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Treatment of chronic rhinosinusitis using low level laser: a single blind placebo
controlled clinical trial

Article  in  Physiotherapy · May 2015


DOI: 10.1016/j.physio.2015.03.1948

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Physiotherapy Theory and Practice, 29(8):596–603, 2013
Copyright © Informa Healthcare USA, Inc.
ISSN: 0959-3985 print/1532-5040 online
DOI: 10.3109/09593985.2013.775204

RESEARCH REPORT

A pilot study into the effect of low-level laser therapy in


patients with chronic rhinosinusitis
Soofia Naghdi1, PhD, PT, Noureddin Nakhostin Ansari1, PhD, PT, Mojtaba Fathali2, MD,
Jim Bartley3, FRACS, Mitra Varedi4, BSc, PT and Roshanak Honarpishe5, BSc, PT
1
Assistant Professor, Department of Physiotherapy, School of Rehabilitation, Tehran University of Medical Sciences,
Tehran, Iran
Physiother Theory Pract Downloaded from informahealthcare.com by Cornell University on 10/12/13

2
Surgeon and Specialist in Ear, Nose and Throat, School of Rehabilitation, Tehran University of Medical Sciences,
Tehran, Iran
3
Surgeon and Specialist in Ear, Nose and Throat, Institute of Biomedical Technologies, Auckland University of
Technology, Auckland, New Zealand
4
Currently MSc student in Physiotherapy, Department of Physiotherapy, School of Rehabilitation, Tehran University of
Medical Sciences, Tehran, Iran
5
Department of Physiotherapy, School of Rehabilitation, Tehran University of Medical Sciences, Tehran, Iran
For personal use only.

ABSTRACT
Chronic rhinosinusitis (CRS) is a common inflammatory disease of the nose and paranasal sinuses that has a sig-
nificant impact on patients’ quality of life. No study has examined the effectiveness of applying low-level laser
therapy (LLLT) locally over the sinuses in patients with CRS. The aim of this study was to evaluate the effect of
LLLT in patients with CRS. Fifteen adult patients with CRS participated in this pilot pretest–posttest clinical
study. Patients were treated with a 830-nm Ga-Al-As laser in continuous-wave mode at a power output of
30 mW and energy dose of 1 J. Laser irradiation was delivered on six points over each maxillary or frontal sinus
with 33 sec irradiation for each point and a total treatment duration of 198 sec for each sinus. Patients were
given LLLT three times per week for ten treatment sessions. Patients were asked to score their symptoms in accord-
ance with a four-point scale (0–3), and a total symptom score (TSS) for each patient was calculated. Percentage
improvement of TSS was considered as the primary outcome measure. TSS was calculated at baseline (T0), at
2 weeks (T1) and at 4 weeks (T2). The TSS was improved significantly at T1 (39%) and at T2 (46.34%). A large
effect size for LLLT was found (η2p η2p = 0.63). The therapeutic effect was sustained for a mean of 5 months. This
pilot study indicates that LLLT applied for 4 weeks improves symptoms in patients with CRS.

INTRODUCTION
Chronic rhinosinusitis (CRS) is an inflammatory Nevertheless, the terms rhinosinusitis and sinusitis
disease of the nose and paranasal sinuses with symp- can be used interchangeably (Meltzer and Hamilos,
toms that persist for at least 12 weeks with no 2011; Rosenfeld et al, 2007). CRS can have a signifi-
symptom resolution despite adequate medical treat- cant impact on patients’ quality of life.
ment. “Rhinosinusitis” is the current preferred termi- CRS symptoms, which are similar to those of acute
nology because sinus mucosa inflammation almost rhinosinusitis, may include a combination of nasal con-
always occurs with concomitant nasal inflammation. gestion, purulent rhinorrhea, facial pain/pressure, post-
nasal drainage (PND), headache, anosmia (loss of
sense of smell), and cough (Slavin et al, 2005). CRS
Accepted for publication 6 February 2013 appears to have a multifactorial etiology (Benninger
et al, 2003; Eccles, 2011; Marple et al, 2009); associ-
Address correspondence to Dr Soofia Naghdi, Department of Phy-
siotherapy, School of Rehabilitation, Tehran University of Medical ations have also been found between CRS prevalence
Sciences, Tehran, Iran. E-mail: naghdi@sina.tums.ac.ir and environmental factors (Hamilos, 2011). Bacterial

596
Physiotherapy Theory and Practice 597

biofilms have been hypothesized to have an important have evaluated the effectiveness of LLLT in treating
role in the pathogenesis of CRS (Hunsaker and Leid, patients with sinusitis (Krespi and Kizhner, 2011;
2008; Payne, Borish, and Steinke, 2011; Smith, Moustsen, Vinter, Aas-Andersen, and Kragstrup,
Buchinsky, and Post, 2011). The overall consensus is 1991). Krespi and Kizhner (2011) used near-infrared
that CRS is an inflammatory disease (Kilty and Desro- laser Illumination (NILI), with or without photoacti-
siers, 2008; Marple et al, 2009), and inflammation vated (PA) agents in managing symptomatic postsurgi-
from infectious and non-infectious factors plays a key cal patients with CRS. They used a 2-m long diffuser
role in CRS pathogenesis (Eloy et al, 2011; Hamilos, fiber with an active illuminating tip to apply laser intern-
2000; Van Crombruggen et al, 2011). ally to the nasal passage and sinuses. NILI was effective
Systemic antibiotics are often ineffective in the in managing CRS, and the therapeutic effect was main-
treatment of bacterial biofilm infections (Harvey and tained for at least 2 months. A Danish trial, which used
Lund, 2007; Kariyawasam and Scadding, 2011). In LLLT (Ga-Al-As laser, 30 mW/830 nm) for patients in a
the absence of anatomical obstruction, the current general practice setting with acute sinusitis found no
Physiother Theory Pract Downloaded from informahealthcare.com by Cornell University on 10/12/13

evidence indicates that functional endoscopic sinus statistical difference between laser and placebo groups
surgery provides no additional benefit to that obtained (Moustsen, Vinter, Aas-Andersen, and Kragstrup,
by medical treatment (Cherry and Li, 2008; Khalil 1991). In this pilot study, we attempted to identify the
and Nunez, 2006). These CRS treatment difficulties effect of LLLT in patients with CRS refractory to
have led clinicians and researchers to explore new medical treatments, applying LLLT externally over the
therapeutic modalities such as therapeutic ultrasound maxillary and frontal sinuses.
and laser therapy (Ansari, Naghdi, Farhadi, and Jalaie,
2007; Bartley and Young, 2009; Krespi and Kizhner,
2011; Nakhostin Ansari, Naghdi, and Farhadi, 2004; METHODS
Young, Morton, and Bartley, 2010).
Low-level laser therapy (LLLT) is one of the electro-
For personal use only.

Study design
physical agents used in physiotherapy to treat a wide
range of pathologies (Bjordal, Lopes-Martins, Joensen, This study was designed as a pretest–posttest clinical
and Iversen, 2010; Hashmi et al, 2010). Three proper- trial to evaluate the effects of LLLT in patients with
ties of a laser light in comparison with other forms of CRS. The study was approved by the Research
light are: 1) monochromacity; 2) collimation; and 3) Council, School of Rehabilitation, and the Ethics
coherence. LLLT devices use helium–neon (HeNe), Committee of the Tehran University of Medical
and gallium–aluminum–arsenide (Ga-Al-As or Ga-As) Sciences (TUMS). All subjects gave informed
to emit a laser light. LLLT is a form of phototherapy consent. All the patients were recruited and referred
that delivers low-power (≤500 mW) coherent and colli- for treatment at the physiotherapy clinic in the
mated beam of light of a single wavelength (Belanger, School of Rehabilitation, TUMS, by a surgeon and
2010). The photobiomodulation via photochemical specialist in Ear, Nose, and Throat (ENT).
reactions that LLLT induces at a cellular level is referred
to as biostimulation or photobiology (Reddy, 2004).
The photobiomodulation effect of LLLT is attribu- Participants
ted to non-thermal events. It involves the absorption of
photon radiation by chromophores such as cytochrome Patients ≥18 years of age who had symptoms compati-
c oxidase within the mitochondria leading to release of ble with maxillary or frontal CRS, with or without
nitric oxide (NO), and an increase in ATP levels polyp formation, verified by positive CT findings,
(Karu, 1999; Karu, Pyatibrat, and Afanasyeva, 2005). and who had failed medical or surgical therapy were
These events can lead to modulation of cell metabolism, included in the study. Exclusion criteria were: taking
normalization of cell function, inflammation reduction, drugs concurrently; or having a medical pathology
pain relief, and tissue repair (Bjordal et al, 2006; Ferreira for which LLLT is contraindicated.
et al, 2005; Karu, 1999). There is strong evidence that
LLLT used by physiotherapists has anti-inflammatory
effects (Bjordal, Lopes-Martins, Joensen, and Iversen, Outcome measures
2010). In a recent in vitro study, researchers demon-
strated that laser has bacterial biofilm treatment poten- The primary outcome measure was percent improve-
tial; a significant bacterial count reduction was ment of the total symptom score (TSS; Meltzer
achieved in an animal model of acute bacterial rhinosi- et al, 2006). Before and after treatment, patients
nusitis (Krespi, Kizhner, and Kara, 2009; Krespi et al, scored their symptoms (facial pain/pressure, head-
2011). To our knowledge, only two studies to date ache, nasal obstruction, nasal discharge, PND, smell

Physiotherapy Theory and Practice


598 Naghdi et al.

disturbance, fatigue, cough, and overall discomfort) in forehead, for the maxillary and frontal sinuses,
accordance with a four-point scale (0–3) correspond- respectively. A contact technique was used with
ing to none, mild, moderate, or severe. The scores ob- patients wearing laser safety goggles in a supine lying
tained for nine symptoms were summed to obtain a position, and the laser beam was kept stationary and
‘Total Symptom Score’ (TSS). The percent improve- perpendicular to the skin. Six points over each maxil-
ment of the TSS was calculated as the total score pre- lary or frontal sinus were determined (Figure 1). Laser
treatment minus total score posttreatment divided by irradiation was delivered in continuous-wave mode
total score pretreatment multiplied by 100. The with 33 sec irradiation for each point and a total treat-
percent improvement of TSSs were classified as ment duration of 198 sec for each affected maxillary or
follows: no change (0): 0–15%; poor (1): 16–35%; frontal sinus. The total energy applied to each affected
fair (2): 36–60%; good (3): 61–85%; and excellent maxillary or frontal sinus per session was 6 J. The
(4): 86–100% (Ansari, Fathali, Naghdi, and Hasson, LLLT was applied three times a week for ten treat-
2010; Ansari, Naghdi, and Farhadi, 2007; Ansari ment sessions. One physiotherapist applied all laser
Physiother Theory Pract Downloaded from informahealthcare.com by Cornell University on 10/12/13

et al, 2012; Naghdi, Ansari, and Farhadi, 2008). A interventions.


worsening of symptoms was indicated by negative
value.
Procedure

Intervention Before treatment, all patients were examined by an


ENT specialist to verify the diagnosis of CRS. At base-
LLLT was performed by Ga-Al-As infrared diode line (T0, week 0), eligible patients were interviewed
laser (Endolaser 476, Enraf Nonius, Netherland), for demographic data, and to score their symptoms
wavelength 830 nm, average power output of to calculate TSS. The assessment of symptom severity
For personal use only.

30 mW, and energy dose of 1 J. The area of LLLT was repeated after the end of five treatment sessions
application was the skin over the cheeks and the (T1, week 2) and after the end of the treatment (T2,

FIGURE 1. Six points over each maxillary or frontal sinus for delivering low-level laser therapy.

Copyright © Informa Healthcare USA, Inc.


Physiotherapy Theory and Practice 599

week 4). In addition, participants were followed-up by p < 0.001, η2p = 0.63). Post hoc tests using Bonfer-
telephone monthly for 18 months. Patients were called roni revealed that there was a significant difference in
to ask whether their symptoms recurred (yes/no), and TSSs between T0 and T1 ( p = 0.01), T0 and T2
when symptoms took place from the last treatment ( p < 0.001), and T1 and T2 ( p = 0.039).
session. Patients received no drug or other physiother-
apy intervention for the duration of the study and the
follow-up period.
The SPSS version 11.5 was used to analyze the data.
Symptom improvement
Descriptive statistics were calculated for demographic
Before treatment (T0), the patients mainly com-
and outcome variables. The effect of LLLT on TSS
plained of nasal obstruction, PND, fatigue, and
was examined using repeated measures ANOVA.
overall discomfort (median score = 2). Facial pain/
Effect size was reported as partial eta-squared (η2p ). Wil-
pressure, nasal discharge, smell disturbance, and
coxon signed-rank test was used to analyze the effects of
Physiother Theory Pract Downloaded from informahealthcare.com by Cornell University on 10/12/13

cough were scored as mild (median score = 1;


LLLT on individual symptoms and to compare
Table 2).
symptom improvement classification at T1 and T2.
At T1, the median scores for all symptoms except
The alpha level of significance was set to p < 0.05.
overall discomfort were 0 or 1. The median score for
the overall discomfort was not changed. At the end of
treatment (T2), the median score for all symptoms
RESULTS was scored 0 or 1. The severity of all symptoms was
reduced after LLLT (Table 2). Wilcoxon signed rank
Patient characteristics test showed a significant improvement of symptoms at
T1 (2 weeks) for facial pain/pressure, nasal obstruction,
Fifteen patients with CRS (M = 13; F = 2) with a nasal discharge, PND, fatigue, and cough ( p < 0.05).
For personal use only.

mean age of 38 years (standard deviation 9.6; range At the end of treatment (T2), the severity of all symp-
20–52) completed the study protocol. The mean toms was reduced significantly ( p < 0.05; Table 2).
disease duration from the CRS was 124.5 months Between 2 and 4 weeks, anosmia ( p = 0.046) and
(SD 102.41; range 7–360). Four patients had a overall discomfort ( p = 0.01) were improved
septal deviation, 1 had asthma, 1 had asthma and significantly.
allergy, and 1 was smoker. All patients had had appro-
priate antibiotic and/or allergy treatment. Two of 15
patients had had endoscopic sinus surgery or antral Symptom improvement classification
washout. Patients reported no side effects from LLLT.
The frequency of good and excellent improvement at
T2 was twice than that at T1 (4 vs. 2). The fre-
Total symptom scores quency of poor (5 vs. 2) and fair (5 vs. 8) improve-
ments was equal at T1 and T2. At T2, symptoms
Table 1 shows the TSSs pre- and posttreatment. The were worsened in one patient (Table 3). The
percentage improvement of TSSs was 39.0% and median (interquartile range [IQR]) of symptom im-
46.3% at T1 and T2, respectively. Manchly’s test of provement classification at T1 and T2 was poor
sphericity indicated that the assumption of sphericity (IQR 1–2) and fair (IQR 2–3), respectively. There
was not violated (χ 2 = 5.619, p = 0.06). Repeated was no statistically significant difference at T1 and
measures ANOVA with sphericity showed that TSSs T2 for improvement classifications (Wilcoxon
were significantly different (F(2, 28) = 23.393, signed rank test, p = 0.15).

TABLE 1. Total symptom scores pre- and posttreatment.

Total symptom score Mean (SD) Range

Pretreatment (T0, week 0) 12.47 (5.90) 2–21


Posttreatment (T1, week 2) 7.40 (4.31) 0–16
Posttreatment (T2, week 4) 5.33 (2.87) 0–10
Percent improvement (T1, week 2) 39 (25.76) 0–100
Percent improvement (T2, week 4) 46.34 (44.80) -100 to 100

Physiotherapy Theory and Practice


600 Naghdi et al.

TABLE 2. Symptoms before and after low-level laser therapy.

Pretreatment (T0) Posttreatment (T1, week 2) Posttreatment (T2, week 4)

(25th–75th) (25th–75th) (25th-75th)


Symptoms Median percentile Median percentile p value Median percentile p value

Facial pain/pressure 1 0–2 0 0–1 0.03 0 0-0 0.02


Headache 0 0–3 0 0–1 0.06 0 0-0 0.04
Nasal obstruction 2 1–3 1 0–2 0.007 1 1-1 0.006
Nasal discharge 1 0–3 0 0–1 0.04 0 0-1 0.02
Post nasal drip 2 1–3 1 0–2 0.04 1 0-2 0.03
Smell problem 1 0–3 1 0–3 0.18 0 0-2 0.02
Fatigue 2 0–2 0 0–1 0.01 0 0-1 0.02
Cough 1 0–1 0 0–0 0.008 0 0-1 0.008
Physiother Theory Pract Downloaded from informahealthcare.com by Cornell University on 10/12/13

Overall discomfort 2 1–3 2 1–2 0.10 1 1-2 0.01

TABLE 3. Frequency of symptoms improvement classification.

Improvement classification

No change (0), Poor (1), Fair (2), Good (3), Excellent (4),
Time Worse 0–15% 16–35% 36–60% 61–85% 86-100% p value
For personal use only.

T1∗ 0 3 5 5 1 1 0.15
T2∗ 1 0 2 8 2 2

T1, after the end of five treatment sessions at 2 weeks.

T2, after the end of the treatment at 4 weeks.

Follow-up treated sinuses. The penetration depth value (PDV),


the tissue depth at which the incident laser energy is
At 18 months, two patients were lost to follow-up. reduced to 37% of its original value, in human skin
Symptom improvements after treatment completion is approximately 1.0 cm for Ga-Al-As laser (Kolari
were sustained for a mean of 5 months (SD 4.3; and Airaksinen, 1988; Nussbaum, Baxter, and Lilge,
range 0.5–15 months). 2003). The PDV through bone is unknown, but
Ga-Al-As laser radiation could potentially reach the
maxillary and frontal sinuses. Laser power trans-
mission and the extent to which the low-level laser
DISCUSSION irradiation penetrates to the sinus mucosa need
further investigation.
This pilot study was performed to investigate the In the present study, measuring changes in symptom
effects of LLLT using a non-invasive technique in scores was the measure of efficacy, because the diagno-
patients with CRS. The results of the present study sis and treatment of rhinosinusitis are in general pri-
suggest that patients had a significant improvement marily symptom based (Fokkens et al, 2007; Marple
in symptoms following LLLT. Both the TSS and et al, 2009; Meltzer and Hamilos, 2011).
severity of individual symptoms significantly Moreover, clinical trials investigating the efficacy of
improved. To the authors’ knowledge, this is the first new treatments usually use symptom scoring systems
study to examine the effectiveness of applying LLLT as the main outcome measure to evaluate efficacy, of
locally over the sinuses in patients with persistent which changes in symptoms are key benefits for patients
CRS symptoms. (Eccles, 2011). Although a validated disease-specific
We did not measure laser power transmission to instrument is preferred; they are in English, and need
assess the extent to whether Ga-Al-As laser penetrates translation and culturally adaptation for non-English
to the sinuses. With regard to the results obtained, we speaking countries. Instead, the scoring of individual
may postulate that a percentage of LLLT reached the symptoms, and TSS is suggested for efficacy

Copyright © Informa Healthcare USA, Inc.


Physiotherapy Theory and Practice 601

assessments (Meltzer et al, 2006). The TSS and per- clinical outcomes (Bjordal, Lopes-Martins, Joensen,
centage improvement classification system used in and Iversen, 2010). Recent optimal dose-finding
this study have been shown to be valid when assessing reviews of LLLT in the head and neck region
the efficacy of therapeutic ultrasound in patients with suggest that the optimal treatment parameters (e.g.,
CRS (Naghdi, Ansari, and Farhadi, 2008). dose per point, irradiation times, treatment frequency,
In the current study, a large effect size was obtained and interval between sessions) are important to
for LLLT in treating patients with resistant CRS. The achieve meaningful results (Bjordal et al, 2011;
severity of symptoms in terms of TSS and individual Chow, Johnson, Lopes-Martins, and Bjordal, 2009).
symptom scores was significantly improved, which is A limitation of our study was the lack of a control
consistent with the successful results reported by group. However, the mean effect of LLLT was greater
Krespi and Kizhner (2011). However, one of the than placebo (Bjordal, Couppe, and Ljunggren,
patients reported an exacerbation of his symptoms 2001). The laser energy dose used in the present
after the end of the treatment. He developed an study also demonstrated a greater beneficial clinical
Physiother Theory Pract Downloaded from informahealthcare.com by Cornell University on 10/12/13

upper respiratory tract infection while not taking anti- effect than the placebo effect reported by Moustsen,
biotics. In the study by Krespi and Kizhner (2011), Vinter, Aas-Andersen, and Kragstrup (1991).
high energy, 500 J per side, was delivered internally, The mechanisms of LLLT are not fully under-
which caused pain associated with heat. We applied stood. The benefits obtained with LLLT may be
low laser energy per affected sinus per session of 6 J, explained primarily by anti-inflammatory and anti-
and no side effects were noted. bacterial disease-modulating mechanisms (Bjordal
The TSS was significantly better at T2 compared et al, 2003; Krespi and Kizhner, 2011). A review
with that at T1. Also if “good” and “excellent” article has demonstrated that the LLLT modality has
improvements were used as cut-off responder anti-inflammatory effects, and the magnitude of the
thresholds, the frequency of good and excellent im- anti-inflammatory effect is similar to that of non-
provements at T2 was twice than those at T1. These steroidal anti-inflammatory drugs (NSAIDs; Bjordal,
For personal use only.

findings indicate that 10 treatment sessions would Lopes-Martins, Joensen, and Iversen, 2010). A
provide further improvements in patients with CRS. recent study found that LLLT has an anti-inflamma-
Considering that the treatment of CRS is difficult tory effect on Staphylococcus epidermidis similar to
and recommendations made by the World Association dexamethasone (Ma et al, 2012). In patients with
of Laser Therapy (WALT, 2010) for optimal treat- CRS, an increased numbers of neutrophils have
ment effects, we recommend at least 10 treatment ses- been reported (Demoly et al, 1997). The release of
sions of LLLT for patients with CRS. local inflammatory mediators (e.g., bradykinin, pros-
The results found in the present study are not in taglandins, and histamine) and cytokines cause CRS
agreement with those from the Danish trial (Moust- symptoms (Eccles, 2011). Several animal studies
sen, Vinter, Aas-Andersen, and Kragstrup, 1991). have shown a reduction in inflammatory cell infiltra-
The differences could be due to different diseases tion after LLLT (Aimbire et al, 2008; Barbosa et al,
(acute sinusitis vs. CRS), methodologies, outcome 2008; Pessoa, Melhado, Theodoro, and Garcia,
measures, and energy dose. In comparison, the 2004). Recently, a review article concluded that
present study considered clinical criteria as well as LLLT reduces the concentration of signal molecules
CT scanning for sinusitis diagnosis. It is not clear involved in the inflammatory response, and LLLT
how the patients were diagnosed in the Danish can inhibit prostaglandin E2, tumor-necrosis factor-
study. Patients with only pain over a sinus/sinuses in α, cyclooxygenase-2, and interleukin 1 beta (Gao
the acute stage were included. As well, patients were and Xing, 2009). All these effects of LLLT are desir-
treated concurrently with antibiotics and nose drops. able for improving symptoms in patients with CRS.
In the present study, patients had chronic disease, The significant improvement of CRS-related symp-
and no allergy drugs or antibiotics were prescribed. toms is important considering that no drugs were
In their study, outcome measures were pain improve- prescribed concurrently for the patients.
ment, disease duration, and general well-being. In a healthy population, the paranasal sinuses are
Moustsen, Vinter, Aas-Andersen, and Kragstrup considered sterile (Abou-Hamad et al, 2009). Bacteria
(1991) used the same wavelength but only irradiation have been shown to play a role in both the development
of a single point in each sinus (irradiation time on each of and the exacerbation of CRS (Larson and Han,
sinus 90 sec) and only three treatment sessions with 2011). In an animal study, a NIR 940-nm diode laser
one to three days interval. More current authors with diffuser fiber tip was compared with a combination
emphasize the need to irradiate most of the pathology, of laser 635-nm and methylene blue as a photosensiti-
irradiate large affected tissues at several points, and zer in acute bacterial rhinosinusitis in rabbits. This
have more repeated sessions to observe positive study demonstrated that both methods were effective

Physiotherapy Theory and Practice


602 Naghdi et al.

and significant bacterial reduction up to 99.9% was REFERENCES


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The authors thank the patients. We also thank Mrs. effect of low-level laser therapy (LLLT) in cancer therapy-
Kazhal Fathizade, physiotherapist, for the sinus induced oral mucositis. Supportive Care in Cancer 19: 1069–1077
Cherry WB, Li JT 2008 Chronic rhinosinusitis in adults. American
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Journal of Medicine 121: 185–189
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Declaration of interest: The authors report no cacy of low-level laser therapy in the management of neck pain: A
conflicts of interest. The present study was funded systematic review and meta-analysis of randomised placebo or
by the research deputy, TUMS (Grant no. 10635). active-treatment controlled trials. Lancet 374: 1897–1908

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