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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?

#141

Post by lofaszvanitt »

_qua wrote: post #89
xvector wrote: post #87

Earlier quoted context omitted.

I am close with a few folks in medical research and the broken nature of the system and sheer amount of red tape has broken their dreams. It is impossible to get anything done. There is a difference between "reasonable guardrails" and suffocating progress until it's nearly impossible barring Herculean efforts by multibillion dollar entities. It cannot be understated how badly the current bureaucracy has destroyed med…

I don’t disagree but the guy below you wants to grow human shells and try head transplants.

good! old, dinosaur like systems need to be forgotten already.

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

#142

Post by vibrio »

vhanda wrote: post #3
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.

From the article - > this paper was not a retrospective study of electronic health records, it was a randomized clinical trial, which is the gold standard. This means that we’ll be forced to immediately throw away our list of other obvious complaints against this paper. Yes, healthier patients may come in the morning more often, but randomization fixes that. Yes, patients with better support systems may come in the m…

"Forced to throw away" biases is strong. If run well, RCTs surely help manage potential biases, but it does not eliminate them. The slides saw available on X-itter didn't show a Consort diagram (accounting of patient count between screening and endpoint) or the balance of patent characteristics between the arms. This seems to be a single site study, which is significant caveat IMO. The lack of substantial mechanistic explanation, and alleged study redesign mid-stream are also caveats. All that said the reported effect is very large, and I'd like to see a more detailed reporting and analysis. If the effect that size is real, it should be able to be found in some relatively quickly retrospective studies (yes, many caveats there, but that could probably provide very large numbers rapidly in support of the RCT).

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

#143

Post by s1mplicissimus »

tl;dr

Administering immune system related drugs in the morning improves success rate. This is because the immune system is more receptive in the morning, due to evolutionary adaptation. The authors even seem to have isolated the gene sequence that leads to the "sensor" which generates the necessary "data" for the immune system to optimize on.

Really cool research imo

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

#144

Post by vrc »

raverbashing wrote: post #99
AbrahamParangi wrote: post #68

Earlier quoted context omitted.

The razor to use to determine whether something is actually evidenced based under uncertainty is whether you would follow the same policy if it was your own child. There are many things that are simply uncertain and “untrue until proven otherwise” isn’t an exclusively optimal policy.

It's ok, the strongest defenders of EBM are never going to discover anything worthwhile as they get caught in a loop of "no evidence enough to test" and "no evidence for this because nobody tests it"

Counterpoints: the detractors of this purported loop would likely neither fund the vast amounts of research they’d demand be done nor believe the results if they conflicted with their anecdata. I have yet to see a good faith argument against evidence based method that provides an effective and realistic alternative. Because that would take evidence.

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

#145

Post by owenthejumper »

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.

What happens if your study clearly hurts people? What happens if your study clearly helps people? You find out in the first few weeks, what do you do? How do you ensure you collected enough of a sample of a general population to make your study representative? How do you ensure your patients properly consented to the study (past shameful human experiments aside, you likely need many institutions participating, so you can't control everything yourself).

Do I keep going or is the IRB approval process clearer now? There is a reason it exists.

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

#146

Post by NiloCK »

vkou wrote: post #55
sixo wrote: post #50

Earlier quoted context omitted.

Amazing. And shameful (for them.)

> And shameful (for them.) 1. A single positive outcome with N=1 should generally not be the basis for making a medical recommendation. 2. It takes a mountain of research work to go from that to a study that you can draw meaningful conclusions from. 3. The hospital is not in the business of doing research, it's in the business of treating patients.

1. The N=1 positive result isn't the sole basis for expanded effort. The basis the is the compelling, research backed, causal mechanism that predicted the scheduling adjustment's success.

2. Does it? Speaking directly out of my butt here (not in healthcare, not an academic), but the OP spoke of pretty acute symptoms specific to a treatment plan. If the treatment program is at all common, then a very straightforward A/B split of non-intervention / intervention.

Heck, even a questionnaire of past patients cross-referenced with historical records of appointment times could go a long way to validate the hypothesis.

3. This degree of specialization is for insects. If literal MDs in the field are too atomized to even surface research proposals, then that feels like an awful waste of edge-research capability.

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

#147

Post by echelon »

uselesswords wrote: post #139
calf wrote: post #97

Earlier quoted context omitted.

"Evidence-based" is a really problematic term when it is used to protect bureaucracies and medical managerialism, rather than actually interact with scientific processes in an ethical way. Their anecdote is actually a good example of why evidence-based logic is not the end-all.

[flagged]

Barry James Marshall

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

#148

Post by jcims »

raylad wrote: post #48

My father was on chemotherapy with fludarabine, a dna base analog. The way it functions is that it is used in DNA replication, but then doesn’t work, and the daughter cells die. Typically, patients who get this drug experience a lot of adverse effects, including a highly suppressed immune system and risk of serious infections. I researched whether there was a circadian rhythm in replication of either the cancer cells…

You were obviously on to something and it's frustrating yet completely expected to see all replies with pat dismissals that anything like this gets when there is some real potential innovation in healthcare.

Google 'chronotherapy' with some chemo/cancer/immunotherapy related terms and you'll find a ton of research being done. Given that most of it seems to have evolved in the last 8 years my guess is that the concept was 'vetted' by a nobel prize in 2017 for molecular circadian clock, so people feel safe putting their name on studies in this area.

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

#149

Post by jcims »

ch4s3 wrote: post #54
sixo wrote: post #50

Earlier quoted context omitted.

Amazing. And shameful (for them.)

It’s not shameful, it’s how evidence based medicine works. One case is interesting but not a basis for changing a protocol by itself. Tons of things could have influenced the outcome and you need a proper study to know that.

Well the concept is now being studied quite closely. Had someone taken it seriously thirty years ago it's quite possible that the net amount of suffering that millions of patients have endured since then could have been reduced.

https://pmc.ncbi.nlm.nih.gov/articles/PMC9599830/

I'm comfortable calling that shameful. Not on any one in particular, it's a systemic problem that could be reduced with sufficient tenacity and courage to take risks.

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

#150

Post by goda90 »

bloqs wrote: post #122
raylad wrote: post #48

My father was on chemotherapy with fludarabine, a dna base analog. The way it functions is that it is used in DNA replication, but then doesn’t work, and the daughter cells die. Typically, patients who get this drug experience a lot of adverse effects, including a highly suppressed immune system and risk of serious infections. I researched whether there was a circadian rhythm in replication of either the cancer cells…

As a younger person what are the best habits to get into to maintain optimal long term immune health?

Sleep, exercise, a balanced diet of mostly whole fruits and vegetables, and a moderate amount of whole grains, legumes and fresh meat/fish/eggs if you're not choosing a vegan lifestyle. Avoid ultra processed foods, cured meats, alcohol and other recreational drugs. Make sure you get enough vitamin D, which can be hard with certain diets if you're not supplementing, or getting the right amount of sunlight(latitude and time of year matters).

Try to stay low stress, spend time out in nature, maintain good relationships, etc.

Edit: caveat to spending time out in nature: be vigilant of ticks. A tick-bourne disease can mess up your immune system pretty well

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