Steps of the Shoemaker Protocol

Once the diagnosis of Chronic Inflammatory Response Syndrome (CIRS) from water damaged buildings has been established by history, physical, and labs, the Shoemaker protocol is the only peer reviewed published protocol shown to reverse the symptoms and laboratory findings. The steps are as follows:

Remove exposure from water damaged buildings

For many people, this is the most critical, yet most difficult step. Dr. Shoemaker has shown that the best test for determining the safety of a building is an ERMI test from Mycometrics. The ERMI stands for the Environmental Relative Moldiness Index. It is a quantitative PCR analysis that looks at spore equivalents of 36 species of mold. Shoemaker has determined from his database of thousands of patients that the cutoff for safety is an ERMI score of 2 if the MSH is < 35 and C4a is less than 20,000 and 0 if the C4a is greater than 20,000. He later developed a derivative of the ERMI score looking at 5 species, which he calls HERTSMI-2. This test is also done at Mycometrics and the cutoff for safety is a HERTSMI-2 of 10 for someone previously sickened by a water damaged building . More information can be found at http://www.survivingmold.com/diagnosis/hertsmi-2

I recommend that my patients test buildings that they spend a great deal of time at which usually includes their homes and workplaces. If the ERMI or HERTSMI-2 is over the safety cutoffs, I recommend that they remediate or move out of the building. Briefly, remediation involves identifying and correcting all sources of water entry, removing water damaged construction materials, and thorough cleaning of all contents of the building. After remediation, a HERTSMI-2 should be performed. The criteria for a successful remediation is a HERTMI-2 of 10 or less.

If patients choose to move, I recommend that they run an ERMI or HERTSMI-2 before moving into any new buildings.

The industry standard of sampling the air for spores is not an acceptable substitute for many reasons. One of the main limitations is that over 99% of the particles that carry the inflammagens from water damaged buildings are smaller than 3 microns. Spore traps can only detect particles that are larger than 3 microns and therefore miss over 99% of the inflammagens. Studies have shown that for every spore, there can be 100-500 inflammagen carrying fragments. The World Health Organization has stated that if one wants to do air sampling, it should be done in multiple locations per room, at multiple times of the day, multiple days per week. In other words, air sampling done properly is too time consuming and cost prohibitive. Finally, only the ERMI and HERTSMI have been associated with sequential activation of innate immune responses, not air testing. I have seen numerous patients who have been told that their air tests were “normal” yet they had high ERMI or HERTSMI scores and their bloodwork shows persistent inflammation.

Cholestyramine or Welchol

The next step is to interrupt enterohepatic recirculation of biotoxins using either cholestyramine or Welchol for at least a month. The dose of cholestyramine is 4 grams ½ hour before eating 4 times a day. If cholestyramine cannot be tolerated, a less effective alternative is Welchol 2 tablets three times a day with food. A number of people are sensitive to the fillers in cholestyramine so using compounded cholestyramine without fillers is a good alternative. The success of this step can be monitored by seeing improvements in the VCS (Visual Contrast Sensitivity) Test. If there is no improvement, the most common cause is persistent exposure to a water damaged building.

Treatment of MARCONS

MARCONS stands for Multiple Antibiotic Resistant Coagulase Negative Staphylococcus. It colonizes the deep nasal aerobic spaces of the majority of people with CIRS. This bacteria forms biofilms and releases biotoxins that can cleave MSH (melanocyte stimulating hormone), an anti-inflammatory neuropeptide. It is diagnosed by a deep nasal swab, which is sent to DLM labs in Massachusetts. If it is present and there are at least 2 classes of antibiotic resistance, the treatment is the use of compounded BEG spray (bactroban, edta, and gentamicin) 2 sprays three times a day for 1 month. Earlier versions of the protocol involved using Rifampin, but this is no longer necessary.

Correct anti-gliadin antibodies

If these antibodies are found on blood testing, the patient needs to avoid gluten containing foods for at least 3 months. I do find in my practice that most patients feel better avoiding gluten indefinitely.

Correct androgens

Many people with CIRS will have low androgens due to excessive activity of the aromatase enzyme. Dr. Shoemaker has shown that this will correct with VIP. In cases of those with low DHEA levels, supplemental DHEA may help correct androgen levels.

Correct ADH / osmolality

Most people with CIRS will have ADH (antidiuretic hormone) and osmolality levels that are out of proportion to each other. The most common pattern is a relative or absolute deficiency of ADH. Typically, one will see an ADH level either low or low normal with osmolality mid or high normal. ADH causes the kidneys to retain free water. Therefore, when levels are relatively low, patients will commonly experience excessive thirst and urination. In more severe cases, people will experience frequent static shocks.

The treatment is to use desmopressin 0.2 mg every other night. Sodium levels must be checked in 5 days then again in 10 days as hyponatremia can sometimes occur. If hyponatremia occurs, patients may experience poor appetite and nausea.

Correct MMP 9 (Matrix Metalloproteinase 9)

MMP is an enzyme that breaks down extracellular tissue. If MMP 9 is over 332 ng/mL, then this is treated with a low amylose diet and high dose fish oil (2.4 g of EPA, 1.8 g of DHA).

Correct VEGF (Vascular Endothelial Growth Factor)

This substance stimulates the growth of new blood vessels in response to Hypoxia Inducible Factor (HIF). In many people with CIRS, VEGF is suppressed to less than 31 pg/mL. The treatment is a high dose fish oil and a low amylose diet as listed in step 7.

Correct Complement C3a

This can be elevated if there is the presence of bacterial membranes such as those with acute Borreliosis. If high, the Borrelia needs to be treated first with antibiotics. If the levels remain high, a statin can be used to lower the level.

Correct Complement C4a if levels are greater than 2830 ng/ml

In earlier versions of Dr. Shoemaker’s protocol, erythropoietin (Procrit) injections were given. Now that VIP is available, VIP is the current treatment of choice. Note that this lab test needs to be run at National Jewish Hospital in Denver.

Correct TGF-B (Transforming Growth Facter Beta)

If elevated (over 2380 pg/mL), the treatment is losartan up to 25 mg bid. A metabolite of losartan called exp3179 lowers TGF beta.

VIP (Vasoactive Intestinal Polypeptide)

If the patient remains symptomatic after following all of the above steps, then the use of VIP is needed. It is a nasal spray that is dosed at 50 mcg/mL, 1 spray 4 times a day. The first dose should be given in the office. A TGF B and C4a should be drawn before the first spray and again in 15 minutes. If the levels rise, there is a hidden mold exposure.

According to Dr. Shoemaker’s paper published in 2013, administration of VIP will correct C4a, TGF beta, VEGF, MMP-9, estradiol, testosterone, vitamin D3, and PASP. More importantly, it improves the quality of life.

It is critical that there be no continued mold exposure before starting VIP otherwise it will be ineffective. VCS must also be normal and MARCONS must not be present to ensure that VIP will be effective.

Ou, Dave. MD Steps of the Shoemaker Protocol. Atlanta: 2014. Surviving Mold - Steps of the Shoemaker Protocol. Web. 10 Aug 2014. http://www.survivingmold.com

Allergen Avoidance Recommendations

Allergen Avoidance Recommendations

The following recommendations will help you minimize your exposure to toxic molds:

Eliminate Dampness In Your Home

Suggestion 1: Eliminate dampness in your home – check walls and roof for leaks. Waterproof walls and ceilings before painting.

Reason: Mold thrives in damp conditions

Do Not Wallpaper Walls

Suggestion 2: Do not wallpaper walls – paint instead.

Reason: Mold grows on wallpaper and in wallpaper paste.

Avoid Carpets As Floor Covering

Suggestion 3: Avoid carpets as floor covering. Replace with wood floors, vinyl or ceramic tile or terrazzo.

Reason: Mold grow sin carpet pile. Carpets also trap dust which can cause allergic reactions.

Allow Good Air Circulation In Closets

Suggestion 4: Allow good air circulation in closets. Leave space between hanging clothes and check leather clothing, belts, shoes and luggage for signs of mold growth.

Reason: Mold grows in damp, enclosed environments, especially on leather items.

Keep Bathrooms And Laundry Rooms Well Aired

Suggestion 5: Keep bathrooms and laundry rooms well aired. Spread out towels and washcloths for fast drying. Dry clothes as soon as they are taken from washer.

Reason: Mold grows rapidly in damp conditions and on damp fabrics.

Regularly Inspect Bathrooms And Laundry Rooms For Mold Growth

Suggestion 6: Regularly inspect bathrooms and laundry rooms for mold growth. Look for evidence of discoloration in tile grout and caulking. Do not forget to check under sinks, around the commode, shower curtains and shower door runners.

Reason: Mold thrives in damp environments.

Use a Dehumidifier in Humid Environments

Suggestion 7: In humid conditions, use air conditioning or a dehumidifier.

Reason: Mold does not grow well in dry environments.

Avoid Foods Which Contain Molds

Suggestion 8: Avoid foods which contain molds or are related to molds such as Mushrooms, yeast containing foods, fermented meats and pickles, smoked fish and meats, and blue cheese.

Reason: Inhalant allergy symptoms may be aggravated by consumption of these foods.

This list was originally written by the Longevity Medical Centre.

Frequently Asked Mold Questions

Frequently Asked Mold Questions

Q: Do I literally have to clean everything in my house (i.e. plastic storage containers, books, toiletries, candles, knickknacks, canned food etc.) or just the major things like clothing and furniture?
A: Yes, everything.

Q: Is it possible to clean electronic devices that may have mold spores inside of them, seeing as I have no way to clean the inside of these devices (i.e., DVD players, computers)? Is it good enough to simply clean the outside of them?
A: Clean the outside and vacuum the openings.

Q: Do pictures and documents have to be scanned/copied or can the originals be kept? Photos can be washed.
A: Porous frames are trash. Documents need to be copied.

Q: What about books, journals? How do you clean them? Or do they have to be thrown out?
A: Books are difficult. If the books are on a shelf and not opened, HEPA vacuum each one. Opened books are trash.

Q: Do I need to use a new cloth for every item that I clean (one clean cloth per moldy item) or can I use the same cloth for several items?
A: One cloth can be reused. You will be vacuuming, then wiping and vacuuming again anyway.

Q: Can leather furniture be cleaned since it is not porous like cloth?
A: Use quaternary cleaners on leather. Vacuum the nooks and crannies of the piece of furniture and do the same thing again. I know some people will say throw away the leather, but I have seen good results if the leather has a finished (not rough) surface.

Q: Is it likely that I have cross contaminated my car seeing as I drive in it, in my moldy clothes and with other items from my home on a daily basis? If that is the case, do I need to sell my car as well or can it be cleaned?
A: The trouble with cleaning for mold is where do you stop? There are many chemically sensitive people who have to get new cars. For most people the car isn’t the problem. Be careful about the antifreeze system in a car as that system’s glycol ethers are a real problem.

Q: Is it likely that I have contaminated my friends’ homes just by being there as well? If so, is that going to be problematic for me when I go to visit with them? I plan to move in with one of my friends for several months while I look for a new place to buy. I have slept at this person’s house already with my moldy clothes and suitcase quite a few times. Will I need to clean her floors and table tops etc., or is any possible cross contamination from my simply having slept there too minimal to worry about? Have I cross contaminated this person’s bed by sleeping in it?
A: Clothes are much less of a problem if they are laundered before wearing to someone else’s home. I get mold hits from families that come from moldy homes, but the risk of illness and cross contamination from clothes is less if the clothes are removed from the home, cleaned or dry-cleaned.

Q: I plan to purchase a HEPA vacuum cleaner. After I clean things with it will it need to be thrown out, or is replacing the filter sufficient?
A: Replace the filter. A good HEPA will last a long time. Better yet, invest in a central vacuum.

Q: I assume that plates, dishes, silverware etc. can simply be run through the dishwasher. If so, where do I clean them? My current moldy dishwasher before I move out or the dishwasher in my new place?
A: I have not seen people made ill by a cleaned dishwasher. Rub down the outside and vacuum it but the wash cycle is enough to safeguard your silver and china.

Q: I am a little worried that work could be moldy too. None of my coworkers are sick and I have asked about water damage. I am told there has not been any. But I have noticed tiles that you can tell have been wet. Any way to determine if the building is moldy short of doing a test?
A: ERMI is the key concept here. I don’t trust any building to be safe just because a landlord said so. Spend the $300 to know for sure.

Q: Would it be better to clean everything myself or to hire a mold expert?
A: As far as abatement and removal of materials, you need to learn the tricks of the trade. But there is no reason you can’t do the work yourself if you have carpentry skills. The cleaning you probably should do.

Re-posted from the Surviving Mold website, https://www.survivingmold.com/

Toxic Mold Illness: Is Your Home Causing Your Mysterious Symptoms?

If you are suffering from chronic symptoms such as asthma, fatigue, or brain fog, and you’ve struggled to find a proper diagnosis or relief, it might be time to examine your environment more closely.

Toxic mold illness and its effect on the immune system, called chronic inflammatory response syndrome (CIRS) is a perfect example of the power of our environment to impact our health in a dramatic fashion.

Many toxic molds are formed in buildings that have suffered water damage through flooding, condensation or high humidity. It is estimated that as many as 50 percent of homes have poor indoor air quality with water damage and the resultant mold biotoxins and associated inflammatory particles being one of the major contributors. With indoor air pollution accounting for up to 50 percent of all illnesses in the United States, this is a very serious contributor to patients' suffering, and deserves to be raised as a major factor when enquiring into patients' health history and timeline of symptom presentation.

Globally, air pollution is an epidemic, killing an estimated seven million people and is responsible for one in eight global deaths each year. This is a staggering number, and the fact that mold illness is one of the contributors to this epidemic, is still relatively undiscussed and unknown in traditional medical clinics, needs to change. Let’s shed some light on this invisible illness.

The Invisible Illness

Mold is quite literally an invisible killer because often you cannot see it. Caused by multiple different types of fungi, mold reproduces by forming tiny spores, which float away and are unseen by the naked eye.

Not only are mold spores invisible, but they produce even smaller secondary mycotoxins which are able to sneak through the body while wreaking havoc and remaining undetected by the immune system. These mycotoxins are extremely small, fat soluble molecules.

These molecules are particularly dangerous because they are capable of passing through your cell membranes without being carried through the bloodstream – making them extremely difficult for your immune system to identify.

Without identifying and helping your immune system recover from a buildup of toxin exposure, you could unnecessarily suffer from long term negative health consequences. Helping the public understand and become aware of CIRS is one of the best ways we can rectify unnecessary suffering.

Let’s examine the 13 symptoms of mold illness or CIRS, 4 common misconceptions, and 11 steps you can take towards effective treatment.

13 Symptoms of Toxic Mold Illness

The problem with toxic mold illness is it can feel like a phantom illness. The symptoms seem unrelated and can cause doctors to look in all the wrong places for a diagnosis.

Many sufferers of mold illness or CIRS first endure years of misdiagnosis or are even dismissed as having an illness that’s psychosomatic (in the mind). If you are suffering from a myriad of seemingly unrelated symptoms, it’s time to consider your home and work environments.

Here are the 13 most common symptoms of toxic mold illness (Dr. Shoemaker has identified 37 symptoms in total). It’s time to see your doctor if you suffer from any of the following:

  1. Cognitive issues such as headaches, brain fog, memory problems, difficulty concentrating, and mood swings
  2. General fatigue and weakness
  3. Muscle aches, joint pain, and morning stiffness
  4. Numbness and tingling of the skin
  5. Light sensitivity, blurred vision or red eyes
  6. Asthma, persistent coughing, sinus issues or shortness of breath
  7. Skin tingling or numbness
  8. Vertigo and tremors
  9. Metallic taste
  10. Temperature fluctuations or night sweats
  11. Increased urination and excessive thirst
  12. Changes in appetite
  13. Abdominal pain, nausea, diarrhea, and bloating

As you can see, the symptoms of mold illness are varied and may even appear unrelated. It’s the nature of these broad reaching symptoms that keeps the cloud of mystery over CIRS.

Only through drawing more public attention and dispelling common myths around CIRS can we get closer to achieving better diagnoses and treatments. Let’s start that process by taking a closer look at the four common misconceptions surrounding mold illness.

4 Common Misconceptions of Mold Illness

Toxic mold illness is gaining traction in the media but with that come some misconceptions. Let’s clear up some of these fallacies regarding mold illness right now.

1.  Mold Illness Isn’t That Common

Even though mold illness isn’t widely discussed, it is very prevalent and the public needs more information on CIRS. Approximately one in four have the potential for developing CIRS if they are exposed to sufficient biotoxins and inflammagens (other toxic compounds released by water-damaged buildings).

And unfortunately, these biotoxins are estimated to impact as many as half the homes in the United States, making CIRS an illness of major concern. It’s important to spread awareness of mold toxicity and prevalence so that people can take the right steps to keep their family safe in their homes and places of work.

2.  Mold Illness is Caused by Mold

Even though “mold” is in the description, mold illness is actually a complex health condition that fits more appropriately under the title of chronic inflammatory response syndrome or CIRS.

Originally described by Dr. Ritchie Shoemaker in the late 90s, there are now over 1700 scientific articles on CIRS to date.

The causes of CIRS are collectively known as biotoxins and are frequently associated with water-damaged buildings, though they can occur without water damage.

These biotoxins include:

  • Fungi with mycotoxins
  • Bacteria with secondary endotoxins (including Borrelia and Babesia - organisms associated with tick-borne illness)
  • Actinomycetes
  • Mycobacteria
  • Beta Glucans
  • Hemolysins (toxins produced by bacteria, often residing in deep nasal passages).
  • Microbial Volatile Organic Compounds (VOCs)
  • Cell wall fragments
  • Protozoa
  • Building material VOCs

Not everyone will become sick if they are exposed to sufficient levels of any of these toxins. They are fortunate to be part of the 75 percent of the population whose immune system recognizes these toxins and is able to neutralize them.

However, those with specific human leukocyte antigen (HLA) genes have an immune system that isn’t able to identify these toxins. If your body can’t identify these biotoxins, then it is unable to eliminate them from the body. These biotoxins initiate a significant inflammatory response called CIRS.

3. CIRS Looks the Same for Everyone

Actually, it appears that everyone has differing levels of mold sensitivity. Genetic predisposition seems to play a role in how likely you are to develop CIRS.

About 25 percent of the population is genetically susceptible to developing CIRS, while two percent are highly sensitive and more likely to experience disabling symptoms when exposed to biotoxins.

The varying levels of sensitivity to biotoxins makes CIRS a difficult illness to diagnose. Furthermore, those suffering from mold illness are often misdiagnosed or their condition is overlooked altogether.

Only through additional studies, examination, and public awareness can we begin to improve diagnosis rates for CIRS.

4.  Removing Environmental Exposure Cures the Symptoms

It seems obvious that the first step of tackling your CIRS would be removing exposure to biotoxins. But that isn’t always enough.

Sure, removing the source of toxins is great in theory, but even professionals have a hard time fully eliminating all the mold and spores. If it’s at all possible, a complete move from the contaminated area is best. Unfortunately, many cannot afford to completely remove themselves from the toxic environment.

Luckily, there are other steps you can take to help your body repair some of the damage caused by harmful biotoxins or improve your health if you are not able to completely remove yourself from the environment.

Take Action – 10 Treatments of Toxic Mold Illness

If you’ve been diagnosed with CIRS there are steps you can take to help alleviate your symptoms.

The steps of the Shoemaker Protocol outlines a detailed treatment plan on the impacts of toxic mold. 10 treatments I recommend include:

  1. First and foremost, remove yourself from the environment to the best of your ability. Begin the process of remediation of your water-damaged environment. It is best to consult an expert in the field who has been trained in the Shoemaker method of mold remediation.
  2. Invest in a high-quality indoor HEPA air filter capable of removing particles less than 0.1 microns. Most commonly purchased HEPA filters only filter particles to 0.3 microns and above.
  3. Test for and treat any nasal bacterial growth, such as MARCONS .
  4. Use cholestyramine, Welchol (known as Lodalis in Canada) to aid your body in removing the toxins by binding to them. Be sure to avoid constipation while using binders. Add magnesium oxide or citrate powders to prevent constipation during your detoxification process.
  5. Eliminate gluten and remove mycotoxin-rich foods, including wheat, barley, rice, oats, rye, peanuts, and brazil nuts.
  6. Eliminate amylose rich food, sugar and alcohol.
  7. Correct androgens such as DHEA and testosterone.
  8. Correct your cortisol and ACTH levels.
  9. There are several other biomarkers that can be examined and corrected with the guidance of your doctor such as ADH/osmolality, MMP9, VEGF, C3a, C4a, TGF beta-1, and VIP. Be sure to discuss these factors with your doctor.

 

It’s really a wonderful thing to finally see a comprehensive look at human health begin to hit the mainstream. And while it’s an approach you’ve been following for some time now, it’s important that it continues to spread far and wide.

Through the 7 Stages of Health and Transformation we can examine health impacts such as toxic burden through a lens that’s more complete and acknowledges the complexity of human health.

Mold illness is a perfect example of how toxins found in the 1st stage – the Extended Body – can lead to an array of seemingly confusing symptoms. If you are suffering from chronic illness – especially any of the symptoms listed above – be sure to consider mold and its resultant toxic effects, as a possible contributor.

Do your symptoms improve when you’ve been on vacation? Have you been looking for solutions to an illness with little to no success? Mold toxicity is not usually a factor many practitioners look at first. Mold illness is quite literally “out of sight, out of mind” but it could be the solution to your mysterious health woes.

As we mentioned earlier, CIRS is still a relatively unknown illness and spreading the word is vital to helping those that suffer. Share this article to help spread awareness and aid in calling attention to a debilitating and misunderstood illness.

Also, if you’re interested in digging deeper and learning more about CIRS and finding a complete description of both the diagnosis and treatment, you can find out more by clicking here.

Resources:

https://www.survivingmold.com/docs/HOFFMANESSAY1.PDF
https://www.survivingmold.com/docs/CONSENSUS_FINAL_IEP_SM_07_13_16.pdf
https://www.survivingmold.com/docs/MEDICAL_CONSENSUS_1_19_2016_INDOOR_AIR_KB_FINAL.pdf
https://www.truthaboutmold.info/statistics
https://irp-cdn.multiscreensite.com/c4e267ab/files/uploaded/AEDOWicfSFCZ5IZG5OhO_WHO_ 7%20million%20premature%20deaths%20annually%20linked%20to%20air%20pollution_March%202014.pdf
http://www.survivingmold.com/mold-symptoms/molds-mycotoxins-more
http://www.survivingmold.com/docs/Berndtson_essay_2_CIRS.pdf
https://hoffmancentre.com/wp-content/uploads/2016/12/Steps-of-the-Shoemaker-Protocol. pdf

Evidence-Based Medicine in the World of Mold Illness

The practice of evidence-based medicine (EBM) is held out as the gold standard of practice when it comes to evaluating how best to treat certain conditions. As this article will outline, nowhere is this standard in more disrepute than in the evidence-based practices currently in use on how best to treat mold related illness.

What is Evidence-Based Medicine? The term "evidence-based medicine" (EBM) was first used in 1990 by G.H. Gyatt, a professor from McMaster University Canada, but a broader description of EBM appeared in 1992 when the Evidence-Based Working Group published a new approach to teaching the practice of medicine in JAMA. (1) The article stressed that “evidence-based medicine de-emphasizes intuition, unsystematic clinical experience, and pathophysiological rationale as sufficient grounds for clinical decision making and stresses the examination of evidence from clinical research.(2)” The article emphasized that this would require “new skills of the physician, including efficient literature searching and application of formal rules of evidence evaluating the clinical literature.(3)” Tradition, anecdote and theoretical reasoning based on the basic sciences would be replaced by evidence from high-quality, randomised, controlled trials and observational studies, in combination with clinical expertise and the needs and wishes of patients.(4)

On the Internet, numerous articles discuss other potential definitions of the term "evidence-based medicine"(5). Sackett et al. define EBM as “the integration of best research evidence with clinical expertise and patient values”(6). Another definition states that “EBM is nothing more than a process of life-long, self-directed learning in which caring for patients creates the need for clinically important information about diagnosis, prognosis, therapy, and other clinical and health care issues.” A further definition suggests that EBM is “an evolutionary progression of knowledge based on the basic and clinical sciences and facilitated by the age of information technology.(7)”

Many of the above definitions arose from a BMJ article published in 1996, which stated that EBM is the conscientious, explicit and judicious use of the best current evidence in making decisions about the care of individual patients. The practice of evidence-based medicine involves integrating individual clinical expertise with the best available external clinical evidence from systematic research.(8)

Evidence-based medicine requires asking relevant clinical questions concerning the patient’s issues, performing a literature search for relevant research data to support or refute diagnostic and/or treatment approaches, critically appraising the literature regarding its validity and applications, and then implementing one’s findings and insights in a clinical setting.

Twenty-five years ago, evidence-based medicine, which involves utilizing the medical literature to effectively guide medical practice, was considered profound enough to be described by the initial authors as a paradigm shift in the way medicine was to be practiced. The authors reported Thomas Kuhn’s description of a scientific paradigm as “[a way] of looking at the world that defines both the problems that can legitimately be addressed and the range of admissible evidence that may bear on the solution”(9). When defects in an existing paradigm accumulate to the extent that the paradigm is no longer tenable, the paradigm is challenged and replaced by a new way of looking at the world.

Some of the shift toward evidence-based medicine was initiated due to a loss of confidence in the traditional medical model and the studies that had initiated those practices. Larry Dossey M.D. commented on many of the scandals that rocked the confidence of healthcare consumers at the end of the last century(10). “The uncertainties of medicine are cause for celebration,” Dossey wrote. “Modern medicine is losing some of its invincibility. Many of the rules of good health that have guided patients and physicians for decades have taken a beating from which they may not recover. The almost blind allegiance we once had to the treatments offered has been severely undermined by these studies — some of the absolute certainties are no longer as absolutely certain.”

First, there was the Vioxx drug scandal, in which many people died from heart disease after consuming what were thought to be relatively innocuous anti-inflammatory drugs. Compounding the problem was the fact that this particular drug had been marketed as being relatively safe. Furthermore, evidence emerged that the drug companies had known for some time that the drug had an increased incidence of cardiac side effects, but they had chosen to hide these negative findings to ensure a profit.

In the Women’s Health Initiative study(11), hormone replacement therapy (HRT), specifically Premarin and Provera, once a mainstay of post-menopausal symptom management and considered to be safe, was shown to actually increase women’s risk of heart disease, stroke, thrombosis and breast cancer. The risks of increased cardiovascular disease (CVD) and breast cancer were concluded to far outweigh the benefits of osteoporosis protection and colon cancer reduction. Millions of women, to the fanfare of massive nation-wide news coverage, were immediately withdrawn from hormone replacement therapy as a result of these findings. The sales of these two drugs dropped 50% in one month. The American Association of Clinical Endocrinologists, (AACE), the American Congress of Obstetricians and Gynecologists (ACOG) and the North American Menopause Society (NAMS) recommended HRT use only for short-term symptom control.

Later critiques of the study pointed out some bias and manipulation of data, including but not limited to the following:

  1. Many women chosen for the study were not in the typical age range for HRT – they were, on average, 12-15 years past the age of menopause and had significant baseline cardiovascular and coronary artery disease (CAD) at the initiation of the study.
  2. Approximately 74 percent of the women included in the study had never used HRT before and were outside the 3-4 year post-menopausal window of opportunity for HRT, in which cognitive and cardioprotection from HRT was maximal.
  3. Premarin was the estrogen used in the study. Premarin is a conjugated equine estrogen drug with 50 percent estrone (known to increase breast cancer risk prior to the WHI study), equilin and equilenin, both of which have unknown activity on human estrogen receptors. The WHI study was not undertaken with human estrogens (E1=estrone, E2=estradiol and E3=estrone). Premarin is an oral equine-derived preparation and is known to increase liver coagulation proteins, thus increasing the risk of stroke and cardiac events. Transdermal estrogen was not used, which has shown no association with the increased activation of liver clotting proteins. NAMS preaches that there are no randomized, placebo-controlled trials to support the claims of increased efficacy or safety of compounded, bioidentical hormones; however, there is a plethora of studies demonstrating the superior efficacy and safety of pharmaceutical bioidentical hormones over non-bioidentical, synthetic hormones.
  4. Progestin was the chosen progesterone preparation. This is a medroxyprogesterone acetate preparation that had already been shown to have an unfavorable effect on lipid profiles prior to the WHI trial.

Much criticism was levelled against the WHI study when the data were placed within a clinical perspective and further studies reached different conclusions. The results of the WHI and the Heart and Estrogen/Progestin Replacement Study (HERS) trial, when reassessed, were shown to not apply to younger women, specifically those aged 50-60. In most of the subsequent studies, there were no cardiovascular deaths among 6,000 women on HRT, as compared to several deaths in the placebo group (12). There was overwhelming evidence that the anti-atherosclerotic effect of HRT depended on the time of initiation and that early initiation was protective.

With regard to knee surgery, researchers proved that performing arthroscopic surgery on an arthritic knee, once a mainstay of surgical interventions for this condition, was no more effective than administering an anesthetic, making a skin incision, and performing a sham surgery. The outcomes in terms of pain and symptoms after either of these two procedures were virtually the same. The value of mammograms has also been seriously questioned, and it is unclear as to whether or not a mammogram has any influence on the number of women dying from breast cancer each year.

These observations are supported in the literature, which shows that many medical findings and treatment suggestions previously taken as the gold standard do not stand the test of time. John Ioannidis, known as a meta-researcher who has based his career on researching the validity of medical research findings, has shown time and time again in published studies that as many as 90 percent of the published medical information that doctors rely on is flawed (13). Eighty percent of non-randomized studies (the most common type of studies) turn out to be wrong, and 25 percent of gold-standard randomized studies turn out to be wrong, as do 10 percent of platinum-standard large randomized trials. One of his papers (14) discussed his belief that researchers were frequently manipulating data analyses, choosing career-advancing findings rather than good science and using the peer-review process to suppress opposing views (15). In perhaps one of the most ignominious examples of medical science undergoing a dramatic reversal in treatment approach, Dr. Egas Moniz received a Nobel prize in 1949 for his pioneering of the frontal lobotomy in 1936 to treat incurable mental illness (16). Times do change, and sometimes, they change radically.

A Wall Street Journal article written by Ron Winslow entitled Study Questions Evidence Behind Heart Therapies (17) discussed a study that revealed that less than 11 percent of 2,700 recommendations commonly made by cardiologists were supported by scientific evidence. Furthermore, many of the dogmatic recommendations and guidelines created by cardiologists are formed by individuals who are connected in some financial way with the pharmaceutical companies (18). Another study showed that 85 percent of individuals who had stents or angioplasties to treat their blocked coronary arteries did not need them. Furthermore, the group that did have the surgical procedures ended up much sicker than the individuals who treated their condition with drugs alone (19). Thus, more critical evaluation of standards of practice was needed.

The original 1992 Evidence-Based Medicine Working Group set out specific criteria for assessing the strength of evidence that supports clinical decisions (20). Has the diagnostic test been evaluated in a patient sample that included an appropriate spectrum of mild and severe disease, treated and untreated disease and individuals with different but commonly confused disorders (21)? Was there an independent, blind comparison with a gold standard of diagnosis (22)? Was the assignment of patients to treatments randomized (23)? Were all patients who entered the study accounted for at its conclusion (24)? Lastly, were explicit methods used to determine which articles to include at its conclusion (25)?

Evidence-based medicine utilizes specific steps to arrive at conclusions:

  • Ask the right question using an acronym PICO (26). P=Patient or problem, I=Intervention, C=Comparison intervention, O=Outcome.
  • Acquire the best evidence by searching various databases, including but not limited to PubMed, Embase and Cochrane Library. Evidence-based medicine has various levels or grades for use in assessing the strength of studies.
  • Appraising the evidence: Is the study valid and relevant? What were the results of the study? Will the results help in treating the patient?
  • Apply the evidence. Once the evidence is obtained, it must be filtered through the patient’s value systems and the level of the practitioner’s core competencies. Shared decision making is essential once the risks and benefits have been explained.
  • Performance assessment. Whether this approach is helping and assisting the patient to achieve his or her anticipated and expected health goals must be determined. This is done by assessing the four steps listed above.

There are four levels of evidence that are used when assessing the strength of studies via an EBM approach.

  1. Level I – This is considered the top level of evidence, and it is derived from randomized, double-blind, placebo-controlled trials and/or meta-analyses that combine the evidence from these trials. Meta-analyses are considered to be the most eligible for Level I status, but they too have come under some criticism as a means of evaluating critical evidence. Many studies that are combined in a meta-analysis are homogenous and lack sufficient outlying evidence.
  2. Level II – This evidence is not considered quite as reliable as that from Level I. This evidence comes from controlled trials without randomization, cohort or case-control analytic studies and multiple-series studies.
  3. Level III – This evidence is based on expert opinion from those specialized in one particular area under investigation. Most often, there are no control groups, and sample sizes are small. This approach can often lead to a large margin of error unless statisticians compile the evidence from all expert opinions.
  4. Level IV – This evidence is based on personal experience and is the least desirable source of evidence because it lacks statistical validity.
    The original working group emphasised that it would require a specific teaching course and orientation, as taught at the McMaster University Medicine Residency Program, Department of Medicine, in order to critical appraise journal articles and arrive at the bottom line regarding the strength of evidence and how it may bear on the clinical problems in question.

According to the original JAMA article, the residents “learn to present the methods and results in a succinct fashion, emphasizing only the key points. A wide-ranging discussion, including issues of underlying pathophysiology and related questions of diagnosis and management, follow the presentation of articles. They always substantiate decisions or acknowledge the limitations of the evidence and discuss the literature retrieval, the methodology of papers and the application to the individual patient. (27)” This article emphasised that this “new paradigm will remain an academic mirage with little relation to the world of day-to-day clinical practice unless physicians-in-training are exposed to role models who practice evidence-based medicine”. McMaster University recruited internists with training in clinical epidemiology and the “skills and commitment [needed] to practice evidence-based medicine. (28)” This is a tall order for a busy clinically orientated profession, and even this article agrees that practicing in this way is fraught with complexity and difficulty. Furthermore, when first published, the authors asked whether advocating evidence-based medicine in the absence of definitive evidence of its superiority in terms of improving patient outcomes is an internal contradiction (29).

One of the challenges facing a clinically trained and clinically based practitioner who does no in-house research and whose practice is full of competing demands is how to best evaluate the available evidence and make the best treatment decisions for patients who present every day with complex problems. The average physician spends far beyond 40 hours per week in the office, seeing patients, managing staffing issues and dealing with paperwork.

The available paths to researching evidence-based literature and applying that information to complex patients with a multitude of issues are as follows:

  1. Read journal article summaries at night with a critical eye on the quality of the research presented. Many doctors have a strictly clinical background, not a statistically oriented, research-based background, and therefore, they may lack the knowledge to interpret research articles critically.
  2. Read the opinion pieces or position papers of others who have read the original articles and commented on the quality of the research presented in association or interest group publications. Many of the position papers published by specific associations may not have the current best evidence and may not represent the best science available.
  3. Attend conferences where the presenters, one assumes, are leading the field that the conference concerns, have done the necessary research and are presenting information based on Level I and Level II evidence-based research.
  4. Listen to drug company reps who visit one’s office with the details of the research concerning their products, which is presumably biased due to vested interests whether the product in question is a supplement or a drug.
  5. Listen to patients’ summaries of their internet searches and attempt to interpret their evidence into rational decision making.
  6. Read up on what one’s colleagues are discussing and/or referencing in online discussion groups.

From these beginnings, evidence-based medicine has had some major achievements. The Cochrane Collaboration was established to collate and summarise evidence from clinical trials, methodological and publication standards for primary and secondary research were established, national and international infrastructures were built to develop and update clinical practice guidelines, resources and courses were developed to teach critical appraisal and new knowledge bases for implementation and knowledge transition were built (30).

However, since evidence-based medicine was first introduced and adopted, many cracks in the paradigm have appeared that warrant careful appraisal:

  1. The co-opting of clinical trials by invested drug manufacturing and medical device interests and the manipulation of data to suit endpoint outcomes has become more subtle and harder to detect. These companies often set the research agenda, decide what is counted as a disease (i.e., sexual arousal disorder, which is treated with sildenafil), decide which tests and treatments will be compared and choose the efficacy outcome measures (31). In addition, setting inclusion criteria to select those most likely to respond to treatment, manipulating the dosing of both intervention and control drugs and selectively publishing positive studies (while suppressing negative outcomes) in leading peer-reviewed journals, with the assumption that their trials are unbiased, creates serious legitimacy issues regarding the conclusions reached. One review of industry-sponsored trials of antidepressants showed that 37 of 38 had positive findings but only 14 of 36 trials with negative findings were published (32). Psychiatric prescription and drug trials are at the centre of many of these controversies (33). Among the RTC studies in psychiatric journals, those that reported conflicts of interest were five times more likely to report positive results. Large drug companies do not fund and are not interested in treatment interventions that do not support a pharmaceutical intervention.
    Many studies that show the long-term benefits of compounded bioidentical hormone replacement therapy interventions do not make it to mainstream medical journals for these very reasons. A very contentious JAMA-published article, a retrospective observational study, indicated the negative effects of testosterone replacement therapy on cardiovascular disease, and this article changed the way that testosterone therapy was used in male andropause, despite the fact that many prior RCT studies had shown no such impact or favourable outcomes (34).
  2. The co-opting of policy makers (politicians) by the drug industry affects the introduction of certain evidence-based policies (35).
  3. A surplus of evidence results in unmanageable clinical guidelines (36).
  4. Large trials are designed to achieve marginal gains in a saturated therapeutic field and may tend to overestimate potential benefits. After many of the large early gains in research (the use of antiretroviral drugs in HIV and the use of triple antibiotic therapy in H. Pylori), new research has had to shift its focus to marginal gains in often overpowered trials that tend to underestimate harm (adverse effects undetected) and overestimate benefits (effects that are statistically but not clinically significant (37)). GlaxoSmithKline was fined $3 billion for multiple criminal and civil offenses, such as false reporting, the unlawful promotion of medicines and failure to report safety data (38).
  5. The overemphasising of computerised decision support systems and defensive decision-making support technologies, as well as inexperience with complex presentations that do not comply with simple guidelines, may interfere with more experienced and nuanced clinical decision making on the part of an experienced practitioner who is somewhat accustomed to tolerating ambiguity and uncertainty in clinical decision making (39).
  6. Decision making may be driven by non-clinical staff who are incentivised by financial endpoints and not by the nuanced quality of care for complex individual patients. “Patients may often feel tyrannized when their clinical management is inappropriately driven by algorithmic protocols, top-down directives and population targets (40).”
  7. Simple and/or complex algorithms do not fully apply to an aging population with complex presentations and comorbid conditions. Each person is genetically and biochemically unique (as is only too well demonstrated in the CRS population), and although specific guidelines, as outlined by Dr. Shoemaker, must be followed to achieve success, there may still be many comorbid complexities that render the application of these same strict guidelines somewhat problematic, i.e., a patient with CIRS who has had a previous traumatic brain injury, complex early developmental trauma and a borderline personality disorder.

The authors of this critical 2014 BMJ paper, entitled “Evidence-based medicine: A movement in crisis?” suggest launching of a new campaign for what they termed “real evidence-based medicine”. According to them, this is how to best describe what they mean by real evidence-based medicine and the remedying solution:

What is real evidence-based medicine, and how do we achieve it? Real evidence-based medicine:

  • Makes the ethical care of the patient its top priority.
  • Demands individualised evidence in a format that clinicians and patients can understand.
  • Is characterised by expert judgment rather than mechanical rule following.
  • Shares decisions with patients through meaningful conversations.
  • Builds on a strong clinician-patient relationship and the human aspects of care.
  • Applies these principles at community level for evidence-based public health.

Actions to deliver real evidence based medicine:

  • Patients must demand better evidence that is better-presented, better-explained and applied in a more personalised way.
  • Clinical training must go beyond searching and critical appraisal to hone expert judgment and shared decision-making skills.
  • Producers of evidence summaries, clinical guidelines, and decision support tools must take account of who will use them and for what purposes and under what constraints they will be used.
  • Publishers must demand that studies meet usability standards, as well as methodological ones.
  • Policymakers must resist the instrumental generation and use of “evidence” by vested interests.
  • Independent funders must increasingly shape the production, synthesis, and dissemination of high-quality clinical and public health evidence.
  • The research agenda must become broader and more interdisciplinary, embracing the experience of illness, the psychology of evidence interpretation, the negotiation and sharing of evidence by clinicians and patients, and the prevention of harm from over-diagnosis.

I believe some of these revised criteria have been met by Dr. Shoemaker and his co-authors. Dr. Shoemaker has published critiques of what has passed for evidence-based medicine guidelines in the management of mold illness prior to his ground-breaking work. The American College of Occupational and Environmental Medicine (ACOEM) and the American Academy of Asthma, Allergy and Immunology (AAAAI) published in 2002 and 2006, respectively, guidelines reporting that mold exposure was not capable of producing human illness. Much of the ACOEM “evidence” was based on opinion papers by defense consultants in litigation regarding water-damaged buildings (Bruce Kelman and Ronald Gots) and cited no human studies as reference material (41). Dr. Shoemaker cited an article in the Wall Street Journal and an article by Craner that exposed the bias and concealed conflicts of interest of the ACOEM authors: “there is nothing evidence-based in either the ACOEM or AAAAI, as that process begins with the observation of affected patients.” Dr. Shoemaker is clearly using the criteria regarding the best way to practice evidence-based medicine in his criticism of their lack of fulfillment of these criteria in publishing these opinion papers.

I have relied almost exclusively on Dr. Shoemaker and various co-authors of certain papers to understand the complexity of this multilayered condition. Dr. Shoemaker is extremely insistent that the steps to be followed in the diagnosis and treatment of this condition must follow the guidelines set out by his own research, as well as clinical practice and treatment guidelines. It is obvious that he has followed an evidence-based approach in this undertaking. Dr. Shoemaker began his original work with CIRS when he observed that patients with a mysterious disease seemed to improve when prescribed a lipid-lowering drug, cholestyramine. Based on that original observation, he explored the biology and pathophysiology of the disease processes in patients, using the best evidence available at the time, without the influence of financial interests. As he learned, he explored further hypothesises, published numerus studies, wrote books, collaborated with other researchers and lectured on the subject. He continues to utilise the best evidence-based practices in an attempt to understand the genomics that underlie CIRS and how the use of VIP (and the rest of the CIRS protocol) influences the proteomic and Neuroquant findings of affected individuals.

The proof regarding whether an evidence-based approach is effective in managing CIRS patients is whether the patients involved in the study enjoy improved health as compared to controls. At present, there are no long-term randomized trials of the Shoemaker approach to treating CIRS. In other words, his research may not have fulfilled the Level I criteria regarding what type of research best characterises evidence-based medicine. However, his work has nonetheless systematically fulfilled most of the other criteria in that it is patient-centered and documents responses to care that are quantifiable and reproducible.

(*1) Evidence-Based Medicine Working Group. Evidence-based medicine. A new approach to teaching the practice of medicine. JAMA 1992; 268: 2420-5.
(*2) Ibid
(*3) Ibid
(*4) Greenhalgh, T., “Evidence-based medicine: a movement in crisis?” BMJ 2014; 13 June, 348
(*5) http://researchguides.uic.edu/ebm
(*6) Sackett D.L., et al., “Evidence-Based Medicine: How to Practice and Teach EBM.” Edinburgh: Churchill Livingstone.
(*7) Doherty, Steve. “Evidence-based medicine: Arguments for and Against.” Emergency Medicine Australasia 2005; 17: 307-13.
(*8) Sackett, D.L., Rosenberg, W.M.C., Gray, J., Haynes R.B., Richardson W.S., “Evidence-based medicine: what it is and what it isn’t.” BMJ; 312:71-72.
(*9) Kuhn, T.S., The Structure of Scientific Revolutions. Chicago, Ill: University of Chicago Press; 1970
(*10) Dossey, L., Alternative Therapies Sept/Oct 2002, Vol. 8, No.5 32
(*11) Rossouw, J.E.1, Anderson, G.L., Prentice, R.L., LaCroix, A.Z., Kooperberg, C., Stefanick, M.L., Jackson, R.D., Beresford, S.A., Howard, B.V., Johnson, K.C., Kotchen, J.M., Ockene, J. Writing Group for the Women's Health Initiative. (2002). “Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial.” JAMA. 288(3):321-33.
(*12) Family Practice News. (2003). 33(11), 1-2
(*13) Freedman D., (2010). Lies, Damned Lies, and Medical Science. The Atlantic. Nov 2010 Issue.
(*14) Ioannidis, J.P.A., (2005). Why Most Published Research Findings Are False. PLoS Med 2(8): e124. doi:10.1371/journal.pmed.0020124
(*15) Freedman D., (2010). Lies, Damned Lies, and Medical Science. The Atlantic. Nov 2010 Issue.
(*16) Csoka, A., (2015). Innovation in medicine: Ignaz the reviled and Egas the regaled. Med Health Care Philos. Springer Journal, Dec 4.
(*17) Wall Street Journal |Feb 25th 2009
(*18) Rogers, S., (2009). Total Wellness. Aug, p. 1.
(*19) Boden et al., (2007). New England Journal of Medicine. Optimal medical therapy with or without PCI for stable coronary artery disease. April 12, 356; 15:5003-16.
(*20) Evidence-Based Medicine Working Group. (1992). Evidence-based medicine: A new approach to teaching the practice of medicine. JAMA, 268(2420), p. 2422.
(*21) Department of Clinical Epidemiology and Biostatistics, McMaster University. (1981). How to read clinical journals, II: to learn about a diagnostic test. Can Med Assoc J. 124:703-710.
(*22) Godfrey, K., (1985). Simple linear regression in medical research. N Engl J Med, 313, p. 1629-1636
(*23) Department of Clinical Epidemiology and Biostatistics, McMaster University. (1981). How to read clinical journals, V: to distinguish useful from useless or even harmful therapy. Can Med Assoc J, 124, 1156-1162.
(*24) Ibid
(*25) Ibid
(*26) University of North Carolina, Health Sciences Library. (2016). “Forming focused questions with PICO.”
(*27) Evidence-Based Medicine Working Group. (1992). Evidence-based medicine: A new approach to teaching the practice of medicine. JAMA, 268, p. 2420.
(*28) Ibid
(*29) Ibid
(*30) Ibid
(*31) Cohen, D., (2013). “FDA official: Clinical trial system is broken.” BMJ, p. 347.
(*32) Turner, E., Matthews, A.M., Linardatos, E., Tell, R., Rosenthal, R. (2008). “Selective publication of antidepressant trials and its influence on apparent efficacy.” N Eng J Med, 358, p. 252-60.
(*33) Perlis, R.H. et al., (2005). “Industry sponsorship and financial conflict of interest in the reporting of clinical trials in psychiatry.” Am J Psychiatry, 162(10), p.1957-60.
(*34) Vigen, R., MD, MSCS1, et al., (2013). “Association of Testosterone Therapy with Mortality, Myocardial Infarction, and Stroke in Men with Low Testosterone Levels.” JAMA, 310(17), 1829-1836
(*35) Le Couteur, D.G., Doust, J., Creasey, H., Brayne, C. (2013). “Political drive to screen for pre-dementia: Not evidence based and ignores the harm of diagnosis.” BMJ, p. 347.
(*36) Allen, D., Harkins, K. (2005). “Too much guidance?” The Lancet, 365, p. 1768.
(*37) Greenhalgh, T., Howick, J., Maskrey, N. (2014). “Evidence-based medicine: A movement in crisis?” BJM. p. 348.
(*38) Roehr, B., (2012). “GlaxoSmithKline is fined record $3billion in US.” BMJ. 345, p. e4568.
(*39) Greenhalgh, T., Howick, J., Maskrey, N. (2014). “Evidence based medicine: A movement in crisis?” BMJ. p. 348.
(*40) Ibid
(*41) Shoemaker, R. (2010). Surviving Mold: Life in the Era of Dangerous Buildings. Otter Bay Books: Baltimore, p. 310-311.