1,949 karma · joined March 5, 2013
Unlike Eli Lilly (who use chemical synthesis for Zepbound) they use yeast for synthesis and have decided not to contract out production to protect manufacturing trade secrets which makes ramping up slower, have to wait for their Denmark plant upgrade to come online.
Is there a reason you suspect a connective tissue disorder to be the unifying diagnosis? I have not heard this theory before.
Not really. SIBO prevalence increases with age and goes up to 80% in elderly patients.
hEDS prevalence is between 0.005% and 0.02%.
The symptoms/diseases you listed are very common. We don’t really use hypochondriac anymore but the reason these are common is because they’re vague constitutional symptoms that have 1000 different possible causes or nothing at all.
> What is very unorthodox about about my view is that this flexibility is not an essential component so a lack of flexibility is not sufficient to rule it out even if it does reduce the likelihood.
There is nothing unorthodox about this, it’s part of the 2017 international criteria for hEDS.
https://www.ehlers-danlos.com/wp-content/uploads/2022/03/Mal...
It’s extremely challenging if not impossible to obtain informed consent in this situation.
We’ve been through this before where a fancy new treatment with promising early/lab results usurped conventional therapy only to later be found inferior.
Earlier TKIs and NSCLC are a recent example that comes to mind.
Unless the prescription is marked as “do not substitute” pharmacists generally have the discretion to substitute for a generic, in fact a few states require it.
With that said, Viagra was initially developed for high blood pressure and chest pain. Testing didn’t pan out but it worked wonders for erections so it was rebranded. It is also used in pulmonary hypertension.
Majority will have a micro, breast or hand practice and have a side hustle in aesthetics so the overall satisfaction stat you’re citing is not reflective.
There are different hassles in cosmetics like increased overhead, patient expectations (which are much higher in cosmetics) and advertising/patient recruitment. Call can be worse as the patient paying $50k for a rhinoplasty expects the surgeon to answer the phone for every whim.
In this context we are talking about a pain predictor from an xray which is neat but not the point of KL grading.
KL is a system to grade severity of osteoarthritis on radiographs (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925407/) and not a threshold for surgery or predictor of symptoms.
The comparator, current medical standards you reference, would be a model outperforming surgeon assessment in conjunction with radiographic findings. Not the predictive value of KL grade.
Screening intervals are based on doubling time.
> The idea of, say, proactively taking MRIs, blood panels, etc. on people, looking for early stage cancer (and other conditions) throughout the body is not something that's available.
You can pay out of pocket for a “screening MRI” in BC but from my clinical practice the yield is dubious.
> You can't even get an annual physical with a family doctor anymore,
Evidence has shown the physical is useless.
> there's only screening for a handful of specific diseases, and only once you reach certain ages/risk factors
Screening needs pretest probability and a diagnostic test with sufficient accuracy. It simply does not exist for most cancers. Trials are underway for new tests like cfDNA but in 2024 there aren’t any validated options.
Most if not all of the complication/risk (perforation and major bleeding being the ones of note) is from the polypectomy / biopsy part of the colonoscopy.
Not sure what a letter to the editor would accomplish. The nature paper only interpreted radiographs and the only claim of the authors was basically that the model is a better predictor of pain than KLG.
Your comment misinterpreted this as “using the patients' symptoms and objective data” (when they only used objective data) and added “may actually outperform current medical standards” which was not the claim as current medical standards already consider patient symptoms in addition to objective data, as stated in the article reference to the TKA guideline.
When I report a joint xray I’m not assessing the patient’s pain level, they can be asked that.
The harm is from investigating the screening test result and not the test itself.
> If it became a common thing for cancers to be detected, but the detection could reliably say “this is likely low impact, we should just keep an eye on it but not treat it”, this would be a lot less scary
This is already the case for some like prostate cancer and certain lymphomas.
> Cancer diagnoses are partly so scary right now because we’re often mostly catching cancers that have progressed and are causing symptoms
The most aggressive cancers are also the least likely ones to be diagnosed by screening due to growth rates, screening intervals and diagnostic test limitations.
I’m not sure what you mean by “very, very few years”. As a hypothetical would prolonging life for ~3-7 years in a 40-50 year old be considered “almost performative” to you?
“Good old medical care” often means 3-6 month survival for these patients.
5. Diagnosing cancer/disease early does not necessarily improve outcomes.
https://en.wikipedia.org/wiki/Lead_time_bias
https://en.wikipedia.org/wiki/Length_time_bias
> we do essentially nothing to catch it early.
Huh? That’s the whole point of cancer screening which we do a lot of in the West. The benefit of which remain hotly debated. New tests are also constantly being researched.
I think you’re jumping the gun here, this paper was a hot topic when it was published. Patient symptoms combined with objective data is already the medical standard.
Note that:
1. KLG is not a measure of pain but of OA radiographic severity.
2. KLG 3-4 is not a prerequisite for surgery.
From the article:
> While radiographic severity is not part of the formal guideline in allocations for arthroplasty (which only requires evidence of radiographic damage), empirically, patients with higher KLGs are more likely to receive surgery.
TKA patients skew to higher grade for many reasons, one being that studies have shown KLG 2 patients who undergo TKA are more likely to experience dissatisfaction (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344222/).
There are a lot of “ifs” in this paper which did not examine whether KLG 1-2 but ALG-P 3-4 patients benefit from TKA over conservative mgmt or other surgical interventions. It’s also unclear whether this better selects patients for TKA than KLG 1-2 + pain scores and other clinical variables.
All this shows is that KLG is a poor correlate for pain, which is known and not what the score is designed/used for.
Due to current hardware limitations it is not feasible to have a 1T parameter model without MoE.
As an example this is typically something like not offering CPR when death is imminent for another reason.
Pseudomonas infections are rare in healthy patients and few antibiotics work.
Similarly why bleach wipes > soaking in bleach for disinfecting surfaces, as alluded to in this paper.
Yes, the gigantic leap was transformers. No one thought we peaked with 340M or 1.5B parameters, in fact expectations from early work was that massively scaling was going to achieve zero-shot capabilities rather the emergent capabilities you're alluding to which are essentially variations of in-context learning, a relative disappointment.
Subsequent improvements in GPT-4, which seem to be mostly just more RLHF and MoE, are similarly not surprising and are temporizing measures while hardware and datasets are limited. Jury is still out whether the billions spent are worth it in terms of actually getting us closer to AGI.
It seems to be worth it for OpenAI/MS who are trying to be first to market and establish vendor lock-in.
If the intervention is unequivocally futile for preserving life it is permitted to not offer care, there are processes in place.
While unlikely, it is possible to survive necrotizing fasciitis and multiple debridements. Although it will come with many months of reconstructions, rehabilitation and pain.
We are legally and ethically obligated to offer heroic life saving measures if there is a chance of surviving. Quality of life is not a factor in our decision making process.
I do not know the exact discussion was had with this patient and their decision maker when incapacitated but it would be extremely unusual for a previously healthy 32 year old to decline heroic interventions, this is also a very rapidly evolving infection where you don’t have much time to think.
With that said I’ve also met 80+ year olds who want major surgeries that will leave them significantly impaired and almost certainly fail despite having time to think. At the end of the day patient autonomy supersedes our thoughts and opinions.
This article explores surface disinfection (commonly bleach in the hospital). Although provider gowns are removed after entering contaminated rooms, disinfected surfaces commonly come into contact with provider scrubs which are not laundered in between same day patient encounters as well as other patients (such as the table of a CT or MRI).
I don’t see the gymnastics you’re referring to, other studies have looked at laundering processes which is not the focus of this study.
Also relevant for things that travel between rooms and are disinfected in between, like ultrasound machines.
Other studies have reported that spores can survive washing processes in use.
I remember we used to give patients vanco IV bags to drink on discharge for outpatient therapy because the PO formulation was too expensive for some (iirc I paid $300 for a 10 day course).
Thanks for the info!
Pain reduction isn’t the main reason to operate or the metric of interest, there are many ways to alleviate acute pain including casting.
Functional impairment (immediate and delayed) and reducing the risks of posttraumatic arthritis are far more important.
Joint infections (and pseudomonas in general) are an absolute nightmare as the joint space is not vascular.
Bone infections/osteomyelitis are much rarer and for the most part less catastrophic (although they certainly still can be).
As always patient autonomy is paramount and we all value risks differently. For myself as a young healthy adult (not an orthopaedic surgeon) I would rather accept the minimal risks of surgical reduction and fixation for a fracture needing one than risk needing complex reconstruction or joint replacement in 10-20 years which has much higher complication rates and longer recovery.
Personal experience in US academia also suggests not, far more concern for early diagnosis of infection and IPAC than I saw practicing in Canada.
Some places are still old fashioned though, I believe Mayo is still suit and tie.
I was unlucky enough to get CDI in medical school when flagyl was first line and had to pay OOP for PO vanco, I assume that’s changed now.
What’s first line in Canada these days, is fidaxomycin covered?
I don’t think they’ve had the will/need to have done this but they most likely already have the talent.