Complexity in medicine: some thoughts

I have been thinking recently about medicine and complexity, as a result of several conversations over many years. In particular, the Cynefin framework developed by Dave Snowden (see diagram below) seems a useful lens to use (this thought is not original to me – see among others, the articles “The Cynefin framework: applying an understanding of complexity to medicine” by Ben Gray and “Cynefin as reference framework to facilitate insight and decision-making in complex contexts of biomedical research” by Gerd Kemperman). I will also refer to two case studies from the book Five Patients by Michael Crichton, which is still quite relevant, in spite of being written in 1969.


The Cynefin framework developed by Dave Snowden. The central dark area is that of Disorder/Confusion, where it is not clear which of the four quadrants apply (image: Dave Snowden).

The Cynefin framework divides problems into four quadrants: Obvious, Complicated, Complex, and Chaotic. In addition, the domain of Disorder/Confusion reflects problems where there is no clarity about which of the other domains apply. In medicine, this reflects cases where multiple factors are at work – potentially, multiple chronic conditions as well as one or more acute ones. These conditions can exist in all four quadrants. Ben Gray gives the example of a child with a broken arm linked to both a vitamin deficiency and an abusive home environment. Several quite different interventions may be required.

The Obvious Quadrant

The quadrant of the Obvious applies to conditions with clear cause and effect, where there is a single right answer. According to Dave Snowden, the appropriate response is to sense what is going on, categorise the situation as one on a standard list, and then to respond in the way that people have been trained to do. This response may be trivial (a band-aid, say), or it may involve enormous professional skill. In medicine, much of nursing falls in this quadrant, as does much of surgery.

Michael Crichton’s Five Patients discuses the case of Peter Luchesi, a man admitted to Massachusetts General Hospital during 1969 with a crushed arm and nearly severed hand, as the result of an industrial accident:

Three inches above the left wrist the forearm had been mashed. Bones stuck out at all angles; reddish areas of muscle with silver fascial coats were exposed in many places. The entire arm about the injury was badly swollen, but the hand was still normal size, although it looked shrunken and atrophic in comparison. The color of the hand was deep blue-gray.

Carefully, Appel picked up the hand, which flopped loosely at the wrist. He checked pulses and found none below the elbow. He touched the fingers of the hand with a pin and asked if Luchesi could feel it; results were confusing, but there appeared to be some loss of sensation. He asked if the patient could move any of his fingers; he could not.

Meanwhile, the orthopedic resident, Dr. Robert Hussey, arrived and examined the hand. He concluded that both bones in the forearm, the radius and ulna, were broken and suggested the hand be elevated; he proceeded to do this.

Outside the door to the room, one of the admitting men stopped Appel. ‘Are you going to take it, or try to keep it?’

‘Hell, we’re going to keep it,’ Appel said. ‘That’s a good hand.’

Once the surgeons had sensed the problem and categorised it as an arm reconstruction, a team of three surgeons, two nurses, and an anaesthetist (all highly trained in their respective fields) then spent more than 6 hours in the operating theatre, repairing bone, tendons, and blood vessels. Certainly not trivial, but a case of professionals doing what they were trained to do.

The Complicated Quadrant


Public Domain image

The Complicated quadrant is the realm of diagnosis. Information is collected – in medicine, that generally means patient history, blood tests, scans, etc. – and is then subjected to analysis. This identifies the nature of the problem (in an ideal world, at least), which in turn indicates the appropriate response.

Diagnosis by physicians typically searches for the cause of an illness, while diagnosis by nurses typically focuses on severity. This reflects differences in the responses that physicians and nurses have been trained to provide (the triage officer in a modern hospital is typically a nurse).

Decades of work have gone into automating the diagnosis process – initially using statistical analysis, later using expert systems, and most recently using machine learning. At present, the tool of choice is still the human brain.

In general, modern medicine excels when it operates in the Obvious and Complicated quadrants.

The Complex Quadrant

The Complex quadrant is the realm of interactions. It is inherently very difficult to deal with, and cause and effect are difficult to disentangle. The paradigm of information collection and analysis fails, because each probe of the system changes it in some way. The best approach is a sequence of experiments, following each probe with a response that seems reasonable, and hoping to find an underlying pattern or a treatment that works. Michael Crichton provides this example:

Until his admission, John O’Connor, a fifty-year-old railroad dispatcher from Charlestown, was in perfect health. He had never been sick a day in his life.

On the morning of his admission, he awoke early, complaining of vague abdominal pain. He vomited once, bringing up clear material, and had some diarrhea. He went to see his family doctor, who said that he had no fever and his white cell count was normal. He told Mr. O’Connor that it was probably gastroenteritis, and advised him to rest and take paregoric to settle his stomach.

In the afternoon, Mr. O’Connor began to feel warm. He then had two shaking chills. His wife suggested he call his doctor once again, but when Mr. O’Connor went to the phone, he collapsed. At 5 p.m. his wife brought him to the MGH emergency ward, where he was noted to have a temperature of 108 °F [42 °C] and a white count of 37,000 (normal count: 5,000–10,000).

The patient was wildly delirious; it required ten people to hold him down as he thrashed about. He spoke only nonsense words and groans, and did not respond to his name. …

One difficulty here was that John O’Connor could not speak, and so could not provide information about where he felt pain. He appeared to suffer from septicaemia (blood poisoning) due to a bacterial infection in his gall bladder, urinary tract, GI tract, pericardium, lungs, or some other organ. Antibiotics were given almost immediately, to save his life. These eliminated the bacteria from his blood, but did not tackle the root infection. They also made it difficult to identify the bacteria involved, or to locate the root infection, thus hampering any kind of targeted response. In the end (after 30 days in hospital!) John O’Connor was cured, but the hospital never did locate the original root infection.

Similar problems occur with infants (Michael Crichton notes that “Classically, the fever of unknown origin is a pediatric problem, and classically it is a problem for the same reasons it was a problem with Mr. O’Connor—the patient cannot tell you how he feels or what hurts”). As Kemperman notes, medical treatment of the elderly often also falls in the Complex domain, with multiple interacting chronic conditions, and multiple interacting drug treatments. Medical treatment of mental illness is also Complex, as the brain adapts to one treatment regimen, and the doctor must experiment to find another that stabilises the patient.

Similarly Complex is the day-to-day maintenance of wellness (see the Food and Wellness section below) which often falls outside of mainstream medicine.

The Chaotic Quadrant

The Chaotic quadrant is even more difficult than the Complex one. Things are changing so rapidly that information collection and experimentation are impossible. The only possible response is a dance of acting and reacting, attempting to stabilise the situation enough that it moves from Chaotic to Complex. Emergency medicine generally falls in this quadrant – immediate responses are necessary to stop the patient dying. In the airline industry, the ultimate (and extremely rare) nightmare of total engine failure shortly after takeoff (as in US Airways Flight 1549) sits here too – each second of delay sees gravity take its toll.

Success in the Chaotic domain requires considerable experience. In cases where the problem is a rare one, this experience must be created synthetically using simulation-based training.

Food and Wellness

Michael Crichton notes that “The hospital is oriented toward curative treatment of established disease at an advanced or critical stage. Increasingly, the hospital population tends to consist of patients with more and more acute illnesses, until even cancer must accept a somewhat secondary position.” There is, however, a need for managing the Complex space of minor variations from wellness, using low-impact forms of treatment, such as variations in diet. Some sections of this field are reasonably well understood, including:

Traditional culture often addresses this space as well. For example, Chinese culture classifies foods as Yin (cooling) or Yang (heaty) – although there is little formal evidence on the validity of this classification.

There remain many unknowns, however, and responses to food are highly individual anyway. There may be a place here for electronic apps that record daily food intake, medicine doses, activities, etc., along with a subjective wellness rating. Time series analysis may be able to find patterns in such data – for example, I might have an increased chance of a migraine two days after eating fish. Once identified, such patterns suggest obvious changes in one’s diet or daily schedule. Other techniques for managing this Complex healthcare space are also urgently needed.


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Oral rehydration therapy at home #2

Following up my last post on oral rehydration therapy, it was pointed out to me that coconut water is a rich source of potassium. So much so that it can be used to make an alternate home recipe for Oral Rehydration Solution. The recipe, illustrated above, is:

  • 3 metric cups (750 ml) of water
  • 1 metric cup (250 ml) of coconut water
  • 8 metric teaspoons (40 ml) of lemon or lime juice, as a source of citrate
  • 1 metric teaspoon (5 ml) of honey, to supply additional glucose
  • ½ metric teaspoon of salt, to supply additional chloride and sodium
  • ½ metric teaspoon of baking soda (sodium bicarbonate), to supply additional sodium, and as a way of neutralising the acidity in the lemon or lime juice

Oral rehydration therapy at home

Oral rehydration therapy is one of the most cost-effective lifesavers in the history of medicine. It stops people dying from cholera and other diarrheal diseases. It works because of the sodium-glucose co-transport mechanism in the intestines, discovered by Robert K. Crane around 1960.

The WHO has guidelines for Oral Rehydration Solution, and the recipe pictured at the top of this post is my attempt to approximate these guidelines using ordinary kitchen ingredients and easy measurements (doing a computerised search through the space of valid options). The mix actually tastes OK too. The recipe is:

  • 1 litre of water
  • 8 metric teaspoons (40 ml) of lemon or lime juice, as a source of citrate (10 millimoles, by my calculation)
  • 3 metric teaspoons (15 ml) of honey, as a source of glucose and other sugars (90 millimoles)
  • 1 metric teaspoon (5 ml) of cream of tartar (potassium bitartrate), as a source of potassium (19 millimoles)
  • ¾ metric teaspoon of salt, as a source of chloride (73 millimoles) and sodium
  • ¼ metric teaspoon of baking soda (sodium bicarbonate), as an additional source of sodium (giving 87 millimoles in total), and as a way of neutralising the acidity in the lemon or lime juice

The total osmolarity here is just under 300 millimoles, which is above the optimum of 245, but under the upper limit of 310. The specific WHO criteria for glucose (between the sodium level and 111 millimoles), sodium (60–90), potassium (15–25), citrate (8–12) and chloride (50–80) are also satisfied.

Possible substitutions are 13.5 grams of glucose powder for the honey and 2.1 grams of citric acid monohydrate for the lemon juice. The three other ingredients can also be replaced by ½ teaspoon “lite salt” (which provides sodium and potassium), ¼ teaspoon ordinary salt, and ½ teaspoon baking soda.


Angélique du Coudray, pioneer midwife


Angélique du Coudray

Angélique du Coudray (c. 1714–1794) was a pioneering French midwife. In 1759 she published a midwifery textbook, Abrégé de l’art des accouchements. Her introduction notes the fact that incompetence or lack of care can lead to the death of both mother and child, and continues with a politico-religious imperative: “Ignorons-nous que ces deux viâimes étoient chères aux yeux de Dieu, utiles à leur famille, & nécessaires à l’État? C’étoit un dépôt qui nous avoit été confié. Pouvons-nous, en les sacrifiant à un vil intérêt, ne pas trembler sur le compte exact que nous en rendrons un jour à celui qui leur avoit donné l’être?” (“Do we not know that these two lives were dear to the eyes of God, useful to their families, and necessary to the State? They were a deposit which was entrusted to us. Can we, if we sacrifice them to a vile interest, not tremble at the exact account that we shall one day render to Him who gave them to be?”).

To avoid such deaths, du Coudray explains proper prenatal care, and provides instruction on both normal deliveries and a range of common obstetric problems.


Illustration of a normal delivery, from the 1777 edition of Abrégé de l’art des accouchements

Also in 1759, Angélique du Coudray was commissioned by King Louis XV to tour the country training midwives, in the hope of reducing perinatal mortality. She personally trained thousands of midwives, many of whom went on to train others. Her training course was assisted not only by her book, but also by her Machine, a pioneering lifesize obstetric simulator. The Machine included realistic internal structure, such as bones and ligaments, and could be used to practice delivery of a baby in a range of different positions, while giving the trainee midwife a feel for the forces involved.


Angélique du Coudray’s Machine (photo: Ji-Elle)


New antibiotics urgently needed

The World Health Organization (WHO) has recently released a list of bacteria for which new antibiotics are urgently needed. They are hoping for new research and development, especially on multi-drug-resistant gram-negative bacteria. The list is divided into three priority categories:

CRITICAL PRIORITY

HIGH Priority

Medium Priority


Homeopathy

Homeopathy is an alternative medicine based, in large part, on extremely dilute solutions of illness-producing agents. For example, diluted coffee is used to treat insomnia.

Given the levels of dilution used, and the fact that 18 grams of water (about one tablespoon) contains about 6 × 1023 molecules, this means that homeopathic medicines generally contain zero molecules of the active ingredient – that is, they are generally plain water. The 10:23 anti-homeopathy campaign is based on that idea:

Last year, the Australian National Health and Medical Research Council (NHMRC) completed a review of the effectiveness of homeopathy, concluding that there are no health conditions for which there is reliable evidence that homeopathy is effective because no good-quality, well-designed studies with enough participants for a meaningful result reported either that homeopathy caused greater health improvements than placebo, or caused health improvements equal to those of another treatment.

See also a blog post by the report chair here, or listen to this interview with Edzard Ernst, former Professor of Complementary Medicine at Exeter. XKCD makes an economic argument about effectiveness:


Mercury and formaldehyde in vaccines?

The anti-vax community runs regular scare campaigns regarding “toxins in vaccines.” Mercury and formaldehyde are the two most often mentioned. Mercury occurs in the form of the antibacterial thiomersal (thimerosal), but not in vaccines routinely administered to children. Thiomersal is present in multi-dose vials (not in single-use vials) of influenza vaccine, typically at a level of 25 micrograms (0.025 milligrams) per dose. For comparison, though, the normal mercury intake is about 2410 micrograms (2.41 milligrams) per year, so an annual “flu shot” adds very little extra. And even that exaggerates the risk, because thiomersal breaks down into ethylmercury, which is less dangerous than other forms.

Formaldehyde, though toxic in moderate to large quantities, is naturally produced and consumed as part of human metabolism, with a turnover of about 50 grams of formaldehyde per day for a person weighing 50 kg. Formaldehyde occurs naturally in blood at levels of about 2.6 milligrams per litre. Even for a 3.5 kg newborn baby (with 85 mL/kg of blood), that comes to 0.77 milligrams of formaldehyde (and there’s more in body tissue). Vaccines contain at most 100 micrograms (0.1 milligrams) of formaldehyde, and so add very little to the blood (and that is very quickly eliminated). That’s even more true for older children, with their much greater blood volume.

Part of the problem here, I suspect, is widespread confusion between grams, milligrams, and micrograms. At the other end, of course, some people also have problems in economics with understanding the difference between millions, billions, and trillions.