Tag: medicine

Medical records failure

Because stupid people demonize managed care, and the standardization benefits can thus not be reaped across the board.
2015-07-11: Coding is crazy.

I was not able to verify the existence of an ICD-10 code for falling from a non-military spacecraft, but there certainly is an ICD-10 code for being burned due to water-skis on fire

2015-07-23: Until this is fixed, we can’t have nice things. The recent progress with open access journals is a tiny first step, but it’s still not common to attach your raw data to your study for easy replication, or to to publish negative results.

So some of the results of this individual trial shifted, under closer examination, and that is definitely problematic. But fundamentally there is only one thing different about this deworming trial and the rest of social science and medicine: Miguel and Kremer had the decency, generosity, strength of character, and intellectual confidence to let someone else peer under the bonnet.

This kind of statistical replication is almost vanishingly rare. A recent study set out to find all well-documented cases in which the raw data from a randomized trial had been reanalysed. It found just 37, out of many 1000s. What’s more, only 5 were conducted by entirely independent researchers, people not involved in the original trial.

2015-10-25: Epic is benefiting greatly from the lock-in it has created.

instead of ushering in a new age of secure and easily accessible medical files, Epic has helped create a fragmented system that leaves doctors unable to trade information across practices or hospitals. That hurts patients who can’t be assured that their records—drug allergies, test results, X-rays—will be available to the doctors who need to see them. This is especially important for patients with lengthy and complicated health histories. But it also means we’re all missing out on the kind of system-wide savings that President Barack Obama predicted nearly 7 years ago, when the federal government poured billions of $ into digitizing the country’s medical records.

2020-04-20: And then we have the usual problems with IRB / EMR

If you want to report the number of times a patient has cut her nails in the last week, you would need approval. And it’s not easy at all to search the EMR for any of this information. You’d have to hire someone specifically to look through it.

“Why are nearly all notes in Epic . . . basically useless to understand what’s happening to patient during hospital course?” Another doctor’s reply: “Because notes are used to bill, determine level of service, and document it rather than their intended purpose, which was to convey our observations, assessment, and plan. Our important work has been co-opted by billing.”

2020-04-22: The software is only designed for billing, not evidence.

Electronic health record software in the US is not set up to make clinical research faster and easier. We have billing claims as, absurdly, our only reliable and easily integratable national source of raw patient data. What we don’t have is anything useful to produce evidence-based medicine.

2020-04-27: EMR might not capture what matters

Is this loose, informal transmission of anecdotal findings—call it chatter, call it rumor—part of medicine? It isn’t what anyone is taught in medical school; it doesn’t fit in with the professional’s image as a purveyor of rigorously tested interventions. But continuous, iterative clinical knowledge—the kind that can be updated minute by minute—is invaluable during this tumult, when time is of the essence and there’s scant research to fall back on.

2023-07-30: Clinical trials keep getting more expensive due to regulatory capture, lack of competition, and luddite tendencies. Vial might do an end run around this if they don’t get stopped by the enemies of progress

Instead of dealing with the difficulty of collecting data on new medicines, both society and government sidestepped it by focusing on treatments for much rarer illnesses: relatively rare cancers, rheumatoid arthritis, and multiple sclerosis to name a few, not to mention very rare illnesses such as cystic fibrosis or paroxysmal nocturnal hemoglobinuria. The North Star for Vial is to drive a 10x improvement in both the speed and cost of clinical trials. This can sound hyperbolic, but it is likely not impossible, given the massive inflation of trial costs over the last 50 years. In the bull case for Vial, the development of TrialOS would enable companies to pursue 10x as many drug candidates in parallel. This would open the aperture for drug development, giving emerging companies more breathing room in pursuit of their first clinical success.

Vial has now had a front-row seat to 10s of trials. They’ve seen the product features that trial sponsors have adopted and shied away from. Their electronic tablets and eSource solutions have been welcomed with open arms. On the other hand, their remote data capture solutions—which could make the difference between a 2-3x cost reduction and a 10x cost reduction—have been less widely adopted so far.

What if they could aggressively dogfood the most cutting-edge features of their platform? This could further accelerate reductions in trial speed and costs and open the door to massive value capture. Taken individually, no part of their stack is groundbreaking. There is fierce competition to innovate within in silico drug discovery. Organoids are not new technology. Faster chemical synthesis won’t spark a revolution on its own. The fundamental insight is that integrating each part together will give Vial a chance to exploit their true advantage: faster and cheaper trial execution.

2023-07-31: HIPPA is one of the enemies of civilization.

The path forward is therefore clear. We should be doing more to get more data into the hands of more researchers. Unfortunately, we have laws and regulations surrounding privacy that make that extremely difficult. Reform in this area would do a great deal to advance progress in the fields of science, medicine, and health. Privacy concerns also stand in the way of attempts to make healthcare more affordable. The privacy advocates have 2 arguments:

  1. Someone might make a profit while they’re curing disease
  2. We shouldn’t even try to achieve any more medical progress until we achieve socialism

These objections are almost too silly to refute, but I’m including them because it’s useful to understand the irrational motivations of many privacy advocates.

Medicine stagnation

Opportunities to develop cutting edge medical practices are fast disappearing in the United States. When it comes to developing a new, improved way to treat patients, he can do it “quicker, develop it better, and have the ingredients to really take it much further” than he could in the same amount of time in the US Here, he can combine his clinical practice with scientific research and technological development, all at a breakneck pace. Clinical research and translational research is down 70% in the US

First, he blames “the lobbies, restrictions, confidentiality problems, insurance companies regulating what needs to be done, what can be done, what cannot be done…the usual ambulance chasing that occurs.” In the US there’s too much red tape.

Second, there’s an “inhibition of intellect coming together.” Because “provisions for funding are few and far between,” there is a huge amount of “talent divided among 200 universities” that don’t always collaborate.

us medical research too risk averse. and that does not even factor in the bible thumpers yet

Retirement tourism

Norway is now “exporting its elderly and infirm to the Costa Blanca” of Spain to save money on retirement costs. Essentially, a welfare state is exporting its citizens and its services to a place with lower labor rates, cheaper land, and better weather.

How long before national health systems in Europe open their own clinics in Africa, or American insurance companies buy up a few hospitals in Costa Rica?

Antibiotics

For all you antibacterial soap-using dummies.

Unlike (soap and other) traditional cleaners, antibacterial products leave surface residues, creating conditions that may foster the development of resistant bacteria. Alcohol-based hand sanitizers are just about as effective against germs as soap and water. They’re also easier on your skin than hand-washing, and unlike antibacterial soaps, they don’t breed antibiotic-resistant superbacteria.

The bottom line is that you shouldn’t live in fear of high-traffic surfaces. This type of contact simply isn’t the way people get sick.

2010-11-08: We are essentially back to an era with no antibiotics

This new resistance pattern has been reported in many different types of bacteria compared to previously and 10% of these NDM1-containing strains appears to be pan-resistant, which means that there is no known antibiotic that can treat it. A second concern is that there is no significant new drug development for antimicrobials.

2015-01-08: New Antibiotics Platform?

A lot of people have had similar ideas to this one, based on the fact that the overwhelming majority of bacteria in any given environmental sample can’t be readily cultured. These organisms may well be able to produce useful antibiotics and other natural products, but how will you ever be able to tell if you can’t fish any of them out? Using this on a soil sample from Maine and leaving the chip in situ for a month, a number of colonies formed. These were tested for their ability to grow outside the device in fermentation broth, and extracts of these were tested against pre-grown lawns of an S. aureus strain to look for useful antibiotic activity. Lo and behold, one extract cleared out a large spot – it turned out to come from a newly described bacterium (Eleftheria terrae, provisionally). The compound present has been named teixobactin, and here it is. So how useful is the compound? It’s active only against gram-positive organisms, which is too bad, because we could really use some new gram-negative killers (their cell membranes make them a tougher breed). But the mechanism of action turns out to be interesting: studies of S. aureus with labeled precursors showed that teixobactin is a peptidoglycan synthesis inhibitor, but extended exposure and passaging did not yield any resistant strains. That’s close to impossible if an antibiotic is binding a particular protein target – stepping on the selection pressure will usually turn up something that evades the drug. When you don’t see that, it’s often because there’s some nonspecific non-protein-targeted mechanism, which can be problematic, but teixobactin isn’t toxic to eukaryotic cells in culture (and has a favorable tox profile in mice as well). It turns out that it binds to some of the peptidoglycan precursors, lipid II and lipid III. Vancomycin has a similar mechanism (binding to lipid II), but teixobactin has a wider spectrum of activity against lipid II variants (and lipid III as well). This mechanism makes developing resistance not so straightforward – the selection pressure is more of a bounce shot than a direct hit.

2015-02-24: Antibiotics market failure

we seem willing to pay $100K or more for cancer drugs that cure no one and at best add weeks or a few months to life. We are willing to pay 1$0Ks for knee surgery that, at best, improves function but is not lifesaving. So why won’t we pay $10K for a lifesaving antibiotic?

2015-03-31: Medieval salve kills MRSA. Impressive! Not all ancient medical knowledge is homeopathic nonsense.

Take cropleek and garlic, of both equal quantities, pound them well together… take wine and bullocks gall, mix with the leek… let it stand 9 days in the brass vessel

So goes a 1000-year-old Anglo Saxon recipe to vanquish a stye, an infected eyelash follicle. If the 9th Century recipe does lead to new drugs, they might be useful against MRSA skin infections such as those that cause foot ulcers in people with diabetes. These are usually antibiotic-resistant

2016-01-23: Antibiotics synthesis

Antibiotics are generally synthesized in nature by bacteria (or other microbes) as defenses against each other. We have identified antibiotics in the lab, and thus necessarily only those made by bacterial species that we can grow in the lab. Almost all bacterial species cannot be grown in the lab using practical methods. That hasn’t changed for decades. But those bacteria grow fine in the environment, typically the soil. So… can we isolate antibiotics from the soil?

2018-05-21: Phage Therapy

3 months earlier, Patterson had suddenly fallen ill, so severely that he had to be medevaced to Germany and then to UCSD. There were several things wrong—a gallstone, an abscess in his pancreas—but the core of the problem was an infection with a superbug, a bacterium named Acinetobacter baumannii that was resistant to every antibiotic his medical team tried to treat it with. Patterson was wasted, his cheekbones jutting through his skin. Intravenous lines snaked into his arms and neck, and tubes to carry away seepage pierced his abdomen. He was delirious and his blood pressure was falling, and the medical staff had sedated him and intubated him to make sure he got the oxygen he needed. He was dying. … “We are running out of options to save Tom. What do you think about phage therapy?”

2019-11-04: CRISPR Antibiotics

An alarming number of bacteria are now resistant to one or more antibiotics, so this new line of inquiry would certainly be welcomed if it proves effective.

In their recent study, Dr. Edgell and his colleagues successfully used a Crispr-associated enzyme called Cas9 to eliminate a species of Salmonella. By programming the Cas9 to view the bacterium itself as the enemy, Dr. Edgell and his colleagues were able to force Salmonella to make lethal cuts to its own genome.

As we discover more of the benefits of our microbiota, it would also be interesting to have a solution to bacterial infections which doesn’t create problems for our “good bacteria.

2020-02-22: Antibiotics ML

So overall, this is an impressive paper. The combination of what appears to be pretty rigorous ML work with actual assay data generated just for this project seems to have worked out well, and represents, I would say, the current state of the art. It is not the “Here’s your drug!” virtual screening of fond hopes and press releases, but it’s a real improvement on what’s come before and seems to have generated things that are well worth following up on. I would be very interested indeed in seeing such technology applied to other drug targets and other data sets – but then, that’s what people all around academia and industry are trying to do right now. Let’s hope that they’re doing it with the scope and the attention to detail presented in this work.

2020-07-24: SCH-79797

Researchers have found a compound, SCH-79797, that can simultaneously puncture bacterial walls and destroy folate within their cells — while being immune to antibiotic resistance. This is the first antibiotic that can target Gram-positives and Gram-negatives without resistance

2020-08-07: Maybe the non-profit route will work

If something isn’t done now, antibiotic-resistant bacteria could kill as many as 10M people a year by 2050. A little-known Boston nonprofit could be our best hope.

2021-07-28: Biofilms are nasty

This discovery underscores how important it is to include biofilms in any studies of antibacterial compounds because being able to kill planktonic cultures bears no relation to being able to break down biofilm.

2021-10-14: Another approach is to modify bacteria to destroy the MSRA biofilms

Bacteria present a promising delivery system for treating human diseases. Here, we engineered the genome-reduced human lung pathogen Mycoplasma pneumoniae as a live biotherapeutic to treat biofilm-associated bacterial infections. This strain has a unique genetic code, which hinders gene transfer to most other bacterial genera, and it lacks a cell wall, which allows it to express proteins that target peptidoglycans of pathogenic bacteria. We first determined that removal of the pathogenic factors fully attenuated the chassis strain in vivo. We then designed synthetic promoters and identified an endogenous peptide signal sequence that, when fused to heterologous proteins, promotes efficient secretion. Based on this, we equipped the chassis strain with a genetic platform designed to secrete antibiofilm and bactericidal enzymes, resulting in a strain capable of dissolving Staphylococcus aureus biofilms preformed on catheters in vitro, ex vivo, and in vivo. To our knowledge, this is the first engineered genome-reduced bacterium that can fight against clinically relevant biofilm-associated bacterial infections.

2023-05-23: Odd that phage therapy only made progress in former soviet republics

“Phages” are little known outside the former countries of the Soviet Union, which did the most to develop the idea. In Georgia they have been part of the local pharmacopoeia for decades. (Indeed, 2023 marks the Eliava’s centenary.) Little vials containing stale-tasting liquid full of anti-bacterial viruses can be bought at pharmacies across Tbilisi. Now, as worries about antibiotic resistance build, Western firms are taking a second look.

Surgical Robots

The insertion of self-assembling, remote-controlled surgical robots into the body. During insertion these devices are cylindrical but they then unfurl 2 arms for grasping and cauterising, and 2 cameras to give the surgeon stereoscopic vision.

robotic surgery is here, and rapidly improving.

that looks pretty intense. perhaps it will turn surgery into more of a science, with fewer fatal errors.

Da Vinci robots have dramaticaly increased surgeon skill. Augmented medicine is here, sadly only in very localized ways

radiologists can use real-time MRI images to guide the movement of their robotic assistant, which will provide unprecedented accuracy: “The patient lies inside the MRI scanner and the robot accesses the prostate through the perineal wall”

it’s still slower but that will be fixed quickly.

Can a robot handle the slippery stuff of soft tissues that can move and change shape in complex ways as stitching goes on, normally requiring a surgeon’s skill to respond to these changes to keep suturing as tightly and evenly as possible? The robot surgeon took longer (57 minutes vs. 8 minutes for human surgeons) but “the machine does it better”. The procedure was 60% fully autonomous and 40% supervised but it can be made fully autonomous.

2021-08-31: A few reasons this has been slow to arrive:

  1. Telerobotics is as worth paying attention to as the heavy-weight topics in this workshop like climate change or aging.
  2. Telerobotics is a tool to give people god-like abilities, not a subset of robotics that will be subsumed by advanced AI.
  3. Despite decades of work and sweet demo videos, telerobotics is not a ‘solved’ problem.
  4. Without intervention, general purpose telerobotics may never come to fruition. On the flipside, it’s possible to intervene with a coordinated research program so that it does.
  5. We can take a definite approach towards these interventions by designing ARPA-like programs to coordinate and fund this work.

Suspended Animation

These strange tales hint at what was, until quite recently, an underappreciated facet of our nature. Humans, it seems, can hibernate.
2014-03-27: Using torpor to improve ER survival odds

We’ve always assumed that you can’t bring back the dead. But it’s a matter of when you pickle the cells

2014-05-09: Torpor is more common than we thought

For a long time, there was no evidence that primates could hibernate. A species of Madagascan lemur was shown to practise regular bouts of torpor. “If you look at the lemur and look at us, we share 98% of our genes. It would be very strange if the tools of hibernation were all packed into that 2% difference.”

2020-06-13: Rats have it too

2 research groups had markers in the brains of rats which they used to identify the neurons that triggered torpor. They then just activated those neurons to turn on the torpor state. Torpor is a weaker version of suspended animation. However it is 2x as efficient as sleeping or resting.

2023-05-25: Perhaps induced via ultrasound

In response to a series of 3.2-megahertz pulses, the rodents’ core body temperatures dropped by about 3°C. The mice cooled off by shifting body heat into their tails—a classic sign of torpor—and their heart rates and metabolisms slowed. By automatically delivering additional pulses of ultrasound when the animals’ body temperatures began to climb back up, the researchers could keep the mice in this torpid state for up to 24 hours. When they silenced the minispeakers, the mice returned to normal, apparently with no ill consequences.

Microbiome

Human microbiome program?

Because of the importance of beneficial / commensal microbes in human biology, there have been growing efforts to characterize the microbes in various body locations – gut, mouth, lungs, skin, etc. But the efforts so far have simply given a tantalizing taste of how interesting and important these microbes are. So here comes this meeting. Organized by NIH (specifically, Francis Collins at NHGRI), this workshop is geared to discuss the possibility that studies of the human microbiome will be included in the next list of “NIH Roadmap” programs. More on the NIH Roadmap some other time.

Basically, the general idea is – do we need an big scale, organized program to tackle the human microbiome.? To get us in the mood, we had talks by many of the pioneers/leaders in the field (e.g., David Relman, Jeff Gordon, Jim Tiedje) as well as discussion of the NIH Roadmap program. I personally did not need any convincing but it was good to hear some of the ideas presented. In the end, I think there is no doubt that a large scale Human Microbiome Program is needed and would be very beneficial.

In addition to the 10 trillion human cells, there are 100 trillion bacterial cells in a body. Our metagenome may be 100x the human genome.
2010-10-30: Space Standard Microbiome. Venter suggests NASA should replace the microbiome (bacteria species) of astronauts with a standardized, synthetic one to improve survivability of space flight.
2012-06-15: 0.3% Human

Where the human genome carries some 22K protein-coding genes, the human microbiome contributes some 8M protein-coding genes responsible for human survival: 360x more.

The microbiome is one of the most fascinating areas in biology:

in many mammals a microbial community ferments various sweats, oozes and excretions into distinctive scents that reveal age, health and much more to knowing noses in a select social circle.

That’s right, microbes are posting status updates to each other through smells, sharing with other microbes what they’ve learned about host animals.
2012-12-08: American Gut looks amazing. I will of course participate. Since you are only 10% human (the rest is bacteria), even if you do 23andme you don’t really know yourself at all. $99 for 1 bacterial DNA kit, $180 for 2. There are also higher levels, up to the $25k ultra-deep sequencing of your microbiome sample aimed at generating as many individual bacterial genomes as possible.
2015-03-03: a nice summary of The American Gut project

2016-10-01: Poop Bot. As usual, onion’s satire is leading the way:

you can tell the most about someone by sampling their microbiome, and “the sewage system is the great aggregator.” Gross, sure, but Ratti is studying waste to understand everything from heroin use to antibiotic-resistant bacteria—and all with the help of a sewer-slurping robot named Luigi.

2017-09-05: Microbiome 99% unknown

A survey of DNA fragments circulating in the blood suggests the microbes living within us are vastly more diverse than previously known. In fact, 99% of that DNA has never been seen before. The “vast majority” of it belonged to a phylum called proteobacteria, which includes, among many other species, pathogens such as E. coli and Salmonella. Previously unidentified viruses in the torque teno family, generally not associated with disease but often found in immunocompromised patients, made up the largest group of viruses.

2018-10-03: SynBioBeta 2018

In 15 years, brain interfaces will be as common as the cell phone. The radical experiment that has been run over the past 100 years shifting the microbiome of infants and provoking a wide array of immune disorders (allergies, asthma, diabetes)

2019-08-07: Microbiome Friendships?

Now that it is clear that social behavior plays a role in shaping the gut microbiome, the next question is whether microbiomes have had a meaningful impact on our social worlds. Scientists still do not have an answer, but they are tantalized by the possibilities, which could have implications for understanding the evolution of sociality.

2019-12-04: Microbiomes Affect Fear

microbiomes can influence the fear responses of their hosts, possibly by releasing compounds that affect the brain’s neuroanatomy and function.

2022-02-22: Space microbiome

Humans aren’t the only organisms that we have to consider when evaluating the impacts of space travel. While we are traveling on spaceships, microbes are traveling on us. Microgravity has been shown to alter bacterial growth patterns and kinetics, and radiation increases the frequency of mutations—in both cases creating opportunities for increased antimicrobial resistance—all in an environment where astronauts immune systems are compromised. The ISS has a complex microbiome that we fundamentally alter, and that in turn alters us. It’s important to be able to understand the genetic basis of antimicrobial resistance in space. A team of researchers carried out a study with the goal of addressing this question. A considerable number of AMR genes were found in several different locations for Kalamiella piersonii—a microbe potentially involved in causing urinary tract infections. Worryingly, “the potentially very pathogenic microbe E. bugandensis was found in location 2 (forward side panel wall of the Waste and Hygiene Compartment) in flight 1, presenting more than 40 ARGs.” They were also able to detect specific types of potential drug resistance for several microbes within the Pantoea species—which provided a higher level of resolution into observations made in their past analysis.

2023-01-19: person-to-person transmission

Mother-to-infant gut microbiome transmission was considerable and stable during infancy (around 50% of the same strains among shared species (strain-sharing rate)) and remained detectable at older ages. By contrast, the transmission of the oral microbiome occurred largely horizontally and was enhanced by the duration of cohabitation. There was substantial strain sharing among cohabiting individuals, with 12% and 32% median strain-sharing rates for the gut and oral microbiomes, and time since cohabitation affected strain sharing more than age or genetics did.

2023-05-04: Using dental plaque to reconstruct the oral microbiome

Reconstructing an oral microbiome—a soup of 100s of different bacterial species, and millions of individual bacteria—from degraded ancient DNA is “like throwing together pieces of many puzzles and trying to solve them with the pieces mixed up and some pieces missing entirely”.

It took 3 years to adapt DNA sequencing tools and computer programs to work with the much shorter fragments of DNA found in ancient samples. Drawing on dental calculus from 46 ancient skeletons—including a dozen Neanderthals and modern humans who died between 30k and 150 years ago, Warinner identified DNA from 10s of extinct or previously unknown oral bacteria.
Identified as a type of bacterium called a chlorobium, its modern relatives use photosynthesis to survive on small amounts of light and live in anaerobic conditions, such as stagnant water. They aren’t found in modern mouths and appear to have vanished from ancient humans 10 ka BP. This chlorobium might have entered the mouths of ancient people because they drank water in or near caves. Or it might once have been a normal part of some people’s ancient oral microbiome, surviving on faint light penetrating the cheek.

2023-06-08: Sample handling ruins many studies

The authors have tried all sorts of sample-handling variations, and it looks like they have had trouble finding any that don’t change the composition of the microbial samples themselves. Both papers investigated the 2 commercially available stool sample kits (OMNIgene and Zymo), and found that the latter was much more sensitive to temperature variations on storage. And both kits changed the absolute levels of various bacteria types: the OMNIgene-preserved samples had significantly higher amounts of Bacteroidetes species as compared to preservative-free controls, while the Zymo-preserved ones had significantly lower amounts. The second paper also finds that the method used for cell disruption can significantly affect the ribosomal RNA reads used to characterize the bacterial species as well.

Researchers in the field should also be measuring total bacterial load in their samples and monitoring that for signs of variability in their sample handling and people should standardize on 25 PCR cycles, because that can also change things. These effects can help explain the widely varying literature results in human microbiome studies.