Wednesday, October 10, 2007

Donated blood quickly loses vital gas

Aha! Now we know why Jehovah's Witnesses survive better

Donated blood quickly loses some of its life-saving properties as an important gas dissipates, US researchers say, in a finding that explains why many patients fare poorly after blood transfusions. Researchers at Duke University Medical Center in Durham, North Carolina, have found that nitric oxide in red blood cells is the key to transferring oxygen in the blood to tissues. This gas appears to break down almost immediately after red blood cells leave the body, rendering much of the blood stored in blood banks impaired, said Dr Jonathan Stamler, a Duke researcher whose work appears in the Proceedings of the National Academy of Sciences. "If you don't have nitric oxide in there, you can't get oxygen into the tissues," he said. But if you restore this gas, banked blood appears to regain this ability, Stamler said.

"The medical community for the past five to eight years has really been struggling with this issue of blood not being quite as good as we'd hoped," Stamler said. He noted that study after study has shown patients who receive blood transfusions have higher incidents of heart attacks, heart failure, stroke and even death. "This is not a new issue. It has been a long struggle," he said.

While researchers have understood that banked blood is not the same as the blood in the body, the exact difference was not well understood. "I think we have a good explanation and I think we have a solution," Stamler said. He and colleagues at Duke measured levels of nitric oxide in stored human blood obtained from a commercial supplier and found that nitric oxide levels started dropping quickly. They also tested the theory on dogs. When given stored blood, the flow of oxygen-rich blood was impaired. But when they added nitric oxide back to stored blood, blood flow was restored.

A second team at Duke led by Dr. Timothy McMahon documented the depletion of nitric oxide in banked blood. "We were surprised at how quickly the blood changes; we saw clear indications of nitric oxide depletion within he first three hours," he said in a statement. His study appears in the same journal. Both researchers called for clinical trials to study exactly who might benefit from banked blood. And they said researchers should begin studying ways to safely add nitric oxide back into banked blood to see how this might improve its effectiveness. Currently, about five million Americans receive blood transfusions each year, according to the National Institutes of Health.


On scientific medicine

When doctors attack alternative medicine or appear sceptical to its much-trumpeted claims, we are often accused of being bigots with closed minds, protecting a closed shop. Nothing could be further from the truth, but it has taken a layman, the late, great John Diamond, to find the words to set the record straight. For that reason, I would like to quote from his posthumously published book Snake Oil and other Preoccupations (1). Diamond wrote: `I am not an academic and this is not an academic book, even though the facts I list in it have a perfectly good scientific basis to them but when it comes to human motivation I am working blind. I can only guess why most people seem to prefer the unproven to the proven, the anecdotal to the rigorously demonstrated, and the so-called natural to the scientific.' There is much within that passage on the nature of proof, the nature of the scientific method, and the use and abuse of anecdotal evidence.

The alternative practitioner can trace his roots back to Galen in the second century, and a metaphysical belief system based on the balance of natural humours. For example, Galen believed that breast cancer was due to an excess of black bile (melancholia). Inductive support for this belief came from the observation that breast cancer was more common in post-menopausal women than pre-menopausal women, and this was thought to be because the menstrual flux in pre-menopausal women got rid of the putative excess of black bile. The therapeutic consequences of this belief therefore were purgation and venesection (bloodletting). The inductive `proof' that this approach worked were the anecdotes about women with breast cancer who were treated by purgation and venesection, and who lived for several years after diagnosis. Those who died were the victims of the blood-letter who didn't have the courage of his convictions, or the patient herself who lacked the constitutional vigour to sustain prolonged bloodletting.

There is a neo-Galenic doctrine, based on the view that breast cancer is indeed due to an imbalance of nature, only substituting energy fields for the natural humours. According to this view, to restore perfect health you have to restore the balance of these metaphysical energy fields. This might be achieved by acupuncture balancing out the yin and the yang, homeopathy (simularis simulabum curantur), or strange balancing diets.

The Gerson diet, in particular, is very fashionable. In fact, one of my patients, seeking to improve my education, gave me a book describing this approach (2). The first half of the book formulates the hypothesis why this strange diet should improve the balance of the immune system, and the second half of the book consisted of 50 anecdotes of patients with cancer, who were only given six months to live by the medical profession, and who took to the diet and lived for a long time.

The trouble with that kind of evidence is that although we know the numerator (50) we don't know the denominator - for example, 50 out of 1,000 cases treated by neglect could indeed live for many years while the indolent disease progresses on the chest wall. Furthermore, from the evidence available in the book, some of the diagnoses were a little bit shaky and the author neglects to mention whether or not these patients receive conventional treatment at the same time as the magic diet. Finally, I know of no oncologist who gives a patient six months to live. We may say that the median survival for a group with advanced cancer is six months, but among this group certain individuals may lie at extremes of survival. These individuals are the substance of the anecdote.

Perhaps I should leave the last word on this subject to Robert Parks, author of the wonderful book Voodoo Science. Parks wrote: `Alternative seems to define a culture rather than a field of medicine - a culture that is not scientifically demanding. It is a culture in which ancient accretions are given more weight than biological science and anecdotes are preferred over clinical trials. Alternative therapies steadfastly resist change often for centuries or even millennia, unaffected by scientific advances in the understanding of physiology or disease.' (3) If that is the case, then who are the bigots and the ones with the closed minds?

Deductive logic and the randomised controlled trial

The alternative to alternative medicine should be scientific medicine, not `orthodoxy'. By science I mean the application of deductive logic. The deductive approach starts with the formulation of the hypothesis, but for a start the hypothesis must be rational in its explanation of the disease process or therapeutic intervention. By `rational' I mean built upon the growth of knowledge of human biology and physiology from the past 100 years or so, without invoking magic or metaphysical principles.

Even so, the new hypothesis is still perceived as a fictional account of reality and subjected to rigorous test by the design of experiments challenging the new theory with the `hazard of refutation'. These experiments in medical or surgical therapeutics must have control groups treated by observation, placebo or `best available therapy'. Without the control group, we merely have a series of anecdotal reports. What I have just described is in fact a randomised controlled trial.

Breast cancer and the randomised controlled trial

As I have mentioned, up until the eighteenth century, if breast cancer was treated at all it was treated according to the principles of Galen. It wasn't until the mid-nineteenth century that it became widely accepted that cancer was a disease of cellular pathology originating within the breast and spreading centrifugally along the lymphatic system. The therapeutic consequence of this belief led surgeons to embark on radical surgery that involved removing the breast and all the regional lymphatics. It was left to William Halsted in the 1890s to refine the operation into the classic radical mastectomy, with the intention of ridding the body of the primary cancer and its lymph node secondaries. Sadly, the only support for this radical treatment was anecdotal. If the patient survived it was due to the success of the surgeon. If the patient died it was either because the patient came too late or the surgeon lacked the courage of his convictions to complete a truly radical operation.

It was only when Dr Bernard Fisher in the 1960s challenged the conceptual model of the disease that progress started to be made. In other words an antithesis was constructed to challenge the prevailing dogma. Fisher taught that contrary to popular belief, breast cancer cells spread throughout the body through the venous drainage of the breast, and at the time of clinical presentation of the disease, the majority of breast cancers were in fact systemic disorders. If that was indeed the case then there are two therapeutic consequences. Firstly, that radical surgery is shutting the stable door after the horse has bolted. Therefore the role of local therapy is local control, which would equally well be achieved by breast-conserving techniques such as lumpectomy and radiotherapy. The second therapeutic corollary is that if indeed the disease is systemic at the time of diagnosis, then the only way to improve cure rates is through chemotherapy or hormone therapy.

However, the greatness of Dr Fisher, ably supported by surgical acolytes all around the world, was not simply to accept a new set of beliefs in place of an old set of beliefs, but to challenge the new paradigm using deductive logic: in other words, through randomised controlled trials. One of the great success stories of modern medicine has been the painstaking series of randomised controlled trials in the management of early breast cancer over the past 30 years. We now know with extreme confidence that breast conservation is a safe alternative to radical mastectomy; although not in itself improving cure rates, it greatly enhances the patient's quality of life. We also know with extreme confidence that treatment using either endocrine or cytotoxic regimens will improve survival. The final demonstration of that truth has been the dramatic fall in breast cancer mortality in the UK and North America since 1985, following the first publication of the world overview of trials (4).

Using breast cancer as an example, we can demonstrate that the philosophy of science that underpins the randomised controlled trials has led to the dramatic improvement in length of life and quality of life for women inflicted with this dread disease. However, this isn't the end of the story, as new biological hypotheses are being generated with new therapeutic consequences, all of which will be tested in the randomised controlled trial, which is now accepted as the most scientific and ethical way of conducting medicine in times of uncertainty.

The impact of government interference

For both political and humane reasons, governments of all persuasions like to meddle in this process and add guidelines, targets and unwelcome advice on top of our carefully collected evidence. Two examples from the recent past illustrate the dangerous law of unintended consequences when well-meaning meddling is applied on top of clinical science. The first is teaching the practice of breast self-examination (BSE) and the second, applying the two-week target for the urgent diagnosis of cases suspected of having breast cancer.

BSE is superficially attractive in making it the responsibility of women themselves to `catch their breast cancers early' and thus reduce breast cancer mortality. It's a good theory and was introduced as policy in many countries, and also provides an excuse for the women's magazines to publish photographs of beautiful young women fondling their own breasts (which in itself gives out the wrong message that breast cancer is a disease of young women). However, the important point to note is that the advice is based on an assumption - not on evidence. Over the past 10 years, three large randomised controlled trials have compared the outcomes of women who have been intensively trained in BSE with a matched population of women left to their own devices. The outcomes of all three studies were counterintuitive. There was no difference in breast cancer mortality, but those women practising BSE were twice as likely to experience false alarms and unnecessary surgery. This prompted the Canadian Medical Association to issue a warning against the practice!

A more recent example is the two-week rule. Primary care doctors in the NHS were advised to prioritise women with breast symptoms as urgent or not urgent. Those in the former group had to be seen within two weeks and the rest could take their turn. Note the two false assumptions in these guidelines: a) breast cancer is an emergency and even a few weeks can affect outcome; and b) women with breast symptoms atypical of breast cancer can happily wait for up to 12 weeks. Pretty much as predicted, the law of unintended consequences kicked in. So many worried-well pushy middle-class women were seen as emergencies, and so many cancers appeared in the non-urgent group that the net result was a greater delay in cancers being diagnosed than before (6).

Finally, I wish to illustrate the extreme folly of the two-week target for seeing patients suspected of cancer, with an anecdote about a patient I saw recently. The patient who attended my NHS clinic was a charming and sensible woman in her early fifties, with a family history of breast cancer. Three weeks before, she had seen her GP complaining of passing bright red blood at stool. He referred her urgently under the two-week `target' rule to the colo-rectal clinic. The referral was flagged up by some clerical officer in the audit department and the clock started its countdown. Since the colo-rectal clinics are overwhelmed with patients with lower bowel symptoms, nurse-led clinics were set up to take the pressure off the specialist surgeons. The nurse ticked the boxes and the patient was referred for colonoscopy. This examination showed haemorrhoids (piles), the commonest cause of bleeding at stool, and no signs of cancer. Her next appointment followed soon afterwards and she had a CT scan of her abdomen and chest. This was reported as showing a secondary cancer in her right lung. She was then referred for positron emitting tomography, which suggested that she might have cancer in her right breast not her right lung. Note that at no time had anyone actually examined her.

By the time she came to see me she was a confused nervous wreck. After taking a careful history I asked her to disrobe and sit up on the couch. One glance was enough to confirm the breast cancer from the dimple in the lower outer quadrant on the right side. Palpation and biopsy confirmed the diagnosis. After counselling at length she was booked for the next vacant slot on the operating list, which was just over two weeks off. She went off satisfied, but the audit office was not. Apparently we were in breach of the two-week target for cancer.

So in the end, all these delays and unnecessary investigations wasted about 3,000 pounds, and caused substantial anxiety for the patient - and yet they passed the two-week target rule. At the point when the patient is diagnosed and treatment ordered, the computer finds that targets have not been met. This upside-down logic shows the unintended consequences of ill-considered and non-evidence-based political interference.


I hope those examples illustrate the dangers of government intervention in the practice of evidence-based medicine. This is what I choose to describe as ignorance-based interference (IBI). Other examples of IBI include so-called `patient's choice', censoring the right of the National Institute for Clinical Excellence (NICE) to evaluate alternative medicine, and the constant `re-disorganisation' of the NHS (7). My call to the government is this: provide us with the tools to practice evidence-based medicine and then please leave us alone.



Just some problems with the "Obesity" war:

1). It tries to impose behavior change on everybody -- when most of those targeted are not obese and hence have no reason to change their behaviour. It is a form of punishing the innocent and the guilty alike. (It is also typical of Leftist thinking: Scorning the individual and capable of dealing with large groups only).

2). The longevity research all leads to the conclusion that it is people of MIDDLING weight who live longest -- not slim people. So the "epidemic" of obesity is in fact largely an "epidemic" of living longer.

3). It is total calorie intake that makes you fat -- not where you get your calories. Policies that attack only the source of the calories (e.g. "junk food") without addressing total calorie intake are hence pissing into the wind. People involuntarily deprived of their preferred calorie intake from one source are highly likely to seek and find their calories elsewhere.

4). So-called junk food is perfectly nutritious. A big Mac meal comprises meat, bread, salad and potatoes -- which is a mainstream Western diet. If that is bad then we are all in big trouble.

5). Food warriors demonize salt and fat. But we need a daily salt intake to counter salt-loss through perspiration and the research shows that people on salt-restricted diets die SOONER. And Eskimos eat huge amounts of fat with no apparent ill-effects. And the average home-cooked roast dinner has LOTS of fat. Will we ban roast dinners?

6). The foods restricted are often no more calorific than those permitted -- such as milk and fruit-juice drinks.

7). Tendency to weight is mostly genetic and is therefore not readily susceptible to voluntary behaviour change.

8). And when are we going to ban cheese? Cheese is a concentrated calorie bomb and has lots of that wicked animal fat in it too. Wouldn't we all be better off without it? And what about butter and margarine? They are just about pure fat. Surely they should be treated as contraband in kids' lunchboxes! [/sarcasm].

Trans fats:

For one summary of the weak science behind the "trans-fat" hysteria, see here. Trans fats have only a temporary effect on blood chemistry and the evidence of lasting harm from them is dubious. By taking extreme groups in trans fats intake, some weak association with coronary heart disease has at times been shown in some sub-populations but extreme group studies are inherently at risk of confounding with other factors and are intrinsically of little interest to the average person.


No comments: