Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 
Print this page Email this page Users Online: 509

  Table of Contents  
REVIEW ARTICLE
Year : 2023  |  Volume : 16  |  Issue : 1  |  Page : 28-35  

Efficacy of transcranial magnetic stimulation in tobacco abstinence among adult tobacco users compared to usual care or no treatment – A systematic review


1 Department of Public Health and Health Promotion, College of Health Sciences, Brunel University London, Uxbridge, Middlesex, UK
2 Department of Pulmonology and Critical Care, Fortis Hospital Noida, Noida, Uttar Pradesh, India

Date of Submission09-Apr-2021
Date of Decision28-May-2021
Date of Acceptance28-May-2021
Date of Web Publication20-Feb-2023

Correspondence Address:
Dr. Rashmi Mehra
College of Health Sciences, Brunel University London, Uxbridge, Middlesex UB8 3PH
UK
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mjdrdypu.mjdrdypu_257_21

Rights and Permissions
  Abstract 


Objective: This study aimed to systematically identify and assess randomized controlled trials (RCTs) that evaluated the efficacy of transcranial magnetic stimulation (TMS) for increasing tobacco abstinence. Methods: Five electronic databases were searched from inception to May 2021 to identify RCTs evaluating the efficacy of TMS interventions for tobacco cessation or abstinence. Using predetermined eligibility criteria, two reviewers screened literature and assessed the quality of included studies using the Critical Appraisal Skills Programme tool. Results: Out of 222 records, six RCTs with TMS intervention were shortlisted. Two studies assessed TMS in conjunction with other active tobacco cessation treatment, while other four studies used TMS as only active form of treatment. The limited number of included studies had short follow-ups, large dropout rates, and heterogeneous interventions and comparators, which precluded clear detection of treatment effect of TMS interventions. Conclusions: TMS intervention differed significantly from comparator group in their effects on tobacco use. However, low-quality limited evidence with variability in study design among existing studies suggests the need for high-quality, long follow-up and robust RCTs to be conducted.

Keywords: Complementary medicine, systematic review, transcranial magnetic stimulation, tobacco cessation


How to cite this article:
Mehra R, Mehra K. Efficacy of transcranial magnetic stimulation in tobacco abstinence among adult tobacco users compared to usual care or no treatment – A systematic review. Med J DY Patil Vidyapeeth 2023;16:28-35

How to cite this URL:
Mehra R, Mehra K. Efficacy of transcranial magnetic stimulation in tobacco abstinence among adult tobacco users compared to usual care or no treatment – A systematic review. Med J DY Patil Vidyapeeth [serial online] 2023 [cited 2023 Mar 24];16:28-35. Available from: https://www.mjdrdypv.org/text.asp?2023/16/1/28/369832




  Introduction Top


Tobacco has been established as one of the largest preventable causes of death and disease in the world with over 7 million people losing their lives each year to it.[1] Several reports have suggested a strong association of cancer and cardiovascular diseases with tobacco use.[2],[3] Despite the established association with multiple diseases and mortality, the tobacco epidemic continues to grow with over 1100 million smokers across the globe.[1]

The exceptional expanse of tobacco users has largely been attributed to the potentially addictive nature of the nicotine.[4] Tobacco has been ranked to have higher dependence in comparison to methamphetamine, cannabis, lysergic acid diethylamide, or alcohol.[3],[5] This could potentially explain the poor rates of abstinence among those who attempt to quit.[3],[6],[7] Studies suggest that decreased function in brain reward systems during nicotine withdrawal seems to be closely related to craving, relapse, and continued nicotine consumption.[8],[9] Furthermore, nicotine withdrawal induces structural and functional deficits in critical brain areas related to the dopamine system which result in intense somatic, cognitive, and affective withdrawal symptoms including irritability, anger, frustration anxiety, depressed mood, difficulty concentrating, and increased appetite.[10],[11],[12],[13]

Despite considerable evidence supporting the efficacy of different interventions for smoking cessation, a meager 20% of smokers who try to quit seek professional assistance.[14],[15] Both pharmacotherapy and behavioral therapy have been established as fairly effective modalities, with a judicious combination of the two reported to afford better results.[16],[17],[18]

In such a situation, there is a need for tobacco cessation modalities and approaches which help ease the process and improve the quit rate among those who attempt. A survey-based study showed that a significant percentage of smokers (27%) use complementary and alternate medicine (CAM) treatment modalities in addition to, or as replacement of, conventional smoking cessation treatments.[19] The study also found that 67% of smokers seeking treatment indicate that they would be interested in using CAM practices such as yoga, meditation, transcranial magnetic stimulation (TMS), or massage to relieve stress and help them quit smoking.[19] Since then, multiple studies have been conducted to assess the effectiveness of various CAM modalities, including TMS in tobacco cessation.

Transcranial magnetic stimulation

TMS involves delivery of high-frequency magnetic field in certain areas of the brain which acts by mimicking actions of nicotine on brain reward systems by blocking neuronal uptake of dopamine.[8] Tobacco use is associated with a reduction in hippocampal 5-HT which may be reversed by TMS-induced increase in hippocampal 5-HT concentrations.[20],[21],[22] Strafella et al. introduced the effect of high-frequency prefrontal TMS, which was associated with immediate, marked dopamine release, thereby reversing the mechanisms at play during nicotine withdrawal.[23]

At present, only one systematic review on TMS has been done which included previous studies with TMS interventions but assessed craving which is a subjective outcome.[24] This systematic review included only two databases to find relevant literature for the study. Furthermore, it included heterogeneous designs of included studies with few studies conducted among schizophrenic patients which make the comparison with other tobacco users questionable. Owing to the existing lacuna in literature about the effectiveness of TMS, this study was conducted to systematically identify and assess randomized controlled trials (RCTs) that evaluated the efficacy of TMS for tobacco abstinence as an adjunct or monotherapeutic agent in comparison to usual care or no treatment.


  Methods Top


Search strategy and selection criteria

A systematic review was conducted, following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for assessments of intervention studies.[25] The review identified previous studies conducted to assess the efficacy of TMS in tobacco cessation in comparison to “usual care” or no treatment.

The following databases were searched by two researchers (RM and KM) from April 1 to May 01, 2021:

  • Scopus
  • MEDLINE, accessed by PubMed (1966–June 2019) and EMBASE (1980–June 2019) electronic databases
  • EBSCO host including CINAHL, PsycINFO, SocINDEX, SPORTDiscuss, and OpenDIssertations
  • Science Direct.


This was in line with previous systematic review assessing tobacco cessation and other CAM modalities wherein five databases were searched.[26] Following a pilot literature review conducted to assess terms used in other systematic reviews assessing tobacco cessation and a CAM treatment modality, a tentative search strategy was arrived at.[26],[27] The researchers went through multiple rounds of discussions and deliberations, following which a set of core keywords was decided upon which were then used to find suitable articles. These were “tobacco N8 cessation” OR “smoking cessation” OR “tobacco cessation intervention” OR “smoking abstinence” OR “Quit N8 tobacco” AND “transcranial magnetic stimulation” OR “tms” OR “rtms” OR “theta burst stimulation” OR “repetitive transcranial magnetic stimulation”.

This review only included randomized control trials which provided TMS intervention, irrespective of duration of intervention. Further, only those studies which included a control arm (usual treatment, nonactive placebo, and preestablished positive control) were included. Since English was the language of choice for both the researchers, only fully accessible papers in English language could be included in the review. All studies irrespective of year of publication were included. Studies involving interventions in special groups like those with mental disorders were not included. The authors did not include studies which did not report abstinence (self-reported or biochemically assessed). Full-text articles of eligible studies were obtained and evaluated independently by all researchers, based on limits to the inclusion criteria. [Figure 1] presents the PRISMA diagram of the systematic review depicting the studies included in the study.
Figure 1: Preferred Reporting Items for Systematic Reviews and Meta-analyses flowchart of the search strategy

Click here to view


Data extraction

The authors extracted data in a spreadsheet for the final included articles. The data included year of publication, study location, study setting, sample size, mean age of the sample, gender distribution, and smoking status (number of cigarettes a day). A descriptive table was also organized to include the duration and nature of intervention and control groups. Data synthesis was predominantly narrative.

Quality assessment

Quality of individual studies was assessed using the Critical Appraisal Skills Programme tool for RCTs.[28],[29] A number of factors were considered to corroborate the quality of the study including representativeness of the study sample, with appropriate selection and size of the sample. Another important factor was the detailed description of the exposure variable, including sampling method and data collection strategy. These criteria were reviewed by researchers (RM and KM), and consensus was met to provide a narrative assessment of the quality of the study. The findings of the quality assessment are tabulated in [Table 1].
Table 1: Quality assessment of the four studies included in the systematic review using the Critical Appraisal Skills Programme tool

Click here to view



  Results Top


Out of the 222 records obtained in the initial search through the included databases, only six studies were included in the systematic review.[30],[31],[32],[33],[34],[35] The baseline characteristics of participants in the included studies are presented in [Table 2]. Trojak, 2015, did not record the baseline number of cigarettes per day consumed by the participants.[32] Furthermore, a distinctly higher mean Fagerstrom Test for Nicotine Dependence score among the control group of Trojak, 2015 study was found in comparison to the intervention group. This could be a potential confounding factor for better abstinence among the intervention group.
Table 2: Baseline characteristics of participants in the four studies included in the systematic review

Click here to view


The included studies originated from different parts of the world, namely Germany, Israel, France, and the USA [Table 3]. Two of the studies assessed TMS in conjunction with other active tobacco cessation treatment (nicotine replacement therapy [NRT] or cognitive behavioral therapy [CBT]) – Dieler, 2014, and Trojak 2015, while other four studies used TMS as the only active form of treatment.[31],[33],[34],[35] It must be noted that Sheffer et al. did provide educational booklets to all the participants.
Table 3: Summary table of the studies included in the systematic review

Click here to view


TMS when used in conjunction with NRT (Trojak, 2015) and CBT (Deiler, 2014) was found to improve abstinence rates among the study participants. However, a statistically significant difference between intervention and control group was found only till 2nd week of the study (Trojak, 2015), while better abstinence rates persisted till the 3-month follow-up for another study (Deiler, 2014) [Table 3].

All four studies which employed rTMS as intervention compared to sham for the control group showed significantly higher abstinence rate.[31],[33],[34],[35] Abstinence was biochemically confirmed by few studies (Sheffer, 2018; Li, 2020; Zangen, 2021), while Dinur-Klein relied on self-reported abstinence at 6 months. All studies showed an increase in abstinence rate at the last follow-up of their protocol except Trojak et al., 2015, who reported their results to be “ambiguous.”


  Discussion Top


All the six studies included in this systematic review suggest the improvement in tobacco abstinence following adjunctive or monotherapeutic use of TMS. Detailed abstinence outcomes provide converging evidence for its efficacy. This was in line with other studies suggesting increased abstinence and avoiding relapse among substance abusers.[24],[36] This review also points at the limited research conducted on this topic, with only few RCTs which have been conducted. In addition, most of these studies have included small sample size and short follow-up period with no biochemical marker to confirm abstinence. Furthermore, it must be highlighted that there are limited data collected on the safety of this novel technique.

This review has distinct strengths which make it robust and comprehensive. First and foremost, this systematic review has resulted from an extensive search of multiple databases, thereby improving the inclusivity of studies. The present review assessed abstinence from tobacco instead of subjective and heterogeneous measure of craving. Further, literature suggests that craving is not a necessary condition for relapse, thereby implying that abstinence is a better measure for predicting cessation.[37],[38]

However, needless to say, this review also has certain limitations. This review did not include unpublished gray literature or studies in languages other than English. This could have curbed the inclusion of studies published in other languages. Furthermore, a meta-analysis could not be conducted using the included studies due to heterogeneous study protocols and measures of result reporting.

The present study highlights the overwhelming need for more long-term studies with robust sample design to assess the effectiveness of TMS as a treatment modality for tobacco cessation. In addition, there are limited data on side effects and other adverse outcomes among those who are treated for tobacco use using TMS. Broadly, the study highlights the untapped potential of incorporation of complementary approaches into the tobacco cessation clinics which at present restrict themselves to cognitive behavioral therapy, NRT, and other pharmacological interventions (bupropion and varenicline).

Although there is limited, though positive, evidence for the efficacy of TMS for tobacco abstinence, there is growing evidence for the use of TMS in the management of autism and many mental health issues including posttraumatic stress disorder and depression.[39],[40],[41] Such evidence highlights the potential benefits and holistic cessation approaches which could be adopted in future following further research in the area of TMS for tobacco cessation.

From cost-effectiveness point of view, this could pave the way for multiple benefits from a common treatment modality, with investment in a TMS setup potentially improving health status of patient groups suffering from multiple mental health morbidities or varying addictions and mental afflictions. This could culminate into increased usability and cost-effectiveness of TMS as in the case of treatment of major depression along with addiction.[42]


  Conclusions Top


The present systematic review puts forth TMS as a novel therapeutic modality to improve the existing abstinence from smoking. However, the results of this review must be considered with due caution because of limited long-term studies to assess the benefits and harms of TMS. Future studies with comprehensive protocols larger sample sizes, rigorous blinding procedures, and standards of randomization should be conducted.

Acknowledgments

We would like to acknowledge Dr. Subhash Pokhrel, for his constant guidance and support during the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
World Health Organization. WHO Report on the Global Tobacco Epidemic, 2017: Monitoring Tobacco Use and Prevention Policies. Geneva: World Health Organization; 2017.  Back to cited text no. 1
    
2.
Centers for Disease Control and Prevention (CDC). Current cigarette smoking among adults-United States, 2011. MMWR Morb Mortal Wkly Rep 2012;61:889-94.  Back to cited text no. 2
    
3.
Lushniak BD, Samet JM, Pechacek TF, Norman LA, Taylor PA. The Health Consequences of Smoking – 50 Years of Progress: A Report of the Surgeon General. Rockville, MD:2014.  Back to cited text no. 3
    
4.
Benowitz NL. Clinical pharmacology of nicotine: Implications for understanding, preventing, and treating tobacco addiction. Clin Pharmacol Ther 2008;83:531-41.  Back to cited text no. 4
    
5.
van Amsterdam J, Opperhuizen A, Koeter M, van den Brink W. Ranking the harm of alcohol, tobacco and illicit drugs for the individual and the population. Eur Addict Res 2010;16:202-7.  Back to cited text no. 5
    
6.
Buczkowski K, Marcinowicz L, Czachowski S, Piszczek E. Motivations toward smoking cessation, reasons for relapse, and modes of quitting: Results from a qualitative study among former and current smokers. Patient Prefer Adherence 2014;8:1353-63.  Back to cited text no. 6
    
7.
Schauer GL, Berg CJ, Kegler MC, Donovan DM, Windle M. Differences in tobacco product use among past month adult marijuana users and nonusers: findings from the 2003-2012 national survey on drug use and health. Nicotine Tob Res 2016;18:281-8.  Back to cited text no. 7
    
8.
Jarvik ME, Madsen DC, Olmstead RE, Iwamoto-Schaap PN, Elins JL, Benowitz NL. Nicotine blood levels and subjective craving for cigarettes. Pharmacol Biochem Behav 2000;66:553-8.  Back to cited text no. 8
    
9.
Jones RT, Benowitz NL. Therapeutics for nicotine addiction. In: Davis KL, editor. Neuropsychopharmacology: The fifth generation of progress: An official publication of the American College of Neuropsychopharmacology. Lippincott Williams & Wilkins; 2002. p. 1533-43.  Back to cited text no. 9
    
10.
Zhang X, Salmeron BJ, Ross TJ, Gu H, Geng X, Yang Y, et al. Anatomical differences and network characteristics underlying smoking cue reactivity. Neuroimage 2011;54:131-41.  Back to cited text no. 10
    
11.
Martin-Soelch C. Neuroadaptive changes associated with smoking: Structural and functional neural changes in nicotine dependence. Brain Sci 2013;3:159-76.  Back to cited text no. 11
    
12.
Lin F, Wu G, Zhu L, Lei H. Altered brain functional networks in heavy smokers. Addict Biol 2015;20:809-19.  Back to cited text no. 12
    
13.
Lin F, Wu G, Zhu L, Lei H. Region-specific changes of insular cortical thickness in heavy smokers. Front Hum Neurosci 2019;13:265.  Back to cited text no. 13
    
14.
Watts SA, Noble SL, Smith PO, Disco M. First-line pharmacotherapy for tobacco use and dependence. J Am Board Fam Pract 2002;15:489-97.  Back to cited text no. 14
    
15.
Beard E, West R, Michie S, Brown J. Association between electronic cigarette use and changes in quit attempts, success of quit attempts, use of smoking cessation pharmacotherapy, and use of stop smoking services in England: Time series analysis of population trends. BMJ 2016;354:i4645.  Back to cited text no. 15
    
16.
Molyneux A, Lewis S, Leivers U, Anderton A, Antoniak M, Brackenridge A, et al. Clinical trial comparing nicotine replacement therapy (NRT) plus brief counselling, brief counselling alone, and minimal intervention on smoking cessation in hospital inpatients. Thora×2003;58:484-8.  Back to cited text no. 16
    
17.
Heydari G, Masjedi M, Ahmady AE, Leischow SJ, Lando HA, Shadmehr MB, et al. A comparative study on tobacco cessation methods: A quantitative systematic review. Int J Prev Med 2014;5:673-8.  Back to cited text no. 17
    
18.
Mills EJ, Wu P, Spurden D, Ebbert JO, Wilson K. Efficacy of pharmacotherapies for short-term smoking abstinance: A systematic review and meta-analysis. Harm Reduct J 2009;6:25.  Back to cited text no. 18
    
19.
Sood A, Ebbert JO, Sood R, Stevens SR. Complementary treatments for tobacco cessation: A survey. Nicotine Tob Res 2006;8:767-71.  Back to cited text no. 19
    
20.
Ben-Shachar D, Belmaker RH, Grisaru N, Klein E. Transcranial magnetic stimulation induces alterations in brain monoamines. J Neural Transm (Vienna) 1997;104:191-7.  Back to cited text no. 20
    
21.
Balfour DJ, Ridley DL. The effects of nicotine on neural pathways implicated in depression: A factor in nicotine addiction? Pharmacol Biochem Behav 2000;66:79-85.  Back to cited text no. 21
    
22.
Eichhammer P, Johann M, Kharraz A, Binder H, Pittrow D, Wodarz N, et al. High-frequency repetitive transcranial magnetic stimulation decreases cigarette smoking. J Clin Psychiatry 2003;64:951-3.  Back to cited text no. 22
    
23.
Strafella AP, Paus T, Barrett J, Dagher A. Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus. J Neurosci 2001;21:RC157.  Back to cited text no. 23
    
24.
Hauer L, Scarano GI, Brigo F, Golaszewski S, Lochner P, Trinka E, et al. Effects of repetitive transcranial magnetic stimulation on nicotine consumption and craving: A systematic review. Psychiatry Res 2019;281:112562.  Back to cited text no. 24
    
25.
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. J Clin Epidemiol 2009;62:e1-34.  Back to cited text no. 25
    
26.
Maglione MA, Maher AR, Ewing B, Colaiaco B, Newberry S, Kandrack R, et al. Efficacy of mindfulness meditation for smoking cessation: A systematic review and meta-analysis. Addict Behav 2017;69:27-34.  Back to cited text no. 26
    
27.
Kang N, Kim RK, Kim HJ. Effects of transcranial direct current stimulation on symptoms of nicotine dependence: A systematic review and meta-analysis. Addict Behav 2019;96:133-9.  Back to cited text no. 27
    
28.
Guyatt GH, Haynes RB, Jaeschke RZ, Cook DJ, Green L, Naylor CD, et al. Users' Guides to the Medical Literature: XXV. Evidence-based medicine: Principles for applying the Users' Guides to patient care. Evidence-Based Medicine Working Group. JAMA 2000;284:1290-6.  Back to cited text no. 28
    
29.
Guyatt G, Gutterman D, Baumann MH, Addrizzo-Harris D, Hylek EM, Phillips B, et al. Grading strength of recommendations and quality of evidence in clinical guidelines: Report from an American College of Chest Physicians task force. Chest 2006;129:174-81.  Back to cited text no. 29
    
30.
Dieler AC, Dresler T, Joachim K, Deckert J, Herrmann MJ, Fallgatter AJ. Can intermittent theta burst stimulation as add-on to psychotherapy improve nicotine abstinence? Results from a pilot study. Eur Addict Res 2014;20:248-53.  Back to cited text no. 30
    
31.
Dinur-Klein L, Dannon P, Hadar A, Rosenberg O, Roth Y, Kotler M, et al. Smoking cessation induced by deep repetitive transcranial magnetic stimulation of the prefrontal and insular cortices: A prospective, randomized controlled trial. Biol Psychiatry 2014;76:742-9.  Back to cited text no. 31
    
32.
Trojak B, Meille V, Achab S, Lalanne L, Poquet H, Ponavoy E, et al. Transcranial magnetic stimulation combined with nicotine replacement therapy for smoking cessation: A randomized controlled trial. Brain Stimul 2015;8:1168-74.  Back to cited text no. 32
    
33.
Sheffer CE, Bickel WK, Brandon TH, Franck CT, Deen D, Panissidi L, et al. Preventing relapse to smoking with transcranial magnetic stimulation: Feasibility and potential efficacy. Drug Alcohol Depend 2018;182:8-18.  Back to cited text no. 33
    
34.
Li X, Hartwell KJ, Henderson S, Badran BW, Brady KT, George MS. Two weeks of image-guided left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation improves smoking cessation: A double-blind, sham-controlled, randomized clinical trial. Brain Stimul 2020;13:1271-9.  Back to cited text no. 34
    
35.
Zangen A, Moshe H, Martinez D, Barnea-Ygael N, Vapnik T, Bystritsky A, et al. Repetitive transcranial magnetic stimulation for smoking cessation: A pivotal multicenter double-blind randomized controlled trial. World Psychiatry 2021;20:397-404.  Back to cited text no. 35
    
36.
Kedzior KK, Gerkensmeier I, Schuchinsky M. Can deep transcranial magnetic stimulation (DTMS) be used to treat substance use disorders (SUD)? A systematic review. BMC Psychiatry 2018;18:137.  Back to cited text no. 36
    
37.
Wray JM, Gass JC, Tiffany ST. A systematic review of the relationships between craving and smoking cessation. Nicotine Tob Res 2013;15:1167-82.  Back to cited text no. 37
    
38.
Gass JC, Motschman CA, Tiffany ST. The relationship between craving and tobacco use behavior in laboratory studies: A meta-analysis. Psychol Addict Behav 2014;28:1162-76.  Back to cited text no. 38
    
39.
Yan T, Xie Q, Zheng Z, Zou K, Wang L. Different frequency repetitive transcranial magnetic stimulation (rTMS) for posttraumatic stress disorder (PTSD): A systematic review and meta-analysis. J Psychiatr Res 2017;89:125-35.  Back to cited text no. 39
    
40.
Masuda F, Miyazaki T, Nakajima S, Tsugawa S, Wada M, Tarumi R, et al. A systematic review and meta-analysis on excitability and inhibitory imbalance of the motor cortex as indexed with TMS in autism spectrum disorder. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 2019;12:395.  Back to cited text no. 40
    
41.
Tavares DF, Myczkowski ML, Alberto RL, Valiengo L, Rios RM, Gordon P, et al. Treatment of bipolar depression with deep TMS: Results from a double-blind, randomized, parallel group, sham-controlled clinical trial. Neuropsychopharmacology 2017;42:2593-601.  Back to cited text no. 41
    
42.
Simpson KN, Welch MJ, Kozel FA, Demitrack MA, Nahas Z. Cost-effectiveness of transcranial magnetic stimulation in the treatment of major depression: A health economics analysis. Adv Ther 2009;26:346-68.  Back to cited text no. 42
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
   
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
   Abstract
  Introduction
  Methods
  Results
  Discussion
  Conclusions
   References
   Article Figures
   Article Tables

 Article Access Statistics
    Viewed138    
    Printed10    
    Emailed0    
    PDF Downloaded15    
    Comments [Add]    

Recommend this journal