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Effectiveness of high-intensity interval training versus moderate-intensity continuous training in patients with fibromyalgia: A pilot randomized controlled trial

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Objective To compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) combined with strengthening and stretching exercises in patients with fibromyalgia. Design Interventional, single-blinded, randomized-controlled trial. Setting Outpatient rehabilitation center. Participants Sixty women diagnosed with fibromyalgia were randomized to HIIT, MICT and Control groups. Interventions HIIT included a 5-min warm-up at 50% of peak-HR, four cycles of 4-min at 80–95% of peak-HR followed by 3-min recovery intervals at 70% of peak-HR. MICT consisted of 45-min at 65-70% of peak-HR. Each aerobic training session was followed by standardized strengthening and stretching exercises. The programs performed using cycle-ergometers 5-sessions per-week for 6-weeks. The control group did not participate in any supervised exercise sessions. Main Outcome Measures The primary outcome measure was the Fibromyalgia Impact Questionnaire (FIQ). The secondary outcome measures were visual analogic scale for pain, Short Form Health Survey-36 (SF-36), cardiopulmonary exercise test (CPET) and body composition parameters. Results Fifty-five participants completed the study. There was no significant difference in FIQ between HIIT vs MICT (1.03; 95% confidence interval (CI) -9.67 to 11.75) after treatment. Group-time interactions were significant for the FIQ between interventions and control (HIIT vs Control -16.20; 95% CI -27.23 to -5.13 and MICT vs Control -17.24; 95% CI -28.27 to -6.22) (all P<0.001). There were significant group-time interactions for the pain, SF-36 and CPET parameters between treatments and control (all P<0.05). Body-weight, fat-percentage, fat-mass and body mass index improved significantly (all P<0.05) only in MICT group after treatment. Conclusions The HIIT plus strengthening and stretching exercises and MICT plus strengthening and stretching exercises interventions showed significant improvements for the impact of fibromyalgia, pain degree, functional capacity and quality of life compared to the control group. HIIT was not superior to MICT. Furthermore, body composition parameters were improved significantly only for the MICT.
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ORIGINAL RESEARCH
Effectiveness of High-Intensity Interval Training vs
Moderate-Intensity Continuous Training in Patients
With Fibromyalgia: A Pilot Randomized Controlled
Trial
Tu
gba Atan, MD,
a
Yusuf Karavelio
glu, MD
b
From the
a
Department of Physical Medicine and Rehabilitation, Gaziler Physical Therapy and Rehabilitation Education and Research Hospital,
Ankara; and
b
Department of Cardiology, Faculty of Medicine, Hitit University, Corum, Turkey.
Abstract
Objective: To compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) combined with
strengthening and stretching exercises in patients with fibromyalgia.
Design: Interventional, single-blind, randomized controlled trial.
Setting: Outpatient rehabilitation center.
Participants: Women with fibromyalgia (NZ60) were randomized to HIIT, MICT, and control groups.
Interventions: HIIT included a 5-minute warm-up at 50% of peak heart rate and 4 cycles of 4 minutes at 80%-95% of peak heart rate followed by
3-minute recovery intervals at 70% of peak heart rate. MICT consisted of 45 minutes at 65%-70% of peak heart rate. Each aerobic training session
was followed by standardized strengthening and stretching exercises. The programs performed using cycle ergometers for 5 sessions per week for
6 weeks. The control group did not participate in any supervised exercise sessions.
Main Outcome Measures: The primary outcome measure was the Fibromyalgia Impact Questionnaire (FIQ). The secondary outcome measures
were visual analog scale for pain, Short Form-36 Health Survey (SF-36), cardiopulmonary exercise test (CPET), and body composition
parameters.
Results: Fifty-five participants completed the study. There was no significant difference in FIQ between HIIT vs MICT (1.03; 95% CI, 9.67 to
11.75) after treatment. Group-time interactions were significant for the FIQ between interventions and control (HIIT vs control, 16.20; 95% CI,
27.23 to 5.13 and MICT vs control, 17.24; 95% CI, 28.27 to 6.22) (all P<.001). There were significant group-time interactions for the
pain, SF-36, and CPET parameters between treatments and control (all P<.05). Body weight, fat percentage, fat mass, and body mass index
improved significantly (all P<.05) only in the MICT group after treatment.
Conclusions: The HIIT plus strengthening and stretching exercises and MICT plus strengthening and stretching exercises interventions showed
significant improvements for the effect of fibromyalgia, pain degree, functional capacity, and quality of life compared with the control group. HIIT
was not superior to MICT. Furthermore, body composition parameters were improved significantly only for the MICT group.
Archives of Physical Medicine and Rehabilitation 2020;101:1865-76
ª2020 by the American Congress of Rehabilitation Medicine
Fibromyalgia is a common rheumatic disease characterized by
widespread musculoskeletal pain, tenderness, fatigue, sleep
disorders, and cognitive and somatic complaints.
1
The diagnosis is
usually complicated because there is no objective examination
finding other than tenderness on palpation and there are no
specific laboratory or imaging findings.
2
Fibromyalgia is
widespread worldwide, its prevalence is reported to be 2%-4% of
the general population, and it is more common in women.
3
Recently, the European League Against Rheumatism presented
evidence-based recommendations for the management of fibro-
myalgia. Accordingly, prompt diagnosis and patient education is
required for optimal management. A graduated approach with the
aim of improving health-related quality of life should be followed.
Clinical Trial Registration No.: NCT03924960
Disclosures: none.
0003-9993/20/$36 - see front matter ª2020 by the American Congress of Rehabilitation Medicine
https://doi.org/10.1016/j.apmr.2020.05.022
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journal homepage: www.archives-pmr.org
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Pharmacotherapy is only recommended for severe pain and sleep
disturbances. It should focus first on nonpharmacologic modal-
ities, and the only “strong for” evidence-based recommendation
was the use of aerobic and strengthening exercise.
2
Reviews of trials evaluating the effects of aerobic exercise in
patients with fibromyalgia have indicated that aerobic exercise
reduces pain, fatigue, or depressed mood and simultaneously
improves quality of life and physical fitness.
4,5
Aerobic exercise
with moderate intensity (60%-70% of age-adjusted predicted peak
heart rate) with a frequency of 2 or 3 times per week for at least 4-
6 weeks for a reduction of symptoms is recommended in the
management of fibromyalgia.
6,7
In recent years, high-intensity interval training (HIIT) has
become a popular alternative aerobic exercise method instead of
moderate-intensity continuous training (MICT) in cardiac reha-
bilitation units. It is superior to MICT in improving cardiovas-
cular fitness because it increases peak oxygen consumption
(VO
2
peak).
8
HIIT involves short burst of exercise at very high
intensity (80%-95% of peak heart rate) with recovery periods,
which relieves fatigue and maintains cardiovascular safety.
9
While the MICT lasts 30-60 minutes, HIIT contains 4-6 cycles
of 1-4 minutes with a maximum effort and lasts approximately
20-40 minutes in total. Therefore, another advantage of HIIT is
the need for a shorter time to achieve similar or greater effects
compared with MICT.
10
Our hypothesis is that 6 weeks of 5 weekly sessions of HIIT
will be superior in reducing the effect of fibromyalgia and
improving pain, functional capacity, and quality of life compared
with MICT. To our knowledge, there is no study investigating the
effect of HIIT in patients with fibromyalgia. Therefore, the aim of
this study is to assess the effects of HIIT vs MICT on pain,
functional capacity, and quality of life in women with
fibromyalgia.
Methods
Study design
The study was designed as a single-center, prospective, single-
blind, randomized controlled trial. The study protocol was
approved by the Institutional Human Research Ethics Committee
(approval no.: 19-KAEK-023). All the procedures were
conducted according to the Declaration of Helsinki. This study
was also registered in the Clinicaltrials.gov database
(NCT03924960). The reporting was conducted in accordance
with the Consolidated Standards of Reporting Trials and recom-
mendations for randomized trials. Participants were fully
informed about the experimental procedures and gave their
informed consent.
Participants and Assessments
The patients were recruited from the physical medicine and
rehabilitation outpatient clinic. Patients who were willing to
participate in the study were assessed to evaluate their eligibility
for the study and to provide detailed information about the study.
The inclusion criteria were as follows: (1) 18 years or older; (2)
female sex; (3) diagnosis according to the American College of
Rheumatology 2016 diagnostic criteria for fibromyalgia. These
criteria include a history of generalized pain in at least 4 of 5
regions at a similar level for at least 3 months, widespread pain
index 7 and symptom severity scale score 5, or widespread
pain index of 4-6 and symptom severity scale score 9; a diag-
nosis of fibromyalgia is valid irrespective of other diagnoses; (4)
no participation in a designed sports or exercise training programs
in the previous 3 months; (5) stable medical treatment for
symptoms for at least 4 weeks prior to participation; and (6) no
pregnancy/breastfeeding. Patients were excluded if they had co-
morbid inflammatory rheumatic and/or connective tissue diseases
or cardiovascular and/or musculoskeletal problems that could
prevent participation in an exercise program. During the study, the
recommended pharmacologic treatments with evidence level
1A (amitriptyline, duloxetine/milnacipran, pregabalin, cyclo-
benzaprine)
2
were continued without changing the dose. Among
our patients, only duloxetine and pregabalin use were available.
Apart from this, patients were not allowed to use any other
analgesic drugs (paracetamol, nonsteroidal anti-inflammatory
drugs, opioids) for pain, because it may affect the outcome
measurements. The study began March 2019 and ended
February 2020.
A total of 117 patients who were followed up in our outpatient
clinic with a diagnosis of fibromyalgia were screened, and 60 of
them enrolled in the study. The Consolidated Standards of
Reporting Trials diagram for participants is shown in fig 1.
Baseline demographic and clinical characteristics (duration of
disease, medical treatments, level of physical activity according to
the International Physical Activity Questionnaire
11
) of the
patients who met the initial screening criteria were recorded. In
addition, outcome measures of body composition, pain, and
psychological variables were analyzed.
All participants underwent a symptom-limited maximal
cardiopulmonary exercise test (CPET) at baseline and followed by
6-week exercise intervention of HIIT or MICT. The pre- and
posttest procedure was identical. The test was performed on a
computer-controlled cycle ergometer
a
with using an incremental
protocol. Twelve-lead electrocardiogram
b
and gas exchange vari-
ables
c
were recorded continuously throughout the test. CPET
variables were analyzed by a cardiology specialist.
After the baseline exercise test, participants were randomly
assigned to 3 groups (HIIT: HIIT plus strengthening and stretching
exercises group, MICT: MICT plus strengthening and stretching
exercises group, control: usual care group) using a computer-
generated program including a randomized table of numbers
formed by an independent individual not involved with any other
aspect of the trial. Numbered cards with a random assignment
containing information about the group allocation in an opaque,
sealed envelopes were prepared by the independent individual.
Physiotherapists opened the envelope and applied the planned
treatment program according to the group.
Outcome measurements were repeated within 3 days of
completing the exercise interventions by the same investigators
blinded to the randomization.
List of abbreviations:
BMI body mass index
CPET cardiopulmonary exercise test
FIQ Fibromyalgia Impact Questionnaire
HIIT high-intensity interval training
MICT moderate-intensity continuous training
SF-36 Short Form-36 Health Survey
VAS visual analog scale
VO
2
peak peak oxygen consumption
1866 T. Atan, Y. Karavelio
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Interventions
All exercise sessions were supervised by experienced cardiac
rehabilitation nurses and physiotherapists during HIIT and MICT.
The participants were taught how to exercise in a moderate- or
high-intensity training session with a trial session. Training in-
tensity was based on the peak heart rate, which was recorded
during the baseline CPET.
The HIIT program was performed using cycle ergometers 5
sessions per week for the 6-week intervention (30 sessions). Each
session consisted of a 5-minute warm-up period cycling at 50% of
peak heart rate followed by 4 sets of 4-minute high-intensity in-
tervals at 80%-95% of peak heart rate interspersed with 3 sets of
3-minute of active recovery intervals at 70% of peak heart rate and
5-minute cool down period cycling at 50% of peak heart rate.
Total exercise time was 35 minutes.
The MICT program performed using cycle ergometers 5 ses-
sions per week for the 6-week intervention. Each session consisted
of a 5-minute warm-up period cycling at 50% of peak heart rate
followed by continuously activity at an intensity of 65%-70% of
peak heart rate and 5-minute cool down period cycling at 50% of
peak heart rate. Total exercise time was 55 minutes.
Each aerobic training session was followed by 15 minutes of
standardized strengthening and stretching exercise training for
both intervention groups. Strengthening exercises were performed
for 10 minutes, where major muscle groups were strengthened
through shoulder press, dumbbell press, shoulder elevation with
resistance, biceps curl, squats, hip flexion and extension, and
standing hip exercises using 1-3 kg of weight loads and 1 set of 8-
10 repetitions. Finally, stretching exercises were performed for 5
minutes by holding the main muscle-tendon groups for 20-30
seconds, with 4-5 repetitions for each muscle group. Percentage of
sessions were also recorded to determine adherence with the
training program.
The control group did not participate in any supervised exer-
cise sessions, but they had specific recommendations regarding
exercise for fibromyalgia. They were only contacted once by
telephone to schedule an appointment for the posttest.
Primary outcome measure of the study
Fibromyalgia Impact Questionnaire
The Fibromyalgia Impact Questionnaire (FIQ) was designed to
measure the health status of patients with fibromyalgia. It is a self-
administered test that measures 10 different items related to
physical function, well-being, loss of working day, pain, fatigue,
stiffness, anxiety, and depression. Total score range from 0-100,
with higher scores indicating higher levels of symptoms and
severity.
12
Fig 1 Flow diagram of the study. Abbreviation: CONSORT, Consolidated Standards of Reporting Trials.
Interval training for fibromyalgia 1867
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Secondary outcomes
Visual analog scale for pain
Pain intensity was measured with visual analog scale (VAS),
which is used to measure musculoskeletal pain with very good
reliability and validity (VAS, 0-10cm; 0Zno pain, 10Zse-
vere pain).
13
Short Form-36 Health Survey 36
Short Form-36 Health Survey (SF-36) contains 36 items that are
used to evaluate the quality of life of patients with chronic pain. It
measures 8 different domains that address physical functioning,
physical role limitation, pain, general health, vitality, social
functioning, emotional role limitation, and mental health. The
score of each domain ranges from 0 (worst quality of life) to 100
(best quality of life).
14
Cardiorespiratory fitness
CPET is a method that comprehensively evaluates the exercise
response to the cardiac, pulmonary, musculoskeletal, and
hematologic systems and allows for more precise, objective, and
detailed examination of cardiopulmonary functional capacity.
Oxygen consumption, heart rate, blood pressure, workload,
duration of test, and maximal metabolic equivalent were assessed
at peak cardiovascular response and ventilatory threshold.
During the termination of the test, the respiratory exchange ratio
was intended to reach 1.1, and values above 1.05 were also
accepted.
15
Body composition parameters
All patients were evaluated with a body composition analyzer.
d
Body weight, muscle, and fat measurements were recorded.
Height measurements (without shoes) were taken with a
stadiometer.
Sample size
The sample size estimation was performed using the G*Power
software (version 3.1).
e
It was determined that 17 individuals for
each group must be recruited to detect a difference at 5% type 1
error level with 80% power for an effect size of 0.733 based on the
FIQ scores reported in a previous research.
16
However, including
w20% for possible future losses, 20 individuals were allocated
into the 3 groups.
Statistical analysis
Demographic data and clinical features were reported as mean and
standard deviation. Categorical variable was presented as number
and percent. Visual assessment and Shapiro-Wilk test were used
for normality evaluation. The assumption of normality was
confirmed, and parametric tests were performed. Outcome
measurements were analyzed using a mixed factorial analysis of
variance with repeated measures (3 groups: HIIT vs MICT vs
control2-times: pre- and post intervention). Post hoc compari-
sons were done with Bonferroni test. The effect size was
calculated by the partial eta squared (hp
2
) value. Effect size values
were interpreted as follows: >0.2, large effect size; >0.1, medium
effect size; and >0.05, small effect size. One-way analysis of
variance was conducted to identify the differences between
groups. Data analyses were performed using IBM SPSS Statistics
for Windows version 21.0,
f
and P.05 was considered a statisti-
cally significant difference.
Results
During the 6-week intervention program no adverse events were
reported. Five participants were unable to complete the training
program or outcome measurements post intervention: 1 from
HIIT, 1 from MICT, and 3 from control group. Their data were
excluded from the analyses, and 55 participants completed the
study (see fig 1). Adherence to training was 98.6%2.4% for HIIT
and 95.5%3.8% for MICT intervention (PZ.085).
Demographic and clinical variables did not show any signifi-
cant difference between the 3 study groups (table 1).
There was no significant difference in FIQ as our primary
outcome measurement between HIIT vs MICT (1.03; 95% CI,
9.67 to 11.75) after treatment. Group-time interactions were
significant for the FIQ between interventions and control (HIIT vs
control, 16.20; 95% CI, 27.23 to 5.13 and MICT vs control,
17.24; 95% CI, 28.27 to 6.22) (all P<.001) (fig 2). Effect
sizes were large regarding treatments (hp
2
Z0.262), time
(hp
2
Z0.641), and interaction (hp
2
Z0.480).
Similarly, VAS-pain and SF-36 subgroups showed significant
improvements for the intervention groups (table 2). The CPET
parameters of duration of test, peak power, VO
2
peak, and maximal
metabolic equivalent showed significant group-time interactions
between treatments (all P<.05). The difference between treat-
ments was originating from the HIIT vs control and MICT vs
control (table 3). Body composition parameters of body weight,
fat mass, and body mass index (BMI) did not differ between
treatments but changed over time (all P<.05). There were not
significant changes regarding the interaction between groups,
except for fat percentage. Body weight, fat percentage, fat mass,
and BMI improved significantly (all P<.05) only in the MICT
group after the 6-week intervention (table 4).
Discussion
The main findings from this study reinforce the recommendations
that patients with fibromyalgia should perform structured aerobic
exercises at a high or moderate intensity combined with
strengthening and stretching exercises to improve symptoms of
disease. In both the HIIT plus strengthening and stretching exer-
cises and MICT plus strengthening and stretching exercises
groups, effect of the fibromyalgia measured by the FIQ, which is
the primary outcome measure, showed significant improvement
after the interventions compared with the control group. Similarly,
HIIT plus strengthening and stretching exercises and MICT plus
strengthening and stretching exercises provided comparable im-
provements in pain, quality of life, and functional capacity. In the
literature, various exercises with positive results were used to treat
symptoms of fibromyalgia. It was emphasized that aerobic
exercise and strength training are the most effective treatment for
fibromyalgia symptoms and improve cardiorespiratory fitness.
17,18
Therefore, in this study, we wanted to compare some outcome
measures of fibromyalgia after performing different aerobic ex-
ercise protocols (HIIT or MICT) combined with strengthening and
stretching exercises with a control group. In a study by Dobkin
et al the maintenance of an exercise program in women with
fibromyalgia appeared to be contingent on being able to deal with
stress, pain, barriers to exercise, and disability.
19
HIIT and MICT
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are 2 types of aerobic exercises that have become increasingly
popular in physical activity interventions.
20
HIIT has been pro-
posed as a time-efficient form of exercise that may overcome
motivational barriers associated with traditional MICT exercise.
10
In a review by Ito et al, although MICT is the main training
regimen recommended in the guidelines for cardiac rehabilitation,
HIIT was more effective than MICT regarding short-term effects
in terms of central and peripheral adaptations.
21
In another review,
HIIT provided greater improvements in VO
2
peak than MICT for
patients at high risk of cardiovascular disease.
22
In this study,
contrary the hypothesis and the literature, no significant difference
was observed in disability, pain, quality of life, and functional
capacity between the 2 intervention groups. However, significant
improvements were noted in both groups. Similar to our findings,
there are some studies in the literature that report that HIIT is not
superior to MICT.
23,24
Previous studies have shown that the prevalence of being
overweight is high in patients with fibromyalgia, and that may
been associated with level of pain, symptom severity, disease
activity, fatigue, anxiety, or quality of life. In this study, in
accordance with the literature, baseline BMI values of patients are
high in all 3 groups. Physical exercise also helps maintain healthy
body composition values, which is an important factor in their
relationship to disease symptoms that cause dependence in women
with fibromyalgia.
25
One of the interesting findings of this study
was that the body composition parameters showed a significant
reduction only for the MICT group. In a systematic review and
meta-analysis, HIIT and MICT showed similar efficacy in all body
composition measurements, but HIIT may be a time-efficient
component of weight management programs.
26
The results for
the body composition parameters are not in accordance with
previous findings from independent intervention studies
27,28
and
systematic reviews
26,29
that state HIIT can be considered as an
effective strategy to improve body weight, fat percentage, and
BMI. The differences between these results and ours may be
explained by sources of variability between individuals, including
behavioral or environmental changes and nutritional status.
Aerobic exercise and strength training have been well tolerated
by the patients, with a small number of adverse events.
7,30,31
Additionally, the mean adherence of patients to the intervention
in the included studies was 84%. They reported this as a positive
result, considering that the most of this population had a low level
of physical activity.
32,33
When the characteristics of the patients
were examined in this study, physical activity levels in all groups
were similarly low. In accordance with the literature, no adverse
events were observed in our study, and adherence to both aerobic
and strength training protocols was found to be very high in the
intervention groups.
Study limitations
A limitation of the present study was although adherence to both
supervised exercise programs was very high, feasibility was not
studied. Treatments were compared only within the scope of the
Table 1 Patient characteristics of the study groups
Variables HIIT (nZ19) MICT (nZ19) Control (nZ17) PValue
Age (y), mean SD 46.579.41 47.368.01 52.708.96 .090
Height (cm), mean SD 156.715.39 156.424.41 157.175.60 .907
Initial weight (kg), mean SD 76.3312.09 75.8310.78 79.397.65 .552
Education level
Low, n (%) 15 (78.9) 13 (68.4) 13 (76.5) .545
Intermediate, n (%) 2 (10.5) 3 (15.8) 2 (11.8)
High, n (%) 2 (10.5) 3 (15.8) 2 (11.8)
Duration of disease (mo), mean SD 37.5721.52 24.0014.96 27.8217.66 .071
Medication
Duloxetine, n (%) 3 (15.8) 5 (26.3) 5 (29.4) .595
Pregabalin, n (%) 5 (26.3) 7 (36.8) 10 (58.8) .131
Tobacco
Former, n (%) 2 (10.5) 3 (15.8) 2 (11.8) .056
No, n (%) 16 (84.2) 14 (73.7) 15 (88.2)
Yes, n (%) 1 (5.3) 2 (10.5) 0 (0.0)
IPAQ, total score (MET/min), mean SD 581.52346.29 663.76359.09 441.58404.32 .165
NOTE. Control, usual care group; HIIT, high-intensity interval training plus strengthening and stretching exercises group; MICT, moderate-intensity
continuous training plus strengthening and stretching exercises group.
Abbreviation: IPAQ, International Physical Activity Questionnaire.
Fig 2 Difference between treatments for the Fibromyalgia Impact
Questionnaire.
Interval training for fibromyalgia 1869
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Table 2 Within- and between-group changes (group, time, and interaction effects) for Fibromyalgia Impact Questionnaire, VAS for pain, and SF-36 data
Outcome
Measurements HIIT MICT Control
Mean Difference (95% CI)
PValue*
Group
PValue
hp
2
Time
PValue
hp
2
GroupTime
PValue
hp
2
HIIT vs MICT HIIT vs Control MICT vs Control
FIQ 1.03 (9.67 to
11.75)
16.20 (27.23
to 5.13)
y
17.24 (28.27
to 6.22)
y
Preintervention 66.1911.73 62.9814.75 66.9811.95 .613 <.001
x
<.001
x
<.001
x
Post intervention 35.8017.35 36.9319.63 67.4413.20 .262 .641 .480
Pvalue
z
<.001
z
<.001
z
.725
VAS for pain 0.13 (1.40 to
1.14)
2.08 (3.39 to
0.77)
y
1.95 (3.26 to
0.64)
y
Preintervention 7.781.81 7.891.76 8.291.61 .662 <.001
x
<.001
x
<.001
x
Post intervention 4.211.93 4.362.43 7.881.36 .260 .670 .406
Pvalue
z
<.001
z
<.001
z
.248
SF-36 Physical
functioning
5.42 (17.83 to
6.99)
19.53 (7.07-
31.99)
y
24.95 (12.18-
37.73)
y
Preintervention 44.4723.20 56.1020.88 42.3515.82 .097 <.001
x
<.001
x
<.001
z
Post intervention 78.4218.48 77.6314.46 41.4717.38 .329 .443 .327
Pvalue
z
<.001
z
<.001
z
.764
SF-36 Role
limitations
because of
physical health
8.55 (28.50 to
11.39)
16.17 (4.35 to
36.70)
24.72 (4.19-
45.25)
y
Preintervention 13.1519.30 26.3133.82 16.1721.54 .270 .015
x
<.001
x
.003
z
Post intervention 61.8430.46 65.7835.56 26.4733.62 .149 .513 .202
Pvalue
z
<.001
z
<.001
z
.150
SF-36 Role
limitations
because of
emotional
problems
9.06 (31.17 to
13.04)
26.48 (3.73-
49.23)*
35.55 (12.80-
58.30)
y
Preintervention 22.2035.05 38.6038.91 21.5737.16 .273 .001
x
<.001
x
.001
z
Post intervention 71.9429.94 73.6830.59 19.6031.31 .234 .357 .251
Pvalue
z
<.001
z
.001
z
.668
SF-36 Energy/
fatigue
3.42 (9.12 to
15.96)
21.30 (8.40-
34.21)
y
17.88 (4.98-
30.79)
y
Preintervention 27.6318.88 29.2121.09 25.2915.04 .820 <.001
x
<.001
x
<.001
z
Post intervention 62.6317.97 54.2120.70 22.3517.51 .267 .472 .382
Pvalue
z
<.001
z
<.001
z
.236
SF-36 Emotional
well-being
5.07 (6.71 to
16.87)
13.82 (1.68-
25.96)*
8.74 (3.39 to
20.88)
Preintervention 43.1520.24 40.6316.12 45.1718.64 .760 .024
x
<.001
x
<.001
z
Post intervention 71.7817.45 64.1517.63 42.1119.85 .134 .369 .289
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Table 2 (continued )
Outcome
Measurements HIIT MICT Control
Mean Difference (95% CI)
PValue*
Group
PValue
hp
2
Time
PValue
hp
2
GroupTime
PValue
hp
2
HIIT vs MICT HIIT vs Control MICT vs Control
Pvalue
z
.001
z
.047
z
.232
SF-36 Social
functioning
5.59 (9.63 to
20.81)
14.86 (0.80 to
30.52)
9.26 (6.39 to
24.93)
Preintervention 51.9723.29 50.0022.43 51.4720.19 .960 .071 <.001
x
<.001
z
Post intervention 82.8919.18 73.6822.00 53.6721.99 .097 .472 .264
Pvalue
z
<.001
x
<.001
x
.593
SF-36 Pain 5.65 (18.68 to
7.37)
12.65 (0.75 to
26.06)
18.30 (4.89-
31.71)
y
Preintervention 18.2817.58 29.8616.63 29.2620.64 .103 .005
x
<.001
x
<.001
z
Post intervention 62.8925.63 62.6317.60 26.6115.90 .185 .599 .484
Pvalue
z
<.001
x
<.001
x
.471
SF-36 General health 0.92 (12.57 to
14.41)
17.29 (3.40-
31.18)
y
16.37 (2.48-
30.25)
y
Preintervention 32.6319.17 37.3616.19 30.2916.43 .461 .005
x
<.001
z
.001
x
Post intervention 63.4222.30 56.8424.61 31.1715.86 .185 .440 .286
Pvalue
z
<.001
x
.002
x
.779
SF-36 Health change 4.73 (20.17 to
10.70)
17.43 (34.36 to
0.51)
y
22.17 (6.59-
37.75)
Preintervention 31.5728.67 32.8925.07 27.0523.38 .783 .003
x
<.001
x
.007
x
Post intervention 69.4722.90 77.6320.23 39.1126.99 .200 .524 .174
Pvalue
z
<.001
x
<.001
x
.096
NOTE. Control, usual care group; HIIT, high-intensity interval training plus strengthening and stretching exercises group; MICT, moderate-intensity continuous training plus strengthening and stretching
exercises group. Data expressed as mean SD; hp
2
Zpartial eta squared effect size.
*Pvalue for basal measurements among the 3 groups.
y
Significant differences between groups (P<.05).
z
Pvalue for pre- and postintervention measurements for each group.
x
Significant Pvalues (P<.05).
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Table 3 Within- and between- group changes (group, time, and interaction effects) for CPET parameters
Outcome
Measurements HIIT MICT Control
Mean Difference
(95% CI) P
Value*
Group
PValue
hp
2
Time
PValue
hp
2
GroupTime
PValue
hp
2
HIIT vs MICT HIIT vs Control MICT vs Control
Duration of test
(s)
0.008 (1.35 to 1.36) 2.76 (1.36-4.16)
y
2.75 (1.31-4.18)
y
Preintervention 16.621.82 16.681.80 15.621.79 .162 <.001
x
<.001
x
<.001
x
Post intervention 20.472.16 20.392.10 15.951.98 .362 .695 .458
Pvalue
z
.010
z
<.001
z
.140
Peak power (W) 0.92 (10.06 to 8.22) 17.74 (8.33-27.15)
y
18.66 (9.25-
28.07)
y
Preintervention 92.3611.67 92.9412.19 85.7612.49 0.158 <.001
x
<.001
x
<.001
x
Post intervention 116.9412.51 118.2113.50 88.0513.47 .366 .725 .489
Pvalue
z
<.001
z
<.001
z
.212
Resting HR
(bpm)
1.65 (5.95 to 9.27) 7.39 (0.24 to
1.90)
5.73 (2.09 to
13.56)
Preintervention 92.5213.50 87.8913.16 88.057.84 .210 .061 .309 .221
Post intervention 83.7810.35 85.1011.07 83.4714.65 .102 .020 .139
Pvalue
z
.024
z
.018
z
.068
Resting SBP
(mmHg)
1.18 (11.19 to 13.56) 0.59 (13.33 to
12.13)
1.78 (14.52 to
10.95)
Preintervention 124.7832.12 123.7820.96 120.7611.69 .869 .939 .168 .308
Post intervention 117.8912.03 116.5212.82 123.1110.50 .002 .03 .044
Pvalue
z
.049
z
.018
z
.056
Resting DBP
(mmHg)
2.10 (4.39 to 8.60) 5.06 (1.61 to
11.75)
2.96 (3.72 to
9.64)
Preintervention 85.637.63 82.3610.56 79.7613.85 .275 .181 .061 .834
Post intervention 81.218.96 80.268.75 76.9410.15 .064 .066 .007
Pvalue
z
.970 .069 .502
Peak HR (bpm) 1.26 (10.61 to 13.14) 9.85 (2.3 to
22.07)
8.59 83.63 to
20.81)
Preintervention 163.3118.82 161.2114.45 159.4119.18 .137 .109 .906 .265
Post intervention 159.1514.16 158.7313.09 159.3518.38 .082 .001 .050
Pvalue
z
<.001
z
.012
z
.449
Peak SBP
(mmHg)
7.92 (10.68 to 26.52) 5.34 (24.48 to
13.79)
13.26 (32.40 to
5.87)
Preintervention 197.7822.66 186.4726.62 195.2934.79 .223 .232 .219 .064
Post intervention 187.0532.63 182.5226.61 182.2329.74 .055 .068 .100
Pvalue
z
.438 .083 .300
Peak DBP
(mmHg)
23.52 (28.26 to 75.32) 22.56 (30.72 to
75.86)
0.95 (54.25 to
52.33)
Preintervention 97.7312.58 95.7316.23 97.3523.29 .935 .457 .625 .467
(continued on next page)
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Table 3 (continued )
Outcome
Measurements HIIT MICT Control
Mean Difference
(95% CI) P
Value*
Group
PValue
hp
2
Time
PValue
hp
2
GroupTime
PValue
hp
2
HIIT vs MICT HIIT vs Control MICT vs Control
Post intervention 92.1011.92 90.0515.66 90.3527.54 .030 .005 .029
Pvalue
z
.520 .112 .502
VO
2
peak (mL/
min)
0.01 (0.14 to 0.12) 0.20 (0.06-0.34)
y
0.21 (0.07-0.35)
y
Preintervention 1.450.23 1.470.18 1.390.17 .066 <.001
x
<.001
x
.016
x
Post intervention 1.690.18 1.690.19 1.430.14 .257 .735 .147
Pvalue
z
<.001
z
<.001
z
.059
VO
2
peak (mL/kg/
min)
0.44 (2.13 to 1.24) 3.42 (1.68-5.16)
y
3.86 (2.12-5.60)
y
Preintervention 19.151.83 19.422.24 18.947.18 .067 <.001
x
<.001
x
.001
x
Post intervention 22.682.51 23.312.94 18.105.52 .406 .651 .252
Pvalue
z
<.001
z
.007
z
.062
Maximal MET 0.10 (0.66 to 0.45) 0.94 (0.66 to
0.45)
y
1.04 (0.47-1.62)
y
Preintervention 5.190.52 5.260.81 4.800.69 .100 <.001
x
<.001
x
.001
x
Post intervention 6.370.79 6.510.89 4.880.77 .316 .694 .471
Pvalue
z
<.001
z
<.001
z
.130
Peak RER 0.004 (0.04 to 0.03) 0.0009 (0.04 to
0.03)
0.003 (0.03 to
0.04)
Preintervention 1.080.06 1.090.04 1.080.06 .907 .960 .518 .917
Post intervention 1.070.05 1.080.06 1.070.04 .002 .007 .003
Pvalue
z
.302 .279 .137
NOTE. Control, usual care group; HIIT, high-intensity interval training plus strengthening and stretching ex
ercises group; MICT, moderate-intensity continuous training plus strengthening and stretching exercises group. Data expressed as mean SD; hp
2
Zpartial eta squared effect size.
Abbreviations: DBP, diastolic blood pressure; HR, heart rate; MET, metabolic equivalent; RER, respiratory exchange ratio; SBP, systolic blood pressure.
*Pvalue for basal measurements among the 3 groups.
y
Significant differences between groups (P<.05).
z
Pvalue for pre- and postintervention measurements for each group.
x
Significant Pvalues (P<.05).
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Table 4 Within- and between-group changes (group, time, and interaction effects) for body composition parameters
Outcome
Measurements HIIT MICT Control
Mean Difference (95% CI)
P
Value*
Group
PValue
hp
2
Time
PValue
hp
2
GroupTime
PValue
hp
2
HIIT vs MICT HIIT vs Control MICT vs Control
Body weight (kg) 1.04 (6.99 to 9.07) 3.28 (11.55 to 4.98) 4.32 (12.59 to 3.94)
Preintervention 76.0811.88 75.7410.58 79.397.65 .535 .413 .048
z
.366
Post intervention 75.882.16 74.2410.12 79.248.06 .033 .073 .038
Pvalue
y
.242 .006
z
.875
Fat (%) 0.22 (3.02 to 3.46) 1.40 (4.74 to 1.93) 1.62 (4.96 to 1.71)
Preintervention 37.914.53 38.084.96 39.082.87 .679 .437 .220 .008
z
Post intervention 37.214.42 36.604.71 38.852.76 .031 .057 .129
Pvalue
y
.254 .002
z
.634
Fat mass (kg) 0.49 (4.73 to 5.71) 2.22 (7.60 to 3.14) 2.72 (8.09 to 2.65)
Preintervention 29.437.74 29.277.44 31.357.48 .602 .422 <.001
z
.160
Post intervention 28.867.15 27.546.77 30.904.75 .033 .242 .068
Pvalue
y
.056 <.001
z
.399
Fat free mass (kg) 0.43 (2.99 to 3.85) 1.11 (4.64 to 2.40) 1.55 (5.07 to 1.97)
Preintervention 46.954.90 46.463.96 48.484.25 .372 .540 .568 .190
Post intervention 47.314.78 46.933.97 48.024.04 .023 .006 .062
Pvalue
y
.354 .252 .215
Muscle mass (kg) 0.41 (3.08 to 3.91) 0.08 (3.51 to 3.68) 0.33 (3.93 to 3.27)
Preintervention 44.584.66 44.103.78 44.675.02 .918 .953 .247 .657
Post intervention 44.914.54 44.563.77 44.654.78 .002 .026 .016
Pvalue
y
.367 .248 .953
BMI 0.40 (3.17 to 3.99) 1.55 (5.24 to 2.13) 1.96 (5.65 to 1.72)
Preintervention 31.135.53 30.984.55 32.693.03 .486 .109 .043
z
.378
Post intervention 30.965.11 30.194.45 32.613.61 .082 .076 .037
Pvalue
y
.299 .008
z
.819
NOTE. BMI calculated as weight in kilograms divided by height in meters squared; Control, usual care group; HIIT, high-intensity interval training plus strengthening and stretching exercises group; MICT,
moderate-intensity continuous training plus strengthening and stretching exercises group. Data expressed as mean SD; hp
2
Zpartial eta squared effect size.
*Pvalue for basal measurements among the 3 groups.
y
Pvalue for pre- and postintervention measurements for each group.
z
Significant Pvalues (P<.05).
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established outcome criteria. However, no data were collected on
whether the treatment program was enjoyable and whether its
duration was sufficient. Although the HIIT plus strengthening and
stretching exercises protocol does not seem to have outperformed
the MICT plus strengthening and stretching exercises protocol,
superiority can be demonstrated because of its completion in a
shorter period of time in future feasibility studies. In addition, the
most effective component of the exercise programs (HIIT, MICT,
strengthening, stretching) cannot be determined. Another limi-
tation of the study is that the follow-up period was short for un-
derstanding the maintenance of the long-term effects of
interventions in subjects with fibromyalgia. We also noticed the
potential imbalance in duration of disease and International
Physical Activity Questionnaire scores between groups, which
could confuse results. In addition, these results cannot be gener-
alized to other populations, such as men.
Conclusions
Thirty-sessions of HIIT or MICT plus strengthening and stretching
exercises were beneficial for disability, pain degree, functional
capacity, and quality of life in the treatment of fibromyalgia.
Contrary to our hypothesis, HIIT was not superior to MICT.
Moreover, body composition parameters showed significant
improvement only for the MICT group. Adherence to the training
sessions was similar when HIIT plus strengthening and stretching
exercises and MICT plus strengthening and stretching exercises
were performed in a supervised unit.
Suppliers
a. Ergoline Bicycle Ergometer Ergoselect 200; Ergoline.
b. Meta Control 3000; CORTEX Biophysik GmbH.
c. Metalyzer 3B-MICROMED; CORTEX Biophysik GmbH.
d. MC-980; Tanita, Tokyo, Japan.
e. G)Power software version 3.1; Heinrich Heine University
Du
¨sseldorf.
f. IBM SPSS Statistics for Windows version 21.0; IBM.
Keywords
Cardiorespiratory fitness; Exercise; High-intensity interval
training; Oxygen consumption; Rehabilitation
Corresponding author
Tu
gba Atan, MD, Department of Physical Medicine and
Rehabilitation, Gaziler Physical Therapy and Rehabilitation
Education and Research Hospital, Ankara, Turkey. E-mail
address: tubaatan@gmail.com.
Acknowledgments
We thank all the members of cardiac rehabilitation unit: nurses
Yasemin Yener, Sultan Yetik, Damla Beykoz, Fatma O
¨zkul;
physiotherapists Ays
e Akdal, Cengiz Ciga; and secretaries Nur
Mehtap Barut and Sema O
¨ncu
¨l.
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... Fibromyalgia (FM) is defined as a chronic rheumatic disease and is characterised by chronic widespread pain, muscle stiffness, sleep disturbances and cognitive problems [1][2][3][4]. In addition to these, the following symptoms are also observed: a feeling of fatigue and changes in the psychological state [5]. ...
... Most of the time, the diagnosis is quite difficult to perform because there is no accurate (i.e., validated) diagnostic test to identify the disease. Thus, the diagnosis of this disease is carried out through palpation from tender points specific for FM [1]. ...
... This systematic review aimed to analyse and systematise the characteristics of combined training programs and their effects in individuals diagnosed with Fibromyalgia. In the studies that were analysed, significant values were found for at least one of the evaluated parameters in all studies: (i) physical fitness tests [1,23,33,36,37,[39][40][41]; (ii) decreased symptoms and impact of FM on participants [1,5,15,17,23,33,36,37,41]; (iii) lower limb strength [1,15,33]. These results are in line with other authors who claim that physical exercise programs are important stimuli with positive influence, attenuating the symptoms of the disease, through changes in the hypothalamic-pituitary-adrenal axis (HPA)-resulting in the release of neurotransmitters due to exercise and controlling and/or reducing localised pain [16,42]. ...
Article
Full-text available
Fibromyalgia is a rheumatic disease characterised by chronic widespread muscular pain and its treatment is carried out by pharmacological interventions. Physical exercise and a healthy lifestyle act as an important mechanism in reducing the symptoms of the disease. The aims of this study were to analyse and systematise the characteristics of combined training programs (i.e., type and duration of interventions, weekly frequency, duration and structure of training sessions and prescribed intensities) and to analyse their effects on people diagnosed with fibromyalgia. A systematic literature search was performed using the PRISMA method and then randomised controlled trial articles that met the eligibility criteria were selected. The Physiotherapy Evidence Database scale was used to assess the quality and risk of the studies. A total of 230 articles were selected, and in the end, 13 articles met the defined criteria. The results showed different exercise interventions such as: combined training, high-intensity interval training, Tai Chi, aerobic exercise, body balance and strength training. In general, the different interventions were beneficial for decreasing physical symptoms and improving physical fitness and functional capacity. In conclusion, a minimum duration of 14 weeks is recommended for better benefits. Moreover, combined training programs were the most effective for this population, in order to reduce the symptoms of the disease with a duration between 60 and 90 min, three times a week with a light to moderate intensity.
... Nine hundred forty-two were excluded for not being relevant and 416 did not meet the inclusion criteria. Ultimately, 68 studies were included in this systematic review with meta-analysis (Wigers et al., 1996;Mannerkorpi et al., 2000;Mannerkorpi et al., 2009;Gowans et al., 2001;King et al., 2002;Richards, 2002;Astin et al., 2003;Schachter et al., 2003;Cedraschi, 2004;Redondo et al., 2004;Sencan et al., 2004;Da Costa et al., 2005;Kingsley et al., 2005;Zijlstra, 2005;Gusi et al., 2006;Hammond and Freeman, 2006;Fontaine and Haaz, 2007;Munguía-Izquierdo and Legaz-Arrese, 2007;Rooks, 2007;Tomas-Carus et al., 2007;Tomas-Carus et al., 2009;Tomas-Carus et al., 2018;Tomas-Carus et al., 2021;Günendi et al., 2008;Carson et al., 2010;Fontaine et al., 2010;Sañudo Corrales et al., 2010;Arcos-Carmona et al., 2011;Núñez et al., 2011;Sañudo et al., 2011;Sañudo et al., 2015;Baptista et al., 2012;García-Martínez et al., 2012;Jones et al., 2012;Kayo et al., 2012;Castel et al., 2013;Chan et al., 2014;Chan et al., 2017;Clarke-Jenssen et al., 2014;Giannotti et al., 2014;Martín et al., 2014;Larsson et al., 2015;Latorre Román et al., 2015;Ericsson et al., 2016;Espí-López et al., 2016;Kurt, 2016;Maddali Bongi et al., 2016;Ekici et al., 2017;Windthorst et al., 2017;Assumpção et al., 2018;Kashikar-Zuck et al., 2018;Wong et al., 2018;Andrade et al., 2019;Silva et al., 2019;Atan and Karavelioğlu, 2020;Garrido-Ardila et al., 2020;Izquierdo-Alventosa et al., 2020;Izquierdo-Alventosa et al., 2020;Sauch Valmaña et al., 2020;Serrat et al., 2020;Serrat et al., 2021b;Serrat et al., 2021a;Serrat et al., 2022;Fonseca et al., 2021;Haugmark et al., 2021;Hernando-Garijo et al., 2021;Arroyo-Fernández et al., 2022;de Lorena et al., 2022). The literature searches and study selection process is shown in the PRISMA flowchart (Figure 1), which shows the number of excluded references together with the reasons. ...
... Twenty-four studies (Mannerkorpi et al., 2000;Mannerkorpi et al., 2009;Cedraschi, 2004;Redondo et al., 2004;Rooks, 2007;Tomas-Carus et al., 2007;Tomas-Carus et al., 2009;Tomas-Carus et al., 2021;Sañudo Corrales et al., 2010;Arcos-Carmona et al., 2011;Núñez et al., 2011;Sañudo et al., 2011;Baptista et al., 2012;García-Martínez et al., 2012;Maddali Bongi et al., 2016;Windthorst et al., 2017;Assumpção et al., 2018;Andrade et al., 2019;Silva et al., 2019;Atan and Karavelioğlu, 2020;Sauch Valmaña et al., 2020;Serrat et al., 2021b;Serrat et al., 2021a;Serrat et al., 2022) assessed the effect of PEBT on the physical dimension of QoL. The quality of evidence was high, and there was a medium-sized effect indicating the superiority of PEBT for improving the physical dimension of QoL compared to other interventions (SMD = 0.51; 95% CI 0.33-0.69; ...
... The effect of PEBT on the mental dimension of QoL was assessed in 20 studies (Mannerkorpi et al., 2000;Mannerkorpi et al., 2009;Redondo et al., 2004;Rooks, 2007;Tomas-Carus et al., 2007;Tomas-Carus et al., 2009;Tomas-Carus et al., 2021;Sañudo Corrales et al., 2010;Arcos-Carmona et al., 2011;Núñez et al., 2011;Sañudo et al., 2011;Baptista et al., 2012;García-Martínez et al., 2012;Maddali Bongi et al., 2016;Windthorst et al., 2017;Assumpção et al., 2018;Andrade et al., 2019;Silva et al., 2019;Atan and Karavelioğlu, 2020;Sauch Valmaña et al., 2020). The quality of evidence was high, and there was a medium-sized effect indicating the superiority of PEBT for improving mental QoL compared to the other interventions when assessed immediately after therapy (SMD = 0.48; 95% CI 0.29-0.67; ...
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The aim of our meta-analysis was to compile the available evidence to evaluate the effect of physical exercise-based therapy (PEBT) on pain, impact of the disease, quality of life (QoL) and anxiety in patients with fibromyalgia syndrome (FMS), to determine the effect of different modes of physical exercise-based therapy, and the most effective dose of physical exercise-based therapy for improving each outcome. A systematic review and meta-analysis was carried out. The PubMed (MEDLINE), SCOPUS, Web of Science, CINAHL Complete and Physiotherapy Evidence Database (PEDro) databases were searched up to November 2022. Randomized controlled trials (RCTs) comparing the effects of physical exercise-based therapy and other treatments on pain, the impact of the disease, QoL and/or anxiety in patients with FMS were included. The standardized mean difference (SMD) and a 95% CI were estimated for all the outcome measures using random effect models. Three reviewers independently extracted data and assessed the risk of bias using the PEDro scale. Sixty-eight RCTs involving 5,474 participants were included. Selection, detection and performance biases were the most identified. In comparison to other therapies, at immediate assessment, physical exercise-based therapy was effective at improving pain [SMD-0.62 (95%CI, -0.78 to -0.46)], the impact of the disease [SMD-0.52 (95%CI, -0.67 to -0.36)], the physical [SMD 0.51 (95%CI, 0.33 to 0.69)] and mental dimensions of QoL [SMD 0.48 (95%CI, 0.29 to 0.67)], and the anxiety [SMD-0.36 (95%CI, -0.49 to -0.25)]. The most effective dose of physical exercise-based therapy for reducing pain was 21-40 sessions [SMD-0.83 (95%CI, 1.1--0.56)], 3 sessions/week [SMD-0.82 (95%CI, -1.2--0.48)] and 61-90 min per session [SMD-1.08 (95%CI, -1.55--0.62)]. The effect of PEBT on pain reduction was maintained up to 12 weeks [SMD-0.74 (95%CI, -1.03--0.45)]. Among patients with FMS, PEBT (including circuit-based exercises or exercise movement techniques) is effective at reducing pain, the impact of the disease and anxiety as well as increasing QoL. Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021232013.
... The exercise time ranged from 9 to 54 min for HIIT and 15 to 60 min for MICT, only two studies [58,68] used energy expenditure formulating exercise time. A total of 19 studies [42,43,[46][47][48][50][51][52][53][54]56,57,[59][60][61][62]64,67,69] instructed participants to exercise 3 times/week, nine studies [41,45,49,55,58,63,65,66,68] instructed > 3 times/week, and only one study [44] instructed once per week. A total of 14 studies [41,46,[49][50][51]53,54,58,61,63,64,[67][68][69] had dropouts, of which four studies [49][50][51]64] had <85% attendance rate. ...
... A total of 19 studies [42,43,[46][47][48][50][51][52][53][54]56,57,[59][60][61][62]64,67,69] instructed participants to exercise 3 times/week, nine studies [41,45,49,55,58,63,65,66,68] instructed > 3 times/week, and only one study [44] instructed once per week. A total of 14 studies [41,46,[49][50][51]53,54,58,61,63,64,[67][68][69] had dropouts, of which four studies [49][50][51]64] had <85% attendance rate. ...
... A total of four studies [48,50,67,68] did not report sex ratio, the sex ratio of the remaining studies was 2:3. The participants in 20 included studies [44][45][46][47][48][49][51][52][53][54][55][57][58][59][60][61]63,66,68,69] were people with sedentary obesity, two studies [30,56] were sedentary only, and seven studies [41][42][43]50,62,64,67] were other medical comorbidities (two Type 1 diabetes, two Type 2 diabetes, one prediabetes, one polycystic ovary syndrome, and one fibromyalgia). ...
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Objectives: This systematic review is conducted to evaluate the effect of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on body composition and cardiorespiratory fitness (CRF) in the young and middle-aged. Methods: Seven databases were searched from their inception to 22 October 2022 for studies (randomized controlled trials only) with HIIT and MICT intervention. Meta-analysis was carried out for within-group (pre-intervention vs. post-intervention) and between-group (HIIT vs. MICT) comparisons for change in body mass (BM), body mass index (BMI), waist circumference (WC), percent fat mass (PFM), fat mass (FM), fat-free mass (FFM), and CRF. Results: A total of 1738 studies were retrieved from the database, and 29 studies were included in the meta-analysis. Within-group analyses indicated that both HIIT and MICT can bring significant improvement in body composition and CRF, except for FFM. Between-group analyses found that compared to MICT, HIIT brings significant benefits to WC, PFM, and VO2peak. Conclusions: The effect of HIIT on fat loss and CRF in the young and middle-aged is similar to or better than MICT, which might be influenced by age (18-45 years), complications (obesity), duration (>6 weeks), frequency, and HIIT interval. Despite the clinical significance of the improvement being limited, HIIT appears to be more time-saving and enjoyable than MICT.
... The study strategy is shown in the form of a flow chart (Appendix A). From 429 studies initially detected, a total of eight studies were included, six randomized controlled trials [38][39][40][41][42][43][44] and one randomized cross-over trial [45]. Five were from Europe, [41][42][43][44][45] two from Oceania [39,40] and one from the Middle East [38]. ...
... From 429 studies initially detected, a total of eight studies were included, six randomized controlled trials [38][39][40][41][42][43][44] and one randomized cross-over trial [45]. Five were from Europe, [41][42][43][44][45] two from Oceania [39,40] and one from the Middle East [38]. A total of 380 participants with a mean age ranging from 30.2 to 62.4 years were included. ...
... A total of 380 participants with a mean age ranging from 30.2 to 62.4 years were included. The patients were mostly women (50-100%) diagnosed with fibromyalgia [38], persistent pain condition [39], knee osteoarthritis [40], rheumatoid arthritis [45], adults with juvenile idiopathic arthritis [45], axial spondyloarthritis [41,42], or psoriatic arthritis [43,44]. Details of the participant's characteristics and studies are shown in Appendix A. ...
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In order to assess the impact of high-intensity interval training (HIIT) on biological and body composition variables in patients with musculoskeletal disorders (MSKD), a systematic search on PubMed (Medline), CENTRAL, CINAHL, Web of Science, SPORTDiscus, and Scopus was conducted. Standardized mean differences (SMD) and 95% confidence intervals were calculated and pooled in a meta-analysis using the random-effects model. The effectiveness of HIIT on waist circumference, muscle mass, resting heart rate, resting systolic and diastolic blood pressure, C-reactive protein, body weight, and body fat were determined. GRADE, risk of bias 2, and PEDro scales were employed. HIIT compared to no intervention, minimal intervention, or usual care did not show significant results in its favor on any of the variables studied, except for the resting heart rate when compared with no intervention (SMD = −0.33; 95% CI: −0.63, −0.04; heterogeneity Q value: 0.14; p = 0.93; I2 = 0%). In addition, HIIT also does not seem to be more effective than moderate-intensity continuous training. Based on the results, it seems that HIIT has almost no significant effects on biological and body composition variables, except for resting heart rate, in patients with MSKD.
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Background Exercise is one of the most recommended management strategies by treatment guidelines for fibromyalgia (FM); however, the mechanism through which exercise improves pain in FM is still unknown. Objective We aimed to summarize the hypothesized theoretical mechanisms for the pain-relieving effects of exercise in people with FM. Eligibility Criteria Randomized controlled trials (RCTs) in English reporting mechanisms for pain-relieving effects of exercise in the ‘Introduction’ and ‘Discussion’ sections and significant within- group or between-group effects of exercise interventions were included. Sources of Evidence We searched the databases Ovid MEDLINE(R), EMBASE, CINAHL, COCHRANE, Sports Discuss, and AMED with the keywords: exercise and fibromyalgia until December 2021. Charting Methods Two authors independently performed title/abstract, full-text review, and data abstraction using a data abstraction form. The hypothesized mechanisms from individual studies were grouped into three categories. Results The literature search resulted in 2147 studies, out of which 220 studies were considered for full-text review. A total of 50 RCTs proposing 29 unique mechanisms for the pain-relieving effects of exercise were included. These mechanisms were divided into three categories: physical, neuro-physiological, and psychological. The neuro-physiological category was further subdivided into exercise-induced hypoalgesia (EIH), pain sensitization, the autonomic system, the immune system, the endocrine system, and miscellaneous categories. The most frequently hypothesized mechanisms were EIH ( n = 15), autonomic modulation ( n = 7), improved sleep ( n = 6), muscle oxygenation ( n = 6), self-efficacy ( n = 5), mental health ( n = 4), and benefits of the aquatic environment ( n = 12). While all exercise interventions involved FM patients, most of the supporting evidence for these mechanisms was cited from previous studies conducted on healthy samples. No studies performed analyses to demonstrate causal associations between the mechanisms and outcomes. Conclusion Multiple mechanisms were hypothesized for the positive influence of exercise in people with FM. Future studies using causal analyses, such as mediation analysis, are recommended to validate these mechanisms.
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Objective: To meta-analyse the prevalence and predictors of dropout rates among adults with fibromyalgia participating in exercise randomized controlled trials (RCTs). Data sources: Two authors searched Embase, CINAHL, PsycARTICLES, and Medline up to 01/21/2023. Study selection: We included RCTs of exercise interventions in people with fibromyalgia that reported dropout rates. Data extraction: Dropout rates from exercise and control conditions and exerciser/participant, provider, and design/implementation related predictors. Data synthesis: A random effects meta-analysis and meta-regression were conducted. In total 89 RCTs involving 122 exercise arms in 3.702 people with fibromyalgia were included. The trim-and-fill-adjusted prevalence of dropout across all RCTs was 19.2% (95%CI=16.9%-21.8%), which is comparable to the dropout observed in control conditions with the trim-and-fill-adjusted odds ratio being 0.31 (95%CI = 0.92 to 1.86, P=0.44). Body mass index (R²=0.16, P=0.03) and higher impact of illness (R²=0.20, P=0.02) predicted higher dropout. The lowest dropout was observed in exergaming, compared to other exercise types (P=0.014), and in lower-intensity exercises, compared with high intensity exercise (P=0.03). No differences in dropout were observed for the frequency or duration of the exercise intervention. Continuous supervision by an exercise expert (e.g., physiotherapist) resulted in the lowest dropout rates (P<0.001). Conclusions: Exercise dropout in RCTs is comparable to control conditions, suggesting that exercise is a feasible and accepted treatment modality; however, interventions are ideally supervised by an expert (e.g., physiotherapist) to minimize the risk of dropout. Experts should consider a high BMI and the impact of the illness as risk factors for dropout.
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Background High-intensity interval training (HIIT) remains a promising exercise mode in managing cardiometabolic health. Large-scale analyses are necessary to understand its magnitude of effect on important cardiometabolic risk factors and inform guideline recommendations. Objective We aimed to perform a novel large-scale meta-analysis on the effects of HIIT on cardiometabolic health in the general population. Methods PubMed (MEDLINE), the Cochrane library and Web of Science were systematically searched. Randomised controlled trials (RCTs) published between 1990 and March 2023 were eligible. Research trials reporting the effects of a HIIT intervention on at least one cardiometabolic health parameter with a non-intervention control group were considered. Results This meta-analysis included 97 RCTs with a pooled sample size of 3399 participants. HIIT produced significant improvements in 14 clinically relevant cardiometabolic health parameters, including peak aerobic capacity (VO2) [weighted mean difference (WMD): 3.895 ml min⁻¹ kg⁻¹, P < 0.001), left ventricular ejection fraction (WMD: 3.505%, P < 0.001), systolic (WMD: − 3.203 mmHg, P < 0.001) and diastolic (WMD: − 2.409 mmHg, P < 0.001) blood pressure, resting heart rate (WMD: − 3.902 bpm, P < 0.001) and stroke volume (WMD: 9.516 mL, P < 0.001). Body composition also significantly improved through reductions in body mass index (WMD: − 0.565 kg m⁻², P < 0.001), waist circumference (WMD: − 2.843 cm, P < 0.001) and percentage body fat (WMD: − 0.972%, P < 0.001). Furthermore, there were significant reductions in fasting insulin (WMD: − 13.684 pmol L⁻¹, P = 0.004), high-sensitivity C-reactive protein (WMD: − 0.445 mg dL⁻¹, P = 0.043), triglycerides (WMD: − 0.090 mmol L⁻¹, P = 0.011) and low-density lipoprotein (WMD: − 0.063 mmol L⁻¹, P = 0.050), concurrent to a significant increase in high-density lipoprotein (WMD: 0.036 mmol L⁻¹, P = 0.046). Conclusion These results provide further support for HIIT in the clinical management of important cardiometabolic health risk factors, which may have implications for physical activity guideline recommendations.
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The aim was to assess the impact of high-intensity interval training (HIIT) on patients with musculoskeletal disorders. We conducted a search of Medline, Embase, PEDro and Google Scholar. We conducted a meta-analysis to determine the effectiveness of HIIT on pain intensity, maximal oxygen consumption (VO2 max), disability, and quality of life (QoL). We employed the GRADE and PEDro scales to rate the quality, certainty, and applicability of the evidence. Results showed significant differences in pain intensity, with a moderate clinical-effect (SMD=-0.73; 95% CI: -1.40 – -0.06), and in VO2 max, with a moderate clinical-effect (SMD=0.69; 95% CI: 0.42 – 0.97). However, the meta-analysis showed no statistically significant results for disability (SMD=-0.34; 95% CI: -0.92 – 0.24) and QoL (SMD=0.40; 95% CI: -0.80 – 1.60). We compared HIIT against other exercise models for reducing pain intensity and increasing VO2 max. The meta-analysis showed no significant differences in favour of HIIT. Meta-regression analysis revealed that pain intensity scores were negatively associated with VO2 max (R2=82.99%, p=0.003). There is low-moderate evidence that the HIIT intervention for patients with musculoskeletal disorders can reduce pain intensity and increase VO2 max but has no effect on disability and QoL. Results also showed that HIIT was not superior to other exercise models in reducing pain intensity and increasing VO2 max.
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Purpose: Patient-Reported Outcomes (PROs) and its measures (PROMs) are key to outcome assessment in Fibromyalgia (FM) trials. The aim of this review was to investigate which domains and instruments were assessed in recent FM trials and to compare them to recommendations by the Outcome Measures in Rheumatology (OMERACT) initiative. In addition, we investigated the overlap with a generic health assessment approach, i.e. eight domains suggested by the Patient-Reported Outcome Measurement Information System® (PROMIS®). Methods: In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines , a systematic literature search in scientific databases including PubMed, PsycInfo, and Embase was conducted to identify studies that assessed at least two dimensions of health-related quality of life (HRQoL) from 2015 to June 2022. Non-rand-omized and randomized controlled trials were included in the analysis. We extracted PROs and PROMs used in each study. Results: From 1845 identified records, 107 records out of 105 studies met the inclusion criteria. Studies investigated 50 PROs using 126 different PROMs. Most frequently assessed domains were pain, depression, fatigue, and anxiety (> 95% of the studies). The disease-specific FIQ was the most frequently applied PROM (82%). Overall, only 9% of the studies covered all domains deemed mandatory by OMERACT. Very few studies covered all eight generic health domains suggested by PROMIS. Conclusion: The majority of trials covered most OMERACT domains or generic PROMIS health domains. There was, however, great variability in the instruments used to assess the domains, which points at a limited degree of standardization in the field.
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Background: Both high-intensity interval training and moderate-intensity continuous training demonstrate beneficial physiological outcomes for active and insufficiently active populations. However, it remains unclear whether compliance to exercise in supervised settings translates to long-term adherence to physical activity in real-world, unstructured environments. To our knowledge, no comprehensive review is available on compliance and/or adherence rates to either modes of exercise for insufficiently active individuals. Furthermore, it is unclear which training modality insufficiently active individuals comply and/or adhere more readily to. Based on these gaps, the following two questions will be addressed: (1) What are compliance and adherence rates to high-intensity interval training for insufficiently active adults aged 18-65 years and (2) How do compliance and adherence rates differ between high-intensity interval training and moderate-intensity continuous training? Methods: Both observational and experimental studies that report on compliance and/or adherence rates to high-intensity interval training will be included. Relevant studies will be retrieved from Medline, EMBASE, PsychINFO, SPORTDiscus, CINAHL, and Web of Science using a pre-specified search strategy. Pre-defined inclusion and exclusion criteria will be used by two independent researchers to determine eligible studies. Of those meeting the inclusion criteria, data extraction and narrative synthesis will be completed, and where applicable, random-effects meta-analyses will be computed to compare compliance and adherence rates between high-intensity interval training and moderate-intensity continuous training. Meta-regressions and sensitivity analyses will be used to further explore factors that could influence aggregate effect sizes. Risk of bias will be assessed using established tools by the Cochrane association, and quality assessment of the cumulative evidence will be assessed using the GRADE approach. Discussion: Results from this study may have the potential to inform future physical activity recommendations and guidelines on the ideal mode of exercise for the general population. This review will add to the body of literature on the feasibility of high-intensity interval training for an insufficiently active population, conclusively addressing the ongoing debate of whether it is an appropriate exercise choice for this demographic. With this new information, individuals working towards a healthier lifestyle through physical activity engagement may be better equipped to make an evidence-based decision. Systematic review registration: This review has been registered in the PROSPERO database and assigned the identifier CRD42019103313.
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High Intensity Interval Training (HIIT) has been suggested as an effective alternative to traditional Moderate Intensity Continuous Training (MICT) that can yield improvements in a variety of health outcomes. Yet, despite the urgent need to find effective strategies for the treatment of pediatric obesity, only a few studies have addressed the impact of HIIT on eating behaviors and body composition. This study aimed to compare the effect of HIIT versus MICT on eating behaviors in adolescents with obesity, and assess whether the participants' baseline dietary status is associated with the success of the intervention. Forty-three adolescents with obesity were randomly assigned to a 16-week MICT or HIIT intervention. Body composition and 24-hour ad libitum energy intake were assessed at baseline (T0) and at the end of the program (T1). Restrained eating, emotional eating and external eating were assessed using DEBQ at baseline. Both interventions led to significant weight, BMI, and FM% reductions, with better improvements in FM% in the HIIT group; whereas 24-hour ad libitum energy intake increased to a similar extent in both groups. HIIT provides better body composition improvements over MICT, despite a similar increase in energy intake. Restrained eaters experienced less weight loss and smaller BMI reductions compared to unrestrained eaters adolescents, with higher baseline cognitively restrained adolescents showed greater increased of their ad libitum energy intake. •HIIT favors better body composition improvements compared with MICT •Both MICT and HIIT increased ad libitum energy intake in adolescents with obesity •Weight loss achievement is better among unrestrained eaters.
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The link between fibromyalgia syndrome (FMS) and obesity has not been thoroughly investigated. The purpose of this study was to examine the relationships among body mass index (BMI) and body composition parameters, including fat mass, fat mass percentage, and visceral fat, as well as FMS features, such as tender point count (TPC), pain, disease activity, fatigue, sleep quality, and anxiety, in a population of FMS women and healthy controls. A total of seventy-three women with FMS and seventy-three healthy controls, matched on weight, were included in this cross-sectional study. We used a body composition analyzer to measure fat mass, fat mass percentage, and visceral fat. Tender point count (TPC) was measured by algometry pressure. The disease severity was measured with the Fibromyalgia Impact Questionnaire (FIQ-R) and self-reported global pain was evaluated with the visual analog scale (VAS). To measure the quality of sleep, fatigue, and anxiety we used the Pittsburgh Sleep Quality Questionnaire (PSQI), the Spanish version of the multidimensional fatigue inventory (MFI), and the Beck Anxiety Inventory (BAI), respectively. Of the women in this study, 38.4% and 31.5% were overweight and obese, respectively. Significant differences in FIQ-R.1 (16.82 ± 6.86 vs. 20.66 ± 4.71, p = 0.030), FIQ-R.3 (35.20 ± 89.02 vs. 40.33 ± 5.60, p = 0.033), and FIQ-R total score (63.87 ± 19.12 vs. 75.94 ± 12.25, p = 0.017) among normal-weight and overweight FMS were observed. Linear analysis regression revealed significant associations between FIQ-R.2 (β(95% CI)= 0.336, (0.027, 0.645), p = 0.034), FIQ-R.3 (β(95% CI)= 0.235, (0.017, 0.453), p = 0.035), and FIQ-R total score (β(95% CI)= 0.110, (0.010, 0.209), p = 0.032) and BMI in FMS women after adjusting for age and menopause status. Associations between sleep latency and fat mass percentage in FMS women (β(95% CI)= 1.910, (0.078, 3.742), p = 0.041) and sleep quality and visceral fat in healthy women (β(95% CI)= 2.614, (2.192, 3.036), p = 0.008) adjusted for covariates were also reported. The higher BMI values are associated with poor FIQ-R scores and overweight and obese women with FMS have higher symptom severity. The promotion of an optimal BMI might contribute to ameliorate some of the FMS symptoms.
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Objective The purpose of this study was to evaluate the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on cardiovascular disease (CVD) risk factors in adults with overweight and obesity. Methods Twenty-two articles were included by searching six databases, the total number of subjects was 620 in these articles. Outcomes were synthesised using a random-effects meta-analysis of the Standardized mean difference (SMD) in CVD risk factors. Results HIIT and MICT resulted in statistically significant reductions in Weight, BMI, fat%, total cholesterol(TC), and improvement in VO2max. Compared with MICT, subgroup of durations of HIIT training interval ≥2 min can significantly increase VO2max (SMD = 0.444, 95% CI:0.037~0.851,P = 0.032), subgroup of energy expenditure of HIIT equal to MICT can significantly increase VO2max (SMD = 0.399, 95% CI:0.106~0.692,P = 0.008). Conclusions HIIT appears to provide similar benefits to MICT for improving body composition, VO2maxand TC, but HIIT spent less time than MICT by 9.7 min on one session. HIIT is superior to MICT in improving cardiopulmonary fitness when durations of HIIT training interval ≥2 min or energy expenditure of HIIT same as MICT. PROSPERO ID: CRD42016045835.
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Introduction: The Medical Outcome Study Short Form 36 (SF-36) is widely used for measuring Health-Related Quality of Life (HRQoL) and has undergone rigorous psychometric evaluation using Classic Test Theory (CTT). However, Item Response Theory-based evaluation of the SF-36 has been limited with an overwhelming focus on individual scales and cross-sectional data. Purpose: This study aimed to examine the longitudinal item and category stability of the SF-36 using Rasch analysis. Method: Using data from the 1921-1926 cohort of the Australian Longitudinal Study on Women's Health, responses of the SF-36 from six waves of data collection were analysed. Rasch analysis using Winsteps version 3.92.0 was performed on all 36 items of the SF-36 and items that constitute the physical health and mental health scales. Results: Rasch analysis revealed issues with the SF-36 not detected using classical methods. Redundancy was seen for items on the total measure and both scales across all waves of data. Person separation indexes indicate that the measure lacks sensitivity to discriminate between high and low performances in this sample. The presence of Differential Item Functioning suggests that responses to items were influenced by locality and marital status. Conclusion: Previous evaluations of the SF-36 have relied on cross-sectional data; however, the findings of the current study demonstrate the longitudinal efficacy of the measure. Application of the Rasch Measurement Model indicated issues with internal consistency, generalisability, and sensitivity when the measure was evaluated as a whole and as both physical and mental health summary scales. Implications for future research are discussed.
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Background: Fibromyalgia (FM) is characterized by chronic and generalized musculoskeletal pain. There is currently no cure for FM, but palliative treatments are available. One type of treatment is strength training (ST). However, there is a need for more information on optimal training protocols, intensity, and volume needed to improve symptoms. The aim of this study was to analyze the effects of ST in the treatment of FM through a systematic review of experimental research. Methods: Medical Subject Headings search terms and electronic databases including Scientific Electronic Library Online, PubMed, Science Direct, Web of Science, and Physiotherapy Evidence Database were used to identify studies. Results: The inclusion criteria were met by 22 eligible studies. Most of the studies were conducted in the United States (36%), Finland (23%), Brazil (18%), and Sweden (18%). The studies showed that ST reduces the number of tender points, fatigue, depression, and anxiety, and improves sleep quality and quality of life in patients with FM. The intervention period ranged from 3 to 21 weeks, with sessions performed 2 times a week in 81.81% of the studies, at initial intensities of 40% of 1-repetition maximum. The repetitions ranged from 4 to 20, with no specific protocol defined for ST in FM. Conclusion: The main results included reduction in pain, fatigue, number of tender points, depression, and anxiety, with increased functional capacity and quality of life. Current evidence demonstrates that ST is beneficial and can be used to treat FM. Trial registration: CRD42016048480.
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We aimed to analyze the evidence on the effects of physical exercise in patients with fibromyalgia (FM) and to assess the characteristics of published studies, especially the quality of the evidence, through an umbrella review. This umbrella review followed the PRISMA guidelines and was documented in the PROSPERO registry (CRD42017075687). We searched the PubMed, Web of Science, SportDiscus, Scopus, Cinahl, and Cochrane Library databases. The methodological quality of systematic reviews was assessed using AMSTAR 2. We only selected systematic reviews (with or without meta-analyses) investigating the effects of any type of physical exercise in patients with FM syndrome. Thirty-seven systematic reviews (total = 477) fulfilled the criteria. Most studies were rated as being of low or moderate quality. A variety of exercises were used as treatment for FM symptoms, with positive results. Most of the reviews investigated the effects of aerobic exercise and strength training. No serious adverse events were reported. The largest effects of exercise were seen in terms of improved pain intensity and quality of life. Altogether, exercise may be an effective treatment for FM symptoms. Thus, aerobic exercise and strength training are effective programs for the treatment of FM. By summarizing the findings and effect sizes of the reviewed studies, we observed that the evidence for improvement of pain level and quality of life was the strongest. The results have potential to influence evidence-based practice. Future studies should analyze the long-term effects of exercise.
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Recently, high-intensity interval training (HIIT) has been recognized as a safe and effective alternative to moderate-intensity continuous training for older patients with cardiovascular disease (CVD) in cardiac rehabilitation settings in an effort to improve health outcomes. This brief review considers general principles and suggestions for prescription of HIIT for older patients with CVD, specific challenges pertaining to older adults, the physiologic mechanisms by which HIIT contributes to improvements in peak Vo2, and the effects of HIIT on cardiovascular health in older patients with coronary artery disease and heart failure.
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Background: Exercise training is commonly recommended for individuals with fibromyalgia. This review is one of a series of reviews about exercise training for fibromyalgia that will replace the review titled "Exercise for treating fibromyalgia syndrome", which was first published in 2002. Objectives: To evaluate the benefits and harms of mixed exercise training protocols that include two or more types of exercise (aerobic, resistance, flexibility) for adults with fibromyalgia against control (treatment as usual, wait list control), non exercise (e.g. biofeedback), or other exercise (e.g. mixed versus flexibility) interventions.Specific comparisons involving mixed exercise versus other exercises (e.g. resistance, aquatic, aerobic, flexibility, and whole body vibration exercises) were not assessed. Search methods: We searched the Cochrane Library, MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Thesis and Dissertations Abstracts, the Allied and Complementary Medicine Database (AMED), the Physiotherapy Evidence Databese (PEDro), Current Controlled Trials (to 2013), WHO ICTRP, and ClinicalTrials.gov up to December 2017, unrestricted by language, to identify all potentially relevant trials. Selection criteria: We included randomised controlled trials (RCTs) in adults with a diagnosis of fibromyalgia that compared mixed exercise interventions with other or no exercise interventions. Major outcomes were health-related quality of life (HRQL), pain, stiffness, fatigue, physical function, withdrawals, and adverse events. Data collection and analysis: Two review authors independently selected trials for inclusion, extracted data, and assessed risk of bias and the quality of evidence for major outcomes using the GRADE approach. Main results: We included 29 RCTs (2088 participants; 98% female; average age 51 years) that compared mixed exercise interventions (including at least two of the following: aerobic or cardiorespiratory, resistance or muscle strengthening exercise, and flexibility exercise) versus control (e.g. wait list), non-exercise (e.g. biofeedback), and other exercise interventions. Design flaws across studies led to selection, performance, detection, and selective reporting biases. We prioritised the findings of mixed exercise compared to control and present them fully here.Twenty-one trials (1253 participants) provided moderate-quality evidence for all major outcomes but stiffness (low quality). With the exception of withdrawals and adverse events, major outcome measures were self-reported and expressed on a 0 to 100 scale (lower values are best, negative mean differences (MDs) indicate improvement; we used a clinically important difference between groups of 15% relative difference). Results for mixed exercise versus control show that mean HRQL was 56 and 49 in the control and exercise groups, respectively (13 studies; 610 participants) with absolute improvement of 7% (3% better to 11% better) and relative improvement of 12% (6% better to 18% better). Mean pain was 58.6 and 53 in the control and exercise groups, respectively (15 studies; 832 participants) with absolute improvement of 5% (1% better to 9% better) and relative improvement of 9% (3% better to 15% better). Mean fatigue was 72 and 59 points in the control and exercise groups, respectively (1 study; 493 participants) with absolute improvement of 13% (8% better to 18% better) and relative improvement of 18% (11% better to 24% better). Mean stiffness was 68 and 61 in the control and exercise groups, respectively (5 studies; 261 participants) with absolute improvement of 7% (1% better to 12% better) and relative improvement of 9% (1% better to 17% better). Mean physical function was 49 and 38 in the control and exercise groups, respectively (9 studies; 477 participants) with absolute improvement of 11% (7% better to 15% better) and relative improvement of 22% (14% better to 30% better). Pooled analysis resulted in a moderate-quality risk ratio for all-cause withdrawals with similar rates across groups (11 per 100 and 12 per 100 in the control and intervention groups, respectively) (19 studies; 1065 participants; risk ratio (RR) 1.02, 95% confidence interval (CI) 0.69 to 1.51) with an absolute change of 1% (3% fewer to 5% more) and a relative change of 11% (28% fewer to 47% more). Across all 21 studies, no injuries or other adverse events were reported; however some participants experienced increased fibromyalgia symptoms (pain, soreness, or tiredness) during or after exercise. However due to low event rates, we are uncertain of the precise risks with exercise. Mixed exercise may improve HRQL and physical function and may decrease pain and fatigue; all-cause withdrawal was similar across groups, and mixed exercises may slightly reduce stiffness. For fatigue, physical function, HRQL, and stiffness, we cannot rule in or out a clinically relevant change, as the confidence intervals include both clinically important and unimportant effects.We found very low-quality evidence on long-term effects. In eight trials, HRQL, fatigue, and physical function improvement persisted at 6 to 52 or more weeks post intervention but improvements in stiffness and pain did not persist. Withdrawals and adverse events were not measured.It is uncertain whether mixed versus other non-exercise or other exercise interventions improve HRQL and physical function or decrease symptoms because the quality of evidence was very low. The interventions were heterogeneous, and results were often based on small single studies. Adverse events with these interventions were not measured, and thus uncertainty surrounds the risk of adverse events. Authors' conclusions: Compared to control, moderate-quality evidence indicates that mixed exercise probably improves HRQL, physical function, and fatigue, but this improvement may be small and clinically unimportant for some participants; physical function shows improvement in all participants. Withdrawal was similar across groups. Low-quality evidence suggests that mixed exercise may slightly improve stiffness. Very low-quality evidence indicates that we are 'uncertain' whether the long-term effects of mixed exercise are maintained for all outcomes; all-cause withdrawals and adverse events were not measured. Compared to other exercise or non-exercise interventions, we are uncertain about the effects of mixed exercise because we found only very low-quality evidence obtained from small, very heterogeneous trials. Although mixed exercise appears to be well tolerated (similar withdrawal rates across groups), evidence on adverse events is scarce, so we are uncertain about its safety. We downgraded the evidence from these trials due to imprecision (small trials), selection bias (e.g. allocation), blinding of participants and care providers or outcome assessors, and selective reporting.