Supplementary Online Content
Barber MD, Brubaker L, Burgio KL, et al. Factorial comparison of 2 transvaginal
surgical approaches and of perioperative behavioral therapy for women with apical
vaginal prolapse: the OPTIMAL randomized trial. JAMA.
doi:10.1001/jama.2014.1719.
eTable 1. Inclusion and exclusion criteria for the OPTIMAL Trial
eTable 2. Components and Aims of OPTIMAL Perioperative Behavioral Therapy
and Pelvic Floor Muscle Training Program
eTable 3. Demographics and Baseline Characteristics Across Treatment Cells
eTable 4. Surgical Procedures and Perioperative Outcomes
eTable 5. Postoperative Treatments for Urinary Incontinence or Pelvic Organ
Prolapse
eTable 6. Pelvic Organ Prolapse Outcomes
eTable 7. Patient-Reported and Measured Secondary Outcomes
eTable 8. Adverse Events Related to the Surgical Outcome
eBox. Severity Grade Determined by a Modified Version of the Dindo
Classification System
eTable 9. Pelvic Floor Distress Inventory Results
This supplementary material has been provided by the authors to give readers
additional information about their work.
Corrected: This Supplement was corrected online June 25, 2015.
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
eTable 1. Inclusion and exclusion criteria for the OPTIMAL Trial.
Inclusion Criteria
1) POPQ Stage 2 to 4 pelvic organ prolapse
2) Prolapse of the vaginal apex or cervix to at least half way into the vaginal canal (POPQ Point
C > -TVL/2)
3) Vaginal bulge symptoms as indicated by an affirmative response to either question 4 or 5 of
the PFDI:
a.
Do you usually have a sensation of bulging or protrusion from the vaginal area?
b.
Do you usually have a bulge or something falling out that you can see or feel in
the vaginal area?
4) Vaginal surgery for prolapse is planned, including a vaginal apical suspension procedure.
5) Stress incontinence symptoms as indicated by an affirmative response to any of the 3 items in
the PFDI Stress incontinence subscale:
a.
Do you usually experience urine leakage related to coughing, sneezing or
laughing?
b.
Do you usually experience urine leakage related to physical exercise such as
walking, running, aerobics, or tennis?
c.
Do you usually experience urine leakage related to lifting or bending over?
6) Documentation of transurethral stress leakage on an office stress test or urodynamics with or
without prolapse reduction within the previous 12 months
7) A TVT is planned to treat stress urinary incontinence.
8) A BPMT visit can be performed at least 2 weeks and not more than 4 weeks before surgery.
9) Available for 24-months of follow-up.
10) Able to complete study assessments, per clinician judgment.
11) Able and willing to provide written informed consent.
Exclusion Criteria
1) Contraindication to SSLF, ULS, or TVT in the opinion of the treating surgeon.
2) History of previous surgery that included a SSLF or ULS. (Previous vaginal vault
suspensions using other techniques or in which the previous technique is unknown are
eligible).
3) Pelvic pain or dyspareunia due to levator ani spasm that would preclude a BPMT program.
4) History of previous synthetic sling procedure for stress incontinence.
5) Previous adverse reaction to synthetic mesh.
6) Urethral diverticulum, current or previous (i.e., repaired).
7) History of femoral to femoral bypass.
8) Current cytotoxic chemotherapy or current or history of pelvic radiation therapy.
9) History of two inpatient hospitalizations for medical comorbidities in the previous 12
months.
10) Subject wishes to retain her uterus. [Both ULS and SSLF include removal of the uterus, if not
previously removed].
BPMT = Behavioral therapy with pelvic floor muscle training; SSLF = Sacrospinous ligament
fixation; ULS = Uterosacral vaginal vault suspension (ULS); TVT = Tension Free Vaginal Tape;
POPQ = Pelvic Organ Prolapse Quantification examination to assess vaginal support; TVL =
Total vaginal length. PFDI = Pelvic Floor Distress Inventory
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
eTable 2. Components and Aims of OPTIMAL Perioperative Behavioral Therapy and Pelvic Floor
Muscle Training Program
Pelvic Floor Muscle Examination - performed at each visit
Aim 1: To evaluate participant’s skill to perform pelvic floor muscle exercise.
Aim 2: Based on evaluation of participant performance, to individualize pelvic floor muscle exercise
recommendations including duration (1-10 seconds) and number of pelvic floor muscle contractions (4560/day divided over 3 exercises sessions), and position for exercise (supine, sitting, and/or standing).
Aim 3: To improve participant’s pelvic floor muscle exercise skill via teaching and practice.
Pelvic Floor Exercise Progression
Visit 1 (pre-operative):
Initial contraction duration of 1-3 seconds. Goal: Maximal duration of 7 seconds before surgery
2-4 Day post-hospital discharge telephone call:
Resume exercise at comfort level with goal maximal contraction duration by visit 2 of 3 seconds
Visit 2 (2 weeks post-operative):
Initial contraction duration of 1-3 seconds. Goal maximum duration by visit 3 of 10 seconds
Visits 3 (4-6 weeks post-operative) & Visit 4 (8 weeks post-operative):
Initial contraction duration of 1-10 sec. Goal maximum duration by visit 4 of 10 sec
Visit 5 (12 weeks post-operative): Provided maintenance exercise program of 15 pelvic floor muscle
contractions/day at maximum achieved contraction duration.
Behavioral Therapy Aims and Specific Education/Strategies - assessed at each visit; interventions as
indicated
Aim 1: Protect surgical repair by reducing intra-abdominal pressure during activity. Interventions
included education on proper lifting techniques and contracting pelvic floor muscles during lifting
Aim 2: To prevent/manage SUI. Intervention included functional use of pelvic floor muscles, known as
The “Knack” or “Stress Strategy”1-3
Aim 3: To reduce urgency and prevent UUI. Intervention included urge suppression using pelvic floor
contractions; deep breathing and/or mental distraction.4
Aim 4: Prevent/manage dysfunctional voiding and protect surgical repair. Interventions included: toilet
posture; relaxation of pelvic floor muscles to initiate urine stream; taking time to fully empty bladder; not
straining.
Aim 5: Prevent/manage colorectal symptoms & dysfunctional defecation and protect surgical repair.
Interventions included stool consistency management; timely response to gastrocolic reflex to defecate;
pelvic floor muscle relaxation to allow stool passage; not straining.
Aim 6: Reinforce and problem-solve to ensure correct practice and adherence.
SUI: Stress Urinary Incontinence; UUI: Urgency Urinary Incontinence
1. Burgio KL, Whitehead WE, Engel BT. Urinary incontinence in the elderly. Bladder –sphincter biofeeback and
toileting skills training. Ann Intern Med. 1985;103(4):507-515.
2. Goode PS, Burgio KL, Locher JL, et al. Effect of behavioral training with or without pelvic floor electrical
stimulation on stress incontinence in women: a randomized controlled trial. JAMA. 2003;290(3):345-352.
3. Miller JM, Ashton-Miller JA, DeLancey JOL. A pelvic muscle precontraction can reduce cough-related urine loss
in selected women with mild SUI. J Am Geriatr Soc. 1998;46(7): 870-874.
4. Burgio KL, Locher JL, Goode PS, Hardin JM, McDowell BJ, Candib D. Behavioral versus drug treatment for
urge incontinence in older women: A randomized clinical trial. JAMA 1998;280(23):1995-2000.
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
eTable 3. Demographics and Baseline Characteristics Across Treatment Cells
Variable
ULS / BPMT
N=91
ULS / Usual Care
N=97
SSLF / BPMT
N=95
SSLF / Usual Care
N=91
Mean (SD)
58.7 (10.5)
55.8 (11.0)
56.3 (11.2)
58.1 (10.7)
Min, Max
29.0, 80.0
31.0, 78.0
32.0, 79.0
35.0, 80.0
>=29 and <=40
4 (4.4%)
6 (6.2%)
11 (11.6%)
4 (4.4%)
>40 and <=50
16 (17.6%)
29 (29.9%)
24 (25.3%)
16 (17.6%)
>50 and <=60
35 (38.5%)
31 (32.0%)
24 (25.3%)
37 (40.7%)
>60 and <=70
23 (25.3%)
19 (19.6%)
26 (27.4%)
21 (23.1%)
>70 and <=80
13 (14.3%)
12 (12.4%)
10 (10.5%)
13 (14.3%)
74 (81.3%)
8 (8.8%)
0 (0.0%)
0 (0.0%)
9 (9.9%)
84 (86.6%)
4 (4.1%)
0 (0.0%)
0 (0.0%)
9 (9.3%)
80 (84.2%)
7 (7.4%)
1 (1.1%)
1 (1.1%)
6 (6.3%)
77 (84.6%)
3 (3.3%)
3 (3.3%)
1 (1.1%)
7 (7.7%)
19 (20.9%)
72 (79.1%)
22 (22.7%)
75 (77.3%)
19 (20.0%)
76 (80.0%)
15 (16.5%)
76 (83.5%)
63 (69.2%)
29 (31.9%)
1 (1.1%)
15 (16.5%)
65 (67.0%)
27 (27.8%)
2 (2.1%)
22 (22.7%)
62 (65.3%)
27 (28.4%)
2 (2.1%)
18 (18.9%)
61 (67.0%)
26 (28.6%)
1 (1.1%)
17 (18.7%)
3.0
3.0
3.0
2.0
Age, yrs
Age, n (%)
Race, n (%)
White/Caucasian
Black/African American
Asian
American Indian/Alaskan
Other
Ethnicity, n (%)
Hispanic
Non-Hispanic
Insurance
Private/HMO
Medicaid/Medicare
Self-Pay
Other
Vaginal Deliveries,
Median
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
Variable
Min, Max
Cesarean deliveries,
Median
Min, Max
Menstrual status, n (%)
Pre-menopausal
Post-menopausal
Not sure
Currently using estrogen replacement
therapy, n (%)
Oral/Patch
Vaginal
Current smoker, n (%)
Diabetes mellitus, n (%)
Connective tissue disease (SLE, Marfans,
Sjogrens, Scleroderma), n (%)
Prior hysterectomy, n (%)
Prior stress urinary incontinence surgery,
n (%)
Prior pelvic organ prolapse surgery,
n (%)
Body mass index, kg/m2
Mean (SD)
Min, Max
Pelvic Organ Prolapse Quantification
(POPQ) Stage, n (%)*
2
3
4
Regularly perform pelvic floor muscle
exercises, n (%)
ULS / BPMT
N=91
0.0, 15.0
ULS / Usual Care
N=97
0.0, 9.0
SSLF / BPMT
N=95
0.0, 8.0
SSLF / Usual Care
N=91
0.0, 12.0
0.0
0.0, 4.0
0.0
0.0, 2.0
0.0
0.0, 4.0
0.0
0.0, 2.0
21 (23.1%)
64 (70.3%)
6 (6.6%)
33 (34.0%)
59 (60.8%)
5 (5.2%)
29 (30.5%)
59 (62.1%)
7 (7.4%)
23 (25.3%)
64 (70.3%)
4 (4.4%)
11 (12.1%)
24 (26.4%)
8 (8.8%)
15 (16.5%)
9 (9.3%)
25 (25.8%)
6 (6.2%)
9 (9.4%)
11 (11.6%)
18 (18.9%)
11 (11.6%)
12 (13.3%)
15 (16.5%)
21 (23.1%)
8 (8.8%)
8 (9.0%)
1 (1.1%)
23 (25.3%)
3 (3.2%)
25 (25.8%)
1 (1.1%)
22 (23.2%)
0 (0.0%)
30 (33.0%)
4 (4.4%)
3 (3.1%)
2 (2.1%)
4 (4.4%)
3 (3.3%)
6 (6.2%)
6 (6.3%)
11 (12.1%)
28.6 (4.9)
19.3, 44.5
28.8 (5.5)
19.8, 46.3
30.0 (6.2)
19.6, 49.8
28.0 (5.1)
19.7, 44.9
35 (38.5%)
51 (56.0%)
36 (37.1%)
59 (60.8%)
37 (38.9%)
54 (56.8%)
36 (39.6%)
48 (52.7%)
5 (5.5%)
2 (2.1%)
4 (4.2%)
7 (7.7%)
19 (21.1%)
19 (19.8%)
26 (27.4%)
16 (17.8%)
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
Variable
Prior supervised pelvic floor muscle
exercise program, n (%)
Vaginal bulge symptoms, n, (%)
Any
Bothersome
Prolapse beyond the hymen, n (%)
Anterior (POPQ Aa or Ba > 0)
Posterior (POPQ Ap or Bp > 0)
Apical (POPQ C > 0)
Apical descent greater than or equal to
½ of total vaginal length (n, %)
(POPQ C>=-1/2*TVL)
Most distal point of vaginal segment,
mean cm (SD)#:
Anterior
Posterior
Apical
Maximum descent of any segment, mean
cm, (SD)#
POPQ value, median (minimum,
maximum)##
Aa
Ba
C
Ap
Bp
GH
PB
TVL
Sexually active in last 3 months, n (%)
ULS / BPMT
N=91
ULS / Usual Care
N=97
SSLF / BPMT
N=95
SSLF / Usual Care
N=91
4 (4.5%)
3 (3.1%)
6 (6.3%)
1 (1.1%)
91 (100.0%)
80 (94.1%)
97 (100.0%)
84 (93.3%)
95 (100.0%)
87 (93.5%)
91 (100.0%)
79 (91.9%)
63 (69.2%)
12 (13.2%)
26 (28.6%)
77 (79.4%)
14 (14.4%)
27 (27.8%)
62 (65.3%)
26 (27.4%)
29 (30.9%)
67 (73.6%)
21 (23.1%)
31 (34.1%)
89 (97.8%)
94 (96.9%)
93 (98.9%)
89 (97.8%)
2.3 (2.3)
0.3 (2.7)
-0.9 (3.4)
1.9 (1.9)
0.1 (2.3)
-1.4 (3.1)
2.0 (2.4)
0.9 (2.8)
-0.7 (3.6)
2.4 (2.4)
0.8 (3.1)
-0.8 (3.8)
2.3 (2.2)
2.1 (1.8)
2.3 (2.1)
2.5 (2.3)
1.0 (-2.0, 3.0)
2.0 (-2.0, 11.0)
-2.0 (-5.0, 11.0)
-2.0 (-3.0, 3.0)
-2.0 (-3.0, 11.0)
4.5 (3.0, 8.0)
3.0 (1.0, 6.0)
9.0 (7.0, 12.0)
(46.3%)
1.0 (-3.0, 3.0)
2.0 (-3.0, 11.0)
-3.0 (-5.0, 11.0)
-1.0 (-3.0, 3.0)
-1.0 (-3.0, 11.0)
4.5 (2.0, 7.0)
3.0 (1.0, 6.0)
9.5 (3.0, 12.0)
(60.7%)
1.0 (-3.0, 4.0)
1.0 (-2.0, 10.0)
-2.0 (-6.0, 10.0)
-1.0 (-3.0, 3.0)
-1.0 (-3.0, 10.0)
5.0 (2.0, 10.0)
3.0 (0.0, 5.0)
10.0 (5.5, 12.0)
(56.5%)
1.0 (-2.0, 3.0)
2.0 (-2.0, 9.0)
-2.0 (-6.0, 8.0)
-1.0 (-3.0, 3.0)
-1.0 (-3.0, 10.0)
4.0 (2.0, 8.0)
3.0 (1.0, 7.0)
9.0 (6.0, 12.0)
(48.2%)
BPMT = Behavioral and Pelvic Floor Muscle Therapy; POPQ = Pelvic Organ Prolapse Quantification; ULS, uterosacral ligament suspension;
SSLF, sacrospinous ligament suspension
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
Pelvic Organ Prolapse Quantification (POPQ) Stages: Stage 2 -The vagina is prolapsed between 1 cm above the hymen and 1 cm below the
hymen; Stage 3 -The vagina is prolapsed more than 1 cm beyond the hymen but is less than totally everted; Stage 4 - The vagina is everted to
within 2 cm of its length. #Most distal point of each compartment and overall are measured in cm relative to the hymen during maximum strain with descent to the hymen =
0, descent proximal to the hymen as a negative value and descent distal to the hymen as positive value using the POPQ system. The most distal
point of the apical segment is equal to POPQ point C; Most distal point of the anterior segment = POPQ point Ba if Ba >C or is = C if Ba<C;
most distal point of posterior segment = POPQ point Bp if Bp >C or is = C if Bp<C. ##POPQ values provided for descriptive purposes only. In the POPQ system, the positions of C, Ba and Bp are measured at the most
dependent location (the point of greatest prolapse) of the apex, anterior vaginal wall and posterior vaginal wall respectively during a straining.
Values are measured in cm and are negative if above the hymen, and positive if below the hymen. TVL (total vaginal length), GH (genital
hiatus) and PB (perineal body) are measured as positive values.
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
eTable 4. Surgical Procedures and Perioperative Outcomes
Variable
Hysterectomy, n (%)
Anterior prolapse repair, n (%)
Posterior prolapse repair, n (%)
Uterosacral Ligament
Suspension (ULS), n (%) – all
Prior hysterectomy
Concomitant hysterectomy
Sacrospinous Ligament
Fixation (SSLF), n (%) – all
Prior hysterectomy
Concomitant hysterectomy
No vaginal vault suspension, n
(%) – all
Prior hysterectomy
Concomitant hysterectomy
TVT, n (%)
Overall
271 (72.5%)
224 (59.9%)
190 (50.8%)
Treatment Group
Sacrospinous
Uterosacral
Ligament
Ligament
Fixation
Suspension
N=186
N=188
137 (72.9%)
134 (72.0%)
115 (61.2%)
109 (58.6%)
95 (50.5%)
95 (51.1%)
186 (49.7%)
41 (11.0%)
143 (38.2%)
178 (94.7%)
40 (21.3%)
136 (72.3%)
8 (4.3%)
1 (0.5%)
7 (3.8%)
186 (49.7%)
58 (15.5%)
128 (34.2%)
8 (4.3%)
7 (3.7%)
1 (0.5%)
178 (95.7%)
51 (27.4%)
127 (68.3%)
P value*
0.71
0.45
0.99
Treatment Group
BPMT
Usual Care
N=186
N=188
P value*
140 (75.3%)
111 (59.7%)
95 (51.1%)
131 (69.7%)
113 (60.1%)
95 (50.5%)
0.17
0.97
0.87
93 (50.0%)
93 (49.5%)
0.21
93 (50.0%)
93 (49.5%)
<0.01
0.33
<0.01
N/A 0 (0.0%)
2 (1.1%)
LR
2 (1.1%)
0 (0.0%)
N/A - LR
1 (0.5%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
186 (98.9%)
185 (99.5%) N/A - LR 185 (99.5%)
186 (98.9%)
N/A – LR
Adjusted
Adjusted
P value*
mean (SE)
mean (SE)
[minimum,
[minimum,
maximum]
maximum]
146.2, (5.6)
149.5, (5.6)
Operative time in minutes,
-3.2 (-10.4, 3.9)
[58.0, 318.0]
[72.0, 305.0]
0.38
169.3, (15.0)
187.6, (14.9)
Estimated blood loss in ml,
-18.3 (-43.3, 6.8) [25.0, 800.0] [25.0, 1000.0]
0.15
Duration of hospitalization,
2.4, (0.1)
2.3, (0.1)
days,
0.0 (-0.1, 0.2)
[1.0, 7.0]
[1.0, 5.0]
0.52
ULS = uterosacral ligament suspension; SSLF= sacrospinous ligament fixation; CI = Confidence Interval; SE = Standard Error of Adjusted Mean.
N/A – LR = The P value is not shown due to low reliability of test.
2 (0.5%)
1 (0.3%)
0 (0.0%)
371 (99.2%)
Adjusted
Treatment
Difference*
(95% CI)
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
* Statistical testing is performed using general (for continuous outcome) and generalized (for dichotomous outcomes) linear models controlling for
surgical treatment, BPMT treatment, and the interaction between surgical and BPMT treatments as well as design variables (prior or concomitant
hysterectomy and surgeon for surgical models and clinical site for BPMT models). The hysterectomy status design variable was excluded from the
hysterectomy outcome model.
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
eTable 5. Postoperative Treatments for Urinary Incontinence or Pelvic Organ Prolapse
Variable
Treatment group
ULS
SSLF
N=188
N=186
Retreatment for urinary incontinence, n (%)
Missing, n
Surgery, n
Medications, n
Pessary for urinary incontinence, n
Supervised PME (outside of study), n
Timed voiding/fluid management, n
Periurethral bulking injection, n
Intravesical botulinum toxin injection, n
Neuromodulation, n
Other, n
Retreatment for pelvic organ prolapse, n (%)
45 (27.3%)
23
7
25
1
5
5
3
0
1
17
44 (27.0%)
23
6
22
1
3
3
1
0
0
21
OR
(95% CI)
P
value*
1.0
(0.6, 1.7)
0.91
Treatment Group
BPMT
Usual
N=186
Care
N=188
48
41
(30.0%)
(24.4%)
26
20
8
5
29
18
1
1
0
8
2
6
2
2
0
0
1
0
17
21
OR
(95% CI)
P
value*
1.4
(0.8, 2.3)
0.24
0.9
2.5
8 (5.0%)
8 (5.2%)
(0.3, 2.6)
0.81
11 (7.2%)
5 (3.0%)
(0.8, 7.6)
0.11
Missing, n
27
31
34
24
Surgery, n
5
4
4
5
Pessary, n
5
5
8
2
Either Pessary or Surgery
8
8
11
5
Other, n
0
1
1
0
BPMT = Behavioral and Pelvic Floor Muscle Therapy; ULS, uterosacral ligament suspension; SSLF, sacrospinous ligament suspension; OR =
Odds Ratio; CI = Confidence Interval; PME = Pelvic Muscle Exercise
* Statistical testing is performed using longitudinal generalized linear mixed models controlling for surgical treatment, BPMT treatment, the
interaction between surgical and BPMT treatments, and clinical site [BPMT outcome] or surgeon and hysterectomy status[surgical outcome] design
variable.
NOTE: Excluded from the denominator are patients who have not been retreated prior to their 24 month visit and have missing retreatment
information at 24 months
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
eTable 6a. Pelvic Organ Prolapse Outcomes for Surgical Comparison: Months 6, 12, and 24
6 months
Vaginal bulge
symptoms
(n,%)
Any
Bothersome
Prolapse beyond
the hymen (n,%)
Anterior (POPQ
Aa or Ba >0)
Posterior (POPQ
Ap or Bp>0)
Apical (POPQ C
>0)
Apical descent
greater than 1/3rd
of total vaginal
length (n, %)
(POPQ C>2/3*TVL)
BPMT
Usual Care
Most distal point
of vaginal
segment# (mean
cm, SE):
Anterior
Posterior
Apical
Maximum descent
of any segment
[mean cm, SE]#
ULS
SSLF
16/170
(9.4%)
14/170
(8.2%)
27/169
(16.0%)
23/169
(13.6%)
14/168
(8.3%)
15/170
(8.8%)
1/170
(0.6%)
1/169
(0.6%)
2/168 (1.2%)
3/167 (1.8%)
12 months
Odds Ratio
(95% CI)*
P
value
0.5 (0.2, 0.9)
0.03
0.5 (0.2, 1.0)
0.053
0.9 (0.4, 1.9)
25/165
(15.2%)
20/162
(12.3%)
1.2 (0.6, 2.2)
NA-LN
--
2/165 (1.2%)
2/162 (1.2%)
NA-LN
--
2/165 (1.2%)
2.8 (0.9, 8.1)
-1.0 (0.2)
-2.0 (0.1)
-2.2 (0.1)
-6.5 (0.2)
-6.8 (0.2)
-0.8 (0.1)
-0.8 (0.1)
0.01
0.80
5/86 (5.8%)
-1.0 (0.2)
0.4 (0.2, 0.8)
31/165
(18.8%)
28/165
(17.0%)
11/82
(13.4%)
SSLF
0.04
19/162
(11.7%)
14/162
(8.6%)
N/A - INT
ULS
0.5 (0.3, 1.0)
SSLF
10/169
(5.9%)
5/83 (6.0%)
P
value
ULS
18/167
(10.8%)
7/85 (8.2%)
24 months
Odds Ratio
(95% CI) *
1.4 (0.4,
4.4)
Treatment
Difference
(95% CI) *
-0.0 (-0.4,
0.3)
0.2 (-0.0,
0.5)
0.4 (-0.1,
0.8)
-0.0 (-0.3,
0.3)
Odds Ratio
(95% CI)*
P
value
0.9 (0.5, 1.6)
0.70
0.8 (0.5, 1.5)
0.49
20/153
(13.1%)
1.0 (0.5, 1.8)
0.89
3/155 (1.9%)
5/153 (3.3%)
NA-LN
--
1/155 (0.6%)
3/152 (2.0%)
NA-LN
--
16/155
(10.3%)
21/152
(13.8%)
N/A - INT (P value for
BPMT*Surgery
interaction = 0.03)
12/74
(16.2%)
9/75 (12.0%)
1.4 (0.6, 3.7)
0.44
4/81 (4.9%)
12/77
(15.6%)
0.3 (0.1, 0.8)
0.02
ULS
SSLF
29/151
(19.2%)
25/151
(16.6%)
32/154
(20.8%)
30/154
(19.5%)
0.58
20/155
(12.9%)
NA-LN
--
4/162 (2.5%)
NA-LN
--
19/165
(11.5%)
16/162
(9.9%)
N/A - INT
0.06
9/80 (11.3%)
6/81 (7.4%)
1.6 (0.6, 4.6)
0.58
10/85
(11.8%)
10/81
(12.3%)
P
value
ULS
SSLF
0.83
-0.8 (0.2)
-0.7 (0.2)
0.07
-2.0 (0.1)
-2.0 (0.1)
0.09
-6.3 (0.2)
-6.4 (0.2)
0.92
-0.6 (0.2)
-0.5 (0.2)
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
0.37
0.9 (0.4, 2.3)
0.83
Treatment
Difference
(95% CI)*
P
value
ULS
SSLF
0.53
-0.8 (0.2)
-0.6 (0.2)
-0.3 (-0.6, 0.1)
0.12
0.83
-2.0 (0.1)
-1.9 (0.1)
-0.0 (-0.3, 0.2)
0.78
0.87
-6.3 (0.2)
-6.1 (0.2)
-0.2 (-0.6, 0.2)
0.37
0.68
-0.6 (0.2)
-0.4 (0.2)
-0.2 (-0.5, 0.1)
0.22
-0.1 (-0.4,
0.2)
-0.0 (-0.3,
0.2)
0.0 (-0.4,
0.5)
-0.1 (-0.4,
0.3)
Treatment Difference
(95% CI)*
N/A – INT = P values are shown within BPMT group due to significant treatment interaction in the statistical model.
BPMT = Behavioral and Pelvic Floor Muscle Therapy; ULS, uterosacral ligament suspension; SSLF, sacrospinous ligament suspension; POPQ,
Pelvic Organ Prolapse Quantification; CI = Confidence Interval; SE = Standard Errors of Adjusted Mean.
* Statistical testing for continuous outcomes (i.e. Most distal point through POPQ values) is performed using longitudinal general linear models
controlling for surgical treatment, BPMT treatment, the interaction between surgical and BPMT treatments, as well as design variables (prior or
concomitant hysterectomy and surgeon). Additionally, since these models incorporate 6-month, 12-month, and 24-month time points, time point
and related interactions are included in the models. These interactions include those between time and each treatment (Surgical and BPMT), as
well as the three-way interaction between time and the two treatments. Statistical testing for dichotomous outcomes (i.e. Vaginal Bulge Symptoms
through Apical Descent) is performed using longitudinal generalized linear models controlling for the same variables with the following
exceptions: due to convergence issues, hysterectomy status is excluded from Vaginal bulge symptom (both Any and Bothersome), and the threeway interaction between time and the two treatments is excluded from the models for Vaginal bulge symptoms (both Any and Bothersome).
# Most distal point of each compartment and overall are measured in cm relative to the hymen during maximum strain with descent to the hymen
= 0, descent proximal to the hymen as a negative value and descent distal to the hymen as positive value using the POPQ system. The most distal
point of the apical segment is equal to POPQ point C; Most distal point of the anterior segment = POPQ point Ba if Ba >C or is = C if Ba<C; most
distal point of posterior segment = POPQ point Bp if Bp >C or is = C if Bp<C. The adjusted mean and standard errors for continuous outcomes
were output from the Surgical comparison models.
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
eTable 6b. Pelvic Organ Prolapse Outcomes for BPMT Comparison: Months 6, 12, and 24
6 months
BPMT
Usual Care
12 months
Odds Ratio
(95% CI)*
P
value
BPMT
Usual Care
Odds Ratio
(95% CI) *
P
value
Anatomic failure (PMT
Intervention long-term
primary outcome;
assessed only at 24
months)
Prolapse beyond the
hymen (n,%)
Anterior (POPQ Aa
or Ba >0)
Posterior (POPQ Ap
or Bp >0)
Apical (POPQ C >0)
Apical descent > 1/3rd
of total vaginal length
(n, %)
(POPQ C>-2/3*TVL)
ULS
SSLF
Most distal point of
vaginal segment
(adjusted mean, SE)#:
Anterior
Posterior
Apical
ULS SSLF
BPMT
37/153
(24.2%)
14/169
(8.3%)
15/169
(8.9%)
0.9 (0.4,
2.0)
1/169 (0.6%)
2/169 (1.2%)
4/168 (2.4%)
16/168
(9.5%)
11/82
(13.4%)
5/86
(5.8%)
24 months
Odds Ratio
Usual Care
(95% CI)*
P value
42/164
(25.6%)
0.9 (0.6, 1.6)
0.82
18/149
(12.1%)
22/159
(13.8%)
0.9 (0.4, 1.7)
0.65
25/161
(15.5%)
20/166
(12.0%)
1.4 (0.7, 2.6)
N/A - LN
1/161 (0.6%)
3/166 (1.8%)
N/A - LN
3/149 (2.0%)
5/159 (3.1%)
N/A - LN
0/168 (0.0%)
N/A - LN
2/161 (1.2%)
4/166 (2.4%)
N/A - LN
2/149 (1.3%)
2/158 (1.3%)
N/A - LN
12/168
(7.1%)
N/A - INT
15/161
(9.3%)
20/166
(12.0%)
N/A – INT
21/149
(14.1%)
16/158
(10.1%)
N/A – INT
0.01##
7/85 (8.2%)
5/83 (6.0%)
BPMT
Usual Care
-1.1 (0.1)
-1.2 (0.1)
-2.1 (0.1)
-2.3 (0.1)
N/A - INT
N/A - INT
-6.3 (0.2)
-6.9 (0.2)
-6.9 (0.2)
-7.0 (0.2)
2.0 (0.7,
5.7)
0.9 (0.2,
3.3)
Treatment
Difference
(95% CI)*
0.1 (-0.2,
0.4)
0.2 (-0.1,
0.5)
N/A - INT
0.6 (-0.0,
1.2)
0.1 (-0.5,
0.7)
0.85
0.20
9/80 (11.3%)
0.84
6/81 (7.4%)
10/85
(11.8%)
10/81
(12.3%)
BPMT
Usual Care
0.56
-0.9 (0.1)
-0.9 (0.1)
0.12
-2.2 (0.1)
-2.1 (0.1)
N/A - INT
N/A - INT
0.06
-6.3 (0.2)
-6.7 (0.2)
0.71
-6.8 (0.2)
-6.2 (0.2)
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
0.36
1.0 (0.4, 2.8)
0.96
12/74 (16.2%)
4/81 (4.9%)
4.9 (1.4,
16.8)
0.01
0.5 (0.2, 1.6)
0.24
9/75 (12.0%)
12/77 (15.6%)
0.6 (0.2, 1.7)
0.35
BPMT
Usual Care
Treatment
Difference
(95% CI)*
0.64
-0.8 (0.1)
-0.8 (0.1)
0.53
-2.0 (0.1)
-2.1 (0.1)
N/A - INT
N/A - INT
0.29
-6.2 (0.2)
-6.7 (0.2)
0.07
-6.4 (0.2)
-6.0 (0.2)
Treatment
Difference
(95% CI) *
0.1 (-0.3,
0.4)
-0.1 (-0.4,
0.2)
N/A - INT
0.3 (-0.3,
0.9)
-0.6 (-1.2,
0.0)
-0.0 (-0.4,
0.3)
0.1 (-0.2,
0.3)
N/A - INT
0.5 (-0.2,
1.1)
-0.4 (-1.0,
0.2)
0.87
0.70
0.02##
0.15
0.22
Maximum descent of
any segment# [adjusted
mean, SE]
Vaginal bulge
symptoms (n,%)
Any
Bothersome
-0.9 (0.1)
-1.0 (0.1)
0.1 (-0.2,
0.4)
21/168
(12.5%)
18/168
(10.7%)
22/171
(12.9%)
19/171
(11.1%)
1.0 (0.5,
2.1)
1.0 (0.5,
2.1)
0.41
0.92
0.96
-0.7 (0.1)
-0.8 (0.1)
28/163
(17.2%)
24/163
(14.7%)
22/164
(13.4%)
18/164
(11.0%)
0.1 (-0.2,
0.4)
0.48
1.3 (0.7, 2.5)
0.41
1.4 (0.7, 2.9)
0.35
-0.7 (0.1)
-0.6 (0.1)
31/151
(20.5%)
27/151
(17.9%)
30/154
(19.5%)
28/154
(18.2%)
-0.0 (-0.4,
0.3)
0.85
1.1 (0.6, 2.0)
0.75
1.0 (0.5, 1.9)
1.00
BPMT = BPMT, Behavioral and Pelvic Floor Muscle Therapy; POPQ = Pelvic Organ Prolapse Quantification; CI = Confidence Interval; ULS,
uterosacral ligament suspension; SSLF, sacrospinous ligament suspension; SE = Standard Error of Adjusted Mean.
NA – INT = The interaction effect was significant so tests within surgical groups are shown.
* Statistical testing for continuous outcomes (i.e. Most distal points) is performed using longitudinal general linear models controlling for surgical
treatment, BPMT treatment, the interaction between surgical and BPMT treatments, as well as clinical site design variable. Additionally, since
these models incorporate 6-month, 12-month, and 24-month time points, time point and related interactions are included in the models. These
interactions include those between time and each treatment (Surgical and BPMT), as well as the three-way interaction between time and the
two treatments. Statistical testing for dichotomous outcomes (i.e. Anatomic failure through Apical descent and Vaginal bulge symptoms) is
performed using longitudinal generalized linear models controlling for the same variables.
# Most distal point of each compartment and overall are measured in cm relative to the hymen during maximum strain with descent to the hymen
= 0, descent proximal to the hymen as a negative value and descent distal to the hymen as positive value using the POPQ system. The most
distal point of the apical segment is equal to POPQ point C; Most distal point of the anterior segment = POPQ point Ba if Ba >C or is = C if
Ba<C; most distal point of posterior segment = POPQ point Bp if Bp >C or is = C if Bp<C. The adjusted mean and standard errors for these
continuous outcomes were output from the BPMT comparison models.
## P value for BPMT*Surgery interaction
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
eTable 6c. Pelvic Organ Prolapse Outcomes Across Treatment Cells: Months 6, 12, and 24
Variable
ULS /
BPMT
Anatomic Failure (Part
2 of the PMT
Intervention long-term
primary outcome;
assessed only at 24
months)
Prolapse Beyond the
Hymen (n,%)
Anterior (POPQ Aa or
Ba >0)
Posterior(POPQ Ap or
Bp >0)
Apical (POPQ C >0)
6 month
ULS /
SSLF /
Usual Care
BPMT
SSLF /
Usual Care
ULS /
BPMT
12 months
ULS / Usual
SSLF /
Care
BPMT
7/85
(8.2%)
2/85
(2.4%)
0/85
(0.0%)
7/86
(8.1%)
1/86
(1.2%)
1/86
(1.2%)
8/84
(9.5%)
0/84
(0.0%)
0/83
(0.0%)
14/80
(17.5%)
11/85
(12.9%)
0/80 (0.0%)
2/85 (2.4%)
1/80 (1.3%)
1/85 (1.2%)
11/82
(13.4%)
7/85
(8.2%)
5/86
(5.8%)
5/83
(6.0%)
9/80
(11.3%)
7/83 (8.4%)
0/83 (0.0%)
3/82 (3.7%)
SSLF /
Usual Care
ULS / BPMT
24 months
ULS / Usual
SSLF /
Care
BPMT
SSLF / Usual
Care
19/77
(24.7%)
19/85
(22.4%)
18/76
(23.7%)
23/79
(29.1%)
9/75
(12.0%)
3/75
(4.0%)
1/75
(1.3%)
11/78
(14.1%)
2/78 (2.6%)
11/81
(13.6%)
1/81
(1.2%)
1/81
(1.2%)
9/81
(11.1%)
9/74 (12.2%)
11/81
(13.6%)
1/81 (1.2%)
0/74 (0.0%)
3/81 (3.7%)
3/81 (3.7%)
1/74 (1.4%)
0/81 (0.0%)
10/85
(11.8%)
6/81
(7.4%)
10/81
(12.3%)
12/74
(16.2%)
4/81 (4.9%)
9/75
(12.0%)
12/77
(15.6%)
2/77 (2.6%)
rd
Apical Descent > 1/3
of total vaginal length
(n, %)
(POPQ C>-2/3*TVL)
Most distal point of
vaginal segment
[mean, SD]#:
Anterior
-1.1, 2.1
-1.2, 1.2
-1.1, 1.5
-1.1, 1.3
-0.9, 1.5
-1.0, 1.5
-0.8, 1.6
-0.9, 1.9
-0.9, 1.6
-1.1, 1.3
-0.8, 1.6
-0.7, 1.6
Posterior
-1.9, 2.1
-2.2, 0.9
-2.2, 1.2
-2.4, 0.8
-2.1, 1.0
-2.1, 1.4
-2.1, 1.1
-2.1, 1.8
-2.1, 1.2
-2.1, 1.0
-2.0, 1.2
-2.1, 1.5
Apical
-6.5, 3.1
-7.0, 1.6
-7.0, 2.0
-7.2, 1.4
-6.5, 1.7
-6.8, 1.9
-6.9, 2.0
-6.4, 2.8
-6.5, 1.9
-6.8, 1.3
-6.5, 2.1
-6.2, 2.3
-0.9, 2.0
-1.0, 1.2
-0.9, 1.4
-1.0, 1.2
-0.7, 1.4
-0.9, 1.6
-0.7, 1.5
-0.8, 1.9
-0.8, 1.5
-0.8, 1.3
-0.6, 1.6
-0.6, 1.5
10/82
(12.2%)
6/88
(6.8%)
6/88
(6.8%)
11/86
(12.8%)
10/86
(11.6%)
16/83
(19.3%)
13/83
(15.7%)
10/77
(13.0%)
8/77
(10.4%)
9/85
(10.6%)
18/86
(20.9%)
16/86
(18.6%)
13/79
(16.5%)
12/79
(15.2%)
16/73
(21.9%)
13/73
(17.8%)
13/78
(16.7%)
12/78
(15.4%)
15/78
(19.2%)
14/78
(17.9%)
17/76
(22.4%)
16/76
(21.1%)
Maximum descent of
any segment# [mean,
SD]
Vaginal Bulge
Symptoms (n,%)
Any
Bothersome
8/82 (9.8%)
6/85 (7.1%)
ULS, uterosacral ligament suspension; SSLF, sacrospinous ligament suspension; POPQ, Pelvic Organ Prolapse Quantification; SD = Standard Deviation.
# Most distal point of each compartment and overall are measured in cm relative to the hymen during maximum strain with descent to the hymen = 0,
descent proximal to the hymen as a negative value and descent distal to the hymen as positive value using the POPQ system. The most distal point of the
apical segment is equal to POPQ point C; Most distal point of the anterior segment = POPQ point Ba if Ba >C or is = C if Ba<C; most distal point of
posterior segment = POPQ point Bp if Bp >C or is = C if Bp<C. The mean and standard deviations for these continuous outcomes are unadjusted,
calculated directly from the data and not output from models.
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
eTable 7. Patient-Reported and Measured Secondary Outcomes
Variable
Patient Global
Impression of
Improvement,
n (%)
Time
Period
6 Month
12Month
24Month
Incontinence
Severity Index
Baseline
Value
Very much better
Much better
A little better
No change
A little worse
Much worse
Very much worse
Missing
Very much better
Much better
A little better
No change
A little worse
Much worse
Very much worse
Missing
Very much better
Much better
A little better
No change
A little worse
Much worse
Very much worse
Missing
N
Mean (SD)
Min, Max
Treatment group measure
ULS /
BPMT
32 (35.2%)
25 (27.5%)
12 (13.2%)
4 (4.4%)
6 (6.6%)
3 (3.3%)
1 (1.1%)
8 (8.8%)
34 (37.4%)
23 (25.3%)
10 (11.0%)
6 (6.6%)
2 (2.2%)
1 (1.1%)
2 (2.2%)
13 (14.3%)
27 (29.7%)
26 (28.6%)
10 (11.0%)
4 (4.4%)
6 (6.6%)
0 (0.0%)
2 (2.2%)
16 (17.6%)
85
5.4 (3.3)
0.0, 12.0
ULS /
Usual Care
35 (36.1%)
26 (26.8%)
14 (14.4%)
4 (4.1%)
6 (6.2%)
1 (1.0%)
2 (2.1%)
9 (9.3%)
34 (35.1%)
31 (32.0%)
8 (8.2%)
4 (4.1%)
7 (7.2%)
0 (0.0%)
1 (1.0%)
12 (12.4%)
25 (26.3%)
30 (31.6%)
13 (13.7%)
4 (4.2%)
4 (4.2%)
1 (1.1%)
1 (1.1%)
19 (19.6%)
90
5.4 (3.2)
0.0, 12.0
SSLF /
BPMT
35 (36.8%)
28 (29.5%)
14 (14.7%)
2 (2.1%)
7 (7.4%)
1 (1.1%)
0 (0.0%)
8 (8.4%)
33 (34.7%)
25 (26.3%)
14 (14.7%)
6 (6.3%)
6 (6.3%)
1 (1.1%)
1 (1.1%)
9 (9.5%)
26 (27.4%)
24 (25.3%)
16 (16.8%)
5 (5.3%)
3 (3.2%)
4 (4.2%)
1 (1.1%)
16 (16.8%)
92
5.4 (2.9)
0.0, 12.0
SSLF /
Usual Care
29 (31.9%)
30 (33.0%)
13 (14.3%)
3 (3.3%)
4 (4.4%)
2 (2.2%)
1 (1.1%)
9 (9.9%)
31 (34.1%)
28 (30.8%)
13 (14.3%)
4 (4.4%)
2 (2.2%)
1 (1.1%)
0 (0.0%)
12 (13.2%)
23 (25.6%)
24 (26.7%)
17 (18.9%)
3 (3.3%)
7 (7.8%)
0 (0.0%)
2 (2.2%)
15 (16.5%)
86
5.4 (3.2)
0.0, 12.0
Interaction
P value
Surgical Effect
BPMT Effect
P value
(Surgical)=
.46
p=0.70
p=0.80
p=0.68
p=0.72
p=0.32
p=0.65
P value
(BPMT) =
.36
P value
(Surgical)=
.52
P value
(BPMT) =
.60
P value
(Surgical)=
.96
P value
(BPMT) =
.91
Mean Difference between groups
(95% CI), P value
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
Change
from
Baseline
to 6 Mo
Change
from
Baseline
to 12 Mo
Change
from
Baseline
to 24 Mo
Pelvic Muscle Baseline
Strength
(Brink Score)
Change
from
Baseline
to 6 Mo
Change
from
Baseline
to 24 Mo
N
Adjusted Mean
(SE)#
Min, Max
N
Adjusted Mean
(SE) #
Min, Max
N
Adjusted Mean
(SE) #
Min, Max
N
Mean (SD)
Min, Max
N
Adjusted Mean
(SE) #
77
83
84
79
-2.8 (0.5)
-3.6 (0.5)
-3.1 (0.4)
-2.9 (0.5)
-12.0, 8.0
69
-12.0, 9.0
76
-12.0, 6.0
75
-12.0, 12.0
69
-3.1 (0.5)
-3.3 (0.5)
-3.0 (0.5)
-3.5 (0.5)
-12.0, 10.0
60
-12.0, 9.0
65
-11.0, 8.0
59
-12.0, 7.0
59
-2.7 (0.5)
-2.5 (0.5)
-2.0 (0.5)
-2.9 (0.5)
-11.0, 10.0
89
8.0 (1.6)
5.0, 12.0
82
0.6 (0.2)
-11.0, 11.0
95
7.7 (2.1)
3.0, 12.0
83
0.4 (0.2)
-12.0, 10.0
91
8.0 (1.8)
3.0, 12.0
83
0.2 (0.2)
-12.0, 7.0
87
8.1 (2.4)
3.0, 12.0
79
0.1 (0.2)
Min, Max
-5.0, 5.0
-5.0, 6.0
-9.0, 6.0
-4.0, 5.0
N
Adjusted Mean
(SE) #
Min, Max
72
0.5 (0.3)
80
0.1 (0.2)
73
-0.1 (0.2)
75
0.2 (0.2)
-4.0, 4.0
-4.0, 5.0
-6.0, 5.0
-4.0, 5.0
P value for
three-way
interaction
with time
(Surgical
model)=.01
(BPMT
model)=.01
P value
(Surgical)
=.27
P value
(BPMT)
=.85
P value
(Surgical)
=.38
0.3 (-0.9, 1.4),
p=0.67a
-0.7 (-1.9, 0.5),
p=0.25b
-0.1 (-1.3, 1.1),
p=0.91a
0.2 (-1.0, 1.4),
p=0.73b
-0.7 (-2.0, 0.6),
p=0.28a
0.4 (-0.9, 1.7),
p=0.53b
0.8 (-0.4, 2.0),
p=0.19c
-0.3 (-1.4, 0.9),
p=0.66d
0.2 (-1.0, 1.4),
p=0.73c
0.4 (-0.8, 1.6),
p=0.49d
-0.1 (-1.4, 1.1),
p=0.83c
0.9 (-0.4, 2.2),
p=0.17d
0.4 (-0.4, 1.1),
p=0.34
0.2 (-0.3, 0.6),
p=0.41
0.9 (0.2, 1.7),
p=0.01
0.1 (-0.4, 0.5),
p=0.82
P value
(BPMT)
=.13
ULS, uterosacral ligament suspension; SSLF, sacrospinous ligament fixation; CI=Confidence Interval; SE = Standard Error of Adjusted Mean.
* Statistical testing for continuous outcomes is performed by modeling change from baseline using longitudinal general linear models controlling for surgical
treatment, BPMT treatment, the interaction between surgical and BPMT treatments, as well as design variables (prior or concomitant hysterectomy and surgeon
for surgical models and clinical site for BPMT models). Additionally, since these models incorporate 6-month, 12-month, and 24-month time points, time point
and related interactions are included in the models. These interactions include those between time and each treatment (Surgical and BPMT), as well as the three-
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
way interaction between time and the two treatments. The Patient Global Impression of Improvement (PGI-I) outcomes were modeled as multinomial responses,
and each time point was modeled separately. The models control for the same variables that the continuous outcome models include, with the exception of time
point and related interactions (due to the non-longitudinal nature of the model) and surgeon for the 24-month outcome (due to convergence issues).
# Adjusted means and standard errors are output from the statistical models. For Incontinence Severity Index, the adjusted means and SEs are output from the
surgical model (controlling for design variables prior or concomitant hysterectomy and surgeon), and for the Brinks, the adjusted means and SEs are output from
the BPMT model (controlling for design variable clinical site).
NOTE: Patient reported outcome scale range for the Incontinence Severity Index23 is 0-12 with higher scores indicating greater severity.
a
Surgical effect (adjusted mean difference between ULS and SSLF groups in change from baseline) within BPMT group
Surgical effect (adjusted mean difference between ULS and SSLF groups in change from baseline) within Usual Care group
c
BPMT effect (adjusted mean difference between BPMT and Usual Care groups in change from baseline) within ULS surgical group
d
BPMT effect (adjusted mean difference between BPMT and Usual Care groups in change from baseline) within SSLF surgical group
b
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
eTable 8. Adverse Events Related to the Surgical Outcome
Variable
Treatment Group
Adjusted OR*
(95% CI)
P value*
Uterosacral
Ligament
Suspension
Sacrospinous
Ligament
Fixation
N=188
N=186
140 (74.5%)
142 (76.3%)
0.9 (0.6, 1.4)
0.65
Serious AE, n (%)
31 (16.5%)
31 (16.7%)
0.9 (0.5, 1.6)
0.83
Expected AE, n (%)
130 (69.1%)
130 (69.9%)
0.9 (0.6, 1.5)
0.80
Participants with any Adverse Event
(AE), n (%)
Perioperative Adverse Events (Surgery through 4-6 week postoperatively) – n (%)
Participants with:
Bladder injury
22 (11.7%)
18 (9.7%)
1.2 (0.6, 2.4)
0.60
During mid-urethral sling
18 (9.6%)
18 (9.7%)
1.0 (0.5, 2.0)
1.00
Other
4 (2.1%)
0 (0.0%)
N/A - LR
6 (3.2%)
0 (0.0%)
N/A - LR
Suture removed intra-operatively
5 (2.7%)
0 (0.0%)
N/A - LR
Stent placement
1 (0.5%)
0 (0.0%)
N/A - LR
Additional Procedure
0 (0.0%)
0 (0.0%)
N/A - LR
Ureteral injury – delayed
recognition*
1 (0.5%)
0 (0.0%)
N/A - LR
Urethral injury
0 (0.0%)
0 (0.0%)
N/A - LR
Rectal injury
0 (0.0%)
1 (0.5%)
N/A - LR
Major vascular injury
0 (0.0%)
0 (0.0%)
N/A - LR
Blood transfusion
7 (3.7%)
4 (2.2%)
Intraoperative ureteral obstruction
Treatment:
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
1.9 (0.5, 7.8)
0.38
Neurologic pain requiring
13 (6.9%)
23 (12.4%)
Narcotic pain medication
10 (5.3%)
18 (9.7%)
Nerve block
0 (0.0%)
2 (1.1%)
Physical therapy
2 (1.1%)
3 (1.6%)
Other medication
8 (4.3%)
13 (7.0%)
0 (0.0%)
3 (1.6%)
0.5 (0.2, 1.0)
0.049
1.5 (0.8, 2.6)
0.18
treatment **
Treatment:
Surgical (return to operating
for suture removal)
Long-term complications n (%)
Participants with:
Vaginal granulation tissue at 6 to 24
months***
36 (19.1%)
26 (14.0%)
Mesh erosion/exposure at 4 weeks to
24 months***
3 (1.6%)
1 (0.5%)
Suture exposure at 6 to 24 months***
29 (15.4%)
32 (17.2%)
N/A - LR
0.9 (0.5, 1.5)
0.60
Severity (Dindo Scores) for Expected Adverse Events n (%)
Participants with Expected AE severity
(most severe per participant), n (%)
No such events
30 (16.0%)
22 (11.8%)
I
29 (15.4%)
38 (20.4%)
II
74 (39.4%)
74 (39.8%)
III
33 (17.6%)
24 (12.9%)
IV
1 (0.5%)
0 (0.0%)
V
0 (0.0%)
0 (0.0%)
N/A
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
0.58
Summary of Serious Adverse Events
Participants with any SAE
31 (16.5%)
31 (16.7%)
40
44
157 (83.5%)
155 (83.3%)
I
3 (1.6%)
2 (1.1%)
II
11 (5.9%)
11 (5.9%)
III
15 (8.0%)
17 (9.1%)
IV
1 (0.5%)
1 (0.5%)
V
1 (0.5%)#
0 (0.0%)
No such events
157 (83.5%)
155 (83.3%)
Not assessable
2 (1.1%)
0 (0.0%)
24 (12.8%)
22 (11.8%)
5 (2.7%)
9 (4.8%)
Number of SAEs
0.9 (0.5, 1.6)
0.83
N/A
0.75
N/A
0.74
Dindo Classification:
No such events
Participants with SAE by relationship to
study
Unlikely
Likely
N/A = Not applicable; OR = Odds Ratio; CI = Confidence Interval.
N/A – LR = The Adjusted OR and P value isn’t shown due to reliability of test.
* Not identified during surgical procedure.
** Defined a priori as acute-onset pain involving the buttock, groin and/or lower extremity, usually
unilateral, occurring on the side or sides where vault suspension stitches have been placed and within
one week of the index surgery requiring an alteration of routine postoperative care (e.g., nerve block,
physical therapy, return to OR for suture removal, addition of medications used to treat neuropathic
pain such as anticonvulsants or tricyclic anti-depressants, or the increase or persistence of narcotic pain
medication use beyond 14 days after surgery).
***Not mutually exclusive. Location and need for or type of treatment not collected. Mesh erosion excludes
from the denominator patients who did not receive TVT at surgery.
#Patient death not attributable to study surgery.
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
eBox. Severity Grade Determined by a Modified Version of the Dindo Classification System, Which
is Based on the Level of Therapy Required to Treat an Eventa
Grade
Definition
I
Any deviation from the normal intraoperative or postoperative course without the
need for pharmacological treatment or surgical, endoscopic, and radiological
interventions
Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgesics,
diuretics, electrolytes, and physiotherapy. This grade also includes wound infections
opened at the bedside
II
Requiring pharmacological treatment with drugs other than such allowed for grade I
complications.
IIa
Oral administration of drugs other than such allowed for grade I, including antibiotics
for wound or bladder infections
IIb
IV administration of drugs other than such allowed for grade I, including antibiotics;
blood transfusions and total parenteral nutrition are also included
III
Requiring surgical, endoscopic or radiological intervention
IIIo
Additional surgical measures required during OPTIMAL procedure
IIIa
Intervention not under general anesthesia
IIIb
Intervention under general anesthesia
IV
V
Suffix
“d”
Life-threatening complication (including CNS complications)* requiring IC/ICU
management
IVa
Single organ dysfunction (including dialysis)
IVb
Multiorgan dysfunction
Death of a patient
If the patient suffers from a complication at the time of discharge, the suffix “d” (for
“disability”) is added to the respective grade of complication. This label indicates the
need for a follow-up to fully evaluate the complication.
*Brain hemorrhage, ischemic stroke, subarachnoidal bleeding, but excluding transient ischemic attacks.
CNS, central nervous system; IC, intermediate care; ICU, intensive care unit.
a
Adapted from Dindo D, Demartines N, Clavien PA. Classification of surgical complications. Ann Surg.
2004;240(2):205-213. ©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
eTable 9. Pelvic Floor Distress Inventory Results
Variable
Urinary
Distress
Inventory
(UDI) Score
N
Time
Frame
Baseline
Baseline
to 6 Mo
Change
Adjusted mean
(SE)
[Min, Max]
Baseline
to 12 Mo
Change
Baseline
to 24 Mo
Change
Pelvic Organ
Prolapse
Distress
Baseline
Surgical Treatment Comparison
ULS
SSLF
N=188
N=186
175
Adjusted Mean
Treatment
Difference
(95% CI)
BPMT Treatment Comparison
BPMT
Usual Care
N=186
N=188
179
178
176
123.0 (63.2)
130.0 (57.4)
128.1 (60.4)
124.9 (60.4)
[9.6, 292.3]
[28.2, 280.0]
[15.2, 280.0]
[9.6, 292.3]
163
165
163
165
-96.2 (5.9)
-99.7 (5.8)
-94.6 (4.9)
-87.9 (4.9)
[-276.5, 49.0]
[-256.0, 95.1]
[-276.5, 49.0]
[-264.0, 95.1]
153
159
156
156
-98.6 (5.9)
-98.3 (5.8)
-91.7 (5.0)
-91.8 (4.9)
[-276.5, 65.6]
[-244.0, 73.1]
[-276.5, 65.6]
[-259.2, 73.1]
144
148
146
146
-86.6 (5.9)
-88.4 (5.8)
-81.4 (5.0)
-80.1 (5.0)
[-274.6, 107.5]
[-261.5, 77.6]
[-274.6, 107.5]
[-242.4, 77.6]
175
179
178
176
120.2 (70.4)
127.4 (66.8)
126.0 (67.8)
121.6 (69.5)
3.6 (-9.6, 16.7)
-0.3 (-13.5, 12.9)
1.8 (-11.5, 15.0)
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
P
value
0.60
0.96
0.79
Adjusted Mean
Treatment
Difference
(95% CI)
P
value
-6.7 (-19.7, 6.2)
0.31
0.1 (-12.9, 13.2)
0.98
-1.3 (-14.4, 11.8)
0.84
Inventory
(POPDI)
Score
Baseline
to 6 Mo
Change
N
Adjusted mean
(SE)
Baseline
to 12 Mo
Change
[Min, Max]
Baseline
to 24 Mo
Change
Colorectalanal Distress
Inventory
(CRADI)
Score
N
Baseline
Baseline
to 6 Mo
Change
[0.0, 300.0]
[0.0, 296.4]
[0.0, 300.0]
[7.1, 292.3]
163
165
163
165
-85.3 (6.2)
-91.7 (6.0)
-86.8 (5.3)
-73.2 (5.2)
[-267.3, 121.4]
[-278.0, 54.2]
[-267.3, 98.2]
[-278.0, 121.4]
153
159
156
156
-87.7 (6.2)
-93.0 (6.1)
-83.7 (5.3)
-80.0 (5.3)
[-241.7, 130.4]
[-273.2, 42.9]
[-263.7, 130.4]
[-273.2, 33.9]
144
148
146
146
-77.1 (6.2)
-78.6 (6.1)
-73.3 (5.4)
-65.2 (5.3)
[-252.4, 131.5]
[-288.7, 131.5]
[-252.4, 131.5]
[-288.7, 131.5]
175
179
178
176
107.7 (85.6)
113.4 (82.2)
111.8 (85.5)
109.3 (82.3)
[0.0, 380.4]
[0.0, 357.1]
[0.0, 357.1]
[0.0, 380.4]
163
165
163
165
-67.7 (6.5)
-74.4 (6.4)
-67.9 (6.1)
-60.2 (6.0)
[-283.6, 84.5]
[-295.7, 89.5]
[-276.4, 64.3]
[-295.7, 89.5]
153
159
156
156
-73.0 (6.6)
-70.1 (6.4)
-66.9 (6.1)
-61.7 (6.0)
[-363.3, 126.2]
[-295.7, 115.1]
[-269.3, 126.2]
[-363.3, 115.1]
6.5 (-7.5, 20.4)
5.3 (-8.8, 19.4)
1.5 (-12.7, 15.7)
6.7 (-9.2, 22.7)
0.36
0.46
0.84
0.41
-13.6 (-27.4, 0.2)
0.054
-3.7 (-17.6, 10.3)
0.61
-8.0 (-22.1, 6.1)
0.26
-7.7 (-23.6, 8.2)
0.34
-5.1 (-21.2, 10.9)
0.53
Adjusted mean
(SE)
[Min, Max]
Baseline
to 12 Mo
Change
-2.9 (-19.0, 13.2)
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017
0.73
Baseline
to 24 Mo
Change
144
148
-62.1 (6.6)
-51.1 (6.5)
[-363.3, 96.7]
[-283.6, 206.2]
-10.9 (-27.2, 5.3)
0.19
146
146
-52.5 (6.2)
-46.2 (6.1)
[-280.0, 151.5]
[-363.3, 206.2]
-6.3 (-22.5, 10.0)
0.45
CI=Confidence Interval; SE=Standard Error of Adjusted Mean.
NOTE: Patient reported outcome scale ranges: Pelvic Floor Distress Inventory (PFDI) scales, Urinary Distress Inventory (UDI) (0-300), Pelvic Organ
Prolapse Distress Inventory (POPDI) (0-300), and Colorectal-anal Distress Inventory (CRADI) (0-400) with higher scores indicting greater
symptom bother.
©2015AmericanMedicalAssociation.Allrightsreserved.
Downloaded From: http://jama.jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/929845/ on 06/18/2017