Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

De, 2020

Type of study:

prospective, triple-blind, parallel group,

randomized, active-control trial

Setting and country:

Department of Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical

Sciences, New Delhi, India

Funding and conflicts of interest:

None

Inclusion criteria:

age > 18 years,

history of segmental LBP with radiation to the legs below the knee for more than 3 months, pain refractory to

conventional medical treatment with predominant leg pain over back pain involving up to 2 lumbar levels, and

average pain score ≥ 50 on a 100-point VAS with no bowel/bladder dysfunction

Exclusion criteria:

Patients with coagulopathy and/or on anticoagulants,

infection at the site of injection, hypersensitivity to LA and/or the radiographic contrast agent, signs of bilateral

radiating leg pain, evidence of significant sensory or motor deficit, presence of anatomical deformity of the spine and severe psychiatric illness, presence of cancer as a cause of

back pain, inability to communicate in Hindi/English,

history of previous back surgery or implant insertion, and presence of diabetes mellitus, multiple sclerosis, a cardiac pacemaker, or pregnancy

N total at baseline:

Intervention: 25

Control: 25

Important prognostic factors²:

age ± SD:

I: 41.92 ± 14.53

C: 41.4 ± 10.64

Sex:

I: 52% M

C: 36% M

Duration of pain, months

(mean ± SD)

I: 35.8 ± 22.4

C:38 ± 23.15

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

All patients received a selective diagnostic nerve root block (SNRB) with 1 mL 2% lidocaine. A positive

response was defined as 75% reduction in pain within 1 to 24 hours of injection.

The lumbar pulsed radiofrequency (LPRF) group received TF epidural 1 mL of 0.5% bupivacaine with PRF of the DRG.

Three cycles of PRF (2 Hz and 45 V) were applied for 180 seconds.

Describe  control (treatment/procedure/test):

All patients received a selective diagnostic nerve root block (SNRB) with 1 mL 2% lidocaine. A positive

response was defined as 75% reduction in pain within 1 to 24 hours of injection.

The LA group received TF epidural 1 mL of 0.5%

bupivacaine.

Length of follow-up:

Two weeks, 1 months, 2 months, 3 months, 6 months

Loss-to-follow-up:

None after randomization

Incomplete outcome data:

Intervention:

N = 0 (0%)

Control:

N = 0 (0%)

Outcome measures and effect size (include 95%CI and p-value if available):

VAS (0-100)

Baseline

I: 82.4 ± 9.69

C: 81.2 ± 10.53

3 months

I: 41.2 ± 5.26

C: 60.0 ± 7.64

6 months

I: 46.4 ± 5.69

C: 68.8 ± 8.81

Modified Oswestry Disability Questionnaire ODI score (%)

Baseline

I: 64.8  ± 11.23

C: 65.29 ± 9.58

3 months

I: 18.72 ± 4.73

C: 40.17 ± 7.69

6 months

I: 28.59 ± 5.44

C: 47.04 ± 7.34

“In the LPRF group, patients showed at 3 and 6 months 71.11%, and 55.87% reductions in ODI scores from baseline in the respective intervals

(Figures 8 and 9).”
In LA group, this was 34.87% and 27.95%.

Author’s conclusion:

“we can conclude that PRF

of the DRG applied for a longer duration results in long term pain relief and improvement in the functional quality of life in patients with chronic LRP. Experimental data have shown that PRF results in neuromodulatory effects on the DRG, resulting in pain relief with no side-effects.”

Khalifa, 2017

Type of study:

Setting and country:

Department of Anesthesia, Zagazig Faculty of Medicine, Zagazig, Egypt

Funding and conflicts of interest:

None

Inclusion criteria:

Patients with lumbar radiculopathy with MRI-proved LDP for more than 3 months with weak or no response to conservative treatment were included. Radicular

pain should be more than back pain if also associated.

Exclusion criteria:

Radiculopathy with irrelevant MRI finding;

Back pain more than radicular pain;

Spinal canal stenosis;

Failed back surgery;

Multiple disc degeneration;

Presence of motor or sphincteric disorders; Patients with work troubles or psychological

Problems; Patients who decided to shift to either surgery or

tramadol during the follow-up period.

N total at baseline:

Intervention: 50

Control: 50

Important prognostic factors²:

age ± SD:

I: 37.5±9

C: 39.3±8.8

Sex:

I: 62.2% M

C: 68.9% M

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

4 min of PRF at 42°C after positive sensory stimulation at 0.4–0.7 V and motor at 0.8–1.3 V on the affected

nerve roots, after which we injected 2 ml of 4 mg/ml

methylprednisolone solution in normal saline.

Describe  control (treatment/procedure/test):

we injected 3 ml of 8 mg/ml methylprednisolone solution in normal saline for each clinically affected lumbar root with positive MRI finding.

Length of follow-up:

One week; Four weeks;

eight weeks; 12 weeks

Loss-to-follow-up:

Intervention:

N =5 (10 %)

Reasons: lost communication (n=3); underwent spine surgery (n=2)

Control:

N = 5 (10%)

Reasons: underwent spine surgery (n=3); tramadol required before 3 months (n=2)

Incomplete outcome data:

NR

Outcome measures and effect size (include 95%CI and p-value if available):

VAS

Baseline

I: 7.53 ± 0.5
C: 7.5 ± 0.5

3 months

I: 4±1.2

C: 7.5±0.5

Author’s conclusion:

PRF of lumbar dorsal root ganglia is more effective than lumbar TES injection up to

3 months of follow-up in patients with radiculopathy due to lumbar disc prolapse.

Limitations

Long-term evaluations were

not reported; side effects were not reported

Koh, 2015

Type of study:

randomized, double-blinded, active-comparator controlled study

Setting and country:

pain management

clinic of the Asan Medical Center in Seoul, South

Korea

Funding and conflicts of interest:

None

Inclusion criteria:

age ≥20 years old, pain intensity ≥4 out of 10 on the numerical rating scale (NRS), chronic LRP lasting ≥12 weeks, dominant leg pain with less intense back pain, and the previous failure of conservative management such as physiotherapy, exercise therapy, or

analgesic medications. Epidural injections administered ≥12 weeks prior to recruitment were permitted because

most of the patients visiting our clinic had a history of interlaminar or transforaminal epidural injections. MRI was obtained in all patients and the diagnosis of spinal stenosis was confirmed. All eligible

patients received conventional diagnostic/therapeutic

fluoroscopy-guided TFEI with local anesthetics and steroid before enrolment. Patients who demonstrated

pain reduction (≥2–points or at least 30% reduction in NRS score) for short duration ≤6 weeks following epidural block were finally enrolled.

Exclusion criteria:

patient refusal to participate in

the study, age <20 years, unbearable pain >9–points on

NRS, pain <4–points on NRS, acute pain of onset lasting

<12 weeks, signs of progressive motor weakness or neurologic deficits, allergies to steroids or contrast dyes,

coagulopathy, steroid injection within the previous 12 weeks, systemic infection, injection site infection, malignancy, unstable medical or psychiatric condition, and

patients presenting with S1 radicular symptoms

N total at baseline:

Intervention: 31

Control: 31

Important prognostic factors²:

age ± SD:

I: 65.97 ± 7.25

C: 65.16 ± 8.96

Sex:

I: 35.5% M

C: 32.3% M

Total duration of pain (months), median (IQR)

I: 15 (29-36)

C: 13 (23-48)

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

In the experimental PRF group, three cycles of PRF were performed at 42°C for 120 seconds.

Describe  control (treatment/procedure/test):

In the control group, cannula positioning and the sensory/motor stimulation were performed using the same procedure as the PRF group, except the PRF generator was not activated.

Length of follow-up:

Four weeks, eight weeks, 12 weeks

Loss-to-follow-up:

Intervention:

N = 0

Control:

N = 0

Incomplete outcome data:

Intervention:

N = 7 (22.6%)

Reasons: lost to further follow-up

Control:

N = 6 (19.4%)

Reasons: lost to further follow-up

Outcome measures and effect size (include 95%CI and p-value if available):

NRS (0-10); median (95% CI)

Baseline

I: 7.39 (7.01–7.76)

C: 7.00 (6.57–7.43)

3 months

I: 5.69 (4.88–6.50)

C: 6.18 (5.50–6.87)

ODI (0-100%); median (95% CI)

Baseline

I: 45.07 (40.29–49.85)

C: 41.55 (36.55–46.55)

3 months

I: 37.62 (32.67–42.57)

C: 37.99 (32.53–43.44)

Patients satisfaction at 3 months (7-point Likert scale; %)

I: 32.3%

C: 16.1%

Author’s conclusion:

The TFEI provided significant short term pain relief and PRF can be applied in conjunction with TFEI to achieve higher treatment efficacy compared with TFEI alone.

Limitations:

Long-term evaluations were

not reported.

Lee, 2016

Type of study:

prospective randomized study

Setting and country:

Dongsan Medical Center, Keimyung University

School of Medicine, Daegu, Korea

Funding and conflicts of interest:

No conflicts of interest, academic funding

Inclusion criteria:

Age between 20 and 70 years; presentation with symptomatic cervical or lumbar radicular pain; Imaging findings of a cervical or lumbar intervertebral disc

pathology compatible with pain symptoms; Severe cervical or lumbar radicular pain than cervical or lumbar axial pain; Presentation with a VAS of > 4 and an ODI or Neck Disability

Index NDI of > 30% after first TFESI

Exclusion criteria:

Severe allergy to injectants; History of spine surgery; Spinal instability; Spinal stenosis or degenerative spondylolisthesis; Infection on the spine;

Tumor or tumor metastasis in the involved spinal area;

Pregnancy

N total at baseline*:

Intervention: 19

Control: 19

*lumbar procedures is only N I: 9; C: 11)

Important prognostic factors²:

age ± SD:

I: 54.3 ± 12.1

C: 50.8 ± 12.7

Sex:

I: 15.8% M

C: 57.9% M

Mean pain duration, weeks

I: 5.05

C: 4.79

Groups comparable at baseline?

Although subjects of our study were randomly allocated, PRF and TFESI group had statistical

differences in sex ratios.

Describe intervention (treatment/procedure/test):

PRF: The catheter needle was advanced toward the DRG until the patient reported a tingling sensation and/or dysesthesia at less than 0.3V. PRF treatment was administered at 5 Hz and a 5 ms pulsed width for 240

seconds at 45V under the constraint that the electrode tip temperature not exceed 42°C

Describe  control (treatment/procedure/test):

Patients received 2 mL of 0.125% bupivacaine mixed with 5 mg dexamethasone as 1st TFESI was conducted.

Length of follow-up:

Two weeks;

Four weeks;

eight weeks;

12 weeks

Loss-to-follow-up:

N = 6 (13.6%)

Reasons: drop-out (n=5), pain flare up (n=1)

Unknown in which group

Incomplete outcome data:

NR

Outcome measures and effect size (include 95%CI and p-value if available):

VAS (0-10), mean (SD)

Baseline

I: 4.8 (0.8)

C: 5.0 (1.0)

3 months

I: 2.8 (1.2)

C: 2.5 (1.5)

ODI score (0-100%), mean (SD)

Baseline

I: 46.6 (8.4)

C: 43.8 (10.0)

3 months

I: 21.8 (12.9)

C: 21.1 (14.3)

Author’s conclusion:

Mean VAS scores for cervical and lumbar radicular pain were significantly lower 12 weeks after treatment in both study groups. NDI and ODI scores also declined after treatment. However, no statistically significant difference was observed between the PRF and TFESI groups in terms of VAS, ODI, or NDI scores at any time during follow-up. PRF administered to a DRG might be as effective as TFESI in terms of attenuating radicular pain caused by disc herniation, and its use would avoid the adverse effects of steroid.

Limitations:

Small sample size; low

baseline VAS; long term

evaluations were not

reported.

Moore, 2020

Type of study:

randomised, triple-blinded, sham controlled

study

Setting and country:

Department of Pain Medicine, St James's Hospital, Dublin, Ireland

Funding and conflicts of interest:

Funding by Chronic Pain Research Fund and Abbvie scholarship. Nothing to declare.

Inclusion criteria:

aged 18–60 years,

described unilateral monosegmental radicular pain in the cervical or lumbosacral nerve roots, symptoms were consistent with MRI findings of a contained herniated disc at one level consistent with the clinical dermatome of complaint, had pain lasting more than 3 months, failed

conservative medical management (medication and physical therapy),

radicular pain was the primary complaint with minimal axial pain, and NRS score > 3

Exclusion criteria:

described atypical or bilateral radicular pain patterns, primarily back or neck pain, cognitive impairment or language barriers that could impair the patients understanding and reporting of outcomes, malignancy,

vertebral fractures, multiple sclerosis, connective tissue diseases, active

infection, pregnancy or breast feeding, prior spinal surgery, lumbar spine interventions in the last 6 months (including epidural injections or PRF), coagulation disorder or anti-coagulant treatment, psychiatric

disorder, allergy to local anaesthetics or contrast medium, and preoperative NSAID, corticosteroid, methotrexate, immunosuppressant

therapy or opioid therapy within the preceding six weeks. In addition, patients were excluded from the study if appropriate nerve stimulation during insertion of the RF needle or adequate pain relief (more than

50%) 1-h post DRG block were not achieved.

N total at baseline:

Intervention: 5

Control: 5

Important prognostic factors²:

age:

48 (range 35–60)

Sex:

45% M

Duration of pain (months):

291.7

Groups comparable at baseline?

Unknown, not reported per arm

Describe intervention (treatment/procedure/test):

The PRF group received one pulsed radiofrequency treatment to the DRG, settings: ≤ 42 °C, 120 s with 2 Hz pulses (20 milliseconds at 500,000 Hz) and output at 45 V.

Describe  control (treatment/procedure/test):

The sham group waited for 120 s with the RF needle in position, but the RF machine was turned off.

Length of follow-up:

Baseline, 1 month, 3 months, 6 months

Loss-to-follow-up:

Intervention:

N = 1 (20%)

Reasons: withdrew consent for 2^nd CSF sample (n=1)

Control:

N = 0

Incomplete outcome data:

NR

Outcome measures and effect size (include 95%CI and p-value if available):

NRS (0-10)

Baseline

I: 7.6

C: 6.8  ± 0.37

3 months

I: 2.6 ± 0.51

C: 6.8

6 months

MD: 2.8 points

GPE scores at 3 months (patient satisfaction), mean

I: 6

C: 4

Author’s conclusion:

This study confirms PRF is an effective treatment for chronic neuropathic radicular pain and superior to local anaesthetic administration on its own.

Limitations:

Very small study sample

Note:

In the current analysis, patients with cervical pain were excluded.

Napoli, 2023

Type of study:

prospective multicenter double-blind randomized clinical trial

Setting and country:

Department of Radiological, Oncological, and Pathological Sciences, Policlinico Umberto I–Sapienza University of Rome, Rome, Italy

Funding and conflicts of interest:

No problems noted.

Inclusion criteria:

Patients aged 18-75 y with unilateral radiculopathy, pain duration > 12 weeks, not responding to at least 1 attempt of conventional non-surgical therapy and pain intensity ≥ 4 on NRS underwent MRI. MRI findings: single-level posterolateral or intraforaminal disk herniation at L3-4 or L4-5 or L5-S1

Exclusion criteria:

Motor deficit, cauda equina syndrome, prior steroid injection, prior surgery, MRI contraindication

N total at baseline:

Intervention: 174

Control: 177

Important prognostic factors²:

age ± SD:

I: 55 ± 16

C: 54 ± 16

Sex:

I: 63% M

C: 64% M

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

In the PRF and TFESI group, therapeutic PRF was then

administered in one 10-minute session with E-dose control.

Once the appropriate spread of contrast material was confirmed using CT fluoroscopy, a local anesthetic mixed with steroid solution (1 mL lidocaine [20 mg per milliliter] and 2 mL dexamethasone [10 mg per milliliter] or 2 mL triamcinolone acetonide [40 mg per milliliter]) was administered immediately after the PRF administration,

Describe  control (treatment/procedure/test):

In participants undergoing TFESI alone, once the appropriate spread of contrast material was confirmed using CT fluoroscopy, a mixed local anesthetic and steroid solution identical to that used in the PRF and TFESI group was administered within 10 minutes to avoid temporal bias.

Length of follow-up:

1, 4, 12 and 52 weeks

Loss-to-follow-up:

Intervention:

N = 11 (6.3%)

Reasons: did not complete questionnaire at week 12 (n=4) or at week 52 (n=7)

Control:

N = 1 (0.6%)

Reasons: did not complete questionnaire at week 12 (n=1)

Incomplete outcome data:

NR

Outcome measures and effect size (include 95%CI and p-value if available):

NRS

Baseline

I: 8.1 ± 1.1

C: 7.9 ± 1.1

12 weeks

I: 1.7 ± 0.2

C: 4.1 ± 0.2

ODI score

Baseline

I: 52.0 ± 18.4
C: 54.7 ± 15.1

12 weeks

I: 14.5 ± 1.58

C: 29.0 ± 1.8

mean global perceived effect scale (-5 to +5), mean ± SD

I: 3.7 ± 0.3

C: 1.8 ± 0.2

Author’s conclusion:

: In the treatment of sciatica caused by lumbar disk herniation, pulsed radiofrequency combined with transforaminal epidural

steroid injection is more effective for pain relief and disability improvement than steroid injection alone.

Shanthanna, 2014

Type of study:

single-center, placebo-controlled, triple-blinded RCT

Setting and country:

Canada

Funding and conflicts of interest:

None

Inclusion criteria:

age 18 years or older; a history of CLR pain of at least 4 months’ duration; an average pain score of 5 on

a VAS of 0–10; and failure of conservative therapy (e.g.,

physiotherapy, medication trial). The patients were further

screened for clinical features of lumbosacral radicular pain.

Exclusion criteria:

Any contraindication to neuraxial injections, a history of predominant back pain over leg pain, significant anatomic deformity (either congenital or acquired) making it difficult to access the foramen as evidenced by CT/MRI, severe psychiatric illness, presence of cancer accounting for back pain, inability to communicate in English, allergy to local anesthetics or contrast medium,

and a history of motor findings in the affected leg

N total at baseline:

Intervention: 16

Control: 15

Important prognostic factors2:

Age (range):

I: 57 (35 - 83)

C: 57 (35 - 83)

Sex:

I: 62.5% M

C: 53.3% M

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

PRF at 42°C for 120

seconds to the DRG

Describe  control (treatment/procedure/test):

low intensity (<0.2 V) sensory stimulation (50 Hz),

without any active treatment for the same duration

Length of follow-up:

24 hours; one week; Four

weeks; eight weeks; 12 weeks

Loss-to-follow-up:

Intervention:
N = 2 (12.5%)

Reasons: surgery (n=1); reason unknown (n=1)

Control:

N = 1 (6.7%)

Reasons: inability to place needle (n=1)

Incomplete outcome data:

NR

Outcome measures and effect size (include 95%CI and p-value if available):

Mean VAS (0-10)

3 months

Shown in figures.

MD: -0.75 (95% CI -3.12, 1.63) in favor of PRF

ODI score

3 months

MD: -8 (95% CI -22, 7)

No separate data for intervention and control group reported.

Author’s conclusion:

At 3 months, the relative success of PRF-DRG was small. A large-scale trial to establish efficacy is not practically feasible considering the small effect size, which would necessitate recruitment of a challengingly large number

of participants over a number of years. Until clear parameters for application of PRF are established, clinicians will need to use their individual judgment regarding its clinical applicability, given the present evidence.

Limitations:

Small sample size; no initial

VAS data was included; long

term evaluation was not

reported.

Vigneri, 2020

Type of study:

RCT

Setting and country:

Pain Medicine Unit of Santa Maria Maddalena Hospital, Occhiobello, Italy

Funding and conflicts of interest:

None

Inclusion criteria:

older than or equal to 18 years with: single leg-radiating pain (with or without LBP) confirmed by clinical examination and lasting for >6 months,  unresponsiveness to oral medications, physical therapy, or

ultrasound-guided caudal or periradicular injections, MRI showing neural compression or spinal canal narrowing and/or electromyographic test suggestive of radiculopathy, and the presence of definite or probable NP

Exclusion criteria:

LBP more severe than radiating pain, a possible or unlikely NP, MRI not  consistent with clinical symptoms, pain improvement after previous treatments, patients affected by central neurological impairment or peripheral distal neuropathies in the lower limbs, certified psychiatric disorders, radiculopathies with significant motor deficits requiring urgent surgery (eg, cauda equina syndrome), and  reported allergy to anesthetics

N total at baseline:

I: 21

C: 20

Important prognostic factors2:

Age (SD):

I: 56.8 (12.1)

C: 56.1 (12.5)

Sex:

I: 71.4% M

C: 40% M

Duration of pain, mean (SD) (y)

I: 3.7 (4.9)

C: 3.7 (5.0)

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

each patient in this group received PRF for 2 cycles of 240 seconds each at a

frequency of 2-Hz (20 ms of current and 480 ms without

stimulation resulting in 2 active phases/second), voltage between 65 and 80 V, and a tip temperature of 42°C. After 5 minutes, a 2 mL injection containing 0.25% of bupivacaine

was delivered and, if no motor impairment occurred in the next 15 minutes, followed by the administration of 3 mL of

the contrast medium iopamidol to observe the myelogram spreading to the nerve root of interest.

Describe  control (treatment/procedure/test):

2 cycles of sham sensory stimulation were done to give a tingling sensation radiating to the painful area. The catheter was placed using the same procedure as the PRF-EA group and sensory

stimulation with no active treatment was delivered for 2 cycles of 240 seconds

Length of follow-up:

Baseline, 1 and 6 months

Loss-to-follow-up:

Intervention:

None

Control:

None

Incomplete outcome data:

NR

Outcome measures and effect size (include 95%CI and p-value if available):

Mean NRS (0-10), mean (SD)

Baseline

I: 7.67 (0.91)

C: 7.55 (1.10)

6 months

I: 4.33 (2.71)

C: 6.75 (2.00)

ODI, mean (SD)

Baseline

I: 35.83 (9.23)

C: 38.00 (10.75)

6 months

I: 20.71 (15.43)

C: 31.38 (13.29)

Author’s conclusion:

High-voltage PRF of dorsal root ganglion delivered

through multifunctional electrode provided significant pain relief and may be considered a valuable treatment in chronic lumbosacral radicular pain with neuropathic features.

Study reference

(first author, publication year)

Was the allocation sequence adequately generated?

Definitely yes

Probably yes

Probably no

Definitely no

Was the allocation adequately concealed?

Definitely yes

Probably yes

Probably no

Definitely no

Blinding: Was knowledge of the allocated

interventions adequately prevented?

Were patients blinded?

Were healthcare providers blinded?

Were data collectors blinded?

Were outcome assessors blinded?

Were data analysts blinded?

Definitely yes

Probably yes

Probably no

Definitely no

Was loss to follow-up (missing outcome data) infrequent?

Definitely yes

Probably yes

Probably no

Definitely no

Are reports of the study free of selective outcome reporting?

Definitely yes

Probably yes

Probably no

Definitely no

Was the study apparently free of other problems that could put it at a risk of bias?

Definitely yes

Probably yes

Probably no

Definitely no

Overall risk of bias

If applicable/necessary, per outcome measure

LOW

Some concerns

HIGH

De, 2020

Probably yes;

The technician operating the computer-generated random number table machine was not involved in the study.

Probably yes;

Sealed opaque envelopes were opened by the technician not involved in the study.

Probably yes;

Patient, physician, and outcome assessor were blinded. Statisticians were not mentioned.

Probably yes;

No patients were lost to follow-up after randomization.

No information

Definitely yes

No other problems noted

LOW

(all outcomes)

Khalifa, 2017

Probably yes;

Reason: Randomly allocated through closed envelope

Probably no;

Reason: Not reported

Probably yes;

Reason: Patients and the assessing physician were blinded

Probably no;

Reason: Loss to follow-up was infrequent and equal in both groups (10%)

No information

Definitely yes

No other problems noted

LOW

(all outcomes)

Koh, 2015

Probably yes;

Reason: computer-based randomization

Probably no;

Reason: Not reported

Probably yes;

Reason: patients and the outcome assessor were blinded.

Probably no;

Reason: there were missing data at follow-up at each evaluation stage (seven subjects in the fourth week, 10 subjects in the eighth week, and 13 subjects in the twelfth week – similar in both groups).

Probably yes;

Reason: Research protocol registration number was included

Definitely yes

No other problems noted

Some concerns

(all outcomes)

Reason: loss to follow-up

Lee, 2016

Probably no;

Reason: study is randomized, yet method is not described

Probably no;

Reason: Not reported

Definitely no;

Reason: No blinding

Probably yes;

Reason: loss to follow-up is infrequent and reasons are described. It is not mentioned in which group patients were lost to follow-up.

Probably yes;

Reason: Research protocol registration number was included

Definitely yes

No other problems noted

HIGH

(all outcomes)

Reason: lack of blinding

Moore, 2020

Definitely yes;

Reason: Randomisation was performed by an independent Clinical

Nurse Specialist using a computerised, random number generator.

Probably yes;

Reason: A randomisation envelope is mentioned, but no further details are provided.

Probably yes;

Reason: The

clinician, the patient and the independent data collectors were all

blinded to the randomisation until the study was completed.

Probably yes;

Reason: loss to follow-up is infrequent

No information

Definitely yes

No other problems noted

LOW

(all outcomes)

Napoli, 2023

Probably yes;

Reason: A computer-generated permuted-block scheme was used for randomization, with unstratified variable-block sizes of 2 and 4. An independent statistician generated the randomization sequence.

Probably yes;

Reason: conceal allocations in sealed opaque envelopes

Probably yes;

Reason: principal investigator at each site who assessed the outcomes and participants, was blinded to randomization and treatment; the treating physician could not be blinded. An independent statistician was blinded too.

Probably yes;

Reason: loss to follow-up is infrequent in both groups

Probably yes;

Reason: Research protocol registration number was included

Definitely yes

No other problems noted

LOW

(all outcomes)

Shanthanna, 2014

Probably yes;

Reason: randomization technique was carried out by the sealed opaque envelope method

Probably yes;

Reason: randomization technique was carried out by the sealed opaque envelope method

Probably yes;

Reason: patients, caregivers, and outcome assessors were blinded

Probably yes;

Reason: loss to follow-up is infrequent in both groups

Probably yes;

Reason: Research protocol registration number was included

Definitely yes

No other problems noted

LOW

(all outcomes)

Vigneri, 2020

Probably yes;

Reason: participants were randomized in a 1:1 ratio by computerized system

Probably yes;

Reason: Results of allocation were put

in a sealed envelope and delivered to the only nurse with access to the PRF generator and aware of stimulation/sham

progress

Probably yes;

Reason: patients,

treating physicians and assessors were blinded to intervention.

Probably yes;

Reason: No loss to follow-up

No information

Definitely yes

No other problems noted

LOW

(all outcomes)