Yes - non experts like myself need to be very careful when rejecting the opinions of experts.
A Fair enough statement, and article, I think.
Though the Internet probably has also made it possible for (on the long tail) some people with a background in adjacent knowledge domains, to become experts in new domains. E.g. a guy like Karl Pfleger, ex Google AI engineer, into Longevity Biotech angel investor. Its more of an issue when a professional baker or interior decorator (or business tech guy like myself, as an off the cuff example) thinks they can quickly catch up to the knowledge / expertise level of a PHD/MD in biology studying aging.
And of course, just as studies have shown that something like 70% of drivers think they are better than average drivers, many more people probably think they are domain experts than actually are.
So, yes - something we probably want to be careful of here.
Iād also note I donāt blame my colleagues for that. Offlabel usage often needs to be substantiated with human clinical trials. CYP3A4 inhibitors (i.e. grapefruit) can make Viagra a bit of a challenge in medical management. Iād note itās way too easy to get Viagra prescription online with all these ED telemed startups and patients using it for non labeled use.
@tongMD would you agree with this rough estimate of the risk level for taking SGLT2i inhibitors and Fournierās gangrene, or do you believe the combination of SGLT2 inhibitor plus rapamycin (plus other supplements ā¦) raises the risk significantly above this level?
Thank you and all other health professionals for joining and contributing to this community. I know I am learning immensely. Just a small note to convey my appreciation.
Since I am only taking the minimum dose of 50 mg, not the usual 100mg, the increased effectiveness would not push to 100mg when taking grapefruit juice. BTW, I only take grapefruit juice on the days I take rapamycin and I donāt take any supplements or prescription drugs on that day.
āgrapefruit juice increased the mean oral bioavailability of sildenafil by 23%.ā
It depends. You have to run a lot of factors thatās based on the individual and thereās limited data.
At the very least, I personally test CBC w diff to check, and if thereās mild neutropenia that is uncomplicated, I personally do serial CBCs weekly for 4 weeks and then 3 mo later and watch for sx and non-low grade fever. I also checked WGS and specifically for āDuffy nullā, CXCL2/CXCR2 etc etc
" I personally do serial CBCs weekly for 4 weeks"
I go to a local Quest facility for my blood and usually see the same lab tech.
Though I donāt check as often as you, I go often enough that I can tell by the way the tech looks at me, he wonders what the hell is going on.
This is EVERY doctorās visit for me and everyone in my family for the past 20 years. Utterly worthless unless youāre bleeding out of your eyes.
OT rant:
My sisterās life was ruined due to the inability of doctors to diagnose her with Lyme Disease. This included me fighting with the insurance company to first send her to Boston Eye and ear (how a MA hospital didnāt think of Lyme is unbelievable. Second, I got them to agree to send her to The Mayo Clinic. 7 days there and they didnāt figure it out and, after the first 3 days, shifted the focus to psychiatric! Every doctor ended up going there (psych) except her sinus surgeon. They did this with her sinuses all but gone after 9 sinus surgeries and massive amounts of both fungal and bacterial infection in her sinuses plus osteomyelitis eating away the bone in her face. But, yeah, itās all āin her headā. /rant
Emergency medicine, neurosurgery (an amazing one saved my grandmotherās life) and the like: Doctors save lives.
Most of the rest: not so much. We know way more than they do about a lot of stuff where that just shouldnāt be the caseā¦
I canāt say in any particular individual case, especially in East Coast where itās endemic. But thereās way too much noise regarding patients with suspected Lyme such that everyone just gets blowed off easily - itās kind of like COVID patients demanding ivermectin treatment - in my geographic area.
There is a very good reason why our infectious disease department automatically declines anyone claiming they have Lyme disease to be admitted or consulted unless they have clear evidence of traveling to an endemic area.
My personal rant: Most doctors suck at diagnosis.
Most doctors see too many patients and therefore donāt have time to make a proper diagnosis
Most doctors donāt actually listen to their patients and are inclined to dismiss the patientās opinions. Dr. thinking: (Iām smarter than you and I know it.)
But if the problem is a common one he will be able to diagnose and treat you. We do need our doctors.
Thatās a product of the system. The bean counters expect all employed physicians to see patients in 5-10 min per patient. Or we get docked due to lack of patient volume. When I had my first rotation in family medicine (back in med school) - my attending was double or triple booked every 15 min. It doesnāt matter if youāre the best diagnostician in the world. 5 min is not enough and thereās only so much you can listen to before youāre forced to cut a patient off due to patient volume targets.
Get a concierge physician. You get an average of 30-35 min. Youāll save on the copay for labs too. Itās not that expensive and can save you a lot in the long run. If your income is too low - there are low cost direct primary care options at an academic center.
After that experience - itās clear to me that you have to avoid āfactory medicineā intended to account for insurance companies, not patient-centered.
My psychiatrist (former professor with deep research background) literally said if he took insurance instead of cash pay of $550/hr - some HMO insurance companies would only pay ~$20 for a visit.
That is literally ludicrous (nobody is going to pay off $200,000-400,000 med school loans + college loans with interest) and itās no surprise decent psychiatrists are not taking insurance. Itās also no surprise that there are all these pill mill startups farmed out to nurse practitioners with no research background.
It was just a rant: an emotional, illogical burst of occasional subjective feelings
By and large, I am currently happy with my personal healthcare system.
The saddest part of your response illustrates the frustration people have in trying to get affordable mental health care.
I know you didnāt come here to get your āfair share of abuseā
increase in extracellular matrix caused by chronic hyperglycemia that leads to increased JNK signaling. The extra matrix increases mechanical stress, which activates JNK. This, in turn, signals the muscle cells to bulk up rather than adapt to the aerobic activity.
So if you want to bulk up, you want high blood sugar? Probably not a good idea, since you wonāt get the aerobic benefit and perhaps it would bulk up the heart muscles, which could be terrible. Iād rather be medium-sized, strong, and aerobically fit.
SGLT2 Inhibition via Empagliflozin Improves Endothelial Function and Reduces Mitochondrial Oxidative Stress
Results: We evaluated 407 patients; 325 frail elders with diabetes successfully completed the study. We propensity-score matched 75 patients treated with empagliflozin and 75 with no empagliflozin. We observed a correlation between glycemia and Montreal Cognitive Assessment (MoCA) score and between glycemia and 5-meter gait speed (5mGS). At 3-month follow-up, we detected a significant improvement in the MoCA score and in the 5mGS in patients receiving empagliflozin compared with non-treated subjects. Mechanistically, we demonstrate that empagliflozin significantly reduces mitochondrial Ca2+ overload and reactive oxygen species production triggered by high glucose in human endothelial cells, attenuates cellular permeability, and improves cell viability in response to oxidative stress.
However, SGLT2i also have a few well-known adverse effects that should be taken into consideration to scale their risk-benefit ratio before prescribing them to the patients. Vaginal fungal infections, urinary tract infections, and polyuria are the most frequently reported side effects of this class [1]. One rare but potentially fatal outcome of this drug that should not be overlooked is Diabetic Ketoacidosis (DKA). The pathophysiology of SGLT-2-associated DKA has received little attention.
Furthermore, a meta-analysis conducted by Liu et al. also reported that SGLT2 inhibitors increase the risk of DKA when compared to the control population i.e., patients who are not consuming SGLT2i [3]. SGLT2 inhibition results in excessive lipolysis and the subsequent rise of free fatty acid levels contributes to the pathogenesis of ketogenesis. This mechanism becomes more accountable for DKA in an insulin-deficient state.
In light of the aforementioned statistics, physicians must take important precautions for their patients before prescribing this drug. They should rule out the possibility of DKA in every patient to avoid potentially fatal complications. Patients should be informed about DKA symptoms such as fruity-smelling breath, muscle aches, headache, lethargy, and deep breaths and glucose levels should be monitored regularly in high-risk patients.
Empagliflozin mitigates endothelial inflammation and attenuates endoplasmic reticulum stress signaling caused by sustained glycocalyx disruption
The disruption of the endothelial cell (EC) glycocalyx (GCX) leads to cellular dysfunction promoting inflammation and cardiovascular disease progression. Recent studies have shown that empagliflozin (EMPA; Jardiance), a sodiumāglucose cotransporter 2 inhibitor used in the treatment of type 2 diabetes, can improve EC functions impacted by GCX disruption although the exact cellular mechanisms remain to be elucidated.
