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SCIENTIFIC ARTICLE
Management of Recurrent Carpal Tunnel
Syndrome: Systematic Review and Meta-Analysis
Miguel C. Jansen, MD, PhD,*†Liron S. Duraku, MD, PhD,*Caroline A. Hundepool, MD, PhD,*
Dominic M. Power, MD, PhD,‡Vaikunthan Rajaratnam, MD,
§
Ruud W. Selles, PhD,*†
J. Michiel Zuidam, MD, PhD*
Purpose Few comparisons have been performed between the outcomes of surgical techniques
for recurrent carpal tunnel syndrome. Using a meta-analysis, this study aimed to compare the
outcomes of different surgical techniques using the Boston Carpal Tunnel Questionnaire
(BCTQ) and visual analog scale (VAS) for pain as outcomes.
Methods The following categories were used to define the study’s inclusion criteria: popu-
lation, intervention, comparator, outcomes, and study design. Studies were examined by 2
reviewers, and the Preferred Reporting Items for Systematic Review and Meta-Analyses
guidelines were followed. The studies were assigned to 1 of the following treatment
groups: decompression with or without neurolysis, autologous fat transfer, hypothenar fat
pad, pedicled or free flap, and “other.”For our primary outcome, we compared improvement
using the BCTQ and VAS for pain between the treatment groups. For our secondary outcome,
postoperative BCTQ and VAS pain values were compared.
Results Fourteen studies were included: 5 case series with postoperative data only and 9 pre-
post studies without a control group. With regard to our primary outcome, the studies reported
an average improvement of 1.2 points (95% confidence interval [CI][1.5, 0.9]) on a scale of
1e5 on the symptoms severity scale (SSS) of the BCTQ, 1.9 points (95% CI [1.37, 0.79]) on
a scale of 1e5 on the function severity scale of the BCTQ, and 3.8 points (95% CI [4.9, 2.6])
on a scale of 1e10 on the VAS for pain. We only found significantly lesser improvement in
the “other”treatment group than in the hypothenar fat pad group and autologous fat transfer
group using the SSS. The hypothenar fat pad group had the best reported postoperative SSS
score of 1.75 (95% CI [1.24, 2.25]), function severity scale score of 1.55 (95% CI [1.20,
1.90]), and VAS pain score of 1.45 (95% CI [0.83, 2.07]).
Conclusions All the techniques showed clinically important improvements in all the outcomes.
We found lesser improvement in the “other”treatment group than in the hypothenar fat
pad group and autologous fat transfer group using the SSS. We found that the hypothenar fat
pad group had the best reported postoperative values in our secondary analysis. (J Hand Surg
Am. 2021;-(-):1.e1-e19. Copyright Ó2021 by the American Society for Surgery of the
Hand. All rights reserved.)
Type of study/level of evidence Therapeutic IV.
Key words Hand surgery, meta-analysis, recurrent carpal tunnel syndrome.
From the *Department of Plastic, Reconstructive Surgery and Hand Surgery, Erasmus Medical
Centre, Rotterdam, the Netherlands; the †Department of Rehabilitation Medicine, Erasmus
Medical Centre, Rotterdam, the Netherlands; the ‡Queen Elizabeth Hospital Birmingham,
Birmingham Hand Centre, Birmingham, United Kingdom; and the §Department of Orthopaedic
Surgery, Khoo Teck Puat Hospital, Singapore.
Received for publication July 9, 2020; accepted in revised form May 5, 2021.
No benefits in any form have been received or will be received related directly or indirectly
to the subject of this article.
Corresponding author: Miguel C. Jansen, MD, PhD, Erasmus Medical Centre,
s-Gravendijkwal 230, Room EE 15.89, 3015 CE Rotterdam, the Netherlands; e-mail:
miguel_jansen@hotmail.com.
0363-5023/21/---0001$36.00/0
https://doi.org/10.1016/j.jhsa.2021.05.007
Ó2021 ASSH rPublished by Elsevier, Inc. All rights reserved. r1.e1
CARPAL TUNNEL SYNDROME (CTS) is a common
condition and has an estimated prevalence of
around 5.8% in women and 0.6% in men in
the general population.
1
Carpal tunnel release (CTR)
is one of the most common surgical procedures per-
formed on the hand, and it has been estimated that
during their lifetime, around 1.9% of men and 4.1%
of women undergo CTR.
2
Although the success rate of CTR is high (around
80%), it has been estimated that 2%e10% of patients
require a revision surgery for recurrent CTS.
3e10
The
recurrence of CTS is defined as the reappearance of
CTS symptoms after a symptom-free interval of at
least 3 months following CTR.
5
Multiple causes of
the recurrence of CTS have been described, such as
circumferential fibrosis, reconstitution of the trans-
verse carpal ligament, or more rare causes such as a
tumor in the carpal tunnel.
7,11
Multiple techniques have been used to treat
recurrent CTS, including revision decompression,
autologous fat transfer, or resurfacing of the median
nerve using a hypothenar fat pad flap or pedicled
flaps, all with variable results.
12e18
However, min-
imal comparative research has been conducted on
the reported outcomes of different surgical tech-
niques for recurrent CTS. So far, only 1 systematic
review has been conducted on this subject, by
Soltani et al
19
in 2013, with a total of 14 included
studies. Their study focused on the success rates of
different surgical techniques for recurrent CTS, and
they found that decompression with the use of
vascularized flap coverage has a higher success rate
than a simple repeated decompression. Although the
review by Soltani et al
19
was one of the first to
perform an in-depth analysis of the outcomes of
different surgical techniques, the different outcome
measures of the included studies were categorized
into the dichotomous outcome “resolved/improved”
or “unchanged/worse.”Although these results pro-
vide valuable insights into the success rates of
different surgical techniques, the different outcome
measures used in the included studies were not
necessarily directly comparable. This might have
influenced the generalizability of their results. In
addition, since 2013, multiple studies have been
published reporting the treatment outcomes of
different surgical techniques for the treatment of
recurrent CTS.
12,16,18,20e25
Therefore, this study aimed to evaluate the
current evidence of various surgical techniques
used for the treatment of recurrent CTS by perform-
ing a meta-analysis of treatment outcomes using
comparable and validated patient-reported outcome
measurements, such as the Boston Carpal Tunnel
Questionnaire (BCTQ) and visual analog scale (VAS)
for pain.
26,27
METHODS
Search strategy
In February 2020, we performed a systematic litera-
ture search in 7 databases: Medline, Web of Science,
Cochrane, PubMed publisher, Google Scholar, Sco-
pus, and EMBASE. This search was conducted with
the aid of a medical librarian of the Erasmus Medical
Center, Rotterdam. The search strings and databases
to identify all articles concerning surgical treatment
for recurrent CTS are shown in Appendix E1
(available online on the Journal’swebsite at www.
jhandsurg.org).
Study selection
The following categories were used to define the
study’s inclusion criteria: population, intervention,
comparator, outcomes, and study design. All pub-
lished studies (prospective or retrospective) reporting
the outcomes of various surgical treatments for
recurrent CTS were considered for inclusion. Subse-
quently, the abstracts and titles of the published
studies identified using the search terms were inde-
pendently screened by 2 reviewers (M.C.J. and
L.S.D.). Differences between the reviewers were
discussed until an agreement was reached. Next, the
full text of these articles was assessed based on the
following eligibility criteria:
1. Article was written in English.
2. Article was original (no reviews).
3. A minimum of 5 patients were included in the
study.
4. Article was concerned with the surgical manage-
ment of recurrent CTS. Article had to mention a
symptom-free period of at least 3 months for all
patients before the recurrence of symptoms, or
recurrent CTS was diagnosed by a physician. In
addition, when patients with both persistent and
recurrent CTS were included in a study, the results
had to be presented separately for patients with
persistent and those with recurrent CTS.
5. Postoperative BCTQ or VAS pain scores were
included in the reported outcome measurements.
6. Article was published after 1990.
The quality of evidence of the included articles
was based on The Oxford Centre for Evidence-Based
Medicine’s levels-of-evidence system (Appendix E2,
available online on the Journal’swebsite at
www.jhandsurg.org).
28
Subsequently, an assessment
1.e2 OUTCOMES OF RECURRENT CTS SURGICAL TREATMENT
J Hand Surg Am. rVol. -,-2021
of bias was conducted using the National Institutes of
Health’s tool for series studies (Appendices E3eE5,
available online on the Journal’s website at
www.jhandsurg.org).
29
The Preferred Reporting Items
for Systematic Review and Meta-Analyses guidelines
were followed.
25
The checklist is available in
Appendix E5.
The studies were assigned to 1 of the following
treatment groups: decompression with or without
neurolysis, autologous fat transfer, hypothenar fat
pad, pedicled or free flap, and “other”based on the
reported intervention. The “other”treatment group
consisted of studies that could not be assigned to any
of the other treatment groups.
Data extraction
The following details were extracted from the
included studies: authors, publication year, number of
hands treated, percentage of female patients, type of
surgeries performed for recurrent CTS, mean time of
follow up, and outcome measurements (BCTQ
symptom severity scale [SSS]/functional status scale
[FSS] and VAS pain scores). When a study presented
multiple surgical techniques separately, the outcomes
were extracted separately for the different treatment
groups.
Validated outcome measurements
We chose the BCTQ because this is a widely used
and validated measurement tool to quantify function
and symptoms for patients with CTS. The BCTQ
covers 2 domains: the SSS and FSS, including 11 and
8 items, respectively. Based on these items, scores
between 1 and 5 (BCTQ score; 1 ¼no complaints,
5¼maximum complaints possible) are calculated for
the SSS and FSS separately. In addition, we chose the
VAS pain scale because this is also a validated
measurement tool and pain, as a symptom, is
commonly reported by patients with recurrent
CTS. For the VAS pain score, patients rate their pain
between 0 and 10 (VAS pain score; 0 ¼no pain,
10 ¼worst pain imaginable).
Statistical analysis
For our primary analysis, we conducted a meta-
analysis to compare pooled improvement between
the different surgical techniques with the defined
procedural categories using the BCTQ and VAS pain
scores. For our secondary analysis, we compared the
pooled, reported postoperative treatment outcomes of
the different surgical techniques for the management
of recurrent CTS using the BCTQ and VAS pain
scores. We used forest plots for both the primary and
secondary analyses.
Moreover, when standard deviations were not re-
ported in the included studies, we estimated these
based on the median, range, and sample size, as
described by Hozo et al.
30
The pooled means and
effect sizes were calculated by extracting the average
scores on the BCTQ and VAS for each study and
pooling these values using a random-effect model
using the DerSimonian-Laird method. In this
random-effect model, the studies were weighted
based on the precision of the study results. To test for
differences between the treatment groups, we used
the method proposed by Borenstein et al.
31
Hetero-
geneity testing was performed using the I
2
statistic.
The I
2
statistic can be interpreted as the proportion of
total variation within study estimates that is caused by
heterogeneity between the studies. Variability in the
sample might obscure some differences between
groups that can be more apparent if the heterogeneity
between the groups is low. In short, an I
2
statistic of
less than 30% can be interpreted as mild heteroge-
neity, whereas an I
2
statistic of more than 50% can be
interpreted as notable heterogeneity. However, the
practical impact of heterogeneity in a meta-analysis
also strongly depends on the size and direction of
treatment effects.
32
Because of multiple testing, we considered P<.005
as statistically significant.
RESULTS
For the BCTQ, 4 case series with only postoperative
data and 5 pre-post studies without a control group
were included. However, some studies evaluated
multiple treatments and were, therefore, assigned to
multiple treatment groups. For the VAS pain scores,
5 pre-post studies without control groups were
included. Figure 1 shows the inclusion process. All
autologous fat transfers were performed immediately,
and none were performed in a delayed fashion. In-
formation on the included studies is shown in
Table 1.
22e24,33e38
Based on power calculations for
the meta-analysis by Hedges et al,
39
the power of the
samples for the different outcomes was sufficient to
detect significant, minimum clinically important dif-
ferences (MCIDs) if they existed, which was reported
as a difference of 0.8, 0.5, and 1.1 for the SSS, FSS,
and VAS pain, respectively.
40,41
Primary outcomes: the effect size of treatment effects
Five, 4, and 5 studies (Tables 2, 3)wereusedtocompare
improvement using the SSS, FSS, and VAS pain scores,
respectively (Figs. 2e4).
20e22,24,25,33,34,37,42e44
OUTCOMES OF RECURRENT CTS SURGICAL TREATMENT 1.e3
J Hand Surg Am. rVol. -,-2021
The amount of SSS score improvement (95%
confidence interval) on a scale of 1e5 was 1.1
(1.3, 0.9) for the decompression with or without
neurolysis group, 1.2 (1.3, 1.1) for the autolo-
gous fat transfer group, 1.7 (2.2, 1.2) for the
hypothenar fat pad group, and 0.8 (1.1, 0.6) for
the “other”group (eg, neurolysis and the application
of a caprolactone/lactide film; Mesofol [Biomet
Deutschland GmbH, Berlin, Germany]) (Fig. 2).
When testing for subgroup differences, the amount of
improvement was lesser for the “other”group than
for the hypothenar fat pad (P¼.001) and autologous
fat transfer groups (P¼.004).
The amount of FSS score improvement (95%
confidence interval) on a scale of 1e5 was 1.0
(1.3, 0.7) for the decompression with or
without neurolysis group, 1.3 (1.7, 0.9) for
the hypothenar fat pad group, and 1.2
(1.4, 0.9) for the “other”group (Fig. 3). There
were no statistically significant differences in FSS
score improvement.
The amount of VAS pain score improvement (95%
confidence interval) on a scale of 0e10 was 4.9
(5.5, 4.3) for the hypothenar fat pad group, 4.0
(5.5, 2.5) for the pedicled or free-flap group,
and 3.0 (4.2, 1.8) for the “other”group (eg,
autologous vein insulator, Canaletto device [Eur-
ymedTM, Saint Dezery, France]) (Fig. 4). There were
no statistically significant differences in the VAS pain
score improvement.
Records idenfied through
database searching
(n = 2159)
Screening
Included
Eligibility
Idenficaon
Records aer duplicates removed
(n = 1118)
Records screened
(n = 1118)
Records excluded
(n = 1038)
Full-text arcles assessed
for eligibility
(n = 78)
Full-text arcles excluded, with reasons
- Case reports (n =3)
- Reviews (n = 6)
- Non-English (n = 3)
- No full-text available (n = 5)
- No outcome of interest (n = 46)
- Leer to the editor (n = 1)
Studies included
(n = 14)
FIGURE 1: Flowchart of the selection of included articles.
1.e4 OUTCOMES OF RECURRENT CTS SURGICAL TREATMENT
J Hand Surg Am. rVol. -,-2021
TABLE 1. Overview of the BCTQ Outcomes of Revision Surgery for Recurrent CTS, per Surgical Technique
Author, Year
Level of Evidence
Number of
Hands Treated
(Patients)
Number of
Women (%)
Surgical
Technique
Mean Follow
Up in Months
(Range)
BCTQ-SSS (SD)
Postoperative
BCTQ-FSS (SD)
Postoperative
Neurolysis
Impelmans et al,
33
2001
Level III
21 (20) 16 (80%) Redecompression þ
external neurolysis
36 (2e100) 2.50 (0.20) 3.00 (0.20)
Luria et al,
34
2008
Level IV
41 (41) 13 (32%) Endoscopic
redecompression
12 2.00 (0.30) 2.00 (0.20)
Pace et al,
35
2018
Level III
17 (17) 10 (59%) Redecompression 53 (16e155) 1.84 (0.81) 2.12 (1.36)
Sun et al,
24
2019
Level IV
114 (112) 84 (75%) Redecompression 6 1.91 (0.60) 1.92 (0.70)
Autologous fat transfer
Impelmans et al,
33
2001
Level III
23 (20) 19 (91%) Free fat graft 36 (2e100) 2.30 (0.20) 2.60 (0.20)
Hypothenar fat pad
De Smet et al,
36
2002
Level III
8 (8) 6 (75%) Hypothenar fat pad
flap
31 (9e66) 2.70 (1.05) 2.55 (1.15)
Lattré et al,
37
2016
Level III
8 (8) 6 (75%) Hypothenar fat pad
flap
12 1.09 (0.20) 1.16 (0.20)
Lattré et al,
37
2016
Level III
8 (8) 5 (63%) Hypothenar fat pad
flap
12 1.22 (0.27) 1.14 (0.14)
Pace et al,
35
2018
Level III
16 (16) 7 (44%) Hypothenar fat pad
flap
53 (16e155) 2.54 (1.18) 2.50 (1.32)
Pedicled flap
De Smet et al,
36
2002
Level III
6 (6) 3 (50%) Distal ulnar fat flap 31 (9e66) 2.67 (0.71) 2.26 (0.71)
Goitz et al,
38
2005
Level IV
10 (7) 6 (86%) Microvascular
omental transfer
79 (54e105) 3.10 (0.70) 3.10 (0.90)
Other
Nassar et al,
22
2014
Level IV
14 (14) 11 (79%) Neurolysis and
application of
Mesofol
26 (18e39) 1.88 (0.37) 1.69 (0.35)
Sun et al,
23
2019
Level IV
20 (18) 10 (56%) Palmaris longus
interposition
15 (7e26) 2.25 (range, 1.09e4.45) 2.18 (range, 1.25e4.13)
SD, standard deviation.
OUTCOMES OF RECURRENT CTS SURGICAL TREATMENT 1.e5
J Hand Surg Am. rVol. -,-2021
For all the outcomes, the forest plots in
Figures 2e4show relatively high within-subgroup
heterogeneity (0%e88%) between the studies.
Secondary outcomes: reported postoperative outcomes
The pooled average of the reported postoperative SSS
score for the outcomes was 2.1 (1.8, 2.4). The means
of the postoperative pooled SSS scores for the
different treatment groups can be seen in Figure 5.
The pooled postoperative SSS scores for the
hypothenar fad pad (1.8 [1.2, 2.3]), decompression
with or without neurolysis (2.0 [1.8, 2.3]), and
“other”groups (2.0 [1.7, 2.4]) were better than that
of the pedicled or free-flap group (2.9 [2.5, 3.3])
(P<.005). Furthermore, the postoperative SSS
scores for the hypothenar fat pad and decompression
with or without neurolysis groups were better
than that of the autologous fat transfer group (2.5
[2.4, 2.6]) (P<.005).
Considering the postoperative FSS score, the
average score was 2.2 [1.8, 2.5] (Fig. 6). The
hypothenar fat pad treatment (1.6 [1.2, 1.9]), decom-
pression with or without neurolysis (2.2 [1.8, 2.6]),
and “other”treatment groups (1.9 [1.4, 2.4]) had better
pooled postoperative outcomes than the autologous fat
transfer group (3.0 [2.9, 3.1]) (P<.005).
Considering the postoperative VAS pain score,
the average score was 2.8 [2.0, 3.6] (Fig. 7). The
pooled reported postoperative VAS pain score for
the hypothenar fat pad group (1.4 [1.0, 1.9]) was
better than that for the “other”group (3.0 [2.3, 3.8])
(P<.001).
DISCUSSION
In this study, we reported validated outcomes
measured using the BCTQ and VAS pain scores for
the different surgical procedures used for the man-
agement of recurrent CTS. When improvements with
TABLE 2. Overview of VAS for the Pain Outcomes of Revision Surgery for Recurrent CTS, per Surgical
Technique
Author, Year
Level of Evidence
Number of
Hands Treated
(Patients)
Number of
Women (%) Surgical Technique
Mean
Follow Up in
Months (Range)
VAS for
Pain 0e10 (SD)
Postoperative
Decompression with or
without neurolysis
Autologous fat transfer
Hypothenar fat pad
Wichelhaus et al,
25
2015
Level IV
18 (18) 14 (78%) Hypothenar fat pad
flap
22 (6e53) 1.5 (1.9)
Athlani et al,
20
2017
Level IV
34 (34) 15 (44%) Hypothenar fat pad
flap
36 (24e60) 1.4 (0e6)*
Pedicled or free flap
Dahlin et al,
42
2002
Level IV
15 (15) 10 (67%) Pedicled ulnar flaps
(n ¼5), pedicled
forearm flap (n ¼1),
groin flap (n ¼1),
scapular flaps
(n ¼3), free lateral
arm flaps (n ¼5)
102 (3e168) 5.0 (1e10)*
Cheung et al,
43
2017
Level IV
14 (12) 7 (58%) Abductor digiti minimi
flap
44 (4e170) 2.9 (1.5)
Other
Varitimidis et al,
44
2001
Level IV
15 (15) 9 (60%) Autologous vein
insulator
43 (24e78) 3.1 (1.1)
Carmona et al,
21
2019
Level III
21 (21) 16 (76%) Canaletto device 12 (7e19) 3.8 (0e9)*
Carmona et al,
21
2019
Level III
19 (19) 12 (63%) Canaletto device and
Dynavisc gel
11 (6e23) 2.3 (0e7)*
SD, standard deviation.
*Range.
1.e6 OUTCOMES OF RECURRENT CTS SURGICAL TREATMENT
J Hand Surg Am. rVol. -,-2021
TABLE 3. Overview of Studies Reporting Pre- and Postoperative BCTQ Scores for Revision Surgery for Recurrent CTS, per Surgical Technique
Author, Year
Number of
Hands
(Patients)
Surgical
Technique
Mean
Preoperative
BCTQ-SSS (SD)
Mean
Postoperative
BCTQ-SSS (SD)
D
BCTQ-SSS
Mean
Improvement (%)
Mean
Preoperative
BCTQ-FSS
(SD)
Mean
Postoperative
BCTQ-FSS
(SD)
D
BCTQ-FSS
Mean
Improvement
(%)
Decompression with or
without neurolysis
Impelmans et al,
33
2001
Level III
21 (20) Redecompression þ
external neurolysis
3.3 (0.2) 2.3 (0.2) 1.0 (43%)
Luria et al,
34
2008
Level IV
41 (41) Endoscopic
redecompression
3.3 (0.2) 2.0 (0.3) 1.3 (57%) 3.1 (0.3) 2.0 (0.2) 1.1 (52%)
Sun et al,
24
2019
Level IV
114 (112) Redecompression 3.0 (0.6) 1.9 (0.6) 1.1 (55%) 2.7 (0.7) 1.9 (0.7) 0.8 (47%)
Autologous fat transfer
Impelmans et al,
33
2001
Level III
23 (20) Free fat graft 3.7 (0.2) 2.5 (0.2) 1.2 (44%)
Hypothenar fat pad
Lattré et al,
37
2016
Level III
8 (8) Hypothenar fat pad
flap
3.1 (0.8) 1.1 (0.2) 2.0 (95%) 2.7 (0.8) 1.2 1.5 (88%)
Lattré et al,
37
2016
Level III
8 (8) Hypothenar fat pad
flap
2.7 (0.7) 1.2 (0.3) 1.5 (88%) 2.3 (0.7) 1.1 (0.1) 1.2 (92%)
Pedicled or free flap
Other
Nassar et al,
22
2014
Level IV
14 (14) Neurolysis and the
application of
Mesofol
2.7 (0.3) 2.0 (0.3) 0.7 (41%) 2.8 (0.2) 1.7 (0.4) 1.1 (60%)
OUTCOMES OF RECURRENT CTS SURGICAL TREATMENT 1.e7
J Hand Surg Am. rVol. -,-2021
the reported MCID were compared, which was a
difference of 0.8, 0.5, and 1.1 for the SSS, FSS, and
VAS pain scores, respectively, the improvement for
all the included surgical techniques was greater than
the MCID.
40,41
This means that, on an average, all the
included surgical treatments are effective for clini-
cally relevant improvement.
When improvement was compared, we only
found lesser improvement for the “other”treatment
group than for the hypothenar fat pad and autolo-
gous fat transfer groups using the SSS. We did not
find differences between the treatment groups when
improvement was compared using the FSS and
VAS pain scores. This might be partially explained
by the limited number of studies available for
analysis and the heterogeneity between these
studies. However, with regard to the size of the
improvement in the outcomes (Figs. 2e4), there
may have been a trend toward a greater improve-
ment when recurrent CTS was treated using the
hypothenar fat pad. Looking at the postoperative
BCTQ and VAS pain scores (Figs. 5e7), this trend
may have been supported by the favorable reported
postoperative scores for the hypothenar fat pad
compared with that for the other techniques. These
results are in line with the high success rates re-
ported for the hypothenar fat pad (89%e93%) by
Soltani et al.
19
However, in contrast to our study,
Soltani et al
19
also reported relatively high success
rates for the pedicled and free flaps.This may be
explained by the inclusion of different studies and
outcome measurements.
To our knowledge, this is the first meta-analysis to
compare the outcomes of different surgical tech-
niques for recurrent CTS using validated outcome
measurements. Although Soltani et al
19
conducted a
systematic review to compare the efficacy of flap and
nonflap surgeries for recurrent CTS, they compared
the percentage of patients who experienced
improvement/resolution with different treatment out-
comes. They grouped the hypothenar fat pad within
the flap surgery treatment group for analysis.
Furthermore, they found that flap surgery likely leads
to better success rates. Although this is in line with
FIGURE 2: Forest plot for the mean differences between preoperative and postoperative BCTQ-SSS scores for the treatment groups:
autologous fat transfer, hypothenar fat pad, decompression with or without neurolysis, and ”other.”Blue squares represent values re-
ported in the study, and red diamonds represent the pooled mean differences for the treatment group. For the subgroup differences, the
amount of improvement is significantly lesser for the “other”group (eg, neurolysis and the application of Mesofol) than for the
hypothenar fat pad group (P¼.001) and autologous fat transfer group (P¼.004).
1.e8 OUTCOMES OF RECURRENT CTS SURGICAL TREATMENT
J Hand Surg Am. rVol. -,-2021
our finding that the hypothenar fat pad flap has
favorable reported outcomes, this effect may be
explained by other types of flap surgery in the flap
surgery treatment group described by Soltani et al.
19
FIGURE 3: Forest plot for the mean differences between preoperative and postoperative BCTQ-FSS scores for the different treatment
groups: hypothenar fat pad, decompression with or without neurolysis, and “other.”The blue squares represent the mean differences
reported in the study, and the red diamonds represent the pooled mean differences for the treatment group, with their width as the CI.
When calculating subgroup differences, there were no statistically significant differences between the subgroups.
FIGURE 4: Forest plot for the mean differences between pre- and postoperative VAS pain scores for the different treatment groups:
hypothenar fat pad, pedicled or free flap, and “other.”The blue squares represent the mean differences reported in the study, and the red
diamonds represent the pooled mean differences for the treatment group, with their width as the CI. When calculating subgroup dif-
ferences, there were no statistically significant differences between the subgroups.
30
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J Hand Surg Am. rVol. -,-2021
Several limitations of this study should be
considered. First, when comparing the outcomes, a
selection bias may have played an important role.
Patient characteristics between the treatment groups
might have differed, and therefore, the outcomes of
the treatments may not have been comparable.
However, based on the information of the included
studies, we were not able to correct for this in our
analyses. Second, our forest plots showed variable
within-subgroup heterogeneity (0%e88%) between
the studies. This means that these studies might have
had low comparability. However, this high hetero-
geneity between the studies can be partially explained
by the small sample sizes of the studies because
including studies with small sample sizes can lead to
an overestimation of heterogeneity.
45
In addition, we
used a random-effect model for our analyses, which
can take into account high levels of heterogeneity in
comparison with a fixed-effect model. Third, for
some analyses, only 1 study was available for a
treatment group. Therefore, pooled values for these
treatment groups might not be generalizable and
should be interpreted with caution. Fourth, the
absence of standardization of the timing of outcome
measurement further limits the conclusions that may
be drawn. However, for the majority of the patients,
the outcomes were measured more than 1 year after
surgery. Therefore, the outcomes are less likely to
have been influenced by patients recovering from
their surgery. Fifth, the majority of the included
studies were case series or before-after studies with
no control group. Therefore, the included studies did
not have a high level of evidence. However, no
studies with a higher level of evidence were avail-
able. Sixth, we assumed that the patients underwent a
complete division of the transverse carpal ligament
during the primary procedure. Although the majority
of the studies have explicitly defined recurrent CTS
FIGURE 5: Postoperative pooled means for postoperative BCTQ-SSS for the different treatment groups with CI for the different
treatment groups: hypothenar fat pad, pedicled or free flap, and “other.”The blue squares represent the mean differences reported in the
study, and the red diamonds represent the pooled mean differences for the treatment group, with their width as the CI. The postoperative
SSS for the hypothenar fad pad group, decompression with or without neurolysis group, and “other”group were significantly better than
that of the pedicled or free-flap group (P<.005). Furthermore, the postoperative SSS scores for the hypothenar fat pad and decom-
pression with or without neurolysis groups were significantly better than that of the autologous fat transfer group (P<.005).
1.e10 OUTCOMES OF RECURRENT CTS SURGICAL TREATMENT
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as the absence of CTS symptoms for a minimum of 3
months after a primary surgery, persistent CTS may
have been inappropriately defined as recurrent CTS in
some of the studies. This could especially be true in
studies in which secondary CTS was considered as
recurrent CTS when a diagnosis of recurrent CTS
FIGURE 6: Postoperative pooled means for postoperative BCTQ-FSS for the different treatment groups with a CI. The hypothenar fat
pad shows the best reported pooled postoperative FSS score of the different surgical techniques for recurrent CTS, thus not taking into
consideration the preoperative values. The hypothenar fat pad treatment, decompression with or without neurolysis treatment,
and “other”treatment groups had significantly better pooled reported postoperative outcomes than the autologous fat transfer group
(P<.005).
FIGURE 7: Postoperative pooled means for postoperative VAS for pain for the different treatment groups with a CI. The pooled re-
ported postoperative VAS for pain score of the hypothenar fat pad group.
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was made by a physician without specifying the exact
criteria based on which this diagnosis was made.
However, a revision surgery and the release of re-
sidual compression points would help resolve many
of the symptoms, without the need for the adjunctive
procedures described. Seventh, the follow up of the
patients was different between different studies and
may have introduced variability in the outcome as-
sessments. However, the majority of the studies had a
relatively long follow up period, and therefore, the
reported outcomes are not likely to have been influ-
enced by recovery from surgery. Eighth, to improve
the size of the treatment groups in this study, we
combined some surgical techniques into 1 group. For
example, decompression and neurolysis were com-
bined with free and pedicled flaps. This might have
influenced the generalizability of our results.
Afinal consideration should be regarding the
evolution of surgical practice, development and
availability of biological materials and devices for
implantation, and modification of the healing process.
There are no comparative data for these practices, and
future studies may need to include these in-
terventions, creating further challenges for the
acquisition of higher-level data.
In conclusion, our study showed that all the tech-
niques resulted in an improvement in the BCTQ and
VAS pain scores, which exceeded the MCID.
Furthermore, our study showed some differences in
improvement on the SSS but not on the FSS and VAS
for pain between the treatment groups. However,
there may be a trend toward greater improvement
when using a hypothenar fat pad. The paucity of the
studies and heterogenicity of the sample in this re-
view must be considered when interpreting the find-
ings. Still, it is not clear which technique delivers the
best outcomes, although there are substantial differ-
ences in invasiveness between the techniques.
Although conducting a randomized controlled trial to
determine the efficacy of different interventions in
recurrent CTS would be challenging, further research
with controlled prospective case-matched studies
may be helpful in providing guidance for this clinical
problem following a common surgical intervention in
hand surgery.
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36. De Smet L, Vandeputte G. Pedicled fat flap coverage of the median
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pad flap surgery for end stage and recurrent carpal tunnel syndrome.
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38. Goitz RJ, Steichen JB. Microvascular omental transfer for the
treatment of severe recurrent median neuritis of the wrist: a
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OUTCOMES OF RECURRENT CTS SURGICAL TREATMENT 1.e13
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APPENDIX E1. Search Results and Search Terms
Source References References After Deduplication
EMBASE 821 808
Medline (Ovid) 729 177
Cochrane 36 12
Web of Science 473 109
Google Scholar (100 top ranked) 100 12
Total 2,159 1,118
EMBASE
(“carpal tunnel syndrome”/de OR (“median nerve”/de AND (“nerve compression”/de OR “nerve decompression”/de)) OR (((carpal*) NEAR/3
(tunnel* OR tunnel* OR canal*)) OR ((median*) NEAR/3 (nerve*) NEAR/3 (compression* OR decompression*))):ab,ti,kw) AND (“recurrent
disease”/de OR “reoperation”/de OR (recurren* OR revision* OR recurring OR revising OR reoperat* OR re-operat*):ab,ti,kw) NOT ([animals]/lim
NOT [humans]/lim) NOT ([Conference Abstract]/lim)
Medline
(Carpal Tunnel Syndrome/ OR (Median Nerve/ AND Nerve Compression Syndromes/) OR (((carpal*) ADJ3 (tunnel* OR tunel* OR canal*)) OR
((median*) ADJ3 (nerve*) ADJ3 (compression* OR decompression*))).ab,ti,kf.) AND (Recurrence/ OR Reoperation/ OR (recurren* OR revision*
OR recurring OR revising OR reoperat* OR re-operat*).ab,ti,kf.) NOT (exp animals/ NOT humans/) NOT (news OR congres* OR abstract* OR
book* OR chapter* OR dissertation abstract*).pt.
Cochrane
((((carpal*) NEAR/3 (tunnel* OR tunel* OR canal*)) OR ((median*) NEAR/3 (nerve*) NEAR/3 (compression* OR decompression*))):ab,ti)
AND ((recurren* OR revision* OR recurring OR revising OR reoperat* OR re-operat*):ab,ti)
Web of Science
TS¼((((((carpal*) NEAR/2 (tunnel* OR tunel* OR canal*)) OR ((median*) NEAR/2 (nerve*) NEAR/2 (compression* OR decompression*))))
AND ((recurren* OR revision* OR recurring OR revising OR reoperat* OR re-operat*))) NOT ((animal* OR rat OR rats OR mouse OR mice OR
murine OR dog OR dogs OR canine OR cat OR cats OR feline OR rabbit OR cow OR cows OR bovine OR rodent* OR sheep OR ovine OR pig OR
swine OR porcine OR veterinar* OR chick* OR zebrafish* OR baboon* OR nonhuman* OR primate* OR cattle* OR goose OR geese OR duck OR
macaque* OR avian* OR bird* OR fish*) NOT (human* OR patient* OR women OR woman OR men OR man)))
Google Scholar
“carpal tunnel|tunel|canal”|“median nerve compression”recurrence|recurrent|revision|recurring|revising|reoperation
1.e14 OUTCOMES OF RECURRENT CTS SURGICAL TREATMENT
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APPENDIX E2. The Oxford Centre for Evidence-Based Medicine Levels-of-Evidence System Specifications
Level Type of Study Design
1A Systematic review/meta-analysis (with homogeneity*) of RCTs
1B Individual randomized controlled trial (with narrow confidence interval†,‡)
1C All or none§
2A Systematic review/meta-analysis (with homogeneity*) of cohort studies
2B
2C
Individual cohort study (including low-quality randomized controlled trial; eg, <80% follow up)“Outcomes”
research; ecological studies
3A Systematic review/meta-analysis (with homogeneity*) of case-control studies
3B Individual case-control study
4
5
Case series (and low-quality cohort and case-control studiesk)
Expert opinion without explicit critical appraisal or based on physiology, bench research, or “first principles”
RCT, randomized controlled trial.
*By homogeneity, we mean a systematic review that is free of worrisome variations (heterogeneity) in the directions and degrees of results between
individual studies. Not all systematic reviews with statistically significant heterogeneity are worrisome, and not all worrisome heterogeneity is
statistically significant.
†See note above for advice on how to understand, rate, and use trials or other studies with wide confidence intervals.
‡Clinical decision rule (these are algorithms or scoring systems that lead to a prognostic estimation or a diagnostic category).
§Met when all patients died before the treatment became available, but some now survive with treatment; or when some patients died before the
treatment became available, but none now died with treatment.
kBy poor-quality cohort study, we mean that one fails to clearly define comparison groups and/or fails to measure exposures and outcomes in the
same (preferably blinded), objective way in both exposed and nonexposed individuals; identify or appropriately control known confounders; and carry
out a sufficiently long and complete follow up of patients. By poor-quality case-control study, we mean one that fails to clearly define comparison
groups; measure exposures and outcomes in the same (preferably blinded), objective way in both cases and controls; and identify or appropriately
control known confounders.
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APPENDIX E3. Quality Assessment for Case-Series Studies Reporting the BCTQ or the VAS Pain Scores Using
the NIH Tool
BCTQ 1 2 34567 8 9Rating
De Smet et al,
44
2002 þþþþþþ þ þ Good
Goitz et al, 2005 þþþþþþ Fair
Pace et al,
43
2018 þþþþ -þþ þ þ Good
Sun et al,
24
2019 þþþþþþþNA þGood
VAS pain 1 2 34567 8 9
Cheung et al, 2017 þþþþþþþ þ þ Good
NA, not applicable; NIH, National Institutes of Health.
1. Was the study question or objective clearly stated?
2. Was the study population clearly and fully described, including a case definition?
3. Were the cases consecutive?
4. Were the subjects comparable?
5. Was the intervention clearly described?
6. Were the outcome measures clearly defined, valid, reliable, and implemented consistently across all study participants?
7. Was the length of follow up adequate?
8. Were the statistical methods well described?
9. Were the results well described?
+
-
?
Yes No Unclear
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APPENDIX E4. Quality Assessment for Before-After (Pre-Post) Studies With No Control Group Reporting the
BCTQ Score Using the NIH Tool
BCTQ 123456789101112Rating
Impelmans et al,
41
2001 þþþ ?þþþ NA Fair
Luria et al,
42
2008 þþþþþþþþþ NA Good
Nassar et al,
22
2014 þþþþ ?þþþþ NA Good
Lattré et al, 2016 þþþþ ?þþþ þ NA Good
Sun et al,
24
2019 þþþþþþþþþ NA Good
VAS for pain 123456789101112Rating
Varitimidis et al,
45
2001 þþþ ?þþþ NA Fair
Dahlin et al, 2002 þþþ ?þþþþ NA Fair
Wichelhaus et al,
25
2015 þþþþ ?þþþþ NA Good
Athlani et al,
20
2017 þþþþ ?þþþþ NA Good
Carmona et al,
21
2019 þþþþ ?þþþþ NA Good
NA, not applicable; NIH, National Institutes of Health.
1. Was the study question or objective clearly stated?
2. Were the eligibility/selection criteria for the study population prespecified and clearly described?
3. Were the participants in the study representative of those who would be eligible for the test/service/intervention in the general or
clinical population of interest?
4. Were all eligible participants who met the prespecified entry criteria enrolled?
5. Was the sample size sufficiently large to provide confidence in the findings?
6. Was the test/service/intervention clearly described and delivered consistently across the study population?
7. Were the outcome measures prespecified, clearly defined, valid, reliable, and assessed consistently across all study participants?
8. Were the people assessing the outcomes blinded to the participants’exposures/interventions?
9. Was the loss to follow up after baseline 20% or less? Were those lost to follow up accounted for in the analysis?
10. Did the statistical methods examine changes in outcome measures from before to after the intervention? Were statistical tests
performed that provided Pvalues for the pre-to-post changes?
11. Were outcome measures of interest taken multiple times before the intervention and multiple times after the intervention (ie, did
they use an interrupted time-series design)?
12. If the intervention was conducted at a group level (eg, a whole hospital, community, etc), did the statistical analysis take into
account the use of individual-level data to determine effects at the group level?
+
-
?
Yes No Unclear
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APPENDIX E5. PRISMA 2009 Checklist
Section/Topic Number Checklist Item
Reported on
Page Number
Title
Title 1 Identify the report as a systematic review, meta-analysis,
or both.
1
Abstract
Structured
summary
2 Provide a structured summary, including (as applicable)
background; objectives; data sources; study eligibility
criteria, participants, and interventions; study appraisal
and synthesis methods; results; limitations;
conclusions and implications of key findings; and
systematic review registration number.
2, 3
Introduction
Rationale 3 Describe the rationale for the review in the context of
what is already known.
4
Objectives 4 Provide an explicit statement of questions being
addressed with reference to participants, interventions,
comparisons, outcomes, and study design (PICOS).
4, 5
Methods
Protocol and
registration
5 Indicate if a review protocol exists, if and where it can be
accessed (eg, website address), and, if available,
registration information, including registration
number.
6
Eligibility
criteria
6 Specify study characteristics (eg, PICOS, length of
follow up period) and report characteristics (eg, years
considered, language, publication status) used as the
criteria for eligibility, giving a rationale.
6, Tables 1e3
Information
sources
7 Describe all information sources (eg, databases with
dates of coverage, contact with study authors to
identify additional studies) in the search and date last
searched.
6
Search 8 Present full electronic search strategy for at least 1
database, including any limits used, in a way that it can
be repeated.
6, Appendix E1
Study selection 9 State the process for selecting studies (ie, screening,
eligibility, included in systematic review, and, if
applicable, included in the meta-analysis).
6
Data collection
process
10 Describe method of data extraction from reports (eg,
piloted forms, independently, in duplicate) and any
processes for obtaining and confirming data from
investigators.
6
Data items 11 List and define all variables for which data were sought
(eg, PICOS, funding sources) and any assumptions
and simplifications made.
6
Risk of bias in
individual
studies
12 Describe methods used for assessing risk of bias of
individual studies (including specification of whether
this was done at the study or outcome level), and
describe how this information is to be used in any data
synthesis.
6, Appendices E4,E5
Summary
measures
13 State the principal summary measures (eg, risk ratio,
difference in means).
6, 7
Synthesis of
results
14 6, Figures 2e4
(Continued)
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APPENDIX E5. PRISMA 2009 Checklist (Continued)
Section/Topic Number Checklist Item
Reported on
Page Number
Describe the methods of handling data and combining
the results of studies, if done, including the measures
of consistency (eg, I
2
) for each meta-analysis.
Risk of bias
across studies
15 Specify any assessment of the risk of bias that may affect
the cumulative evidence (eg, publication bias,
selective reporting within studies).
6, Appendices E4,E5
Additional
analyses
16 Describe the methods of additional analyses (eg,
sensitivity or subgroup analyses, meta-regression), if
done, indicating which were prespecified.
6
Results
Study selection 17 Give the numbers of studies screened, assessed for
eligibility, and included in the review, with reasons for
exclusions at each stage, ideally with a flow diagram.
8
Study
characteristics
18 For each study, present the characteristics for which
data were extracted (eg, study size, PICOS, follow-up
period) and provide the citations.
9e10, Tables 1e3
Risk of bias
within studies
19 Present data on the risk of bias of each study and, if
available, any outcome level assessment (see item 12).
Appendices E4,E5
Results of
individual
studies
20 For all outcomes considered (benefits or harms), present
for each study, provide (a) simple summary data for
each intervention group and (b) effect estimates and
confidence intervals, ideally with a forest plot.
Figures 2e4
Synthesis of
results
21 Present the results of each meta-analysis done, including
confidence intervals and measures of consistency.
9e10, Figures 2e4
Risk of bias
across studies
22 Present the results of any assessment of the risk of bias
across studies (see item 15).
Appendices 4,5
Additional
analysis
23 Give the results of additional analyses, if done (eg,
sensitivity or subgroup analyses, meta-regression [see
item 16]).
Not applicable
Discussion
Summary of
evidence
24 Summarize the main findings, including the strength of
evidence for each main outcome; consider their
relevance to key groups (eg, health care providers,
users, and policy makers).
11
Limitations 25 Discuss limitations at the study and outcome levels (eg,
risk of bias) and review level (eg, incomplete retrieval
of identified research, reporting bias).
11
Conclusions 26 Provide a general interpretation of the results in the
context of other evidence, and present implications for
future research.
11
Funding
Funding 27 Describe the sources of funding for the systematic review
as well as other support (eg, supply of data) and the
role of funders for the systematic review.
1
PICOS, population, intervention, comparator, outcomes, and study design; PRISMA, Preferred Reporting Items for Systematic Review and Meta-
Analyses.
OUTCOMES OF RECURRENT CTS SURGICAL TREATMENT 1.e19
J Hand Surg Am. rVol. -,-2021
