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Administering immunotherapy in the morning seems to matter. Why?

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Re: Administering immunotherapy in the morning seems to matter. Why?

#111

Post by echelon »

cannonpr wrote: post #88
echelon wrote: post #78

Earlier quoted context omitted.

We've been able to clone mammals for 30 years and haven't acted on it. We're still toying with molecular systems beyond the limit of detection. Clone humans. Cut off their brain stem during development. Turn off cephalization signals for good measure. Scale it up to industrial scale. Research problems solved. We'd have every study at our fingertips. We'd have organs and tissue and blood for everyone. We could possibl…

You might be surprised at how little of the body still functions without brain function, well, some bits of the brain, including basic homeostasis and immune system function.

We're not at all trying.

If you toss out the old rule book and provide unlimited funding, it can be made to work.

Re: Administering immunotherapy in the morning seems to matter. Why?

#112

Post by dotancohen »

vlovich123 wrote: post #93
_qua wrote: post #65

Earlier quoted context omitted.

Even simple studies are expensive and difficult. You need IRB approval, data collection and organization, staff to do those things. It seems simple from the outside but making it happen takes time, effort, and money which then means also applying for grants which is a process in and of itself.

If a study like this needs a complicated IRB approval or extra data collection vs what’s already being collected for health records, you’re doing it wrong and the process has become more important than the problem you’re trying to solve.

  > the process has become more important than the problem you’re trying to solve.
This holds true in almost every professional field for which life is on the line. Medicine, class 3 electronics, aviation.

We have a word for this, which roughly translates to "rule of paperwork". Bureaucracy.

Re: Administering immunotherapy in the morning seems to matter. Why?

#113

Post by rendaw »

iamtheworstdev wrote: post #24
rendaw wrote: post #6

I'm doing CedarCure. You're required to not exercise or bath/shower for 2h after taking, which is fairly difficult in the morning, so I asked the doc if I could do it in the evening instead (despite explicit instructions to do it in the morning). The doc said it was fine, confirmed by the pharmacist. I should know better by now than to trust doctors to act based on research and not gut feeling, but I hope this doesn'…

a brand new study comes out and you're mad the doctors didn't know about it a year ago? do you carry any of the blame on yourself since you knew there were explicit instructions but apparently waiting to shower or exercise was too much of an inconvenience for you?

If the medicine instructions didn't state that they should be taken in the morning it might be reasonable, but presumably the producer had some reason for including that instruction. Furthermore, the linked study implies that this effect was suspected before but not confirmed - it's possible and even likely that the CedarCure makers knew this and specified the instructions as such.

> There’s a really interesting phenomenon in the immunotherapy field that has been going on for what seems to be several years now

> All of this culminated in a really incredible review paper

(review paper references papers from multiple years prior)

And no, it's absurd to imply I do carry blame here. I'm not a medical professional and that's exactly why I asked two specialists for help understanding the criticality of the instructions... that's the point. Even if they didn't know, they could have deferred to the written instructions rather than coming up with an original conclusion.

Re: Administering immunotherapy in the morning seems to matter. Why?

#114

Post by [deleted] »

abhishaike wrote: post #45
zevets wrote: post #2

This is bad science. Patients schedule when they go to immunotherapy appointments. People who go in the morning are still working/doing things, where once you get _really_ sick, you end up scheduling mid-day, because its such a hassle to do anything at all.

Writer of the article here: randomization fixes most of this, but the other commenters are correct in that doesnt fully account for the clinic performance (e.g. nurse performance, which does dip during the night according to the literature). I previously thought it wasn't a major issue for clinical trials, since a separate team independent from the main ward are giving the drugs, but there isn't super strong evidence…

[deleted]

Re: Administering immunotherapy in the morning seems to matter. Why?

#115

Post by willguest »

echelon wrote: post #110
nothrabannosir wrote: post #102

Earlier quoted context omitted.

This comment, more than any other, has sold me on the value of red tape in medical research.

Our genome is a machine, from the nucleotides to the packing, to the enzyme activity, to the metabolic flux. Our bodies are bigger machines made of lots of little machines. Our minds or conscious egos or "souls" are the neurotransmitter and activation activity of the connectome and all of its cells and synaptic weights and metabolic activity. They're our lived experiences for as long as our brains can function. Minds…

My guess is that you're either a dev or an orthopaedic surgeon, well-versed in managing the machinistic aspects of systems, but with little motivation to go beyond them.

There is decent experimental evidence to demonstrate that we are more than gene expression and the machine analogy you insist on is not a good one for understanding biological systems - see work by Michael Levin, as example.

There is a wider paradigmatic shift underway that moves from thinking about parts to processes. This refocus on relations rather than objects is very important and, for biological systems, points to a fundamentally social/collective aspect to their nature.

The machine metaphor also fails when you can no longer explain how the machine works. This is true in many areas of medicine (e.g. anasthesia) and, while we continue to believe (sometimes with enormous zeal) in the concepts that helped us in the past, we cling to them at the cost of building better understanding.

What you say isn't "wrong", but it is too limited to be a useful guide in asking new questions about things like immunotherapy treatments.

Re: Administering immunotherapy in the morning seems to matter. Why?

#116

Post by trhway »

levocardia wrote: post #91
trhway wrote: post #52

Earlier quoted context omitted.

>some other variable that incidentally varies by time of day. glucose level? low in the morning, and cancer likes glucose (among other effects of low glucose a cancer site would probably have lower local acidity, and the high local acidity is one of the tools used by cancer to protect and spread itself) .

AM/PM glucose differences are probably going to be swamped by mundane stuff like who has a snack before treatment vs. who doesn't. Are you not supposed to eat before immunotherapy? If so, maybe (non)compliance with that requirement is what's underneath.

i'd think the local acidity (build up of lactic acid resulting from glucose over-consumption by the cancer cells) would take a bit to build back up once glucose ups after the night.

Re: Administering immunotherapy in the morning seems to matter. Why?

#117

Post by vkou »

vlovich123 wrote: post #94
vkou wrote: post #70

Earlier quoted context omitted.

Its not easy to ask if it messes with staff scheduling.

Clearly they did it for one patient and it was a good result. Doctors and staff generally care about their patients and given there’s plausible scientific reasoning why this worked, they’d help figure out how to make staffing work for 3-5 more patients for a limited time. Additionally, positive results like this start to travel by word of mouth so if this is successful it means more funding for the hospital and more…

In any medical system in the world, you'll find that staff scheduling is the singular, most important constraint for patient care.

That they did it for one patient does not mean that they can do it for everyone - especially when it's not clear if it actually helped, due to a small sample size.

Re: Administering immunotherapy in the morning seems to matter. Why?

#118

Post by vkou »

renewiltord wrote: post #98
_qua wrote: post #65

Earlier quoted context omitted.

Even simple studies are expensive and difficult. You need IRB approval, data collection and organization, staff to do those things. It seems simple from the outside but making it happen takes time, effort, and money which then means also applying for grants which is a process in and of itself.

Indeed, as any ethicist worth his salt would argue: we don’t want anyone saving lives without proper approval.

Any ethicist worth your salt would presumably have no problem approving experiments that will also cost lives.

There are an endless number of parameters in medicine that can be fiddled with. If an N=1 sample were enough to convince you, all sorts of garbage would meet that pattern.

Re: Administering immunotherapy in the morning seems to matter. Why?

#119

Post by agumonkey »

EricPhy wrote: post #100

“Let’s pretend you have very early-stage cancer. The dendritic cells are in their normal cycle of desperately presenting tumor fragments to T cells, the T-cells rightfully getting upset, activating themselves, and going off to hunt the cancer. But cancer simply shuts them down by expressing an immune blocker protein: PD-L1. In response, the T-cell mostly shuts down, wanders back to the lymphatic system, and gets a li…

Yeah, so many things use the same memory response curve to adjust their behavior, but that model can fail rapidly in these conditions. Very interesting to read though.

Re: Administering immunotherapy in the morning seems to matter. Why?

#120

Post by OrderlyTiamat »

They changed the study target effect (which hour range), design (interventional vs observational) and inclusion/ exclusion criteria multiple times.

I don't really care at that point what their conclusion says, because I have no idea how to interpret the statistics in a theoretically sound way now.

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