If we compile statistics, we can look for the points where nobody has ever meaningfully recovered.
We do. This is where the guidance to stop resuscitation after 15 minutes without a rhythm comes in. Unless you're a child who drowned in cold fresh water, of course, or an adult who apparently died of hypothermia. The problem is that there are so very many different sets of facts, and people are far more resilient than you can imagine. And in the heat of the moment, we tend to opt to fight rather than to let go. Which is actually OK, I think.
For your example, ECMO can only be useful for acute lung failures including injury. It's useless in chronic cases where the lungs simply aren't going to improve.
Well, yes, ECMO is probably a bad example, because it's by definition an acute therapy that can't be continued more than a few days, at least at the current state of the art. Even there it's a bit questionable in the case of chronic disease exacerbated by acute cardiopulmonary collapse from a (presumably) reversible cause. But other therapies, like the simple $10K/day ICU bed, are much harder to argue against, unless you've given specific instructions. It reminds me a little of the old instructions for tuning a carburetor - turn the screw until the engine dies, then back up half a turn. Most of the really futile ICU cases I've seen didn't START as futile cases, but they sure ended that way.
Most other western countries have a bit less tendency to heroic medicine than the U.S.
I'm not actually all that impressed with medicine in "most other Western countries" as a touchstone for our own. Every country has its own social norms and conventions, all of which fold over into health care. We tend to value privacy, autonomy, personal space, personal choice, and hope for recovery more than most, and it costs us a lot of money.
I think the problem is that we don't know in advance when the "last days of life" are for anyone. Or at least we don't know if prospectively, and knowing it after the fact is kind of pointless in terms of limiting costs.
If there are treatments that are virtually never helpful, we need to stop using them. There aren't many interventions that actually fit that description, though, and even the most invasive of them - ECMO, for example (basically continuous heart-lung bypass) - have their place in restoring people to health in the right circumstances. Eventually the circumstances are such that death is inevitable, but recognizing that point is not something we know how to do with certainty. Even when we're pretty sure, communicating our own conviction is very hard. And where there is no certainty, there is the great likelihood of erring on the side of treatment.
Hospice care, which tends to be very inexpensive compared to attempts at cure, is helping because it gives people a viable alternative path. Most physicians with whom I deal (a very large number, as it turns out) are big fans of hospice care. Not because it's cheap, but because it helps make the case for avoiding further torture. It's not a bad way to reduce costs, though, and that's not irrelevant.
A doctor's opinion: TFA's got it right.
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How Doctors Die
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· Score: 4, Insightful
I'm a board-certified physician (among other things). There is no way that I would allow my colleagues to inflict the kind of death on me that they are forced to inflict on so many. Part of this is certainly that I know full well that we all exit this mortal coil toes-up, and there's no getting around it. Part of this is the personal reluctance to experience the diminished autonomy, indignity, pain,and hopelessness that comes with fanatically-treated terminal illness.
But a big part of it, I think, is just that I know that there are so, so many things that are worse than simply dying. Dying in agony, for one. Dying after having bankrupted my wife or my children. Dying after being reduced to a stinking thing in a bed long enough that only those who loved me most even want to be near me, and that only because they feel they must. Physicians see these things all the time, and we see the road that leads to them. We're not (that) stupid, and we would rather exit early on that road, not at its terminus.
As long as I have the capacity for joy I will strive to remain alive to experience that joy. When the capacity - or the joy - is gone for good, I have given quite strict instructions not only to my family but to some other clear-headed and insistent people who will do their best to ensure that I too will be gone without further "heroic" intervention.
The only problem that I have with the article is that it pretends that everyone should make the same decisions. Everyone has their own decisions to make, and without my knowledge and experience I might not make the same ones. I think as physicians we owe it to the people for whom we care to educate as well as we can and help them to understand why we might personally decide one way or another. But I will never tell them how they "ought" to decide - it's really their choice. Taking that choice away from a person leads too easily to very real outcomes that are much nastier than simply a life that ends later than it ought.
The article is pretty good, actually, in that it doesn't try very hard to claim that they're curing the world of its ills. There's a little in there, but mostly it deals with Fragile X.
Randi Hagerman (the researcher quoted extensively in the article) is one of the leading lights in Fragile X research. She and her husband, Paul, described the gene, developed the RFLP that we now use to diagnose the illness, and did much of the fundamental work to explain the genetic-expression behavior of the gene. It is not a simple inheritance model, and the expression of the gene is quite confusing. She's a superstar.
As far as the broader issue of autism (and even more confusingly, autism spectrum), Fragile X has always seemed to me to be a blind alley. People with Fragile X (I've worked in that community as a physician) have a very specific affect and behavior pattern that doesn't look a lot like the behavior of people with autism (a community I know all too well as a physician and a parent of an autistic young man). Most of the early research in autism was tainted by the inclusion of Fragile X patients, and most of the combined research is just confusing.
I hope that the drug proves useful in Fragile X, although pharmacotherapy for these kinds of disorders has frustrated us over and over again. These are simply very hard diseases to affect very much. At the least, though, it'll be another step toward understanding a serious disease. And I'll continue to wait and watch for anything that will help in autism, but I REALLY don't expect much from this specific drug.
The FDA has had a table of valid genetic biomarkers for medications for several years now. While many of these are cancer drugs looking at specific metatabolic or receptor issues, our old friend warfarin (a "blood thinner" with a narrow therapeutic index, a reputation for causing a lot of trouble and a genomic profile that accounts for about half of the known variation in the drug) and the pain drug codeine are on that list as well. There's even a research website devoted to genetic calculation of warfarin dosing.
Carbamazepine (Tegretol) can cause a rare life-threatening reaction called Stevens-Johnson Syndrome (Toxic Epidermal Necrolysis), but it's mostly limited to individuals with a specific Human Leukocyte Antigen (HLA-B*1502). Again, known for quite a while and a part of the basic biology of the drug.
It's a fairly well-written article, but it's kind of breathless about stuff that I was really excited about back in the '90's when my medical school teachers were really excited about it too. The best news is that the FDA has really stepped up in the past few years to make this actionable data that a practicing clinician can use.
Okay, so let's give credit - this is a legitimate researcher doing interesting (if highly preliminary) work. From his bio, accessible from TFA, you find that:
We have been assessing CSF and plasma samples from human subjects at the Washington University ADRC and have found that decreased CSF [alpha-beta] and increased tau are harbingers of cognitive decline in cognitively normal elderly.
Which suggests that the increase in CSF beta protein seen in sleep deprivation might actually be a harbinger of protection from Alzheimer Disease (AD). Or not, and it's not possible to know right now. Your speculation is just as valid as mine.
The problem is that we don't know if the protein causes the neuronal damage in AD or is a side effect of the damage, like a clot or a scar. Dr. Holzman's research bio makes that clear, and it also makes it clear that the damage, whatever it is, starts decades before the protein levels become abnormal. So if you want to avoid sleep deprivation, that's cool, and the fact that most people reading this site are hopelessly sleep deprived most of the time is probably cool too. Either way, our other lifestyle issues will likely collect us long before our brains start to rot.
On the plus side, we now know how to make mice demented. It's not much, but it's something.
Amen. The vaccine has showed animal immunogenicity, which is not a bad thing, but since the animals in question don't get AIDS from HIV, their immune systems don't react the same way that human ones do. Which means you need to proceed to human testing, and that takes a long time.
Phase I trials are important, and announcing them is not a bad thing. And nobody particularly expects cures in the HIV-positive population, although circulating HIV may be interesting (if the virus can cause a practical immune response in subjects with HIV but who have fairly normal T4 counts and you can show reduced circulating viral load, you have an interesting data point for efficacy).
My biggest problem with this kind of press release is that they don't include the details. I'd be interested in knowing why this vaccine is likely to work better than the last two hundred that have been tried, what the actual animal studies showed, and so on. Oh well. I'm not going to be waiting up this weekend to hear more. It will be a couple of years before we know whether this one works.
Unfortunately (OK, it's not unfortunate at all, actually), option #1 isn't just taboo, it's impossible in any human society. Even if we had a completely accurate test (which we certainly do NOT have), and even if you could somehow prevent all positive contacts from continuing their infectious behavior (and I'm not sure anything short of summary execution would be reliable), you'd still have leakers, avoiders, corruption, and resistance. Not even North Korea has managed to avoid HIV, although they're close, at least by report. Largely, I suspect, because summary execution is a routine thing for them.
Option #2 is science fiction for now. The genetic resistance to HIV is conferred by the lack of a particular cell-surface receptor, so you'd have to find a way to effectively eliminate that piece of genetic material from every genome in the body. And since T cells are quite long-lived, you'd have to mess with a lot of quiescent DNA to do it. Maybe some day, but not soon.
Which leaves vaccination. I'm in agreement with your skepticism on this one, not because it's impossible but because HIV, due to its unique targeting system, has been very intractable. You do have to target relatively stable regions of its proteins or its DNA, but this isn't unique to HIV, and we've solved it with polyvalent vaccines elsewhere (think Menactra, or the recent HPV vaccine, or even the flu shot). HIV is a pretty wimpy virus from a spread perspective, so a good polyvalent vaccine would seem possible. The problem is practical immunogenicity, and that's the issue that has torpedoed previous vaccines.
Fine, as long as you work my hours. I work in a job where I may be setting up at 0500 for a multi-person network-heavy presentation scheduled to go at 0630, and I have zero time for argument. I've had great support and lousy support, and yes, I bring my own network hardware in case the local admin doesn't have what I need.
That said, I almost never have a problem, because good network admins do indeed work with me, and lousy ones either (a) aren't there to complain, or (b) trust me far more than they should. Oh, and I ask (and explain and discuss and compromise) long before any equipment sees power. It's only polite.
I've never (ten years or so) had a local hardware issue extend into the host network. It seems to be fairly hard to do that if you're not an idiot (and if your own equipment is truly solid, which mine is).
Sadly, I actually used your cogent comments to waste a fair bit of time and go look at the original press paper (in German, it's at this link). It's a story of an intrepid science fair paper. Let's hear the Google translation:
Perhaps the most "exciting moment in human history", as Nico Marquardt promises Completes had chosen on Friday, 13 April 2029 at 22:45 am Central European Time. Then flies from the iron and Iridium existing space-potato, 320 metres in diameter and 200 billion tons, only 32500 kilometres of the earth over.
There, I hope that gave you a flavor. BTW, there is no mention here either of any named individual in NASA or ESA that is standing behind the numbers quoted.
The article is breathless about how wonderfully catastrophic this all is, but I do have some questions about the math. For one, are there really 40,000 satellites in geostationary orbit (or geosynchronous orbit)? That's the quoted number - I was under the impression that there were rather fewer. And how on earth do they get a figure of 1:450 that the satellite will hit one of them? And that that hit will guarantee the catastrophic outcome they so desire?
For another, I'm not getting a picture of a long observational period and multiple telescopes. Only one telescope is mentioned, and the science fair aspect makes it more suspicious. It looks more like a novel hypothesis ("what if it rams a satellite?") combined with some serious guesswork.
And finally, did anybody else get a little bothered by the description of a 160-meter radius asteroid that weighs 200 billion tons? That gives a density of a little under 12 kilograms per cubic centimeter, which would make it a rather unique and valuable material. As near as I can tell, Wikipedia being your friend and all, they missed by three orders of magnitude. Speaking of correcting the numbers...
Let's see. We begin with the original source of data, "telescopic observations." Good, but perhaps a bit, shall we say, lacking in nine-digit precision. Then we add the element of a bright schoolboy (always a favorite in the papers) doing something big and being validated (instantly!) by "NASA" (not a person, but apparently the entire agency). Oh, and "NASA" told "ESA", but we still don't have the identity of anyone other than the putative schoolboy.
So far, doing well.
Then we hit the big problems. First, we have the scare factor of "40,000" satellites surrounding Earth. Most of which, actually, are in LEO, with a few more in geosynchronous orbit. Which makes the space around the Earth only about 99.999% empty space, rather than a few more nines. As it turns out, space is big.
But it sounds good to imply that somehow there's this asteroid belt around the earth, and that the "killer" asteroid might hit a satellite.
Well, WHICH ONE? They have a lot of different masses, they are going in different directions, and we pretty much have to get a specific momentum change in the right direction in order to get just the right perturbation. Hitting a small piece of space junk is one thing, but the variation in weight of those "40,000" satellites is orders of magnitude. And that makes a big difference in orbital perturbation, even if the difference in orbital velocity is small compared to the velocity of the asteroid. We're talking about a subtle effect here.
And let's not figure in things like elastic collisions, off-center collisions, pieces flying off, or anything else. Nope, it's gonna happen perfectly, just like that seven-ball four-cushion bank shot we all can hit again and again.
Heck, they even called the pocket. Right into the Atlantic, after an orbit measuring in the decades. Now I will grant that the orbit is pretty well known, but again, that little "satellite assist" must be just precise as heck.
A nice touch gives us the "destroy both coasts and darken the world indefinitely." While it's good to be so certain, couldn't they be more specific about the method of destruction? Seeing as how they apparently know everything else, and all.
And finally, we have the 450:1 odds. Not 500:1, and certainly not 1000:1, but exactly 450. Cool. About as believable as my old homework excuses, but infinitely cooler. Can you say "significant figures"? I knew you could.
I think it's what you get when you let AFP (my source of news of the world for sure) loose in spring.
Yeah, I know. They have a legal exemption from liability for the contents of the traffic they carry, subject to certain restrictions. Which isn't common-carrier status, although it acts a little like it.
But if they start to routinely "deeply inspect" traffic, a frisky plaintiff's attorney is going to see gravy in the "knew or should have known they were defaming my client" kind of stuff, and here we go.
Never mind that it's evil, or that it's a great step to losing their common-carrier status.
Never mind that it's a true violation of privacy.
Never mind that I block cookies pretty well and I run with NoScript most of the time and I don't see very many ads, and besides, half of the time I'm inside my employer's VPN.
But even more than that, I have seven other users in my household, half of them teenagers. If they want to sniff all of my NAT-ed packets coming out, they're going to discover that I'm a geek who has four Facebook sites, likes art and hates it, plays Runescape incessantly (the 10-year-old), likes the Wiggles, and works as a beauty consultant. So go ahead and hand me the ad for the latest XBox game (I hate games). Offer my kids server hardware, and see if you can get my wife to click on fun games to play with the Backyardigans. Oh, wait, you already do. It's called "not targeting advertising", and it's free.
So what we have is a thoroughly broken high-cost borderline-illegal absolutely-unethical service offered to advertisers in a difficult economic period. By people who we all hate a lot, and who will rapidly become targets for everything from blocking to legislative action to you name it.
I knew there would be some kind of career move for spam kings in the future. I just thought it would pay better.
I predict a less than stellar outcome for these idiots, and they deserve every painful moment.
Give it a rest. Vaccines don't cause autism. Mercury in vaccines especially doesn't cause autism, because there isn't any mercury in most vaccines, and there hasn't been any for years. This was effectively ended by going to single-dose vaccines to prevent the need to stabilize or sterilize the multi-dose vials. It increased cost, but it eliminated a small (but nonzero) dose of a heavy metal. There's still no evidence of significant harm during the mercury era, but that era ended years ago.
Britain did a lovely experiment with mass hysteria and autism, dropping their MMR immunization rate substantially in response to this kind of fear-mongering. The result: measles made a comeback, and diagnoses of autism continued to increase. We still don't understand whether (or why) autism is on the rise, but vaccinations were effectively ruled out a long time ago.
As far as the massive money made on the flu shot, give that a rest too. Vaccines are hard to convince drug companies to make, because the liability exposure is large and the profit on the drug is quite small. In the USA, if it weren't for federal intervention (surveillance and liability coverage), we wouldn't have domestic manufacture of any of them. Remember that flu shot shortage a few years ago? It happened because a British manufacturer of the vaccine, Chiron, had a facility declared ineligible (for quality reasons) to ship product. In the USA, there isn't enough domestic manufacturing capacity to make up that kind of a hit.
As far as how benign influenza is, try that line out on the half dozen families in my state who had a previously healthy school-age child die suddenly from the flu a couple of years ago. We had a bad strain come through that year, and we saw a lot of cases of partial or complete airway obstruction from the necrotizing tracheobronchitis that seems to be caused by certain kinds of flu A. Or just talk to the hundreds of people who were hospitalized last year, or the tens of thousands who lost a week from work and felt like they got hit by a car. Or talk to me - I'm a hospital pediatrician practicing in a site where I see all of this and more, and where I've seen directly the difference that the flu shot makes. And yes, I get mine, and I have done so every year for a LONG time.
If you're a healthy adult and you don't mind a moderate statistical risk that you're going to feel like crap for a week at some point in the next six months, by all means run and hide from the shot. But don't let the vaccines-cause-civilization-decay folks panic you out of something that has kept a lot of my patients healthy.
He's a rich man who is getting sick and old, and he's mad because it has turned out to be hard to find out how to stop people from getting sick and old. He's upset, and I understand that, but he also missed most of the points that might be out there to get.
No question that medicine is a different culture than engineering. I've spent a lot of time in both, and I know. I also know that medicine is NOT particularly creative, and you don't really want it to be. You want your illness to be routine and fixable, and being routine means that nobody has to sweat particularly hard to figure it out. The sweat, and there's plenty, has to be done in research and development, and the difference in development effort between a new therapy for a disease and a new electronic entertainment device is remarkable.
He talks about how the two cultures deal with failure. In engineering, particularly in microelectronics, failure means that you spend money, time, and energy fixing something you broke. In medicine, failure means that you kill somebody. This used to happen a lot, and the modern biomedical research culture is highly biased against failure. It's not OK to die in a study any more, even if the condition we're studying is in and of itself fatal. Changing this would speed up the process of research, but who's volunteering to die for the cause? (And no, offshoring it is NOT the answer - foreign governments are wising up to this quickly, as are domestic ethics consultants.)
He derides modern statistical techniques, misunderstanding the difference between statistical failure and subgroup averaging, and he flatters himself a prophet when he recommends something that pharmaceutical researchers have been doing for thirty years: analyzing failure to see if you can find partial success somewhere.
He writes off in a sentence or two the hardest problem of all, which is figuring out what in the heck is really going on (preparatory to changing it). In engineering, the complexity is finite and human-directed, and the systems are designed with severable components to make the process of debugging and analysis easier. In medicine, the complexity is engineered by a billion years of evolution, not all of it productive or even useful, and very poorly understood. In an organism such as people, where 50,000 poorly-understood genes interact with factorial complexity, just figuring out which end to push on can be maddening. It's the reason that peer review was invented: if you're up a creek with a paddle-less enzyme, there are probably only a few hundred people in the world who can tell whether you're a genius or just confused. Peer review at its best is just like open source. At it's worst it's a lot like open source at it's worst, but the less said of that the better.
I would love to see more acceptance of modern information techniques and more flexibility in medical research. I would love to see better use of rapid prototyping and model systems, and we're heading that way. We've actually come a huge way in medicine just in the last decades, and the pace is accelerating. TFA is just a measure of the fact that, just like software, sometimes the better the system gets, the more you can see how imperfect it is.
It's an interesting study, and they're doing it right, but there's no particular breakthrough yet. This is an in vitro study with no clinical implications yet. TB is a significant problem where I work (I'm a doctor in the Western US), but there are some hurdles to get over before I can start using clavulanate.
Clinical utility is the Holy Grail here - the biochemical activity of a drug is critical, but the effect of the drug on the infection in an infected person is a lot more complicated. You have to get an effective concentration of the antibiotic into the area of the organism, get the bug to take up appropriate quantities of it, and not injure the patient in the process. Every step of this can kill an otherwise promising use of the drug.
In the case of clavulanate, we know that it causes significant side effects. I use it a LOT in kids (Augmentin is your friend for a variety of conditions, and clavulanate is what makes Augmentin Augmentin), and it causes pretty impressive diarrhea at fairly low doses. Diarrhea, especially if it involves altered intestinal flora, is a set-up for C. difficile colitis, which can be deadly. If we need high concentrations of clavulanate, we may not be able to give enough of it to patients. Or there may be other toxicities, although it's been quite benign in widespread use to date.
Another problem is that the bacterium can mutate proteins to avoid drugs, and TB is pretty good at this. MDR TB didn't happen by accident, and mutation of beta-lactamases to avoid clavulanate is not unheard of. Overproduction of the enzyme is also possible, and would then increase the required dose of the drug (and see above).
A final problem is the physical defenses of the bug. The cell wall for TB is quite effective and strong, and the bacterium has a variety of transport mechanisms to get antibiotics out of the cell. Again, we may not be able to get enough clavulanate into the cell long enough to kill it.
Having said all of that, I'm delighted both that the work is being done and that these initial results are promising. It will be fun to see what happens clinically.
But someone pointed out what may be obvious, which is that after the full regiment there are going to be few enough of these bacteria left that the human immune system can finish the job of wiping them out completely, leaving no antibiotic-resistant bacteria at all. Is this accurate? In essence, yes. In fact, people who have immune deficiencies are particularly likely to develop resistant bugs, and we suspect that at least part of the problem is that the immune system can't quite finish the job.
Yep. I've got patients who do the same (I live in an area where we have a lot of Hispanic immigrants, legal and otherwise). Nothing I can do about it except to talk with them, which I do. I try to encourage them to be reasonable and to take an entire course when they start one (nothing's worse than an occasional antibiotic pill). I have mixed success, but I don't expect perfection and I think my attitude helps the situation. I do get a lot of "do you suggest I start this" kinds of calls and questions and I treat those calls as victories.
This gets me into the whole doctor-as-gatekeeper-for-pills thing that drives me nuts. I challenge colleagues once in a while: in an environment where all medications were available at retail, could they still justify their fees? Could they market themselves well enough to avoid starvation? I think I could, because of the kind of medicine I practice (and because I can sometimes go a dozen patients between giving a prescription), but it's definitely something honest physicians should be asking themselves.
In the no-Rx-required environment, though, there's no question that resistance emerges rapidly. Fortunately, the antibiotics available in Mexico are a small subset of the ones we use here, and most of the ones that patients can buy OTC have broad therapeutic indices (overdose doesn't hurt you much) and are from antibiotic classes (penicillins, macrolides) where we have later-generation alternatives that avoid the common resistances. It's a fluid situation, though, and one that has infectious disease specialists always a little on edge.
Always a concern, but the trend in medicine over the past decade or so has been to reduce the number of times we prescribe, even as we increase both the dose and duration of care when we do pull the trigger. Antibiotic resistance has been strongly linked to inadequate dosing (killing only the susceptible bugs, while letting the borderline-resistant clones reinforce themselves), as well as to courses too short or patient noncompliance.
Patients are part of the problem too, since there is a tendency (cultural in some cases, personal in others) to demand that a doctor "do something" to fix the problem. Antibiotics were perceived for a long time as something harmless to give in those circumstances, but that perception is fading fast. If anything, the trend now is to err on the side of letting things play out a little more to see if antibiotic therapy is really needed.
This has also caused physicians to have to explain the situation better. I know for myself that when I am explaining to a suspicious parent the reason that I'm not going to give their child an antibiotic for their viral infection, I don't waste a lot of time explaining resistance. If they already understand resistance, they're not asking for antibiotics. If they don't, it just sounds like I'm making things up. I focus instead on side effects and cost, and my typical (true) statement is "about all I can do with antibiotics would be to give your child diarrhea to go with her cold." This is surprisingly effective, especially in the parents of non-potty-trained toddlers.
None of which stops me from pulling out the stops when I'm faced with a septic kid or a real infection that needs to be nuked. In those cases, though, I'm very careful to make sure that the regimen I use is appropriate, considering the resistance patterns and the risk of making them worse.
Now if we could only get the idiots who lace animal feed with antibiotics to do the same. Ever wonder where resistant strains start? Hint: it ain't just in the hospitals.
I'm a skeptic about a lot of things in medicine (I live in that world), especially "wonder drugs", and the writer of TFA demonstrates his limited skills in microbiology enough to make me cringe. But the science here is going to be fun to see.
Don't get me wrong - we need to know the doses, the regimen, the side effects at antimicrobial dosing, and all the rest of the nuts-and-bolts pharmacology. On the other hand, the putative mechanism, which is to interfere with sharing of genes between bacteria, is in itself ground-breaking. Used properly (that is, not overused and used with care), this could prevent rapid resistance emergence in bacteria where the treatment itself takes weeks to months (osteomyelitis, for example, or infection with certain stubborn bugs). These drugs (etidronate and pamidronate) have their own not-insignificant side effect profile, of course, and there are no guarantees at this stage.
I'll be interested in the actual research, because TFA is filtered through a layer of ignorance and sensationalism, but it sounds interesting.
Yeah, I get asked for it once in a while in my pediatric practice. I'm pretty much fine with it as long as I know their hearts are normal and they don't have depression or postural hypotension. I'm not always sure it helps that much, but some musicians I know swear by it. Like you said, it's safe, at least marginally effective, and not subject to abuse.
I'd think that it would be excellent for flashback management, but I'd love to see some research on it.
It's not a new drug that was tried by Harvard and McGill, it was an old favorite, propranolol. This is a nonselective beta blocker that has anti-adrenaline actions (oversimplifying radically) in the CNS as well as across the body, and it's used for a dozen purposes other than this one. This was actually fascinating research, because they're basically using an old standby drug to help desensitize certain traumatic memories. There was no assertion in the original article (other than the Star Trek pandering at the end) that the memories were eliminated entirely, although eliminating emotional tags to memories would have the side effect of making them harder to recall.
We know that the beta blockers have significant mood and activity side effects. In fact it's a common limitation on their use. In this case, though, it looks like the researchers are capitalizing on these side effects to make people's handling of trauma better. Cool. This is a use that will probably see more significant human clinical trials in the short run. Propranolol is a very cheap and very well-understood medication.
In the case of the rat studies with the actual new drug, it's early but interesting work that might or might not have human implication in the future. I'll be nervous about it without a lot more research, and I suspect that the greater degree of wiring in the human brain and the relative resilience of memory are going to be harder nuts to crack, at least in the short term.
Okay, after reading the entire hysterical FA, I want that ten minutes of my life back. A sensationalistic article published on a slow-news Sunday in the Globe and Mail (where I always look for good peer-reviewed scientific evidence) says that a study "will be published" in June that will revolutionize the way that I, a practicing physician, view chronic disease.
Or maybe not. I can't tell whether the study was prospective, controlled, or blinded. I can't tell what cancers were examined. I CAN tell you that four years is ridiculously short for a study examining the emergence of cancer, which appears (we're not sure yet) to take decades in most cases. Since the journal is not named, I don't know its reputation or whether the study was peer-reviewed (and by what peers). In other words, I have no information that allows me to evaluate the claim, except that the claim itself was published in the newspaper. This in itself is not a good sign.
It is a violation of scientific ethics to pre-announce your results in the lay press without also revealing the details of your methods and the limitations of your study. In the case of a "miracle" result for a common supplement, it rises to the level of being truly suspicious. Extraordinary claims really do require extraordinary proof, and making such a claim in a Sunday supplement in the complete absence of accompanying evidence is the stuff of psychics and snake oil.
I am skeptical. I am willing to be convinced, but I'm also willing to entertain cash bets on the probability of this being true and clinically useful.
"I hope that there is a special level of hell for people who prey on the desperate in this fashion."
Absent that lovely thought (and you would not believe the things I have thought of doing to these loathsome creeps), I would simply hope that one day they wake up, look in the mirror, and realize that their entire life has been devoted to torturing people too innocent to understand why they're being hurt.
And that over the next hour, in a fit of shame, they take their electric razor and, layer by layer, remove their own genitalia until they die.
I believe they are postulating this as a cause, not an effect. Autism is a syndrome of behavior, and it's hard to extrapolate a behavior into having metabolic side effects, unless it affects diet or activity in some way. Absent a credible biochemical mechanism, supplementation with any food enters the realm of true snake oil, and should be treated as such.
On the other hand, if they have identified a rare genetic defect that causes an autistic-like syndrome and they can cure that rare disorder, I am quite happy with that. I just don't believe it will have much to do with the vast majority of autism.
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If we compile statistics, we can look for the points where nobody has ever meaningfully recovered.
We do. This is where the guidance to stop resuscitation after 15 minutes without a rhythm comes in. Unless you're a child who drowned in cold fresh water, of course, or an adult who apparently died of hypothermia. The problem is that there are so very many different sets of facts, and people are far more resilient than you can imagine. And in the heat of the moment, we tend to opt to fight rather than to let go. Which is actually OK, I think.
For your example, ECMO can only be useful for acute lung failures including injury. It's useless in chronic cases where the lungs simply aren't going to improve.
Well, yes, ECMO is probably a bad example, because it's by definition an acute therapy that can't be continued more than a few days, at least at the current state of the art. Even there it's a bit questionable in the case of chronic disease exacerbated by acute cardiopulmonary collapse from a (presumably) reversible cause. But other therapies, like the simple $10K/day ICU bed, are much harder to argue against, unless you've given specific instructions. It reminds me a little of the old instructions for tuning a carburetor - turn the screw until the engine dies, then back up half a turn. Most of the really futile ICU cases I've seen didn't START as futile cases, but they sure ended that way.
Most other western countries have a bit less tendency to heroic medicine than the U.S.
I'm not actually all that impressed with medicine in "most other Western countries" as a touchstone for our own. Every country has its own social norms and conventions, all of which fold over into health care. We tend to value privacy, autonomy, personal space, personal choice, and hope for recovery more than most, and it costs us a lot of money.
I think the problem is that we don't know in advance when the "last days of life" are for anyone. Or at least we don't know if prospectively, and knowing it after the fact is kind of pointless in terms of limiting costs.
If there are treatments that are virtually never helpful, we need to stop using them. There aren't many interventions that actually fit that description, though, and even the most invasive of them - ECMO, for example (basically continuous heart-lung bypass) - have their place in restoring people to health in the right circumstances. Eventually the circumstances are such that death is inevitable, but recognizing that point is not something we know how to do with certainty. Even when we're pretty sure, communicating our own conviction is very hard. And where there is no certainty, there is the great likelihood of erring on the side of treatment.
Hospice care, which tends to be very inexpensive compared to attempts at cure, is helping because it gives people a viable alternative path. Most physicians with whom I deal (a very large number, as it turns out) are big fans of hospice care. Not because it's cheap, but because it helps make the case for avoiding further torture. It's not a bad way to reduce costs, though, and that's not irrelevant.
I'm a board-certified physician (among other things). There is no way that I would allow my colleagues to inflict the kind of death on me that they are forced to inflict on so many. Part of this is certainly that I know full well that we all exit this mortal coil toes-up, and there's no getting around it. Part of this is the personal reluctance to experience the diminished autonomy, indignity, pain,and hopelessness that comes with fanatically-treated terminal illness.
But a big part of it, I think, is just that I know that there are so, so many things that are worse than simply dying. Dying in agony, for one. Dying after having bankrupted my wife or my children. Dying after being reduced to a stinking thing in a bed long enough that only those who loved me most even want to be near me, and that only because they feel they must. Physicians see these things all the time, and we see the road that leads to them. We're not (that) stupid, and we would rather exit early on that road, not at its terminus.
As long as I have the capacity for joy I will strive to remain alive to experience that joy. When the capacity - or the joy - is gone for good, I have given quite strict instructions not only to my family but to some other clear-headed and insistent people who will do their best to ensure that I too will be gone without further "heroic" intervention.
The only problem that I have with the article is that it pretends that everyone should make the same decisions. Everyone has their own decisions to make, and without my knowledge and experience I might not make the same ones. I think as physicians we owe it to the people for whom we care to educate as well as we can and help them to understand why we might personally decide one way or another. But I will never tell them how they "ought" to decide - it's really their choice. Taking that choice away from a person leads too easily to very real outcomes that are much nastier than simply a life that ends later than it ought.
The article is pretty good, actually, in that it doesn't try very hard to claim that they're curing the world of its ills. There's a little in there, but mostly it deals with Fragile X.
Randi Hagerman (the researcher quoted extensively in the article) is one of the leading lights in Fragile X research. She and her husband, Paul, described the gene, developed the RFLP that we now use to diagnose the illness, and did much of the fundamental work to explain the genetic-expression behavior of the gene. It is not a simple inheritance model, and the expression of the gene is quite confusing. She's a superstar.
As far as the broader issue of autism (and even more confusingly, autism spectrum), Fragile X has always seemed to me to be a blind alley. People with Fragile X (I've worked in that community as a physician) have a very specific affect and behavior pattern that doesn't look a lot like the behavior of people with autism (a community I know all too well as a physician and a parent of an autistic young man). Most of the early research in autism was tainted by the inclusion of Fragile X patients, and most of the combined research is just confusing.
I hope that the drug proves useful in Fragile X, although pharmacotherapy for these kinds of disorders has frustrated us over and over again. These are simply very hard diseases to affect very much. At the least, though, it'll be another step toward understanding a serious disease. And I'll continue to wait and watch for anything that will help in autism, but I REALLY don't expect much from this specific drug.
The FDA has had a table of valid genetic biomarkers for medications for several years now. While many of these are cancer drugs looking at specific metatabolic or receptor issues, our old friend warfarin (a "blood thinner" with a narrow therapeutic index, a reputation for causing a lot of trouble and a genomic profile that accounts for about half of the known variation in the drug) and the pain drug codeine are on that list as well. There's even a research website devoted to genetic calculation of warfarin dosing.
Carbamazepine (Tegretol) can cause a rare life-threatening reaction called Stevens-Johnson Syndrome (Toxic Epidermal Necrolysis), but it's mostly limited to individuals with a specific Human Leukocyte Antigen (HLA-B*1502). Again, known for quite a while and a part of the basic biology of the drug.
It's a fairly well-written article, but it's kind of breathless about stuff that I was really excited about back in the '90's when my medical school teachers were really excited about it too. The best news is that the FDA has really stepped up in the past few years to make this actionable data that a practicing clinician can use.
Okay, so let's give credit - this is a legitimate researcher doing interesting (if highly preliminary) work. From his bio, accessible from TFA, you find that:
Which suggests that the increase in CSF beta protein seen in sleep deprivation might actually be a harbinger of protection from Alzheimer Disease (AD). Or not, and it's not possible to know right now. Your speculation is just as valid as mine.
The problem is that we don't know if the protein causes the neuronal damage in AD or is a side effect of the damage, like a clot or a scar. Dr. Holzman's research bio makes that clear, and it also makes it clear that the damage, whatever it is, starts decades before the protein levels become abnormal. So if you want to avoid sleep deprivation, that's cool, and the fact that most people reading this site are hopelessly sleep deprived most of the time is probably cool too. Either way, our other lifestyle issues will likely collect us long before our brains start to rot.
On the plus side, we now know how to make mice demented. It's not much, but it's something.
Amen. The vaccine has showed animal immunogenicity, which is not a bad thing, but since the animals in question don't get AIDS from HIV, their immune systems don't react the same way that human ones do. Which means you need to proceed to human testing, and that takes a long time.
Phase I trials are important, and announcing them is not a bad thing. And nobody particularly expects cures in the HIV-positive population, although circulating HIV may be interesting (if the virus can cause a practical immune response in subjects with HIV but who have fairly normal T4 counts and you can show reduced circulating viral load, you have an interesting data point for efficacy).
My biggest problem with this kind of press release is that they don't include the details. I'd be interested in knowing why this vaccine is likely to work better than the last two hundred that have been tried, what the actual animal studies showed, and so on. Oh well. I'm not going to be waiting up this weekend to hear more. It will be a couple of years before we know whether this one works.
Unfortunately (OK, it's not unfortunate at all, actually), option #1 isn't just taboo, it's impossible in any human society. Even if we had a completely accurate test (which we certainly do NOT have), and even if you could somehow prevent all positive contacts from continuing their infectious behavior (and I'm not sure anything short of summary execution would be reliable), you'd still have leakers, avoiders, corruption, and resistance. Not even North Korea has managed to avoid HIV, although they're close, at least by report. Largely, I suspect, because summary execution is a routine thing for them.
Option #2 is science fiction for now. The genetic resistance to HIV is conferred by the lack of a particular cell-surface receptor, so you'd have to find a way to effectively eliminate that piece of genetic material from every genome in the body. And since T cells are quite long-lived, you'd have to mess with a lot of quiescent DNA to do it. Maybe some day, but not soon.
Which leaves vaccination. I'm in agreement with your skepticism on this one, not because it's impossible but because HIV, due to its unique targeting system, has been very intractable. You do have to target relatively stable regions of its proteins or its DNA, but this isn't unique to HIV, and we've solved it with polyvalent vaccines elsewhere (think Menactra, or the recent HPV vaccine, or even the flu shot). HIV is a pretty wimpy virus from a spread perspective, so a good polyvalent vaccine would seem possible. The problem is practical immunogenicity, and that's the issue that has torpedoed previous vaccines.
Fine, as long as you work my hours. I work in a job where I may be setting up at 0500 for a multi-person network-heavy presentation scheduled to go at 0630, and I have zero time for argument. I've had great support and lousy support, and yes, I bring my own network hardware in case the local admin doesn't have what I need.
That said, I almost never have a problem, because good network admins do indeed work with me, and lousy ones either (a) aren't there to complain, or (b) trust me far more than they should. Oh, and I ask (and explain and discuss and compromise) long before any equipment sees power. It's only polite.
I've never (ten years or so) had a local hardware issue extend into the host network. It seems to be fairly hard to do that if you're not an idiot (and if your own equipment is truly solid, which mine is).
There, I hope that gave you a flavor. BTW, there is no mention here either of any named individual in NASA or ESA that is standing behind the numbers quoted.
The article is breathless about how wonderfully catastrophic this all is, but I do have some questions about the math. For one, are there really 40,000 satellites in geostationary orbit (or geosynchronous orbit)? That's the quoted number - I was under the impression that there were rather fewer. And how on earth do they get a figure of 1:450 that the satellite will hit one of them? And that that hit will guarantee the catastrophic outcome they so desire?
For another, I'm not getting a picture of a long observational period and multiple telescopes. Only one telescope is mentioned, and the science fair aspect makes it more suspicious. It looks more like a novel hypothesis ("what if it rams a satellite?") combined with some serious guesswork.
And finally, did anybody else get a little bothered by the description of a 160-meter radius asteroid that weighs 200 billion tons? That gives a density of a little under 12 kilograms per cubic centimeter, which would make it a rather unique and valuable material. As near as I can tell, Wikipedia being your friend and all, they missed by three orders of magnitude. Speaking of correcting the numbers...
Let's see. We begin with the original source of data, "telescopic observations." Good, but perhaps a bit, shall we say, lacking in nine-digit precision. Then we add the element of a bright schoolboy (always a favorite in the papers) doing something big and being validated (instantly!) by "NASA" (not a person, but apparently the entire agency). Oh, and "NASA" told "ESA", but we still don't have the identity of anyone other than the putative schoolboy.
So far, doing well.
Then we hit the big problems. First, we have the scare factor of "40,000" satellites surrounding Earth. Most of which, actually, are in LEO, with a few more in geosynchronous orbit. Which makes the space around the Earth only about 99.999% empty space, rather than a few more nines. As it turns out, space is big.
But it sounds good to imply that somehow there's this asteroid belt around the earth, and that the "killer" asteroid might hit a satellite.
Well, WHICH ONE? They have a lot of different masses, they are going in different directions, and we pretty much have to get a specific momentum change in the right direction in order to get just the right perturbation. Hitting a small piece of space junk is one thing, but the variation in weight of those "40,000" satellites is orders of magnitude. And that makes a big difference in orbital perturbation, even if the difference in orbital velocity is small compared to the velocity of the asteroid. We're talking about a subtle effect here.
And let's not figure in things like elastic collisions, off-center collisions, pieces flying off, or anything else. Nope, it's gonna happen perfectly, just like that seven-ball four-cushion bank shot we all can hit again and again.
Heck, they even called the pocket. Right into the Atlantic, after an orbit measuring in the decades. Now I will grant that the orbit is pretty well known, but again, that little "satellite assist" must be just precise as heck.
A nice touch gives us the "destroy both coasts and darken the world indefinitely." While it's good to be so certain, couldn't they be more specific about the method of destruction? Seeing as how they apparently know everything else, and all.
And finally, we have the 450:1 odds. Not 500:1, and certainly not 1000:1, but exactly 450. Cool. About as believable as my old homework excuses, but infinitely cooler. Can you say "significant figures"? I knew you could.
I think it's what you get when you let AFP (my source of news of the world for sure) loose in spring.
Yeah, I know. They have a legal exemption from liability for the contents of the traffic they carry, subject to certain restrictions. Which isn't common-carrier status, although it acts a little like it.
But if they start to routinely "deeply inspect" traffic, a frisky plaintiff's attorney is going to see gravy in the "knew or should have known they were defaming my client" kind of stuff, and here we go.
Never mind that it's evil, or that it's a great step to losing their common-carrier status.
Never mind that it's a true violation of privacy.
Never mind that I block cookies pretty well and I run with NoScript most of the time and I don't see very many ads, and besides, half of the time I'm inside my employer's VPN.
But even more than that, I have seven other users in my household, half of them teenagers. If they want to sniff all of my NAT-ed packets coming out, they're going to discover that I'm a geek who has four Facebook sites, likes art and hates it, plays Runescape incessantly (the 10-year-old), likes the Wiggles, and works as a beauty consultant. So go ahead and hand me the ad for the latest XBox game (I hate games). Offer my kids server hardware, and see if you can get my wife to click on fun games to play with the Backyardigans. Oh, wait, you already do. It's called "not targeting advertising", and it's free.
So what we have is a thoroughly broken high-cost borderline-illegal absolutely-unethical service offered to advertisers in a difficult economic period. By people who we all hate a lot, and who will rapidly become targets for everything from blocking to legislative action to you name it.
I knew there would be some kind of career move for spam kings in the future. I just thought it would pay better.
I predict a less than stellar outcome for these idiots, and they deserve every painful moment.
Give it a rest. Vaccines don't cause autism. Mercury in vaccines especially doesn't cause autism, because there isn't any mercury in most vaccines, and there hasn't been any for years. This was effectively ended by going to single-dose vaccines to prevent the need to stabilize or sterilize the multi-dose vials. It increased cost, but it eliminated a small (but nonzero) dose of a heavy metal. There's still no evidence of significant harm during the mercury era, but that era ended years ago.
Britain did a lovely experiment with mass hysteria and autism, dropping their MMR immunization rate substantially in response to this kind of fear-mongering. The result: measles made a comeback, and diagnoses of autism continued to increase. We still don't understand whether (or why) autism is on the rise, but vaccinations were effectively ruled out a long time ago.
As far as the massive money made on the flu shot, give that a rest too. Vaccines are hard to convince drug companies to make, because the liability exposure is large and the profit on the drug is quite small. In the USA, if it weren't for federal intervention (surveillance and liability coverage), we wouldn't have domestic manufacture of any of them. Remember that flu shot shortage a few years ago? It happened because a British manufacturer of the vaccine, Chiron, had a facility declared ineligible (for quality reasons) to ship product. In the USA, there isn't enough domestic manufacturing capacity to make up that kind of a hit.
As far as how benign influenza is, try that line out on the half dozen families in my state who had a previously healthy school-age child die suddenly from the flu a couple of years ago. We had a bad strain come through that year, and we saw a lot of cases of partial or complete airway obstruction from the necrotizing tracheobronchitis that seems to be caused by certain kinds of flu A. Or just talk to the hundreds of people who were hospitalized last year, or the tens of thousands who lost a week from work and felt like they got hit by a car. Or talk to me - I'm a hospital pediatrician practicing in a site where I see all of this and more, and where I've seen directly the difference that the flu shot makes. And yes, I get mine, and I have done so every year for a LONG time.
If you're a healthy adult and you don't mind a moderate statistical risk that you're going to feel like crap for a week at some point in the next six months, by all means run and hide from the shot. But don't let the vaccines-cause-civilization-decay folks panic you out of something that has kept a lot of my patients healthy.
He's a rich man who is getting sick and old, and he's mad because it has turned out to be hard to find out how to stop people from getting sick and old. He's upset, and I understand that, but he also missed most of the points that might be out there to get.
No question that medicine is a different culture than engineering. I've spent a lot of time in both, and I know. I also know that medicine is NOT particularly creative, and you don't really want it to be. You want your illness to be routine and fixable, and being routine means that nobody has to sweat particularly hard to figure it out. The sweat, and there's plenty, has to be done in research and development, and the difference in development effort between a new therapy for a disease and a new electronic entertainment device is remarkable.
He talks about how the two cultures deal with failure. In engineering, particularly in microelectronics, failure means that you spend money, time, and energy fixing something you broke. In medicine, failure means that you kill somebody. This used to happen a lot, and the modern biomedical research culture is highly biased against failure. It's not OK to die in a study any more, even if the condition we're studying is in and of itself fatal. Changing this would speed up the process of research, but who's volunteering to die for the cause? (And no, offshoring it is NOT the answer - foreign governments are wising up to this quickly, as are domestic ethics consultants.)
He derides modern statistical techniques, misunderstanding the difference between statistical failure and subgroup averaging, and he flatters himself a prophet when he recommends something that pharmaceutical researchers have been doing for thirty years: analyzing failure to see if you can find partial success somewhere.
He writes off in a sentence or two the hardest problem of all, which is figuring out what in the heck is really going on (preparatory to changing it). In engineering, the complexity is finite and human-directed, and the systems are designed with severable components to make the process of debugging and analysis easier. In medicine, the complexity is engineered by a billion years of evolution, not all of it productive or even useful, and very poorly understood. In an organism such as people, where 50,000 poorly-understood genes interact with factorial complexity, just figuring out which end to push on can be maddening. It's the reason that peer review was invented: if you're up a creek with a paddle-less enzyme, there are probably only a few hundred people in the world who can tell whether you're a genius or just confused. Peer review at its best is just like open source. At it's worst it's a lot like open source at it's worst, but the less said of that the better.
I would love to see more acceptance of modern information techniques and more flexibility in medical research. I would love to see better use of rapid prototyping and model systems, and we're heading that way. We've actually come a huge way in medicine just in the last decades, and the pace is accelerating. TFA is just a measure of the fact that, just like software, sometimes the better the system gets, the more you can see how imperfect it is.
It's an interesting study, and they're doing it right, but there's no particular breakthrough yet. This is an in vitro study with no clinical implications yet. TB is a significant problem where I work (I'm a doctor in the Western US), but there are some hurdles to get over before I can start using clavulanate.
Clinical utility is the Holy Grail here - the biochemical activity of a drug is critical, but the effect of the drug on the infection in an infected person is a lot more complicated. You have to get an effective concentration of the antibiotic into the area of the organism, get the bug to take up appropriate quantities of it, and not injure the patient in the process. Every step of this can kill an otherwise promising use of the drug.
In the case of clavulanate, we know that it causes significant side effects. I use it a LOT in kids (Augmentin is your friend for a variety of conditions, and clavulanate is what makes Augmentin Augmentin), and it causes pretty impressive diarrhea at fairly low doses. Diarrhea, especially if it involves altered intestinal flora, is a set-up for C. difficile colitis, which can be deadly. If we need high concentrations of clavulanate, we may not be able to give enough of it to patients. Or there may be other toxicities, although it's been quite benign in widespread use to date.
Another problem is that the bacterium can mutate proteins to avoid drugs, and TB is pretty good at this. MDR TB didn't happen by accident, and mutation of beta-lactamases to avoid clavulanate is not unheard of. Overproduction of the enzyme is also possible, and would then increase the required dose of the drug (and see above).
A final problem is the physical defenses of the bug. The cell wall for TB is quite effective and strong, and the bacterium has a variety of transport mechanisms to get antibiotics out of the cell. Again, we may not be able to get enough clavulanate into the cell long enough to kill it.
Having said all of that, I'm delighted both that the work is being done and that these initial results are promising. It will be fun to see what happens clinically.
Yep. I've got patients who do the same (I live in an area where we have a lot of Hispanic immigrants, legal and otherwise). Nothing I can do about it except to talk with them, which I do. I try to encourage them to be reasonable and to take an entire course when they start one (nothing's worse than an occasional antibiotic pill). I have mixed success, but I don't expect perfection and I think my attitude helps the situation. I do get a lot of "do you suggest I start this" kinds of calls and questions and I treat those calls as victories.
This gets me into the whole doctor-as-gatekeeper-for-pills thing that drives me nuts. I challenge colleagues once in a while: in an environment where all medications were available at retail, could they still justify their fees? Could they market themselves well enough to avoid starvation? I think I could, because of the kind of medicine I practice (and because I can sometimes go a dozen patients between giving a prescription), but it's definitely something honest physicians should be asking themselves.
In the no-Rx-required environment, though, there's no question that resistance emerges rapidly. Fortunately, the antibiotics available in Mexico are a small subset of the ones we use here, and most of the ones that patients can buy OTC have broad therapeutic indices (overdose doesn't hurt you much) and are from antibiotic classes (penicillins, macrolides) where we have later-generation alternatives that avoid the common resistances. It's a fluid situation, though, and one that has infectious disease specialists always a little on edge.
Always a concern, but the trend in medicine over the past decade or so has been to reduce the number of times we prescribe, even as we increase both the dose and duration of care when we do pull the trigger. Antibiotic resistance has been strongly linked to inadequate dosing (killing only the susceptible bugs, while letting the borderline-resistant clones reinforce themselves), as well as to courses too short or patient noncompliance.
Patients are part of the problem too, since there is a tendency (cultural in some cases, personal in others) to demand that a doctor "do something" to fix the problem. Antibiotics were perceived for a long time as something harmless to give in those circumstances, but that perception is fading fast. If anything, the trend now is to err on the side of letting things play out a little more to see if antibiotic therapy is really needed.
This has also caused physicians to have to explain the situation better. I know for myself that when I am explaining to a suspicious parent the reason that I'm not going to give their child an antibiotic for their viral infection, I don't waste a lot of time explaining resistance. If they already understand resistance, they're not asking for antibiotics. If they don't, it just sounds like I'm making things up. I focus instead on side effects and cost, and my typical (true) statement is "about all I can do with antibiotics would be to give your child diarrhea to go with her cold." This is surprisingly effective, especially in the parents of non-potty-trained toddlers.
None of which stops me from pulling out the stops when I'm faced with a septic kid or a real infection that needs to be nuked. In those cases, though, I'm very careful to make sure that the regimen I use is appropriate, considering the resistance patterns and the risk of making them worse.
Now if we could only get the idiots who lace animal feed with antibiotics to do the same. Ever wonder where resistant strains start? Hint: it ain't just in the hospitals.
I'm a skeptic about a lot of things in medicine (I live in that world), especially "wonder drugs", and the writer of TFA demonstrates his limited skills in microbiology enough to make me cringe. But the science here is going to be fun to see.
Don't get me wrong - we need to know the doses, the regimen, the side effects at antimicrobial dosing, and all the rest of the nuts-and-bolts pharmacology. On the other hand, the putative mechanism, which is to interfere with sharing of genes between bacteria, is in itself ground-breaking. Used properly (that is, not overused and used with care), this could prevent rapid resistance emergence in bacteria where the treatment itself takes weeks to months (osteomyelitis, for example, or infection with certain stubborn bugs). These drugs (etidronate and pamidronate) have their own not-insignificant side effect profile, of course, and there are no guarantees at this stage.
I'll be interested in the actual research, because TFA is filtered through a layer of ignorance and sensationalism, but it sounds interesting.
Yeah, I get asked for it once in a while in my pediatric practice. I'm pretty much fine with it as long as I know their hearts are normal and they don't have depression or postural hypotension. I'm not always sure it helps that much, but some musicians I know swear by it. Like you said, it's safe, at least marginally effective, and not subject to abuse.
I'd think that it would be excellent for flashback management, but I'd love to see some research on it.
It's not a new drug that was tried by Harvard and McGill, it was an old favorite, propranolol. This is a nonselective beta blocker that has anti-adrenaline actions (oversimplifying radically) in the CNS as well as across the body, and it's used for a dozen purposes other than this one. This was actually fascinating research, because they're basically using an old standby drug to help desensitize certain traumatic memories. There was no assertion in the original article (other than the Star Trek pandering at the end) that the memories were eliminated entirely, although eliminating emotional tags to memories would have the side effect of making them harder to recall.
We know that the beta blockers have significant mood and activity side effects. In fact it's a common limitation on their use. In this case, though, it looks like the researchers are capitalizing on these side effects to make people's handling of trauma better. Cool. This is a use that will probably see more significant human clinical trials in the short run. Propranolol is a very cheap and very well-understood medication.
In the case of the rat studies with the actual new drug, it's early but interesting work that might or might not have human implication in the future. I'll be nervous about it without a lot more research, and I suspect that the greater degree of wiring in the human brain and the relative resilience of memory are going to be harder nuts to crack, at least in the short term.
Okay, after reading the entire hysterical FA, I want that ten minutes of my life back. A sensationalistic article published on a slow-news Sunday in the Globe and Mail (where I always look for good peer-reviewed scientific evidence) says that a study "will be published" in June that will revolutionize the way that I, a practicing physician, view chronic disease.
Or maybe not. I can't tell whether the study was prospective, controlled, or blinded. I can't tell what cancers were examined. I CAN tell you that four years is ridiculously short for a study examining the emergence of cancer, which appears (we're not sure yet) to take decades in most cases. Since the journal is not named, I don't know its reputation or whether the study was peer-reviewed (and by what peers). In other words, I have no information that allows me to evaluate the claim, except that the claim itself was published in the newspaper. This in itself is not a good sign.
It is a violation of scientific ethics to pre-announce your results in the lay press without also revealing the details of your methods and the limitations of your study. In the case of a "miracle" result for a common supplement, it rises to the level of being truly suspicious. Extraordinary claims really do require extraordinary proof, and making such a claim in a Sunday supplement in the complete absence of accompanying evidence is the stuff of psychics and snake oil.
I am skeptical. I am willing to be convinced, but I'm also willing to entertain cash bets on the probability of this being true and clinically useful.
"I hope that there is a special level of hell for people who prey on the desperate in this fashion."
Absent that lovely thought (and you would not believe the things I have thought of doing to these loathsome creeps), I would simply hope that one day they wake up, look in the mirror, and realize that their entire life has been devoted to torturing people too innocent to understand why they're being hurt.
And that over the next hour, in a fit of shame, they take their electric razor and, layer by layer, remove their own genitalia until they die.
Or is that too morbid?
I believe they are postulating this as a cause, not an effect. Autism is a syndrome of behavior, and it's hard to extrapolate a behavior into having metabolic side effects, unless it affects diet or activity in some way. Absent a credible biochemical mechanism, supplementation with any food enters the realm of true snake oil, and should be treated as such.
On the other hand, if they have identified a rare genetic defect that causes an autistic-like syndrome and they can cure that rare disorder, I am quite happy with that. I just don't believe it will have much to do with the vast majority of autism.