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COMMENT PAGE FOR: | |
Administering immunotherapy in the morning seems to matter. Why? | |
ImHereToVote wrote 9 hours 53 min ago: | |
Fasted state? | |
yoko888 wrote 14 hours 22 min ago: | |
This reminded me of how my grandma always insisted on taking her meds | |
first thing in the morning before breakfast, before anything. She | |
didnât know anything about circadian rhythms, but sheâd say, | |
âThatâs when my body feels strongest.â At the time, I thought it | |
was just a habit. Now, reading this, Iâm wondering if she was | |
unknowingly syncing with her immune systemâs peak time. | |
s1mplicissimus wrote 16 hours 11 min ago: | |
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 | |
pmlnr wrote 17 hours 42 min ago: | |
Body meridian clock, that's why. | |
aitchnyu wrote 18 hours 44 min ago: | |
If a hospital cannot serve everybody in the morning, should they create | |
a dorm with only artificial light that has sunrise at 12 pm and sunset | |
at 12 am to shift circardian rythms? | |
Noelia- wrote 18 hours 49 min ago: | |
A while back, a colleague told me his doctor always scheduled his | |
immunotherapy infusions for the morning, saying it would be more | |
effective. I thought it was just something they said, but seeing all | |
this new data, Iâm realizing thereâs actually real science behind | |
it. | |
OrderlyTiamat wrote 19 hours 34 min ago: | |
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. | |
HexPhantom wrote 21 hours 57 min ago: | |
In a way it feels like we're scratching the surface of a new layer of | |
treatment optimization | |
EricPhy wrote 22 hours 22 min ago: | |
âLetâs 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 little bit more âexhaustedâ. It believes that it activated | |
itself for no reason, and thus will require a much higher bar for doing | |
anything else in the future. The more times this occurs, the more | |
exhausted the T-cell becomes, the more unwilling to ever activate | |
again. In the limit, it will simply kill itself. Hence why you need | |
immunotherapy to revitalize these cells!â | |
Thatâs a powerful analog for depression and burnout in humans. | |
agumonkey wrote 19 hours 37 min ago: | |
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. | |
cluckindan wrote 21 hours 44 min ago: | |
And not necessarily just an analog, given how there is an immune | |
component to stress. | |
Kiyo-Lynn wrote 1 day ago: | |
I once accompanied a family member through immunotherapy. The treatment | |
times were mostly arranged by the hospital, and the doctor suggested | |
doing it in the morning. | |
We just thought it was to avoid the afternoon rush. | |
Looking back, though, they really did seem to feel better with morning | |
treatments. | |
Now I realize the timing itself might actually affect how well it | |
works. | |
I really hope that in the future, doctors will consider not just the | |
drug and the dosage, but also when itâs given. | |
Spooky23 wrote 1 day ago: | |
They do - for metastatic melanoma, the goal is before 4:30, which is | |
linked to higher survival rates. | |
Kiyo-Lynn wrote 1 day ago: | |
I didnât know there were already examples like metastatic | |
melanoma where the timing is clearly defined. | |
It makes me wonder if other treatments could also benefit from | |
getting the timing right. | |
Thanks for sharing this. Iâll definitely look into it more. | |
more_corn wrote 1 day ago: | |
Because the immune system sleeps at night and wakes up in the morning? | |
parsabg wrote 1 day ago: | |
I wonder if the same would also be true for immunosuppressants | |
administered for autoimmune conditions. Given they mostly interact with | |
the signaling pathways, I guess in theory they should also be more | |
effective in the morning if there is more immune cell activity going | |
on. | |
georgeburdell wrote 1 day ago: | |
Not a medical doctor. Does this also have implications for other | |
immunotherapy like allergy shots? | |
owenthejumper wrote 1 day ago: | |
Sicker patients get emergency treatment in the hospital in the | |
afternoon while healthier ones in the morning in the clinic | |
anthuswilliams wrote 1 day ago: | |
The article is reporting on randomized clinical trials, which are not | |
subject to this dynamic. | |
Spooky23 wrote 1 day ago: | |
Cancer treatments typically donât happen in an inpatient setting. | |
owenthejumper wrote 1 day ago: | |
Of course they do | |
BDGC wrote 1 day ago: | |
If youâre interested in circadian biology, which underlies | |
chronoimmunotherapy, please check out UCSDâs BioClock Studio. We | |
create tutorial videos and other media to teach circadian biology | |
concepts: | |
[1]: https://bioclock.ucsd.edu/ | |
raylad wrote 1 day ago: | |
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 | |
doesnât 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 or the immune cells: lymphocyte and other | |
progenitors, and found papers indicating that the cancer cells | |
replicated continuously, but the progenitor cells replicated primarily | |
during the day. | |
Based on this, we arranged for him to get the chemotherapy infusion in | |
the evening, which took some doing, and the result was that his immune | |
system was not suppressed in the subsequent rounds of chemo given using | |
that schedule. | |
His doctor was very impressed, but said that since there was no | |
clinical study, and it was inconvenient to do this, they would not be | |
changing their protocol for other patients. | |
This was around 1995. | |
Gravityloss wrote 7 hours 57 min ago: | |
I've heard similar things about fasting. | |
jcims wrote 15 hours 40 min ago: | |
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. | |
refulgentis wrote 6 hours 53 min ago: | |
? The other replies don't dismiss it... | |
bloqs wrote 19 hours 31 min ago: | |
As a younger person what are the best habits to get into to maintain | |
optimal long term immune health? | |
bregma wrote 13 hours 10 min ago: | |
You want to live a long time? Avoid any of the things that make it | |
worthwhile. | |
mschuster91 wrote 14 hours 17 min ago: | |
- Get vaccinated fully and regularly. Any kind of infection is much | |
harder to deal with for the body than a vaccine. Particularly | |
important are the measles and Covid shots, an infection with either | |
of the actual pathogens can wipe out your immune system history and | |
you lose a lot of protection. | |
- practice safe sex, get tested regularly (even if both you and | |
your partners are exclusive) and get that HPV shot. Yes, even if | |
you're male. Cancer on your bits ain't pretty. | |
- keep the drug consumption reasonable, especially smoking and | |
alcohol | |
- the better quality the food, the better your health. Should be a | |
no-brainer and I know about food deserts, lack of time etc | |
stronglikedan wrote 14 hours 31 min ago: | |
Don't be a germaphobe. Don't wash your hands a lot. Give your | |
immune system a little work out each day by not babying it. | |
Try not to take any medicines unless you absolutely need them, and | |
stay away from hand sanitizers. If you do need to clean anything, | |
soap is more than enough and water is usually enough. | |
I thought it was normal to be over 50 and not take any medicines, | |
but all the doctors and staff were surprised by this when I got my | |
colonoscopy recently. | |
kmarc wrote 13 hours 42 min ago: | |
Above 50? My 30+ year old American friends are all running on | |
pills, daily, many different of them. I was shocked. | |
So I am rather with you. It should be normal not to take | |
medicines. | |
unshavedyak wrote 13 hours 32 min ago: | |
What sort of pills? Vitamins or ? | |
kmarc wrote 13 hours 25 min ago: | |
Some yes, and then all sorts of mood boosters, painkillers, | |
etc. Basically all the stuff I later saw during a commercial | |
break at a bar during some sports game. (this should be | |
banned, TBH) | |
webstrand wrote 14 hours 21 min ago: | |
By hand sanitizers, do you mean something other than the | |
isopropyl-gel based hand sanitizers? If not, I would have guessed | |
that would be little different than using a strong soap. | |
That said, unfortunately there's some element of luck to it. | |
There's compelling evidence that C-section babies have abnormal | |
immune responses and less diverse body flora. And I imagine | |
childhood circumstance affects things too, city vs country | |
affecting the childhood exposure to pathogens and non-pathogens | |
for training. | |
goda90 wrote 15 hours 30 min ago: | |
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 | |
FollowingTheDao wrote 14 hours 13 min ago: | |
Maybe your schema will work for someone whoâs on the very top | |
point of the bell curve of human population but human genetic and | |
environmental variability will over rule your advice for the | |
majority of people. | |
pinkmuffinere wrote 11 hours 42 min ago: | |
The states known for âhippieâ/âgranolaâ attitudes, | |
which largely align with the advice given here, tend to live | |
longer than the states that donât (scroll through the list in | |
[1] to see this). Usually I would insist on a study, but the | |
effect is so striking, and the mechanism by which it would work | |
is so obvious, that I think this simple list is enough. And | |
Iâm sure there are studies too, Iâm just too lazy to find | |
and link one. | |
[1]: https://en.wikipedia.org/wiki/List_of_U.S._states_and_... | |
throwaway290 wrote 18 hours 1 min ago: | |
Don't compromise it chronically. Protected sex etc. | |
ReptileMan wrote 18 hours 13 min ago: | |
Normal weight and enough sleep. | |
HexPhantom wrote 21 hours 55 min ago: | |
It's frustrating (but not surprising) that even with a clear positive | |
outcome, the system couldn't adapt without a clinical trial to back | |
it up | |
taneliv wrote 21 hours 34 min ago: | |
Isn't it also quite understandable? Otherwise we risk the new way | |
working well for half the patients and killing the other half, to | |
exaggerate. | |
irrational wrote 1 day ago: | |
Is it the time of day or how long the patient has been awake that | |
matters? It seems like someone could change their sleep cycle to | |
match the doctors schedule if the latter. | |
sixo wrote 1 day ago: | |
Amazing. And shameful (for them.) | |
bravesoul2 wrote 1 day ago: | |
What's the p value? 0.5? | |
vkou wrote 1 day ago: | |
> 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. | |
NiloCK wrote 15 hours 50 min ago: | |
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. | |
Aerroon wrote 12 hours 28 min ago: | |
And if the A/B test says that your intervention made the | |
situation worse? Now the doctor is held liable for that. | |
s1artibartfast wrote 9 hours 41 min ago: | |
Not how it works. Doctors have wide latitude to treat patient | |
based on their personal medical intuition. You already have | |
doctors dosing patients at all times of day. If an A/B test | |
shows evening is optimal, all the morning administrators will | |
not suddenly become liable retroactively. Hell, they wont | |
even be liable if they keep doing it in the morning because | |
it fits their schedule better. | |
vidarh wrote 19 hours 32 min ago: | |
Given the scheduling was clearly not based on a medical | |
recommendation in the first place given they were prepared to | |
change it, then even a single datapoint suggesting it might have | |
an impact should be reason to do at least minimal investigation | |
into whether #3 might be better served by altering the schedule. | |
Since they clearly could alter the schedule, offering a limited | |
number of later slots and comparing results would seem like the | |
prudent response. | |
TeMPOraL wrote 18 hours 4 min ago: | |
> Since they clearly could alter the schedule, offering a | |
limited number of later slots and comparing results would seem | |
like the prudent response. | |
There's a difference between a doctor entertaining a | |
medically-irrelevant suggestion from a patient (or patient's | |
family), vs. assuming that the subsequent improvement was | |
related to it, and then making that decision for some other | |
patients (or suggesting it to them). The former is being | |
accommodating, the latter is making treatment changes without | |
good reason. | |
Improvement or no change aren't the only two possible outcomes | |
for a patient. They could also get worse. What's worse, often | |
neither improvement nor decline are obviously related to the | |
treatment, or treatment changes. | |
Maybe it's the circadian rhythm thing. Maybe it's some delayed | |
effects of something unrelated about the patient, that just | |
coincided with your intervention. Maybe it's just a response to | |
a change - any change. Or maybe it's just completely random. | |
The point is, you don't know. You might feel like you do, or | |
maybe it really looks obvious - but from N=1 you don't actually | |
know, not enough to potentially bet other people's health on | |
it. | |
Because maybe you do go ahead, and make a schedule change to | |
another few patients - and few days later, suddenly and for no | |
apparent reason, one of them goes into critical condition and | |
dies soon after. Good luck convincing the grieving family, your | |
colleagues, the board - and your own conscience - that the | |
schedule change could not have possibly caused this. You | |
won't, because you don't actually know. | |
vidarh wrote 16 hours 56 min ago: | |
They are already making treatment choices without good reason | |
when they set or change the schedules. | |
They could already have made it worse with prior scheduling | |
decisions, without having any idea. | |
Intentionally choosing to ignore a possibly harmful effect of | |
the current lack of scheduling rules seems to me as blatantly | |
unethical or worse as taking reasonable steps within what is | |
already permitted to try to address a possible negative | |
effect. | |
If concerned about making the schedule change for them: | |
Provide the option. Add appropriate warnings if you like. | |
But also consider that any grieving families that finds out | |
after the fact that there might be a known benefit to | |
changing the scheduling would be equally hard to convince | |
that you've not acted unethically and done harm. | |
chiefalchemist wrote 1 day ago: | |
It shameful in the sense we all know there are circadian rhythms. | |
We know the human body is not uniform from waking to shut eye. | |
With this in mind health care therapies should be intentionally | |
administered at various times - as wide as possible; from that | |
perhaps outcomes will vary. You donât need a study to look for | |
opportunities to optimize a process. | |
vlovich123 wrote 1 day ago: | |
I agree n=1 generally isnât enough, but something like this is | |
easily something you ask for volunteers for as an experiment. | |
Thereâs 0 risk, youâre taking the same drug. The only reason | |
a given time is selected anyway is for administrative ease not | |
because thereâs medical requirements. | |
vkou wrote 1 day ago: | |
Its not easy to ask if it messes with staff scheduling. | |
raylad wrote 5 hours 33 min ago: | |
I posted this above, but for clarity: | |
This was Sloan-Kettering. | |
They gave morning infusions because it was convenient for | |
them. | |
To get my father the evening infusion we had to hire private | |
duty nurses to come to his apartment. | |
vlovich123 wrote 1 day ago: | |
Clearly they did it for one patient and it was a good result. | |
Doctors and staff generally care about their patients and | |
given thereâs plausible scientific reasoning why this | |
worked, theyâd 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 patients seeking care from them. Thatâs | |
how it should work but bureaucracy of medical care is | |
typically resistant to things like that. | |
vkou wrote 19 hours 55 min ago: | |
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. | |
vlovich123 wrote 14 hours 40 min ago: | |
I didnât say everyone. I said do it as a pilot for 2-5 | |
more patients so that you donât write it off as a | |
fluke, then give a talk at a conference. If youâre | |
having good results then you can talk with the | |
administrators how to make this a more serious program if | |
thereâs actually good results and desire to scale this | |
up. | |
Nowhere do you start from 0 and go to 100. You take baby | |
steps scaling up to see if the results hold. | |
tilne wrote 1 day ago: | |
Regarding 3: Shouldnât the medical system be optimizing for | |
patient outcomes rather than the business their in? | |
Regarding the first two: I think the anecdote being from 1995 | |
suggests there would have been time to put together said mountain | |
of research. | |
Iâm not agreeing that this is shameful for the original doctor, | |
but I do think itâs shameful if avenues for potential research | |
are not taken because itâs inconvenient for the hospitals. | |
Spooky23 wrote 1 day ago: | |
It is at cancer centers. Community oncologists donât have the | |
resources to do it. | |
Example: | |
[1]: https://www.medicalnewstoday.com/articles/cancer-time-... | |
raylad wrote 5 hours 34 min ago: | |
This was Sloan-Kettering. | |
They gave morning infusions because it was convenient. To get | |
my father the evening infusion we had to hire private duty | |
nurses to come to his apartment. | |
vkou wrote 1 day ago: | |
Yes, it should. | |
But cost is also important to patients. Or it would be in any | |
universe that made sense. | |
ch4s3 wrote 1 day ago: | |
Itâs not shameful, itâs 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. | |
jcims wrote 15 hours 36 min ago: | |
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. [1] 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. | |
[1]: https://pmc.ncbi.nlm.nih.gov/articles/PMC9599830/ | |
refurb wrote 11 hours 45 min ago: | |
> 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. | |
You can only say that with hindsight because of the data over | |
the past 30 years. | |
What if the data showed the opposite? Then the doctor would | |
have given his patients a worse outcome all on a "hunch". | |
ch4s3 wrote 13 hours 26 min ago: | |
There's limited time and a finite supply of doctors and | |
researchers. They can't study everything that's promising all | |
at once, and good ideas fall through the cracks all of the | |
time. | |
JamesSwift wrote 12 hours 34 min ago: | |
I think this clears a bar of things that are useful and | |
simple to study. Theres basically no effort involved. If it | |
ends up beneficial we just update job postings from 'daytime | |
infusion tech' to 'nighttime infusion tech'. Instant | |
improvement in outcomes. I doubt you even need to clear this | |
in any way to get the study greenlit. | |
teekert wrote 22 hours 20 min ago: | |
It is not shameful indeed. One never knows what the father had | |
experienced if he had been given the therapy during the day. | |
The oncologist could have written a paper (there are many single | |
case papers), or started a trial by himself (requires a lot of | |
organizing) if he was very intrigued. But of course one canât | |
do that for every above average case. | |
I have to say, in this particular case there is a very plausible | |
mechanism and the trial would not be that hard. So it is a real | |
shame that nothing was done with this. | |
raylad wrote 5 hours 36 min ago: | |
Previous rounds of chemo were done on the normal morning | |
infusion schedule and he ended up with a completely depleted | |
immune system and was put in strict quarantine. He also got | |
multiple infections that were life threatening. | |
This is the reason I started looking into the alternate dosing | |
schedule. | |
echelon wrote 1 day ago: | |
> Itâs not shameful, itâs how evidence based medicine works. | |
Yeah, but I'll bet nothing happened as an outcome of this. No | |
study, no communication to anyone else. That information probably | |
just withered on the vine. | |
I did a molecular bio undergrad and had classes with a bunch of | |
pre-med students. They had zero interest in the science, just | |
getting A's. They did care about appearance and money, driving | |
cool cars, and dating hot partners. I know my experience is | |
purely anecdotal and not indicative of all doctors, but I came | |
away from my undergrad experience highly unimpressed with our | |
medical feedstock. The only students in upper level electives | |
that cared were the research-track students. | |
I talk to my doctors regularly about medicinal chemistry and | |
biochem -- they don't know anything. It's embrassing how little | |
they retain or care. | |
uselesswords wrote 17 hours 1 min ago: | |
Hereâs my anecdote for your anecdote. While there certainly | |
are doctors who care about the flashy lifestyle, I know plenty | |
more who truly care. | |
Also medicine is an evidence-based practice because | |
fundamentally our knowledge is woefully incomplete. Doctors are | |
basically applied statisticians, the chemistry and biochemistry | |
people are the researchers. | |
calf wrote 1 day ago: | |
"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. | |
uselesswords wrote 16 hours 56 min ago: | |
So if one person injects themselves with honey and wakes up | |
tomorrow cured from Covid, we should inject everyone with | |
honey? Thatâs the exact opposite of a scientific process. | |
Evidence-based medicine is the scientific process. Love | |
seeing the grandstanding on this thread against EBM without a | |
single practical alternate proposal. Instead of complaining, | |
what do you propose instead? | |
calf wrote 3 hours 56 min ago: | |
The other commenter already said, ought not to let the | |
information wither on the vine. That's a reasonable take. | |
Second, "evidence-based X" is largely a euphemism and | |
increased usage under political austerity. In Western | |
society especially in academia by "medicine" we already | |
assume some semblance of applied science, and so | |
"evidence-based medicine" has been well critiqued in | |
medical and other scientific literature, in relation to how | |
institutions like hospital administrators and (austerity) | |
state policies might misuse the term, etc. You are not | |
aware of this issue, so just read some of the literature. | |
echelon wrote 15 hours 50 min ago: | |
Barry James Marshall | |
uselesswords wrote 11 hours 17 min ago: | |
Classic HN reply. No elaboration, explanation, nothing. | |
What exactly am I supposed to have read from your mind? | |
AbrahamParangi wrote 1 day ago: | |
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 âuntrue | |
until proven otherwiseâ isnât an exclusively optimal policy. | |
h2782 wrote 17 hours 37 min ago: | |
> 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. | |
What? This makes no sense. How do you explain anti-vaxxer | |
parents with this perspective? Parents may feel they know best, | |
but feeling and fact have nothing to do with each other. | |
raverbashing wrote 22 hours 24 min ago: | |
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" | |
ch4s3 wrote 13 hours 28 min ago: | |
The opposite approach exposes people to a lot of unnecessary | |
and dangerous medical treatment. The evidence based approach | |
has uncovered that stenting doesn't work[1], yet a lot of do | |
something proponents are still installing them at great risk | |
to patients and at great cost to medical systems. | |
[1]: https://lowninstitute.org/stents-dont-work-a-look-ba... | |
vrc wrote 16 hours 7 min ago: | |
Counterpoints: the detractors of this purported loop would | |
likely neither fund the vast amounts of research theyâd | |
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. | |
wyldfire wrote 1 day ago: | |
Though it could certainly inspire such a study. | |
ch4s3 wrote 1 day ago: | |
Sure, but someone needs to fund, organize, and conduct the | |
study. If you're not at a research hospital it's not as easy | |
for a one off case to generate a study. | |
daveguy wrote 1 day ago: | |
That's why doctors publish case studies all the time -- to | |
inspire larger scale and statistically sound studies. | |
more_corn wrote 1 day ago: | |
Or you could consider if thereâs reason to believe | |
thereâs a causal relationship, if there is you could change | |
your protocol (offer it in the evening as an option), measure | |
the improvement, publish the result and simultaneously | |
improve your patient outcomes and move science forward. | |
vlovich123 wrote 1 day ago: | |
This is a fairly innocuous change the doctor should be | |
organizing on their own to publish a pilot study. In terms of | |
funding very little would be required since youâre just | |
making a small adjustment to when an existing drug regimen is | |
happening which you already isnât a controlled factor | |
requiring FDA oversight or anything. | |
_qua wrote 1 day ago: | |
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. | |
renewiltord wrote 22 hours 46 min ago: | |
Indeed, as any ethicist worth his salt would argue: we | |
donât want anyone saving lives without proper approval. | |
refurb wrote 11 hours 43 min ago: | |
What a intellectually lazy response. | |
No, it would be more accurate to say "any ethicist | |
worth his salt would argue: don't make changes that | |
could be harmful based on a hunch" | |
southernplaces7 wrote 2 hours 47 min ago: | |
I think it was a bit tongue in cheek, not so much | |
lazy. Also, considering the kinds of gatekeeping and | |
forced "concerns" I've seen some ethicists push forth | |
just for the sake of showcasing their fixations | |
instead of really looking at costs and benefits, I | |
don't think it's far off the mark on reality to argue | |
that medical ethics is worth considerable scrutiny | |
too, and shouldn't hid behind a mantle of being above | |
criticism. | |
vkou wrote 19 hours 52 min ago: | |
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. | |
vlovich123 wrote 1 day ago: | |
If a study like this needs a complicated IRB approval or | |
extra data collection vs whatâs already being collected | |
for health records, youâre doing it wrong and the | |
process has become more important than the problem | |
youâre trying to solve. | |
owenthejumper wrote 16 hours 5 min ago: | |
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. | |
vlovich123 wrote 14 hours 34 min ago: | |
I think once again - when the process becomes the | |
metric itâs insane. What time things are being | |
administered is already random and not regulated or | |
organized. âWhat if it hurtsâ isnât relevant | |
for something like this because the reasoning is that | |
the baseline is that âwhenâ doesnât matter, | |
youâre still giving the same dosage. âWhat if it | |
clearly helps?â What if. Then you publish a paper | |
or give a talk at a conference and try to better | |
mobile the medical community. Or see if the | |
administrators are willing to help scale this up | |
further. | |
> How do you ensure you collected enough of a sample | |
of a general population to make your study | |
representative? | |
You donât need to. This would be a pilot study to | |
check whether thereâs maybe a there there before | |
you do it larger scale to measure predictive power at | |
population level. | |
> Do I keep going or is the IRB approval process | |
clearer now? There is a reason it exists. | |
I think youâre completely failing to engage with | |
the argument that this particular case about time | |
shifting delivery of a drug should not need | |
meaningful IRB engagement other than âIâd like to | |
change the time I deliver the drug for 2 more | |
patients because we had one patient respond | |
positively and this isnât believed to be a | |
factorâ âok cool yupâ. | |
Youâve jumped from no IRB to full IRB without | |
considering the context of the problem being solved | |
which is why I said when the process becomes the goal | |
vs the problem youâre trying to solve - youâre | |
imaging the worst and most complicated situations | |
possible for a case that would never demand it. | |
owenthejumper wrote 4 hours 9 min ago: | |
You are approaching things from software | |
development perspective of "what's the worst that | |
can happen? I rollback". In the topic discussed, | |
you cannot rollback. While you might have a | |
reasonable suspicion that changing the time will | |
improve some outcomes in most, you cannot be sure | |
that it won't greatly reduce positive outcomes in | |
many. The IRB is often in place not to stop | |
positive outcomes, but to reduce negative ones. | |
Panzer04 wrote 15 hours 20 min ago: | |
We can appreciate that process is important, but at | |
some point you're falling down a slippery slope here, | |
surely? | |
We're talking about a factor that no one has | |
previously had reason to consider important. | |
Of course, I don't know hard it truly is to undertake | |
a study. I have to imagine for something like this | |
you could write up a basic study protocol in fairly | |
short order. | |
dotancohen wrote 20 hours 54 min ago: | |
> the process has become more important than the | |
problem youâre 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. | |
darkwater wrote 19 hours 28 min ago: | |
And I think there is a reason why the bureaucracy | |
exists in these cases. "Move fast and break things" | |
doesn't work very well there. | |
echelon wrote 1 day ago: | |
It's no wonder biology hasn't even entered into the | |
punch-card phase. | |
When I did my bio undergrad I was keenly aware our bodies | |
are just scaled up molecular machines. I was hoping for a | |
future where we'd grow MHC-neutral clonal bodies for | |
organ harvesting. | |
Nope. We're in the stone age. | |
refurb wrote 11 hours 41 min ago: | |
It's almost as if your undergrad biology gave you just | |
enough information to make assumptions that aren't | |
true? | |
The medical journals are filled with studies that | |
"should have worked" and didn't. | |
Heck, there are a ton of studies that "should have | |
worked" that were harmful. | |
So much for "we're just scaled up molecular machines". | |
_qua wrote 1 day ago: | |
Move fast and break things in human medicine means | |
unethical researchers maim and kill people, often | |
marginalized people. Nazis, Japanese experimenting on | |
prisoners, Tuskegee airmen syphilis experiments, | |
Cincinnati radiation experiments and many others stand | |
as testament to what ambitious unethical scientists | |
will do to further their knowledge and career. Thus we | |
have strict guardrails that slow down how we do things. | |
xvector wrote 1 day ago: | |
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 medical progress. | |
We are seeing the same problem with nuclear | |
overregulation result in worse outcomes and more | |
deaths for people globally. | |
There is real suffering and a human cost, measurable | |
in lives, to slowing down progress - just as there is | |
one for reckless progress. | |
_qua wrote 1 day ago: | |
I donât disagree but the guy below you wants to | |
grow human shells and try head transplants. | |
lofaszvanitt wrote 16 hours 46 min ago: | |
good! old, dinosaur like systems need to be | |
forgotten already. | |
short_sells_poo wrote 18 hours 12 min ago: | |
This is why we can't have nice things. I don't | |
(mostly) doubt that poster's good intentions, but | |
it takes only a few people with undirected ideas | |
and flexible morals or empathy to necessitate | |
strict rules around medical research. | |
tomcam wrote 1 day ago: | |
Transplant a few heads and suddenly you never get | |
invited to another Christmas party | |
tough wrote 17 hours 51 min ago: | |
2017 | |
[1]: https://nationalpost.com/health/worlds... | |
echelon wrote 1 day ago: | |
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 possibly even do whole head transplants and | |
cure all non-blood, non-brain cancers. | |
But we're playing in the sand. | |
nothrabannosir wrote 21 hours 57 min ago: | |
This comment, more than any other, has sold me on | |
the value of red tape in medical research. | |
echelon wrote 21 hours 17 min ago: | |
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 experience and produce wonderful | |
things. | |
If you divorce the body from the mind, there is | |
no "person". Just a very complicated machine. A | |
very valuable machine full of parts. | |
A human body in a vegetative state is not a | |
person. It's a dormant machine. People may have | |
emotional attachment to that vestige, but it is | |
no longer capable of being a person. It is not a | |
person. | |
We use brain dead humans for organ transplant all | |
the time. If you understand the premise, then it | |
isn't that far-fetched that we might grow | |
vegetative humans in a lab for medical use and | |
research. | |
Bodies that never have brains can never become | |
persons. They're no different from plants. | |
willguest wrote 20 hours 13 min ago: | |
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. | |
cannonpr wrote 1 day ago: | |
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. | |
echelon wrote 21 hours 15 min ago: | |
We're not at all trying. | |
If you toss out the old rule book and provide | |
unlimited funding, it can be made to work. | |
darkwater wrote 19 hours 24 min ago: | |
Yeah, sure. There are probably going to be only | |
a few tens of thousands "unknown unknowns" | |
side-effects but hey, who cares? We will figure | |
them out, we are out of the stone age cave now! | |
egocodedinsol wrote 1 day ago: | |
Hereâs a link to the abstract: [1] apparently it was prospective and | |
randomized. Iâm a little shocked by the effect size. | |
[1]: https://ascopubs.org/doi/abs/10.1200/JCO.2025.43.16_suppl.8516 | |
munchler wrote 1 day ago: | |
This paper was not a retrospective analysis, it was a randomized | |
clinical trial. | |
egocodedinsol wrote 1 day ago: | |
Yeah Iâm checking - I saw several other oncologists suggesting | |
song a separate discussion. | |
levocardia wrote 1 day ago: | |
Hazard ratio of 0.45 seems implausibly high, especially when it's just | |
the exact same treatment dichotomized to before/after 3pm. My money is | |
on something other than a real circadian effect: either the result of a | |
'fishing expedition' in the data, or some other variable that | |
incidentally varies by time of day. Maybe breaking randomization, | |
leaving the drugs out for too long at room temp, etc. If you really | |
believe this is an important and biologically plausible effect it | |
should be a top candidate for a replication attempt. | |
trhway wrote 1 day ago: | |
>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) . | |
levocardia wrote 1 day ago: | |
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. | |
trhway wrote 20 hours 2 min ago: | |
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. | |
NotGMan wrote 1 day ago: | |
Perhaps it's due to overnight fasting, that people in the morning don't | |
eat yet/as much? | |
Autophagy is increased during fasting, it usually takes 3 days of water | |
fasting to fully ramp up to its maximum, so no food overnight might | |
just slightly start it up. | |
I watched a youtube video of guy who did low carb and fasted at least | |
24h before and after chemo (or even 48h, forgot which) and he didn't | |
experience the negative side effects of chemo as much. | |
Laaas wrote 1 day ago: | |
Light affects us deeply. Very probably true for more than | |
immunotherapy. | |
unnamed76ri wrote 1 day ago: | |
I used to be on a chemo drug and had to take folic acid every day to | |
stop it from doing bad things to me. | |
I had awful ulcers in my mouth from the chemo drug and had been taking | |
the folic acid in the morning. Through forgetfulness I ended up | |
shifting the folic acid to the afternoon and the ulcers went away and | |
never came back. | |
HexPhantom wrote 21 hours 52 min ago: | |
How many side effects people just accept because no one thought to | |
tweak the schedule | |
cenamus wrote 18 hours 10 min ago: | |
And to think about how often such things are figured out | |
individually, but go unnoticed, because there's basically 0 chance | |
for the average person to get anyone to do a study on it. | |
unnamed76ri wrote 9 hours 54 min ago: | |
I did make sure to bring it up to my doctor in case the idea | |
could help anyone else. | |
hypercube33 wrote 16 hours 46 min ago: | |
My guess on some of this has to do with a few things. Hormone | |
levels vary throughout the day along with immune system activity; | |
My allergies are always worse in the morning than the day. I'm | |
sure time is a huge component in a lot of medical things but I | |
haven't personally seen any studies on this. | |
Most people also fast at night (sleeping) and are less physically | |
active etc etc. | |
tomcam wrote 1 day ago: | |
Thanks for sharing, and Iâm very glad you are here to discuss it. | |
jmward01 wrote 1 day ago: | |
I wonder if other basic processes could be at play here like when | |
patients go to the bathroom. If you do this in the morning they may be | |
more likely to not need that for a while while in the evening they may | |
do that immediately. I'm not saying this is the mechanism, just | |
pointing out that there are a lot of timing dependent things in a | |
person's schedule that could be a factor here. It is a great thing to | |
point out though. I hope a lot more research goes into the idea of | |
timing and integrating medication into a schedule most effectively. | |
HexPhantom wrote 21 hours 49 min ago: | |
We tend to treat the body like a static system when it's actually | |
dynamic across the day | |
rendaw wrote 1 day ago: | |
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't mean the last | |
year of taking it was a wash... | |
amluto wrote 14 hours 19 min ago: | |
If the reasoning in the OP is right, then one might infer that the | |
evening is the right time to take it. The goal of cancer | |
immunotherapy is to convince your body to treat the cancer as | |
harmful. The goal of allergy immunotherapy is to convince your body | |
to tolerate allergens. If you are more likely to consider antigens | |
harmful in the morning and tolerable in the evening, then evening is | |
better. | |
As a giant confounding effect, it seems that allergy immunotherapy | |
might work, at least in part, by convincing your body to make large | |
amounts of IgG antibodies to the allergen, and IgG antibodies are in | |
the âkill it but donât sneeze at itâ category, which isnâ�… | |
same thing as having your T cell population tolerate the antigen. | |
aitchnyu wrote 18 hours 48 min ago: | |
From a lazy search, the measures are to trigger a reaction, but not | |
intense enough send you to hospital. Fasted state (first thing in | |
morning) can enhance absorption and avoid interference with food. | |
(hot) showers cause vasodilation and exercise causes increased heart | |
rate, both which increase allergen absorption enough trigger adverse | |
reaction. If you have taken it for a year, your doctor may probably | |
not worry about a too-intense reaction. | |
I'm also taking dust mite immunotherapy and assumed this article | |
applies to me. | |
HexPhantom wrote 21 hours 51 min ago: | |
Yeah, that tension between convenience and protocol is so real and | |
frustrating | |
Nevermark wrote 1 day ago: | |
> I could do it in the evening instead (despite explicit instructions | |
to do it in the morning) | |
Have either you or your doctor identified the reason for the morning | |
recommendation? | |
Maybe restart consideration of timing there? | |
Doctors are going to take your practical need to break one part of | |
protocol, to maintain the rest of the protocol, seriously. They can't | |
resolve the practicalities of patients' lives. | |
mjevans wrote 1 day ago: | |
Explicitly clear, but otherwise not overly specific, medication | |
instructions would be best. | |
Say exactly what matters. | |
E.G. 'Take once a day at a similar time.' VS overly specific but not | |
required 'take in the morning / evening / lunch / some other | |
assumption that doesn't matter.' HOWEVER maybe "Take once a day with | |
your first (full) meal." OR "Take once a day with your primary meal." | |
might make more sense for medications that interact with food. | |
iamtheworstdev wrote 1 day ago: | |
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? | |
rendaw wrote 20 hours 32 min ago: | |
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. | |
> Thereâs 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. | |
tomcam wrote 1 day ago: | |
Where did they say theyâre mad? | |
bjornasm wrote 1 day ago: | |
They explicitly fault the doctor for not acting on research that | |
wasn't available. | |
unaindz wrote 1 day ago: | |
The last paragraph heavily implies it | |
justsomehnguy wrote 1 day ago: | |
There is always an option what taking it in the evening is magnitudes | |
better than not taking it in the morning at all because you skipped | |
it because you need a shower. | |
Always remember what you are just an another patient with your own | |
quirks. | |
tialaramex wrote 1 day ago: | |
For the drug I take every day (Levothyroxine), research found that | |
evening was worse, but the explanation was poor compliance - people | |
forget to do it more often compared to the morning. Same reason the | |
contraceptive pill is less effective than you'd expect in real | |
populations, compliance is poor. If you're the sort of person who | |
can actually take it on time, every day, without fail, it's | |
extremely effective, if you aren't, not so much. The choice to | |
include "dummy" pills is because of improved compliance - | |
remembering to take it every single day on the same schedule is | |
just easier, so adjust the medication not the instructions. | |
pbhjpbhj wrote 1 day ago: | |
What annoys me here is that these things are hidden - if the | |
patient knows that compliance is better (ie their chance of | |
staying with the medicine and so of getting better) does it | |
really reduce said compliance? | |
detourdog wrote 1 day ago: | |
I looked up CedarCure and what I found is that it is a pesticide. | |
What is the treatment about? | |
annoyingnoob wrote 1 day ago: | |
[1]: https://synapse.inc/medicine/9101/ | |
tines wrote 1 day ago: | |
OP is an insect going in for assisted suicide. | |
iamtheworstdev wrote 1 day ago: | |
looks like a sublingual immunotherapy treatment for allergies to | |
japanese cedar pollen. | |
rendaw wrote 1 day ago: | |
It's an immunotherapy drug for cedar pollen allergy. | |
zevets wrote 1 day ago: | |
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. | |
abhishaike wrote 1 day ago: | |
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 to support that. I will update the article to admit this! | |
This said, I am inclined to believe that this isn't a major concern | |
for chronotherapy studies, since I haven't yet seen it being raised | |
in any paper yet as a concern and the results seem far too strong to | |
blame entirely on 'night nurses make more mistakes'. Fully possible | |
that that is the case! I just am on the other side of it | |
munchler wrote 1 day ago: | |
The appointment schedule was randomized, so your objection is | |
incorrect. | |
majormajor wrote 1 day ago: | |
I always have seen mid-day appointments as also a luxury for those | |
doing well (at least professionally/financially). If you have to go | |
first thing in the morning, it's often because your boss wants you in | |
relatively early and won't let you take time mid-day. If you're in a | |
position where you can go in at 2PM and not have to sacrifice sleep | |
to do so, that feels healthier. | |
Given the highly-evident strong circular nature of the body, a | |
hypothesis that it has something to do with that seems highly likely, | |
certainly worth following up on. | |
pbhjpbhj wrote 1 day ago: | |
Surely your boss legally has to let you attend a health | |
appointment? Though they might not have to pay you. That seems like | |
a very basic workers right, the sort of thing you'd have a general | |
strike over if it didn't exist?? | |
mjevans wrote 1 day ago: | |
The most vulnerable, at least among those who have a job at | |
least, often have the most draconian restrictions on when and | |
what they can do. | |
Believe they are being treated like robots. Maybe even literally | |
like gears rented by the hour, not even robots. | |
JumpCrisscross wrote 1 day ago: | |
> mid-day appointments as also a luxury for those doing well | |
Irrelevant to this study given randomization. | |
detourdog wrote 1 day ago: | |
I can schedule appointments whenever I want. I'm an early riser and | |
prefer my appointments first thing in the morning. | |
vhanda wrote 1 day ago: | |
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 weâll 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 morning more often, but randomization fixes that. | |
Yes, maybe morning nurses are fresher and more alert, but, again, | |
randomization fixes that. | |
vibrio wrote 16 hours 14 min ago: | |
"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). | |
gus_massa wrote 1 day ago: | |
How many dose this treatment has? How many between them? | |
How many patients dropped out? (Or requested a schedule change) Do | |
they count like live or dead? | |
leereeves wrote 1 day ago: | |
> Yes, maybe morning nurses are fresher and more alert, but, again, | |
randomization fixes that | |
How does randomization fix that? | |
finnh wrote 1 day ago: | |
exactly. that one clause casts doubt on all the other reasoning; | |
randomization controls for patient selection bias but not diurnal | |
clinic performance | |
phanimahesh wrote 1 day ago: | |
It would if the clinic is a controlled setting and they can | |
control when the nursing shift begins. | |
tines wrote 1 day ago: | |
What does randomization mean in this context, and why does it fix | |
those problems? | |
kelnos wrote 1 day ago: | |
Patients in the study are randomly assigned to the early group or | |
the late group. They don't get to schedule their own appointments | |
for whatever time of day they want. | |
tines wrote 1 day ago: | |
How does this control for the "alert nurses" variable? In that | |
case, patients would do better in the morning, regardless of | |
the patient. | |
d_tr wrote 1 day ago: | |
Based on these graphs and the differences in outcomes they | |
show, you are not talking about "alert vs less alert" nurses | |
but about "nurses doing their job vs nurses basically slowly | |
killing dozens of patients". | |
simmerup wrote 1 day ago: | |
Why do you think you're going to poke holes in a research | |
article when you've clearly only just heard of the concept | |
and havent even read the article | |
tines wrote 1 day ago: | |
If I thought I could poke holes in the research, I wouldn't | |
be posting on HN. I'm asking questions to learn because | |
obviously I don't understand :) | |
anigbrowl wrote 1 day ago: | |
Why would you assume nurses are scheduled on a 9-5 basis? | |
ajkjk wrote 1 day ago: | |
[1] The same thing it means in every context: that (with enough | |
samples) you can control for confounders. | |
[1]: https://en.wikipedia.org/wiki/Randomized_controlled_tria... | |
tines wrote 1 day ago: | |
Supposing that patients did better in the morning because, say, | |
the nurses were more alert, no matter how many samples you take | |
you'll find the patients do better in the morning. How does | |
"more samples" help control for confounders rather than just | |
confirm a bias? | |
ajkjk wrote 1 day ago: | |
"more samples" is not what controls for confounders. | |
Controlling for confounders is what controls for confounders, | |
which you can only do with enough samples that you can | |
randomize out the effect of the confounder. | |
Whether or not they controlled for nurse-alertness is | |
something you'd have to read the paper (or assume the | |
researchers are intelligent) for. | |
tines wrote 1 day ago: | |
I guess I'm asking, how do you randomize out the confounder | |
in this case. | |
bravesoul2 wrote 1 day ago: | |
Have every dose be observed by another doctor? | |
ajkjk wrote 1 day ago: | |
I imagine that that particular confounder is not possible | |
to eliminate via randomization. Perhaps you collect a | |
bunch of data on nurse awakeness--day shift vs | |
night-shift, measuring alertness somehow, or measuring | |
them on other activities known to be influenced by | |
alertness--and then ensure your results don't correlate | |
with that. | |
There is also the mechanistic side: if you have lots of | |
plausible mechanism for what's going on, and you can | |
detect indicators for it that don't seem to correlate | |
with nurse alertness, that's a vote against it mattering. | |
Same if you have of lots of expertise on the ground and | |
they can attest that nurse alertness doesn't seem to have | |
an affect. There are lots of ways, basically, to reach | |
pretty good confidence about that, but they might not be | |
as rigorous as randomized assignments can be. | |
JumpCrisscross wrote 1 day ago: | |
> How does "more samples" help control for confounders rather | |
than just confirm a bias? | |
I think you're correct that randomising patient assignments | |
doesn't control for provider-side confounders. Curious if the | |
study also randomised nursing assignments. | |
NhanH wrote 1 day ago: | |
Patients are assigned the time for their visits. The time itself | |
is randomized | |
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