Here is my presentation on the evidence for a few common veterinary practices.

INTRODUCTION
Experienced clinicians often have an enormous knowledge base about the health problems their patients present with and the available diagnostic and therapeutic options. This knowledge is built over time from a variety of sources: basic pathophysiology and clinical information learned in school; practice tips and pearls imparted by professors and speakers at continuing education meetings; review articles and primary research papers in veterinary journals; textbooks; advice from mentors and colleagues in practice; and of course clinical experience with previous cases.

This knowledge base smoothly and efficiently informs the day-to-day activities of clinical practice. When cases with familiar features are seen, the appropriate diagnostic and treatment steps often come to mind automatically, or with minimal prodding. Unlike students and new graduates, experienced clinicians often have little sense of dredging up facts committed to memory and more of a sense of simply knowing things. One of the hallmarks of expertise is that the collating of observations and relevant knowledge into a coherent picture of the problem and a plan become less deliberate and more automatic with time.¹

While this process, which is a universal and automatic feature of how the human brain functions, leads to greater efficiency than the explicit, conscious use of algorithms and reference sources employed by less experienced practitioners, it has a number of potential limitations. One problem, for example, is that the knowledge one relies on often can no longer be connected to its original source. We often simply know things without being aware of how we came to know them. This limits our ability to judge the reliability of the source of our knowledge. In fact, such established, automatic knowing often generates a sense of certainty greater than that which accompanies deliberately seeking and finding information.² We are more likely to trust what we already know, even if we don’t remember where we learned it, than we are to trust what we have just discovered after searching a trustworthy source of information.

There are also a large number of well-characterized cognitive biases and sources of errors inherent in how our brains acquire, process, store, and utilize information that can lead us astray.³ These are more likely to create error when our reasoning is automatic rather than deliberate, as it necessarily must be in an efficient clinical environment that is not devoted primarily to teaching.

One of the major functions of evidence-based veterinary medicine (EBVM) is to provide tools and resources to make the knowledge base we employ more reliable. This includes generating better quality information through research and facilitating the integration of that information into clinical decision making. When the relevant evidence is of high quality, this can add confidence to our decisions.

More commonly, when the evidence has significant limitations, we may end up with less confidence in our knowledge than we would have without an explicit evaluation of the evidence. However, this is not as undesirable an outcome as it may appear. A clear, accurate understanding of the uncertainty associated with a particular practice protects us, and our patients, from the dangers of acting with unjustified confidence. We are more likely to weigh thoughtfully the risks and benefits of action in the context of an individual case when we understand the degree of uncertainty about our ability to predict or manipulate the patient’s condition.

Being clear about the sources of our knowledge, and the appropriate level of confidence to have in them, also aids in fulfilling our duty to provide clients with informed consent. Surveys of veterinary clients have shown that they value truthfulness highly in the information we provide to them, and that they want to be made aware of the uncertainties involved in the treatment of their animals.^4-5 Only if we understand the reliability and limitations of the information we employ in making our recommendations can we give clients the knowledge and guidance they need to make informed choices.

The purpose of these lectures is to examine some widespread or long-standing beliefs and practices in small animal medicine and assess their evidentiary foundations. In some cases, this may clearly validate or invalidate these beliefs. In most cases, however, such an exploration will likely not lead to greater certainty but to a clearer understanding of the degree of uncertainty associated with these beliefs. Hopefully, this will be useful in making clinical decisions and in communicating with clients. The exercise may also be useful in illustrating how to make use of the research literature in establishing and maintaining the knowledge base that informs one’s clinical practice.

Some of the topics that will be covered include:

1. Pheromone therapy for behavioral problems in dogs and cats
2. Anti-histamines for treatment of atopic dermatitis in dogs
3. Steroids for anaphylaxis and acute allergic reactions

REFERENCES

1. Benner, P. From novice to expert. Amer J Nursing, 1982; 82(3):402-7.
2. Burton, R. On Being Certain: Believing You’re Right Even When You’re Not. New York: St. Martin’s Press. 2008
3. McKenzie, BA. Veterinary clinical decision-making: cognitive biases, external constraints, and strategies for improvement. J Amer Vet Med Assoc. 2014;244(3):271-276.
4. Mellanby RJ, Crisp J, De Palma G, et al. Perceptions of veterinarians and clients to expressions of clinical uncertainty. J Small Anim Pract 2007;48:26–31.
5. Stoewen DL, et al.  (2014) Qualitative study of the information expectations of clients accessing oncology care at a tertiary referral center for dogs with life-limiting cancer. J Am Vet Med Assoc. 2014;245(7):773-83.

Slides

Here are my notes and slides from my presentation of low-level lasers.

WHAT IS LASER THERAPY?
Laser therapy is, at its simplest, the application of light to living organisms to obtain health benefits. However, there is a bewildering amount of detail behind this simple idea. The wavelength and power of the laser used, the location and duration of exposure, the number of treatments, the conditions for which treatment might be useful, and many other variables are subject to extensive debate. Generally, low-level or “cold” lasers (which is really a misnomer since many do generate heat during use) utilize wavelengths between 600-1000nm and power levels from 5-500mW. More powerful lasers are used in surgery, but these function primarily to cut or cauterize tissue, break up uroliths, or otherwise cause controlled damage. Low-level lasers are intended to have biological effects on tissue, known as photobiomodulation, without causing damage.

The FDA classifies lasers, from Class 1 to Class 4, based primarily on their potential to harm the user or the patient. Low-level laser therapy typically involves Class 3 lasers, though more powerful Class 4 devices are sometimes used for non-surgical therapy.

WHAT ARE THE POSSIBLE USES FOR LASER THERAPY?
The most common recommended uses of low-level laser therapy are to facilitate wound healing, reduce inflammation, and improve musculoskeletal pain or disease. However, proponents of laser therapy, and companies selling therapeutic lasers, often claim or suggest that low-level lasers can treat nearly any medical condition. Lasers have been promoted for use in specific clinical problems (allergic skin disease, gingivitis, bacterial and viral infections, envenomation, etc.), vaguely defined general health improvement (enhancing immune function, normalizing metabolic function, “energizing” cells, etc.), and unscientific nonsense (fixing “Qi-stagnation”¹). Some practitioners recommend using laser as a means of stimulating acupuncture points, which adds the question of the efficacy of acupuncture and the selection of such points to the original question of the potential utility of laser therapy itself.

Sorting through the claims made for lasers, from the reasonable to the ridiculous, is challenging due to the heterogeneity of lasers and therapeutic approaches employed and the complexity and inconsistency of the available research on medical lasers.

WHAT IS THE EVIDENCE FOR LASER THERAPY?
The principles of Evidence-based Veterinary Medicine (EBVM) can help us sort through the evidence concerning low-level laser therapy and try and identify the strengths and limitations of the evidence for specific potential uses. Though there are various ways to organize our evaluation of the existing evidence, it is generally agreed that some sort of hierarchy of evidence is appropriate, with the most reliable types evidence at the apex and the most available, but less reliable evidence, at the base. Figure 1 illustrates one way of visualizing such a hierarchy of evidence.

Figure 1. Hierarchy of evidence. (CAT-critically-appraised topic, RCT-randomized clinical trial, CE- continuing education)

Within the levels of this hierarchy, there are multiple types of evidence which themselves have different levels of reliability. Randomized clinical trials, for example, provide better evidence than case reports, and studies in the species one intends to treat are more likely to predict outcomes than studies in another species. However, this scheme provides a convenient overview of one useful way to think about the types of evidence available to guide decisions about the use of lasers.

Systematic reviews of multiple clinical trials, with detailed analysis of the limitations of each trial and an overall assessment of the quality of evidence are the most trustworthy source of evidence on any clinical intervention. Unfortunately, such reviews are often not available in veterinary medicine, and there are none for low-level laser therapy.

Controlled clinical trials of naturally occurring disease in the target species are the next most reliable form of evidence, and there appear to be none available for veterinary patients. Some studies in clinical patients do exist, though they have significant limitations.

For example, a pilot study adding laser therapy to standard treatment for dogs with acute intervertebral disk disease suggested laser treatment might have shortened time to ambulation after surgery.² However, the absence of randomization, blinding, and placebo control limit the strength of this conclusion, and another similar study did not report a clinical benefit.³

There have been many experimental studies of laser therapy for a variety of conditions in veterinary species, however the methodological quality is variable and the results are mixed. Some studies of wound healing, for example, show possible benefits⁴ while many others do not.^5-9 Small studies looking at lasers for skin disease have also found mixed results (some beneficial effect on non-inflammatory alopecia¹⁰, no apparent effect on atopic pedal pruritis¹¹), though again there are significant methodological limitations in these studies.

Two systematic reviews of lab animal studies are available. One found that there were some potentially beneficial effects in bone healing models, though there were few studies to review.¹² The other reviewed in vitro and animal model studies relevant to wound healing and concluded rather strongly that, “these studies failed to show unequivocal evidence to substantiate the decision for trials with [low-level laser therapy] in a large number of patients…We conclude that this type of phototherapy should not be considered a valuable (adjuvant) treatment for this selected, generally therapy-refractory condition in humans.”¹³

The evidence, as usual, is much more voluminous for use of lasers in human medicine. There are literally hundreds of systematic reviews available for specific conditions, often with several different reviews of the same set of studies for particular indications. There is great inconsistency in the results. Most reviews conclude that the evidence is not strong enough to support definitive statements about efficacy. Some reviews do show some positive results, with weak to moderate evidence supporting a benefit for particular conditions, though in some cases other reviews of the same evidence reach different conclusions.

There is an enormous body of in vitro evidence showing effects of laser light on various tissues. It is clear that laser has significant biological effects in such models, and some of the effects seen could potentially have clinical benefits in living patients.

Finally, there are, of course, innumerable anecdotes regarding the effects of laser therapy, and some laser advocates are absolutely convinced by their own experiences that low-level laser is a powerful therapeutic tool. However, such anecdotal evidence can be found for most every intervention available, and equally strong anecdotal support by thousands of people over centuries has existed for many therapies that scientific research has shown conclusively to be ineffective, such as bloodletting and homeopathy. Therefore, the value of such evidence is limited to suggesting hypotheses for further research, and it cannot validate any claims about laser therapy.

IS LASER THERAPY SAFE?
Most experimental and clinical studies of low-level laser therapy have found few adverse effects. Inappropriate use of higher-power lasers or excessive duration of treat can result in heating of tissues and thermal damage in some cases. There are also potential risks to operators of laser equipment. And in the absence of research evaluating the long-term effects of ongoing laser treatment, the potential for some of the many biological effects of light on cellular metabolism to result in harm is unknown.

Safety guidelines, from government agencies, manufacturers, and the medical literature, are available and should be scrupulously followed.

BOTTOM LINE
Lasers have significant measurable effects on living tissues in laboratory experiments, so it is plausible that they might have clinical benefits. The extensive research done in humans, however, has so far only found limited evidence to support the use of lasers in a few conditions, and high-quality controlled studies often contradict the positive findings of initial, small and poorly controlled trials.

The experimental evidence in veterinary species is mixed and low quality, and there are no high-quality published clinical trials validating laser therapy for specific indications. It is possible that high-quality research may one day validate some of the claimed benefits for laser therapy. However, at present the best that can be said about this intervention is that it appears promising for some conditions, such as wounds and musculoskeletal pain.

The growing popularity of lasers is based largely on anecdotal evidence and economic factors. Laser units are being aggressively marketed to veterinarians, often using unsubstantiated claims of clinical benefits. Laser therapy represents a potential source of income for practitioners and, of course, for laser device manufacturers. It appears likely that this profit potential contributes to an enthusiasm for laser therapy not matched by the quality of scientific evidence for its benefits to patients.

Veterinary therapies often lack robust high-quality clinical trial evidence to support their use, and this is not itself a reason to avoid these therapies. However, when employing interventions that have not yet been rigorously demonstrated to be safe and effective, we have a duty to acknowledge the limitations of the evidence. Clients should be fully informed about the uncertainties concerning the effectiveness of laser therapy and the potential for unforeseen effects. Established therapies with stronger evidence identifying their risks and benefits should take precedence over promising but unproven therapies like laser treatment. And those interested in promoting low-level laser, particularly those marketing laser equipment and training, should proportion their claims to the available evidence and assume some responsibility for developing the evidence base further so that practitioners and animal owners can make better-informed decisions about this practice.

REFERENCES

1. Petermann, U. Pulse laser as ATP-generator: the use of low level laser-therapy in alleviating Qi-shortcomings. Zeitschrift für Ganzheitliche Tiermedizin. 2012 26 1 8-14
2. Draper WE, Schubert TA, Clemmons RM, Miles SA. Low-level laser therapy reduces time to ambulation in dogs after hemilaminectomy: a preliminary study. J Small Anim Pract. 2012;53(8):465–469.
3. Williams, C. Barone, G. Is Low Level Laser Therapy an Effective Adjunctive Treatment to Hemilaminectomy in Dogs with Acute Onset Parapleglia Secondary to Intervertebral Disc Disease? Proceedings, American College of Veterinary Internal Medicine Forum, Denver, CO. June, 2010.
4. Efficacy of low level LASER therapy on wound healing in dogs. Indian Journal of Veterinary Surgery 2011 32 2 103-106 Singh, M., Bhargava, M. K., Sahi, A., Jawre, S., Singh, R., Chandrapuria, V. P., Kocchar, G.
5. Grayson LC; Cassie NL; Juergen P. et al. Effect of laser treatment on first-intention incisional wound healing in ball pythons (Python regius). Am J Vet Res. October 2015;76(10):904-12.
6. Kurach LM, Stanley BJ, Gazzola KM, et al. The Effect of Low-Level Laser Therapy on the Healing of Open Wounds in Dogs. Vet Surg. 2015 Oct 8. doi: 10.1111/vsu.12407. [Epub ahead of print]
7. Madhya Pradesh Pashu Chikitsa Vishwavidyalaya, Jabalpur, MP, India. Low level laser therapy for the healing of contaminated wounds in dogs: histopathological changes. Indian Journal of Veterinary Surgery. 2013 34 1 57-58
8. In de Braekt MM, van Alphen FA, Kuijpers-Jagtman AM, et al. Effect of low level laser therapy on wound healing after palatal surgery in beagle dogs. Lasers Surg Med. 1991;11(5):462-70.
9. Petersen SL, Botes C, Olivier A, et al. The effect of low level laser therapy (LLLT) on wound healing in horses. Equine Vet J. 1999 May;31(3):228-31.
10. Olivieri, L. Cavina, D. Radicchi, G. et al. Efficacy of low-level laser therapy on hair regrowth in dogs with noninflammatory alopecia: a pilot study. Veterinary Dermatology, 2015, 26, 1, pp 35-e11
11. Stich, A. N.; Rosenkrantz, W. S.; Griffin, C. E. Clinical efficacy of low-level laser therapy on localized canine atopic dermatitis severity score and localized pruritic visual analog score in pedal pruritus due to canine atopic dermatitis. Veterinary Dermatology, 2014, 25, 5, pp 464-e74
12. Tajali, SB. MacDermid, JC. Houghton, P. et al. Effects of low power laser irradiation on bone healing in animals: a meta-analysis. Journal of Orthopaedic Surgery and Research 2010, 5:1
13. Lucas, C. Criens-Poublon, LJ. Cockrell, CT. et al. Wound healing in cell studies and animal model experiments by Low Level Laser Therapy; were clinical studies justified? a systematic review. Lasers Med Sci. 2002;17(2):110-34.

Slides

Here are the notes and slides from my presentation on Overdiagnosis.

WHAT IS OVERDIAGNOSIS?

A 5 year-old Labrador retriever presents for an acute cranial cruciate ligament rupture. Otherwise, the dog is healthy in every way with no clinical symptoms other than lamenesss. However, pre-operative bloodwork shows moderate elevations in ALT, and an ultrasound exam shows some indistinct, mildly hypoechoic nodular lesions in the liver. An ultrasound-guided needle biopsy is performed which ultimately shows benign nodular hyperplasia. Unfortunately, the dog dies of complications from the biopsy procedure. What this dog really died from, however, was overdiagnosis.

Veterinarians, especially early in their careers, are often fearful of misdiagnosis; incorrectly identifying disorders in their patients or diagnosing diseases the patients do not actually have. However, few worry about the dangers of overdiagnosis; the correct diagnosis and treatment of disorders patients do have but which will never cause clinical symptoms or mortality.

Overdiagnosis is now recognized as a common and serious problem in human medicine which causes significant harm in terms of cost and suffering for patients and their caregivers. There are annual international conferences on preventing overdiagnosis, and a consortium of seventy specialty groups has created the online resource Choosing Wisely (www.choosingwisely.org) to help physicians and patients make better decisions and reduce overdiagnosis and overtreatment. Changes in clinical practice guidelines for many conditions, including highly publicized changes in breast cancer and prostate cancer screening programs, have resulted from the recognition that overdiagnosis harms patients. Yet the subject of overdiagnosis is virtually unknown in veterinary medicine.

HOW COMMON IS OVERDIAGNOSIS

A challenge in controlling overdiagnosis is that there is no absolute way to know in advance if a finding in a particular patient is going to prove clinically important or not. This can only be known after sufficient time has passed to evaluate whether or not the finding has resulted in disease or death. However, it is possible to evaluate the frequency of overdiagnosis in a population based on the frequency of diagnosis and mortality data for specific conditions and populations. As an example, CT imaging of clinically healthy people frequently leads to diagnosis of cancers which, based on mortality figures, are never going to lead to early mortality (Table 1).

Table 1. Detection and risk of mortality from cancer using CT imaging in asymptomatic humans. (From Welch, 2012¹)

Similar data is available for many other diseases suggesting that overdiagnosis is extremely common in human medicine. There is no published data specifically addressing the frequency of overdiagnosis in veterinary medicine.

WHAT IS THE HARM OF OVERDIAGNOSIS?

The diagnosis of diseases that are unlikely to ever cause significant illness or mortality causes harm in several ways. The testing leading to diagnosis, and the treatment often offered once such a diagnosis is made, have financial costs. It is estimated, for example, that overdiagnosis and overtreatment of clinically irrelevant lesions detected through mammography costs $4 billion annually in the United States alone.² Another study suggests that unnecessary treatment of people with mild hypertension in the U.S., with no benefit in terms of reducing symptoms or early mortality, may cost $32 billion annually.³

These are only estimates for the costs of overdiagnosis for two diseases in one country, so the global financial cost is undoubtedly much greater. And despite the impulse to feel that no price should be put on efforts to improve health and treat disease, it is undeniable that such waste raises the overall costs of healthcare and reduces access for some people, all without any benefit to patients.

There are no estimates of the costs of overdiagnosis in veterinary medicine. The economic model of the veterinary profession is quite different from human medicine, and the financial costs of overdiagnosis may not impact the overall cost of veterinary care or the availability of care as dramatically. However, these costs are still a waste of client resources, and they can reduce the ability of some clients to pay for subsequent care that may be necessary or beneficial for their animals.

The financial costs of overdiagnosis, however, have not been the major drivers of change in clinical practice in human medicine. This has been the physical and emotional harm to patients. Diagnostic testing and treatment for conditions not destined to cause illness or death can cause both physical injury an psychological distress. It has been estimated that, for example, that prostate specific antigen (PSA) screening for prostate cancer in men will identify cancer in 30-100 patients who would never have been clinically effected for every death such testing prevents.¹ And for these men who are overdiagnosed and go on to have biopsies or treatment, up to 50% will experience sexual dysfunction, 30% will have urination difficulties, and 1-2 per thousand screened will die as a result of unnecessary treatment. Research has also shown that quality of life diminishes after a diagnosis of prostate cancer, and that the risk of suicide and cardiovascular death increases immediately following such a diagnosis.^4-5

Similar evidence of physical and psychological harm from overdiagnosis is available for many other conditions in human medicine. There has been, however, no published research on the risks of overdiagnosis in the veterinary field.

WHAT CAUSES OVERDIAGNOSIS?

Overdiagnosis is driven by numerous factors. Screening tests, imaging, and other diagnostics employed without specific clinical justification frequently lead to the detection of abnormalities. Such abnormalities are far less likely to be clinically important than those which cause symptoms, and therefore they often represent overdiagnosis. However, once an abnormality is detected, some of the psychological harm to patients or caregivers has already occurred. And because of the anxiety induced by the finding and the desire of both clients and doctors to take some action, even when it is unclear this will benefit the patient (a phenomenon known as “commission bias”⁶), further testing and even therapy often results from an initial overdiagnosis.

Overdiagnosis also stems from the development of more sensitive tests, which identify conditions earlier and prior to the onset of clinical symptoms. Expanded definitions of disorders which encompass patients previously not consider to have these disorders can also lead to overdiagnosis and overtreatment. Psychologically, doctors are prone to overdiagnosis because they are likely to be punished, in the form of blame or even litigation, for failing to diagnose a medical condition if it does eventually lead to symptoms or death. However, doctors are almost never punished for unnecessarily diagnosing and treating conditions which would never have cause any harm if undiagnosed.

The inappropriate reliance on anecdotal evidence and clinical experience to guide diagnostic practices also contributes to overdiagnosis. Even in the face of strong evidence, for example, that mammography of women under 50 years of age leads to significantly more harm from overdiagnosis than benefit from earlier diagnosis and treatment, there has been significant resistance to the change in screening guidelines implemented to reduce this harm. Much of that resistance is justified with the use of anecdotes of women who had been diagnosed and treated for breast cancer because they and their doctors believed, rightly or wrongly, that this intervention had saved their lives.

Any doctor who believes their use of screening or other diagnostic interventions in asymptomatic patients has saved someone’s life will be very reluctant to stop using those interventions regardless of the evidence that they do more harm than good. Individual stories are always more psychologically compelling than statistically data. But acting on our emotional response to such stories and ignoring the evidence for regarding overdiagnosis ultimately causes more unnecessary suffering for real patients.

Patients are similarly inclined to seek diagnosis and take action on it even if the statistical evidence suggests it is in their best interests not to. Doing so gives people a sense of control over their fate, or that of their animals. Even if this sense of control is an illusion, it tends to outweigh rational considerations. One survey found that 98% of people mistakenly diagnosed with cancer through screening were still glad they had had the test once the follow-up evaluation showed they actually did not have cancer.⁷ Like doctors, patients are inclined to take action rather than choosing inaction, even when inaction is demonstrably the better choice.

Finally, we cannot ignore the potential influence of financial interests on overdiagnosis. Companies selling diagnostic tools and veterinarians using them receive income from the use of these tools. And the follow-up testing and treatment of diseases, even when they are overdiagnoses, also generates revenue. While doctors are unlikely to intentionally pursue unnecessary testing and treatment purely for financial gain, it would be naive to imagine such revenue has no impact on doctors’ decision making. Federal law prohibits doctors from referring patients to diagnostic facilities in which they have a financial interest because research has shown such an interest increases the number of tests done and the costs to patients.^8-9 There is no reason to believe veterinarians to be exempt from the same potential for financial self-interest to influence clinical decisions.

HOW DO WE REDUCE OVERDIAGNOSIS & OVERTREATMENT?

The first step in reducing the harms from overdiagnosis is to understand the phenomenon and its causes. This includes developing the data to identify overdiagnosis of specific conditions. Because overdiagnosis can only be identified in retrospect in individual patients, we must gather and analyze epidemiologic data to recognize the level of risk for overdiagnosis of particular diseases. We cannot safely rely on anecdotes and uncontrolled clinical experience alone to drive our diagnostic and therapeutic practices. We need data.

In the meantime, in the absence of such data, the best strategy is to understand the limitations of our diagnostic tests, including important measures such as their positive and negative predictive value, which help us to appreciate the likely significance and reliability of test results in particular patient populations.  We should also ensure that we have an appropriate clinical index of suspicion for any condition before we begin testing for it. “Fishing expeditions,” “shotgun diagnostics,” indiscriminate imaging, and other such irrational diagnostic practices raise the risk of overdiagnosis.

We must also learn to accept the inevitable uncertainty in medicine and be honest with clients about our ability to predict and control all patient outcomes. We need to recognize and disclose that testing and treatment have costs and risks as well as benefits, especially in patients without significant clinical symptoms associated with the disorders we are trying to diagnose and treat. Though it is psychologically more difficult for us, it is often wiser to avoid action when there is not good evidence to show that our actions will truly benefit our patients. Don’t just do something, stand there!

REFERENCES

1. Welch, HG. Schwartz, L. Woloshin, S. (2012) Overdiagnosed: Making people sick in the pursuit of health. Boston: Beacon Press.
2.  Ong, M. Mandl, KD.  National Expenditure For False-Positive Mammograms And Breast Cancer Overdiagnoses Estimated At $4 Billion A Year. Health Aff April 2015 vol. 34 no. 4 576-583
3. Martin, SA. Boucher, M. Wright, JM. Et al. Mild hypertension in people at low risk. BMJ 2014;349:g5432
4. Heijnsdijk EA, Wever EM, Auvinen A et al: Quality-of-life effects of prostate-specific antigen screening. N Eng J Med 2012; 367: 595.
5. Fang F et al: Immediate Risk of Suicide and Cardiovascular Death After a Prostate Cancer Diagnosis: Cohort Study in the United States. JNCI 2010; 102: 307.
6. McKenzie, BA. Veterinary clinical decision-making: cognitive biases, external constraints, and strategies for improvement. JAVMA. 2014;44(3):271-276.
7. Schwartz, LM. Woloshin, S. Fowler, FJ., et al. Enthusiasm for Cancer Screening in the United States FREE  JAMA. 2004;291(1):71-78.
8. Levin, David C.; Rao, Vijay M. (2008). “Turf Wars in Radiology: Updated Evidence on the Relationship Between Self-Referral and the Overutilization of Imaging”. Journal of the American College of Radiology 5 (7): 806–810.
9. Gazelle, G.S.; Halpern, E.F.; Ryan, H.S.; Tramontano, A.C. (November 2007). “Utilization of diagnostic medical imaging: comparison of radiologist referral versus same-specialty referral”. Radiology 245 (2): 517–22.

Slides