Non-drug Approaches to Treating Raynaud’s Phenomenon


First author, year, country

Study funding source

Treatment group

Control group

Core inclusion criteria

Number of patients randomized/analyzed

Mean age (years)

Females (%)

Primary outcomes

Key secondary outcomes

Behavioral approaches

Büttner, 1991, Germany [6]

NR

Biofeedback three times per week for 5 weeks

Hand exercises three times per week for 5 weeks (placebo intervention)

RP

Tx: NR/10

35–59

NR

Number attacks pre-post

Duration of attacks

Tx = 4.8–3.4

Tx = reduction from 17 to 15 min

Control: NR/10

Control 3.9–3.1

Control = reduction from 28 to 21 min

P = NS

P = < 0.05 for difference between groups before and after intervention

Freedman, 1983, USA [18]

NHLBI

1. Temperature biofeedback in 10 biweekly sessions

Sham frontalis EMG bio-feedback in 10 biweekly sessions

Primary RP

Tx (1): NR/8

20–65

Overall: 88

Decrease in attack frequency

None

Tx (2): NR/8

Tx (3): NR/8

Control: NR/8

Tx (1): 93 %

2. Temperature biofeedback under cold stress in 10 biweekly sessions

Tx (2): 67 %

Tx (3): 33 %

3. Autogenic training in ten biweekly sessions

Control: 17 %

P < 0.05 for 1 and 2, but not 3, versus control

Freedman, 1984, USA [17]

NHLBI

1. Temperature biofeedback in ten biweekly sessions

Sham frontalis EMG biofeedback in ten biweekly sessions

RP secondary to systemic sclerosis

Tx (1): NR/8

NR

Overall: 92

Decrease in attack frequency

None

Tx (2): NR/8

No significant differences

Control: NR/8

2. Autogenic training in ten biweekly sessions

Guglielmi, 1982, USA [26]

Rehabilitation Services Administration

Skin temperature biofeedback

1. Sham biofeedback (EMG relaxation of forehead muscles)

RP, not taking vasoactive medication or medication for Raynaud’s

Tx: 12/12

Tx: 33

NR

Total attacks in 5 months

None

Tx: 225

Control (1): 204

Control (1): 34

Control (2): 254

Control (1): 12/12

2. No treatment

P = NS

Control (2): 34

Control (2): 15/12

Raynaud’s Treatment Study Investigators, 2000, USA [57]

NIH

Temperature biofeedback with suggestions for warmth imagery and passive volition delivered in ten 1-h sessions over 5–10 weeksa

Sham (frontalis muscle

Surface EMG biofeedback) delivered in ten 1-h sessions over 5-10 weeksa

Primary RP with ≥2 attacks per day during previous cold season

Tx: 81/81

Tx: 44

Overall: 70b

Daily attacks at 1 year c

Daily attacks at 2 months c

Tx = 0.23

Tx = 0.12

Control: 74/74

Control: 46

Control = 0.16

Control = 0.15

P = 0.38

P = 0.57

Sporbeck, 2012, Germany [63]

Physiomed Elektromedizin AG

Biofeedback three times per week for 4 weeks

Waiting list

RP secondary to systemic sclerosis

Tx: NR/8

Tx: 50

Tx: 88

Scleroderma VAS RP item at 4 weeks

Scleroderma VAS RP item at 12 weeks

Tx = NR

Tx = NR

Control: NR/10

Control: 59

Control: 90

Control = NR

Control = NR

P = 0.021 (favors Tx)

P = 0.093 (favors Tx)

Surwit, 1978, USA [67]

NIMH

Autogenic relaxation training or autogenic relaxation training with biofeedback during six biweekly sessions

Waiting list

Primary RP

Tx: NRd/15

23–54

100

Number attacks pre-post

Attack intensity

Control: NRd/15

Greater reduction in Tx group

Tx = 32 % reduction

P = NS

Control = 10 % reduction

P = NS

Other approaches

Al-Awami, 2004, Austria [1]

NR

Low level laser therapy every other day for ten sessions total

Sham level laser therapy every other day for ten sessions total

RP for 2 years or more with average of ≥4 episodes per week, age 18–65

Tx: NR/24

Median age:

Tx: 67

Daily attacks at 6 weeks

Daily attacks at 3 months

Control: 91

Control: NR/23

Tx: 45

Tx = 3

Tx = 3

Control: 46

Control = 5

Control = 6

P = 0.007

P = 0.02

Severity attacks (0–10) at 6 weeks

Severity attacks (0–10) at 3 months

Tx = 1

Tx = 0

Control = 4

Control = 4

P = 0.02

P = 0.04

Appiah, 1997, Germany [2]

NR

Acupuncture with seven treatments over 2 weeks

No treatment

Age 18–60 years, primary RP

Tx: NR/17

Tx: 46

Tx: 71

Daily attacks e

None

Tx = reduction from 1.4 to 0.6

Control: NR/16

Control: 42

Control: 69

Control = reduction from 1.6 to 1.2

P = NS

Hahn, 2004, Germany [27]

NR

Acupuncture weekly for 8 weeks

Sham acupuncture weekly for 8 weeks

Secondary RP

Tx: NR/11

Tx: 47

Tx: 91

Daily attacks

Duration attacks

Tx = reduction from 15 to 12 min

Tx = reduction from 1.9 to 1.4

Control = reduction from 31 to 16 min

P = NS

Control: NR/8

Control: 41

Control: 75

Control = reduction from 2.8 to 1.8

Severity attacks (0–5)

Tx = reduction from 2.6 to 2.1

P = NS

Control = reduction from 3.0 to 3.0

P = NS

Hirschl, 2002, Austria [33]

NR

Low level laser therapy for 30–40 min in five sessions per week for 3 weeks

Sham laser therapy for 30–40 min in five sessions per week for 3 weeks

Primary RP

Crossover design: 18 (15)

53

80

Daily attacks (1–5)f

None

Tx = 0.67

Control = 0.72

P = 0.520g

Hirschl, 2004, Austria [34]

NR

low level laser therapy for 30–40 min in five sessions per week for 3 weeks

sham laser therapy for 30–40 min in five sessions per week for 3 weeks

primary RP and not taking vasoactive medication

Crossover design: 50 (48)

46

79

Intensity of attacks (1–5)f

Daily attacks f

Tx = 2.3

Tx = 1.6

Control = 2.8

Control = 2.0

P < 0.001g

P = 0.001g

Ko, 2002, Canada [43]

Thermoflow

Ceramic-impregnated gloves for 3 months

Placebo gloves for 3 months

Age ≥ 18 years, “Pal” questionnaire criteria for RP

Tx: 49/30

Tx: 52

Tx: 67

Pain VAS e

None

Tx = 50.8

Control: 44/30h

Control = 57.9

Control: 54

Control: 87

Sporbeck, 2012, Germany [63]

Physiomed Elektromedizin

Deep oscillation three times per week for 4 weeks

Waiting list

RP secondary to systemic sclerosis

Tx: NR/10

Tx: 53

Tx: 80

Scleroderma VAS RP item at 4 weeks

Scleroderma VAS RP item at 12 weeks

Tx = NR

Tx = NR

Control: NR/10

Control: 59

Control: 90

Control = NR

Control = NR

P = 0.055 (favors Tx)

P = 0.081 (favors Tx)


EMG = electromyographic; NHLBI = National Heart, Lung, and Blood Institute; NIH = National Institutes of Health; NIMH = National Institutes of Mental Health; NR = not reported; NS = not statistically significant; RP = Raynaud phenomenon; Tx = treatment; VAS = visual analog scale

aTrial also included separate sustained-release nifedipine versus placebo comparison

bIncluded all four trial arms

cGeometric means adjusted for baseline values and clinical center. Intent to treat analysis used to include all randomized patients

dA total of 32 patients were randomized, of which data were reported for 30

eAppears to be a statistically significant different, although no between groups results were reported, and these could not be calculated because the number of patients included in means was not reported

fData presented here for third of 3 weeks of treatment

g P value for multiple assessments over 3-week period

hTrial report described a regression approach to imputation for missing data, but not possible to determine if imputed data presented




Table 19.2
Assessment of risk of bias in randomized controlled trials of non-drug treatments for Raynaud’s phenomenon










































































































































































Trial, year, country
Cochrane risk of bias tool domains

Random sequence generation
Allocation concealment
Blinding of participants and personnel
Blinding of outcome assessmenta

Incomplete outcome data
Selective outcome reporting
Study funding and author–industry financial tiesa

Other sources of bias

Behavioral approaches

Büttner, 1991, Germany [6]
Unclear risk
Unclear risk
Low risk
Low risk
Unclear risk
Unclear risk
Low risk
Low risk

Freedman, 1983, USA [18]
Unclear risk
Unclear risk
Low risk
Low risk
Unclear risk
Unclear risk
Low risk
Low risk

Freedman, 1984, USA [17]
Unclear risk
Unclear risk
Low risk
Low risk
Unclear risk
Unclear risk
Low risk
Low risk

Guglielmi, 1982, USA [26]
Unclear risk
Unclear risk
Low risk
Low risk
Low risk
Low risk
Low risk
Low risk

Raynaud’s Treatment Study Investigators 2000, USA [57]
Low risk
Low risk
Unclear risk
Unclear risk
Low risk
Low risk
Low risk
Low risk

Sporbeck, 2012, Germany [63]
Unclear risk
Unclear risk
High risk
High risk
Unclear risk
Unclear risk
Low risk
Low risk

Surwit, 1978, USA [67]
Unclear risk
Unclear risk
High risk
High risk
Low risk
Unclear risk
Low risk
Low risk

Other approaches

Al-Awami, 2004, Austria [1]
Low risk
Low risk
Low risk
Low risk
Unclear risk
Unclear risk
Unclear risk
Low risk

Appiah, 1997, Germany [2]
Unclear risk
Unclear risk
High risk
High Risk
Unclear risk
Unclear risk
Low risk
Low risk

Hahn, 2004, Germany [27]
Unclear risk
Unclear risk
Unclear risk
Low risk
Unclear risk
Unclear risk
Low risk
Low risk

Hirschl, 2002, Austria [33]
Unclear risk
Unclear risk
Low risk
Low risk
Low risk
Unclear risk
Unclear risk
Low risk

Hirschl, 2004, Austria [34]
Unclear risk
Unclear risk
Low risk
Low risk
Low risk
Unclear risk
Unclear risk
Low risk

Ko, 2002, Canada [43]
Low risk
Unclear risk
Low risk
Low risk
Unclear risk
Unclear risk
High risk
Low risk

Sporbeck, 2012, Germany [63]
Unclear risk
Unclear risk
High risk
High risk
Unclear risk
Unclear risk
High risk
Low risk


aAdditional domain added to standard Cochrane Risk of Bias tool [59, 60]


Our descriptions of RCTs are focused on outcomes directly relevant to RP attacks, and risk of bias ratings done using the Cochrane Risk of Bias tool, a standard evaluation system for RCTs [32]. The Cochrane Risk of Bias tool is used to evaluate the design and execution of individual RCTs and identify factors that could influence the validity of published results from RCTs. Domains of the Risk of Bias tool include randomization sequence generation; allocation concealment; blinding of participants, personnel, and outcome assessors; handling of incomplete outcome data; selective outcome reporting, and other possible sources of bias. Based on evidence that study sponsorship and author–industry financial ties are associated with outcomes [59, 60], we evaluated the risk of bias from this factor as well. See Table 19.3 for descriptions of Risk of Bias domains. In addition to bias, in evaluating RCTs, we considered the sample size of the RCTs. It is increasingly well documented that results from small, substantially underpowered trials are highly imprecise. Due to publication biases, very small trials that are published often report large and statistically significant effects that are false positives and do not replicate in larger, well-conducted studies, whereas very small studies with negative findings are typically not published [38, 39].
Tags:
Jun 3, 2017 | Posted by in RHEUMATOLOGY | Comments Off on Non-drug Approaches to Treating Raynaud’s Phenomenon

Full access? Get Clinical Tree
Get Clinical Tree app for offline access