When I was a young doctor working in the countryside I contracted pneumonia. It took me a long time to recognize my main symptom – breathlessness – because I thought that symptoms were what patients, not doctors, had, and that therefore I could not myself have any. I therefore considered my feeling of being unwell to be an illusion. In the abstract I knew that doctors got ill and died, of course, but I found it difficult to believe this in practice, especially in my own case. When the symptom was severe enough, however, the penny dropped, and I looked at my own x-ray with something akin to pride.
Pneumonia, like almost all infectious diseases, is much less common now than it was then, but still remains a common enough cause of hospital admission and of death among the elderly. But according to a paper published in a recent edition of the New England Journal of Medicine, the annual cost of pneumonia requiring hospital treatment is $10 billion, a modest sum compared with the estimated costs of other diseases that one reads about in the same journal. Perhaps hospitals should try harder to raise their prices for treating pneumonia.
The paper is titled “Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults” – community being everywhere except the hospital, one of the commonest places to catch pneumonia. For eighteen months they enrolled all adults aged 18 and above whom physicians at five hospitals diagnosed as having pneumonia and needing to be admitted to the hospital. They then used a variety of diagnostic tests for bacterial and viral pathogens to be found in these patients, and compared them with a sample of patients attending one of the hospitals for non-respiratory problems.
By assuming that all patients in the hospitals’ catchment areas who needed hospitalization for pneumonia were admitted to the five hospitals and no others, they worked out the population rate of admission for hospitalization for pneumonia: 2.48 cases per year per thousand of population at risk. Assuming (what is almost certainly false) that having had pneumonia once does not mean increased susceptibility to having it again, the figure means than an adult has about a one in seven chance of being admitted to the hospital for pneumonia at some time in his life.
Unsurprisingly, the risk increased enormously with age. Between the ages of 50 and 64 you are 4 times more likely to need hospitalization for pneumonia than between the ages of 18 and 49, 9 times more likely between the ages of 65 and 79, and 25 times more likely after the age of 80. This makes me rather proud, the member of a small elite in fact, to have had pneumonia when I was only 27.
Man is a creature that likes to change his mental state, even if it is for the worse. It is the change that he seeks, not the end result; Nirvana for him is a constantly fluctuating or dramatic state of mind. This, for obvious reasons, is particularly so for the bored and dissatisfied. In the prison in which I worked, for example, the prisoners would take any pills that they happened to find in the hope that they would have some — any — effect on their mental state, irrespective of the dangers that might be involved in producing it.
A recent article in the New England Journal of Medicine draws attention to an increase in the United States of reported side-effects caused by the consumption of synthetic cannabinoids. These were first synthesised in the 1980s as research tools, but soon escaped the laboratory. (How, at whose instigation and for what reasons, one would like to know?) Now there are illicit chemical laboratories, mainly in Europe, producing an ever wider range of such cannabinoids, the law limping after them with its prohibitions, only for new compounds that are legal (until banned) to be synthesised almost immediately. The story is a tribute, in a way, to human ingenuity.
Between January and May 2014, poison control centers throughout the United States received 1085 calls concerning possible side-effects of synthetic cannabinoids, but in the same period in 205 received 3572 such calls, which mysteriously the CDC calculated as a 229 percent increase, when it is a 329 percent increase.
Of the 2961 calls concerning cases in which the medical condition and outcome was known, 335 were serious, which is to say life-threatening or resulting in significant disability, and a further 1407 necessitated medical treatment. 1219, therefore, were minor and quickly self-limiting.
There were 15 known deaths among the subjects of the 2961 calls, only one of which involved multiple drugs. This does not mean, of course, that the other 14 deaths can be attributed indubitably to the cannabinoids, for the figures are completely uncontrolled and it is impossible to say how many would have died anyway. Still, it is more likely than not that most of the deaths were caused by the drugs, directly or indirectly, given the age range of those who took them.
One of the problems of assessing the side-effects of cannabinoids is that they do not cause a characteristic syndrome that is easily recognizable. All the side-effects that they cause — agitation, tachycardia, drowsiness and lethargy, vomiting, confusion — can be caused by a host of other conditions, and not just by intoxication with artificial cannabinoid. However, the hospital in which I used to work, which now treats several cases a week, is able to detect the various substances in the urine or saliva within two hours, and can thus distinguish between Exodus, Damnation, Space-Cadet, Pirate and Annihilation, as they are popularly known.
Needless to say, the raw figures from the CDC do not tell us everything that we should like to know about the epidemiology of the consumption of synthetic cannabinoids. We do not know even whether the increase in the numbers of calls received by the poison control centers represents a real increase in the numbers of patients attending hospitals with the side-effects caused by synthetic cannabinoids, or an increase in the awareness among doctors of the possible diagnosis.
More importantly, since we do not know how many people take these drugs and in what quantities, we cannot say what proportion of people who take them experience serious effects. We do not even know the proportion of those who experience serious effects are diagnosed as suffering from them. As is always the case, further research is required.
Novels should have good first lines: “Call me Ishmael”; “It was the best of times, it was the worst of times”; “Every happy family is happy in the same way”; “There was no possibility of going for a walk that day”; “It is a truth universally acknowledged… etc.” One does not expect scientific papers to grab one’s attention in quite the same way.
But a paper published in a recent edition of the New England Journal of Medicine opens interestingly, if not quite with the same literary flair as that of Melville, Dickens or Tolstoy, etc. It begins:
The increase in the rate of obesity, a chronic disease with serious health consequences, largely explains the recent trebling of the prevalence of type 2 diabetes.
This is an odd way of putting it, as if the authors themselves did not quite believe what they were saying. They would not have written “Cancer, a chronic disease with serious health consequences…” because to have cancer is to have bad health. Poverty is not caused by having too little money; poverty is having too little money.
Perhaps it doesn’t matter much what one calls obesity—disease or the wages of sin, or at least of weakness—because everyone is agreed that it is a bad thing and ought, if possible, to be reduced.
The authors conducted a double blind trial against placebo of a drug called liraglutide, which was injected daily subcutaneously for 56 weeks. 3731 fat patients from 191 clinics on 5 continents with a high body-mass index were allocated either to the drug or to placebo (2487 to active treatment, 1244 to placebo), both groups being given standard advice about diet and exercise.
The first thing to note is that only 71.9 percent of the treatment group, and 64.4 percent of the placebo group, completed the trial. When one considers that compliance during trials, with the relatively intense attention it gives to patients, is considerably higher than in normal clinical conditions, the actual usefulness of the drug, at least in the epidemiological sense, is much reduced.
I like to have a prejudice overthrown from time to time: it helps to persuade me that my other prejudices are reasonable because I am a reasonable man who is open to the evidence. This is especially the case where the prejudice is one that I do not really care much about. I can give it up without much regret.
A paper in a recent edition of the New England Journal of Medicine overthrew one such minor prejudice, namely that the more thoroughly a person was investigated for an occult cancer after suffering an unexpected deep vein thrombosis (DVT) or pulmonary embolus (PE), the more likely that one would be found.
The association between spontaneous DVT and cancer has long been known. Its discoverer was Armand Trousseau, a great French physician of the middle of the nineteenth century, who noticed that people who suffered DVTs often had cancers such as that of the pancreas, in those days always diagnosed at post mortem. By a strange and tragic coincidence, Trousseau himself suffered a DVT and a few months later was dead – of pancreatic cancer. This is a story from medical history that, once heard, is never forgotten.
It has been found that about 10 per cent of people have diagnosable cancer within a year of having had a DVT or PE. So it seems to stand to reason that if people who suffer such events are investigated up hill and down dale immediately afterwards, some cancers will be caught earlier and treated, and therefore survival will be increased.
Some Canadian researchers tested this hypothesis. They randomly divided 854 patients with either DVT or PE into two groups: those who were tested for cancer by simple methods such as physical examination, blood tests and chest x-ray, and those who, in addition to all these, had CT scans of the abdomen and pelvis. They were then followed up for a year to see whether there was any difference in outcome.
Some patients stick in one’s mind longer than others. I remember, for example, a Welshman with the sing-song intonation of the Welsh who told me on his arrival in hospital that he needed his diazzies [diazepam], and temazzies [temazepam] and his flurazzies [flurazepam] and his lorazzies [lorazepam] and his bromazzies [bromazepam] and his oxazzies [oxazepam]. All these are tranquilizing drugs of the benzodiazepine group, and need was not quite the word for his consumption of them.
On another occasion a patient, a heroin addict, accused me of murdering him because I would not prescribe diazepam for him. In actual fact, I believed that precisely the opposite was almost the case: that if I prescribed for him what he wanted, his chances of dying by overdose, intentionally or unintentionally, would be much increased.
A paper in a recent edition of the British Medical Journal suggests that I was right. It examined the question of whether people prescribed opioid analgesics were more likely to die of overdose if they were also prescribed benzodiazepine tranquilizers than if they were not.
The authors examined the records of patients treated in the U.S. Veterans Administration system between the years 2004 and 2009. Their sample was of 422,786 patients who were prescribed opioids at some time in those years, a figure which I found prima facie astonishing, though perhaps wrongly. Of those 422,786, 2,400 died by overdose, and the authors compared the rate of prescribing of benzodiazepines in addition to opioids among those who had died by overdose with those who had not. What they found was that those who were prescribed both classes of drugs were 3.86 times as likely to die by overdose as those who were prescribed opioids alone. More surprisingly, perhaps, was the fact that those who had ever been prescribed benzodiazepines as well as opioids, but were not currently in receipt of a dual prescription, were 2.33 times more likely to die by overdose than those who had never received a dual prescription.
For a number of reasons these results do not show, in the strictest pharmacological sense, that dual prescription causes additional deaths, the most important of which is that patients prescribed benzodiazepines (usually to calm them down, or get them out of the doctor’s office without a terrible scene taking place) may be more psychologically disturbed than those not prescribed them, and therefore more likely to take overdoses in the first place. There is a dose-response relationship between the dose of benzodiazepine prescribed and the risk of death by overdose, but even this does not prove that dual prescription causes death, because it is likely that those prescribed higher doses of benzodiazepines are yet more psychologically disturbed.
As everyone knows, fresh human blood rejuvenated Dracula no end: stored blood simply would not do for him.
Blood has long been a fluid endowed with mystic significance. Only comparatively recently in human history have people donated it to strangers with anything like a good grace. I once worked in a remote country, much given to drunkenness, where people would only give blood to their relatives, though fortunately they lived in large families. A man there once had an accident requiring rapid and repeated transfusion. His family had all been at a party. After transfusion, he himself was drunk.
It has long been thought that the longer human blood had been stored in blood banks, the less good its quality. There were two papers in a recent edition of the New England Journal of Medicine that tested this hypothesis, which (within limits, of course) turned out to be false, as so many hypotheses do. I think most people would instinctively feel, because it stands to reason, that fresh blood is best; we agree with Dracula.
Normally, blood is taken from donors, treated chemically and tested for viruses and refrigerated. In practice it is not kept more than six weeks, though this period is to an extent arbitrary and by convention. In the first trial, conducted in Canada, Britain, France, the Netherlands and Belgium, critically ill patients in need of blood transfusions were allocated randomly to receive either blood that was less than a week old or blood that was three weeks old.
One short passage in the paper was slightly troubling from the point of view of medical ethics: “At sites where deferred consent was permitted, written informed consent was obtained from the patient or surrogate decision maker as soon as possible after enrollment.” This appears to mean, unless I have misunderstood, that consent was retrospective, in other words that the patients were asked “Do you consent to having been experimented upon?” Even where such consent was not given, refusal was all but pointless, for they were then asked whether, nevertheless, they consented to the use of the data gathered in their case.
It so happened that I was preparing an introduction to an anthology of the writings of Edmund Burke when I read an article in a recent edition of the New England Journal of Medicine with the title “Social Distancing and the Unvaccinated.” One of Burke’s main contentions, at least according to me, is that politics are, or ought to be, more than the application of abstract first principles to practical affairs: and, as if to prove him right, along came this article.
The question was this: if it is permissible for parents to refuse to have their children immunized against preventable childhood diseases, does the state have the right, through one or other of its agencies, to exclude those children temporarily from school or other social institutions if there is an epidemic developing?
This question can be answered neither by a single abstract principle alone nor by appeal to scientific fact. The matter is complex, and on this occasion arose in the context of an outbreak of measles in California that soon spread and was in part occasioned by a reduction in the rate of immunization against the disease consequent upon the fraudulent activities of Dr Andrew Wakefield, a British doctor who claimed falsely to have discovered a link between the measles, mumps and rubella vaccine and the development of childhood autism.
In addition, two sets of parents in New York legally challenged the exclusion of their children from school because they were unimmunized against chickenpox after an infected child was found in the school. The article did not make clear whether the exclusion was primarily to protect the unimmunized children themselves or others in the school, or both (no immunization conferring 100 per cent immunity, and the more cases encountered the greater the likelihood of spread).
Scientific considerations are relevant to, but not probative of, any answer. The article, strangely, made no mention of the fact that parents’ rights, which we all accept within quite wide limits, nevertheless may impinge on those of their children, for example that to life itself: in which case parents’ rights have to be, or at any rate are, overridden.
If the parents’ decision not to immunize were one of life or death, either for their or other children, most (but perhaps not all) people would agree that their say in the matter should not count. But in fact it is rarely one of life and death, but rather one of transient illness with very occasional severe complications. Just how great is the risk of the latter is dependent on factors other than the parents’ decision not to immunize: measles is much less serious a disease in rich than in poor countries, for example. Moreover, some questions, for example, how long it is necessary to socially distance (Orwellian phrase) children in order to abrogate the risk of spreading may not be completely answerable in the current state of knowledge.
How many days off school for one child equal the risk of contraction of a mild illness by another? There is no way of answering this question except by the exercise of judgment in particular circumstances. This is precisely what Burke would have predicted: what we decide cannot be determined by appealing to conflicting rights alone, the more fundamental of them prevailing. Sometimes one will prevail, sometimes another; there is no way of making politics a matter of such accurate calculation that no faculty of judgment, with its permanent possibility of error, will ever have to be exercised.
The article focuses on religious objectors to immunization, but they are probably outnumbered by Californian-style cranks, paranoiacs and believers in all you read on the internet.
I am slightly ashamed of how much I liked Burma when I visited it nearly a third of a century ago. What a delight it was to go to a country in which there had been no progress for 40 years! Of course it was a xenophobic, klepto-socialist, Buddho-Marxist military dictatorship run by the shadowy, sinister and corrupt General Ne Win, and so, in theory, I should have hated it. Instead, I loved it and wished I could have stayed.
Since then there has probably been some progress, no doubt to the detriment of the country’s charm. Burma (now Myanmar) is slowly rejoining the rest of the world, and one consequence of this will be the more rapid advance of treatment-resistant malaria.
A recent paper in the Lancet examined the proportion of patients in Burma with malaria in whom the parasite, Plasmodium falciparum, was resistant to what is now the mainstay of treatment, artemisinin, a derivative of a herbal remedy known for hundreds of years to Chinese medicine. The results are not reassuring.
There was a time, not so very long ago, when the global eradication of malaria was envisaged by the WHO, and it looked for a time as if it might even be achieved. The means employed to eradicate it was insecticide that killed the mosquitoes that transmitted the malarial parasites, but a combination of pressure from environmentalists who were worried about the effects of DDT on the ecosystem and mosquito resistance to insecticides led to a recrudescence of the disease.
At the same time, unfortunately, resistance to antimalarial drugs emerged. Control of malaria, not its eradication, became the goal; an insect and a protozoan had defeated the best efforts of mankind. And this is no small matter: the last time resistance to a mainstay of treatment for malaria, chloroquine, emerged in South-East Asia, millions of people died as a result in Africa for lack of an alternative treatment.
What most surprised me about this paper was the method the authors used to determine the prevalence of resistance to artemisinin in the malarial parasites of Burma: for I remember the days when such prevalence was measured by the crude clinical method of giving patients chloroquine and estimating how many of them failed to get better.
The genetic mutations that make the parasite resistant to artemisinin have been recognized. The authors were able to estimate the percentage of patients with malarial parasites that had mutations associated with drug resistance. Nearly 40 percent of their sample had such mutations, and in a province nearest to India the figure was nearly half. The prospects for the geographical spread of resistance are therefore high.
Nor is this all. Artemisinin resistance was first recognized in Cambodia 10 years ago but the mutations in Burma were different, suggesting that resistance can arise spontaneously in different places at the same time. From the evolutionary point of view, this is not altogether surprising: selection pressure to develop resistance to artemisinin exists wherever the drug is widely used.
One way of reducing the spread of resistance is the use in treatment of malaria of more than one antimalarial drug at a time, but this will only retard the spread, not prevent it altogether. As with tuberculosis, it is likely that parasites resistant to all known drugs will emerge. The authors of the paper end on a pessimistic note:
The pace at which the geographical extent of artemisinin resistance is spreading is faster than the rate at which control and elimination measures are being developed and instituted, or new drugs being introduced.
In other words, deaths from malaria will increase rather than continue to decrease, which is what we have come to think of as the normal evolution of a disease.
When I was a boy in London I used to love what we called pea-soupers, that is to say fogs so thick that you couldn’t see your hand in front of your face at midday. They came every November and buses, with a man walking slowly before them to guide them, would loom up suddenly out of the gloom with their headlights like the glowing eyes of monsters. It took my father so long to drive to work that by the time he arrived it was time for him to come home again. I loved those fogs, but then the government went and spoiled the fun by passing the Clean Air Act. They never returned, those wonderful, exciting fogs.
Little did I know (or care) that those wonderful, exciting fogs killed thousands by bronchitis. But many years later I got bronchitis for the first and only time in my life from breathing the polluted winter air of Calcutta. I have also traveled in Communist countries where it seemed that the only thing the factories produced was pollution. I don’t need persuading that clear air is a good thing, not only aesthetically but also from the health point of view.
Southern California used to have some of the worst air pollution in the United States, but the quality of the air in Los Angeles has improved over the last two or three decades. Researchers who reported their findings in a recent edition of the New England Journal of Medicine conducted what is called a natural experiment: they estimated the pulmonary capacity of children who grew up as the level of pollution declined.
Most research on the health effects of air pollution has concentrated on deaths from cardiovascular disease among adults, usually of a certain age. But it is known that relatively poor lung function among younger people predicts cardiovascular disease later in life quite well. There is also an association between air pollution and early death from cardiovascular disease, though of course an association does not by itself prove causation. Does air pollution cause poor lung function in children?
The researchers measured lung function in three cohorts of children, 2120 in all, aged 11 to 15, who were of those ages between 1994 and 1998, 1997 and 2001, and 2007 and 2011. During this period, atmospheric pollution in Los Angeles declined markedly, as measured by levels of nitrogen dioxide, ozone and particulate matter.
Lung function, estimated by forced expiratory volume, improved (or at any rate increased) as air pollution declined. The numbers of children with lower than predicted function declined from 7.9 percent to 6.3 percent to 3.6 percent in the three cohorts. The improvement occurred among whites and Hispanics, boys and girls, and even those with asthma, i.e. the asthmatics, were less incapacitated.
The authors thought that the improvement in lung function was likely to persist into adulthood or, to put it in a slightly less cheerful way, damage done in childhood by air pollution might be permanent. This is not quite so pessimistic as it sounds, for there is probably no age at which an improvement in the quality of the air is not capable of producing an improvement in health.
The main drawback of the study was that there was no control group, that is to say a population whose cohorts of children experienced no improvement in the quality of the air they breathed. Perhaps the function of their lungs would have shown the same improvement as well, though I rather doubt it.
One little semantic point about the paper: children aged 11 were referred to as students rather than as pupils. Perhaps this is because we nowadays expect people to grow up very quickly, but not very far.
In the past, medical journals, pharmaceutical companies and researchers themselves have been criticized for publishing selectively only their positive results, that is to say, the results that they wanted to find. This is important because accentuation of the positive can easily mislead the medical profession into believing that a certain drug or treatment is much more effective than it really is.
On reading the New England Journal of Medicine and other medical journals, I sometimes wonder whether the pendulum has swung too far in the other direction, in accentuating the negative. To read of so many bright ideas that did not work could act as a discouragement to others and even lead to that permanent temptation of ageing doctors, therapeutic nihilism. But the truth is the truth, and we must follow it wherever it leads.
A recent edition of the NEJM, for example, reported on three trials, two with negative results and one with mildly positive ones. The trials involved the early treatment of stroke, the prophylaxis of HIV injection, and the treatment of angina refractory to normal treatment (a growing problem). Only the latter was successful, but it involved 104 patients as against 6729 patients in the two unsuccessful ones.
The successful trial involved the insertion of a device that increased pressure in the coronary sinus, the vein that drains the blood from the heart itself. For reasons not understood, this seems to redistribute the blood flow in the heart muscle, thus relieving angina. In the trial, the new device relieved and reduced angina symptoms, and improved the quality of life in the patients who received it compared with those who underwent a placebo-operation. The trial was too small, however, to determine whether the device improved survival, though even if it did not a reduction of symptoms and an improvement in the quality of life is worthwhile.
The trial of chemoprophylaxis of HIV was, by contrast, a total failure. The trial recruited 5029 young women in Africa who were given an anti-HIV drug in tablet or cream form, and others who were given placebos. The rate at which they became infected with HIV was compared, and no difference was found.
In large part this was because the patients did not take or use the pills or cream, though they claimed to have done so. A drug that few take is not of much use however effective it might be in theory, especially in prophylaxis rather than treatment. And this points to another problem of pharmaceutical research: in drug trials that require patients’ compliance with a regime, that compliance may be high during the trial itself (thanks to the researchers’ vigilance and enthusiasm) but low in “natural” conditions, when the patients are left to their own devices.
The trial of magnesium sulphate in the early treatment of stroke was also a failure. It had been suggested by experiments on animals that this chemical protects brain cells from degeneration after ischaemic stroke. It stood to reason, then, that it might improve the outcome in humans in ischaemic stroke, at least if given as soon as suspected.
Alas, it was no to be. The trial, involving 1700 patients, showed that the early administration of magnesium sulphate did not improve outcome in the slightest. At 90 days there was no difference between those who received it and those who had received placebo.
Is an idea bad just because it does not work? Could it be that those who discover something useful are just luckier than their colleagues? Perhaps there ought to be a Nobel Prize for failure, that is to say for the brightest idea that failed.
image illustration via shutterstock / PathDoc
How informed is informed? What is the psychological effect of being told of every last possible complication of a treatment? Do all people react the same way to information, or does their reaction depend upon such factors as their intelligence, level of education, and cultural presuppositions, and if so does the informing doctor have to take account of them, and if so how and to what degree? An orthopedic surgeon once told me that obtaining informed consent from patients now takes him so long that he had had to reduce the number of patients that he treats.
An article in a recent edition of the New England Journal of Medicine extols the ethical glories of informed consent without much attention to its limits, difficulties and disadvantages.
It starts by referring to a trial of the level of oxygen in the air given to premature babies, of whom very large numbers are born yearly. Back in the 1940s it was thought that air rich in oxygen would compensate for premature babies’ poor respiratory system, but early in the 1950s British doctors began to suspect, correctly, that these high levels of oxygen caused retinal damage leading to permanent blindness. Fifty years later, the optimal level of oxygen is still not known with certainty, and a trial was conducted that showed that while higher levels of oxygen caused an increased frequency of retinopathy, lower levels resulted in more deaths. The authors of the trial have been criticized because they allegedly did not inform the parents of the possibility that lower levels of oxygen might lead to decreased survival, which was reasonably foreseeable.
How reasonable does reasonability have to be? Many of the most serious consequences of a treatment are totally unexpected and not at all foreseeable (no one suspected that high levels of oxygen for premature babies would result in blindness, for example, and it took many years before this was realized). Ignorance is, after all, the main reason for conducting research.
But suppose parents of premature babies had been asked to participate in a trial in which their offspring were to be allocated randomly to an increased risk of blindness or an increased risk of death. Surely this frankness would have been cruel, all the more so as the precise risks could not have been known in advance. Parents would feel guilt alike if their babies died or were blind.
Now that the answer is known, more or less, parents can be asked to choose in the light of knowledge: but their informed consent will be agonizing because there is no correct answer. Personally, I would rather trust the doctor sufficiently to act in my best interests in the light of his knowledge and experience. So far in life I have not had reason to regret this attitude, though I am aware that it has its hazards also. But
…why should they know their fate?
Since sorrow never comes too late,
And happiness too swiftly flies.
Thought would destroy their paradise.
No more; where ignorance is bliss,
‘Tis folly to be wise.
And I have often thought what medical ethicists would have made of the pioneers of anesthesia. They did not seek the informed consent of their patients, in part, but only in part, because they hadn’t much information to give. What moral irresponsibility, giving potentially noxious and even fatal substances to unsuspecting experimental subjects without warning them of the dangers!
And there are even some medical ethicists who think we should not take advantage of knowledge gained unethically. All operations should henceforth be performed without anesthesia, therefore.
Medical history is instructive, if for no other reason than that it might help to moderate somewhat the medical profession’s natural inclination to arrogance, hubris and self-importance. But the medical curriculum is now too crowded to teach it to medical students and practicing doctors are too busy with their work and keeping up-to-date to devote any time to it. It is only when they retire that doctors take an interest in it, as a kind of golf of the mind, and by then it is too late: any harm caused by their former hubris has already been done.
Until I read an article in a recent edition of the Lancet, I knew of only one eminent doctor who had been shot by his patient or a patient’s relative: the Nobel Prize-winning Portuguese neurologist Egas Moniz, who was paralyzed by a bullet in the back. It was he who first developed the frontal lobotomy, though he was also a pioneer of cerebral arteriography. As he was active politically during Salazar’s dictatorship, I am not sure whether his patient shot him for medical or political reasons, or for some combination of the two.
Of late the New England Journal of Medicine has seemed like the burial ground of good ideas. Researchers follow a promising lead only to find that their new idea fails the crucial test of experience: and the difference between success and failure in research is made to appear as much a matter of chance or luck as of brilliance or skill.
In the first issue of the Journal for 2015, Dutch researchers from 16 different hospitals report an unequivocal success in the treatment of ischemic stroke.
Until now the only proven worthwhile treatment of patients with the kind of stroke that results from the blockage of a cerebral artery is the infusion within four and a half hours of the drug called alteplase, which dissolves thrombus (and which is manufactured from the ovaries of Chinese hamsters). But even with the use of this drug the prognosis is not very good, and there are several contra-indications to its use.
Everyone knows the pleasures of having his prejudices confirmed by the evidence. The pleasures of changing one’s mind because of the evidence are somewhat less frequently experienced, though none the less real. Among those pleasures is that of self-congratulation on one’s own open-mindedness and rationality. It would therefore delight me to learn that my prejudice about obesity — that it is a natural consequence of overeating, which is to say of human weakness and self-indulgence — was false.
I therefore read with interest and anticipation a recent article in the New England Journal of Medicine with the title “Microbiota, Antibiotics, and Obesity.” The connection of antibiotics with obesity had not previously occurred to me; perhaps the real reason why so many people now have the appearance of beached whales was about to be revealed to me.
It is easier to advise than to have or to retain a sense of proportion, especially when it is most needed. I have never known anyone genuinely comforted by the idea that others were worse off than he, which perhaps explains why complaint does not decrease in proportion to improvement in general conditions. And he would be a callow doctor who tried to console the parents of a dead child with the thought that, not much more than a century ago, an eighth of all children died before their first birthday.
Still, it is well that from time to time medical journals such as the Lancet should carry articles about medical history, for otherwise we might take our current state of knowledge for granted. Ingratitude, after all, is the mother of much discontent. To know how much we owe to our forebears keeps us from imagining that our ability to diagnose and cure is the consequence of our own peculiar brilliance, rather than simply because we came after so much effort down the ages.
A little article in the Lancet recently was written by two historians who are in the process of analyzing the results of 9000 coroners’ inquests into accidental deaths in Tudor England. It seems astonishing to me that such records should have survived for more than four centuries, but also that the state should have cared enough about the deaths of ordinary people to hold such inquests (coroners’ inquests had already been established for 400 years at the time of the Tudors). In other words, an importance was given to individual human life even before the doctrines of the Enlightenment took root: the soil was already fertile.
When I was working in Africa I read a paper that proved that intravenous corticosteroids were of no benefit in cerebral malaria. Soon afterwards I had a patient with that foul disease whom I had treated according to the scientific evidence, but who failed to respond, at least as far as his mental condition was concerned – which, after all, was quite important. To save the body without the mind is of doubtful value.
I gave the patient an injection of corticosteroid and he responded as if by miracle. What was I supposed to conclude? That, according to the evidence, it was mere coincidence? This I could not do: and I have retained a healthy (or is it unhealthy?) skepticism of large, controlled trials ever since. For in the large numbers of patients who take part in such trials there may be patients who react idiosyncratically, that is to say, differently from the rest.
A paper in a recent edition of the New England Journal of Medicine brought back my experience with cerebral malaria. Animal experimentation had shown that progesterone, one of the class of steroids produced naturally by females, protected against the harmful effects of severe brain injury. The paper does not specify what exactly it was necessary to do to experimental animals to reach this conclusion, but it does say that it has been proven in several species. What is not said is often as eloquent as what is said.
If brevity is the soul of wit, verbosity is often the veil of ignorance. There was an instance of this in a recent article in the New England Journal of Medicine, with the title “Conduct Disorder and Callous-Unemotional Traits in Youth.” At considerable length and with much polysyllabic vocabulary, it told us much that we already knew (some of it true by definition). It mistook the illusion of progress for progress itself.
The paper starts with a definition:
The term “conduct disorder” refers to a pattern of repetitive rule-breaking behavior, aggression and disregard for others.
It sounds to me like a recipe for success in the modern art world, where “transgressive” is a term of the highest praise. But, says the paper, such problems have received increased attention recently, for two reasons: first, young people with conduct disorder sometimes “perpetrate violent events,” and second, the Diagnostic and Statistical Manual of Mental Disorders has modified its criteria for diagnosis. This latter seems to me an odd reason for increased attention. (Whose attention, by the way, the authors do not specify. The attention is like the pain in the room as described by Mrs Gradgrind. She thought there was a pain somewhere in the room, but couldn’t positively say that she had got it.)
The truth, the whole truth, and nothing but the truth: that is what one swears to tell in a court of law. One lies there and then. It is a noble ideal that one swears to, but one that in practice is impossible to live up to. Not only is the truth rarely pure and never simple, as Oscar Wilde said, but it is never whole, even in the most rigorous of scientific papers.
Not that scientific papers are often as rigorous as they could or should be. This is especially so in trials of drugs or procedures, the kind of investigation that is said to be the gold standard of modern medical evidence.
Considering how every doctor learns that the most fundamental principle of medical ethics is primum non nocere, first do no harm, it is strange how little interest doctors often take in the harms that their treatment does. Psychologically, this is not difficult to understand: every doctors wants to think he is doing good, and therefore has a powerful motive for disregarding or underestimating the harm that he does. But in addition, trials of drugs or procedures often fail to mention the harms caused by the drug or procedure that they uncover.
This is the royal road to over-treatment: it encourages doctors to be overoptimistic on their patients’ behalf. It also skews or makes impossible so-called informed consent: for if the harms are unknown even to the doctor, how can he inform the patient of them? The doctor becomes more a propagandist than informant, and the patient cannot give his informed consent because such consent involves weighing up a known against an unknown.
A paper in a recent edition of the British Medical Journal examined a large series of papers to see whether they had fully reported adverse events caused by the drug or procedure under trial. It found that, even where a specific harm was anticipated and looked for, the reporting was inadequate in the great majority of cases.
In my youth the government encouraged people to eat more eggs and butter and drink more milk for the sake of their health. Perhaps it was the right advice after a prolonged period of war-induced shortage, but no one would offer, or take, the same advice today. Nutritional advice is like the weather and public opinion, which is to say highly changeable.
How quickly things go from being the elixir of life to deadly poison! A recent paper from Sweden in the British Medical Journal suggests that, at least for people aged between 49 and 75, milk now falls into the latter category, especially for women.
Milk was once thought to protect against osteoporosis, the demineralization of bone that often results in fractures. It stood (partially) to reason that it should, for milk contains many of the nutrients necessary for bone growth.
On the other hand, it also stood (partially) to reason that it should do more harm than good, for consumption of milk increases the level of galactose in the blood and galactose has been found to promote ageing in many animals, up to and including mice. If you want an old mouse quickly, inject a young one with galactose.
In other words, there is reason to believe both that the consumption of milk does good and that it does harm. Which is it? This is the question that the Swedish researchers set out to answer.
Low back pain is a condition so common that, intermittently, I suffer from it myself. It comes and goes for no apparent reason, lasting a few days at a time. Nearly 40 years ago I realized that, though I had liked to think of myself as nearly immune from nervous tension, anxiety could cause it.
I was in a far distant country and I had a problem with my return air ticket. At the same time I suffered agonizing low back pain, which I did not connect with the problem of my ticket. When the problem was sorted out, however, my back pain disappeared within two hours.
In general, low back pain is poorly correlated with X-ray and MRI findings. Epidemiological research shows that the self-employed are much less prone to it than employees, and also that those higher in the hierarchy suffer it less than those lower – and not because they do less physical labor. Now comes evidence, in a recent paper from Australia published in the Lancet, that the recommended first treatment usually given for such pain, acetaminophen, also known as paracetamol, is useless, or at least no better than placebo (which is not quite the same thing, of course).
Hope springs eternal, but so do financial crises in hospitals. Once, while researching the history of the hospital in which I was working at the time, I discovered that it had been so short of money in the 1840s that it had been forced to sell some land to a railway company that wanted to build a line near the hospital. The physicians were against the sale, for they feared the noise of the trains might kill the patients, “especially the brain cases.” They were overruled, and when the first train went by they observed the patients anxiously to monitor the adverse effect on them. There was none.
However, psychiatric hospitals seem often to be built near railway lines, which act as a magnet to the patients who are suicidal. Patients of such hospitals who commit suicide while on the premises usually do so by hanging, while those who do so outside usually jump from a tall building or throw themselves in front of trains.
A paper from Germany in a recent edition of the British Journal of Psychiatry analyzes the characteristics of 100 suicides of psychiatric patients who threw themselves in front of trains conveniently near to the hospitals in which they were resident at the time. It took the authors ten years to collect their sample, whom they compared with other patients of the same age, sex and psychiatric diagnosis who did not throw themselves in front of trains. The object of the exercise was to see whether such suicides could be predicted and therefore prevented. The authors rather laconically remark that when a man throws himself in front of a train — and nearly two-thirds of the cases were men — it is likely that he really means to die.
There is no new thing under the sun, least of all panic at the approach of an epidemic of a deadly disease. In 1720, the preface to Loimologia, Nathaniel Hodges’ account of the Great Plague of London in 1665, first published in Latin in 1672, referred to the outbreak of plague in Marseilles:
The Alarm we have of late been justly under from a most terrible Destroyer in a neighbouring Kingdom, very naturally calls for all possible Precautions against its Invasion and Progress here…
In fact, though no one was to know it, no epidemic of plague was ever to occur in Western Europe again; and it is doubtful whether the precautions referred to made much difference.
The death rate from the Ebola virus is probably greater than that from bubonic plague, though of course the plague spread much faster and killed far more people in total than Ebola ever has: and at least we, unlike our plague-ridden ancestors, know the causative organism of the Ebola disease, even if we are not certain how the virus first came to infect Mankind.
You might have supposed that trust in the medical profession would have risen as medicine became more effective at warding off death and disease, but you would have been mistaken. In fact, precisely the reverse has happened throughout the western world, but particularly in the United States. Half a century ago, nearly three quarters of Americans had confidence in the medical profession qua profession; now only about a third do so.
According to international surveys reported in an article in a recent New England Journal of Medicine, Americans are among the most mistrustful of doctors of any western people. Asked whether, all things considered, doctors in their country could be trusted, 58 percent of Americans answered in the affirmative; by contrast, 83 percent of the Swiss answered positively. Positive answers were returned by 79, 78, and 76 percent of the Danish, Dutch and British respectively. Americans were 24th of 29 nations polled in their trust of doctors. Furthermore, just fewer than half of Americans in the lowest third of the income range thought that doctors in general could be trusted, and younger Americans were also less likely to trust their doctors than older ones.
Curiously enough, though, Americans were among the most satisfied of nations with their last encounter with their doctor. Only the Swiss and Danes were more satisfied than they, and then not by very much (64, 61 and 56 percent respectively). In other countries, then, people were more likely to trust doctors in general than be satisfied by their last visit to the doctor; in America, it was about the same proportion.
What, if anything, does this mean?
How informed is informed consent and does it matter much, or as much as medical ethicists say it does? Do doctors have a duty only to make sure that their message is sent, or also a duty to make sure that it is received, and if received that it is retained? The prayer of General Absolution in the Book of Common Prayer refers to those things which we have done and ought not to have done, and those things which we ought to have done and have not done. When it comes to informed consent, there are also those things which patients have heard and ought not to have heard, and those things which they ought to have heard and have not.
This is proven in a recent paper in the British Medical Journal. Patients with stable angina in ten hospitals in the United States were asked what they thought the benefits were of the percutaneous coronary procedures they were about to undergo. The scientific evidence on this matter is more or less universally accepted: such procedures improve angina symptoms but do not increase life expectancy or reduce the rate of heart attacks.