If you want to save lives, you've got to catch it early. But is it worth it?

Ovarian Cancer is not something I spend a lot of time working on, but it’s a terrible disease, mostly because it’s usually diagnosed very late, making it very difficult to successfully treat.  Sure, the BRCA gene story has segment some of those people, but then they’re having prophylactic surgery (removal of breast and/or ovaries) to avoid the future possibility of cancer.  One would think that a better option is needed.

The study presented is really interesting in how effective it is at identifying early disease and thereby limiting surgical removal of actual diseased organs and effecting cures.  A simple blood test done regularly over time can screen people and help target those with hints of problems, escalating interventions as required.  This approach clearly works, and actually works very well.  

Now the problem is the money.  How much does it cost to save someone’s life?  There is a metric known as QALY (Quality Adjusted Life Year) that’s used to calculate the “value” of an intervention.  Sometimes the calculation gets very complex, but it usually only takes into account the health care costs, not the societal costs, so it’s not always a great way to measure “value”.  A standard, conservative figure for QALY value is $50,000.  That means that a treatment would cost $50,000 for every year of life saved.  Some inexpensive blood pressure medications come in around $15-30,000; an annual screening mammogram for women over 50 works out around that $50k number.  The challenge comes in when you stretch the target audience – for women over 40, the number rises to around $200k.  In the case of screening for prostate cancer, there’s never been a figure calculated because it’s not clear screening actually saves lives, but that’s another story.

Here we have a very clear option for screening that is very good at finding the target.  It now will have to wait for the economics to be determined and whether or not saving these lives “is worth it”.

From the Journal of Clinical Oncology / By Chae Young Han, PhD, Karen H. Lu, MD, Gwen Corrigan, Alexandra Perez, CMA, Sharlene D. Kohring, HSD, Joseph Celestino, BS, Deepak Bedi, MD, Enrique Bedia, MD, Therese Bevers, MD, David Boruta, MD, Matthew Carlson, MD, Laura Holman, MD, Leroy Leeds, MD, Cara Mathews, MD, Georgia McCann, MD, Richard G. Moore, MD, Matthew Schlumbrecht, MD, Brian Slomovitz, MD, Dan Tobias, MD, Yvette Williams-Brown, MD, Michael W. Bevers, MD, Jinsong Liu, MD, Terrie G. Gornet, BS, Beverly C. Handy, MD, Zhen Lu, MD, Jacob S. Bedia, BS, Steven J. Skates, PhD, and Robert C. Bast Jr, MD

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

Purpose

The Normal Risk Ovarian Screening Study (NROSS) tested a two-stage screening strategy in postmenopausal women at conventional hereditary risk where significantly rising cancer antigen (CA)-125 prompted transvaginal sonography (TVS) and abnormal TVS prompted surgery to detect ovarian cancer.

Methods

A total of 7,856 healthy postmenopausal women were screened annually for a total of 50,596 woman-years in a single-arm study (ClinicalTrials.gov identifier: NCT00539162). Serum CA125 was analyzed with the Risk of Ovarian Cancer Algorithm (ROCA) each year. If risk was unchanged and <1:2,000, women returned in a year. If risk increased above 1:500, TVS was undertaken immediately, and if risk was intermediate, CA125 was repeated in 3 months with a further increase in risk above 1:500 prompting referral for TVS. An average of 2% of participants were referred to TVS annually.

Results

Thirty-four patients were referred for operations detecting 15 ovarian cancers and two borderline tumors with 12 in early stage (I-II). In addition, seven endometrial cancers were detected with six in stage I. As four ovarian cancers and two borderline tumors were diagnosed with a normal ROCA, the sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23), and 70% of ROCA-detected cases (12 of 17) were in stage I-II. NROSS screening reduced late-stage (III-IV) disease by 34% compared with UKCTOCS controls and by 30% compared with US SEER values. The positive predictive value (PPV) was 50% (17 of 34) for detecting ovarian cancer and 74% (25 of 34) for any cancer, far exceeding the minimum acceptable study end point of 10% PPV.

Conclusion

While the NROSS trial was not powered to detect reduced mortality, the high specificity, PPV, and marked stage shift support further development of this strategy.

Weight Loss Drugs Often Stall

Most people are familiar with the concept of a weight setpoint.  The setpoint is the body’s somewhat “natural” weight – seems like we always drift back to a particular number.  When we diet, if we get too severe in our restriction, the body moves into a kind of starvation state, our energy utilization (fat burn) drops and we hang onto the weight.  And we slowly drift back to where we were (unless you’ve yo-yo’d so much that you actually end up drifting even higher).  It’s really hard to reset our set points.  

The new GLP-1 weight loss medications – Wegovy, Ozempic, Mounjaro have proven themselves to be very helpful for many, if not most people.  Most overweight people (that’s nearly ½ of America) have some measure of insulin resistance, and thus these medications make sense, and work.  Of course, like all medications, there can be side effects, and some can be really severe.  Even so, they are a tremendous step forward for many, many people who have struggled with their weight.

As many of us would have expected, it appears that the GLP-1 meds may not be able to eliminate the set point problem.  It is likely that most people will be able to RESET their set points to a lower number, then seemingly virtually everyone will plateau.  This is no surprise – a metabolic process will work according to the overall environment.  Likely the situations that influenced the weight gain in the first place will continue to have some sway of the future.  

It doesn’t mean that people should avoid the medication.  If there’s a good reason to start it, it’s worth the try.  Only understand that the weight loss rainbow may not end in a kettle of gold.  Though for many, it’s a lot more than spare change!

FROM MEDPAGE TODAY/ BY SOPHIE PUTKA

The GLP-1 Agonist Plateau No One's Talking About

— Weight stabilization is no surprise to specialists, but for patients it's more complicated

The declines in body weight that patients experience with injectables like semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro) are no exception to the concept that nothing lasts forever.

Eventually, everybody reaches a "plateau," even on newer GLP-1 receptor agonists. It's a phase at which the body reaches a new "settling point," specialists said, and weight, along with other metabolic markers like blood pressure and HBA1c stabilize, or fluctuate only slightly. For some, this may mean a gradual increase in appetite or "food noise"; others may be able to maintain their current state.

Studies have shown that, on average, this plateau happens at a little over a year with semaglutide. Even so, physicians say some patients are surprised to learn that there's a limit to what these medications can do.

"Everyone will plateau, of course. No one on my watch has disappeared. No one has vanished," Jody Dushay, MD, an endocrinologist at Beth Israel Deaconess Medical Center in Boston, told MedPage Today. "It's alarming to me that people find that surprising, but everyone will reach a plateau and there's no way to know when you start the medication what that will be, what percent weight loss that will be, and how quickly they will reach it."

Gitanjali Srivastava, MD, an obesity medicine specialist at Vanderbilt University Medical Center in Nashville, Tennessee, noted that "we see that often and it's a question that gets asked frequently. There's going to be a new homeostatic balance that's achieved, and we see that with any other disease phenomenon."

For example, Srivastava told MedPage Today that a patient will not become hypotensive after a certain amount of time on a blood pressure medication, or have blood glucose levels decrease indefinitely with diabetes medications. "Evolutionarily, we need to be able to do that, so we can protect against the extremes," she added. "Because the alternative is that you continue to wither away, and that can be dangerous."

It's still unclear what may predispose patients to longer or shorter responses to GLP-1 agonists, but Dushay said that, typically, early responses tend to predict later ones. If a patient experiences steep weight loss on lower doses of semaglutide, for example, they can stay on a lower dose for longer, with more time to uptitrate if necessary. Patients on semaglutide for type 2 diabetes also tend to experience less weight loss overall, she said.

Karl Nadolsky, DO, an endocrinologist and obesity medicine specialist at Holland Hospital in Michigan, told MedPage Today in an email that "a history of childhood obesity with any suspicion [of] specific genetic or syndromic etiology" might also hint at a predisposition to hyporesponse.

Specialists have said that before prescribing this class of medication, they thoroughly discuss what to expect, from side effects to plateauing and the possibility of non-response. Dushay noted that it's important that providers set these expectations with patients, and for patients to seek out doctors who have the time and clinical experience to do so.

In clinical trials that looked at semaglutide 2.4 mg per week, participants' weight loss tapered off around week 60, with about 10% to 15% of body weight lost. Semaglutide's effect on blood pressure and HBA1c appeared to plateau even earlier. Spanning 2 years, patients hit a weight plateau once again around 60 weeks, and were able to maintain that weight for the remainder of the study. In the Surmont Trial which looked at various doses of tirzepatide for 72 weeks, participants on the 5-mg dose had reached a plateau within 60-72 weeks, but this was not the case on the higher doses. A 2-year trial is expected to offer more insight.

However, clinicians are more interested in what such averages hide. It's nearly impossible to know how well a patient will respond to semaglutide or tirzepatide, and individuals may have wildly different medical histories, medications, and comorbidities that all affect how well, and for how long, a given drug may work.

Fatima Cody Stanford, MD, MPH, MPA, MBA, an obesity medicine specialist at Massachusetts General Hospital in Boston, pointed out that a patient's expectation may not match their ultimate response to a GLP-1 agonist. "Everybody comes in and they're like, 'I want to do what this person did' -- they have their family, their friend, their sister, their brother, cousin, aunt, and I'm like, 'well, we don't know,'" she said. "The only people that I expect to respond almost identically are identical twins."

Stanford said she would like to see studies on GLP-1 agonists in the future that stratify patient response by various characteristics like genetics. Right now, she noted, weight-loss drugs require a lot of trial and error. Predicting the likelihood of success for individual patients would save time -- and money. "When a new cancer drug comes out, not everyone's like, 'ooh, there's a new cancer drug, let's just start everyone on that.' Right? Nobody does that," she said. "I want to know who the drug is right for."

"If I know that, on average, this person is going to be a really poor responder to a GLP-1 agonist, I won't [prescribe it]," she added. "It is a really arduous pathway for a lot of reasons -- access, coverage, prior authorization. It's burdensome. It's burdensome on the patient, it's burdensome on the system, it's burdensome on me."

Experts said it's common for patients to want more. For example, they may bring their blood glucose within a normal range, go off of blood pressure medications, and maintain overall positive health outcomes with a GLP-1 agonist, but hit a "plateau" and still want to lose weight.

Ultimately, this is where psychological and societal ambitions collide with clinical ones.

Patients are "having to negotiate with what society tells them, so they're still 200 pounds and society says 'for your height and weight you should be 125,' even though their health looks amazing," Stanford said. "Not always, but often, they still want to be whatever this number is."

Dushay said it's rare for patients to achieve the weight loss goal they arrive at an initial consult with. Often, Dushay's noticed, this goal is the weight they were on their wedding day. "I think that some of it is literally [that] they want to weigh that," she said. "But I think there is a big component of 'I want to rewind time.'"

"I've almost never had someone hit a plateau when they were like, 'okay, I'm good.'"

In the meantime, clinicians have strategies to move past a plateau if a patient hasn't yet met important clinical goals. Generally, some said they might increase the dose if possible, if the patient can tolerate it well. Failing that, they can supplement with a second drug that targets a different neuronal or hormonal pathway, like phentermine (Lomaira). Dushay said that in practice she's noticed that "drug holidays" or stopping and restarting a GLP-1 agonist, have typically not affected plateaus.

You didn't get Long COVID, but that doesn't mean it didn't do long term damage

Nearly everyone has had COVID by now.  If you got it early, you probably got it worse than others, but not necessarily.  Many people have suffered, and many people have continued to suffer.  Long COVID has recently be shown to have blood abnormalities (we knew that ages ago) that can prove “it’s not in your head”.  But more than that, every time one gets COVID, there’s a risk that bad things will happen – and persist.  Here’s a study that shows that if you get COVID you have 1.50 times the risk of having hypertension (high blood pressure) then if you didn’t get COVID, but if you were hospitalized for COVID, the risk of HBP goes up to 2.2x’s.  We’ve said this is a blood vessel disease, and this just bears it out. 

Don’t assume that everything is fine if you have COVID and you get over it.  Even Long COVID can be delayed by a couple of months!  Don’t assume – follow up with your doctor and make sure other problems don’t develop.

FROM AHA JOURNAL / BY VINCENT ZHANG, MOLLY FISHER, WEI HOU, LILI ZHANG, TIM Q. DUONG

Incidence of New-Onset Hypertension Post–COVID-19: Comparison With Influenza

Abstract

BACKGROUND:

SARS-CoV-2 may trigger new-onset persistent hypertension. This study investigated the incidence and risk factors associated with new-onset persistent hypertension during COVID-19 hospitalization and at ≈6-month follow-up compared with influenza.

METHODS:

This retrospective observational study was conducted in a major academic health system in New York City. Participants included 45 398 patients with COVID-19 (March 2020 to August 2022) and 13 864 influenza patients (January 2018 to August 2022) without a history of hypertension.

RESULTS:

At 6-month follow-up, new-onset persistent hypertension was seen in 20.6% of hospitalized patients with COVID-19 and 10.85% of nonhospitalized patients with COVID-19. Persistent hypertension incidence among hospitalized patients did not vary across the pandemic, whereas that of hospitalized patients decreased from 20% in March 2020 to ≈10% in October 2020 (R2=0.79, P=0.003) and then plateaued thereafter. Hospitalized patients with COVID-19 were 2.23 ([95% CI, 1.48–3.54]; P<0.001) times and nonhospitalized patients with COVID-19 were 1.52 ([95% CI, 1.22–1.90]; P<0.01) times more likely to develop persistent hypertension than influenza counterparts. Persistent hypertension was more common among older adults, males, Black, patients with preexisting comorbidities (chronic obstructive pulmonary disease, coronary artery disease, chronic kidney disease), and those who were treated with pressor and corticosteroid medications. Mathematical models predicted persistent hypertension with 79% to 86% accuracy. In addition, 21.0% of hospitalized patients with COVID-19 with no prior hypertension developed hypertension during COVID-19 hospitalization.

CONCLUSIONS:

Incidence of new-onset persistent hypertension in patients with COVID-19 is higher than those with influenza, likely constituting a major health burden given the sheer number of patients with COVID-19. Screening at-risk patients for hypertension following COVID-19 illness may be warranted.

There IS evidence that COVID shots affect your heart

This subject could get me in trouble but it's the truth. There is a very small number of people who get heart inflammation (myocarditis) after COVID immunization.  But I have test (Multifunction Cardiogram) that has shown low levels on heart inflammation in patients who shouldn't have that, but they've had the SHOT.  

As I've said time and again every medical intervention needs to be considered in context - the individual matters.  

FROM RSNA / BY TAKEHIRO NAKAHARA, YU IWABUCHI, RAITA MIYAZAWA, KAI TONDA, TOHRU SHIGA, H. WILLIAM STRAUSS, CHARALAMBOS ANTONIADES, JAGAT NARULA, MASAHIRO JINZAKI

Assessment of Myocardial 18F-FDG Uptake at PET/CT in Asymptomatic SARS-CoV-2–vaccinated and Nonvaccinated Patients

Abstract

Background

Patients who developed myocarditis after SARS-CoV-2 vaccination show abnormalities on cardiac MRI scans. However, whether myocardial changes occur in asymptomatic individuals after vaccination is not well established.

Purpose

To assess myocardial fluorine 18 (18F) fluorodeoxyglucose (FDG) uptake on PET/CT images in asymptomatic patients vaccinated against SARS-CoV-2 compared with nonvaccinated patients.

Materials and Methods

This retrospective study included patients who underwent 18F-FDG PET/CT for indications unrelated to myocarditis during the period before (November 1, 2020, to February 16, 2021) and after (February 17, 2021, to March 31, 2022) SARS-CoV-2 vaccines were available. Myocardial and axillary 18F-FDG uptake were quantitatively assessed using maximum standardized uptake value (SUVmax). The SUVmax in all patients and in patients stratified by sex (male or female), age (<40 years, 41–60 years, >60 years), and interval between vaccination and PET/CT were compared using the Mann-Whitney U test or the Kruskal-Wallis test with post ad hoc Dwass-Steel-Critchlow-Fligner multiple comparison analysis.

Results

The study included 303 nonvaccinated patients (mean age, 52.9 years ± 14.9 [SD]; 157 female, 146 male) and 700 vaccinated patients (mean age, 56.8 years ± 13.7; 344 female, 356 male). Vaccinated patients had overall higher myocardial 18F-FDG uptake compared with nonvaccinated patients (median SUVmax, 4.8 g/mL [IQR, 3.0–8.5 g/mL] vs 3.3 g/mL [IQR, 2.5–6.2 g/mL]; P < .001). Myocardial SUVmax was higher in vaccinated patients regardless of patient sex (median range, 4.7–4.9 g/mL [IQR, 2.9–8.6 g/mL]) or age (median range, 4.7–5.6 g/mL [IQR, 2.9–8.6 g/mL]) compared with corresponding nonvaccinated groups (sex: median range, 3.2–3.9 g/mL [IQR, 2.4–7.2 g/mL]; age: median range, 3.3–3.3 g/mL [IQR, 2.3–6.1 g/mL]; P < .001 to P = .015). Furthermore, increased myocardial 18F-FDG uptake was observed in patients imaged 1–30, 31–60, 61–120, or 121–180 days after their second vaccination (median SUVmax range, 4.6–5.1 g/mL [IQR, 2.9–8.6 g/mL]) (P < .001 to P = .001), and increased ipsilateral axillary uptake was observed in patients imaged 1–30, 31–60, and 61–120 days after their second vaccination (median SUVmax range, 1.5–2.0 g/mL [IQR, 1.2–3.4 g/mL]) compared with the nonvaccinated patients (P < .001 to P < .001).

Conclusion

When compared with nonvaccinated patients, asymptomatic patients who received their second vaccination 1–180 days prior to imaging showed increased myocardial 18F-FDG uptake on PET/CT scans.

Don't get stuck holding the bill!

Everybody should have some form of health insurance.  Unfortunately, coverage is very often not what people want it to be.  Regularly there are copays, co-insurance and just plain non-covered situations, so being surprised is not an uncommon occurrence.  

The story attached is a another one of those surprises.  A very expensive drug has often been dosed in an office, but over time, more people decided to do the injection themselves.  So Medicare decided that everyone should inject themselves.  The guy in the story has Parkinson’s making self-injection very difficult, and potentially impossible.  Now he’s stuck with the bill (unless the class action suit wins).  

The morale is that you need to know your responsibilities.  My practice is almost entirely cash – there really aren’t surprises.  Insurance is designed to make sure that really big ticket items will be covered.  Of course, many of those items come with a 20% copay….  

Maybe the best thing to do is make sure you get ahead of your health.  Don’t wait for the problem.  Be proactive!  We can help.

FROM MEDPAGE TODAY / BY CHERYL CLARK

A 'SAD' Story: Patient Stuck With $176K Bill After Medicare Policy Switch

— CMS abruptly decided patients can self-administer Stelara -- even those with Parkinson's

For 5 years, retiree George Beitzel went to a Sacramento-area clinic every 2 months so a nurse could give him an injection of the costly drug ustekinumab (Stelara), which his doctors prescribed for his Crohn's disease.

To have a licensed professional give the shots was especially important for Beitzel, now 84, because he has Parkinson's disease.

"I shake like a bug," making it impossible to safely give himself the injections, Beitzel told MedPage Today.

Even though Stelara is among the most expensive drugs on the market, costing upwards of $40,000 per dose, Medicare had always paid for his injections under Part B, which covers drugs delivered by a doctor's office or a clinic. With his co-payments covered by his supplemental plan, "I never had to pay a thing," he said.

But all of that changed on October 15, 2021, unbeknownst to Beitzel and the clinic that continued administering his injections for another 7 months. That's according to a class-action lawsuitopens in a new tab or window filed last week by the non-profit Center for Medicare Advocacy (CMA) on behalf of Beitzel and another patient, in U.S. District Court, Eastern District of California, against HHS Secretary Xavier Becerra.

What CMS quietly and abruptly did that day was alter its payment policy on Stelara, said CMA's Litigation Director Alice Bers. It decided -- based on Medicare claims data whose use for this purpose is controversial -- that since more than 50% of Stelara users inject the drug themselves, to reclassify the drug as a "SAD," or a self-administered drugopens in a new tab or window, for everyone, and would no longer cover it when administered in an outpatient setting.

Although he was unaware of it at the time, each injection he received at the clinic after October 15 will now cost Beitzel $43,543.47, or as much as $176,000. Medicare has told him as much in numerous letters denying his appeals.

"Some of the denial letters said Mr. Beitzel should have been aware that Stelara was not covered because he could have read it in his 2021 Medicare & You handbook," Bers said.

"That's ridiculous and added insult to injury," she said. Not only did the over 100-page handbook, which came out in the fall of 2020, not mention Stelara, she said. It had buried and vague wording that did not tell him Medicare would reclassify the drug a year later: "Part B doesn't cover other types of drugs in a hospital outpatient setting (sometimes called 'self-administered drugs' or drugs you'd normally take on your own)."

A CMS spokesperson said the agency does not comment on pending litigation.

Beitzel sought help from Melissa Brown, an attorney with McGeorge School of Law's Elder Law Clinic in Sacramento, which is co-counsel in the lawsuit.

Their request for injunctive relief is Beitzel's last effort in the year-long, paperwork- and stress-laden battle against Medicare's multi-layered and complicated appeals process, which has been fraught with frustrating, confusing, and contradictory rulings along the way, Bers said.

Now, to get SAD drugs covered, Medicare beneficiaries -- including those with frailty, movement, or seizure disorders -- must get them from their Part D drug plan pharmacies, most of which require high co-pays, if they cover expensive drugs like Stelara at all. Then they must inject it themselves or find a qualified person who could safely do it for them. Otherwise, the Stelara and other SAD drugs are no longer covered outpatient benefits.

Stelara, used by 22,000 beneficiaries in the year ending May 2023, is so expensive, costing the Medicare program nearly $2.7 billion during that period, it is one of the 10 drugs earmarkedopens in a new tab or window in August for negotiation under the Biden Administration's Inflation Reduction Act.

Since May 2022, Beitzel has stopped going to the clinic for injections. He pays his drug plan $1,390 in cost-sharing for every Stelara dose, and has a retired health provider friend give him the injections.

What's perhaps equally difficult to understand, Bers said, is that the agency says its rules don't require it or providers to give advance notice to beneficiaries that the drug is no longer covered under Part B, leaving patients to find out about the change only when the shocking bills come in the mail months later.

And because he didn't know, and the clinic either didn't know or didn't understand, Beitzel continued receiving four injections at the clinic after the policy change -- in October and December of 2021, and February and April of 2022.

Beitzel only learned something might be wrong when he received a Medicare Summary Notice (MSN) dated March 1 that his October and December doses were "non-covered," and that he may be billed $43,543,47 for each of them. It didn't say why.

"I almost fell over because I've been doing this for 5 years and it didn't cost anything and nobody ever said anything," Beitzel told MedPage Today in a call with the center's attorneys on the line. He said the infusion center's billing department told him it was a "paper mistake" and not to worry about it.

Months later, he received another MSN denial dated June 10. It said he owed another $89,438.28 for the third and fourth doses. The infusion center appealed but was denied, but for the first time provided a reason: "We find that the above services are deemed self-administered drugs. Therefore ... no payment can be made," the lawsuit said.

"I still feel distressed and stressful," Beitzel told MedPage Today as he mentioned the foot-high stack of paperwork on his case. "And when you have Crohn's, stress is not a good thing to have. Every time I read this stuff it upsets me."

The class action also names another plaintiff, identified as K.K., a 72-year-old psoriasis patient in Darien, Connecticut with a rare form of painful arthritis that damages bones in one's hands and feet. Since 2016, she also has received Stelara injections, every 3 months, all covered by Medicare's Part B. That is, until October 15, 2021, when the regional Connecticut Medicare Administrative Contractor (MAC) changed the policy the same way.

Like Beitzel, she wasn't told about the change and continued receiving injections from a nearby hospital outpatient department.

Now, in notices she received months later, Medicare says she owes more than $116,000 for two of the doses. She appealed, and during one appeal process, was told verbally by an administrative law judge that she wouldn't be responsible for the payments. But in the ruling, the judge's decision was reversed, saying, "I am not able to ignore Medicare policy and guidance."

The lawsuit said "Ms. K. experienced and continues to experience distress, anxiety, and outrage about the termination of Part B coverage for Stelara without notice and Medicare's decisions finding that she is financially liable for the cost of the injections she received at the hospital."

The lawsuit said she had to stop taking the drug because her Part D plan requires such a high cost for it. And she suffered pain and a serious rash that "looks like a third degree burn," and covered about "50% of her body and tormenting her with itching with no relief." Now, she is back on the drug through the manufacturer.

In addition to asking the court to certify the case as a class action, the lawsuit wants the court to issue a permanent injunction requiring Becerra to ensure notice is provided when a drug changes status to self-administered; waive patients' liability for the costs; and modify the program so people with medical conditions who can't inject themselves can get them administered by a healthcare professional.

Bers said the lawsuit was filed on behalf of potentially thousands of Medicare beneficiaries who could and are finding themselves with similarly outrageous amounts of debt because of surprise SAD drug policies, and not just those taking Stelara.

Medicare contractors moved three rheumatology drugs to the SAD list a decade ago, also without warning, but efforts by the American College of Rheumatology persuadedopens in a new tab or window them to move them back to Part B, the lawsuit said. But as of August, two of the three drugs, Simponi and Orencia, are back on the list.

The lawsuit also mentions that several regional MACs have proposed SAD change decisions on other drugs covered under Part B, such as the injectable biologic for psoriasis, tezepelumab-ekko (Tezspire). But effortsopens in a new tab or window by the American College of Allergy, Asthma & Immunology have thwartedopens in a new tab or window that.

Bers said her review of the 12 regional MAC decisions on Stelara consistently categorize it now as a SAD drug, but some appear to be inconsistent in their reasons for it.

To Beitzel, the Medicare agency's actions are not just hurtful and heartless, they're dangerous.

"I kept getting these letters from Medicare that I didn't understand, and it's just like a big bureaucracy is stepping on this little bitty hand," Beitzel told MedPage Today.

Beitzel said he would like to ask a Medicare representative if he would let Beitzel give him an injection, if he had the chance: "He'd see me, my hand shaking, and he'd say, 'No, I don't want you to get even close to me.'"

Treating ED reduces Alzheimer's?

The article has a clickbait title – Viagra cuts Alzheimer’s risk by 70%.  So what’s the real story?

Originally sildenafil (sold as Viagra) was researched because it increases Nitric Oxide (NO) which can be a real game changer for heart health.  As the research went on, other “things” started popping up, and the marketing machine took over from the scientists.  Now that the drug is off patent the cardiac research is showing up again.  

Since NO is huge regarding blood flow (opens vessels = vasodilates), it’s not a stretch to think that there might be first brain benefits, as well as the obvious “second brain” effects.  But this study DOESN’T PROVE ANYTHING.  It only hints at possibilities.

It’s a computer model of a biological model based off of insurance data.  Insurance data is often quite flawed, as well as a potential sampling bias in the group evaluated – maybe the folks using Viagra are less cognitively impaired than the others, so maybe the 70% is substantially overestimated.  

Could there be benefit? I think absolutely.  Is taking Viagra for this a good idea?  Probably not. Are there other things to do besides take Viagra?  Absolutely – there are numerous natural ways to improve NO levels that help all kinds of things, and it just might ward off early Alzheimer’s.  But proof?  No. 

FROM GREEK REPORTER / BY THOMAS KISSEL

Viagra Lowers the Risk of Alzheimer’s by Almost 70%, Study Finds

Research published recently suggests that Pfizer’s erectile dysfunction drug Viagra can decrease the risk of developing Alzheimer’s disease by up to 69 percent.

The research, which was published in Nature, found that the medication has a direct effect on brain health and significantly reduces the toxic proteins that can cause dementia.

The study’s findings are so promising that the drug may someday be used to counter dementia. A new team of experts is preparing to conduct another study that builds on this data but tests the generic version of Viagra, sildenafil, in patients suffering from early Alzheimer’s.

The team of researchers arrived at Viagra’s viability as a treatment for dementia after analyzing 1,600 approved drugs hoping to find one that could be repurposed to fight the root causes of dementia.

“Sildenafil, which has been shown to significantly improve cognition and memory in preclinical models, presented as the best drug candidate. Sildenafil may have neuroprotective effects and reduce levels of toxic tau proteins,” said Dr. Feixiong Cheng, the lead researcher on the study, which was conducted by the Cleveland Clinic.

Despite the excitement surrounding the study’s promising results, some experts are advising people to not get their hopes up quite yet, as clinical trials are still necessary.

Coffee and Viagra offer new hope in fight against Alzheimer’s

Another recent study uncovered another unlikely weapon in the fight against dementia: coffee. Research suggests that coffee consumption may significantly decrease your chances of developing the disease.

The study sheds light on the mysterious disease, for which there is no cure as of now. While coffee does not mitigate or fight Alzheimer’s like some medications do, the study found that people with no memory loss who also drank larger than average amounts of coffee were at less of a risk of developing mild cognitive impairment, which is considered a pre-stage of Alzheimer’s disease.

“With Alzheimer’s disease, there’s currently a lack of any effective disease-modifying treatments. Our research group is specifically looking at modifiable risk factors that could delay the onset of the disease, and even a five-year delay could have massive social and economic benefits,” said lead author Samantha Gardener, who is a research fellow at Edith Cowan University in Western Australia.

“Worldwide, a high proportion of adults drink coffee every day, making it one of the most popular beverages consumed,” Gardener added.

The popularity and ubiquitousness of coffee could make it a viable method of deferring the onset of Alzheimer’s disease. But she also stressed that further studies are necessary. Gardener and her team are not yet sure what ingredient in coffee itself contributes to the delaying of Alzheimer’s.

“This is, obviously, preliminary data and it needs a lot more research before being recommended, but it’s really positive, and hopefully in the future, it can be incorporated as a modifiable lifestyle factor that can delay Alzheimer’s disease onset,” Gardener said.

Solving the cholesterol problem you never heard of

Lp(a), known as LP little “a” (Lp is lipoprotein), is an independent risk factor for cardiovascular disease.  The easiest way to think about Lp(a) is that it’s a genetically determined type of cholesterol carrier that makes the other risky cholesterols worse if it’s elevated.  

The problem has been two-fold – 

1. Lp(a) has only recently been measured by most doctors (I’ve been measuring it for about 10 years), and

2. Very little will change the Lp(a) level by much.  

As a consequence of #1, many patients who suffer “surprise” events (they have “normal” cholesterol but usual tests) are ultimately found to have elevated Lp(a). 

#2 leads to the strategy that lowering other cholesterol risks in the hope that you could avoid the consequences.  

The article attached reports the first successful attempt to meaningfully lower the Lp(a) (62%) with an oral medication, without screwing other stuff up, at least in an obvious way.  Phase I trials are small, and are testing for safety, but this one actually shows promise for efficacy as well.  For people with elevated Lp(a) this could be a real gamechanger.  It’s early, but fingers crossed.

FROM JAMA NETWORK / BY STEPHEN J. NICHOLLS, MBBS, PHD1; STEVEN E. NISSEN, MD2; CYNTHIA FLEMING, RN, MSN

Muvalaplin, an Oral Small Molecule Inhibitor of Lipoprotein(a) Formation

A Randomized Clinical Trial

Key Points

Question  Can muvalaplin, an orally administered small molecule inhibitor of lipoprotein(a) (Lp[a]) formation, achieve safe and tolerable plasma concentrations adequate to reduce steady-state Lp(a) levels without modulating plasminogen activity in humans?

Findings  In this first-in-human phase 1 study involving healthy participants, muvalaplin administered orally as single ascending doses ranging from 1 mg to 800 mg and as multiple ascending doses ranging from 30 mg to 800 mg for 14 days caused dose-dependent plasma concentration increases. Muvalaplin administration was not associated with concerns about safety or tolerability, and it reduced Lp(a) levels but not plasminogen activity.

Meaning  The observed safety, tolerability, pharmacokinetics, and exploratory pharmacodynamics of muvalaplin in healthy participants support further clinical evaluation in patients with elevated Lp(a) levels.

Abstract

Importance  Lipoprotein(a) (Lp[a]) is associated with atherosclerotic disease and aortic stenosis. Lp(a) forms by bonding between apolipoprotein(a) (apo[a]) and apo B100. Muvalaplin is an orally administered small molecule that inhibits Lp(a) formation by blocking the apo(a)-apo B100 interaction while avoiding interaction with a homologous protein, plasminogen.

Objective  To determine the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of muvalaplin.

Design, Setting, and Participants  This phase 1 randomized, double-blind, parallel-design study enrolled 114 participants (55 assigned to a single-ascending dose; 59 assigned to a multiple-ascending dose group) at 1 site in the Netherlands.

Interventions  The single ascending dose treatment evaluated the effect of a single dose of muvalaplin ranging from 1 mg to 800 mg or placebo taken by healthy participants with any Lp(a) level. The multiple ascending dose treatment evaluated the effect of taking daily doses of muvalaplin (30 mg to 800 mg) or placebo for 14 days in patients with Lp(a) levels of 30 mg/dL or higher.

Main Outcomes and Measures  Outcomes included safety, tolerability, pharmacokinetics, and exploratory pharmacodynamic biomarkers.

Results  Among 114 randomized (55 in the single ascending dose group: mean [SD] age, 29 [10] years, 35 females [64%], 2 American Indian or Alaska Native [4%], 50 White [91%], 3 multiracial [5%]; 59 in the multiple ascending dose group: mean [SD] age 32 [15] years; 34 females [58%]; 3 American Indian or Alaska Native [5%], 6 Black [10%], 47 White [80%], 3 multiracial [5%]), 105 completed the trial. Muvalaplin was not associated with tolerability concerns or clinically significant adverse effects. Oral doses of 30 mg to 800 mg for 14 days resulted in increasing muvalaplin plasma concentrations and half-life ranging from 70 to 414 hours. Muvalaplin lowered Lp(a) plasma levels within 24 hours after the first dose, with further Lp(a) reduction on repeated dosing. Maximum placebo-adjusted Lp(a) reduction was 63% to 65%, resulting in Lp(a) plasma levels less than 50 mg/dL in 93% of participants, with similar effects at daily doses of 100 mg or more. No clinically significant changes in plasminogen levels or activity were observed.

Conclusion  Muvalaplin, a selective small molecule inhibitor of Lp(a) formation, was not associated with tolerability concerns and lowered Lp(a) levels up to 65% following daily administration for 14 days. Longer and larger trials will be required to further evaluate safety, tolerability, and effect of muvalaplin on Lp(a) levels and cardiovascular outcomes.

Long COVID continues to be a COMPLICATED story

Most people know somebody who’s had COVID and then has suffered for a long time as a consequence – just never quite right yet.  Those are the “usual” Long COVID people.  Unfortunately, many have not gotten connected with folks who can help them, and thus, their suffering persists longer than may be necessary (we can help those people).  Now, though, there’s another bunch of patients who might be getting Long COVID MONTHS after seemingly being “cured”.  

Most Long COVID patients (86%) tend to improve after a year (doesn’t that sound like a really long time? It does to me.).  But “it (was) common for symptoms to resolve then re-emerge months later.”

Yikes.  

Interestingly, when they compared COVID vs non-COVID groups for symptoms, there really wasn’t a significant difference (18.3% vs 16.1%).  That means that 1 in every 5 or 6 people is walking around every day with symptoms that fall into the Long COVID-type buckets, whether or not they ever had COVID.  This seems like the basic issue – lots of people are walking around with “stuff” that’s not being handled (we can help those people, too.)

Oh, and by the way, the CDC reports that Long COVID has fallen to only 6% of the population. Heck, nothing to worry about – it’s ONLY 20 million people!

FROM MEDPAGE TODAY / BY JUDY GEORGE

Long COVID Symptoms May Emerge Months After Infection

— Fewer Americans have long COVID but many have significant activity limitations, CDC data show

Long COVID symptoms may emerge months after SARS-CoV-2 infection, data from the prospective multicenter INSPIRE study suggested.

Symptom prevalence decreased over 1 year among long COVID patients, but persisted or emerged at different time points in some cases, reported Sharon Saydah, PhD, of the CDC's National Center for Immunization and Respiratory Diseases, and co-authors in the Morbidity and Mortality Weekly Report.

For about 16% of study participants, symptoms lasted 12 months after their initial SARS-CoV-2 test. At 3, 6, 9, and 12 months after testing, some people had ongoing symptoms, while others had emerging symptoms not reported previously.

"It was common for symptoms to resolve then re-emerge months later," noted co-author Juan Carlos Montoy, MD, PhD, of the University of California San Francisco.

"A lot of prior research has focused on symptoms at one or two points in time, but we were able to describe symptom trajectory with greater clarity and nuance," Montoy said in a statement. "It suggests that measurements at a single point in time could underestimate or mischaracterizes the true burden of disease."

INSPIRE was designed to assess long-term symptoms and outcomes among people with COVID-like illness who had a positive or negative SARS-CoV-2 test result at study enrollment. Participants who completed baseline and 3-, 6-, 9-, and 12-month surveys were included to identify emerging and ongoing symptoms.

A total of 1,741 people completed all quarterly surveys through 12 months, including 1,288 COVID test-positive and 453 COVID test-negative participants. Most participants were female.

Outcomes included self-reported symptoms in eight categories: extreme fatigue; cognitive difficulties; cardiovascular; pulmonary; musculoskeletal; gastrointestinal; constitutional; or head, eyes, ears, nose, and throat.

The prevalence of any symptom decreased substantially from baseline to 3-month follow-up -- from 98.4% to 48.2% for COVID-positive participants, and from 88.2% to 36.6% for COVID-negative participants.

Persistent symptoms decreased over the year. Emerging symptoms were reported for every symptom category at each follow-up period for both groups.

At 12 months, symptom prevalence was similar between groups, at 18.3% in the COVID-positive group and 16.1% in the COVID-negative group (P>0.05).

"We were surprised to see how similar the patterns were between the COVID-positive and COVID-negative groups," Montoy noted. "It shows that the burden after COVID may be high, but it might also be high for other non-COVID illnesses. We have a lot to learn about post-illness processes for COVID and other conditions."

In other research published in the Morbidity and Mortality Weekly Report, a national survey showed the prevalence of long COVID fell to 6.0%.

The survey also found that one in four people with long COVID (26.4%) had significant activity limitations, reported Nicole Ford, PhD, of the CDC's National Center for Immunization and Respiratory Diseases, and co-authors. The findings came from the Census Bureau's Household Pulse Survey from June 1-13, 2022 to June 7-19, 2023.

Among people who reported a history of previous SARS-CoV-2 infection, long COVID prevalence fell from 18.9% in 2022 to 11% in 2023. In the overall U.S. population -- irrespective of history of previous COVID-19 -- the prevalence of long COVID dropped from 7.5% to 6.0%.

Among both groups, prevalence declined from June 2022 through January 2023 before stabilizing.

The percentage of people with significant activity limitations didn't change over time, the researchers said. Only adults under age 60 experienced significant rates of decline (P<0.01).

"These findings highlight the importance of COVID prevention, including staying up to date with recommended COVID-19 vaccination, and could inform healthcare service needs planning, disability policy, and other support services for persons experiencing severe activity limitation from long COVID," Ford and colleagues wrote.

"Limited ability to carry out day-to-day activities because of long COVID symptoms can have a significant impact on quality of life, functional status, and ability to work or provide care to others," they added. "Long COVID in U.S. adults has also been associated with lower likelihood of working full time and higher likelihood of being unemployed."

The reports of (my) death are greatly exaggerated

Chat GPT agains tolls the bell of impending doom, etc.  Or not.  

The whole generative AI space is very promising, and some really interesting results have come out of evaluating the technology in the healthcare space.  This article’s title again makes the case that the computer is better than the doctor.  And for some cases, that’s true – where you might think it would be helpful.  Like in the case of some real oddities, complex collections of stuff that’s uncommon, etc.  But there continues to be issues around some stuff that the regular doc would be thinking of long before the computer got around to it.  And don’t get me started on the MSU (Make S**t Up) quotient that I’ve touched on before – it continues to be a real problem.  

The future of AI assisted healthcare is, indeed, very bright.  But don’t get ahead of yourself – it’s like consulting Dr. Google – oh, I have cancer….but it really just looks like a splinter…..

FROM MEDPAGE TODAY / BY MICHAEL DEPEAU-WILSON

AI Beat Clinicians at Figuring Out Difficult Diagnoses

— GPT-4 may help with diagnoses that have been missed by clinicians, study author says

A generative artificial intelligence (AI) program diagnosed elderly patients with extensive medical histories and long hospital stays more accurately than clinicians, suggesting the technology could help identify missed diagnoses, according to a new study.

An analysis of medical histories for six patients over the age of 65 with delayed diagnoses revealed that GPT-4 (Generative Pre-trained Transformer 4, made by OpenAI) accurately diagnosed four out of six patients, according to Yat-Fung Shea, MBBS, of the Department of Medicine at Queen Mary Hospital and University of Hong Kong, and coauthors.

By comparison, clinicians accurately diagnosed only two out of six of those same patients, according to a research letter published in JAMA Network Open.

When differential diagnoses were included, AI's accuracy improved to five out of six patient diagnoses, compared with three out of six correct patient diagnoses made by clinicians.

Differential diagnoses were also generated using a medical diagnostic decision tool known as Isabel DDx Companion. This tool accurately diagnosed none of the patients in the initial attempt, and two out of six patients when provided differential diagnosis information.

"GPT-4 may be able to provide potential diagnoses which have been missed by clinicians," Shea told MedPage Today in an email. "If a doctor encounters elderly patients, who have been admitted into hospital for work-up for at least a month but [are] still without a definite diagnosis, he/she can consider using GPT-4 to analyze the medical histories."

"GPT-4 may help clinicians to analyze clinical situations with diagnostic difficulties, especially in alerting clinicians to possible underlying malignancies or side effects of drugs," he added.

The AI program was able to successfully diagnose patients as a result of the extensive medical histories available for each of them, Shea said, including radiological and pharmacological information.

Shea noted that they chose to work with older patients because they often suffered from multiple comorbidities, which can require prolonged efforts to achieve a correct diagnosis. With GPT-4, clinicians could potentially identify diagnoses they might have otherwise missed, which would help close the time to initial diagnosis in this population.

The AI program successfully diagnosed patients with a range of conditions, including polymyalgia rheumatica (patient 2), mycobacterium tuberculosis-related hemophagocytic lymphohistiocytosis (patient 3), metronidazole-induced encephalopathy (patient 5), and lymphoma (patient 6).

Still, GPT-4 had trouble with certain aspects of diagnosing patients, including multifocal infections. The AI program failed to pinpoint the source of a recurrent infection in one patient, and it did not suggest the use of clinically relevant testing for infections in most of the patients in the study.

Shea noted that GPT-4 should be seen as a tool that can increase a clinician's confidence in a diagnosis or even offer clinicians suggestions similar to those of a specialist. This would be especially beneficial in lower-income countries that lack the wide availability of specialists to assist with consulting on older patients.

"Our results showed that GPT-4 has the potential to improve clinician responses," Shea said. "GPT-4 may alert clinicians [of] certain overlooked things in the clinical history, e.g. potential side effects of drugs or abnormal findings on imaging. These may be relevant especially when certain subspecialties are not immediately available for consultation."

Shea also noted that the study was limited by a very small sample size. The analysis was conducted using the medical histories for six patients (two women and four men) in a single hospital unit -- the Division of Geriatrics in the Department of Medicine at Queen Mary Hospital. All of the patients had delayed definitive diagnosis for longer than 1 month in 2022. Their histories were entered into GPT-4 chronologically starting at admission, at 1 week after admission, and before final diagnosis. The data were entered into the AI program on April 16, 2023.

The authors also cautioned that the AI program is susceptible to regurgitating wrong information based on incorrect medical histories.

They concluded that use of generative AI in diagnosing patients showed promise, especially when extensive medical histories were available, but it also presented several new challenges for clinicians.

Could there be anything more OBVIOUS concerning Long COVID?

DUH!  It takes an expert panel to recommend that we need to study Long COVID more.  This is specifically around cognitive issues – brain fog, trouble with executive function, stuff like that.  There’s a report from a modeling study of 1.2 million people that demonstrated that 2.2% still had issues months after being sick.  Plus the specter of long term neurodegeneration is possible in those folks, maybe even likely.  That’s 26,000 people in the study.  If we consider that 35% of Americans have been known to test positive for COVID (very much an understated number), this would translate to about ¼ of a million cognitively impaired Americans.  That’s a huge problem, still largely undefined and in conventional practices, largely unaddressed.  

If you are one of the folks who feels like things still aren’t quite right, PLEASE call – don’t expect things to improve on their own if they haven’t by now.  There is help available.

 FROM MEDPAGE TODAY / BY JUDY GEORGE

Long COVID Cognitive Research Needs an Overhaul, Task Force Says

— Expert group issues recommendations for future studies

Long COVID cognitive research needs better studies, an international task force urged.

The approach to assessing cognitive dysfunction after SARS-CoV-2 infection requires an overhaul to better understand long COVID prevalence, trajectory, mechanisms, phenotypes, and psychosocial factors, said experts from the NeuroCOVID International Neuropsychology Taskforce.

"As one of the most common symptoms of post-COVID-19 condition and one for which affected individuals may seek accommodations and disability benefits in accordance with the Americans With Disabilities Act, it is imperative that we use more rigorous studies of cognitive outcomes," wrote task force member Sara Weisenbach, PhD, of McLean Hospital and Harvard Medical School in Boston, and co-authors, in a viewpoint paper published in JAMA Psychiatry.

Long COVID cognitive dysfunction, including "brain fog," can affect even relatively young people and can last for months. A modeling study based on 1.2 million COVID patients showed that 2.2% had cognitive problems lasting 3 months or longer after symptomatic infection. Moreover, data from patients with severe COVID suggested SARS-CoV-2 infection may raise the risk of subsequent neurodegeneration.

"Since the beginning of the SARS-CoV-2 pandemic, the medical community has experienced an influx of patients reporting new cognitive difficulties months after infection clearance," Weisenbach told MedPage Today.

"There is evidence in the research literature of objective cognitive impairment in some individuals following infection; however, many studies have methodological weaknesses that limit the conclusions that can be drawn and applied in clinical settings," she said.

The task force outlined three recommendations based on initial guidelines the group proposed in 2021.

The first calls for a rigorous assessment of post-COVID cognitive dysfunction. Studies relying on self-reported data early in the pandemic have skewed perceptions about the frequency of cognitive dysfunction, Weisenbach and co-authors pointed out, and objective and subjective findings often don't align with each other. Comprehensive test batteries should be used, and studies should include control groups, diverse samples, and when possible, pre-pandemic and post-pandemic data, they argued.

The group's second recommendation was for new research to identify clinical phenotypes. COVID severity, age, family history, and pre-existing cognitive or psychiatric disorders are factors to consider, the task force observed. Other phenotypes may be based on COVID-19 variants, vaccination status, or history of other viral illnesses or pre-existing autoimmune conditions.

Finally, psychosocial factors need to be assessed given the controversies surrounding post-COVID-19 cognitive dysfunction, including skepticism of its existence and disagreement on its cause, Weisenbach and co-authors said.

"This controversy is familiar to neuropsychologists, who frequently evaluate patients with similarly controversial conditions, such as myalgic encephalomyelitis, or chronic fatigue syndrome," the task force said. "Perhaps because psychiatric disorders can co-occur with these multifaceted conditions, many have dismissed these conditions as being psychosomatic with nonbiologic underpinnings."

"This broad dismissal is contrary to scientific evidence and can be harmful for patients and communities affected," the group added. It's possible that in some people, cognitive symptoms may reflect an interplay between illness and psychological and social factors, and in others it's associated with a postviral syndrome and persistent inflammation, they suggested.

Clinical studies will likely have different results than those from large cohorts, Weisenbach and colleagues noted.

"Together, these data will allow improved clarity regarding the pathophysiology of post-COVID-19 cognitive dysfunction and factors that contribute to symptom persistence," they wrote. "Ultimately, this will create opportunities for the development of effective treatment interventions using a personalized medicine approach."