The uncertainty principle
in clinical medicine.

Or more correctly "the observer effect" apparently. The uncertainty principle of Heisenberg sounds appropriate though. I'm often enough left scratching my head. Little in clinical medicine is absolutely certain and often all that can be offered at the first consultation is a rough first approximation. One does need this step of forming a testable hypothesis, before ordering pathology tests or imaging. These are otherwise of very limited value.

The observer effect as applied to medicine refers to "the drug doctor." The doctor is part of the treatment, for good or bad. Our attitude makes a difference, and so do just the normal history taking and examination. A wise teacher advised me to watch cancer patients for the appearance of complications and spread, "unobtrusively." Blood pressure readings at a clinic are higher than at home. The best way to avoid this "white coat effect" is to use an automatic machine with the person alone in a side room, set to wait 5 minutes then do 3 recordings at 2-minutely intervals.

Reducing uncertainty
the boy scout way

Be prepared. Ensure your clothing will allow for quick examination of the parts of your body likely to need looking at. Take a urine sample just in case. More things are missed by not looking than by not seeing, so make it easy to look and thereby reduce the chance of misdiagnosis.

Redundancy is good

Not in employment, but certainly so in our body, in the sense of more than one means to an end. Many examples of this are found in our biochemistry and physiology. Jet fighters with two completely independent computer systems and commercial jets with multiple hydraulic systems are good examples in aviation.

Amy Neuzil puts it very nicely talking about MTHFR mutation management
"Every system in the human body has a glorious level of redundancy – we are literally designed to fail in eight hundred ways and still function normally."

The working out of the uncertainty principle in clinical medicine, in the first sense mentioned above, can be reduced by redundancy in the diagnostic process. Double checking is the thing. One example is when testing for inflammation, to use both ESR (erythrocyte sedimentation rate,) and CRP (C-reactive protein.)

Using two parameters which move in opposite directions2 can be very useful. TSH and T4, vitamin B 12 and homocysteine, serum zinc and copper are examples.

Number needed to treat

Quite apart from you not being the (mythical) "average person" the treatment is designed for, things just don't work all the time - at least not in the way one hopes for.

Probably no two people on this planet, have exactly the same chemistry. We each have a unique pattern of activities of the thousands of enzymes which facilitate our metabolism. The same treatment can have quite different effects in different people.

The great Roger J. Williams experienced this when he was given morphine after an operation.

The NNT is the number of people who would have to undergo some treatment for a prescribed time to achieve a particular desired result in one of them. There would be very few treatments with NNT of 1

Waiting a bit can be helpful

Quoting Dr. Liz Harris1
"Inappropriate, symptomatic prescribing may delay diagnosis by modifying or obscuring the disease presentation."

This doesn't mean sitting at home getting worse, worrying and delaying going for help. It may mean not pushing for treatment if the health professional is uncertain what is best, or being prepared to put up with some discomfort (and uncertainty) temporarily.

Concrete examples

In this uncertain world, there are plenty of examples of very "soft" criteria.

Mr. A had three blood test over as many years, showing his red blood cells were larger than most people's (98, compared to reference range of 80 to 96.)

His vitamin B 12 level was 267 (a fifth of the way up RR of 150 to 700,) and homocysteine 9.5 (just into the upper half of RR 3.7 to 13.9.) This combination of tests made B 12 deficiency possible.

A couple of injections of vitamin B 12 later, the homocysteine test was 8.5 (10% lower,) leaving the question still uncertain.It needs to be 12.5% lower to prove deficiency.

Mrs. C's shoulder X-ray showed calcification of her Supraspinatus tendon and she could get off balance, both of which can be due to vitamin B 12 deficiency.

Her B 12 blood test was 350 (a quarter of the way up RR 200 to 800.)

She had three injections of B 12 and reported that this "helped shoulder a tiny bit and helped the balance."

Probable but unproven B 12 deficiency.

We are often left having to rely on our gut feeling or our patient's preference. I am delighted if my patients use some method of accessing their own intuition, to make their own decisions. I have some patients who check everything with kinesiology muscle testing or dowsing with a pendulum. In my experience these methods can be quite accurate. This sounds like I'm passing the buck and avoiding responsibility, but all decisions are ultimately taken by the person who is affected most directly. What I don't want is someone meekly accepting a course of action then reneging later. Better to deal with the uncertainty principle head on now.

Anita Moorjani on uncertainty

From p 137 of "Dying To Be Me" is the following passage...
"Since my NDE, I've learned that strongly held ideologies actually work against me. Needing to operate out of concrete beliefs limits my experiences because it keeps me within the realm of only what I know - and my knowledge is limited. And if I restrict myself to only what I'm able to conceive, I'm holding back my potential and what I allow into my life. However, if I can accept that my understanding is incomplete, and if I'm able to be comfortable with uncertainty, this opens me up to the realm of infinite possibilities....My sense is that the very act of needing certainty is a hindrance to experiencing greater levels of awareness."
From page 166
"Having concrete beliefs limits my life experiences because they keep me locked into only what I know, and my knowledge in this world is limited by my physical senses. Being comfortable with uncertainty, on the other hand, opens me up to all possibilities. Ambiguity is wide open to infinite potential."

Ayn Rand's take on it

In Atlas Shrugged, she has John Galt saying...
"Do not say that you’re afraid to trust your mind because you know so little...Live and act within the limit of your knowledge and keep expanding it to the limit of your life. Redeem your mind from the hockshops of authority. Accept the fact that you are not omniscient, but playing a zombie will not give you omniscience – that your mind is fallible, but becoming mindless will not make you infallible – that an error made on your own is safer than ten truths accepted on faith, because the first leaves you the means to correct it, but the second destroys your capacity to distinguish truth from error."

Historical perspective

Reading Reminiscences and Opinions of University of Melbourne 1955 medical graduates the following was pertinent...
"An autopsy was performed after most deaths in hospital at that time, virtually as a routine.... Autopsy provided an important audit, clinical diagnosis was often tentative in an age predating sophisticated radiology, and not infrequently it was only on the autopsy table that a correct final diagnosis emerged."
Obviously for tentative, read incorrect.

I'm sold on electronic prescribing because of an experience years ago, prior to modern CT and US scanning.

One of my patients was on an anti-depressant medication called Concordin but got Coumadin dispensed, partly because of my poor handwriting and partly because of a careless pharmacist3. Both drugs came as a 5mg tablet. The patient didn't recognize the mistake.

She got abdominal pain and attended hospital where appendicitis was diagnosed. Operation was scheduled for the next morning and she asked for her usual medication and the error was discovered, most likely saving her life. She had bled internally as Coumadin is an anticoagulant called warfarin, the same as used in rat poison.

A cat scan would show this up, nowdays.

Notes and references for the uncertainty principle page

1. Dr. Liz Harris To prescribe or not to prescribe: the eternal dilemma. Medical Observer 30th October 1992

2. Thyroid stimulating hormone (TSH) is the accelerator for the thyroid gland. Thyroxine (T4) is its output. In diseases of the gland when it cannot maintain its output, the body attempts to stimulate it by raising TSH.

In vitamin B 12 deficiency, re-methylation of homocysteine is inefficient and it banks up. Elevated homocysteine often indicates vitamin B 12 deficiency, but HCY in the top half of the reference range combined with B12 low in its range, is very suspicious

Zinc and copper are both stored on metallothionein. Too much of either will displace the other and increase its loss.The ratio of serum zinc to copper is a better guide regarding zinc deficiency than either level alone.

3 MRC Cognition and Brain Sciences Unit
Aoccdrnig to a rscheearch at Cmabrigde Uinervtisy, it deosn't mttaer in waht oredr the ltteers in a wrod are, the olny iprmoetnt tihng is taht the frist and lsat ltteer be at the rghit pclae. The rset can be a toatl mses and you can sitll raed it wouthit porbelm. Tihs is bcuseae the huamn mnid deos not raed ervey lteter by istlef, but the wrod as a wlohe.
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