Introduction
Methods
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• We used dppc2 instead of standardized mean difference (SMD) mentioned in our PROSPERO protocol because dppc2 also takes into account before-intervention values which can significantly influence the outcomes after the interventions.
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• The Cochrane Collaboration’s tool for assessing risk of bias was used instead of PEDro’s risk of bias tool based on Armijo-Livo et al.’s study, who pointed out that many trials that have adequate quality base on the PEDro cutoff of ≥5 points, do not meet the accepted quality standards such as generation of random sequence, concealment of allocation, and blinding of study assessors defined by the Cochrane risk of bias tool. Previous studies have shown that these features can have a substantial impact on the estimates of treatment effect [23].
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• We expanded our search to a larger number of databases such as PEDro because it is a physiotherapy-specific database and to perform a more comprehensive search.
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• We did not search Persian-language databases separately to avoid publication bias.
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• In addition, we did not limit our search to English language to avoid language bias.
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• We used the Mendeley desktop software because it was available free of charge and also provided more options.
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• We also used the Stata software for meta-analysis instead of RevMan for its better properties.
Study selection criteria
PICOS criteria for the study
Population
Intervention and comparator
Outcomes
Study design
Eligibility criteria
Search strategy
Data extraction
Quality (risk of bias) assessment
Statistical analysis
Assessment of publication bias
Sensitivity analysis
Results
Identification of studies
Overview of the included studies
Author, Year | Country | Prolotherapy group | Control group(s) | Needle | DPT interval | DPT frequency | Sample size | Age (years) Mean | Duration of symptoms Mean | Outcome measures | Follow-ups | Adverse events |
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Kim, 2014 [15] | Korea | Ultrasound-guided injection, 1.5 ml of 20% dextrose + 0.5 ml of 0.5% lidocaine (2 ml of 15% dextrose solution) | Ultrasound-guided injection, 2 ml of autologous PRP (Huons HC-1000 System) | 22-gauge | 2 weeks | 2 | 20 DPT (n = 11) PRP (n = 9) | DPT, 37.8 PRP, 36.2 | DPT, 2.9 y PRP, 2.8 y | FFI | 2 weeks (before the second injection) 10 weeks (2 months after the last injection) 28 weeks (6 months after the last injection) | None |
Ersen, 2018 [14] | Turkey | Ultrasound-guided injection, 3.6 ml of 15% dextrose + 0.4 ml lidocaine (4 ml of 13.5% dextrose solution) | Plantar fascia and Achilles tendon stretching exercises 3 times a week for 3 months + same exercise protocol on their own 3 times/day for the other days | 27-gauge | 3 weeks | 3 | 50 DPT (n = 26) Exercise (n = 24) | DPT, 45.1 Exercise, 46.3 | DPT, 32.8 m Exercise, 34.3 m | VAS, FFI, AOFAS | 21 days 42 days 90 days 360 days | None |
Ugurlar, 2018 [16] | Turkey | Ultrasound-guided injection, 3 ml of 5% dextrose + 1 ml of bupivacaine 5 mg/ml + 6 ml of 0.9% physiologic sodium chloride solution (10 ml of 1.5% dextrose solution) | 1. ESWT, 6 Hz, 2000 pulse, 4 bars 2. PRP, 2 ml prepared by Arthrex ACP Double Syringe System 3. Corticosteroid, 1 ml betamethasone 40 mg/ml + 2 ml bupivacaine 5 mg/ml | Not specified | 1 week | 3 | 158 DPT (n = 40) ESWT (n = 39) PRP (n = 39) Betamethasone (n = 40) | DPT, 37.5 ESWT, 39.2 PRP, 38.4 Betamethasone, 40.1 | DPT, 13.2 m ESWT, 15.7 m PRP, 13.9 m Betamethasone, 14.5 m | VAS, FFI-R | 1 month 3 months 6 months 12 months 24 months 36 months | None |
Umay Atlas, 2018 [13] | Turkey | 3 ml of 15% dextrose + plantar fasciitis exercise treatment | 3 ml of saline + plantar fasciitis exercise treatment | 22-gauge | 3 weeks | 3 | 30 DPT (n = 15) Saline (n = 15) | DPT, 47.06 Saline, 50.60 | DPT, 10.0 m Saline, 11.0 m | VAS, FFI, AOFAS | 3 months (after the first injection) | None |
Mansiz-Kaplan, 2020 [12] | Turkey | 5 ml of 30% dextrose + 4 ml of saline + 1 ml of 2% lidocaine (10 ml of 15% dextrose) | 9 ml of saline + 1 ml of 2% lidocaine | 22-gauge | 3 weeks | 2 | 65 DPT (n = 30) Saline (n = 30) | DPT, 46.7 Saline, 46.2 | Median of 7 m in both groups | VAS, FFI, PF thickness | 7 weeks (1 month after the last injection) 15 weeks (3 months after the last injection) | None |
Asheghan, 2020 [4] | Iran | Ultrasound-guided injection, 2 ml of 20% dextrose | Radial ESWT, 10 Hz, 2000 shock waves, 2 bars (3 sessions, 1 week apart) | 25-gauge | 1 week | 2 | 59 DPT (n = 30) ESWT (n = 29) | DPT, 46.5 ESWT, 43.7 | DPT, 4.5 m ESWT, 4.5 m | VAS, FAAM, PF thickness | 6 weeks (after the first treatment session) 12 weeks (after the first treatment session) | None |
Raissi, 2021 [11] | Iran | Ultrasound-guided injection, 2 ml of 20% dextrose + 1 ml of 1% lidocaine hydrochloride (3 ml of 13.33% dextrose solution) | Ultrasound-guided injection, 1 ml of 40 mg methylprednisolone plus 1 ml of normal saline + 1 ml of 1% lidocaine hydrochloride | 22-gauge | - | 1 | 40 DPT (n = 20) Methylprednisolone (n = 20) | DPT, 50.3 Methylprednisolone, 42.15 | > 8 weeks | NRS, FAAM, PF thickness | 2 weeks 12 weeks | None |
Kesikburun, 2021 [1] | Turkey | Ultrasound-guided injection, 1.5 ml of 30% dextrose + 1.5 ml of 2% lidocaine (3 ml of 15% dextrose) | Focused ESWT 4–6 Hz, 1800–2000 shock waves + Radial ESWT, 15–21 Hz, 3000–3500 pulses, 1.8–3.0 bars (3 sessions, 2 weeks apart) | 25-gauge | 2 weeks | 3 | 27 DPT (n = 15) ESWT (n = 14) | DPT, 57.4 ESWT, 51.2 | DPT, 12.6 m ESWT, 12.7 m | VAS, FFI | 6 weeks (after the last intervention) 12 weeks (after the intervention) | None |
Quality assessment
Author, Year | Selection bias | Performance bias | Detection bias | Attrition bias | Reporting bias | Total | ||
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Random sequence generation | Allocation concealment | Score | Category | |||||
Kim, 2014 [15] | Low | High | Low | Low | High | Low | 4 | High |
Ersen, 2018 [14] | Low | Unclear | High | Low | High | Low | 3 | High |
Ugurlar, 2018 [16] | Low | Unclear | High | High | Low | Low | 3 | High |
Umay Atlas, 2018 [13] | Low | Unclear | Low | Low | Low | Low | 5 | Unclear |
Mansiz-Kaplan, 2020 [12] | Low | Low | Low | Low | High | Low | 5 | High |
Asheghan, 2020 [4] | Low | Unclear | High | High | High | Low | 2 | High |
Raissi, 2021 [11] | Low | Unclear | Low | Low | High | Low | 4 | High |
Kesikburun, 2021 [1] | Low | Low | High | High | High | Low | 3 | High |
Immediate-term effects on pain
Short-term effects on pain
Long-term effects on pain
Immediate-term effects on foot function
Short-term effects on foot function
Long-term effects on foot function
Immediate-term effects on plantar fascia thickness
Short-term effects on plantar fascia thickness
Potential sources of heterogeneity
Potential factors | dppc2 (95% CI) | No. of studies | Heterogeneity χ2 | P-value | I2 | |
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Country | Iran | -0.158 (-0.729, 0.413) | 2 | 1.46 | 0.228 | 31.3% |
Turkey | -1.558 (-2.925, -0.190) | 5 | 68.39 | 0.000 | 94.2% | |
Korea | 0.278 (-0.768, 1.324) | 1 | - | - | - | |
Dextrose volume | < 10 ml | -0.778 (-1.653, 0.097) | 6 | 33.74 | 0.000 | 85.2% |
10 ml | -1.499 (-4.564, 1.566) | 2 | 44.58 | 0.000 | 97.8% | |
Dextrose concentration | ≥ 15% | -1.321 (-2.903, 0.261) | 5 | 64.71 | 0.000 | 93.8% |
< 15% | -.0.437 (-1.084, 0.210) | 3 | 6.77 | 0.034 | 70.5% | |
Needle | 22-gauge | -1.755 (-3.570, 0.061) | 4 | 45.10 | 0.000 | 93.3% |
25-gauge | -0.009 (-0.509, 0.492) | 2 | 0.36 | 0.546 | 0.0% | |
27-gauge | -0.997 (-1.682, -0.312) | 1 | - | - | - | |
Number of DPT sessions | 1 | -0.493 (-1.234, 0.248) | 1 | - | - | - |
2 | -0.908 (-3.054, 1.238) | 3 | 47.74 | 0.000 | 95.3% | |
3 | -1.138 (-2.391, 0.115) | 4 | 34.23 | 0.000 | 91.2% | |
Interval between DPT sessions | None | -0.493 (-1.234, 0.248) | 1 | - | - | - |
1 week | 0.061 (-0.286, 0.409) | 2 | 0.02 | 0.892 | 0.0% | |
2 weeks | -0.019 (-0.699, 0.661) | 2 | 0.54 | 0.463 | 0.0% | |
3 weeks | -2.577 (-4.296, -0.857) | 3 | 22.37 | 0.000 | 91.1% | |
Ultrasound guidance | Yes | -0.217 (-0.589, 0.154) | 6 | 8.78 | 0.118 | 43.1% |
No | -3.292 (-3.980, -2.605) | 2 | 0.88 | 0.347 | 0.0% | |
Use of anesthetics | Yes | -0.750 (-1.671, 0.171) | 6 | 49.26 | 0.000 | 89.8% |
No | -1.816 (-5.644, 2.013) | 2 | 29.15 | 0.000 | 96.6% | |
Blinding | Yes | -1.588 (-2.921, -0.255) | 5 | 46.96 | 0.000 | 91.5% |
No | 0.022 (-0.301, 0.346) | 3 | 0.39 | 0.823 | 0.0% | |
Performance bias | Low | -1.755 (-3.570, 0.061) | 4 | 45.10 | 0.000 | 93.3% |
High | -0.236 (-0.726, 0.253) | 4 | 7.35 | 0.062 | 59.2% | |
Detection bias | Low | -1.588 (-2.921, -2.255) | 5 | 46.96 | 0.000 | 91.5% |
High | 0.022 (-0.301, 0.346) | 3 | 0.39 | 0.823 | 0.0% | |
Attrition bias | Low | -0.747 (-1.694, 0.201) | 6 | 44.97 | 0.000 | 88.9% |
High | -1.834 (-5.613, 1.944) | 2 | 31.27 | 0.000 | 96.8% | |
Total bias | High | -0.623 (-1.405, 0.158) | 7 | 53.08 | 0.000 | 88.7% |
Unclear | -3.812 (-5.096, -2.529) | 1 | - | - | - |