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Low-level laser therapy for tinnitus

Low-level laser therapy for tinnitus (Protocol)
Peng Z, Chen XQ, Gong SS, Chen CF
This is a reprint of a Cochrane protocol, prepared and maintained by The Cochrane Collaboration and published in The CochraneLibrary 2012, Issue 4 Low-level laser therapy for tinnitus (Protocol)
Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

CONTRIBUTIONS OF AUTHORS Low-level laser therapy for tinnitus (Protocol)
Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Low-level laser therapy for tinnitus
Zhe Peng1, Xiu-Qi Chen2, Shu-Sheng Gong1, Cheng-Fang Chen1 1Department of Otorhinolaryngology - Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
2Department of Pediatrics, First Affiliated Hospital, Guangxi Medical University, Nanning, China Contact address: Shu-Sheng Gong, Department of Otorhinolaryngology - Head and Neck Surgery, Beijing Tongren Hospital, CapitalMedical University, Beijing, 100730, China.
Editorial group: Cochrane Ear, Nose and Throat Disorders Group.
Publication status and date: New, published in Issue 4, 2012.
Citation: Peng Z, Chen XQ, Gong SS, Chen CF. Low-level laser therapy for tinnitus. Cochrane Database of Systematic Reviews 2012,
Issue 4. Art. No.: CD009811. DOI: 10.1002/14651858.CD009811.
Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effectiveness of low-level laser therapy for the treatment of subjective idiopathic tinnitus.
Low-level laser therapy for tinnitus (Protocol)
Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
). This suggests the fundamental importance of the This is one of a number of tinnitus reviews produced by the central auditory pathways in the maintenance of the symptom, Cochrane Ear, Nose & Throat Disorders Group, which use a stan- irrespective of trigger.
dard Background. The following paragraphs ('Description of the Many environmental factors can also cause tinnitus. The most condition') are based on earlier work in the following reviews and relevant and frequently reported are: reproduced with permission: ; • acute acoustic trauma (AAT) (for example, explosions or • airbag inflation (toy-pistols ( Description of the condition
• exposure to occupational noise; 'urban noise pollution' Tinnitus can be described as the perception of sound in the absence of external acoustic stimulation. For the patient it may be trivial or it may be a debilitating condition The quality of the perceived sound can vary enormously from simple sounds such • exposure to recreational and amplified music ( as whistling or humming to complex sounds such as music. The patient may hear a single sound or multiple sounds. Tinnitus maybe perceived in one or both ears, within the head or outside thebody. The symptom may be continuous or intermittent. Tinnitus is described in most cases as subjective - meaning that it cannot beheard by anyone other than the patient. While, for the patient, this Over 50 years ago, Heller and Bergman demonstrated that if 'nor- perception of noise is very real, because there is no corresponding mal' people (with no known cochlear disease) were placed in a external sound it can be considered a phantom, or false, perception.
quiet enough environment, the vast majority of them would ex- Objective tinnitus is a form of tinnitus which can be detected perience sounds inside their head. They concluded that tinnitus- by an examiner, either unaided or using a listening aid such as like activity is a natural phenomenon perceived by many in a quiet a stethoscope or microphone in the ear canal. This is much less enough environment ( common and usually has a definable cause such as sound generated Mazurek has shown that pathologic changes in the cochlear neuro- by blood flow in or around the ear or unusual activity of the tiny transmission, e.g. as a result of intensive noise exposure or ototoxic muscles within the middle ear. Tinnitus may be associated with drugs, can be a factor in the development of tinnitus normal hearing or any degree of hearing loss and can occur at any In the 'neurophysiological model' of tinnitus ( It is important to distinguish between clinically significant and it is proposed that tinnitus results from the ab- non-significant tinnitus (and several different classi- normal processing of a signal generated in the auditory system.
fications have been proposed (; ; This abnormal processing occurs before the signal is perceived ). Dauman, for example, makes a distinction be- centrally. This may result in 'feedback', whereby the annoyance tween 'normal' (lasting less than five minutes, occurring less than created by the tinnitus causes the individual to focus increasingly once a week and experienced by most people) and 'pathological' on the noise, which in turn exacerbates the annoyance and so a tinnitus (lasting more than five minutes, occurring more than once 'vicious cycle' develops. In this model tinnitus could therefore re- a week and usually experienced by people with hearing loss).
sult from continuous firing of cochlear fibres to the brain, fromhyperactivity of cochlear hair cells or from permanent damage tothese cells being translated neuronally into a 'phantom' sound- like signal that the brain 'believes' it is hearing. For this reason Almost any form of disorder involving the outer, middle or in- tinnitus may be compared to chronic pain of central origin - a sort ner ear or the auditory nerve may be associated with tinnitus of 'auditory pain' (; ).
(). However, it is possible to have se- The relationship between the symptom of tinnitus and the activ- vere tinnitus with no evidence of any aural pathology. Conversely, ity of the prefrontal cortex and limbic system has been empha- tinnitus can even exist without a peripheral auditory system: uni- sised. The limbic system mediates emotions. It can be of great lateral tinnitus is a common presenting symptom of vestibular importance in understanding why the sensation of tinnitus is in schwannomas (acoustic neuromas), which are rare benign tumours many cases so distressing for the patient. It also suggests why, when of the vestibulo-cochlear nerve. When these neuromas are removed symptoms are severe, tinnitus can be associated with major depres- by a translabyrinthine route, the cochlear nerve can be severed.
sion, anxiety and other psychosomatic and/or psychological dis- Despite the effective removal of their peripheral auditory mecha- turbances, leading to a progressive deterioration of quality of life nisms, 60% of these patients retain their tinnitus postoperatively Low-level laser therapy for tinnitus (Protocol)
Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
and spasmolytic drugs. The use of anticonvulsants in treating tin- Epidemiological data reports are few. The largest single study was nitus is the subject of a Cochrane review ). An- undertaken in the UK by the Medical Research Council Institute tidepressants are commonly prescribed for tinnitus. However, two of Hearing Research and was published in 2000 (). This reviews (; ) showed that there is no in- longitudinal study of hearing questioned 48,313 people; 10.1% dication that tricyclic antidepressants have a beneficial effect.
described tinnitus arising spontaneously and lasting for five or Although a number of studies have suggested that Ginkgo biloba more minutes at a time and 5% described it as moderately or may be of benefit in the treatment of tinnitus severely annoying. However, only 0.5% reported tinnitus having a Cochrane review showed that there was a severe effect on their life. This is another of the paradoxes of no evidence that it is effective where tinnitus was the primary tinnitus: the symptom is very common but the majority of peo- ple who experience it are not particularly concerned by it. These Hyperbaric oxygen therapy (HBOT) can improve oxygen supply figures from the UK are broadly consistent with data collected to the inner ear which it is suggested may result in an improvement by the American Tinnitus Association (ATA) which suggests that in tinnitus, however a Cochrane review found insufficient evidence tinnitus may be experienced by around 50 million Americans, or 17% of the US population ). Data also exist for Japan, Studies have been carried out into the effect of cognitive be- Europe and Australia ), and estimates suggest havioural therapy (CBT) on tinnitus ). Another that tinnitus affects a similar percentage of these populations, with Cochrane review has shown that CBT can have an effect on the 1% to 2% experiencing debilitating tinnitus (). The qualitative aspects of tinnitus and can improve patients' ability to Oregon Tinnitus Data Archive ) contains data on manage the condition ).
the characteristics of tinnitus drawn from a sample of 1630 tinni- Other options for the management of patients with tinnitus in- tus patients. The age groups with the greater prevalence are those clude transcranial magnetic stimulation (), tinnitus between 40 and 49 years (23.9%) and between 50 and 59 years masking (use of 'white noise' generators) (mu- sic therapy reflexology, hypnotherapy and tra- Olszewski showed in his study that the risk of tinnitus increases in ditional Chinese medicine (TCM), including acupuncture patients over 55 years old who suffer from metabolic conditions and cervical spondylosis ().
Description of the intervention
Firstly a patient with tinnitus may undergo a basic clinical assess- Laser was discovered in the 1960s. Laser is light that is generated ment. This will include the relevant otological, general and family by high-intensity electrical stimulation of a medium, which can history, and an examination focusing on the ears, teeth and neck be a gas, liquid, crystal, dye or semiconductor (). The and scalp musculature. Referral to a specialist is likely to involve light produced consists of coherent beams of single wavelengths a variety of other investigations including audiological tests and in the visible to infrared spectrum, which can be emitted in a radiology. Persistent, unilateral tinnitus may be due to a specific continuous wave or pulsed mode disorder of the auditory pathway and imaging of the cerebello- Mester first reported the earliest clinical application of the low-level pontine angle is important to exclude, for example, a vestibular laser in 1972 (Since then, low-level laser therapy schwannoma (acoustic neuroma) - a rare benign tumour of the (LLLT) has come to the forefront of clinical research. Hundreds cochleo-vestibular nerve. Other lesions, such as glomus tumours, of randomised, double-blind, placebo-controlled phase III clinical meningiomas, adenomas, vascular lesions or neuro-vascular con- trials have been published from over a dozen countries flicts may also be detected by imaging ( Low-level laser therapy (LLLT) uses low-powered laser light in therange of 1 to 1000 mW, at wavelengths from 632 to 1064 nm, tostimulate a biological response. LLLT uses laser to aid tissue repair relieve pain and stimulate At present no specific therapy for tinnitus is acknowledged to be acupuncture points ). Surgical applications of satisfactory in all patients. Many patients who complain of tinni- laser ablate tissue by intense heat and are different from LLLT, tus, and also have a significant hearing impairment, will benefit which uses light energy to modulate cell and tissue physiology to from a hearing aid. Not only will this help their hearing disability achieve therapeutic benefit without a macroscopic thermal effect but the severity of their tinnitus may be reduced.
(sometimes termed cold laser). LLLT is non-invasive, painless and A wide range of therapies have been proposed for the treatment of can be easily administered in primary care settings.
tinnitus symptoms. Pharmacological interventions used include LLLT acts by inducing a photochemical reaction in the cell, a pro- cortisone (vasodilators, benzodiazepines, lidocaine cess referred to as biostimulation or photobiomodulation ( Low-level laser therapy for tinnitus (Protocol)
Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
). It is an irradiation technique that has the ability to in- ;), promotes local blood duce biological processes using photon energy. There are studies flow in the inner ear associated with suppression of the sympa- showing proliferation and angiogenesis after irradiation in skeletal thetic nerve action potential, and activates repair mechanisms in muscle tissue cells post-myocardial infarction. Most evidence of the inner ear through photochemical and photophysical stimula- efficacy is based on the increase in energy state and the activation tion of the hair cell mitochondria of mitochondrial pathways. It has been reasonably well established Additionally, studies have shown that laser leads to activation of that mitochondria are a principal intracellular target of red and related cortical areas in healthy subjects. The mechanism leading near infrared light Cytochrome C oxidase (unit IV to the observed activated neuronal network by means of trans- of the mitochondrial respiratory chain) is a chromophore that ab- meatal cochlear laser (TCL) is vague (). It can- sorbs light as far into the infrared as 1000 nm ().
not be explained by a supra-sensory stimulation of the tympanic In recent years, LLLT has been widely used in the treatment of membrane, since subjects are not able to differentiate between real tinnitus. The laser emits dual wavelength beams which are red and placebo stimulation.
and near infrared. These laser beams are cool to the touch and Different low-level laser therapy studies have focused on the deter- do not cause discomfort. They are aimed into the auditory canal mination and the modulation of irradiation parameters that seem and through the mastoid bone behind the ear. The patients are to play a pivotal role in its effectiveness awake during the period of therapy. The wavelength nature of these lasers allows them to penetrate tissue. Although the laser beams The biological effects of low-level laser ther- lose intensity rapidly, they can have an effect on tissues 2 to 5 cm apy are supposed to depend largely on well-controlled parameters, inside the body. The mechanism of action of low-level laser on the e.g. wavelength, waveform, power, dosage per site, duration of ir- inner ear and on tinnitus is not well understood. Previous studies radiation, type of irradiated cell and time interval between injury evaluating low-level laser for the treatment of tinnitus have been and irradiation.
equivocal, with both positive ; ; ; and negative effects (; ; ) reported.
Why it is important to do this review
The incidence of adverse effects of LLLT is low and similar to that The effects of low-level laser directed at the auditory canal or the of placebo, with no reports of serious events ).
mastoid bone behind the ear are not known (; ; ; ; ). Therefore this Cochrane review will How the intervention might work
provide an up-to-date, detailed analysis of the current evidence Several hypotheses have been proposed for the mechanism of ac- tion of LLLT. The prevailing opinion is that the respiratory chainplays a central role in the effect induced by laser therapy (). Laser energy in the red and near infrared light spectrumis capable of penetrating tissue. It stimulates mitochondria in O B J E C T I V E S
the cells to produce energy through the production of adenosinetriphosphate (ATP) (). Mitochondria are the power To assess the effectiveness of low-level laser therapy for the treat- supplies of all cells; they metabolise fuel and produce energy for ment of subjective idiopathic tinnitus.
the cell in the form of ATP. It has been reported that LLLT irra-diation increases the production of ATP IncreasedATP production may lead to enhanced cell metabolism, promot- ing the damage recovery process, returning cells to a healthy stateand reversing many degenerative conditions.
For ear disorders, low-level laser has been reported to alter the col- Criteria for considering studies for this review
lagen organisation within the cochlea, especially within the basilarmembrane. This should increase the stiffness of the basilar mem-brane (). Also, LLLT has a beneficial Types of studies
effect on the recovery of cochlear hair cells after acute hair cell loss Randomised controlled trials.
(), increases cell proliferation (), syn-thesis of ATP (and collagen ), releaseof growth factors (including nerve growth factor (NGF), brain- Types of participants
derived neurotrophic factor (BDNF), glial cell line-derived neu- Adults in whom there is a complaint of persistent, distressing, rotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF)) subjective tinnitus of any aetiology.
Low-level laser therapy for tinnitus (Protocol)
Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Types of interventions
Searching other resources
Studies where the patients received low-level laser therapy. Com- We will scan the reference lists of identified publications for ad- parisons will include the following.
ditional trials and contact trial authors if necessary. In addition, • Low-level laser therapy versus placebo we will search PubMed, TRIPdatabase, The Cochrane Library and • Low-level laser therapy versus drug/other therapy Google to retrieve existing systematic reviews relevant to this sys-tematic review, so that we can scan their reference lists for ad-ditional trials. We will search for conference abstracts using the Types of outcome measures
Cochrane Ear, Nose and Throat Disorders Group Trials Register.
Data collection and analysis
• Improvement in tinnitus severity and disability, measured by a validated tinnitus-specific questionnaire. Commonly usedtinnitus questionnaires are listed in ( Selection of studies
Two authors (Zhe Peng, Xiu Qi Chen) will independently reviewthe titles, abstracts and keywords of all records retrieved to identify studies which meet the inclusion criteria outlined above. We will • Improvement of quality of life resolve disagreements by consensus.
• Change in socio-economic impact associated with work • Change in anxiety and depression disorders Data extraction and management
• Change in psychoacoustic parameters • Change in tinnitus loudness The same two review authors will carry out data extraction inde- • Change in overall severity of tinnitus pendently. Each review author will review approximately the same • Change in thresholds on pure-tone audiometry number of studies. We will use a standardised extraction form for • Adverse effects of treatment data collection. Unresolved disagreement on inclusion, 'Risk ofbias' assessment and data collection will be referred to the othertwo authors (Shusheng Gong, Chengfang Chen). Extracted datawill include the following.
Search methods for identification of studies
1. Study details: first author; year of publication; country of We will conduct systematic searches for randomised controlled publication; publication type.
trials. There will be no language, publication year or publication 2. Study eligibility: type of study; participants; types of status restrictions. We may contact original authors for clarification intervention; types of outcomes/measures.
and further data if trial reports are unclear, and we will arrange 3. Methods: study inclusion criteria; study exclusion criteria; translations of papers where necessary.
detail of participants (age, sex, aetiology, hearing level, durationof tinnitus, severity of tinnitus); setting; study intervention(wave, session, frequency); study control; matching of interventions; compliance; similarity between groups; duration We will identify published, unpublished and ongoing studies of follow-up.
by searching the following databases from their inception: the 4. Information on methods for 'Risk of bias' assessment.
Cochrane Ear, Nose and Throat Disorders Group Trials Register; 5. Outcome: primary outcomes, secondary outcomes and the Cochrane Central Register of Controlled Trials (CENTRAL, other outcomes at the end of treatment and/or the end of follow- The Cochrane Library); PubMed; EMBASE; CINAHL; LILACS; up. We will also extract the number and type of adverse events.
KoreaMed; IndMed; PakMediNet; CAB Abstracts; Web of Sci- 6. Conclusions.
ence; BIOSIS Previews; ISRCTN;; ICTRP and We will contact authors for clarification and missing data infor- We will model subject strategies for databases on the search strategydesigned for CENTRAL (see ). Where appropriate,we will combine subject strategies with adaptations of the highly Assessment of risk of bias in included studies
sensitive search strategy designed by the Cochrane Collaboration Zhe Peng and Xiu Qi Chen will independently undertake assess- for identifying randomised controlled trials and controlled clinical ment of the risk of bias of the included trials, with the following trials (as described in the Cochrane Handbook for Systematic Reviews taken into consideration, as guided by the Cochrane Handbook for of Interventions Version 5.1.0, Box 6.4.b. ( Systematic Reviews of Interventions Low-level laser therapy for tinnitus (Protocol)
Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
• sequence generation; • 0% to 40%: might not be important; • allocation concealment; • 30% to 60%: may represent moderate heterogeneity; • 50% to 90%: may represent substantial heterogeneity; • incomplete outcome data; • 75% to 100%: considerable heterogeneity.
• selective outcome reporting; and The importance of the observed value of the I² statistic depends • other sources of bias.
on (i) the magnitude and direction of effects and (ii) the strength We will use the Cochrane ‘Risk of bias' tool in Review Manager of evidence for heterogeneity (e.g. P value from the Chi² test or a (RevMan) 5 which involves describing each of confidence interval for I²) ( these domains as reported in the trial and then assigning a judge-ment about the adequacy of each entry: 'low', 'high' or 'unclear' Assessment of reporting biases
risk of bias.
We will test for potential publication bias using a funnel plot orother corrective analytical methods, depending on the number of Measures of treatment effect
clinical trials included in the systematic review. We will attempt We will analyse the data using Review Manager 5. We will assess to reduce any effects of reporting bias by obtaining and including the treatment effect for dichotomous data outcome measures using missing trial data and data from unpublished trials where possible.
the risk ratio (RR) and for continuous data we will use the meandifference (MD), with 95% confidence intervals. We will combine data statistically if they are available and of sufficient quality and A pooled statistical analysis of treatment effects will proceed only in the absence of significant heterogeneity.
in the absence of significant clinical or statistical heterogeneity.
Where it is appropriate to pool data and heterogeneity is detected, Unit of analysis issues
we will use the random-effects model. We will analyse the clinicalheterogeneity of the included trials to determine whether it is To protect the accuracy of the results, we will only include ran- appropriate to carry out the meta-analysis.
domised controlled trials. We will not include other non-standard If the trial data cannot be pooled, we will describe the outcomes designs such as cross-over trials and cluster-randomised trials.
in the text of the review.
Dealing with missing data
Subgroup analysis and investigation of heterogeneity
We will contact authors for missing data information. If the data No subgroup analyses are planned.
are missing at random, analyses based on the available data willtend to be unbiased; if the data are said to be 'not missing atrandom', publication bias and selective reporting bias may exist.
The principal options for dealing with missing data are based on We will perform sensitivity analyses by repeating the analysis ex- the recommendations in the Cochrane Handbook for Systematic cluding internal reports and conference abstracts. We will use study Reviews of interventions, Chapter 16 ).
quality in a sensitivity analysis.
Assessment of heterogeneity
We will assess clinical heterogeneity by examining types of par- ticipants (e.g. cause of tinnitus), interventions and outcomes ineach study. We will assess statistical heterogeneity among trials by We are grateful to Paolo Baldo, John Phillips, Malcolm Hilton, inspecting the forest plots and using the Chi² test and the I² statis- Jonathan Hobson and Michael Bennett for their previous tic. When interpreting the I² statistic, we will use the following Cochrane reviews on which the Background to this protocol is Low-level laser therapy for tinnitus (Protocol)
Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Indicates the major publication for the study Table 1. Tinnitus questionnaires
No. of items/factors
Tinnitus Questionnaire () 52 items, 5 factors a = 0.91 for total scale; for subscales a = 0.76 to a = 0.94 Tinnitus Handicap Questionnaire (27 items, 3 factors a = 0.93 for total scale Tinnitus Severity Scale Alpha not reported Subjective Tinnitus Severity Scale (16 items Low-level laser therapy for tinnitus (Protocol)
Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 1. Tinnitus questionnaires
Scale 28 items, 3 factors Alpha not reported Tinnitus Handicap Inventory 25 items, 3 scales a = 0.93 for total scale Tinnitus coping strategy questionnaire ( 33 Tinnitus coping style questionnaire 40 Tinnitus cognitions questionnaire - A P P E N D I C E S
Appendix 1. CENTRAL search strategy
#1 MeSH descriptor Tinnitus explode all trees#2 tinnit*#3 (#1 OR #2)#4 MeSH descriptor Laser Therapy explode all trees#5 MeSH descriptor Lasers explode all trees#6 laser* OR lllt#7 #4 OR #5 OR #6#8 #3 AND #7 Protocol first published: Issue 4, 2012 Low-level laser therapy for tinnitus (Protocol)
Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Zhe Peng: lead author, searching, selection of studies, data extraction, drafting and co-drafting of the protocol/review, assistance withstatistics, data analysis and data presentation, update of the review.
Xiu-Qi Chen: selection of studies, data extraction, assistance with statistics, data analysis, update of the review.
Shu-Sheng Gong: selection of studies, assistance with statistics.
Cheng-Fang Chen: searching, assistance with data extraction.
• None, Not specified.
• None, Not specified.
Low-level laser therapy for tinnitus (Protocol)
Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.



P000 - ESAMI DI STATO CONCLUSIVI DEI CORSI DI STUDIO DI ISTRUZIONE SECONDARIA SUPERIORE PROVA DI ITALIANO (per tutti gli indirizzi: di ordinamento e sperimentali) Svolgi la prova, scegliendo una delle quattro tipologie qui proposte. TIPOLOGIA A - ANALISI DEL TESTO L. PIRANDELLO, Il piacere dell'onestà

Microsoft word - 157-164-palynology - pragnya.docx

VISTAS IN GEOLOGICAL RESEARCH (ISBN: 81-900907-0-4) Special Publication in Geology (14), January 2016, pp.157 - 164 A Palynological Investigation of Quaternary Sediment Core from Cauvery Delta, Tamilnadu, India MOHAPATRA , A. KRISHNAMURTHY , P. SRINIVASAN , P. SINGH , P. P. DAS *1Department of Geology, Raveneshaw University, Cuttack - 753003, India