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Effectiveness of Hyperbaric Oxygen for Fibromyalgia: A Meta-Analysis of Randomized Controlled Trials

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  • Fondazione Paolo Procacci

Abstract and Figures

Background: Hyperbaric oxygen therapy (HBOT) has been reported as an emerging treatment regimen for fibromyalgia syndrome (FMS), with a paucity of solid evidence. Accordingly, a systematic review and meta-analysis were performed to address the effectiveness of HBOT on FMS. Methods: We searched the Cochrane Database, EMBASE, Medline, PubMed, Clinicaltrials.gov, and PsycINFO, and the reference sections of original studies and systematic reviews from inception to May 2022. Randomized controlled trials (RCTs) on the treatment of FMS with HBOT were included. Outcome measures included pain, Fibromyalgia Impact Questionnaire (FIQ), Tender Points Count (TPC), and side effects. Results: Four RCTs, with 163 participants, were included for analysis. Pooled results showed that HBOT could benefit FMS with significant improvement at the end of treatment, including FIQ (SMD = -1.57, 95% CI -2.34 to -0.80) and TPC (SMD = -2.50, 95% CI -3.96 to -1.05). However, there was no significant effect on pain (SMD = -1.68, 95% CI, -4.47 to 1.11). Meanwhile, HBOT significantly increased the incidence of side effects (RR = 24.97, 95% CI 3.75 to 166.47). Conclusions: Collectively, emerging evidence from RCTs indicates that HBOT can benefit FMS patients in FIQ and TPC throughout the observation time phrases. Although HBOT has some side effects, it does not cause serious adverse consequences.
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Citation: Cao, C.; Li, Q.; Zhang, X.;
Varrassi, G.; Wang, H. Effectiveness
of Hyperbaric Oxygen for
Fibromyalgia: A Meta-Analysis of
Randomized Controlled Trials. Clin.
Pract. 2023,13, 583–595. https://
doi.org/10.3390/clinpract13030053
Academic Editor: Mats Eriksson
Received: 18 February 2023
Revised: 15 April 2023
Accepted: 21 April 2023
Published: 26 April 2023
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
Article
Effectiveness of Hyperbaric Oxygen for Fibromyalgia:
A Meta-Analysis of Randomized Controlled Trials
Chunfeng Cao 1, , Qianlu Li 2 ,† , Xinran Zhang 1, Giustino Varrassi 3,* and Haiqiang Wang 4,*
1
Department of Orthopedics, The Yongchuan Hospital of Chongqing Medical University, 439# Xuanhua Road,
Yongchuan, Chongqing 402160, China
2Department of Neurology, The Yongchuan Hospital of Chongqing Medical University, 439# Xuanhua Road,
Yongchuan, Chongqing 402160, China
3Department of Research, Polo Procacci Foundation, Via Tacito 7, 00193 Roma, Italy
4Institute of Integrative Medicine, Shaanxi University of Chinese Medicine, Xixian Avenue, Xixian District,
Xi’an 712046, China
*Correspondence: giuvarr@gmail.com (G.V.); drwanghq@163.com or hqwang@sntcm.edu.cn (H.W.)
These authors contributed equally to this work.
Abstract:
Background: Hyperbaric oxygen therapy (HBOT) has been reported as an emerging
treatment regimen for fibromyalgia syndrome (FMS), with a paucity of solid evidence. Accordingly, a
systematic review and meta-analysis were performed to address the effectiveness of HBOT on FMS.
Methods: We searched the Cochrane Database, EMBASE, Medline, PubMed, Clinicaltrials.gov, and
PsycINFO, and the reference sections of original studies and systematic reviews from inception to
May 2022. Randomized controlled trials (RCTs) on the treatment of FMS with HBOT were included.
Outcome measures included pain, Fibromyalgia Impact Questionnaire (FIQ), Tender Points Count
(TPC), and side effects. Results: Four RCTs, with 163 participants, were included for analysis. Pooled
results showed that HBOT could benefit FMS with significant improvement at the end of treatment,
including FIQ (SMD =
1.57, 95% CI
2.34 to
0.80) and TPC (SMD =
2.50, 95% CI
3.96 to
1.05). However, there was no significant effect on pain (SMD =
1.68, 95% CI,
4.47 to 1.11).
Meanwhile, HBOT significantly increased the incidence of side effects (RR = 24.97, 95% CI 3.75 to
166.47). Conclusions: Collectively, emerging evidence from RCTs indicates that HBOT can benefit
FMS patients in FIQ and TPC throughout the observation time phrases. Although HBOT has some
side effects, it does not cause serious adverse consequences.
Keywords: hyperbaric oxygen therapy; fibromyalgia; systematic review; meta-analysis
1. Introduction
Fibromyalgia syndrome (FMS) is characterized by chronic widespread skeletal mus-
cle pain. It is the third most common musculoskeletal disorder after lumbar pain and
osteoarthritis [
1
,
2
]. FMS patients can present with a range of dysfunction, including
persistent fatigue, sleep disorders, cognitive retardation, functional bowel disease, pares-
thesias, and mood disturbance [
3
,
4
]. The prevalence of FMS in the general population is
0.2–6.6% [
5
], predominantly in females and three times higher than that of males [
6
]. The
treatment of FMS is varied with indefinite curative effects [
7
]. Previous studies [
8
] have
shown that pharmacological interventions are moderately effective for FMS. In spite of
multiple medication options, most patients still experience pain restricting movement. It
has become increasingly recognized that non-pharmacological interventions should be con-
sidered as complementary therapy for chronic pain added to a multidisciplinary treatment
approach [
4
,
7
,
9
,
10
], such as aerobic exercise, meditative exercise therapy, and cognitive
behavioral therapy.
A non-invasive treatment regimen as hyperbaric oxygen therapy (HBOT) provides
100% oxygen at a pressure greater than that at sea level. Peripheral tissue hyperoxia
Clin. Pract. 2023,13, 583–595. https://doi.org/10.3390/clinpract13030053 https://www.mdpi.com/journal/clinpract
Clin. Pract. 2023,13 584
promotes various biochemical effects that are beneficial in conditions such as infections,
ischemia, and wound healing. In the past 20 years, HBOT has been used to treat more
than 100 diseases worldwide, despite scant scientific evidence of its benefits and safety [
11
].
Recently, HBOT has shown good efficacy in the treatment of cluster headaches and mi-
graines, idiopathic trigeminal neuralgia, complex regional pain syndrome, FMS, and other
aspects [
12
16
]. It may alter the glial function and correct abnormal brain activity associated
with FMS through anti-inflammatory effects [1719].
EULAR recommendations for the management of FMS were updated in 2017 based
on systematic reviews [
7
]. Due to insufficient evidence on medical efficacy, HBOT is not
recommended by the recommendations, although it has been successfully used in the
treatment of fibromyalgia. As well, there have been no systematic reviews summarizing
emerging studies on HBOT in FMS until now. Therefore, we aimed to verify the efficacy
and safety of HBOT in FMS by conducting a meta-analysis.
2. Methods
Because the study is a systematic review, approval from an ethics committee is not
required. No systematic review protocol was published prior to the conclusion of this study.
International Prospective Register of Systematic Reviews (PROSPERO) was used to register
this systematic review and meta-analysis and was successful on 9 May 2021 (Registration
No. CRD42021247078)
2.1. Study Selection
We conducted a systematic electronic search in Cochrane Database, EMBASE, Medline,
PubMed, Clinicaltrials.gov, and PsycINFO to identify studies published before 21 May 2022
using the following strategy: “(FMS OR fibromyalgia OR musculoskeletal disease) AND
(HBOT OR hyperbaric oxygenation OR hyperbaric oxygen therapy)” without language
restrictions. Search strategies were tailored for each database. Three independent authors
(QLL, XRZ, and CCF) screened study titles and abstracts and read the full text to assess
study eligibility. Eligible studies were limited to RCTs.
2.2. Eligibility Criteria
The following standards were required: (1) adult patients (>18 years of age) with
FMS based on the American College of Rheumatology (ACR) criteria [
20
]; (2) the type of
intervention as compared HBOT with no treatment or other treatment options; (3) outcome
measures reporting at least one items related to FMS symptom after follow up, including
pain, tender points count (TPC), press pain threshold, fibromyalgia impact questionnaire
(FIQ) and side effects; (4) the study was published in full paper form, and type of studies
limited to RCTs.
Clinical controlled studies, retrospective and cohort studies were excluded. First, the
headings are filtered to exclude duplicate studies. Subsequently, a careful review of the
abstract and full text with the elimination of irrelevant papers.
2.3. Data Collection Process
Two authors (CFC and QLL) extracted the data independently and repeatedly using
Microsoft Office Excel 2007, which was piloted between the reviewers for consistency and
accuracy. After reviewing the content of each article, the reviewer independently extracts
the information according to the entries shown in the table. In cases where the literature
was insufficient for analysis, we emailed the authors for more information. When the data
of two researchers are inconsistent, a third author (KLM) is invited to participate in data
extraction and discussion.
Clin. Pract. 2023,13 585
2.4. Rik of Bias (RoB) in Individual Studies
Cochrane Collaboration’s ROB 2 assessment instrument assessed the risk of bias of the
recruited articles by two authors (QLL and XRZ) [
21
]. Five domains of bias were assessed
by Cochrane Collaboration’s RoB 2: detect randomization process, intended interventions,
missing outcome data, the measurement of the outcome, and the selection of reported
results. RoB 2 makes judgments about the direction of bias for each domain and the overall.
The study will be judged to be at low, moderate, or high ROBs if all domains measures
are at low ROBs, at least one domain measure is at moderate ROBs (no measures with
high ROBs), and one measure at high ROBs or multiple measures with substantially lowers
confidence, respectively.
2.5. Assessment of Heterogeneity
Prior to the meta-analysis, we used standard Cochran’s Q tests and the I
2
statistic
to assess heterogeneity between compare trials. A statistically significant threshold was
required to a pvalue < 0.05. The interpretation of I
2
values is based on the Deeks [
22
].
The higher the I
2
, the more heterogeneity will be. The value of I
2
has four levels, which
were 0–40% (not important), 30–60% (‘moderate’ heterogeneity), 50–90% (‘substantial’
heterogeneity), and 75–100% (‘considerable’ heterogeneity), respectively.
2.6. Assessment of Treatment Effect
RevMan 5.3 software was used for all statistical analyses. When data were continuous,
a random-effects model was used to calculate the standardized mean difference (SMD). All
effect sizes were determined by 95% confidence intervals (CIs).
3. Results
3.1. Hallmarks of Included Studies
We preliminarily reviewed 1295 relevant studies (Table 1) by PubMed (1137 citations),
EMBASE (66 citations), Cochrane (52 citations), Ovid Medline (19 citations), Ovid PsycINFO
(5 citations), and Clinicaltrail.gov (16 citations). Title and abstract were used as preliminary
screening methods, and 881 were excluded. Five studies eventually were selected, four of
which were included in this meta-analysis. In the absence of a control group, one study
was excluded [23].
Table 1. Search strategy and results.
Database Step Search Algorithm Items
PubMed
#1 “Fibromyalgia” [Mesh Terms] 8800
#2 “Musculoskeletal Disease” [ Mesh Terms] 1849
#3 “Chronic Pain Syndrome” [All Fields] 705
#4 “FMS“ [All Fields] 9726
#5 (((#1) OR (#2) OR (#3) OR #4) 1,139,600
#6 “oxygen therapies, hyperbaric” [ Mesh Terms] 12,098
#7 “Hyperbaric Oxygenation” [All Fields] 12,467
#8 “Hyperbaric Oxygenations” [All Fields] 12,468
#9 “Hyperbaric Oxygen Therapies” [All Fields] 12,661
#10 “Hyperbaric Oxygen Therapy” [All Fields] 14,330
#11 “HBOT” [All Fields] 907
#12 (((((#6) OR #7) OR #8) OR #9)OR #10) OR #11) 619
#13 #5 AND #12 1137
Clin. Pract. 2023,13 586
Table 1. Cont.
Database Step Search Algorithm Items
Embase
#1 ‘fibromyalgia’/exp 21,930
#2 ‘musculoskeletal disease’ 38,748
#3 ‘chronic pain syndrome’ 1223
#4 ‘FMS’ 13,022
#5 #1 OR #2 OR #3 OR #4 72,195
#6 ‘Hyperbaric Oxygen Therapy’ 19,726
#7 ‘HBOT’ 1220
#8 #6 OR #7 19,743
#9 #5 AND #8 66
Cochrane
#1 MeSH descriptor: “Fibromyalgia” explode all trees 1429
#2 MeSH descriptor: “Musculoskeletal Diseases” explode
all trees 42,086
#3
Chronic Pain Syndrome: ti, ab, kw (Word variations have
been searched) 303
#4 FMS: ti, ab, kw (Word variations have been searched) 704
#5 #1 or #2 or #3 or #4 45,416
#6 MeSH descriptor: [Balneotherapy] explode all trees 261
#7
Spa therapy:ti,ab,kw (Word variations have been searched)
122
#8 Thermal water:ti,ab,kw (Word variations have
been searched) 79
#9 Balneology:ti,ab,kw (Word variations have
been searched) 211
#10 BT:ti,ab,kw (Word variations have been searched) 1373
#11 #6 or #7 or #8 or #9 or #10 1848
#12 (#5 and #11) restricted as clinical trials 52
Ovid
Medline
#1 Fibromyalgia. mp. 10,642
#2 Musculoskeletal disease. mp. 896
#3 Chronic Pain/ 16,300
#4 #1 or #2 or #3 27,075
#5 oxygen therapies, hyperbaric. mp. 0
#6 Hyperbaric Oxygenation/ 12,083
#7 Hyperbaric Oxygen Therapy. mp. 3382
#8 #5 or #6 or #7 12,614
#9 #4 and #8 19
Ovid
PsycINFO
#1 Fibromyalgia. mp. 3596
#2 exp Musculoskeletal Disorders/ 18,206
#3 exp Chronic Pain/ 13,747
#4 #1 or #2 or #3 31,384
#5 Hyperbaric Oxygen Therapy. mp. 122
#6 exp Oxygenation/ 962
#7 #5 or #6 1082
#8 #4 and #7 5
Clin. Pract. 2023,13 587
Table 1. Cont.
Database Step Search Algorithm Items
Clinicaltrials.
gov
#1 Fibromyalgia 1088
#2 Musculoskeletal Diseases 18,733
#3 Diseases 273,674
#4 Musculoskeletal 19,065
#5 Chronic Pain Syndrome 45
#6 Pain Syndrome 1612
#7 Chronic Pain 2003
#8 Syndrome 28,720
#9 Chronic 25,425
#10 Pain 21,325
#11 FMS 1167
#12 Hyperbaric Oxygenation 171
#13 Oxygenation 1136
#14 Hyperbaric 410
#15 Hyperbaric Oxygen Therapy 171
#16 Oxygen Therapy 3596
#17 Hyperbaric Oxygen 208
#18 Therapy 140,000
#19 Oxygen 3833
#20 HBOT 91
#21
Musculoskeletal Diseases OR Fibromyalgia OR Chronic
Pain Syndrome OR FMS|Hyperbaric Oxygenation OR
Hyperbaric Oxygen Therapy OR HBOT
16
3.2. Participant Hallmarks
In total, 163 participants were included, including 82 patients undergoing HBOT
intervention and 81 controls. In two of the studies, all the cases were women. The average
observational time was 8.25 weeks (range, 3 weeks to 3 months). The reported age of
participants was included in three studies involving the HBOT group and three studies
involving the control group. The mean age for the HBOT group was 46.38, while the mean
age for the control group was 43.69. The four studies included data from three countries.
Two occurred in Israel, one in Turkey, and one in Spain. Table 2shows a detailed list of
study hallmarks. Figure 1demonstrates the flowchart of the screening process.
Clin. Pract. 2023,13 588
Table 2. Detailed information and characteristics of included studies.
Studies Country Mean Age (Y) Female/
Male
Sample Size
(n) Duration (Y) Intervention
Outcomes Follow-
Up
HBOT con HBOT con HBOT con HBOT con HBOT con
Efrati 2015
[19]Israel
50.4
±
10.9 48.1
±
11.1
NA NA 24 26 6.75 ±5.9 6.2 ±5.1
hyperbaric oxygen
therapy at 2.0 ATA.
40 daily sessions,
5 days/week,
90 min each.
no treatment
TPC (of
18),Pain
threshold,
FIQ, SF-36
2M
Hadanny
2018 [24]Israel
48.3
±
10.6 43.1
±
10.6
30 0 15 15 NA NA
hyperbaric oxygen
therapy at 2.0 ATA and
psychological therapy.
60 daily sessions, 5 days a
week. 90 min each.
psychological
therapy
WPI, TPC
(of 18),
FIQ, SF-36
3M
Yildiz 2004
[12]Turkey 40.46 ±
4.79
39.88 ±
4.71 35 15 26 24 4 ±1.1
hyperbaric oxygen
therapy at 2.4 ATA.
15 sessions, one session
per day for 5 days of the
week, 90 min each.
breathed air at
1 ATA for
90 min
TPC,
6MWT,
VAS,
Pressure
pain
threshold
3W
Izquierdo-
Alventosa
2020 [25]
Spain NA NA 33 0 17 16 NA NA
hyperbaric oxygen
therapy at 1.45 ATA.
40 sessions, five sessions
per week, 90 min each.
usual
medication
VAS,
pressure
pain
threshold
10W
HBOT = Hyperbaric Oxygen Therapy, con = control, NA = not available, Y = years, M = months, W = weeks, ATA = atmosphere absolute, WPI = Widespread pain index,
FIQ = Fibromyalgia functional impairment, 6MWT = Fatigue following the completion of the 6-min walking test, VAS = visual analog scale.
Clin. Pract. 2023,13 589
Clin. Pract. 2023, 13, FOR PEER REVIEW 8
Figure 1. Flowchart of the literature screening process.
3.3. ROBs of Included Studies (Figure 2)
None of the four studies had low ROBs. There are two studies at high risk of bias, as
they had at least one high judgment in the key domains [19,24]. The remaining two
studies were designated at some concerns (unclear intended interventions and random-
ization process) [12,25].
Figure 1. Flowchart of the literature screening process.
3.3. ROBs of Included Studies (Figure 2)
None of the four studies had low ROBs. There are two studies at high risk of bias, as
they had at least one high judgment in the key domains [
19
,
24
]. The remaining two studies
were designated at some concerns (unclear intended interventions and randomization
process) [12,25].
Clin. Pract. 2023,13 590
Figure 2.
ROBs (2.0) within the included studies. Green circle and ‘+’, low risk; red circle and
’,
high risk; yellow circle and ‘?’, unclear risk [12,19,24,25].
3.4. Effects of HBOT Interventions
So far, there has been no consensus regarding therapy sessions of HBOT. Amongst
four included studies, two intervention sessions were 40 daily sessions, one was 60 daily
sessions, and one was 15 sessions; all interventions were 5 days/week and 90 min each. A
detailed list of HBOT (including pressure, therapy time, and therapy session) is shown in
Table 2.
3.5. Primary Outcome Measures
3.5.1. Pain
Two studies used VAS (Visual Analogue Scale) scores to assess pain and showed the
difference between HBOT and control groups at two weeks at the end of HBOT sessions
(Figure 3). VAS had no statistical difference effect (SMD =
1.68, 95% CI,
4.47 to 1.11,
p= 0.24). Considerable heterogeneity among these studies (I
2
= 96%) was revealed by test
statistics and adopted the random-effects model.
Figure 3.
Forest plot for the comparison of pain at the end of treatment, showing the effect not
favoring hyperbaric oxygen therapy [12,25].
Clin. Pract. 2023,13 591
3.5.2. Fibromyalgia Impact Questionnaire (FIQ)
Functional capacity in daily-living activities was evaluated by the FIQ [
26
]. Two
studies of the 4 RCTs used the FIQ as outcome measures at the end of HBOT sessions
(Figure 4). And patients were randomly assigned to treat and crossover groups in two
studies. HBOT improved FIQ by
157% when compared with controls (SMD =
1.57, 95%
CI
2.34 to
0.80, p< 0.0001). Considerable heterogeneity was identified among these
studies (I2= 77%), and a random-effects model was adopted.
Figure 4.
Forest plot for the comparison of FIQ at the end of treatment, showing the effect favoring
hyperbaric oxygen therapy [19,24].
3.5.3. Tender Points Count (TPC)
TPC was measured by two studies as the outcome at the end of HBOT sessions
(Figure 5). And two studies were assigned to treated and crossover groups. Compared with
the control group, HBOT improved the clinical efficacy of TPC by
250%
(SMD = 2.50
,
95% CI
3.96 to
1.05, p= 0.0007). There was considerable heterogeneity between these
studies (I2= 93%), and a random-effects model was used.
Figure 5.
Forest plot for the comparison of TPC at the end of treatment, showing the effect favoring
hyperbaric oxygen therapy [12,19,24].
3.5.4. Side Effects
Two studies described side effects at the end of HBOT sessions (Figure 6). The most
side effects were middle ear barotrauma. HBOT significantly increased the incidence of
side effects (RR = 24.97, 95% CI 3.75 to 166.47, P= 0.0009) with no heterogeneity (P= 0.59,
I2= 0%). A fixed-effects model was adopted.
Figure 6.
Forest plot for the side effects, showing the effect favoring hyperbaric oxygen therapy [
19
,
24
].
Clin. Pract. 2023,13 592
4. Discussion
Despite widespread application, there are very few RCTs assessing HBOT benefits
for patients with FMS. This is the first systematic review and meta-analysis of RCTs on
HBOT for FMS. This meta-analysis presents a novel line of evidence that HBOT can benefit
FMS with FIQ and TPC at the end of treatment. However, the findings of the current
meta-analysis indicate that HBOT therapy did not improve the pain scores. The use of
HBOT, compared to placebo, was associated with a significant increase in side effects.
Nevertheless, patients with mild barotraumas as side effects resolved spontaneously and
completed the treatment protocol.
There are a number of studies supporting the use of HBOT to decrease inflammation
and pain in rat models [
27
32
]. However, level 1 evidence for HBOT favors pain relief and
inflammation decreases is lacking. RCTs with large sample sizes have not been conducted.
In 2004, Yildiz et al. [
12
] conducted a randomized controlled study with 50 patients to
evaluate the effect of HBOT on fibromyalgia, and the results demonstrated a decrease in
pain scores. In addition, 49 women with FMS took part in Izquierdo-Alventosa’s [
25
] ran-
domized controlled trial; the result showed that the perceived pain significantly improved
only in the HBOT group as opposed to the physical exercise group and control group.
However, there are no similar results from the meta-analysis after combining the data. The
reason may be related to the use of different VAS scoring standards in the two included
studies. Furthermore, as a result of the subjects’ inadequate physical exercise routines,
they were unable to adjust to the pace of the recommended physical activity. This lack of
adaptation could potentially result in excessive exertion and subsequently cause persistent
sensations of discomfort and pain.
Repeated treatment with HBOT produced a two-stage antinociceptive response in
rat models [
33
]. After the last HBOT treatment, mice treated with HBOT for 60 min at
3.5 ATA four times a day had a robust antinociceptive response (suppression of abdominal
constrictions) for up to 6 h. When the rats underwent abdominal contraction testing after
additional time intervals, the antinociceptive effect of HBOT was not obvious for 12 h, and
it began to re-emerge 24 h later after the last treatment of HBOT and lasted for up to 14 days
post-treatment. This may also be the reason for the inconsistencies in pain relief among the
RCTs included in different sessions.
Three studies [
12
,
19
,
24
] described changes in tenderness thresholds, all showing sig-
nificant increases in pain thresholds after HBOT treatment. However, the tenderness
thresholds of the three studies were obtained from different parts of the body, so we did
not perform a pooled analysis. The two studies [
19
,
24
] that utilized the FIQ (Fibromyal-
gia Impact Questionnaire) included patient assessments for various symptoms, such as
difficulty with work, pain, fatigue, morning fatigue, stiffness, anxiety, and depression. At
the conclusion of treatment, all patients experienced a significant improvement in their
physical function. This seems to be another confirmation that HBOT can relieve pain in
patients with FMS.
The etiology of FMS is still unknown, with several hypotheses proposed. It has been
hypothesized that local hypoxia may lead to degenerative muscle changes that lead to
chronic pain [
34
], which in turn leads to decreased ATP and elevated lactate concentrations.
HBOT improves muscle oxygenation in fibromyalgia patients by improving the body’s
oxygen tension, thus restoring aerobic metabolism and correcting local tissue hypoxia and
acidosis [
12
]. Furthermore, HBOT causes hyperoxia, amplifying the diffusion gradient of
oxygen between tissue and cells, thus raising plasma dissolved oxygen to levels beyond the
physiological requirements of many tissues at rest [
35
]. A recent study examined 185 FMS
patients with sicca and/or xerostomia symptoms and found a link between auto-antibodies
and FMS, with one-third of them positive for a biomarker of Sjögren’s syndrome, and most
of them were also positive for one or more tissue-specific auto-antibodies [
36
]. Guggino
et al. [
37
] confirmed the involvement of the immune system in the pathogenesis of FM and
highlighted the impact of HBOT treatment, especially the changes in pro-inflammatory
cytokines produced by the CD4 T cell subpopulation. These may also be the reasons why
Clin. Pract. 2023,13 593
HBOT can improve symptoms in patients with FMS. Furthermore, according to the study
by Efrati et al. [
19
], HBOT can correct abnormal brain activity associated with pain. This
involves reducing activity in overactive areas, primarily located in the back of the brain,
and increasing activity in inactive areas, mainly located in the frontal lobe. These findings
align with current understanding of how the brain responds to pain.
High heterogeneity (0% to 96%) was noted between included studies due to several
factors. Firstly, the sustained effectiveness of HBOT is closely related to the time and session
of treatment. Notably, exposure times and press for HBOT varied. Secondly, the definition
of “quality of life” was not consistent due to different economic levels and regional cultures.
Thirdly, due to the special hallmarks of the intervention, almost all included randomized
controlled studies were not perfect in terms of blind methodology. Finally, the proportion
of females in all the studies was higher. Men and women may have different levels of pain
threshold. These factors may be contributive to the inter-group differences, affecting the
entire heterogeneity of included studies.
The limitations of this systematic review are mainly ascribed to the quantity and
quality of included studies. This meta-analysis, including four RCTs, could not identify
the underlying factors leading to heterogeneity. Therefore, it is necessary to conduct
large-sample RCTs and additional studies for subgroup analyses in the future.
5. Conclusions
The systematic review and meta-analysis support the effectiveness of HBOT in TPC
and the improvement of functions in FMS with emerging evidence from 163 participants.
Although HBOT has some side effects, it does not cause serious adverse consequences.
Prolonged treatment sessions may help with pain relief. However, significant differences
in the quality and heterogeneity of currently available evidence should be noted. Larger
sample RCTs with unified regimens and longer follow-up times are needed.
Author Contributions:
H.W. conceived the study. C.C., Q.L. and X.Z. investigated and retrieved the
published papers. C.C., Q.L. and X.Z. analyzed data. C.C. and Q.L. wrote the original draft. G.V. and
H.W. reviewed and edited the manuscript. All authors have read and agreed to the published version
of the manuscript.
Funding:
This study was supported by the National Natural Science Foundation of China (Grant
number 81572182 to H.W.) and Yongchuan Natural Science Foundation of Chongqing, China (2021yc-
jckx20027 to Q.L.).
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement:
The datasets supporting this systematic review and meta-analysis are
from previously reported studies and datasets which have been cited. The processed data are shown
in Table 2and Figure 3to Figure 6.
Acknowledgments: We thank all the researchers and participants involved in the included studies.
Conflicts of Interest: The authors declare no conflict of interest.
References
1.
Spaeth, M. Epidemiology, costs, and the economic burden of fibromyalgia. Arthritis Res. Ther.
2009
,11, 117. [CrossRef] [PubMed]
2.
De Oliveira Paes Leme, M.; Yuan, S.L.K.; Oliveira Magalhaes, M.; Ferreira de Meneses, S.R.; Marques, A.P. Pain and quality of life
in knee osteoarthritis, chronic low back pain and fibromyalgia: A comparative cross-sectional study. Reumatismo
2019
,71, 68–74.
[CrossRef]
3.
Wolfe, F.; Brahler, E.; Hinz, A.; Hauser, W. Fibromyalgia prevalence, somatic symptom reporting, and the dimensionality of
polysymptomatic distress: Results from a survey of the general population. Arthritis Care Res.
2013
,65, 777–785. [CrossRef]
[PubMed]
4.
Mease, P. Fibromyalgia syndrome: Review of clinical presentation, pathogenesis, outcome measures, and treatment. J. Rheumatol.
Suppl. 2005,75, 6–21. [PubMed]
Clin. Pract. 2023,13 594
5.
Marques, A.P.; Santo, A.; Berssaneti, A.A.; Matsutani, L.A.; Yuan, S.L.K. Prevalence of fibromyalgia: Literature review update.
Rev. Bras. Reumatol. Engl. Ed. 2017,57, 356–363. [CrossRef] [PubMed]
6. Queiroz, L.P. Worldwide epidemiology of fibromyalgia. Curr. Pain. Headache Rep. 2013,17, 356. [CrossRef] [PubMed]
7.
Macfarlane, G.J.; Kronisch, C.; Dean, L.E.; Atzeni, F.; Hauser, W.; Fluss, E.; Choy, E.; Kosek, E.; Amris, K.; Branco, J.; et al. EULAR
revised recommendations for the management of fibromyalgia. Ann. Rheum. Dis. 2017,76, 318–328. [CrossRef] [PubMed]
8.
Vincent, A.; Whipple, M.O.; McAllister, S.J.; Aleman, K.M.; St Sauver, J.L. A cross-sectional assessment of the prevalence of
multiple chronic conditions and medication use in a sample of community-dwelling adults with fibromyalgia in Olmsted County,
Minnesota. BMJ Open 2015,5, e006681. [CrossRef]
9.
Gouvinhas, C.; Veiga, D.; Mendonca, L.; Sampaio, R.; Azevedo, L.F.; Castro-Lopes, J.M. Interventional Pain Management in
Multidisciplinary Chronic Pain Clinics: A Prospective Multicenter Cohort Study with One-Year Follow-Up. Pain. Res. Treat.
2017
,
2017, 8402413. [CrossRef]
10.
Qaseem, A.; Wilt, T.J.; McLean, R.M.; Forciea, M.A.; Clinical Guidelines Committee of the American College of Physicians.
Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American
College of Physicians. Ann. Intern. Med. 2017,166, 514–530. [CrossRef]
11.
Edwards, M.L. Hyperbaric oxygen therapy. Part 2: Application in disease. J. Vet. Emerg. Crit. Care
2010
,20, 289–297. [CrossRef]
[PubMed]
12.
Yildiz, S.; Kiralp, M.Z.; Akin, A.; Keskin, I.; Ay, H.; Dursun, H.; Cimsit, M. A new treatment modality for fibromyalgia syndrome:
Hyperbaric oxygen therapy. J. Int. Med. Res. 2004,32, 263–267. [CrossRef]
13.
Kiralp, M.Z.; Yildiz, S.; Vural, D.; Keskin, I.; Ay, H.; Dursun, H. Effectiveness of hyperbaric oxygen therapy in the treatment of
complex regional pain syndrome. J. Int. Med. Res. 2004,32, 258–262. [CrossRef] [PubMed]
14.
Gu, N.; Niu, J.Y.; Liu, W.T.; Sun, Y.Y.; Liu, S.; Lv, Y.; Dong, H.L.; Song, X.J.; Xiong, L.Z. Hyperbaric oxygen therapy attenuates
neuropathic hyperalgesia in rats and idiopathic trigeminal neuralgia in patients. Eur. J. Pain
2012
,16, 1094–1105. [CrossRef]
[PubMed]
15.
Yildiz, S.; Uzun, G.; Kiralp, M.Z. Hyperbaric oxygen therapy in chronic pain management. Curr. Pain Headache Rep.
2006
,10,
95–100. [CrossRef] [PubMed]
16.
Bennett, M.H.; French, C.; Schnabel, A.; Wasiak, J.; Kranke, P. Normobaric and hyperbaric oxygen therapy for migraine and
cluster headache. Cochrane Database Syst. Rev. 2008,16, 1–33. [CrossRef]
17.
Hui, J.; Zhang, Z.J.; Zhang, X.; Shen, Y.; Gao, Y.J. Repetitive hyperbaric oxygen treatment attenuates complete Freund’s adjuvant-
induced pain and reduces glia-mediated neuroinflammation in the spinal cord. J. Pain 2013,14, 747–758. [CrossRef]
18.
Efrati, S.; Fishlev, G.; Bechor, Y.; Volkov, O.; Bergan, J.; Kliakhandler, K.; Kamiager, I.; Gal, N.; Friedman, M.; Ben-Jacob, E.; et al.
Hyperbaric oxygen induces late neuroplasticity in post stroke patients–randomized, prospective trial. PLoS ONE
2013
,8, e53716.
[CrossRef]
19.
Efrati, S.; Golan, H.; Bechor, Y.; Faran, Y.; Daphna-Tekoah, S.; Sekler, G.; Fishlev, G.; Ablin, J.N.; Bergan, J.; Volkov, O.; et al.
Hyperbaric oxygen therapy can diminish fibromyalgia syndrome–prospective clinical trial. PLoS ONE
2015
,10, e0127012.
[CrossRef]
20.
Wolfe, F.; Clauw, D.J.; Fitzcharles, M.A.; Goldenberg, D.L.; Katz, R.S.; Mease, P.; Russell, A.S.; Russell, I.J.; Winfield, J.B.; Yunus,
M.B. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom
severity. Arthritis Care Res. 2010,62, 600–610. [CrossRef]
21.
Sterne, J.A.C.; Savovic, J.; Page, M.J.; Elbers, R.G.; Blencowe, N.S.; Boutron, I.; Cates, C.J.; Cheng, H.Y.; Corbett, M.S.; Eldridge,
S.M.; et al. RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ 2019,366, l4898. [CrossRef] [PubMed]
22.
Deeks, J.J.; Altman, D.G. Chapter 9. Analysing Data and Undertaking Meta-Analyses. In Cochrane Handbook for Systematic Reviews
of Interventions; Wiley: Hoboken, NJ, USA, 2011.
23.
Atzeni, F.; Casale, R.; Alciati, A.; Masala, I.F.; Batticciotto, A.; Talotta, R.; Gerardi, M.C.; Salaffi, F.; Sarzi-Puttini, P. Hyperbaric
oxygen treatment of fibromyalgia: A prospective observational clinical study. Clin. Exp. Rheumatol.
2019
,37 (Suppl. S116), 63–69.
24.
Hadanny, A.; Bechor, Y.; Catalogna, M.; Daphna-Tekoah, S.; Sigal, T.; Cohenpour, M.; Lev-Wiesel, R.; Efrati, S. Hyperbaric Oxygen
Therapy Can Induce Neuroplasticity and Significant Clinical Improvement in Patients Suffering From Fibromyalgia with a
History of Childhood Sexual Abuse-Randomized Controlled Trial. Front. Psychol. 2018,9, 2495. [CrossRef] [PubMed]
25.
Izquierdo-Alventosa, R.; Ingles, M.; Cortes-Amador, S.; Gimeno-Mallench, L.; Sempere-Rubio, N.; Chirivella, J.; Serra-Ano, P.
Comparative study of the effectiveness of a low-pressure hyperbaric oxygen treatment and physical exercise in women with
fibromyalgia: Randomized clinical trial. Ther. Adv. Musculoskelet. Dis. 2020,12, 1–14. [CrossRef] [PubMed]
26.
Burckhardt, C.S.; Clark, S.R.; Bennett, R.M. The fibromyalgia impact questionnaire: Development and validation. J. Rheumatol.
1991,18, 728–733. [PubMed]
27.
Warren, J.; Sacksteder, M.R.; Thuning, C.A. Therapeutic effect of prolonged hyperbaric oxygen in adjuvant arthritis of the rat.
Arthritis Rheum. 1979,22, 334–339. [CrossRef]
28. Davis, T.R.; Griffiths, I.D.; Stevens, J. Hyperbaric oxygen treatment for rheumatoid arthritis; failure to show worthwhile benefit.
Br. J. Rheumatol. 1988,27, 72. [CrossRef]
29.
Koo, S.T.; Lee, C.H.; Choi, H.; Shin, Y.I.; Ha, K.T.; Ye, H.; Shim, H.B. The effects of pressure on arthritic knees in a rat model of
CFA-induced arthritis. Pain Physician 2013,16, E95–E102.
Clin. Pract. 2023,13 595
30.
Zelinski, L.M.; Ohgami, Y.; Chung, E.; Shirachi, D.Y.; Quock, R.M. A prolonged nitric oxide-dependent, opioid-mediated
antinociceptive effect of hyperbaric oxygen in mice. J. Pain 2009,10, 167–172. [CrossRef]
31.
Ohgami, Y.; Zylstra, C.C.; Quock, L.P.; Chung, E.; Shirachi, D.Y.; Quock, R.M. Nitric oxide in hyperbaric oxygen-induced acute
antinociception in mice. Neuroreport 2009,20, 1325–1329. [CrossRef]
32.
Sumen, G.; Cimsit, M.; Eroglu, L. Hyperbaric oxygen treatment reduces carrageenan-induced acute inflammation in rats. Eur. J.
Pharmacol. 2001,431, 265–268. [CrossRef] [PubMed]
33.
Chung, E.; Zelinski, L.M.; Ohgami, Y.; Shirachi, D.Y.; Quock, R.M. Hyperbaric oxygen treatment induces a 2-phase antinociceptive
response of unusually long duration in mice. J. Pain 2010,11, 847–853. [CrossRef] [PubMed]
34.
Lund, N.; Bengtsson, A.; Thorborg, P. Muscle tissue oxygen pressure in primary fibromyalgia. Scand. J. Rheumatol.
1986
,15,
165–173. [CrossRef] [PubMed]
35. Leach, R.M.; Rees, P.J.; Wilmshurst, P. Hyperbaric oxygen therapy. BMJ 1998,317, 1140–1143. [CrossRef] [PubMed]
36.
Applbaum, E.; Lichtbroun, A. Novel Sjogren’s autoantibodies found in fibromyalgia patients with sicca and/or xerostomia.
Autoimmun. Rev. 2019,18, 199–202. [CrossRef]
37.
Guggino, G.; Schinocca, C.; Lo Pizzo, M.; Di Liberto, D.; Garbo, D.; Raimondo, S.; Alessandro, R.; Brighina, F.; Ruscitti, P.;
Giacomelli, R.; et al. T helper 1 response is correlated with widespread pain, fatigue, sleeping disorders and the quality of life in
patients with fibromyalgia and is modulated by hyperbaric oxygen therapy. Clin. Exp. Rheumatol. 2019,37 (Suppl. S116), 81–89.
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... The best results are achieved with a multidisciplinary approach, considering the complex and multifaceted nature of FMS. Various non-pharmacological therapies have been researched and tested, including balneotherapy [107], hyperbaric oxygen [107], and acupuncture [108] among others. However, while these treatments can be beneficial, pharmacological therapy remains a crucial component in managing fibromyalgia and achieving satisfactory outcomes. ...
... The best results are achieved with a multidisciplinary approach, considering the complex and multifaceted nature of FMS. Various non-pharmacological therapies have been researched and tested, including balneotherapy [107], hyperbaric oxygen [107], and acupuncture [108] among others. However, while these treatments can be beneficial, pharmacological therapy remains a crucial component in managing fibromyalgia and achieving satisfactory outcomes. ...
Article
Full-text available
Purpose of Review Fibromyalgia Syndrome (FMS) is a complex chronic pain condition characterized by widespread musculoskeletal pain and numerous other debilitating symptoms. The purpose of this review is to provide a comprehensive overview, based on everyday clinical practice, of the drugs presently employed in the treatment of FMS. Recent Findings The treatment of FMS is based on a multimodal approach, with pharmacologic treatment being an essential pillar. The drugs used include tricyclic antidepressants, serotonin and noradrenaline reuptake inhibitors, other antidepressants, anticonvulsants, myorelaxants, and analgesics. The effectiveness of these medications varies, and the choice of drug often depends on the specific symptoms presented by the patient. Many drugs tend to either address only some domains of the complex FMS symptomatology or have a limited effect on pain. Summary Each treatment option comes with potential side effects and risks that necessitate careful consideration. It may be beneficial to divide patients into clinical subpopulations, such as FMS with comorbid depression, for more effective treatment. Despite the complexities and challenges, the pharmacological treatment remains a crucial part for the management of FMS. This review aims to guide clinicians in prescribing pharmacological treatment to individuals with FMS.
... Also, occupational therapists can assist in finding adaptive strategies to manage daily tasks and reduce the impact of fibromyalgia on daily life [87]. Moreover, some studies support the efficacy of Hyperbaric Oxygen Therapy (HBOT) in Tender Points Count (TPC) and the enhancement of functions in fibromyalgia [88]. ...
Article
Full-text available
Fibromyalgia is a complex and often misunderstood chronic pain disorder. It is characterized by widespread musculoskeletal pain, fatigue, and heightened sensitivity, and has evolved in diagnostic criteria and understanding over the years. Initially met with skepticism, fibromyalgia is now recognized as a global health concern affecting millions of people, with a prevalence transcending demographic boundaries. The clinical features and diagnosis of fibromyalgia encompass a range of symptoms beyond pain, including sleep disturbances and cognitive difficulties. This study emphasizes the importance of a comprehensive evaluation for accurate diagnosis, considering the shift from tender point reliance to a more holistic approach. Etiology and pathophysiology involve genetic predisposition, neurotransmitter dysregulation, central sensitization, and immune system involvement. Risk factors such as gender, age, family history, and comorbid conditions contribute to susceptibility. The impact on quality of life is profound, affecting physical and social aspects, often accompanied by mood disorders. Management approaches include pharmacological interventions, non-pharmacological therapies, lifestyle modifications, and alternative treatments. This study also delves into emerging research, exploring advances in neurobiological understanding, brain imaging, genetic markers, glutamate modulation, cannabinoids, gut microbiome, and digital health tools for fibromyalgia management. Overall, this study provides a nuanced and up-to-date overview of the complexities surrounding fibromyalgia, aiming to enhance understanding and support for individuals grappling with this challenging condition.
... Also, occupational therapists can assist in finding adaptive strategies to manage daily tasks and reduce the impact of fibromyalgia on daily life (83). Moreover, some studies support the efficacy of Hyperbaric Oxygen Therapy (HBOT) in Tender Points Count (TPC) and the enhancement of functions in fibromyalgia (84). ...
Preprint
Full-text available
Fibromyalgia is a complex and often misunderstood chronic pain disorder. It is characterized by widespread musculoskeletal pain, fatigue, and heightened sensitivity, and has evolved in diag-nostic criteria and understanding over the years. Initially met with skepticism, fibromyalgia is now recognized as a global health concern affecting millions of people, with a prevalence trans-cending demographic boundaries. The clinical features and diagnosis of fibromyalgia encompass a range of symptoms beyond pain, including sleep disturbances and cognitive difficulties. The study emphasizes the importance of a comprehensive evaluation for accurate diagnosis, considering the shift from tender point reliance to a more holistic approach. Etiology and pathophysiology involve genetic predisposition, neurotransmitter dysregulation, central sensitization, and immune system involvement. Risk factors such as gender, age, family history, and comorbid conditions contribute to susceptibility. The impact on quality of life is profound, affecting physical and social aspects, often accompanied by mood disorders. Management approaches include pharmacological interventions, non-pharmacological therapies, lifestyle modifications, and alternative treatments. The study also delves into emerging research, exploring advances in neurobiological understanding, brain imaging, genetic markers, glutamate modulation, cannabinoids, gut microbiome, and digital health tools for fibromyalgia manage-ment. Overall, this study provides a nuanced and up-to-date overview of the complexities sur-rounding fibromyalgia, aiming to enhance understanding and support for individuals grappling with this challenging condition.
Article
Full-text available
Background Fibromyalgia (FM) is characterized by chronic pain and fatigue, among other manifestations, thus advising interventions that do not aggravate these symptoms. The main purpose of this study is to analyse the effect of low-pressure hyperbaric oxygen therapy (HBOT) on induced fatigue, pain, endurance and functional capacity, physical performance and cortical excitability when compared with a physical exercise program in women with FM. Methods A total of 49 women with FM took part in this randomized controlled trial. They were randomly allocated to three groups: physical exercise group (PEG, n = 16), low-pressure hyperbaric oxygen therapy group (HBG, n = 17) and control group (CG, n = 16). Induced fatigue, perceived pain, pressure pain threshold, endurance and functional capacity, physical performance and cortical excitability were assessed. To analyse the effect of the interventions, two assessments, that is, pre and post intervention, were carried out. Analyses of the data were performed using two-way mixed multivariate analysis of variance. Results The perceived pain and induced fatigue significantly improved only in the HBG ( p < 0.05) as opposed to PEG and CG. Pressure pain threshold, endurance and functional capacity, and physical performance significantly improved for both interventions ( p < 0.05). The cortical excitability (measured with the resting motor threshold) did not improve in any of the treatments ( p > 0.05). Conclusions Low-pressure HBOT and physical exercise improve pressure pain threshold, endurance and functional capacity, as well as physical performance. Induced fatigue and perceived pain at rest significantly improved only with low-pressure HBOT. Trial registration ClinicalTrials.gov identifier NCT03801109.
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The revised edition of the Handbook offers the only guide on how to conduct, report and maintain a Cochrane Review. The second edition of The Cochrane Handbook for Systematic Reviews of Interventions contains essential guidance for preparing and maintaining Cochrane Reviews of the effects of health interventions. Designed to be an accessible resource, the Handbook will also be of interest to anyone undertaking systematic reviews of interventions outside Cochrane, and many of the principles and methods presented are appropriate for systematic reviews addressing research questions other than effects of interventions. This fully updated edition contains extensive new material on systematic review methods addressing a wide-range of topics including network meta-analysis, equity, complex interventions, narrative synthesis, and automation. Also new to this edition, integrated throughout the Handbook, is the set of standards Cochrane expects its reviews to meet. Written for review authors, editors, trainers and others with an interest in Cochrane Reviews, the second edition of The Cochrane Handbook for Systematic Reviews of Interventions continues to offer an invaluable resource for understanding the role of systematic reviews, critically appraising health research studies and conducting reviews.
Article
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The objective of our study was to compare pain and health-related quality of life among patients with knee osteoarthritis (OA), chronic nonspecific low back pain (CNLBP) and fibromyalgia (FM). This cross-sectional study included 87 subjects, who were divided into three groups according to their diagnosis: knee OA (n=29), CNLBP (n=29) and FM (n=29), between March 2013 and March 2014. Pain intensity was measured using the Numeric Pain Rating Scale (NPRS), quality of pain using the McGill Pain Questionnaire (MPQ) and health-related quality of life using the 36-item Short-Form Health Survey (SF-36). Painful body areas were marked on a pain map. No statistically significant differences between groups were found for NPRS. Regarding MPQ, the knee OA group presented a lower pain-rating index in contrast to the CNLBP and FM groups, and no significant differences were found between the CNLBP and FM groups. A greater number of characteristic pain descriptors and painful locations were found in the FM group than in the CNLBP or knee OA groups. Regarding SF-36, the FM group presented statistically significant lower values for bodily pain in contrast to the knee OA group. Even though the global pain intensity was similar between groups, the findings suggest that the FM group presented the worst pain experience and a lower health-related quality of life than the knee OA group in terms of bodily pain. They also suggest that the pain experience was worse for the CNLBP group than for the knee OA group but health-related quality of life was similar.
Article
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Background: Fibromyalgia syndrome (FMS), a condition considered to represent a prototype of central sensitization syndrome, can be induced by different triggers including childhood sexual abuse (CSA). Recent studies have demonstrated hyperbaric oxygen therapy (HBOT) can induce neuroplasticity and improve clinical outcome of FMS. The aim of the current study was to evaluate the effect of HBOT on patients suffering from FMS with a history of CSA. Materials and methods: A prospective randomized clinical trial conducted between July 2015 and November 2017 included women with a history of CSA who fulfilled fibromyalgia diagnosis criteria for at least 5 years prior to inclusion. Included participants (N = 30) were randomly assigned to treatment group, treated with 60 HBOT sessions and a control/crossover group received psychotherapy. After the control period, the control/crossover group was crossed to HBOT. Clinical outcomes were assessed using FMS questioners, post-traumatic stress disorder (PTSD) questioners and quality of life questioners. Objective outcome were assessed using brain function and structure imaging. Findings: Following HBOT, there was a significant improvement in all FMS questionnaires (widespread pain index, Fibromyalgia symptoms severity scale, Fibromyalgia functional impairment), most domains of quality of life, PTSD symptoms and psychological distress. The same significant improvements were demonstrated in the control following crossover to HBOT. Following HBOT, brain SPECT imaging demonstrated significant increase in brain activity in the prefrontal cortex, orbital frontal cortex, and subgenual area (p < 0.05). Brain microstructure improvement was seen by MRI-DTI in the anterior thalamic radiation (p = 0.0001), left Insula (p = 0.001), and the right Thalamus (p = 0.001). Conclusion: HBOT induced significant clinical improvement that correlates with improved brain functionality and brain microstructure in CSA related FMS patients. Trial Registration: www.Clinicaltrials.gov, identifier: NCT03376269. url: https://clinicaltrials.gov/show/NCT03376269
Chapter
This chapter describes the principles and methods used to carry out a meta-analysis for a comparison of two interventions for the main types of data encountered. A very common and simple version of the meta-analysis procedure is commonly referred to as the inverse-variance method. This approach is implemented in its most basic form in RevMan, and is used behind the scenes in many meta-analyses of both dichotomous and continuous data. Results may be expressed as count data when each participant may experience an event, and may experience it more than once. Count data may be analysed using methods for dichotomous data if the counts are dichotomized for each individual, continuous data and time-to-event data, as well as being analysed as rate data. Prediction intervals from random-effects meta-analyses are a useful device for presenting the extent of between-study variation. Sensitivity analyses should be used to examine whether overall findings are robust to potentially influential decisions.
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Assessment of risk of bias is regarded as an essential component of a systematic review on the effects of an intervention. The most commonly used tool for randomised trials is the Cochrane risk-of-bias tool. We updated the tool to respond to developments in understanding how bias arises in randomised trials, and to address user feedback on and limitations of the original tool.
Article
Objectives: Hyperbaric oxygen therapy (HBOT) has been used as treatment for different clinical conditions, including fibromyalgia (FM). HBOT modulates brain activity, ameliorates chronic pain and modifies the ratio of immune cells. Clinical studies have provided evidence that FM is associated with immune system dysregulation. In the present study we aimed to evaluate the effect of HBOT on immune system and on the quality of life-style of FM patients. Methods: Patients with primary FM and controls were treated with HBOT. Physical, emotional and social assessment, quality of sleep, tender points, intensity score, WPI and symptom severity were evaluated before and after HBOT. Furthermore, a characterisation of CD4 T lymphocytes and their cytokine production was performed by flow cytometry. The expression of TNF-α, IFN-γ, IL-17, IL-9 and IL-22 was also assessed by RT-PCR. Finally, the serum levels of serotonin were evaluated by ELISA. Results: Our results confirm the participation of immune system in the pathogenesis of FM and highlight the impact of HBOT treatment, with particular regard to the changes on proinflammatory cytokines production by CD4 T cells subsets. Conclusions: FM patients show a Th1 signature and the activation of this subset is modulated by HBOT.
Article
OBJECTIVES: Fibromyalgia (FM) is a syndrome of unknown aetiology that is characterised by widespread musculoskeletal pain, fatigue and disordered sleep, and often associated with neuropsychiatric and cognitive symptoms. Current treatment options are only partially effective, but hyperbaric oxygen therapy (HBOT) seems to be capable of relieving some of the symptoms. The aim of this study was to evaluate the efficacy and safety of HBOT after fewer sessions than generally used, chosen on the basis of pre-clinical and clinical data showing its rapid and sustained antinociceptive effect. METHODS: Patients with FM underwent HBOT (100% oxygen at 2.5 ata with air breaks) administered on three days per week for a total of twenty 90-minute sessions. Pain, fatigue, the quality of sleep, symptoms of anxiety and depression, and the patients' health-related quality of life were prospectively assessed before and after ten and twenty sessions. RESULTS: Twenty-eight of the 32 study patients completed the 20 HBOT sessions. Pain scores and the symptoms of anxiety (but not those of depression) significantly improved after both 10 and 20 sessions, whereas fatigue and FM symptom severity scores significantly improved only after 20 sessions. There was no significant change in the quality of sleep. The adverse effects were limited. CONCLUSIONS: These findings support the view that HBOT is an effective, rapid and safe means of treating various symptoms of FM.
Article
Introduction A significant proportion of patients with fibromyalgia (FM) complain of dry eyes and mouth. Many Sjögren's syndrome (SS) patients also complain of FM symptoms, and there is literature that suggests that there is interplay between these two disorders. Recently, the presence of novel tissue specific autoantibodies (TSAs), SP-1, CA6, and PSP, has been observed in the early stages of SS. These early markers present themselves before the classic autoantibodies, such as SS-A/Ro, SS-B/La, ANA, and RF. Objective This study aims to examine the relationship between SS and FM by testing patients with FM who also complain of xerostomia and sicca symptoms, for SS- related biomarkers. Methods A cohort of 185 patients who met both the 1990 and 2010 preliminary diagnostic criteria for FM and who admitted to symptoms of sicca and/or xerostomia were selected for this study. Serum from 151 study patients was sent to a tertiary lab, Immco Diagnostics, for testing of the classic autoantibodies (SS-A/Ro, SS-B/La, ANA and RF) and TSAs (SP-1, CA6, PSP), while the rest (34 patients) were tested for TSAs only. Results Of the 151 patients who were evaluated for both the early and classic SS markers, 49 (32%) tested positive for SS autoantibodies. Of those, 4 (3%) tested positive for the classic SS markers only, 40 (26%) of the patients tested positive for the early SS markers only, and 5 (3%) tested positive for both the early and classic SS markers. Of the 34 patients who were tested for early SS markers only, 10 (29%) tested positive and 24 (71%) tested negative. Further analysis of all the patients that tested positive for the TSAs (n = 55), found 83.6% (46) were positive for SP-1, 12.7% (7) were positive for CA6 and 20.0% (11) were positive for PSP. 85.5% (47) of these patients were positive for only one of the TSAs and 14.5% (8) were positive for more than one TSA. Conclusion Approximately 1/3 of FM patients that were tested for both the TSAs and classic Sjögren's markers tested positive for a SS biomarker, and the majority of those patients tested positive for one or more of the TSAs. This suggests that autoimmunity, specifically early- stage Sjögren's syndrome, may be involved in the pathophysiology of fibromyalgia.