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in order to build the disease networks of tomorrow, we will need to move beyond the current linear approaches to science and to how scientists work. We all like a good story that unfolds in a straightforward way, but the story of disease plays out across a poly-nodal information network, similar to what an air traffic controller might track in the skies above a major airport. Biomedical researchers’ “lock and key” and linear-pathway representations are incomplete, and should be supplemented with disease maps that can now be built using molecular data.
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Cultural barriers are the real stumbling block. As humans, we are highly evolved to adjust to our surroundings: we tend to adapt to a culture, well-conceived or not, and lose sight of its failings.
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We must also build the infrastructure and cultivate the relationships needed to share disease maps with basic researchers, practicing doctors, drug developers, and even the public at large. And that could prove to be even more difficult, because the current closed nature of the medical-information system and its self-directed incentive structure block such sharing. Patents, trademarks, and competition for resources (people, money, and accolades) seal off information and prevent molecular data from being analyzed and shared. Rewards in biomedical research go to “solo workers,” and do nothing to acknowledge the work that can be done only by multi-functional groups.
While physic gardens are steeped in much wonderful myth and legend, botany is also incredibly important to modern medicine. The latest and most cutting edge cancer drugs are derived from plants. A physic garden brings an array of healing herbs into one potent place and becomes a space for learning, research and experimentation. A physic garden is also a valuable way of conserving rare and endangered species.
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A physic garden is a place where plants with medicinal properties grow. For thousands of years people have been using plants to cure all kinds of ills. London’s first physic garden opened in 1673 – an enchanting walled garden in Chelsea where the city’s apothecaries tended exotic species from around the world. The garden then stretched right down to Thames, and both students and botanical curiosities would arrive by boat. Still open, it’s been a green-fingered physician’s dream for over 300 years.
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While physic gardens are steeped in much wonderful myth and legend, botany is also incredibly important to modern medicine. The latest and most cutting edge cancer drugs are derived from plants. A physic garden brings an array of healing herbs into one potent place and becomes a space for learning, research and experimentation. A physic garden is also a valuable way of conserving rare and endangered species.
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drugs are having a difficult time beating the placebo effect, and increasingly so. In fact, they're finding the placebo effect is getting stronger in people, making it more difficult for drugs to show any improvement over it. The credit for the increased placebo effect has been attributed to the increase in consumer advertising, which makes many consumers "believe" more in the drugs and their effects.
Proponents of so-called complementary and alternative medicine (CAM) are forcing us to answer a question no one has explicitly asked – should there be a scientific basis to medicine? Proponents are generally very coy about this topic, and in most venues want to pretend that they are being scientific, while really promoting “other” forms of evidence and “other” ways of knowing. They promote health care freedom laws designed to weaken the scientific standards of medicine, while simultaneously infiltrating academia with assurances that they are science-based.
Robot-assisted surgery today is dominated by the da Vinci Surgical System, a device that scales down a surgeon’s hand movements in order to allow him to perform operations using tiny incisions. That leads to less tissue damage, and thus a quicker recovery for patients. Thousands of da Vincis have been made, and they are reckoned to be used in over 200,000 operations a year around the world, most commonly hysterectomies and prostate removals.
But the da Vinci is far from perfect. It is immobile and weighs more than half a tonne, which limits its deployability, and it costs $1.8m, which puts it beyond the reach of all but the richest institutions. It also uses proprietary software. Even if researchers keen to experiment with new robotic technologies and treatments could afford one, they cannot tinker with da Vinci’s operating system.
the impact of personalized medicine in the short term might be positive at the patient’s bedside, but vast clinical trials to demonstrate the safety of new drugs will impose huge development costs that manufacturers might never recover. (Currently, only about one in five drugs approved by US regulators ever recoup their development costs.) This situation would not be sustainable in the long term.
If society is to derive the maximum benefit from personalized medicine – which will require companies to pursue it
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Personalized drug therapy uses biological indicators, or “biomarkers” – such as DNA sequences or the presence or absence of drug receptors – as an indicator of how patients should be treated, as well as to estimate the likelihood that the intervention will be effective. This concept is not new: it has been known for decades, for example, that people who have a genetic deficiency of an enzyme called G6PD can experience severe and precipitous anemia if they are exposed to certain drugs.
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Similarly, ethnic groups and individuals vary widely in their ability to clear medications from the bloodstream, owing to differences in the activity of the enzymes that metabolize, or degrade, drugs. That is important because low metabolizers clear certain drugs slowly and have more medication in their systems for longer periods of time than high metabolizers. Thus, the former might be prone to overdose, and the latter to insufficient levels of the same drug.
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One possibility is that people are turning to alternative medicine because their needs are not being met by traditional medicine. As the late medical historian Roy Porter was fond of pointing out, before the 20th century this certainly was the case.4 Medical historians, in fact, are in agreement that until well into the 20th century it was safer not to go to a doctor, thus leading to the success of such nonsense as homeopathy—a totally worthless nostrum that did no harm, thus allowing the body to heal itself.
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Another explanation may be found in examining what CAMers are offering that mainstream physicians are not: TLC. By this I do not just mean a hand squeeze or a hug, but an open and honest relationship with patients and their families that provides a realistic assessment of the medical condition and prospects. People are going alternative because in too many instances physicians have become highly skilled technicians—cogs in the cold machinery and massive bureaucracy of modern HMO medicine.
I witnessed the effect directly over the course of a decade during my mother’s recurring and malignant meningioma brain tumors. She finally succumbed, but in the process I gained a deeper understanding of why people turn to alternative medicine. Don’t get me wrong—my mother’s doctors were brilliant, her care the very best available, and we have no regrets about what might have been. And that’s the point. Even under such ideal conditions I found the whole experience frustrating and unfulfilling: it was nearly impossible to get honest and accurate information about my mom’s condition; neither my father nor I could get doctors to return our calls; misinformation and (usually) no information was the norm; and despite my best efforts, the relationship with her physicians (with one exception—her oncologist whom I befriended), could not have been more detached.
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An article in the May Consumer Reports Health shed some light on this question. It discussed the widely publicized medical study that showed, contrary to expectations, that “raising HDL (good) cholesterol with drugs did nothing to protect against heart attacks.” This, the article said, was surprising because observational studies had shown that people with lower levels of HDL had more heart attacks than those with higher levels of HDL. An observational study, however, shows only a correlation between two variables (e.g., level of HDL and number of heart attacks). The new result came from a randomized clinical study, using one group of patients who receive a given treatment and a “control group” of patients who do not. Unlike an observational study, such a study can show whether or not, for example, higher HDL actually prevents heart attacks. The article went on to emphasize that “we should almost never rely on the results of observational studies, which can only suggest associations with disease but not prove them.”
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implicit in most media reports, is that acting on the results of the unreliable observational studies “couldn’t hurt and might help.” This makes sense if I have a medical problem for which there is no reliable remedy. If nothing else has helped my arthritis, insomnia or back pain, it would make perfect sense to try a remedy that will not do serious harm and has some probability of working.
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With countless biological details emerging from cancer experiments, there is a growing need for minimal mathematical models which simultaneously advance our understanding of single tumors and metastasis, provide patient-personalized predictions, whilst avoiding excessive hard-to-measure input parameters which complicate simulation, analysis and interpretation. Here we present a model built around a co-evolving resource network and cell population, yielding good agreement with primary tumors in a murine mammary cell line EMT6-HER2 model in BALB/c mice and with clinical metastasis data. Seeding data about the tumor and its vasculature from in vivo images, our model predicts corridors of future tumor growth behavior and intervention response. A scaling relation enables the estimation of a tumor's most likely evolution and pinpoints specific target sites to control growth. Our findings suggest that the clinically separate phenomena of individual tumor growth and metastasis can be viewed as mathematical copies of each other differentiated only by network structure.
One of the most difficult things about treating cancer is that each case is a very individual process; tumors recruit blood vessels in order to grow, yet also send out new vessels of their own. This harnessing of the body’s resources is what eventually allows a tumor to metastasize — be carried into other parts of the body where growth continues. On the other hand, sometimes tumors don’t grow at all. Predicting each patient’s unique response to cancer and its progression is a large part of the battle, as an accurate estimate is required to begin appropriate treatment. The field of Oncology is always seeing exciting developments, and this latest one is no different — its benefits touch future and existing cancer patients, alike. Knowing that hindsight is 20/20, it would be a lot easier if there was a “fast-forward button” with which doctors could view each unique case before it develops.
Physicist Sehyo Choe and colleagues at the University of Heidelberg, Germany have developed such a button in the form of a mathematical model. By inputting data about the tumor and its current location of blood vessels, the model allows doctors and researchers to see how the tumor will grow and move — if at all — giving them a very accurate helping hand when it comes to prompt and accurate treatment. Tested on mice, the model accurately predicted the progression of all cancer-stricken subjects, giving researchers that amazing “fast-forward” capability.
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Predicting each patient’s unique response to cancer and its progression is a large part of the battle, as an accurate estimate is required to begin appropriate treatment. The field of Oncology is always seeing exciting developments, and this latest one is no different — its benefits touch future and existing cancer patients, alike. Knowing that hindsight is 20/20, it would be a lot easier if there was a “fast-forward button” with which doctors could view each unique case before it develops.
Physicist Sehyo Choe and colleagues at the University of Heidelberg, Germany have developed such a button in the form of a mathematical model. By inputting data about the tumor and its current location of blood vessels, the model allows doctors and researchers to see how the tumor will grow and move — if at all — giving them a very accurate helping hand when it comes to prompt and accurate treatment. Tested on mice, the model accurately predicted the progression of all cancer-stricken subjects, giving researchers that amazing “fast-forward” capability.
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Co-author Neil Johnson from the University of Miami says that “in the future, treatments will no longer have to be based on population averages. People will get individual treatment based on the predictions of our model.”
Kim Kardashian's artificially thinned-down thighs are bad for your health, says the American Medical Association. Though it's been a common practice in fashion, publishing, and advertising for decades now, photoshopping pictures has also left millions of Americans, particularly women, with unhealthy body image issues. The nation's most revered medical body is now saying enough is enough.
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The AMA this week formally denounced retouching pictures and asked ad agencies to consider setting stricter guidelines for how photos are manipulated before becoming advertisements.
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Last year in France, members of parliament advocated attaching warning labels to imagery that had been digitally enhanced; lawmakers in England have also dabbled with the idea. Perhaps the AMA's new stance will be the nudge America needs to follow our European friends' lead. Unfortunately, our staggering eating disorder statistics seem to not be enough.
Kim Kardashian's artificially thinned-down thighs are bad for your health, says the American Medical Association. Though it's been a common practice in fashion, publishing, and advertising for decades now, photoshopping pictures has also left millions of Americans, particularly women, with unhealthy body image issues. The nation's most revered medical body is now saying enough is enough.
We doctors like people to think we know what we’re talking about, and may indeed be so convincing that we convince ourselves too. Because other people’s lives depend on it, we have a big emotional need to be right, and are uncomfortable with the thought that none of us really knows enough to be a good doctor. Even if we know everything that is known, we still don't know that which is yet unknown. Scientists, on the other hand, are very comfortable with the unknown, indeed it is their bread and butter. When scientists disagree there is no more at stake than the scientists’ amour propre, whereas medical disputes get rancorous because fowever in the background is the thought that the other chap is damaging patients.
Science does not in itself make its practitioners haughty (in fact the contrary if done honestly), whereas medicine does. Most of the blame for that, I think, is because doctors get used to seeing other people undressed while they themselves are clothed. Once you have seen dukes and archbishops in their underpants they’re never quite the same again.
Taken together it becomes ever so easy for us doctors to start believing that we know everything, and that makes us unreasonably unreceptive to new ideas. And that is the reason, Mr Editor, why medical journals must continue force-feeding original scientific studies to their unwilling readers.
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We doctors like people to think we know what we’re talking about, and may indeed be so convincing that we convince ourselves too. Because other people’s lives depend on it, we have a big emotional need to be right, and are uncomfortable with the thought that none of us really knows enough to be a good doctor. Even if we know everything that is known, we still don't know that which is yet unknown. Scientists, on the other hand, are very comfortable with the unknown, indeed it is their bread and butter. When scientists disagree there is no more at stake than the scientists’ amour propre, whereas medical disputes get rancorous because fowever in the background is the thought that the other chap is damaging patients.
Science does not in itself make its practitioners haughty (in fact the contrary if done honestly), whereas medicine does. Most of the blame for that, I think, is because doctors get used to seeing other people undressed while they themselves are clothed. Once you have seen dukes and archbishops in their underpants they’re never quite the same again.
Taken together it becomes ever so easy for us doctors to start believing that we know everything, and that makes us unreasonably unreceptive to new ideas. And that is the reason, Mr Editor, why medical journals must continue force-feeding original scientific studies to their unwilling readers.
Some doctors are scientists—just as some politicians are scientists—but most are not. As medical students they were filled full with information on biochemistry, anatomy, physiology, and other sciences, but information does not a scientist make—otherwise, you could become a scientist by watching the Discovery channel. A scientist is somebody who constantly questions, generates falsifiable hypotheses, and collects data from well designed experiments—the kind of people who brush their teeth on only one side of their mouth to see whether brushing your teeth has any benefit. Most doctors follow familiar patterns and rules, often improvising around those rules. In their methods of working they are more like jazz musicians than scientists.
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I once asked a room of perhaps 150 medically trained educators which of them thought of themselves as scientists. About five put up their hands.
If doctors are not scientists then it seems odd to supply them, as medical journals do, with a steady stream of original scientific studies.
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The inevitable consequence is that most readers of medical journals don't read the original articles. They may scan the abstract, but it's the rarest of beasts who reads an article from beginning to end, critically appraising it as he or she goes. Indeed, most doctors are incapable of critically appraising an article. They have never been trained to do so. Instead, they must accept the judgment of the editorial team and its peer reviewers—until one of the rare beasts writes in and points out that a study is scientifically nonsensical.
Thousands of older people are being put at increased risk of death or developing dementia by taking combinations of common medicines to treat routine illnesses, according to a new study published in the Journal of the American Geriatrics Society.
Many are available over the counter at pharmacies as well as being prescribed by GPs, nurses and chemists.
British scientists behind the study are calling for doctors to recognise how dangerous these drug combinations can be and to prescribe harmless alternatives instead.
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The drugs, including common allergy treatments Piriton and Zantac, as well as Seroxat, an anti-depressant, are thought to be used by half of the 10 million over-65s in Britain. Many of the drugs, when taken in combination, were found to more than treble an elderly patient's chance of dying within two years.
Common bladder medications, heart drugs, eye drops and asthma treatments were also among those found to pose a risk.
All the drugs work by blocking a key chemical in the nervous system called acetylcholine.
The scientists also suggested that in patients showing early signs of mental impairment, high doses could "tip them over" into a more confused state.
When doctors are deciding which drug to prescribe a patient, the idea behind evidence-based medicine is that they inform their thinking by consulting scientific literature. To a great extent, this means relying on medical journals.
The trouble is that pharmaceutical companies, who stand to win or lose large amounts of money depending on the content of journal articles, have taken a firm grip on what gets written about their drugs. That grip was strong way back in 2004, when The Lancet's chief editor Richard Horton lamented that "journals have devolved into information laundering operations for the pharmaceutical industry." It may be even tighter now
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Drug companies exert this hold on knowledge through publication planning agencies, an obscure subsection of the pharmaceutical industry that has ballooned in size in recent years, and is now a key lever in the commercial machinery that gets drugs sold.
The planning companies are paid to implement high-impact publication strategies for specific drugs. They target the most influential academics to act as authors, draft the articles, and ensure that these include clearly-defined branding messages and appear in the most prestigious journals.
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There are now at least 250 different companies engaged in the business of planning clinical publications for the pharmaceutical industry, according to the International Society for Medical Publication Professionals, which said it has over 1000 individual members.
Many firms are based in the UK and the east coast of the United States in traditional "pharma" centres like Pennsylvania and New Jersey.
Precise figures are hard to pin down because publication planning is widely dispersed and is only beginning to be recognized as something like a discrete profession.
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Medical care is about treatment, not faith, and about prevention, not religion. The ability for physicians to opt out of treating people they feel they can't abide by is not a "right to conscience", it's unconscionable.
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The "right to conscience" rule legitimized religious discrimination in all but name, and did so to benefit a narrow reading of one faith. The exemption should ideally be rescinded entirely, but in a political environment so saturated in religion that only one of at least two dozen members of Congress is willing to be open about his lack of belief in God, this is another major step forward, and is giving progressives and humanists reason to think that President Obama will get to the issues that helped his base elect him.
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I’m a John Ioannidis convert, and I accept that there is a lot of medical literature that is erroneous. (Just search for Dr. Ioannidis’ last name on this blog, and you’ll find copious posts praising him and discussing his work.) In fact, as I’ve pointed out, most medical researchers instinctively know that most new scientific findings will not hold up to scrutiny, which is why we rarely accept the results of a single study, except in unusual circumstances, as being enough to change practice. I also have pointed out many times that this is not necessarily a bad thing. Replication is key to verification of scientific findings, and more often than not provocative scientific findings are not replicated. Does that mean they shouldn’t be published?
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As for pseudoscience, I’m half tempted to agree with Dr. Spector, but just not in the way he thinks. Unfortunately, over the last 20 years or so, there has been an increasing amount of pseudoscience in the medical literature in the form of “complementary and alternative medicine” (CAM) studies of highly improbable remedies or even virtually impossible ones (i.e., homeopathy). However, that does not appear to be what Dr. Spector is talking about, which is why I looked up his references. The second reference is to an SI article from 2009 entitled Science and Pseudoscience in Adult Nutrition Research and Practice. There, and only there, did I find out just what it is that Dr. Spector apparently means by “pseudoscience”:
By pseudoscience, I mean the use of inappropriate methods that frequently yield wrong or misleading answers for the type of question asked. In nutrition research, such methods also often misuse statistical evaluations.
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Sarah Finocchario-Kessler, at the University of Kansas, used data from one such drug trial to see what the effect of religious beliefs (and other psychological factors) was on medication taking.
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One recent study looked at whether people with HIV took their medicine as they were supposed to. Most trials of new drugs monitor this, and it can be done very easily simply using special bottles that record each time they're opened. -
Sarah Finocchario-Kessler, at the University of Kansas, used data from one such drug trial to see what the effect of religious beliefs (and other psychological factors) was on medication taking.
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Big Herba is clearly big business, and on a purely financial level, it’s hard not to be impressed by what they’ve achieved. But that success — $2.5B in revenues concentrated in the seven companies above — makes it equally difficult to give them a pass on their research deficit. Simply put, the leading natural health products companies have the coin for research, they just choose to spend it on marketing products and buying their competitors instead. The result: while pharma typically spends upwards of 15-20% of revenues on research, Big Herba contributes less than a tenth of that.
To the question of why, I’d like to propose simply that they don’t need to. The products are clearly selling well already, and without the regulatory approvals pharmaceuticals require, spending money on research presents more risk than reward. After all, if you don’t conduct research, you can’t find out that your product doesn’t work.
In other words, Big Herba is behaving exactly as Big Pharma might if it had no government oversight. And if that doesn’t give you reason for pause before you pop that next Ginko tablet, I don’t know what will.
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A skeptic challenges a natural health product for the lack of an evidentiary base. A proponent of that product responds that the skeptic has made a logical error – an absence of evidence is not evidence of absence, and in such a scenario it’s not unreasonable to rely on patient reporting and traditional uses as a guide. The skeptic chimes back with a dissertation on the limits of anecdotal evidence and arguments from antiquity — especially when the corresponding pharma products have a data trail supporting their safety and efficacy. The proponent responds that it’s unfair to hold natural health products to the same evidentiary standard, because only pharma has the money to fund proper research, and they only do so for products they can patent. You can’t patent nature, so no research into natural health products gets done.
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