Sure. As I stated in my original comment, I'm excited about CGMs being widely available. The example in my comment was very specifically answering "why do doctors perform unnecessary interventions?".
You don't know if it's a false positive or not until you do further interventions. Realizing it's unnecessary is only evident in hindsight.
E.g. CT scan shows an incidental, tiny lung nodule. You do a biopsy. Unfortunately, during the process of getting a biopsy, you develop a pneumothorax (an uncommon but well-known complication of a lung biopsy) and need a chest tube, hospitalization, etc. You get discharged and you're fine, but man, that wasn't fun. Biopsy comes back negative for cancer. Nodule goes away on its own with time.
Edit: that being said, I'm excited about OTC CGMs! But the "data" we have in medicine is not as accurate as other fields and always subject to false positives/negatives.
The standard of care in the US is immunohistochemistry (IHC), with FISH testing in equivocal cases so not really ELISA based.
HER2 testing is done on all breast cancers as it affects treatment choices though the majority of breast cancers are not HER2 positive. (HER2 is also expressed in some normal tissue (notably cardiac) and is also seen in other cancers as well).
You're right that benefits of screening vary widely depending on type of cancer, type of test, and even a patients own co-morbidities. However, there are a lot of inaccuracies in this comment.
False positives on a screening test are bad because you follow a screening test up with a confirmatory test (a biopsy for cancer) - sometimes the procedure for the biopsy results in additional complications and even death in rare cases (and if it's a false positive, a patient goes through all of that for a benign finding).
I want to be very clear that oncologists are not going to start cancer treatment on the results of a screening test, you need confirmation.
It also only looks at HER2 and CA15-3 (aka MUC1) expression - what about breast cancers that don't express either of these?
I realize this is an early technology and I think it should continue to be explored, but I would anticipate that if compared head to head with screening mammograms, it would be inferior.
For patients with relapsed disease, this kind of technology would be neat to non-invasively re-assess biomarker status but as a screening tool, I find it lacking (and certainly a positive screening will require dedicated imaging and biopsy anyway).
Hey friend, I'm so sorry you're going through that and I wish you the best of luck in your journey.
I would argue though that it's not rocket science...currently, it's a lot harder with many more unknowns. Some of the issues we face are:
- Imperfect screening tests: the (very real) risk of both false positives and false negatives
- Lack of great prognostic models: if we think a certain cancer has a 25% chance of metastasizing within 5 years and I have 4 patients in front of me, how do I know which is the one?
- How do we identify if we're actually changing the trajectory of cancer with certain treatments? If a treatment fails, is it because we didn't choose the right treatment or is it reflective of underlying aggressive disease biology?
- Mass amounts of data from new technologies: this is obviously great and has allowed us to become granular with cancer in a way we haven't been able to before. It's important to recognize that widespread next generation sequencing is something we've had for less than a decade, and we have identified a lot of risk factors with this BUT it's also raised many questions (e.g. what mutations are actually significant?).
- Being human: every individual has their own values. Some patients will hear that it's a 1% chance this will become cancer and be okay with monitoring it. Some patients hear 1% and think it's too much of a risk and want intervention.
I think, with time and more data, we will become a lot better at this. But it's really not easy.
The general public definitely doesn't have a great understanding of the word "cancer." Patients often don't know that prostate cancer is not the same as lung cancer is not the same as colon cancer, etc.
And unfortunately, cancer is a lot more nuanced than that with a lot of heterogeneity even within a cancer type, e.g. an 80 year old male incidentally found to have an elevated PSA and subsequent low grade prostate cancer has a biologically different disease than a 35 year old who comes in with de novo metastatic prostate cancer.
I wish we had better ways of predicting what a patient's life will look 1 or 5 or 10 years down the line. We're developing the tools to do that, but there is still a significant amount of uncertainty and we can't eliminate that anxiety for patients. I don't know if re-naming low risk prostate cancer will do that either, but I can't say I feel strongly about it one way or another.
I hope that the population starts to get a better understanding of what "cancer" really is (i.e. a very wide spectrum of diseases), the inherent uncertainty associated with the diagnosis, and that we continue to get better predictive tools in the meantime.
I see neurodivergent individuals (or at least, significantly neurodivergent that a more individualized approach is needed) relatively rarely in my field of work (adult oncology, where the average patient is much older and has often had significant exposure to the healthcare system). Every patient I've seen has been very different in terms of needs and their prior experiences and so I have difficulty imagining a "standardized" curriculum for these patients that is specific enough to add value but broad enough to apply to every medical student, but I'm happy to be corrected on this.
And, I mean, if we're talking about neurodivergence more broadly and including people who generally "pass" as neurotypical, then that's a huge chunk of the population. Really, any time you talk to a patient, you should be assessing where they're at, in terms of general understanding and preferences, and should always tailor your approach to an individual.
I'll finish up my fellowship this summer and it will have been a solid 10 years from when I started medical school. The vast majority of people have no idea what goes into medical training (even my own parents remain confused) - and that's okay, there's no need for everyone to know these ins-and-outs, but when we're passing judgment on the medical curriculum and adding additional things, it does become important.
You can talk about adding a class in medical school addressing neurodivergence and disability, but how do you really address that spectrum of diversity in a single class? And what aspects do you really retain a decade out when patients with neurodivergence can be relatively rare (depending on your specialty)?
In the end, I think the best learning comes from seeing patients (especially, again, as the spectrum of what these patients experience is so diverse and individual). I am always grateful to patients who provide guidance along with parents or caregivers and nurses who had often cared for that patient before for their advice on how to approach a specific patient, along with individual behavior plans if in place.
As you've said, the human body is complex. We don't always know what's wrong - of course we do our best with the tests we have, but often we're ruling things out and are left without a clear answer. When I try to tell patients that "I don't know", they're frustrated with me. And frequently, it's the patients that are mad that I don't have a pill or procedure that can fix it immediately.
You say that doctors like diseases that we can treat...well, of course we do. I want to help people! Why would I enjoy having to tell someone they're feeling badly but I can't figure out why with my current available tests and data? It doesn't mean that the symptoms aren't real, I just don't know what's causing them.
People think modern medicine means we have all the answers, but that's not the case by a long shot and the vast majority of human experience and condition is still unknown, and I do wish people understood that more.
(And, side note, insurances put up a fight with a ton of doctor-prescribed orders as well, it's a huge problem in the system. I'm sure all healthcare workers would love universal dietitian coverage.)
That's fair, this definitely may be a functional cure for many people and that's absolutely something to be celebrated.
The language around "cure" is complicated in general. We often use it in diseases like cancer but with modern therapies, we do have some patients on long-term therapy making their cancer more of a chronic one - are they cured? On the other hand, we rarely use the word cure with diseases like hypertension or diabetes which can devastating diseases in their own right but can be controlled effectively with medication.
So yes, what should really matter is the actual outcomes - are people living longer? Is their quality of life better? And, with exa-cel/Casgevy, the latter is absolutely true (and the first will be known after time).
Realistically, this treatment is not going to be available in places with a high prevalence of malaria for a long time, so I don't think this is too much of a concern.
CRISPR is definitely an awesome technology, and I'm glad that after many decades of research, we're finally getting approved treatments as a result.
That being said, I do want to clarify that this isn't a "cure" for sickle cell disease. It is not editing the gene causing sickle cell itself, but rather allowing for increasing production of HbF (fetal hemoglobin) by knocking down a suppressor. Hydroxyurea, a current standard of care option in sickle cell disease, also increases HbF production but response can be variable among patients (but when it works, absolutely improves quality of life!)
In addition, I think we always need to keep in mind potential toxicities and hopefully, we learn more about this when the publication actually comes out. It's important to note that giving this therapy requires giving high dose chemotherapy beforehand, and I'd also be interested in knowing how long this therapy actually lasts as I do expect the product may wane with time.
But still, so excited to see CRISPR technology coming to the public and the potential for this technology in many different disease states!
No, this treatment would not - it does not act by "fixing" hemoglobin S (which causes sickle cell disease), but rather increasing production of hemoglobin F (fetal hemoglobin).
The truth is, in medicine, we often fall into a trap of treating a number rather than the patient, and Vitamin D abnormalities are a classic example of this.
It's well known that by our current reference ranges, the vast majority of humans will be Vitamin D "deficient" but it's unclear what "sufficiency" truly is (https://www.nejm.org/doi/full/10.1056/nejmp1608005). Outside of known effects on bone health (e.g hyperparathyroidism), trials studying Vitamin D supplementation in a variety of disease states have not panned out.
All in all, I think this labeling is unlikely to cause significant harm given the unclear nature of Vitamin D deficiency, though I don't fully understand the need for this label in the first place as Vitamin D over-supplementation is unlikely as well.