPWT.

We selected these outcome measures based on feedback received from our patient and

clinician stakeholders. Patients with LSS who participated in our community group discussions

told us that their general concerns were about their level of pain and function; they had a

specific concern about the distance they could walk before needing to sit down. The SSS was an

obvious choice for a self-reported measure of pain and function, because it contains both

Symptom Severity and Physical Function subscales and was validated for use within the LSS

population.

We decided to use the SPWT as our objective measure of walking performance instead of the

Shuttle Walk Test, because the SPWT more closely resembles the way LSS patients

walk in real-life settings.34 Performed on level ground, the SPWT instructs patients to walk at

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their normal pace and to continue walking until their symptoms rise to a level that they must sit

down and rest. A physical therapist walks behind the patient, measures the distance walked in

meters, and records the total time walked in minutes. The developer of the SPWT consulted

with our research team about the specific details of conducting this pragmatic test of walking

performance.

We also used the SenseWear armband (BodyMedia Inc) to record physical activity for our

secondary outcome measure.35,36 This small, wireless accelerometer is worn over the triceps

muscle. It combines information from skin temperature and a biaxial accelerometer, enabling

the device to estimate energy expenditure from activities that do not require ambulation.

Physical activity measured by the SenseWear has compared well with reference standards such

as doubly labeled water (ICC: 0.48 to 0.81) 35, 36 and indirect calorimetry (ICC: 0.11 to 0.92).37-41

After finishing the testing procedures at baseline, subjects were fitted with the Sensewear

armband and instructed to wear the monitor for 7 days. Data from the activity monitor were

inspected to ensure they were sufficient, which we defined as at least 4 days with 10 hours of

physical activity data per day.42-44 Subjects without sufficient data were asked to wear the

portable monitor for an additional week prior to starting study-related interventions. We used

the same procedures to collect physical activity data at the follow-up examinations.

We also obtained several other self-reported measures using validated instruments widely

employed in rehabilitation trials. A patient global index of change (PGIC) and treatment

satisfaction (SAT) questionnaire were given to our research participants at the follow-up

examinations. The PGIC asked patients to rate their level of “overall status change since first

beginning treatment” on a 7-point scale, ranging from “very much worse” (–3) to “very much

better” (+3). The SAT questionnaire asked patients to rate their level of satisfaction with the

treatment on a 6-point scale, ranging from “extremely dissatisfied” (–3) to “extremely satisfied”

(+3).

We used a modified comorbidity disease index45 to gather self-reported information about

19

the number of comorbid medical conditions that were diagnosed in addition to LSS. We used a

Falls History Form to ask questions about the number of falls over the past year and level

of current fear of falling.46 The Activities Specific Balance Confidence scale47 was administered

to assess participants’ level of confidence about not losing balance during routine activities of

daily living. We used the 10-item Oswestry Low Back Pain Disability Index48 and the 11-item

Tampa Scale for Kinesiophobia49 to assess self-reported disability from back pain and fear of

movement, respectively. We screened for depressive symptoms utilizing the short-form version

of the Patient Reported Outcomes Measurement Information System (PROMIS) depression

scale.50 Last, we used a 6-item treatment expectancy and credibility questionnaire specifically

modified for use in patients with chronic low back pain.51 Table A provides a summary of all

outcome measures and the times at which they were collected during the trial.

In addition to these self-reported measures, a research physical therapist performed some

physical examination procedures at baseline to capture additional clinical data. This therapist

recorded range of motion of the lumbar spine as well as that of the hip and knee joints, and

palpation of these structures was performed for local tenderness. Tests for balance and

mobility included a modified version of the Short Physical Performance Battery52: 4-meter gait

speed, timed chair stands, and timed single-leg standing. Blood pressure measurements were

taken on all participants, as well as height and weight for calculation of body mass index.

20

Table A. Outcome Measures and Other Information Gathered at Baseline and Follow-up

•

•

Table X: Timeline of Outcome Measures

Measure Baseline Mid 2 o treatment Follow-up 6 mo

Follow-up

Primary Outcomes

Self-report = SSS • • • •

Performance-based = SPWT • • Secondary Outcome

Physical activity • Real-time activity = SWA*

•

Exploratory Outcomes

Falls history • • •

Activities Balance Confidence Scale (ABC)

• • •

Oswestry • • • •

Side effects, adverse events

• • •

Cointerventions~ •

RAND-36 • • •

SPPB • • •

PGIC • •

Satisfaction • •

Other Variables

Demographics •

Comorbidities (MCDI) •

Baseline history and physical exam

•

Psychosocial Measures

Fear (TSK) •

Depression (PROMIS) •

Expectancy (CEQ) •

~Cointerventions include new medications, injections, hospitalizations, surgery, chiropractic care, physical therapy, or acupuncture treatment.

*Note about SWA: At baseline and follow-up assessments, the SenseWear Armband was be given to all subjects to take home and wear continuously for 1 week.

Abbreviation Key: SSS = Swiss Spinal Stenosis questionnaire SPWT = Self-paced Walking Test SWA = SenseWear Armband; ABC = Activities Balance Confidence Scale RAND-36 = RAND 36-item Health Survey SPPB = Short Physical Performance Battery; PGIC = Patient Global Index of Change; MCDI = Modified Comorbidity Disease Index; TSK = Tampa Scale for Kinesiophobia; PROMIS = Patient Reported Outcomes Measurement Information System; CEQ = Credibility/Expectancy Questionnaire

21

We also used a portable Doppler unit and sphygmomanometer to record the Ankle Brachial

Index (ABI). The ABI is a highly sensitive and specific screening test for peripheral artery disease

and lower leg vascular claudication.53,54 Any patient with an ABI below 0.8 was excluded

from participating in our study, because of the possibility of vascular rather than neurogenic

claudication. We also excluded patients with severe high blood pressure, using the American

College of Sports Medicine criteria (systolic > 200 or diastolic > 110).

Blinding

Blinding of the treating clinicians and research participants was not possible, because both

group were obviously aware of the intervention they were giving or receiving. We attempted to

minimize bias by having an independent physical therapist perform all baseline physical

examinations and follow-up reassessments. Our primary outcome measures (SSS) were a

patient-report questionnaire and an objective outcome measure of walking performance

(SPWT), conducted in a manner to minimize examiner bias. Participants were instructed to walk

as far as they could until they needed to sit down and rest. The physical therapist observing the

subjects was not permitted to coach or provide any encouragement; he simply recorded the

total distance and time walked. Because the SenseWear armband is worn at the subject’s

home, the exploratory measure of physical activity was also not subject to examiner bias; data

are uploaded directly from the device.

Study Setting

All treatments were provided at no charge to the participants or their insurance carriers. The

medical care was provided by a physical medicine physician at his outpatient clinical practice

setting. Participants who attended the group exercise classes were given complimentary access

to those classes or a temporary membership to a local community center. A chiropractor or a

physical therapist in a research-based physical therapy clinic at the University of Pittsburgh

treated participants in the manual therapy arm. All locations were chosen because of their real-

22

world settings.

Follow-up

For all 3 arms of the study, the respective interventions were completed over a 6-week period.

Participants returned for 2 follow-up research examinations, at 2 months (2 weeks

after completion of care) and 6 months (4 months after completion of care).

Analytical and Statistical Approaches

The analysis of our primary aim consisted of a between-groups comparison of the changes in

the primary subjective (SSS) and objective (SPWT) outcomes from baseline values to 2 months

(primary end point). The analysis of our secondary aim was a comparison of the between-group

changes in the average amount of physical activity from baseline to 2 months. We defined our

measure of physical activity as the average number of daily minutes spent in light, moderate, or

vigorous physical activity (> 1.5 metabolic equivalents of task [METs]). We also performed these

same analyses comparing the data obtained at 6 months with the baseline measures. Due to

the constraints of our 3-year PCORI contract, we could not obtain any results beyond 6 months.

We also performed a series of secondary responder analyses for each of the outcome measures

associated with our primary and secondary aims. We accomplished this by dichotomizing all

subjects into either “responders” or “nonresponders” based on the prespecified threshold of a

minimum 30% improvement in outcome from baseline. We performed separate responder

analyses for each of the 3 outcome measures (SSS, SPWT, and physical activity), comparing the

proportions of responders at 2 months and 6 months.

We summarized the outcomes and all baseline characteristics with descriptive statistics,

separated by treatment group. We used linear mixed models as the primary analytic method to

assess the significance of treatment for each group, while adjusting for the three baseline

randomization balancing variables: SSS, SPWT, and age. We followed a modified intention-to-

treat principle: All participants who were randomized (N = 259) were included in the analysis,

23

using linear mixed models to account for missing data. We verified the normality assumptions

for the outcome variables for the simple analysis as well the assumptions for the multiple

regression models on the change scores.

For our primary and secondary aims, we also performed a series of secondary responder

analyses using dichotomous outcomes, consistent with the recommendations published by the

Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (IMMPACT).55,56

Per IMMPACT recommendations, we defined treatment responders as those who achieved at

least a 30% improvement in the outcome measure of interest, which is considered “moderate

improvement.” We believe that a 30% improvement in symptoms and/or functional

performance is a clinically important change over 2 months, considering that LSS is a chronic

degenerative disease that tends to deteriorate over time. Our analyses compared the

proportions of subjects considered “responders” by treatment group on these measures—SSS,

SPWT, and physical activity. We assessed differences in the proportion of

responders/nonresponders between the groups using chi-square and Fisher exact tests.

Our first exploratory aim was to explore 6-month attrition and adherence rates, number of falls,

adverse events, and cointerventions. We defined adherence as any participant who did not

drop out after randomization and attended at least 2 of the 3 scheduled medical care visits, or

at least 9 of the 12-scheduled group exercise or manual therapy sessions. We defined attrition

as any participant who did not drop out after randomization and received at least 1 treatment

but who did not show up for the follow-up research examination. At baseline, participants were

asked, “Have you fallen any time during the past year? If yes, how many times did you fall?” At

the 6-month follow-up evaluation, participants were asked, “Have you fallen any time between

now and when you finished your study intervention? If yes, how many times did you fall?”

We defined a serious adverse event as any unanticipated health care problem, directly related

to a study intervention, that caused the participant to seek medical care outside of the study.

We asked all research participants to neither seek any new type of health care nor start any

24

new exercises outside of the study until after their 2-month follow-up evaluation. Therefore,

we asked participants only about which cointerventions they had utilized during the period

between their 2-month and 6-month follow-up evaluations. We summarized these exploratory

outcomes with descriptive statistics of their respective counts and rates, separated by

treatment group. The analysis for this aim consisted of omnibus chi-square tests for the

differences in the rates or proportions of each outcome across the 3 groups.

Our second exploratory aim was to explore potential baseline predictors of treatment

response. We first performed univariate analyses to test for possible associations between

baseline characteristics and response, based on the criterion of responders being defined as

those participants who demonstrated ≥ 30% change on either the SSS or SPWT. We used 2-

sample t-tests for continuous variables and chi-square tests for categorical variables to test

the association between responders and nonresponders and each variable of interest. We

decided a priori that statistical significance would be set at P < 0.10 for variables to be included

in the multivariable logistic regression model. We used the same responder–nonresponder

dichotomous variables for SSS, SPWT, and physical activity created for the secondary responder

analyses associated with our primary and secondary aims.

We then used logistic regression models to test the association between responders and non

responders, treatment groups, and other variables of interest. We put the variables that we

found significant using univariate procedures (P < 0.10) in a multivariable logistic regression

model, and applied a backward elimination procedure. The level of significance for removal

was P < 0.10.

We evaluated heterogeneity of treatment effects by testing the interaction between treatment

and 8 baseline variables using multiple logistic regression models, with responder status as the

dependent variable. These 8 variables were age, sex, body mass index, comorbidities, race,

kinesiophobia, knee osteoarthritis, and depression. We dichotomized age at < 75 years versus ≥

75 years. Se split comorbidities, depression, and the other continuous variables at their

25

respective medians. We considered baseline variables as potential moderators of treatment

effect due to our experience in other studies and the published literature. We compared the P

value for the interaction between the moderator and the treatment variable to 0.05. Regardless

of significance, we presented between-treatment group comparisons as odds ratios and

stratified 95% confidence intervals by the potential moderator. Finally, we explored with

descriptive statistics and responder analyses the between-group differences in Patient Global

Index of Change and Treatment Satisfaction at 2 months and 6 months.

Missing Data

To account for any missing data, we used linear mixed-effects models to study treatment

differences over time for the primary and secondary outcomes. We used a compound

symmetry structure for the correlation structure and the Kenward-Roger approximation

method for the degrees of freedom.57 Linear mixed-effects models use all available data; if a

subject had a measurement at 1 time point and the rest of the data were missing, then that

subject was still used in the analysis. Therefore, these mixed models included data from all

participants who had a baseline examination and were randomized (N = 259).

Ancillary Qualitative Study

Although not part of our original research design, we were able to include an ancillary

qualitative study that involved focus-group discussions with participants from each of the 3

intervention arms. These discussions were recorded, transcribed, coded, and analyzed for

themes using qualitative software. The results of this ancillary qualitative study are available as

a supplemental report upon request, as they will be published separately from the main results

of this trial.

26

RESULTS

Participant Flow

Figure 1 provides a CONSORT participant flow diagram.58 We screened 710 people over the

phone and excluded 412 for not meeting the minimum inclusion criteria; 298 people were

brought into our research facility for a baseline physical examination screening to assess their

eligibility for participation in the trial. Informed consent was obtained from all potentially

eligible patients. A total of 259 people met our inclusion criteria, were enrolled, and were

randomized. A total of 19 enrolled participants dropped out after randomization and never

attended any of the intervention sessions, with a larger number of drop-outs in the group

exercise arm (N = 12). We included in our analysis only those patients who attended at least 1

intervention session.

27

Figure 1. CONSORT flow diagram

Baseline Screening Examination

Assessed for eligibility (n=298)

(n=197)

Excluded as ineligible (n=39)

Abnormal ankle-brachial index (n=12)

Extremely high blood pressure (n=1)

Could not walk without need for an

assistive device (n=2)

Stopped self-paced walking test for

reason other than stenosis (n=24)

2-month follow up exam (n=79)

Lost to follow up (n=5)



2-month follow up re-exam (n=80)


Phone Screens (n=710)

Allocated to Medical Care (n=88)

thdrew after randomization (n=4)

Received Medical Care (n=84)

Allocated to Group Exercise (n=84)

Withdrew after randomization (n=12)

Received Group Exercise (n=72)

Allocated to Manual Therapy (n=87)

Withdrew after randomization (n=3)

Received Manual Therapy (n=84)

Randomized (n=259)

-month follow up exam (n=67)






Did not meet minimum inclusion criteria (n=412)

28

Baseline Data

Table 1 contains the baseline demographic and clinical characteristics of our participants, both

by study total and assigned treatment group. The randomization process worked well;

no significant differences existed between the groups on any demographic or clinical

characteristics. The average age of our participants was 72.4 years (SD = 7.8), with a range of

60-92 years. Many of our participants reported comorbid osteoarthritis of the hip (16.6%)

and/or knee (31.7%), with an average body mass index of 31.0 (SD = 6.6). We achieved good

racial and socioeconomic diversity, with our research participants represented by 21.6%

African American, 47.1% without a college degree, and 51.4% with an annual income below

$40 000.

Our participants had an average of 4.7 (SD = 2.2) medical comorbidities: arthritis (85%);

cataracts (52%); emotional problems (34%); hearing problems (31%); and joint replacement

(30%). As listed in Table 1, the 2 most common types of arthritis reported by our participants

were hip osteoarthritis (16.6%) and knee osteoarthritis (31.7%). At baseline, our participants

had an average SSS Symptom Severity subscore of 20.3 (SD = 4.3; range = 7-35) and walked an

average of 455.3 meters (SD = 480.0) during the SPWT.

Physical activity was recorded from the SWA device, which captures data in terms of METs. One

MET is defined as 1 Kcal/kg/hour and is roughly equivalent to the energy cost of sitting quietly.

The amount of METs expended can be used to create general activity categories as follows:

sedentary = ≤ 1.5 METs; light = > 1.5-3.0 METs; moderate = ≥ 3.0 to 6.0 METs; and vigorous = ≥

6.0 METs. Our subjects were very sedentary, spending an average of about 18 hours per day

(1095.3 ± 150.3 mins/day) in activities ≤ 1.5 METs. They spent less than 3 hours per day (165.5 ±

129.7 mins/day) performing activities >1.5 METs. Table B provides a comparison of the baseline

characteristics of all participants who completed their assigned treatment and those for whom

we had missing data. This table shows that those who withdrew after randomization were

mostly similar with minor exceptions (e.g. marital status).

29

Table B: Baseline characteristics for all participants with and without complete data at each time point. For categorical variables, “F” indicates p-

value from Fisher’s exact test and no “F” indicates p-value from chi-square test. Continuous variable p-values from Wilcoxon rank sum test.

Baseline

Randomized: N=259

2 month follow-up

Received treatment: N=240

6 month follow-up


Started Tx

(n=240)

Withdrew –

no tx

(n=19)

Completed

2mo FU

(n=225)

Missing

2mo FU

(n=15)

Completed

6mo FU

(n=191)

Missing 6mo

FU

(n=49)

Categorical

Measure Category

n (%) n (%) p-

value

p-

value

p-value

Sex Male 113(47.1%) 9(47.4%) 0.98 107(47.6%) 6(40.0%) 0.57 89(46.6%) 24(50.0%) 0.77

Female 127(52.9%) 10(52.6%) 118(52.4%) 9(60.0%) 102(53.4%) 25(51.0%)

Race White 184(76.7%) 17(89.5%) 0.47F 172(76.4%) 12(80.0%) 1.00F 151(79.1%) 33(67.4%) 0.15F

Black 54(22.5%) 2(10.5%) 51(22.7%) 3(20.0%) 38(19.9%) 16(32.7%)

Other 2(0.8%) 0(0.0%) 2(0.9%) 0(0.0%) 2(1.1%) 0(0.0%)

Hispanic Yes 0(0.0%) 0(0.0%) 1.00F 0(0.0%) 0(0.0%) 1.00F 0(0.0%) 0(0.0%) 1.00F

No 240(100.0%) 19(100.0%) 225(100.0%) 15(100.0%) 191(100.0%) 49(100.0%)

Married Yes 120(50.0%) 5(26.3%) 0.05 116(51.6%) 4(26.7%) 0.06 104(54.5%) 16(32.7%) 0.01

No 120(50.0%) 14(73.7%) 109(48.4%) 11(73.3%) 87(45.6%) 33(67.4%)

Education LE 8th

grade or

>8th grade

but not HS

grad

10(4.2%) 0(0.0%) 0.31 10(4.4%) 0(0.0%) 0.62 8(4.2%) 2(4.1%) 0.68

30

Baseline

Randomized: N=259

2 month follow-up


6 month follow-up


Started Tx

(n=240)

Withdrew –

no tx

(n=19)

Completed

2mo FU

(n=225)

Missing

2mo FU

(n=15)

Completed

6mo FU

(n=191)

Missing 6mo

FU

(n=49)

Categorical

Measure Category

n (%) n (%) p-

value

p-

value

p-value

HS grad to

some

college

106(44.2%) 6(31.6%) 100(44.4%) 6(40.0%) 87(45.6%) 19(38.8%)

College

grad or

higher

124(51.7%) 13(68.4%) 115(51.1%) 9(60.0%) 96(50.3%) 28(57.1%)

Household

income

$20K or

less

46(19.2%) 6(31.6%) 0.25 44(19.6%) 2(13.3%) 0.43F 32(16.8%) 14(28.6%) 0.07

$20,001-

$40,000

74(30.8%) 7(36.8%) 67(29.8%) 7(46.7%) 57(29.8%) 17(34.7%)

$40K or

more

120(50.0%) 6(31.6%) 114(50.7%) 6(40.0%) 102(53.4%) 18(36.7%)

Current

Smoker

Yes 15(6.3%) 0(0.0%) 0.61F 15(6.7%) 0(0.0%) 0.61F 12(6.3%) 3(6.1%) 1.00F

No 225(93.8%) 19(100.0%) 210(93.3%) 15(100.0%) 179(93.7%) 46(93.9%)

Tobacco Use Yes, I

currently

smoke

15(6.3%) 0(0.0%) 0.55F 15(6.7%) 0(0.0%) 0.81F 12(6.3%) 3(6.1%)

31

Baseline

Randomized: N=259

2 month follow-up


6 month follow-up


Started Tx

(n=240)

Withdrew –

no tx

(n=19)

Completed

2mo FU

(n=225)

Missing

2mo FU

(n=15)

Completed

6mo FU

(n=191)

Missing 6mo

FU

(n=49)

Categorical

Measure Category

n (%) n (%) p-

value

p-

value

p-value

No, I have

never

smoked

102(42.5%) 11(57.9%) 96(42.7%) 6(40.0%) 80(41.9%) 22(44.9%)

No, I used

to smoke,

but quit

119(49.6%) 8(42.1%) 110(48.9%) 9(60.0%) 95(49.7%) 24(49.0%)

Other/Miss

ing

4(1.7%) 0(0.0%) 4(1.8%) 0(0.0%) 4(2.1%) 0(0.0%)

Predominant

Pain

Legs 43(17.9%) 3(15.8%) 0.63F 42(18.7%) 1(6.7%) 0.53F 39(20.4%) 4(8.2%) 0.12

Low Back 145(60.4%) 10(62.6%) 135(60.0%) 10(66.7%) 113(59.2%) 32(65.3%)

Equal 52(81.7%) 6(31.6%) 48(21.3%) 4(267%) 39(20.4%) 13(26.5%)

Qualitative

description

of leg pain

Pain 114(47.5%) 7(36.8%) 0.37 108(48.0%) 6(40.0%) 0.55 96(50.3%) 18(36.7%) 0.09

Neurologic 126(52.5%) 12(63.2%) 117(52.0%) 9(60.0%) 95(49.7%) 31(63.3%)

Hip OA Yes 39(16.3%) 4(21.1%) 0.53F 35(15.6%) 4(26.7%) 0.28F 32(16.8%) 7(14.3%) 0.68

No 201(83.8%) 15(79.0%) 190(84.4%) 11(73.3%) 159(83.3%) 42(85.7%)

32

Baseline

Randomized: N=259

2 month follow-up


6 month follow-up


Started Tx

(n=240)

Withdrew –

no tx

(n=19)

Completed

2mo FU

(n=225)

Missing

2mo FU

(n=15)

Completed

6mo FU

(n=191)

Missing 6mo

FU

(n=49)

Categorical

Measure Category

n (%) n (%) p-

value

p-

value

p-value

Knee OA Yes 74(30.8%) 8(42.1%) 0.31 71(31.6%) 3(20.0%) 0.56F 59(30.9%) 15(30.6%) 0.97

No 166(69.2%) 11(57.9%) 154(68.4%) 12(80.0%) 132(69.1%) 34(69.4%)

Started Tx

(n=240)

Withdrew

– no tx

(n=19)

Completed

2mo FU

(n=225)

Missing 2mo

FU

(n=15)

Completed

6mo FU

(n=191)

Missing 6mo

FU

(n=49)

Continuous

Measure

Mean ± SD Mean ± SD p-

value

Mean ± SD Mean ± SD p-value Mean ± SD Mean ± SD p-value

Age 72.3 ± 7.8 73.5 ± 8.2 0.47 72.3 ± 7.6 71.4 ± 10.7 0.30 72.8 ± 7.7 70.2 ± 8.0 0.02

BMI 31.0 ± 6.6 31.4 ± 7.6 0.86 30.7 ± 6.3 35.5 ± 9.2 0.03 30.6 ± 6.3 32.6 ± 7.5 0.12

Treatment

Expectancy_A

35.4 ± 11.8 31.0 ± 13.3 0.17 35.6 ± 11.9 31.8 ± 9.0 0.10 35.6 ± 12.1 34.5 ± 10.7 0.36

Treatment

Expectancy_B

42.8 ± 8.9 39.3 ± 9.5 0.10 43.0 ± 8.9 39.5 ± 8.8 0.11 43.1 ± 8.9 41.3 ± 9.0 0.15

Treatment

Expectancy_C

39.4 ± 10.5 35.5 ± 10.9 0.16 39.6 ± 10.3 35.6 ± 13.2 0.22 39.8 ± 10.3 37.7 ± 11.3 0.16

33

Started Tx

(n=240)

Withdrew

– no tx

(n=19)

Completed

2mo FU

(n=225)

Missing 2mo

FU

(n=15)

Completed

6mo FU

(n=191)

Missing 6mo

FU

(n=49)

Continuous

Measure


value


Depression T-

Score

47.6 ± 8.9 51.3 ± 7.5 0.08 47.4 ± 8.8 50.4 ± 10.1 0.24 47.1 ± 8.9 49.2 ± 8.9 0.13

MCDI (comorbidities)

4.7 ± 2.2 5.1 ± 1.6 0.18 4.6 ± 2.2 5.7 ± 1.9 0.03 4.5 ± 2.2 5.4 ± 2.3 0.01

TSK (kinesiophobia) 25.6 ± 4.7 25.7 ± 4.8 0.97 25.6 ± 4.8 26.5 ± 2.7 0.50 25.5 ± 5.0 26.0 ± 3.3 0.91

ABI (Ankle-Brachial

Index)

(min of right/left)

1.1 ± 0.2 1.0 ± 0.1 0.15 1.1 ± 0.2 1.0 ± 0.2 0.42 1.1 ± 0.2 1.1 ± 0.2 0.76

Vibration

(max of

right/left)

33.0 ± 14.7 27.5 ± 16.1 0.15 32.9 ± 14.7 33.2 ± 15.7 0.90 33.0 ± 14.6 32.6 ± 15.1 0.81

Single Leg

Standing(seconds)

13.0 ± 16.3 16.2 ± 21.3 0.72 13.5 ± 16.7 6.4 ± 7.6 0.13 13.4 ± 16.4 11.5 ± 16.0 0.27

Gait Speed (meters/second)

0.9 ± 0.2 0.9 ± 0.2 0.29 0.9 ± 0.2 0.9 ± 0.2 0.17 0.9 ± 0.2 0.9 ± 0.2 0.86

Oswestry

Disability Index

38.3 ± 12.7 38.7 ± 14.1 0.89 38.2 ± 12.7 39.5 ± 13.5 0.43 37.9 ± 12.9 39.6 ± 12.1 0.49

Falls Score 0.7 ± 1.2 0.8 ± 1.7 0.75 0.7 ± 1.2 0.9 ± 0.8 0.11 0.7 ± 1.3 0.7 ± 0.8 0.28

ABC Score (activities, balance, confidence)

69.4 ± 21.2 62.6 ± 22.9 0.22 69.4 ± 21.2 68.4 ± 22.5 0.94 69.4 ± 21.0 69.1 ± 22.3 0.96

34

Started Tx

(n=240)

Withdrew

– no tx

(n=19)

Completed

2mo FU

(n=225)

Missing 2mo

FU

(n=15)

Completed

6mo FU

(n=191)

Missing 6mo

FU

(n=49)

Continuous

Measure


value


RAND_GH 59.8 ± 18.2 56.7 ± 16.4 0.50 60.7 ± 17.8 46.0 ± 19.0 0.00 61.0 ± 18.1 54.7 ± 17.7 0.04

RAND_P 38.3 ± 21.3 33.9 ± 27.7 0.37 38.6 ± 21.4 33.5 ± 19.2 0.27 39.1 ± 20.9 35.1 ± 22.4 0.34

RAND_SF 47.8 ± 10.2 45.1 ± 15.5 0.83 47.8 ± 10.1 47.5 ± 11.8 0.88 48.4 ± 9.9 45.4 ± 11.0 0.10

RAND_EW 76.7 ± 16.3 71.1 ± 17.8 0.19 77.2 ± 15.8 68.0 ± 21.0 0.07 77.8 ± 15.7 72.3 ± 17.7 0.04

RAND_EF 50.5 ± 18.8 40.8 ± 20.2 0.05 51.3 ± 18.6 37.7 ± 18.1 0.01 51.4 ± 18.9 46.7 ± 18.0 0.15

RAND_PF 45.9 ± 20.3 43.9 ± 22.4 0.85 46.5 ± 20.2 37.7 ± 20.5 0.09 46.5 ± 20.1 43.6 ± 21.0 0.41

RAND_RLE 40.8 ± 43.4 40.7 ± 46.5 0.99 40.1 ± 43.6 51.1 ± 41.5 0.37 38.6 ± 43.3 49.7 ± 43.1 0.08

RAND_RLP 74.0 ± 35.1 70.8 ± 34.6 0.53 73.4 ± 35.2 81.7 ± 34.7 0.31 73.6 ± 35.7 75.5 ± 33.3 0.97

SPWT_Total Time (mins)

7.6 ± 6.9 7.3 ± 6.9 0.88 7.7 ± 6.9 5.9 ± 7.0 0.14 7.7 ± 6.8 7.2 ± 7.4 0.19

SPWT_Total

Distance (meters)

457.8 ± 482.1 423.3 ±

463.3

0.67 465.4 ± 483.2 343.8 ± 465.7 0.12 464.9 ± 480.0 430.2 ± 494.3 0.29

SSS_Total 31.4 ± 5.9 33.2 ± 6.5 0.24 31.3 ± 5.9 33.1 ± 6.4 0.27 31.2 ± 5.9 32.3 ± 5.9 0.16

SSS_Symptom_

Severity

20.2 ± 4.3 21.3 ± 4.0 0.33 20.2 ± 4.4 21.0 ± 4.1 0.45 20.0 ± 4.4 21.0 ± 4.0 0.14

SSS_Physical_

Function

11.2 ± 2.5 11.9 ± 3.0 0.21 11.1 ± 2.4 12.1 ± 2.8 0.22 11.1 ± 2.4 11.3 ± 2.8 0.66

35

Started Tx

(n=240)

Withdrew

– no tx

(n=19)

Completed

2mo FU

(n=225)

Missing 2mo

FU

(n=15)

Completed

6mo FU

(n=191)

Missing 6mo

FU

(n=49)

Continuous

Measure


value


Physical Activity (mins/day)

(Sedentary ≤1.5

METs)

1096.2 ± 145.0 1076.6 ±

220.8

0.79 1094.0 ±

146.7

1133.9 ±

111.0

0.45 1097.1 ± 143.7 1092.7 ±

151.5

0.90

Physical Activity (mins/day)

(Light, Moderate

>1.5 METs)

169.5 ± 130.3 115.7 ±

101.4

0.13 173.1 ± 131.0 110.0 ± 106.1 0.06 175.4 ± 130.1 145.9 ± 130.1 0.10

Leg Pain Intensity 5.1 ± 3.0 5.1 ± 3.1 0.88 5.1 ± 3.0 4.9 ± 3.9 0.96 4.9 ± 3.0 5.5 ± 3.2 0.21

Back Pain

Intensity

6.5 ± 2.6 6.3 ± 2.3 0.47 6.5 ± 2.6 7.1 ±

3.0

0.22 6.3 ± 2.6 7.3 ± 2.4 0.01

35

Table 1. Baseline demographic and clinical characteristics, by study total and each treatment group. For

categorical variables, “F” indicates P value from Fisher exact test and no “F” indicates P value from chi-square

test. For continuous variable P values from Wilcoxon rank sum test. For continuous variables, P values from

Kruskal-Wallis test.

Total

(N = 259)

Medical

Care

(n = 88)

Group

Exercise

(n = 84)

Manual

Therapy

(N = 87)

Categorical Measure Category N (%) n (%) n (%) n (%) P Value

Sex Male 122 (47.1%) 42 (47.7%) 45 (53.6%) 35 (40.2%) 0.22

Race White 201 (77.6%) 68 (77.3%) 66 (78.6%) 67 (77.0%) 1.00F

Black 56 (21.6%) 19 (21.6%) 18 (21.4%) 19 (21.8%)

Other 2 (0.8%) 1 (1.1%) 0 (0.0%) 1 (1.1%)

Hispanic Yes 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1.00F

Married Yes 125 (48.3%) 40 (45.5%) 43 (51.2%) 42 (48.3%) 0.75

Education LE eighth grade or >

eighth grade but not HS

grad

10 (3.9%) 1 (1.1%) 4 (4.8%) 5 (5.7%) 0.46F

HS grad to some college 112 (43.2%) 37 (42.0%) 35 (41.7%) 40 (46.0%)

College grad or higher 137 (52.9%) 50 (56.8%) 45 (53.6%) 42 (48.3%)

Household income $20K or less 52 (20.1%) 15 (17.0%) 15 (17.9%) 22 (25.3%) 0.69

$20 001-$40 000 81 (31.3%) 29 (33.0%) 27 (32.1%) 25 (28.7%)

$40 000 or more 126 (48.6%) 44 (50.0%) 42 (50.0%) 40 (46.0%)

Current smoker Yes 15 (5.8%) 7 (8.0%) 2 (2.4%) 6 (6.9%) 0.25

Hip OA Yes 43 (16.6%) 14 (15.9%) 14 (16.7%) 15 (17.2%) 0.97

Knee OA Yes 82 (31.7%) 32 (36.4%) 21 (25.0%) 29 (33.3%) 0.26

Qualitative description

of leg pain Pain 121(46.7%) 44(50.0%) 36(42.9%) 41(47.1%) 0.64

Neurologic

(numbness,

heaviness, tingling,

weakness)

138(53.3%) 44(50.0%) 48(57.1%) 46(52.9%)

Predominant pain Legs 46(17.8%) 15(17.1%) 16(19.1%) 15(17.2%) 0.97

Low back 155(59.9%) 55(62.5%) 49(58.3%) 51(58.6%)

Equal 58(23.4%) 18(20.5%) 19(22.6%) 21(24.1%)

Leg pain intensity Mean ± SD 5.06 ± 3.02 5.16 ± 3.36 5.14 ± 2.76 4.87 ± 2.92 0.66

Back pain intensity Mean ± SD 6.52 ± 2.57 6.80 ± 2.59 6.23 ± 2.41 6.53 ± 2.69 0.17

36

Table 1 (cont’d)

Total (N = 259)

Medical

Care

(n = 88)

Group

Exercise

(n = 84)

Manual

Therapy

(N = 87)

Continuous Measure Mean ± SD Mean ± SD Mean ± SD Mean ± SD P Value

Age 72.4 ± 7.8 72.0 ± 7.4 72.9 ± 8.1 72.1 ± 8.1 0.78

BMI 31.0 ± 6.6 31.2 ± 6.3 30.8 ± 6.5 31.2 ± 7.1 0.56

Treatment expectancy_A 35.1 ± 11.9 35.5 ± 11.5 36.5 ± 11.7 33.3 ± 12.5 0.23

Treatment expectancy_B 42.5 ± 9.0 42.5 ± 8.8 42.2 ± 9.4 42.9 ± 8.8 0.92

Treatment expectancy_C 39.1 ± 10.6 39.7 ± 10.9 39.5 ± 10.2 38.2 ± 10.7 0.47

Depression T score 47.8 ± 8.9 48.3 ± 8.2 48.3 ± 9.1 46.8 ± 9.3 0.31

MCDI (comorbidities) 4.7 ± 2.2 4.9 ± 2.2 4.4 ± 2.2 4.7 ± 2.1 0.29

TSK (kinesiophobia) 25.6 ± 4.7 26.1 ± 4.4 25.3 ± 4.9 25.5 ± 4.9 0.53

ABI (Ankle-Brachial Index)

(min of right/left) 1.0 ± 0.2 1.1 ± 0.2 1.0 ± 0.1 1.0 ± 0.2 0.36

Vibration

(max of right/left) 32.6 ± 14.8 32.0 ± 15.2 31.9 ± 14.5 33.8 ± 14.9 0.53

Single leg standing (seconds) 13.2 ± 16.7 11.9 ± 16.6 13.6 ± 17.0 14.3 ± 16.7 0.21

Gait speed (meters/second) 0.9 ± 0.2 0.9 ± 0.2 1.0 ± 0.2 0.9 ± 0.2 0.59

Oswestry Disability Index 38.3 ± 12.8 38.1 ± 11.9 38.7 ± 13.5 38.1 ± 13.2 0.94

Falls score 0.7 ± 1.2 0.7 ± 1.1 0.6 ± 0.9 0.9 ± 1.5 0.73

ABC score

(activities, balance, confidence) 68.9 ± 21.4 67.6 ± 22.5 69.1 ± 21.1 70.1 ± 20.5 0.85

RAND_GH 59.5 ± 18.1 60.8 ± 17.2 57.4 ± 17.6 60.3 ± 19.3 0.44

RAND_P 38.0 ± 21.7 40.3 ± 20.5 36.7 ± 19.7 36.8 ± 24.7 0.40

RAND_SF 47.6 ± 10.6 46.4 ± 10.5 47.3 ± 11.9 49.0 ± 9.4 0.14

RAND_EW 76.3 ± 16.4 75.8 ± 17.4 75.7 ± 15.1 77.3 ± 16.7 0.56

RAND_EF 49.8 ± 19.0 50.2 ± 18.1 49.4 ± 18.5 49.7 ± 20.6 0.99

RAND_PF 45.8 ± 20.4 44.8 ± 20.6 45.1 ± 19.9 47.5 ± 20.8 0.63

RAND_RLE 40.8 ± 43.6 42.4 ± 43.7 42.6 ± 45.5 37.5 ± 41.9 0.72

RAND_RLP 73.7 ± 35.0 75.9 ± 36.0 72.0 ± 33.7 73.3 ± 35.5 0.49

SPWT total time (mins) 7.6 ± 6.9 8.1 ± 7.7 7.1 ± 6.1 7.5 ± 6.9 0.99

37

Total (N = 259)

Medical

Care

(n = 88)

Group

Exercise

(n = 84)

Manual

Therapy

(N = 87)

Continuous Measure Mean ± SD Mean ± SD Mean ± SD Mean ± SD P Value

SPWT total distance (meters) 455.3 ± 480.0 482.2 ± 529.1 433.4 ± 421.2 449.2 ± 485.2 0.91

SSS total 31.5 ± 6.0 31.4 ± 5.8 31.6 ± 6.0 31.7 ± 6.1 0.91

SSS Symptom Severity 20.3 ± 4.3 20.1 ± 4.4 20.4 ± 4.2 20.5 ± 4.4 0.80

SSS Physical Function 11.2 ± 2.5 11.3 ± 2.5 11.2 ± 2.6 11.2 ± 2.5 0.87

Physical activity (mins/day)

(sedentary = ≤ 1.5 METs) 1095.3 ± 150.3 1087.9 ± 152.8 1097.4 ± 159.7 1100.5 ± 138.3 0.81

Physical activity (mins/day)

(light, moderate = > 1.5 METs) 165.5 ± 129.7 167.4 ± 130.1 157.0 ± 125.5 172.0 ± 133.4 0.80

38

Results of Primary Analyses of Primary and Secondary Aims (Linear Mixed Models)

Table 2 provides the results from the primary analyses of all outcome measures related to the

primary and secondary aims. The results are organized into 3 sections within the table: (1)

group means at each time point; (2) unadjusted within-group changes from baseline; and (3)

adjusted between-group differences from baseline. The models for the between-group analyses

were adjusted for the baseline randomization variables used to balance the groups; these

included baseline SSS, SPWT, and age.

At 2 months, there was a statistical significantly greater reduction in adjusted mean SSS score

(range = 12-55) in the manual therapy and individualized exercises (MTE) group compared with

the medical care (MC) group (2.1; 95% CI, 0.3-3.9) and the group exercise classes (GE) group

(2.4; 95% CI, 0.6-4.3). The MCID for the SSS is 3.02 points; therefore, the adjusted between-

group SSS differences were not clinically significant. There was also improvement in the

adjusted mean SPWT score at 2 months in the MTE group compared with MC (135.1; 95% CI, –

17.2-287.4) and GE (46.2; 95% CI, –110.9-203.4), but these adjusted between-group SPWT

differences were not statistically significant. GE showed a statistically significantly greater

improvement in adjusted mean physical activity at 2 months compared with MC (30.5; 95% CI,

3.1-57.9), but clinical significance is unknown due to the lack an established MCID for physical

activity. The linear mixed models did not reveal any significant adjusted between-group

changes in any of the outcome measures at 6 months.

Results of Secondary Analyses of Primary and Secondary Aims (Responder Analyses) Table 3a

presents the results of the omnibus test of 3-way comparisons of proportions of responders in

each treatment arm at 2 months and 6 months. We performed 3 sets of responder analyses, 1

related to each of the primary and secondary outcome measures (SSS, SPWT, and physical

activity [PA]).

39

Table 2. Primary and secondary outcome measures: unadjusted within-group changes from baseline (outcome to baseline) and adjusted* between-group differences in improvement from baseline.

Outcome, Mean ± SD Baseline 2 Months 6 Months

SSS: Total Score (range = 12-55)

Medical care 31.3 ± 5.8

(n = 84)

29.1 ± 6.9

(n = 79)

29.3 ± 6.8

(n = 67)

Group exercise 31.6 ± 6.0

(n = 72)

29.8 ± 5.7

(n = 67)

29.4 ± 6.7

(n = 59)

Manual therapy 31.6 ± 6.1

(n = 84)

27.2 ± 2.9

(n = 80)

28.4 ± 6.7

(n = 65)

SPWT: Total Distance Walked (meters)

Medical care 482.2 ± 529.1 616.6 ± 620.8 683.3 ± 723.3

Group exercise 433.4 ± 421.2 651.5 ± 639.7 688.3 ± 680.3

Manual therapy 449.2 ± 485.2 698.6 ± 662.7 723.5 ± 781.5

SW: Minutes per Day in Light/Moderate Activity (> 1.5 METs)

Medical care 167.4 ± 130.1 148.0 ± 116.8 159.1 ± 128.3

Group exercise 157.0 ± 125.5 170.1 ± 142.5 155.3 ± 113.1

Manual therapy 172.0 ± 133.4 176.1 ± 135.1 161.9 ± 129.7

Unadjusted Within-group Differences, Outcome to Baseline; Mean ± SD

SSS: Total Score 2 Months 6 Months

Medical care –2.0 ± 5.5 –1.5 ± 5.7

Group exercise –1.7 ± 5.2 –2.2 ± 7.1

Manual therapy –4.1 ± 5.9 –2.6 ± 6.1


Medical care 130.5 ± 478.7 165.4 ± 634.7

Group exercise 219.2 ± 413.0 278.7 ± 512.8

Manual therapy 267.8 ± 507.8 256.6 ± 642.0


Medical care –23.1 ± 85.3 –24.5 ± 85.5

Group exercise 4.3 ± 64.8 0.4 ± 75.9

Manual therapy –6.0 ± 76.0 –30.4 ± 85.6

40

Outcome, Mean ± SD Baseline 2 Months 6 Months

Adjusted* Between-group Differences, Outcome to Baseline; Mean (95% CI)

SSS: Total

Group exercise – medical care 0.3 (–1.5, 2.2) –0.6 (–2.5, 1.4)

Manual therapy – medical care –2.1 (–3.9, –0.3) ^

^P = 0.02

–1.2 (–3.1, 0.7)

Group exercise – manual therapy 2.4 (0.6, 4.3) ^

^P = 0.01

0.6 (–1.4, 2.6)


Group exercise – medical care 87.0 (–75.2, 249.2) 91.5 (–77.9, 260.8)

Manual therapy – medical care 129.7 (–27.2, 286.6) 81.0 (–84.3, 246.2)

Group exercise – manual therapy –42.7 (–205.4, 120.0) 10.5 (–159.4, 180.5)


Group exercise – medical care 30.5 (3.1, 57.9) ^

^P = 0.03

23.1 (–6.4, 52.5)

Manual therapy – medical care 18.7 (–7.6, 45.0) –4.6 (–33.1, 23.8)

Group exercise – manual therapy 11.8 (–15.6, 39.1) 27.7 (–1.9, 57.3)

Notes: SPWT = Self-Paced Walking Test; SSS = Swiss Spinal Stenosis score; SW = SenseWear . *Models were adjusted for baseline randomization variables (SSS, SPWT, age). ^ P < 0.05

41

Table 3a. Responder Analysis: 3-way Comparisons of Responders in Each Group After Dichotomizing Within-person

Change in Outcomes (Omnibus Chi-square Test)

Medical Care Group Exercise Manual Therapy P Value

Baseline to 2 Months N (%) N (%) N (%)

≥ 30% reduction in SSS total score 6 (7.6%)

[n = 79]

2 (3.0%)

[n = 66]

16 (20.0%)

[n = 80]

0.002

≥ 30% increase in SPWT total distance walked 37 (48.7%)

[n = 76]

30 (46.2%)

[n = 65]

49 (65.3%)

[n = 75]

0.04

≥ 30% increase in average number of minutes

per day in activity > 1.5 METs

16 (21.3%)

[n = 75]

18 (29.0%)

[n = 62]

21 (28.4%)

[n = 74]

0.51

Baseline to 6 Months

≥ 30% reduction in SSS total score 7 (10.5%)

[n = 67]

7 (11.9%)

[n = 59]

10 (15.4%)

[n = 65]

0.68

≥ 30% increase in SPWT total distance walked 30 (45.5%)

[n = 66]

30 (50.8%)

[n = 59]

32 (49.2%)

[n = 65]

0.82

≥ 30% increase in average number of minutes

per day in activity > 1.5 METs

12 (19.7%)

[n = 61]

14 (27.5%)

[n = 51]

13 (22.0%)

[n = 59]

0.61

Table 3b. 2-way Comparisons of Manual Therapy and Medical Care, Baseline to 2 Months

Medical Care Manual Therapy P Value

≥ 30% reduction in SSS total score 6 (7.6%) 16 (20.0%) 0.02

≥ 30% increase in SPWT total distance walked 37 (48.7%) 49 (65.3%) 0.04

≥ 30% increase in physical activity (> 1.5 METs) 16 (21.3%) 21 (28.4%) 0.32

Table 3c. 2-way Comparisons of Manual Therapy and Group Exercise, Baseline to 2 Months

Group Exercise Manual Therapy P Value




42

Table 3d. 2-way Comparisons of Medical Care and Group Exercise, Baseline to 2 Months

Medical Care Group Exercise P Value




Table 3e. 2-way Comparisons of Manual Therapy and Medical Care, Baseline to 6 Months

Medical Care Manual Therapy P Value




Table 3f. 2-way Comparisons of Manual Therapy and Group Exercise, Baseline to 6 Months

Group Exercise Manual Therapy P Value




Table 3g. 2-way Comparisons of Medical Care and Group Exercise, Baseline to 6 Months

Medical Care Group Exercise P Value




43

We defined a responder as any participant who showed at least a 30% improvement in his or

her outcome measure from baseline to time point of analysis (2 months or 6 months). There

was a significant between-group difference at 2 months for SSS (P = 0.002) and SPWT (P = 0.04),

but not for physical activity (P = 0.51). We found no significant between-group differences at 6

months for any of the 3 outcomes.

We also performed additional analyses of all 2-way comparisons between groups. Tables 3 b-d

present the between-group comparisons at 2 months, and Tables 3 e-g show the results at 6

months. At 2 months, there was a significantly greater proportion of SSS responders in the

manual therapy arm (20.0%) compared with the group exercise (3.0%) and medical care (7.6%)

arms. There was also a significantly greater proportion of SPWT responders at 2 months in the

manual therapy arm (65.3%) compared with the group exercise (46.2%) and medical care

(48.7%) arms. However, these between-group differences in SSS and SPWT outcomes were no

longer significant at 6 months. There were no significant between-group differences in the

proportions of physical activity responders at either 2 months or 6 months. The proportions of

responders by group are also depicted visually with bar graphs in Figure 2 (2 months) and

Figure 3 (6 months).

Results of Analyses for Exploratory Aim 1

Table 4 lists the rates of anticipated unpleasant side effects and serious adverse events

reported by our participants at the 2-month follow-up evaluation. We defined anticipated

unpleasant side effect as any postintervention symptom that was minor and transient in nature

(≤ 2 days duration). There was a significantly greater (P < 0.001) proportion of musculoskeletal

side effects (transient muscle and joint soreness) reported by the participants in the group

exercise and manual therapy arms. Participants in the medical care arm reported a significantly

greater proportion of transient nonmusculoskeletal side effects. Fortunately, there were no

serious adverse events to report from any participant in any of the 3 treatment arms of this

trial.

44

Table 5 provides a tabulation of the number of falls reported by participants at baseline and at

the 6-month follow-up. We found no significant between-group differences in the number of

falls reported at either time point. Table 6 summarizes the adherence and attrition rates for

each treatment arm at 3 different time points. Although group sizes were balanced at baseline,

a significantly greater proportion of subjects dropped out of the group exercise arm after

randomization and never attended any group exercise class. There were no significant

between- group differences in adherence rates for those participants who attended at least 1

intervention session. The adherence rates were above 90% for each of the 3 intervention

groups. There were no significant between-group differences in attrition rates for the 2- or 6-

month follow-up evaluations.

45

Figure 2. Responder analysis of main outcomes: bar graph of the proportions of responders by group.

Responders are defined as patients who had at least a 30% improvement in their outcome measure at 2 months as compared with baseline. Significant between-group differences (P < 0.05).

Figure 3. Responder analysis of main outcomes: bar graph of the proportions of responders by group. Responders

are defined as patients who had at least a 30% improvement in their outcome measure at 6 months as compared

with baseline. No significant between-group differences.

90

80

70

60

50

40

30

20

10

65.3

28.4

7.6 3.0

SSS Total SPWT Total Distance

Responders at 2 MONTHS (≥30% improvement from baseline)

Sensewear

Medical Care Group Exercise Manual Therapy

Per

cen

t o

f R

esp

on

de

rs

46

Table 4. Reported adverse events and anticipated unpleasant side effects, study total and by treatment group at 2

months (2 weeks after end of intervention). Categories are not mutually exclusive or hierarchical because

participants could report more than 1 side effect. No serious adverse events were reported by any participant in

any of the 3 intervention arms.

Anticipated Side Effects

and

Adverse Events

Total

N =

226

Medical

Care

n = 79

Group

Exercise

n = 67

Manual

Therapy

n = 80

P Value

Muscle soreness 71 (29.6%) 5 (6.0%) 22 (31.9%) 44 (54.3%) 0.001

Joint soreness 52 (21.7%) 1 (1.2%) 11 (15.9%) 40 (49.3%) 0.001

Gastrointestinal 6 (7.2%) 6 (7.2%) 0 0 0.004

Drowsiness 5 (6.0%) 5 (6.0%) 0 0 0.01

Dry mouth 4 (4.8%) 4 (4.8%) 0 0 0.04

Headache 3 (3.6%) 3 (3.6%) 0 0 0.11

Fluid retention 3 (3.6%) 3 (3.6%) 0 0 0.11

Dizziness 4 (1.7%) 2 (2.4%) 1 (1.4%) 1 (1.2%) 1.00

Joint swelling 2 (2.5%) 0 0 2 (2.5%) 0.33

Insomnia 2 (2.4%) 2 (2.4%) 0 0 0.33

Off balance feeling 1 (1.4%) 0 1 (1.4%) 0 0.30

Anxiety 1 (1.2%) 1 (1.2%) 0 0 1.00

Increased BP 1 (1.2%) 1 (1.2%) 0 0 1.00

Mood swings 1 (1.2%) 1 (1.2%) 0 0 1.00

Weight gain 1 (1.2%) 1 (1.2%) 0 0 1.00

Falling 1 (1.2%) 1 (1.2%) 0 0 1.00

Serious adverse events

(study related and requiring outside

medical treatment)

0

0

0

0

1.00

47

Table 5. Number of Falls Reported at Baseline and at 6-month Follow-up Evaluation

All

Subjects Medical

Care Group

Exercise Manual Therapy

Number of participants at baseline N = 259 n = 88 n = 84 n = 87 P Value

Number of Falls (during 1 year prior to baseline)

n (%)

n (%)

N (%)

n (%)

0 150 (57.9%) 52 (59.1%) 49 (58.3%) 49 (56.3%) 0.93 1 73 (28.2%) 24 (27.3%) 27 (32.1%) 22 (25.3%) 0.77

2 20 (7.8%) 8 (9.1%) 4 (4.8%) 8 (9.2%) 0.41

≥ 3 16 (6.2%) 4 (4.5%) 4 (4.8%) 8 (9.2%) 0.36

Number of participants at 6 months N = 191 n = 67 n = 59 n = 65 P Value

Number of Falls (between end-of-care and 6 months)

n (%)

n (%)

n (%)

n (%)

0 107 (56.0%) 35 (52.2%) 38 (64.4%) 34 (52.3%) 0.30

1 53 (27.7%) 17 (25.4%) 15 (25.4%) 21 (32.3%) 0.60

2 17 (8.9%) 10 (14.9%) 3 (5.1%) 4 (6.2%) 0.10

≥ 3 13 (6.8%) 4 (6.0%) 3 (5.1%) 6 (9.2%) 0.62

Table 6. Attrition (drop-out) and treatment adherence rates by group at 2- and 6-month follow-up evaluations.

Treatment adherence was defined as attending ≥75% of treatment or exercise sessions.

All

Subjects Medical

Care Group

Exercise Manual Therapy

Number of participants randomized at baseline

N = 259

n = 88

n = 84

n = 87

P Value

Attrition after randomization (received no intervention)

19 (7.3 %)

4 (4.5%)

12 (14.3%)

3 (3.4%)

0.02

Attrition at 2 months (primary end point for analysis)

33 (12.7%)

9 (10.2%)

17 (20.2%)

7 (8.0%)

0.09

Attrition at 6 months 68 (26.3%) 21 (23.9%) 25 (29.8%) 22 (25.2%) 0.79

Adherence to 6-week intervention (subjects who did not drop out after

randomization)

230 (95.8%)

84 (98.8%)

68 (94.4%)

78 (92.9%)

0.76

Table 7 provides a tabulation of the various cointerventions reported by participants who

completed 6 weeks of each treatment at the 6-month follow-up evaluation. A significantly

48

lower proportion of group exercise participants (49%) were exercising at home as compared

with those in either the medical care (72%) or manual therapy (77%) arms. However, a

significantly greater proportion of group exercise (48%) participants were engaged in

community-based exercises, compared with 18% and 23% of those in the medical care or

manual therapy arms, respectively.

Results of Analyses for Exploratory Aim 2 (Heterogeneity of Treatment Effect)

Our second exploratory aim explored potential baseline associations and predictors of

treatment response for SSS and SPWT in each of the 3 treatment groups (heterogeneity of

treatment effect). We used both simple univariate tests of association (chi-square) and

multivariable logistic regression for predictors of treatment effect. The results of the

unadjusted univariate analysis of baseline characteristics and responder status are displayed in

Table 8. We found significant differences between mean SSS and SPWT scores for the

responders and nonresponders with respect to their association with age and falls score.

The results of the multivariable logistic regression models of responders and nonresponders at

2 months are displayed in Tables 9a and 9b. The MTE group showed a higher rate of SSS

response (20%) compared with either the GE group (3%) or the MC group (7.6%). Using the MC

group as the reference group, the MTE group had greater odds of being SSS responders (OR 3.5;

95% CI, 1.2-9.6), and the GE arm had lower odds of being responders (OR 0.4; 95% CI, 0.08-2.1).

The MTE group also showed a higher rate of SPWT response (65.3%) compared with either the

GE group (46.2%) or the MC group (48.7%). The MTE group had greater odds of being SPWT

responders (OR 2.1; 95% CI, 1.1-4.0) when compared with the MC reference group. The GE

group had about the same odds (OR 0.95; 95% CI, 0.5-1.9) of being SPWT responders as the MC

reference group. We also found a significant association between age and responder status;

younger patients were more likely to be SSS and SPWT responders regardless of group

assignment. Falls score was associated only with SSS responder status, with responders more

likely to report fewer falls at 6 months.

49

Table 7. Cointerventions reported by participants from end-of-care to 6-month follow-up. Note that these data

are derived only from those participants who attended the 6-month follow-up visit.

Cointerventions

(between end-of-care and 6 months)

Total

N = 191

Medical

Care

n = 67

Group

Exercise

N = 59

Manual

Therapy

n = 65

P Value

Exercising at home 127 (66.5) 48 (71.6%) 29 (49.2%) 50 (77.0%) 0.003

Exercising in community setting 55 (28.8%) 12 (17.9%) 28 (47.5%) 15 (23.1%) 0.001

Physical therapy 22 (11.5%) 6 (9.0%) 10 (16.9%) 6 (9.2%) 0.29

Chiropractic 21 (11.0%) 12 (17.9%) 5 (8.5%) 4 (6.2%) 0.07

Added use of assistive device 21 (11.0%) 6 (9.0%) 5 (8.5%) 10 (15.4%) 0.38

Spinal injections 19 (9.9%) 5 (7.5%) 7 (11.9%) 7 (10.8%) 0.69

Added/increased pain meds 19 (9.9%) 6 (9.0%) 7 (11.9%) 6 (9.2%) 0.84

Spine surgery 4 (2.1%) 2 (3.0%) 1 (1.7%) 1 (1.5%) 1.00

Stopped/decreased pain meds 3 (1.6%) 2 (3.0%) 0 (0.0%) 1 (1.5%) 0.78

50

Table 8. Univariate analyses of baseline characteristics and responder status, for the SPWT and SSS outcome

measures. SPWT = Self-paced Walking Test; SSS = Swiss Spinal Stenosis symptom severity score.

SPWT Total Di

N = 216

stanc e SSS Total

N = 225

Responder

(n = 116)

Nonrespo

nder (n =

100)

Responder

(n = 24)

Nonrespo

nder (n =

201)

Characteristic

(categorical measures) n (%) n (%) P Value n (%) n (%) P Value

Sex, no. of female 59 (50.9%) 57 (57.0%) 0.37 15 (62.5%) 103 (51.2%) 0.30

Race, no. African American 31 (26.7%) 19 (19.0%) 0.18 8 (33.3%) 43 (21.4%) 0.19

Marital Status, no. of married 64 (55.2%) 48 (48.0%) 0.29 15 (62.5%) 101 (50.3%) 0.26

Education, no. of college grad or higher 61 (52.6%) 46 (46.0%) 0.33 16 (66.7%) 99 (49.3%) 0.11

Household Income, no. making $40 000 or more

57 (50.4%) 45 (45.0%) 0.43 12 (50.0%) 94 (47.5%) 0.82

Diagnosis of hip OA, no. with yes 20 (17.2%) 15 (15.0%) 0.66 3 (12.5%) 32 (15.9%) 0.66

Diagnosis of knee OA, no. with yes 38 (32.8%) 30 (30.0%) 0.66 9 (31.0%) 62 (31.6%) 0.95

Characteristic

(continuous measures) Mean ± SD Mean ± SD P Value Mean ± SD Mean ± SD P Value

Age, years 71.3 ± 7.7 73.7 ± 7.3 0.02 69.2 ± 6.9 72.7 ± 7.6 0.03

BMI, kg/m2 30.5 ± 6.6 30.9 ± 5.8 0.66 32.5 ± 6.7 30.5 ± 6.2 0.15

Depression T score 47.5 ± 9.2 47.1 ± 8.5 0.71 47.4 ± 10.5 47.4 ± 8.6 1.00

Comorbidities 4.5 ± 2.2 4.7 ± 2.2 0.44 5.00 ± 2.7 4.5 ± 2.2 0.34

Kinesiophobia (TSK) 25.2 ± 4.6 25.9 ± 5.1 0.25 25.2 ± 5.2 25.6 ± 4.8 0.66

Ankle Brachial Index 1.0 ± 0.1 1.1 ± 0.2 0.69 1.0 ± 0.1 1.05 ± 0.2 0.76

Vibration 31.7 ± 15.1 34.2 ± 14.2 0.22 30.8 ± 16.0 33.2 ± 14.5 0.44

Single leg standing 13.6 ± 16.3 12.9 ± 17.0 0.75 17.0 ± 18.2 13.0 ± 16.5 0.27

SPPB gait speed 1.1 ± 0.3 1.2 ± 0.4 0.17 1.0 ± 0.2 0.9 ± 0.2 0.68

Fall score 0.8 ± 1.4 0.5 ± 0.8 0.04 0.3 ± 0.6 0.8 ± 1.2 0.002

Balance score (ABC) 70.3 ± 21.3 67.5 ± 21.4 0.34 76.3 ± 20.7 68.6 ± 21.2 0.09

Tables 9a and 9b. Multivariable logistic regression models (using backward stepwise elimination) of

study participants who responded and who did not respond to intervention based on the SSS and SPWT

at 2 months. SSS Swiss Spinal Stenosis; SPWT = Self-Paced Walking Test. Medical care is the reference

group.

Table 9a. SSS: Primary outcome measure (N=225 participants) at 2 months.

Parameter Odds Ratio 95% Confidence Limits p-value

Intercept -- -- -- 0.11

Treatment Type

Group Exercise 0.41 0.08 2.14 0.049

Manual Therapy 3.45 1.24 9.64 0.001

Age 0.92 0.86 0.98 0.016

Falls score 0.46 0.22 0.95 0.037

Table 9b. SPWT: Secondary outcome measure (N=216 participants) at 2 months.

Parameter Odds Ratio 95% Confidence Limits p-value

Intercept -- -- -- 0.02

Treatment type

Group Exercise 0.95 0.49 1.86 0.17

Manual Therapy 2.08 1.07 4.04 0.01

Age 0.96 0.92 0.99 0.02

51

52

To assess if any baseline variables were moderating the relationship between treatment and

responders and nonresponders, we tested the interaction between treatment and each of

several variables using multiple logistic regression models, with SSS and SPWT responder status

as the outcome. We chose the variables based on their biologically plausible relevance to LSS

and the clinical experience of the investigators. Tables 10 and 11 depict the results of these

moderator analyses for the SSS and SPWT outcomes, respectively. We found no significant

moderators associated with the SSS scores; however, Table 11 shows that baseline depression

(P = .06) and the number of comorbidities (P = .06) were 2 variables that showed a trend

toward significance as potential moderators of SPWT outcome. Age, sex, race, body mass index,

fear avoidance, and knee osteoarthritis were not associated with responder status. The

treatment effect of manual therapy versus medical care appears to be stronger among patients

with depression scores above the median and comorbidity scores below it. The P value for

these interactions was 0.06; although not reaching 0.05, it suggests a potential interaction and

moderating effect. While we were not powered for these stratified analyses, these results

warrant further investigation in future studies, given their clinical plausibility of being potential

treatment moderators.

Patient Global Index of Change and Satisfaction

The results of additional exploratory analyses of the PGIC and SAT scores obtained at 2 months

and 6 months are presented in tables. Descriptive statistics of the item ratings and proportions

of responders/nonresponders for PGIC scores are presented in Tables 12a and 12b; those for

SAT scores are presented in Tables 13a and 13b. The manual therapy arm showed the highest

level of PGIC and SAT scores at both time points, followed by group exercise and medical care.

53

Table 10. Analysis of hypothesized moderators at baseline with treatment response for SSS as the dependent

variable (primary outcome measure). R = responder; NR = nonresponder; SSS = Swiss Spinal Stenosis (total score).

P value is for the interaction term, from a Wald chi-square test for interaction.

Moderator

R

(n)

NR

(n) Effect

Odds

Ratio

95% CI

Lower

95% CI

Upper P Value

Age 24 201 Group exercise versus manual therapy age < 75 0.070 0.009 0.558

0.43

Group exercise versus medical care age < 75 0.291 0.031 2.701

Manual therapy versus medical care age < 75 4.167 1.260 13.783

Group exercise versus manual therapy age ≥ 75 0.397 0.038 4.105

Group exercise versus medical care age ≥ 75 0.548 0.046 6.489

Manual therapy versus medical care age ≥ 75 1.380 0.211 9.014

Sex 24 201 Group exercise versus manual therapy male 0.160 0.018 1.449

0.83

Group exercise versus medical care male 0.333 0.033 3.362

Manual therapy versus medical care male 2.083 0.458 9.480

Group exercise versus manual therapy female 0.113 0.014 0.926

Group exercise versus medical care female 0.437 0.043 4.419

Manual therapy versus medical care female 3.870 0.998 15.013

BMI 24 201 Group exercise versus manual therapy BMI < 30 0.162 0.019 1.413

0.91 BMI = body

mass index

Group exercise versus medical care BMI < 30 0.423 0.037 4.877

Manual therapy versus medical care BMI < 30 2.605 0.492 13.796

Group exercise versus manual therapy BMI ≥ 30 0.104 0.012 0.873

Group exercise versus medical care BMI ≥ 30 0.400 0.042 3.786

Manual therapy versus medical care BMI ≥ 30 3.846 1.091 13.563

Comorbidities 24 201 Group exercise versus manual therapy MCDI < 4 0.117 0.000 0.681

0.99

MCDI = Modified Co-morbidity Disease Index

Group exercise versus medical care MCDI < 4 0.355 0.000 3.034

Manual therapy versus medical care MCDI < 4 2.706 0.386 31.596

Group exercise versus manual therapy MCDI ≥ 4 0.218 0.022 1.093

Group exercise versus medical care MCDI ≥ 4 0.687 0.059 5.078

Manual therapy versus medical care MCDI ≥ 4 3.146 0.856 14.506

54

Moderator R

(n)

NR

(n)

Effect Odds

Ratio 95% CI

Lower 95% CI

Upper P Value

Kinesiophobia 24 201 Group exercise versus manual therapy TSK < 26 0.147 0.017 1.266

0.44 TSK = Tampa Scale for Kinesiophobia

Group exercise versus medical care TSK < 26 0.234 0.025 2.217

Manual therapy versus medical care TSK < 26 1.591 0.423 5.981

Group exercise versus manual therapy TSK ≥ 26 0.108 0.013 0.901

Group exercise versus medical care TSK ≥ 26 0.672 0.058 7.737

Manual therapy versus medical care TSK ≥ 26 6.242 1.260 30.924

Race 24 201 Group exercise versus manual therapy not black 0.095 0.012 0.760

0.90

Group exercise versus medical care not black 0.280 0.030 2.589

Manual therapy versus medical care not black 2.962 0.888 9.882

Group exercise versus manual therapy black 0.171 0.018 1.678

Group exercise versus medical care black 0.607 0.050 7.415

Manual therapy versus medical care black 3.542 0.586 21.397

Knee Osteoarthritis 24 201

Group exercise versus manual therapy no knee OA 0.080 0.010 0.644 0.37

OA = osteoarthritis Group exercise versus medical care no knee OA 0.490 0.043 5.582

Manual therapy versus medical care no knee OA 6.140 1.288 29.270

Group exercise versus manual therapy knee OA 0.280 0.030 2.648

Group exercise versus medical care knee OA 0.417 0.042 4.085

Manual therapy versus medical care knee OA 1.488 0.354 6.263

Depression 24 201 Group exercise versus manual therapy T score < 48.2 0.130 0.000 0.695

0.13 T score; from PROMIS short form

Group exercise versus medical care T score < 48.2 0.156 0.000 0.896

Manual therapy versus medical care T score < 48.2 1.171 0.287 5.173

Group exercise versus manual therapy T score ≥ 48.2 0.172 0.017 0.938

Group exercise versus medical care T score ≥ 48.2 2.516 0.126 153.683

Manual therapy versus medical care T score ≥ 48.2 14.652 1.845 678.035

55

Table 11. Analysis of hypothesized moderators at baseline with treatment response for SPWT as the dependent

variable (secondary outcome measure). R = responder; NR = nonresponder; SPWT = Self-paced Walking Test.

P value is for the interaction term, from a Wald chi-square test for interaction.

Moderator R (n)

NR (n)

Effect Odds Ratio

95% CI Lower

95% CI Upper

P Value

Age 24 201 Group exercise versus manual therapy – age < 75 0.455 0.194 1.063

0.75

Group exercise versus medical care – age < 75 0.793 0.354 1.775

Manual therapy versus medical care – age < 75 1.744 0.769 3.960

Group exercise versus manual therapy – age ≥ 75 0.423 0.132 1.361

Group exercise versus medical care – age ≥ 75 1.231 0.362 4.181

Manual therapy versus medical care – age ≥ 75 2.909 0.926 9.135

Sex 24 201 Group exercise versus manual therapy – male 0.688 0.254 1.863

0.46

Group exercise versus medical care – male 1.000 0.390 2.561

Manual therapy versus medical care – male 1.455 0.537 3.941

Group exercise versus manual therapy – female 0.290 0.110 0.762

Group exercise versus medical care – female 0.740 0.282 1.942

Manual therapy versus medical care – female 2.555 1.066 6.126

BMI 24 201 Group exercise versus manual therapy – BMI < 30 0.526 0.215 1.292

0.86 BMI = body

mass index

Group exercise versus medical care – BMI < 30 0.936 0.373 2.350

Manual therapy versus medical care – BMI < 30 1.778 0.701 4.506

Group exercise versus manual therapy – BMI ≥ 30 0.357 0.124 1.033

Group exercise versus medical care – BMI ≥ 30 0.757 0.279 2.050

Manual therapy versus medical care – BMI ≥ 30 2.118 0.833 5.390

Comorbidities 24 201 Group exercise versus manual therapy – MCDI < 4 0.356 0.093 1.359

0.060 MCDI = Modified

Co-morbidity Disease Index

Group exercise versus medical care – MCDI < 4 2.311 0.724 7.375

Manual therapy versus medical care – MCDI < 4 6.500 1.640 25.76

Group exercise versus manual therapy – MCDI ≥ 4 0.397 0.169 0.932

Group exercise versus medical care – MCDI ≥ 4 0.520 0.224 1.210

Manual therapy versus medical care – MCDI ≥ 4 1.308 0.610 2.809

56

Moderator R

(n)

NR

(n)

Effect Odds Ratio

95% CI Lower

95% CI Upper

P Value

Kinesiophobia 24 201 Group exercise versus manual therapy – TSK < 26 0.306 0.114 0.820

0.35 TSK = Tampa

Scale for Kinesiophobia

Group exercise versus medical care – TSK < 26 0.532 0.197 1.436

Manual therapy versus medical care – TSK < 26 1.742 0.646 4.697

Group exercise versus manual therapy – TSK ≥ 26 0.672 0.260 1.741

Group exercise versus medical care – TSK ≥ 26 1.359 0.547 3.376

Manual therapy versus medical care – TSK ≥ 26 2.022 0.827 4.947

Race 24 201 Group exercise versus manual therapy – not black 0.351 0.160 0.768

0.40 Group exercise versus medical care – not black 0.765 0.356 1.646

Manual therapy versus medical care – not black 2.181 1.033 4.608

Group exercise versus manual therapy – black 1.091 0.252 4.714

Group exercise versus medical care – black 1.600 0.387 6.620

Manual therapy versus medical care – black 1.467 0.376 5.723

Knee Osteoarthritis

24

201 Group exercise versus manual therapy – no knee OA 0.373 0.165 0.843

0.37

OA = osteoarthritis Group exercise versus medical care – no knee OA 1.048 0.470 2.335

Manual therapy versus medical care – no knee OA 2.812 1.236 6.395

Group exercise versus manual therapy – knee OA 0.714 0.200 2.549

Group exercise versus medical care – knee OA 0.750 0.219 2.574

Manual therapy versus medical care – knee OA 1.050 0.348 3.167

Depression 24 201 Group exercise versus manual therapy – T score < 48.2 0.826 0.323 2.112

0.06 T score; from

PROMIS short form Group exercise versus medical care – T score < 48.2 0.895 0.339 2.360

Manual therapy versus medical care – T score < 48.2 1.083 0.443 2.645

Group exercise versus manual therapy – T score ≥ 48.2 0.180 0.059 0.549

Group exercise versus medical care – T score ≥ 48.2 0.917 0.367 2.287

Manual therapy versus medical care – T score ≥ 48.2 5.092 1.717 15.103

57

Table 12a. Patient Global Index Change, Baseline to 2 Months

Treatment Type


PGIC item ratings –3 0 0 0

–2 2 1 1

–1 10 4 3

0 27 13 8

+1 19 26 30

+2 14 16 29

+3 7 4 8

Total n per group 79 64 79

n (%) n (%) n (%)

Nonresponders ≤ 0

Responders ≥ 1

39 (49)

40 (51)

18 (28)

46 (72)

12 (15)

67 (85)

PGIC Question: “Since I first started treatment in this research study, my overall status is . . .” Nonresponders: –3 = very much worse; –2 = much worse; –1 = minimally worse; 0 = no change.

Responders: +1 = minimally better; +2 = much better; +3 = very much better.

Table 12b. Patient Global Index Change, Baseline to 6 Months

Treatment Type

Medical Care Group Exercise

Manual Therapy

PGIC item ratings -3 0 1 1

-2 3 3 5

-1 12 7 7

0 19 12 4

1 22 19 28

2 9 12 16

3 2 5 4


n (%) n (%) n (%)

Nonresponders ≤ 0 34 (51) 23 (39) 17 (26)

Responders ≥ 1 33 (49) 36 (61) 48 (74)

PGIC Question: “Since I first started treatment in this research study, my overall status is . . .”

Nonresponders: –3 = very much worse; –2 = much worse; –1 = minimally worse; 0 = no change.

Responders: +1 = minimally better; +2 = much better; +3 = very much better.

58

Table 13a. Treatment Satisfaction, Baseline to 2 Months

Treatment Type


Treatment satisfaction –3 0 2 1

item ratings –2 3 3 0

–1 9 2 3

+1 24 11 8

+2 27 32 26

+3 16 14 41


n (%) n (%) n (%)

Nonresponders ≤ 1

Responders ≥ 2

36 (46)

43 (54)

18 (28)

46 (72)

22 (15)

67 (85)

Satisfaction Question: “How satisfied are you with the treatment you received in this study”? Nonresponders: –3 = extremely dissatisfied; –2 = dissatisfied; –1 = somewhat dissatisfied.

Responders: +1 = somewhat satisfied; +2 = satisfied; +3 = extremely satisfied.

Table 13b. Treatment Satisfaction, Baseline to 6 Months

Treatment Type


Treatment satisfaction –3 0 0 1

item ratings –2 5 0 0

–1 12 3 2

+1 15 9 6

+2 24 30 20

+3 11 17 36


n (%) n (%) n (%)

Nonresponders ≤ 1

Responders ≥ 2

22 (48)

35 (52)

12 (20)

47 (80)

9 (14)

56 (86)

Satisfaction Question: “How satisfied are you with the treatment you received in this study”? Nonresponders: –3 = extremely dissatisfied; –2 = dissatisfied; –1 = somewhat dissatisfied.

Responders +1 = somewhat satisfied; +2 = satisfied; +3 = extremely satisfied.

59

Missing Data

At our primary outcome end point of 2 months we had a total of 33 participants (12.7%) with

missing data. Participants from the group exercise arm had the largest proportion of missing

data at 2 months (20.2%) compared with the medical care (10.2%) and manual therapy (8%)

arms. One reason for missing data was that some subjects withdrew immediately after

randomization and did not receive any intervention. Significantly more participants withdrew

from the group exercise (14.3%) arm of our study than from the medical care (4.5%)

and manual therapy (3.4%) arms. Some subjects did not adhere to their assigned

intervention and withdrew at various times during the 6-week intervention period. Other

subjects completed their assigned intervention but failed to return for their 2- or 6-month

follow-up.

To account for missing data, we used linear mixed effects models to study treatment

differences over time using SSS and SPWT as the dependent variables in separate models.

These models included (1) unadjusted fixed effect of time, treatment, and treatment by time

interaction; (2) least square means by group over time; (3) differences between group means

over time; and (4) adjusted for covariates of interest. The linear mixed models borrow

information pertaining to the relationships in the outcome at multiple time points such that

persons missing data at certain time points can still be used in the analysis.

For the SPWT models, the unadjusted linear mixed model included a fixed effect of time and

treatment. We tested the interaction between time and treatment and not found it to be

statistically significant (P > 0.05). We then adjusted the linear mixed model with main effect of

time and treatment for the covariates of interest previously used in our primary linear

regression models. We found no statistically significant differences between treatment groups

in any of the models involving SPWT. This is consistent with the results of our primary analysis.

For the linear mixed models involving the SSS as the dependent variable, the first model

included a fixed effect of time, treatment, and treatment by time interaction. The interaction

60

term was significant (P = 0.04), suggesting that the SSS score differed between treatment

groups over time. As with the SPWT models, we then performed an adjusted model with the

previously used covariates. The interaction between treatment and time remained significant,

even after adjusting for covariates of interest, suggesting differences in SSS group means over

time adjusted for covariates of interest. Table 14 provides a summary of all missing data for

each outcome measure and each time point.

61

Table 14. Missing data for each outcome measure by assigned intervention group. See footnotes at bottom of

table for key to specific reasons for missing data.

Medical Care (n = 88)

Group Exercise (n = 84)

Manual Therapy (n = 87)

Missing Swiss Spinal Stenosis (SSS) data at 2 months

Average missing data rate = 13.2%

(across all 3 groups)

1n = 4 2n = 3 3n = 2

10.2% missing data

1n = 12 2n = 3 3n = 2 4n = 1

21.4% missing data

1n = 3 2n = 4 3n = 0

8% missing data

Missing Self-paced Walking Test (SPWT) data at 2 months



1n = 4 2n = 3 3n = 2

5n = 3

13.6% missing data

1n = 12 2n = 3 3n = 2 4n = 1 5n = 1

22.6% missing data

1n = 3 2n = 4 3n = 0

5n = 5

13.8% missing data

Missing SenseWear data at 2 months



1n = 4 2n = 3 3n = 2

6n = 6

17% missing data

1n = 12 2n = 3 3n = 2 4n = 1 6n = 3

25% missing data

1n = 3 2n = 4 3n = 0

6n = 5

13.8% missing data

Missing SSS data at 6 months



1n = 4 2n = 3 3n = 2 7n = 12

23.9% missing data

1n = 12 2n = 3 3n = 2 7n = 8

29.8% missing data

1n = 3 2n = 4 3n = 0 7n = 15

25.3% missing data

Missing SPWT data at 6 months



1n = 4 2n = 3 3n = 2 5n = 1 7n = 12

25.0% missing data

1n = 12 2n = 3 3n = 2 5n = 0 7n = 8

29.8% missing data

1n = 3 2n = 4 3n = 0 5n = 0 7n = 15

25.3% missing data

Missing SenseWear data at 6 months

Average missing data rate = 34%


1n = 4 2n = 3 3n = 2 6n = 5 7n = 12

29.5% missing data

1n = 12 2n = 3 3n = 2 6n = 8 7n = 8

39.3% missing data

1n = 3 2n = 4 3n = 0 6n = 7 7n = 15

33.3% missing data

1 Withdrew after randomization, lost to all follow-up (FU). 2 Withdrew during treatment, lost to all FU. 3 Completed care, lost to all FU. 4 Completed care and 6-month FU, but not 2-month FU. 5 Could not complete SPWT for reason other than stenosis. 6 Did not use SenseWear as instructed. 7 Completed care and 2-month FU, but not 6 months FU.

62

DISCUSSION

Context for Study Results

Our results were mixed with respect to confirming our specific aims and hypotheses. For our

primary aim, we hypothesized that participants in both the GE and MTE arms would show

better clinical outcomes in self-reported pain/function (SSS) and walking performance (SPWT)

compared with those randomized to the MC arm. However, we found that all 3 groups showed

modest reductions in SSS and improvement in SPWT at 2 months, but only the improvements in

SPWT were sustained at 6 months.

The results of our regression analyses for the primary outcomes of pain/function found a

statistically significant improvement in mean SSS scores in the MTE arm compared with the

other 2 arms; however, the magnitude of this effect has only marginal clinical significance

because the adjusted between-group differences did not exceed the MCID. The mean

unadjusted within-group improvement of 4.1 points in SSS score from baseline for MTE group

was only modest, considering that the MCID is 3.02 points. The greatest improvement in

walking performance was found in the manual therapy arm, although this was not statistically

significant when compared with the improvements found in the other 2 study arms. Also the

clinical significance of this magnitude of walking improvement in unknown, as there is no

established MCID for walking performance (SPWT).

Compared with those from the regression models, the results of the secondary responder

analyses for our primary outcomes may be more clinically relevant and easier to interpret. The

responder analyses revealed that there were significantly larger proportions of SPWT and SSS

responders in the manual therapy arm at 2 months as compared with either the group exercise

or medical care arms. However, the short-term results favoring the manual therapy

intervention arm at 2 months did not persist at 6 months. This may be explained in part by the

lack of any follow-up treatment, or “booster sessions,” after the initial 6-week intervention

period.

63

For our secondary aim, we hypothesized that participants in the GE and MTE arms would

demonstrate greater changes in PA compared with participants in the MC arm; however, we

found that only participants in the GE arm showed improvement in their level of PA, compared

with either of the other 2 arms. The GE arm showed significantly greater improvement in PA

compared with the MC arm at 2 months but not at 6 months. It was interesting to find that

both the MC and MTE arms showed less PA at 6 months, with only the GE arm participants

maintaining their baseline PA level. This is in direct contrast with the results showing an overall

improvement in walking performance in all 3 groups. This is not surprising, considering that

none of our research interventions provided a targeted treatment for improving PA. This

reinforces the fact that measures of physical performance (walking capacity) are different from

measures of overall physical activity (average time spent in activities > 1.5 METs). It may also

have been unrealistic in this age group to set a 30% increase in PA as the minimum threshold.

We also found some interesting results from our analyses of our first exploratory aim. One

unexpected finding was that a significantly greater number of participants randomized to GE

dropped out immediately after randomization, compared with the other 2 arms. Although no

significant difference in attrition (drop-out) rates existed between groups at 2 months or 6

months, participants who adhered to the GE intervention still had a higher number of

individuals fail to show for their follow-up examinations (Table 6). Feedback received from

those who dropped out of the GE arm after randomization indicated that lack of motivation to

exercise and transportation issues were the major barriers to attending group exercise classes.

However, for those participants who attended at least 1 intervention session, adherence rates

to the assigned interventions were excellent: above 90% in each of the study arms (Table 6). As

noted in the Results section, we did not have any serious adverse events in any of the 3

treatment groups (Table 4). The higher rate of transient musculoskeletal side effects in the GE

and MTE arms was expected due to the more physical nature of those interventions.

Conversely, the higher rate of gastrointestinal side effects in the MC arm was also expected and

64

anticipated as normal reactions to the oral medications prescribed by our research physician

(Table 4).

A little more than 40% of our participants in all 3 arms reported having experienced at least 1

fall in the past year, and this rate did not change significantly in any of the arms at 6 months

(Table 5). We also analyzed the type and number of cointerventions reported by our

participants between the 2- and 6-month follow-up. A significantly greater proportion of

participants from the manual therapy and medical care arms reported that they were doing

home-based exercises as compared with the group exercise arm. This can be explained by the

fact that in both of these intervention arms, participants were given instructions for home-

based exercises.

Conversely, a significantly greater number of participants in the group exercise arm reported

that they were exercising in a community setting as compared with the other 2 arms. This is

not surprising, considering that patients had become accustomed to a routine of exercising in a

group setting twice a week for 6 weeks, which may have led them into a new routine of

regular exercise. In addition, participants in our focus groups told us that they enjoyed the

socialization aspect of group exercise classes, which enhanced their motivation to continue

exercising in the community setting. A total of only 4 research participants (2.1%) reported

having spinal surgery at 6 months, with no significant differences in surgery rates between the

3 groups.

The largest RCT (SPORT trial) comparing surgical and nonsurgical treatments for LSS concluded

that patients treated with surgery had better results for up to 4 years following surgery.17,18

However, in this study there was no standardization of the interventions available to the

subjects who were not randomized to surgery. A secondary analysis of the SPORT trial data was

performed, which focused on the subset of patients in the nonsurgical arm who received

physical therapy (PT) treatment.59 This study showed that receiving PT within the first 6 weeks

after enrollment was associated with a lower rate of progression to surgery at 1-year follow-up.

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Another RCT published after the SPORT trial compared surgical decompression and physical

therapy for LSS.19 This study showed that both surgical and nonsurgical approaches yielded

similar results on self-reported pain and function at 2 years.

Considering the high prevalence of LSS in older adults, there is a surprising lack of evidence

about the effectiveness of well-defined and standardized nonsurgical management approaches

for this common condition. The results of our study should be viewed in the context of the

results from these previous LSS trials. The secondary analysis of the SPORT trial concluded that

future research studies were needed to compare the safety and effectiveness of clearly defined

nonsurgical treatment protocols. Our study provides new evidence about the safety and

effectiveness of 3 well-defined nonsurgical interventions, which may help clinicians provide

patients with information about nonsurgical options that can then be discussed in a shared-

decision-making process. Our results also support the view that patients with LSS can show

some modest level of clinical improvement over time without surgical intervention.

It is also important to view the results of this study within the greater context of the current

nonsurgical management approach to patients with LSS. The guidelines from leading

professional organizations provide little or no guidance to clinicians or patients about which

nonsurgical methods might benefit patients with LSS. There also seems to be a general feeling

among patients and providers that nothing can be done to help a chronic degenerative

condition like LSS—that a slow decline in function is simply to be expected as part of the natural

progression of the condition. Although the natural history of LSS without any treatment or

intervention is not well known, it appears that many patients with LSS remain stable or improve

over time.60 Participants in our focus groups expressed frustration about how little information

was provided to them about viable nonsurgical treatment options by their primary care

physicians (PCPs). Many told us that their PCPs discouraged participation in group exercise

classes, physical therapy, and/or chiropractic care for 2 basic reasons: (1) fear of potential injury

and (2) lack of evidence for effectiveness.

The results of our study provide new evidence for the safety of community-based group

66

exercise classes as well as clinic-based manual therapy and individualized exercise provided by

physical therapists and chiropractors. There were no serious adverse events associated with

participation in either of these intervention groups. Although musculoskeletal side effects were

very common in these 2 groups, they were minor and transient. In fact, patients in our focus

groups said that they actually enjoyed feeling some muscle soreness after exercising in the

group setting or after having their physical therapy or chiropractic session; they interpreted

this soreness as a positive sign that their muscles and joints had been worked out. Our study

should provide physicians with some assurance that patients with LSS can safely participate in

group exercise classes and will not necessarily be harmed by physical therapists or

chiropractors.

With respect to effectiveness, although the amount of improvement in self-reported

pain/function was only short lived and modest, the magnitude of improvement in walking

performance was larger and sustained at 6 months in all 3 groups. Wide variability in our

walking performance data and no established MCID for the SPWT made it difficult to draw

conclusions about the clinical significance of the observed changes in mean distance walked;

however, at 6 months, the responder analysis showed that about half of the patients in all 3

groups were walking at least 30% farther than they were at baseline.

This finding suggests that although LSS is a chronic degenerative condition, patients can still

make some improvements in their physical function and should not be assumed to have a poor

or guarded prognosis. This should be an important component of shared decision making when

patients with LSS explore nonsurgical treatment options with their PCPs. That said, these

findings should be balanced with the amount of time and cost associated with each

intervention. Most patients would be required to make a copay for each of 12 physical therapy

or chiropractic visits, which would be 4 times costlier to the patient than making just 3 copays

with a physician. The cost of group exercise classes is free or just a few dollars each session at

most community centers.

Uptake of Study Results and Generalizability of Findings

67

The demographic makeup of our study participants (Table 1) is very similar and comparable to

the populations of LSS participants in the previously noted trials by Weinstein et al17,18 and

Delitto et al19 with respect to baseline age, BMI, medical comorbidities, and self-reported

levels of pain and function. The socioeconomic and racial diversity of our participants was

comparable to the general demographics of the urban Pittsburgh population, and thus our

results should be generalizable to most other major metropolitan urban populations in the

United States.

The pragmatic nature of this trial facilitates the implementation and uptake of our results by

many of our stakeholders. Our medical care protocol was straightforward and pragmatic.

Although administered by a physiatrist in our study, this approach to shared decision making

and tailoring medications to each individual patient could easily be implemented by most PCPs.

PCPs could also provide more referrals to chiropractors and physical therapists for nonsurgical

management of LSS; however, information obtained from focus groups of LSS patients revealed

that most PCPs are hesitant to refer their LSS patients to chiropractors and physical therapists,

citing lack of evidence for the safety and effectiveness of such interventions. To overcome this

barrier to the uptake of our study results, our research physiatrist will actively disseminate our

results at PCP grand rounds. We also plan to publish a commentary article about our medical

care protocol in a peer reviewed journal geared toward a PCP readership. In addition, our local

UPMC Healthplan stakeholders will assist us in developing an active dissemination and

implementation plan to increase the uptake of our study results, by increasing awareness

among PCPs who are network providers in this local health plan.

The findings from our group exercise arm are clearly generalizable to the real-world setting.

Most community centers that provide services to older adults offer some type of group exercise

class. We did not have to create any new group exercise protocol for our study; we simply

provided access to existing community-based group exercise classes. The cost of these classes is

minimal or free to most older adults as a benefit under major health insurance plans, which

removes the financial barrier to uptake of the study results. Our stakeholders include the

68

directors of 2 large community centers that service older adults in Pittsburgh. They agreed that

these findings should be disseminated widely to the other community centers in the Pittsburgh

metro area. They will also work with the PI on an active dissemination plan to push these study

results directly to their members and community-dwelling older adults residing in

neighborhoods near their centers.

The findings from the manual therapy and individualized exercise protocol that we developed

for this study are very relevant to the chiropractic and physical therapy professions. Our results

show that utilization of this protocol is a safe and effective intervention for the nonsurgical

management of patients with LSS. Most of the individual procedures within our study protocol

are commonly utilized by chiropractors and physical therapists, making the results potentially

generalizable to clinicians in both professions, who are already familiar with at least some of

these procedures. However, very few physical therapists or chiropractors are currently

combining these individual procedures into a comprehensive “boot camp” approach, as we

utilized in our research protocol. We also discovered a potential barrier to the uptake of these

study results from focus groups and informal discussions; namely, that many chiropractors and

physical therapists lack confidence in their ability to provide effective treatment to patients

with LSS. They shared a collective belief that there was a lack of evidence for the safety and

effectiveness of the nonsurgical methods available to them.

To help overcome this barrier, the PI and coinvestigators are in the process of designing a

weekend-based continuing education course for chiropractors and physical therapists; in it we

will provide a review of the clinical examination, diagnosis, and treatment options for LSS. This

course will also include a hands-on workshop to provide skills and training in the combination

of procedures utilized in our research protocol. We believe that this active dissemination and

implementation strategy will lead to greater uptake of our study results by the chiropractic and

physical therapy professions, who will have greater confidence and skills in managing patients

with LSS. We also believe that this training will lead to a greater rate of referral to these

providers by PCPs.

69

Subpopulation Considerations As discussed in the Results section of this report, we explored the heterogeneity of treatment

effect by performing an analysis of baseline associations and predictors of treatment response.

We found a significant association between age and responder status: Younger patients were

more likely to be SSS and SPWT responders, regardless of group assignment. Falls score was

associated only with SSS responder status, with responders more likely to report fewer falls at 6

months. We did not find any significant moderators associated with either of our primary

outcome measures of self-reported pain/function (SSS) or walking performance (SPWT).

Baseline depression and number of comorbidities showed a trend (P = 0.06) toward significance

as possible moderators of SPWT outcome.

The treatment effect of manual therapy versus medical care appears to be stronger among

patients with depression scores above the median and comorbidity scores below it. Age, sex,

body mass index, fear avoidance, and knee osteoarthritis were not associated with responder

status. It is important to note that we were not sufficiently powered for these stratified

analyses; however, some of these associations warrant further investigation in future research

trials given their clinical plausibility as potential treatment moderators.

Study Limitations

There was large heterogeneity in the clinical response found in our study, and that while some

patients improved in each group and the interventions were shown to be safe, the overall levels

of response (improvement) were low. In addition, our study was unable to identify which

patient characteristics were predictive of treatment response. The large standard deviations

associated with the walking performance and physical activity data reflect the large variation in

the clinical status of patients with LSS. There is a need for further research in the area of

nonsurgical interventions and how they may have differential effects on various subgroups of

LSS patients.

70

Compared with either of the other intervention arms, a significantly greater proportion of

subjects withdrew from the group exercise arm immediately after randomization. This may

have created selection bias, in which those subjects who chose to accept randomization into

group exercise were more motivated toward physical activity than subjects in the other 2 arms

of the study. Increased motivation might be a confounding variable in those results showing

greater physical activity in this group at 2 months. Also, subjects who received the MTE

intervention spent about 45 minutes face to face with a physical therapist or chiropractor for 12

sessions. This increased personal attention might be a confounding variable in those results

showing greater short-term improvement in self-reported pain/function with MTE.

We also found some limitations in the use of the SPWT. We noticed a sense of boredom in

some of our subjects, which may have influenced their decision about when to stop the test

even if they could have walked farther. We also received feedback from participants in our

focus groups about how their walking performance could vary day to day, based on the

natural fluctuations of a chronic degenerative disease such as LSS. They also told us that in real

life, they had challenges with walking over uneven ground, steps, and curbs, which were not

part of the SPWT. Some participants had other medical problems that precluded them from

completing the SPWT, which led to some missing SPWT data at 2- and 6-month follow-ups.

However, subjects agreed that given the choice, the SPWT was still a better measure of their

true walking performance compared with other outcome measures such as the Shuttle Walk

Test or treadmill tests.

There were also some limitations with the use of the physical activity monitor. Although the

device was rather small and unobtrusive, it was still large enough that some subjects found it

uncomfortable to wear 24 hours per day for 7 consecutive days. As noted earlier, this led to the

situation in which we had missing physical activity data for a subset of research participants at

2- and 6-month follow-ups. Participants in our focus groups also gave us important feedback

about their perceptions of the challenges associated with measuring physical activity. They told

us that, similar to the challenges with measurements of walking performance, their level of

71

general physical activity varied by day and by week based on many factors other

than their LSS. Many subjects told us that they wanted to be able to walk farther at any 1

time but that they did not really desire to increase their overall level of physical activity.

This trial allowed for some discretion on the part of our medical care and manual therapy

providers to modify their clinical interventions based on each patient’s needs. The

heterogeneity in providing this care is a limitation that prevented us from assessing which

component(s) of these interventions may have moderated the treatment effects, reducing the

internal validity of the results; however, this heterogeneity is found in the real-

world setting and improves the external validity of these results.

Finally, in retrospect we realize that our original choice of the term usual medical care may not

have been the most accurate terminology. Patients in our focus groups who were randomized

to the medical care arm told us that our research physician gave them much more time and

attention than what they generally had received previously from their other physicians. Also

they told us how much they appreciated our physician’s thoroughness in reviewing all of their

medications, trying his best to minimize the dosages and number of medications and taking the

time to more fully explain all treatment options. In short, our “usual” medical care may have

been “unusual,” which may partly explain our research participants’ generally favorable

response to this intervention.

Future Research

One potential area for future research would be to compare the effectiveness of multimodal

“bundles” of different interventions, possibly with a factorial design. We designed this study as

a comparative effectiveness trial seeking the most effective of these 3 interventions;

however, in real clinical practice it might better serve patients if various combinations of these

interventions are utilized in a multimodal or sequential manner. It is possible that a

combination of 2 or 3 interventions used in our trial might have a synergistic or sequential

effect and provide LSS patients with more clinical benefit than any one individual intervention.

For example, patients with high levels of pain may get more benefit from manual therapy or be

72

more tolerant of exercise when concurrently managed by a physician with appropriate

medications or even an epidural steroid injection. Also, patients who are responding well to

chiropractic or physical therapy treatment might benefit from participating in concurrent group

exercise classes, and vice versa.

Another research question is whether it is more effective to provide “booster sessions,” or

periodic visits to a chiropractor or physical therapist spaced out over time, rather than in a

single bolus of treatment typically given within a 6-week intervention. In the focus groups,

participants told us that they realized LSS was a chronic disorder that could not realistically be

“cured” with 6 weeks of any intervention. They told us that they felt they would benefit from

more regular and periodic visits, or booster sessions, to a physical therapist or chiropractor as

a type of long-term management of their chronic degenerative condition. They also told us that

continuing with regular exercise over the long term was helpful in maintaining the short-term

benefits they gained during 6-week intervention period.

It would also be a novel concept to create more collaboration and coordination of care

between physical therapists, chiropractors, and the community centers that offer group

exercise classes for older adults. After completing an intensive course of individualized physical

therapy or chiropractic care, LSS patients could be transitioned to group exercise classes for

ongoing maintenance of their improved function. These are all testable hypotheses for future

clinical comparative effectiveness research studies.

CONCLUSION

Our study found that the combination of manual therapy and individualized exercise leads to

significantly greater short-term improvement in the primary outcome of pain/function at 2

months compared with either of the other 2 groups. Compared with medical care, group

exercise led to significantly greater improvement in the secondary outcome of physical activity at

2 months. The clinical significance of these short-term improvements and between-group

differences is uncertain. At 6 months, these short-term improvements in self-reported

73

pain/function and general physical activity were not sustained; however, all groups maintained

their within-group improvements in walking performance at 6 months. No serious adverse

events were reported in any of the treatment groups.

Concerns about the rising rates of opioid use and spine surgery in older adults make a

compelling case for the dissemination of research evidence about safe and effective alternative

treatment options for LSS. Previous trials have provided evidence only from comparisons of

surgical versus nonsurgical interventions. This has resulted in a serious evidence gap about

comparisons of different well-defined nonsurgical interventions with each other, rather than

with surgery. The results of our study provide evidence to help fill that gap.

It is simplistic to dichotomize all LSS patients into being either “surgical” or “nonsurgical”

candidates or to suggest that one general approach is clearly better than the other for every

patient. Because no single intervention appears to be superior for the long-term management of

LSS, consideration should be given to patient preference, clinical status, and medical

comorbidities within the context of shared-decision making. The interventions provided in our

study are well defined and pragmatic nonsurgical approaches that could be offered as options to

LSS patients in a stepped approach. More nonsurgical comparative effectiveness studies are

needed to provide additional evidence about the long-term management and prognosis of

patients with LSS.

74

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Appendix A: Manual therapy and individualized exercise

protocol implemented by the study chiropractors and physical

therapists.

All research participants randomized to this group will receive a combination of manual therapy and

exercise therapy from a licensed chiropractor or physical therapist. Each encounter will last a total of

about 45 minutes.

I. WARM-UP PROCEDURE

A. Stationary Bicycle: The warm-up period each visit will gradually be increased from 5 to 20 minutes

over the course of the 6-week treatment plan, depending on each individual’s exercise tolerance.

II. MANUAL THERAPY PROCEDURES

A. Prone Procedures

1. Lumbar Distraction Mobilization. This procedure will be performed in the prone position on a

special treatment table (Cox-Zenith Table) that allows for the caudal section to be distracted away

from the cephalad section, as well as, moved toward the floor and/or laterally. The clinician will

place the heel of one hand over the spinous process of each lumbar vertebra while the other hand

pushes on the caudal section of the table (or by using the attached “T”-bar), creating segmental

distraction and mobilization of each segment.

2. Hip Mobilization. All mobilizations will be Grade 4, taking the joint to full end-range position within

the subject’s tolerance. Apply static deep pressure over the gluteus medius, minimus and piriformis

muscles to loosen these soft tissues, while passively rotating the hip into internal, then external

rotation. Repeat 3 times, bilaterally. Mobilize each hip joint individually into extension by stabilizing

the pelvis/sacrum with the heel of one hand and lifting the subject’s thigh (with flexed knee) off the

table a few inches. The hip joint will be extended to end-range 3 times using contract-relax technique,

isometrically contracting the muscle to be stretched. Mobilize each hip joint individually into full

internal/external rotation 3 times using a contract-relax technique. Mobilize each hip joint

individually into full abduction 3 times using a contract-relax technique to stretch the adductors

muscles and allow for full hip abduction.

B. Side-Posture Procedures

1. Side Posture Mobilization. After completion of the prone procedures, the subject will be placed in

the side posture position, making sure to keep the subject’s lumbar spine in flexion. The clinician

then segmentally mobilizes the lumbar spine into rotation bilaterally, each segment 3 times.

2. Femoral Nerve Mobilization. Place subject in side-lying “slumped” position with cervical and

thoracic spine in flexion with head on a pillow. Perform with the intent of tensioning, the L1 through

L3 nerve roots. Each mobilization is performed 20 repetitions using two different positions. This is 2

sets of neural mobs for each leg, repeated bilaterally. The subject is shown these as self-

80

mobilizations to be performed bilaterally at home on a daily basis.

a. Distal: Involved side up. Hold subject’s thigh and ankle. Hip is extended to

barrier, knee is flexed, rhythmic knee flexion. Repeat 20 times.

b. Proximal: Knee is flexed, hip is extended, rhythmic hip extension. Repeat 20 times.

C. Supine Procedures

Several manual therapy techniques will be performed with the subject lying in the supine position.

1. Individual Knee-to-Chest Mobilization. Flex the subject’s individual hip and knee toward the

chest with external rotation, using a contract-relax technique, one side at a time. Repeat 3

times.

2. Bilateral Knee-to-Chest Flexion Mobilization. Perform with both knees flexed and brought up

toward the chest, creating a flexion mobilization of the lumbar spine. Contract-relax technique

will be used to facilitate this stretch/mobilization.

3. Contralateral Knee-to-Chest Mobilization. Flex hip and knee toward opposite shoulder using

contract- relax technique to stretch piriformis.

4. Hamstring Stretch. Stretch the hamstrings using a straight leg raise procedure with

contract-relax technique.

5. Lumbar Hyperflexion. Bring both legs overhead with knees extended using contract-relax.

6. Rotational Lumbar Mobilization. Perform with the subject’s knees bent and feet flat on the

treatment table. Gently push on both knees laterally, and rotate the lumbar spine to end range

bilaterally, using contract-relax with twist and heels on table.

7. Sciatic Nerve Mobilization. Perform with the intent of tensioning the lumbosacral nerve roots,

L4, L5 and S1. Each mobilization is performed 20 repetitions using three different positions.

The participant is shown these as self-mobilizations to be performed bilaterally at home on a

daily basis.

a. Distal: Hip is flexed, knee extended, rhythmic ankle plantar/dorsi-flexion.

b. Intermediate: Hip is flexed, flexion/extension of the knee with ankle dorsiflexion.

c. Proximal: Ankle in dorsiflexion, knee extended, rhythmic hip flexion.

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III. HOME EXERCISES

The last 10 minutes of each session will be demonstration and review of home-based exercises and neural mobilizations with the subject. There is a specific series of home exercises that subjects will be prescribed sequentially over the course of the 6-week treatment program. These are described in a separate lumbar spinal stenosis exercise booklet created by Dr. Carlo Ammendolia. Note that some of the manual procedures listed above are duplicated on the exercise checklist as self-stretching techniques. Instruct the subject on each visit how to do the next exercise(s) and increased repetitions. Refer to the exercise booklet for details.

1. Stationary Bike - Start with 5 minutes of continuous cycling daily, with goal of increasing to 20 minutes daily within 6 weeks.

2. Lying on Back a. Knee-to-Chest

b. Knee-to-Opposite Chest

c. Double Knee-to-Chest

3. Sitting on Chair

a. Sit to Stand, then Stand to Sit, repeat

4. Nerve Flossing {Neuro-Mobilization)

a. Distal {Ankle)

b. Intermediate {Knee)

c. Proximal (Hip)

d. Sitting Forward - Flex body and arms toward floor

5. Lying on Side

a. Side Sit-up

b. Quadriceps stretch

c. Side Hip-lift

6. Lying on Stomach, pillow under pelvis

a. Torso Extension

b. Back Leg Extension

7. Lying on Back

a. Pelvic Tilt

b. Pelvic Twist

c. Half Sit-up

8. Standing

a. Standing pelvic tilt

b. Groin stretch

9. Walking

a. Walking with posterior pelvic tilt

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Appendix B: Spinal Stenosis Recruitment - Postcard Direct Mailings to selected zip codes within the

City of Pittsburgh (Nov 2013 – Sept 2015)

Month/Year Zip Code Quantity

November 2013 15217 (Squirrel Hill) 1,800 (split)

January 2014 15217 (Squirrel Hill) 1,800 (split)

January 2014 15206 (East Liberty) 3,676

March 2014 15221 (Regent Square) 2,550 (split)

May 2014 15221 (Regent Square) 2,550 (split)

June 2014 15224 (Bloomfield) 1,358

August 2014 15203 (South Side) 1,233

September 2014 15219 (Uptown, Hill District)

1,577

October 2014 15201 (Lawrenceville) 1,822

November 2014 15218 (Edgewood, Swissvale)

2,114

December 2014 15207 (Hazelwood) 1,746

January 2015 15212 (North Side, Brighton Heights)

2,000

February 2015 15227 (Hayes) 2,212 (split)

March 2015 15227 (Hayes) 2,212 (split)

March 2015 15217 (Squirrel Hill) 1,841 (split)

March 2015 15210 (Carrick) 1,699 (split)

March 2015 15217 (Squirrel Hill) 1,841 (split)

April 2015 15210 (Carrick) 1,699 (split)

April 2015 15227 (Hayes) 2,212 (split)

April 2015 15206 (East Liberty) 1,838 (split)

May 2015 15227 (Hayes) 2,212 (split)

May 2015 15206 (East Liberty) 1,838 (split)

June 2015 15213 (Oakland) 2,040

June 2015 15224 (Bloomfield) 1,358

July 2015 15232 (Shadyside) 1,018

July 2015 15207 (Hazelwood) 1,746

July 2015 15218 (Edgewood/Swissvale)

2,114

August 2015 15201 (Lawrenceville) 1,822

August 2015 15221 (East End) 2,559 (split)

August 2015 15221 (East End) 2,559 (split)

September 2015 15203 (South Side) 1,233

September 2015 15208 (Homewood) 1,575

September 2015 15219 (Uptown, Hill District)

1,577

TOTAL N = 61,593

83

Copyright© 2019. University of Pittsburgh at Pittsburgh. All Rights Reserved.

Disclaimer:

The [views, statements, opinions] presented in this report are solely the responsibility of the author(s) and do not necessarily represent the views of the Patient-Centered Outcomes Research Institute® (PCORI®), its Board of Governors or Methodology Committee.

Acknowledgement:

Research reported in this report was [partially] funded through a Patient-Centered Outcomes Research Institute® (PCORI®) Award (587). Further information available at: https://www.pcori.org/research-results/2012/comparing-effectiveness-nonsurgical-treatments-lumbar-spinal-stenosis-reducing

https://www.pcori.org/research-results/2012/comparing-effectiveness-nonsurgical-treatments-lumbar-spinal-stenosis-reducing

https://www.pcori.org/research-results/2012/comparing-effectiveness-nonsurgical-treatments-lumbar-spinal-stenosis-reducing

comparing the effectiveness of nonsurgical treatments for … · 2019. 2. 26. · 1 comparing the...

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