What this story leaves out is why we are moving away from thrombolytics - besides them kinda sucking.
Once a clot has matured they tend to be useless, which is part of why there’s a solid upper cap on time to administration. You cross a line where any clot they’re likely to bust isn’t one you want to bust. So, a window of a couple of hours. Urokinase doesn’t change that, to my knowledge.
Surgical removal of the clot, on the other hand, has recently been shown to offer enormous benefit to at-risk tissue (tissue not yet dead but in the watershed area) 24 hours later, without risk of hitting the wrong clot. It’s no miracle either, but evidence is piling up that it’s got more Pros and fewer Cons.
Thus, no one really following armchair hypotheses (one old non RCT trial not withstanding) about combining two increasingly undesirable drugs.
I respect the guy’s thought and effort, and have to admit he might be right about their combined effectiveness, but this article leaves out a lot of the context as to -why- this isn’t getting attention. Writing a hagiography-by-omission is below what I’ve come to expect from statnews.
Whilst angioplasty or clot retrieval is the optimal treatment (have not seen evidence for clot retrieval for strokes in longer timeframes but will be interested to jump into some research tomorrow) in countries where there are enormous distances between tertiary referral centres (ie Australia) thrombolytic agents are still strongly used.
Our ambulances are equipped with r-tPA or similar (there is a tendency to avoid streptokinase as rural/indigenous populations have high exposure to streptococcus/hx rheumatic fever and therefore high risk of added complications) and in the event of STEMIs can be administered en route to ED. Similarly many peripheral sites will administer tenecteplase or similar in Emergency Departments as there are almost no sites that are set up to perform out-of-hours angioplasty once you are out of the major cities; even less chance for neuro-radiological intervention, I think there are only 6 or 7 sites in the country and they are all in major cities.
If his research does bear fruit, I could see it immediately becoming the standard of care in Australia outside of major centres
I'm a volunteer ambulance officer in Western Australia. We certainly don't carry thrombolytic agents. What we do have though is a protocol for getting stroke patients (with good predicted outcomes) into a helicopter or fixed-wing aircraft ASAP so they can get to a hospital with a thrombectomy (clot retrieval) service. If called promptly, then there shouldn't be many patients that we can't get to the right care within a suitable timeframe.
> "If called promptly, then there shouldn't be many patients that we can't get to the right care within a suitable timeframe."
I worked with stroke centers, doctors, etc in building stroke access systems, and that doesn't fly with reality.
Number 1, is that its hard for patients to recognize they are having a stroke. so "If called promptly" is a bit of unrealistic idealism.
Although they say 4 hours, tPA administered after 1 hour has lost most of its benefit, and places that can do thrombectomy 24/7 (in US dedicated stroke centers) is not numerous. You are losing a lot of that hour just for time for the helicopter to warm up, find a spot, and land + your ambulance time getting to /stabilizing the patient.
I'm sure the patients on your beat had suitable access, but that's a bit of selectivity bias no? In the US, although the majority of the population is within the golden hour, there are still a ton of population that does not have access to a stroke center. I find it extremely hard to believe that this is not the case in Australia - where I have heard stories of people getting a finger cut off and having to drive 3 hours to the nearest hospital.
Remember that Australia is ridiculously urbanised. About 80% of Western Australians live in Perth. Contrasted to the US, the most remote Australians must be a lot further from a referral hospital, but the median Australian might actually be closer.
Is there any possibility that Australia would allow volunteers to administer drugs this dangerous, no matter how effective those drugs were? Not to be rude—I volunteer for an emergency service too.
Asprin, paracetamol, glucose, adrenaline (epinephrine) auto-injectors, salbutamol, glyceryl trinitrate (GTN), methoxyflurane, ondansetron, cophenylcaine (lidocaine + phenylephrine) - that's our volunteer drugs in WA. We're hoping that eventually ketamine will be added. I don't see tPA ever being on that list.
That's interesting. Where I trained (central coast, Hunter New England) they do but only for STEMIs, administering'should' occur after a scan in the Ed otherwise
For those interested, the DAWN Trial (http://www.nejm.org/doi/full/10.1056/NEJMoa1706442) provides more detail on the value of thrombectomy, especially in cases where the collateral circulation is strong.
Unfortunately I don't quite know what to make of the recurring phrase "mismatch between clinical deficit and infarct". Could anyone enlighten me, please?
When a clot blocks off blood flow to an area of the brain you expect that area to die and, as a result, lose its function (“clinical deficit”). The blockage is an infarct; the downstream area suffocating is infarcted.
When you look at the area of brain that should be downstream of a clot and therefore nonfunctional, that’s the “infarct volume”. It’s the volume of brain that we believe is infarcted.
The “mismatch” is when we do a CT, find that, say, the chunk of your brain that moves your right hand is downstream from the infarct, but your right hand is still working. This suggests that that part of your brain has enough blood coming to it from other, less salient, arteries that it’s dying slowly instead of fast.
That “mismatch” area is the one that, if we can go in and surgically pull out the clot, we can save.
+1. How does one come to such a conclusion if one is not a medically trained professional? I found your comment insightful, would you expand upon your own context to the topics of the article?
Research, just like anything else. Doctors have to know a ton about a wide spectrum whereas a guy with time and a computer can pretty much run through the state of clot treatment in a couple of days to weeks.
Here's an alternate and more informative headline for anyone who wants a bit more detail rather than clicking through and trying to skim for the needle in a digital haystack:
>>> "At 88, doctor pursues clot-busting medication combination to aid in treatment of heart attacks and strokes"
This is a much better title. Considering that the now favored course of action is surgery, a potent drug combo would be my choice. Once you start cutting, Docs often want to keep cutting.
Actually, its interventional cardiology for heart attacks and neurointerventional surgery/interventional neuroradiology(NIR) for strokes. (Not IR which cover non-neurological and non-cardiological interventional procedures).
I'm a NIR and most of us are not paid per surgery/intervention. Also these interventions tend to be loss leaders in terms of hospital reimbursements. Funding for stroke centres can be profitable but that's a very long discussion.
In addition, at least 7 randomized clinical trials have shown the benefit of thrombectomy in acute stroke (actually something of a modern medical technological miracle).
Almost anyone at a hospital or university setting is on salary.
Private practice can be another story, and perhaps there your argument would be more compelling. But many physicians, surgeons, specialist go into private practice to get out of bureaucracy, or, increasingly nowadays with providers who do not take insurance, to avoid the endless paperwork and hassling of insurance.
Most people get into medicine for the right reasons; to help other people.
I don't at all presume nefarious intentions. As if physicians don't try to make money. My original comment was a tongue in cheek defense of the status quo because I took offense at the comment that surgeons just like to keep cutting. Sure, I'm "just" a veterinarian, but I like to cut as little as possible.
I do know that doctors like to keep it moving. Surgeons like to start early and finish early. Nobody wants to get bogged down in a specific procedure. As far as profitability (or cost recovery, whatever euphemism) is concerned, doing several short procedures beats one longer procedure, even when surgery time is billed by the minute.
You ignore the fact that many doctors leave the strict employ of the hospital for a private practice that still bills through the hospital. While they are still salaried, they also get a profit share, usually divvied out on productivity. There is no one model. But you're right, I have no idea how it's typically done in IR, NIR, IC etc.
It's rarely up to the interventionalist if and when they will treat a stroke. There are clear guidelines on treating these patients (which mostly take place at comprehensive stroke centres), mostly defined by the neurology service, which functions somewhat independently. These guidelines have been expanding as newer evidence has shown a role in wider time windows but this point remains the same. There is very little opportunity for an individual interventionalist to increase his patient volume independently (at least for ischemic stroke).
I agree in principle with most of the points you make, although I think perverse incentives are largely a function of the US healthcare system in general rather than the domain of any particular specialty.
In specific relation to the original article, I'm extremely doubtful that combing two anti-thrombotic agents would be a miraculous therapeutic regime for treating stroke but I'd be happy to be proved wrong by a legitimate trial. However, I'd worry that we'd be sacrificing patients that could otherwise be treated if we assigned them to an arm of a trial that precludes established therapy.
Considering a large part of the story is about how he's not been able to get people interested or informed for decades, I think you dropped a useful bit of information.
In fairness, that was the lens the narrative played up. The other side is, “doctor pursues combination of two apparently shitty drugs for decades without anything but armchair hypothesis for support despite massively accumulating evidence that they suck independently, fails to garner attention/interest.”
He might be right, but I’d hesitate to lean too hard on the lone genius angle.
For me, it was the persistence of the researcher -- well into his ninth decade -- that caught my eye, rather than the somewhat arcane details of the thrombolytic therapy that he's been pursuing.
A strong sense of purpose seems to be a factor in health and longevity. Is it just good fortune that allows some people to develop that sense of purpose, or can it be consciously and effectively nurtured?
Travel is fairly trivial environmentally. Having a long commute by car is worse than traveling around the world by air every year which is extremely uncommon.
On average a passenger mile on a modern jet uses significantly less fuel than driving that same mile.
Erm no, since you don'r fly a plane for 5 miles usually. Plane flights are by nature long distance and consume way more than your yearly car consumption even if you have a 2 hours commute every day.
Sure, but it is reasonable to consider a long trip vs a longer commute in terms of lifestyle and environmental costs. At which point you care about total fuel costs not direct equivalency.
747 burns approximately 5 gallons of fuel per mile and holds 568 people. They are over 70% full on average which works out to:
568 x .7+ / 5 ~= 80+ MPG. At the equator the world is 24,901 miles ~= 300 gallons at worst though most most people consider around the world to be US > EU > Asia > US which is shorter than that.
On the other hand at 3 gallons (which is far from extreme) / day x 48 x 5 = 720 gallons ignoring all other driving.
PS: On top of that for longer trips aircraft tend to take more direct routes. You can't just drive from NY to LA on a strait line which significantly reduces cars effective MPG.
I found this data[0] care of The Guardian regarding pollution created per passenger mile. The GP said fuel per mile but the GGP was talking about pollution. It’s from 2009 so it’s likely in the right ballpark but not 100% accurate given the model of plane they used (737-400) has been largely replaced with newer/denser/more efficient models (737 Max 7/8/900 series) as have cars gotten more efficient. Basically, if you drive an SUV or high end sports car, you’re in the same ballpark as a full plane. If the plane is half full or you drive a small car, the car wins per passenger-mile (or km in this case).
Aircraft fuel efficiency has gotten dramatically better since 2009. Utilization is over 70%, wingtips added 3% fuel efficiency, plus slightly slower fights, and many older aircraft where retired during the spike in fuel prices.
I'm not suggesting driving instead of flying. I'm saying don't travel, which is a net reduction in fuel burned, regardless of one's daily commute situation.
what could be more fun than turning the earth into a smoking pit of despair to chase a few dopamine drips and satisfy evolutionary urges that are no longer adaptive?
Yes and No. Most of pre-and-during-WW2 leaders were well traveled, that did not prevent them from murdering each other for a pretty long time. The same can be said for current leaders, even the ones engaged in conflicts.
If you try it can be extremely cheap. For example, hitchhiking is free. Depends on the country of course in regards to safety. If you stay in youth hostels it's significantly cheaper than hotels, and you meet more people, etc.
At first I thought oh I guess the symptoms aren't as awful then I realized you interpreted the title differently from me... Wow yeah I guess they hit the title length limit for HN and had to get creative.
I seriously couldn't get past the first full page. Someone needed to give me an idea of what his treatment was. I love that he's old and still doing something. The comments here tell me it's somehow using heart attacks to treat strokes, but this thing had so much crap before giving me a detail I could process.
I hope he saves more people and lives to 120, but yeah, summary... or at least slightly better writing.
>What if tPA worked like the starter motor that turns on a car, and urokinase was the gasoline that ran it?
No comment on the underlying science, but I will express my continued frustration with popsci writers and their counterproductive analogies. It's especially unhelpful when it's wrong on the dumbed-down end. A starter motor does not run on gasoline. It's an electric motor that runs off the battery.
That's the whole point of the analogy. From the next paragraph:
> When a clot forms, tPA in the bloodstream is quickly recruited to the site to begin dissolving it. But too much of a clot-buster could lead to bleeds, so once the process is sparked, the body rapidly clears out tPA. Urokinase comes along, carried on the surface of platelets and certain white blood cells, to finish the job.
tPA kicks off the process, and once it's started, urokinase does the rest. I don't know the biochemistry in enough detail to say whether this is a really good metaphor (can urokinase only be activated if tPA has acted? is urokinase consumed by this process?), but the author is not suggesting that a starter motor runs off gasoline.
Once a clot has matured they tend to be useless, which is part of why there’s a solid upper cap on time to administration. You cross a line where any clot they’re likely to bust isn’t one you want to bust. So, a window of a couple of hours. Urokinase doesn’t change that, to my knowledge.
Surgical removal of the clot, on the other hand, has recently been shown to offer enormous benefit to at-risk tissue (tissue not yet dead but in the watershed area) 24 hours later, without risk of hitting the wrong clot. It’s no miracle either, but evidence is piling up that it’s got more Pros and fewer Cons.
Thus, no one really following armchair hypotheses (one old non RCT trial not withstanding) about combining two increasingly undesirable drugs.
I respect the guy’s thought and effort, and have to admit he might be right about their combined effectiveness, but this article leaves out a lot of the context as to -why- this isn’t getting attention. Writing a hagiography-by-omission is below what I’ve come to expect from statnews.