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@PeterBrukner discusses major headline: Successful antibiotic treatment in a subset of people with chronic low back pain

Tuesday, May 21, 2013

This post was originally published on the BJSM blog site. Used with permission. 

It is not often that something I read in the medical research literature gives me goosebumps and an incredible urge to tell everyone I know about it (thank god for Twitter!). I had that feeling today when, after an article in this morning’s Guardian newspaper, I read two recent papers published by a Danish group of researchers led by Hanne Albert in the European Spine Journal (links below).

Infection and low back pain!?

The papers relate to the possibility of an infective cause in a sub-group of patients with chronic low back pain. This sub-group is those patients with Modic changes. Modic changes (MC) are bone oedema in the adjoining vertebra to one in which there is a disc herniation. MC are present in 46% of patents with chronic low back pain compared to 6% in the general population. MC can only be reliably detected using MR imaging. A number of previous studies have demonstrated the presence of bacteria especially Propionbacterium acnes (P. acnes) in disc nucleus tissue evacuated at surgery from patients with lumbar disc herniation.

Photo by Andreanna Moya Photography. Used with permission. All rights reserved. Source: flickr

Photo by Andreanna Moya Photography. Used with permission. All rights reserved. Source: flickr

The first paper Does nuclear tissue infected with bacteria following disc herniations lead to Modic changes in the adjacent vertebrae? reports on 61 patients who had nuclear disc material removed while undergoing surgery for chronic low back pain. Microbiological cultures were positive in 28 (46%) patients, of which 26/28 were anaerobic cultures, 2 (3%) aerobic and 4 (7%) mixed. In the discs with a nucleus with anaerobic bacteria present, 80% developed MC in the vertebrae adjacent to the previous disc herniation, compared to none in the aerobic group and 44% with negative cultures. They concluded that the occurrence of MCs in the vertebrae adjacent to a previously herniated disc may be due to oedema surrounding an infected disc.

How do intervetebral discs become infected?

Organisms such as P. acnes are commonly found in hair follicles in the skin and in the oral cavity. They frequently invade the circulatory system during tooth brushing where they do not present an immediate risk because the blood stream is an aerobic environment. When an intervertebral disc is herniated, nuclear material extrudes into the spinal canal. Within a short time, neocapillarisation begins in and around the extruded nucleus material, inflammation occurs and brings with it macrophages. So far so good – no debate about any of that.

The innovation of the authors is their proposal that avascular and thus anaerobic disc provides an ideal environment for these anaerobic bacteria to flourish. In this setting, anaerobic bacteria that are normally inconsequential (low virulent) may enter the disc and give rise to a slowly developing infection.

Local inflammation in the adjacent bone (MC Type 1) may be a secondary effect due to cytokine production or microbial metabolites (e.g. propionic acid) entering the vertebrae through normal disc nutrition. P. acnes is known from the skin to trigger an adjacent inflammatory response. P. acnes cannot multiply in the highly vascular aerobic bone and are therefore not present where the MC occur.

All good in theory but what about an RCT?

The second paper is entitled Antibiotic treatment in patients with chronic low back pain and vertebral bone edema (Modic type 1 changes): a double-blind randomized clinical controlled trial of efficacy.  this paper reports the efficacy of antibiotic treatment in this group of patients with MC lesions and chronic low back pain. This double blind RCT study examined 162 patients with chronic low back pain (> 6 months duration) occurring after a previous disc herniation AND who had MC changes in the vertebrae adjacent to the previous herniation. Subjects were randomised to either 100 days of antibiotic treatment (Bioclavid) of two different dosages or placebo. Outcomes were evaluated at baseline, end of treatment and at 1 year follow up.

Primary outcomes were the well accepted disease-specific disability Roland Morris Questionnaire as well as the report of lumbar pain. The antibiotic group made highly statistically significant improvements on all outcome measures; the improvement continued from 100 days follow up until 1 year follow up. For example, on the disease specific disability, the antibiotic group was 15 at baseline, 11 at 100 days and 5.7 at 1 year compared to placebo (15, 14, 14). The report of lumbar pain decreased much more in the antibiotic group who started at a score of 6.7 and improved to scores of  5.0 (100 days) and 3.7 (1 year). The placebo group mean report of lumbar pain stayed constant at 6.3 from baseline through 100 days and 1 year (lower is better, of course).

Biologically plausible time course

Patients also reported that pain relief and improvement in disability commenced gradually, for most patients 6-8 weeks after the start of the antibiotic tablets and for some at the end of the treatment period. Improvements reportedly continued long after the end of the treatment period, at least for another 6 months, and some patients reported continuing improvement at 1-year follow up. The improvement seen in the antibiotic group at 1 year follow up was approximately twice that observed at the end of the 100 day treatment period, suggesting that a biological healing process that starts only when and after the bacteria have been killed.

Half the treatment group took one Bioclavid (amoxycillin-clavulanate 500mg/125mg) tablet three times a day while the other half took two tablets. The authors state that the long duration of antibiotic treatment is commonly prescribed for post-operative discitis. There was a trend towards an improvement with double dose, but did not reach significance.

What should we make of these papers?

This treatment is certainly an exciting possibility for one of the most difficult management challenges in medicine.  At this stage all the authors are saying is that in a particular sub-group of patients with chronic (>6 months) low back pain, those with Modic changes on MRI scan after lumbar disc herniation may respond well to long term antibiotic treatment. We are reluctant to prescribe long term antibiotics for reasons of potential development of resistance but there seems to be a rationale for long term use in this situation. Further studies need to assess the efficacy of shorter terms of treatment. Because this is the BJSM blog, we can point out to readers that the group’s pilot study was not accepted by a number of famous journals but saw the light of day via BJSM’s ‘peer-review fair review’ process. That paper came out in 2008.

I would think on the basis of this research it is reasonable to prescribe the recommended antibiotic program to those who strictly meet the clinical and MR imaging criteria. Especially if the only alternative seems to be surgery which has limited efficacy in these patients and is obviously vast more expensive than a course (albeit prolonged) of antibiotic therapy. Remember if you have this infection surgery will not be treating the cause.

It took the Nobel prize winning research  on Heliobacter and its relationship to stomach ulcers of West Australians Barry Marshall and Robin Warren to alert the skeptical medical community of the potential of infective causes of common conditions. Many investigators are currently seeking infective causes for a wide variety of common and uncommon medical disorders. This research will encourage such investigation. Undoubtedly we will find more causal infective relationships. Further work needs to be done to answer a range of questions (which antibiotic, what dose, how  long etc), but these two papers are an exciting step forward in the management of a very difficult condition. If I were a sufferer of chronic low back pain I would be feeling a little more optimistic after the publication of this research.

Dr Peter Brukner is an experienced team physician and writing in his capacity as CSM co-author, BJSM Senior Associate Editor, and regular blogger. @PeterBrukner

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“Hey Doc, those exercises you suggested…….” ~ Ann Gates (@exerciseworks)

Friday, May 17, 2013

This post was originally published on the BJSM blog site. Used with permission.

Many diseases and long term health conditions respond clinically to exercise medicine. Just like medicines, such as statins, different exercises and physical activities have the ability to transform patient’s lives, control their symptoms and prevent and treat disease successfully.

Photo by inkknife_2000. Used with permission. All rights reserved. Source: flickr

Photo by inkknife_2000. Used with permission. All rights reserved. Source: flickr

The evidence for the clinical practice of ‘exercise as a medicine’ is supported by the UK Chief Medical Officers, the World Health Organization and many international medical organisations. However, it is ultimately prescribed and supported by the health care team that provides direct patient care.

For this reason, within medicine and health care settings we must encourage the perspective that exercise advice and support are critical aspects of ‘world class, personalised patient care’. Many patients may benefit from exercise advice as part of the management and treatment protocols for their diseases and lifestyles. This includes non-communicable diseases and acute problems, such as surgery.

The list of medical evidence supporting specific exercises and fun physical activities for improving quality of life and physical and mental health on personal, national and international levels includes: type 2 diabetes, cancer, heart disease, stroke, osteoporosis, Parkinson’s disease, hypertension, obesity, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), back pain, anxiety, depression, asthma, peripheral arterial disease, pre and post operative surgery…..

Many health professionals practice medicine because they love patient care and using their skills and knowledge to help patients improve their health. Providing quality exercise advice has a similarly clinically satisfying outcome. Patients can improve their mobility, experience life changing better health and more importantly see their symptoms improve and their risks of serious health problems diminish. This may be demonstrated through improved blood pressure control, better lipid profiles or just simply improved strength and balance that helps reduce falls risk.

A great, inspiring video shows how careful motivational support, together with the right exercise advice, at the right time, can transform patient health.

After all, when that patient says:

“Hey Doc, that exercise advice you suggested…….”

“It worked! I can now take my grandchildren to the park, and share in the joy of them growing up…”

“Well, that’s just fantastic!” replied the doctor. “Your blood pressure readings are down, I see you’ve lost weight, and management of your blood pressure is looking good.”

Because patients are worth that ‘brief intervention!”

Ann Gates is a Chronic Disease Exercise Specialist and Founder of “Exercise Works!” (@exerciseworks). Exercise Works! is dedicated to educating and supporting health professionals to understand the benefits and the ability to give constructive exercise advice to patients. They also produce a variety of products to help clinicians give safe and effective, brief intervention, exercise support to each patient consult. To learn more about Exercise Works! check out their website.

Video kindly provided with permissions via FitBehavior : promoting health through inspiring patient stories! @FitBehavior

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How can we get school children physically active? ~ Sigmund A Anderssen, PhD

Tuesday, May 14, 2013

Regular physical activity in school has the potential of improving health outcomes in children and youth, including overweight and obesity. Recent research shed light upon the opportunities and challenges of implementing physical activity interventions in schoolchildren.

Regular physical activity is necessary for normal growth and the development of cardio-respiratory endurance, muscle strength, flexibility, motor skills and agility.  In addition, regular physical activity has an impact on a range of health outcomes in children and youth 1 including overweight and obesity. Children are seen as a critical target group for public health efforts to prevent overweight and obesity.

Photo by Kris Krug. Used with permission. All rights reserved. Source: flickr

Photo by Kris Krug. Used with permission. All rights reserved. Source: flickr

Grydeland et al recently reported the effect of a 20-month school-based intervention on body composition outcomes 2. The intervention succeeded in increasing the overall physical activity among the participants and in particular among girls and low-active participants. Furthermore, the study demonstrated beneficial effects on BMI in girls.

These results on body composition outcomes are promising. However, no intervention effects were seen among boys or among participants of parents with lower levels of education. There appear to be some reasons why the impact was not better and did not reach boys.  Among them were that low cost and applicability in the public school system had high priority in the study by Grydeland, and the intervention components were primarily delivered through the school teachers and dependent on their devotion.

Even with ambitious goals for what activities the children should engage in, the impact depends on what the children actually do.  Just like when patients take their medications it works, if they do not, the treatment does not work. The challenge is to implement physical activity with strong enough impact.

From the literature 3-6 we know:

  • Children become less physically active as they approach adolescence and adulthood
  • Girls are generally less active than boys
  • Children that are physically active during childhood and adolescence are more likely to be physically active as adults
  • Learning different types of physical activities in childhood may help you dare join in activities later in life
  • Mandatory physical activity in school is not prioritized
  • There is no evidence that added physical activity to school curriculum by taking time from other subjects hinder academic performance

The school represents the only available arena where all children, irrespective of social background, can be reached continuously over a long period of time. Therefore we should urge the decision makers to prioritize physical activity at school and ensure that the PE teachers have enough competence. However, if this is just lip service and halfhearted whitewashing, the likely outcome is an increase in social inequalities rather than a reduction in them.

For more information on sports medicine and the younger athlete, turn to Chapter 42 in Clinical Sports Medicine.

Sigmund A Anderssen is Professor in Physical Activity and Health, and Department Head of Sports Medicine at the Norwegian School of Sport Sciences. His main research areas are physical fitness and physical activity surveillance and physical activity in relation to risk factors for diabetes and cardiovascular disease in both children and adults.

References:

  1. Strong WB, Malina RM, Blimkie CJ et al. Evidence based physical activity for school-age youth. J Pediatr 2005; 146:732-37.
  2. Grydeland M, Bjelland M, Anderssen SA, Klepp KI, Bergh IH, Andersen LF, Ommundsen Y, Lien N. Effects of a 20-month cluster randomised controlled school-based intervention trial on BMI of school-aged boys and girls: the HEIA study. Br J Sports Med. 2013 Apr 27. [Epub ahead of print]
  3. Kolle E, Steene-Johannessen J, Andersen LB, Anderssen SA. Objective measures of physical activity level and directly measured aerobic fitness in a population based sample of Norwegian 9- and 15-year olds. Scand J Med Sci Sports. 2010 Feb;20(1):e41-7. doi: 10.1111/j.1600-0838.2009.00892.x.
  4. Telama R, Yang X, Viikari J, et al. Physical activity from childhood to adulthood. A 21-year tracking study.  Am J Prev Med 2005;28:267–73.
  5. Ahamed Y, Macdonald H, Reed K, Naylor PJ, Liu-Ambrose T, McKay H. School-based physical activity does not compromise children’s academic performance. Med Sci Sports Exerc. 2007 39:371-6.
  6. François Trudeau F, Shephard RJ. Physical education, school physical activity, school sports and academic performance. Int J Behav Nutr Phys Act. 2008; 5: 10.
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How do I decide to treat? ~ Peter Brukner OAM, MBBS, FACSP

Friday, May 10, 2013

This post was originally published on the BJSM blog site. Used with permission.

The decision on how to treat a particular condition is sometimes very clear. For that particular condition e.g. a bacterial infection, there is a treatment e.g. specific antibiotic, that is simple, safe and effective in nearly every case.

In musculoskeletal (MSK) medicine, frequently it is not clear which is the best form of treatment. Let’s take tennis elbow as an example. Suggested treatments include anti-inflammatory medication, massage, strengthening, dry needling, corticosteroid or PRP injection, shock wave, surgery and probably a few others. How do I decide?

There are four main factors that I consider when I am deciding on a treatment.

The first is evidence-based medicine (EBM). We live in an era of evidence in medicine. However for various reasons, MSK medicine is generally lacking in evidence for many conditions. This is partly because it is a relatively new specialty, and secondly because most research trials are funded by drug companies and involve their particular drug.

Peter Brukner with Carling Cup 2012

Peter Brukner with Carling Cup 2012

There are minimal funding sources for non- pharmaceutical treatment trials. Anyone who has read Ben Goldacre’s book Big Pharma1 would be somewhat disillusioned about the role of the big pharmaceutical companies in drug research anyway.

The volume of EBM in MSK medicine is slowly growing, but it is probably safe to say that it lags behind other branches of medicine. The other reason why EBM is lacking in musculoskeletal medicine is the difficulty of the research. No two injuries are identical so large numbers are required. There are also fewer objective measures such as blood tests. MSK medicine relies on pain (notoriously unreliable) and various markers of function (range of motion, strength etc.) as outcome measures.

The quality of much of the evidence in MSK medicine while slowly improving is still relatively low. Good RCTs (Oxford Level 1) are rare and much of the evidence is case series (levels 3-4) or individual cases.

When dealing with high level athletes, sometimes it is not appropriate to make the same assumptions about their response to treatment as others. Some would argue that the elite athlete is a different physiological animal and therefore may respond differently to treatment.

There will never be good research evidence for treatment of elite athletes as the concept of a blinded placebo trial will not be tolerated by the elite athlete who is desperate to return to his or her sport as soon as possible.

The second factor that I use is personal experience. Obviously the longer you practice, the more exposure you have to each condition and the broader your experience is in treating that condition. Ultimately you will have seen the more common conditions many times, treated them in various ways and you will know what works or does not work, in your hands anyway.

The third factor that influences how I treat someone is expert opinion. That can be in the form of a textbook, a review or opinion article, a lecture or conference presentation from an expert in the field, or simply discussion with learned colleagues.  I am not shy in picking up the phone and calling a colleague who is more experienced in managing a particular condition. Nowadays with email, messaging and Skype it is nearly always possible to discuss with a colleague. Expert opinion is only Level 5 on the Oxford levels of evidence, but this does not diminish its importance.

The fourth and final factor is the patient’s choice2. The degree of patient involvement varies considerably from case to case.  In situations where there is a clear cut evidence-based expert opinion supported form of treatment then it is fair to firmly recommend the desired treatment. When the research is equivocal or non-existent and opinion divided, then it is reasonable to explain the different alternatives to the patient and invite their involvement in the decision making.

Elite athletes in particular will often be quite knowledgeable about their particular condition due to their own or their colleagues’ past experiences, and may also have been exposed to various folklore treatments common in their particular sport. When their careers could be affected by the choice of treatment then it is certainly reasonable for them to be heavily involved in the choice.

In most situations we use a combination of these four factors to decide on a particular treatment. In the ideal situation there is strong evidence for a particular form of treatment, you have had good experience with that treatment yourself, the experts advocate this treatment and the patient is keen to go ahead. Unfortunately that ideal scenario is the exception rather than the norm.

We must also be aware of our own biases3,4. This may be towards a treatment we enjoy doing (e.g. dry needling), it may be more highly remunerated (shockwave, injections, surgery) or one in which we have a research interest.

For those working with professional athletes and teams there will also be pressure from the athlete, coach, team owner etc to make a decision that maximises the chances of the athlete returning to play as soon as possible5. Sometimes this is not actually in the patient’s best interests6 and there are some startling stories for this paragraph but  not for public consumption. This pressure can be uncomfortable in any setting; it is particularly so when an official threatens that the doctor’s job is in jeopardy unless a certain decision is made. Irrespective of the pressure, it is imperative to remember that as physicians our first duty is to our patient.

Many of you will use the same approach and we recognise the appearance of three of these four factors in Sackett’s7 definition of evidence-based practice – “the integration of best research evidence with clinical expertise and patient values”.

Dr Peter Brukner is an experienced team physician and writing in his capacity as CSM co-author, BJSM Senior Associate Editor, and regular blogger. @PeterBrukner

References

  1. Goldacre B. Big Pharma. HarperCollins, London, 2012
  2. Quill TE, Holloway RG. Evidence, preferences, recommendations – finding the right balance of patient care. NEJM 2012;366(18):1653-5
  3. Kahneman D. Thinking, Fast and Slow Penguin, London 2012
  4. Kahneman D, Lovallo D, Sibony O. Before you make that big decision… Harv Bus Rev 2011;89(6):50-60
  5. Levy D, Delaney JS. A risk/tolerance approach to the pre-participation examination. Clin J Sport Med 2012;22(4):309-10
  6. Matheson GO, Shultz R, Bido J et al. Return-to-play decisions: are they the team physician’s responsibility? Clin  J Sport Med 2011; 21(1):25-30
  7. Sackett DI, Straus S, Richardson WM et al. Evidence-based medicine: how to practice and teach EBM. London. Churchill Livingstone. 1995
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Sit Less to Move More ~ Maureen Ashe, PhD

Tuesday, May 07, 2013

 Abundant evidence exists extolling the benefits of physical activity, and specifically to include more exercise into daily life. Despite this, ample data highlights that many people are inactive [1 2], sedentary, [3], and the group who are most at risk are older adults.

Fortunately, evidence suggests that health behaviours adopted earlier at midlife reduce the risk for developing chronic disease [4]. Prevention strategies to increase physical activity in middle-aged can result in downstream benefits across many domains such as increased fitness, enhanced social engagement, and a positive impact on quality of life.

The question remains: how do we implement sustainable solutions for people to uptake and adhere to a physically active lifestyle? One possible solution is to “re-engineer energy expenditure” [5] back into our lives through activities of daily living and utilitarian walking.

Photo by “AlmaGamil_Philippines”. Used with permission. All rights reserved. Source: flickr

Photo by “AlmaGamil_Philippines”. Used with permission. All rights reserved. Source: flickr

Recently the science [6] and epidemiology [7 8] of sedentary behaviour has emerged in the literature and mass media, challenging previous terminology used to denote someone who did not engage in physical activity. Historically people have used the words sedentary or inactive interchangeably. Guidelines published in 2012 by the Sedentary Behaviour Research Network [9] propose that inactivity is defined by an individual not meeting current recommendations for physical activity, ie, not meeting 150 minutes per week of moderate to vigorous physical activity (MVPA).

In contrast, sedentary behaviour refers to waking activities in a sitting or reclining posture, which are low in energy expenditure defined by less than or equal to 1.5 metabolic equivalent of task (MET) [9].

For some older adults, it may be insurmountable to tackle 150 minutes per week of MVPA at least in the beginning. In contrast, it may be easier to suggest that an activity program begins by simply sitting less throughout the day. If watching TV, have standing breaks during the commercials (or even reduce total TV time altogether!); wash the dishes by hand instead of loading up a dishwasher; and/or walking to the local mailbox or store.

A feasibility study by Gardiner and colleagues [10] highlighted that a brief behavioural intervention for older adults 65 years plus resulted in a three percent reduction in sitting time over a two-week period. An interesting detail of this study was that the sitting time reduction was replaced by a two percent increase in light activity and a one percent increase in MVPA.

Starting with reduced sitting time is a potential way towards increasing physical activity. The science of sedentary behaviour and physical activity, although distinct, still operate collectively when taking a full day approach to active living and health.

Recently, Robinson [11] coined the term “stealth intervention” to describe his behavioral programs designed to tackle the obesity epidemic. He posits interventions such as traditional dancing or raising awareness of food-related environmental issues provide positive health benefits, without actually setting the long-term goal of improving health. Does this make reducing sedentary behaviour a stealth intervention?

For older adults, and especially those with mobility challenges, a “Sit Less to Move More” strategy may be an optimal approach to slowly adopt physical activity, and especially exercise, as a way of life.

Maureen Ashe is an Assistant Professor in the Department of Family Practice at the University of British Columbia, and an investigator at the Centre for Hip Health & Mobility in Vancouver, Canada. Her research interests include investigating older adults’ physical activity and sedentary behaviour patterns and the influence on mobility. More recently, she expanded her focus to include the role of the built and social environments on older adults’ community participation.

References:

1. Troiano RP, Berrigan D, Dodd KW, et al. Physical activity in the United States measured by accelerometer. Med Sci Sports Exerc 2008;40(1):181-8 doi: 10.1249/mss.0b013e31815a51b3[published Online First: Epub Date]|.

2. Ashe MC, Miller WC, Eng JJ, et al. Older adults, chronic disease and leisure-time physical activity. Gerontology 2009;55(1):64-72 doi: 10.1159/000141518[published Online First: Epub Date]|.

3. Matthews CE, Chen KY, Freedson PS, et al. Amount of time spent in sedentary behaviors in the United States, 2003-2004. Am J Epidemiol 2008;167(7):875-81 doi: kwm390 [pii] 10.1093/aje/kwm390[published Online First: Epub Date]|.

4. Willis BL, Gao A, Leonard D, et al. Midlife fitness and the development of chronic conditions in later life. Arch Intern Med 2012;172(17):1333-40 doi: 10.1001/archinternmed.2012.3400[published Online First: Epub Date]|.

5. Stein J. Stay moving, not still. Exercise slows aging and makes us feel better. Los Angeles Times. Los Angeles, 2009.

6. Hamilton MT, Hamilton DG, Zderic TW. Exercise physiology versus inactivity physiology: an essential concept for understanding lipoprotein lipase regulation. Exerc Sport Sci Rev 2004;32(4):161-6 doi: 00003677-200410000-00007 [pii][published Online First: Epub Date]|.

7. Owen N, Bauman A, Brown W. Too much sitting: a novel and important predictor of chronic disease risk? BJSM 2009;43(2):81-3 doi: bjsm.2008.055269 [pii] 10.1136/bjsm.2008.055269[published Online First: Epub Date]|.

8. Proper KI, Singh AS, van Mechelen W, et al. Sedentary behaviors and health outcomes among adults: a systematic review of prospective studies. Am J Prev Med 2011;40(2):174-82 doi: 10.1016/j.amepre.2010.10.015[published Online First: Epub Date]|.

9. Sedentary Behaviour Research Network. Letter to the editor: standardized use of the terms “sedentary” and “sedentary behaviours”. Appl Physiol Nutr Metab 2012;37(3):540-2 doi: 10.1139/h2012-024[published Online First: Epub Date]|.

10. Gardiner PA, Eakin EG, Healy GN, et al. Feasibility of reducing older adults’ sedentary time. Am J Prev Med 2011;41(2):174-7 doi: 10.1016/j.amepre.2011.03.020[published Online First: Epub Date]|.

11. Robinson TN. Stealth interventions for obesity prevention and control: motivating behavior change. In: Dube L, Bechara A, Dagher A, et al., eds. Obesity Prevention: The Role of Brain and Society on Individual Behavior. New York, NY: Elsevier, 2010.

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