Omicron - Is the sky falling?

Spoiler alert! Our knowledge is at an early stage, and much of what I am about to say may change as our knowledge evolves – that is inherent in any new natural phenomenon.

Viruses mutate constantly – when you are producing millions of new virus particles a day, there will be random changes in the RNA sequence. Most of these mutations are minor and have no effect on how the virus behaves but some will cause the virus to be more (or less) easily transmitted and/or more (or less) dangerous to the host (us!).

Most virus mutations are given such catchy names as B.1.1.7, but when the World Health Organization deems a virus to be more dangerous and/or more easily transmitted, it is given a Greek letter name for easier communication. We are all familiar with the Delta variant that is now the dominant strain in the United States and which has caused our case counts to shoot up.

The latest “variant of concern” is Omicron, first identified and sequenced in the Republic of South Africa. It did not necessarily emerge there, but S.A. has a much better public health system than its neighbors. We should be grateful to South Africa for promptly telling the WHO and the world about this new variant. If only China had been equally open, it might have saved precious time for a response to the initial Covid outbreak.

Given the interconnected world in which we live, it is not a surprise that Omicron has spread beyond southern Africa. As of Nov 30, at least 19 countries have reported small numbers of cases. From 1 to 20 cases have been reported from Australia, Canada, Israel, Japan, Hong Kong and 12 western European countries. While there have been no cases identified yet in the U.S., I would be shocked if there are not already a handful here. While much publicity was given to two flights from South Africa to Amsterdam carrying infected people, it is now known that the variant was present in the Netherlands at least a week earlier.

What do we know about Omicron?

1.It seems to be more easily transmitted than the original virus, though not necessarily more than Delta.

2.So far, it does not appear to cause more serious disease than existing strains.

3.Existing vaccines should give at least moderate protection against getting seriously ill, though I suspect will be less effective at preventing infection.

4.The best current therapy, monoclonal antibody infusions, will be much less effective against Omicron, because they target the spike protein and this has been greatly changed in Omicron.

5.The newly approved pills, which target a different part of the virus, should be similarly effective against Omicron, though their benefit is only moderate.

What should you do?

1.If you have not already done so, PLEASE get vaccinated and get your booster.

2.I would wear a mask whenever you are in large groups indoors (theatres, stores, etc.)

3.If you are immune compromised and/or over 75, I would avoid non-essential travel

Stay tuned! We will have more and better details in the next few weeks

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Home (Safely) for the Holidays

One of the worst aspects of the Covid pandemic has been the isolation. Last year, many of us had to forego our holiday family traditions and get-togethers in the interest of safety. This year, with the widespread availability of vaccines, we hope to once again be with our loved ones around the holidays. At the same time, the Delta variant and the rising case count seen in many states makes us nervous, as do reports of break-through infections in vaccinated people. What can/should we do?

A few facts can guide our behavior. The first is that no activity in life is 100% safe. If you are travelling “over hill and dale to grandma’s house” in a car, you are accepting the risk of being injured or killed in an accident. You can of course minimize this risk by wearing a seatbelt, not driving under the influence of alcohol and obeying traffic laws. Second, while no vaccine is 100% effective, the current Covid vaccines are pretty darn good, reducing your risk of getting seriously ill by some 90%.

Here are some possible holiday scenarios and my suggestions for how to handle each:

Scenario 1: everyone attending your get-together who is eligible (is over 5 years old) has been vaccinated, including a booster where appropriate, and no one is immunocompromised or a frail elder. In this situation, I would feel free to socialize freely and not wear masks or require any tests. Go ahead: hug each other. [It goes without saying that someone who is sick should not attend!]

Scenario 2: everyone is vaccinated, but you will have a frail elder or someone who has a compromised immune system with you. In this situation you need to be more careful. Again, strictly advise guests to stay away if they are sick, but in addition, I would ask everyone coming, including children, to do an at-home antigen test the morning of the gathering and stay away if positive. [Any person testing positive should also follow through with their primary care doctor or local public health nurse.]

Scenario 3: at least some of your potential guests are not vaccinated. Here it gets sticky. If everyone else is fully vaccinated and in good health, you must decide if you are willing to accept the risk of getting infected, knowing that the vaccine you received will probably mean you will have nothing worse than a bad cold. Ask them to do a home test the morning of the event and stay away if the test is positive and/or they have any cold symptoms. You should warn all your invitees that there will be unvaccinated guests so they can decide if they want to attend.

3a: If you will have elderly grandparents or friends/family with compromised immune systems with you, I suggest you tell the unvaccinated that they would be putting others at risk and that while you hope to see them next year, they are not welcome this year. There is always Zoom.

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Medical Debt

I have not yet seen a pig fly, but I did recently see something I would have felt just as unlikely: a front-page story in the Rupert Murdoch-owned Wall Street Journal that could have been written by Bernie Sanders.

The headline read “$100,000 in debt: arbitrary hospital prices hit some hard.” It was the story of a hard-working South Dakota woman who died of cervical cancer after a long series of tests and treatments who was forced to use up all her retirement savings to pay down her medical debt. (Unmentioned was why this woman did not have the routine medical care that should prevent most women from dying of this disease that is easily cured when found early.)

https://www.wsj.com/articles/hospital-prices-arbitrary-healthcare-medical-bills-insurance-11635428943?st=qypiqn1wayhirth&reflink=desktopwebshare_permalink (may be paywall)

The article described the random and arbitrary nature of hospital pricing and how people with different health insurance plans might have dramatically different out-of-pocket costs for the same tests at the same hospital. It also emphasized how little control most people had over their medical costs. Many hospitals charge their highest prices to patients when a procedure is not covered by their insurance plan.

Standard right-wing dogma is that health care is “just another consumer choice,” whose pricing should be left to the marketplace. Omitted from this thinking are such factors as limited choice (the woman in the story lived in rural South Dakota with only one hospital anywhere close), the fact that very sick people are rarely in a position to negotiate prices and the incomprehensible pricing structure used by most hospitals.

Couple this story with research published this summer showing that U.S. debt collection agencies held $140 billion in unpaid medical bills last year and you have to ask why people are not out in the streets demanding change.

In part this is probably because medical costs hit the poor hardest: 35% of people living in households with an annual income below $24,000 reported skipping medical care because of cost versus 7% of all those with incomes under $180,000. The poor, with day-to-day worries about paying for food and utilities, are the least able to work for political change.

In the long run, we all pay. One in six patients with heart failure reported skipped or delayed medical care because of cost, and this was associated with higher overall spending because of increased hospitalizations.

The mark of a healthy society is how it cares for its most vulnerable citizens. By this measure, we are failing. When the dust settles in Washington, it is time to take up the cudgel again and fight for affordable care for all.

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Should I keep taking my aspirin?

Many news outlets led this past week with the headline “government panel advises those 60 and older against using aspirin to prevent heart attacks.” What alarming new data led to this recommendation? None, really. Let’s look carefully at the reasoning behind this decision.

Aspirin has a long history of use for heart attack and stroke prevention. It works by preventing platelets from clumping together and blocking blood vessels. As far back as 1974, a study in Britain showed that giving aspirin to patients admitted to hospital with a heart attack reduced deaths. An influential study published in 1988 looked at a series of trials and concluded that giving aspirin to people who had suffered heart attacks lowered their likelihood of future heart attacks, strokes and deaths.

Why not put aspirin in the water supply? Platelets are our first line of defense against bleeding. If you cut yourself, platelets rush to the torn blood vessels and plug the holes until a more permanent clot can seal the break. Thus, aspirin’s effect on platelets increases your risk of bleeding.

Another British study, published 21 years ago, looked at 5000 men 45-69 with hypertension but no prior heart attack. The men taking aspirin had 20% lower risk of heart attack and stroke, but this was outweighed by an increased risk of stomach and other internal bleeding.

The U.S. Preventive Services Task Force commissioned a review of all the many trials looking at aspirin as primary prevention, that is, giving it to people with no known coronary disease. The data included 13 trials, enrolling a total of 162,000 people. Very similar to the 2000 British study, they found that those taking aspirin had 10-18% fewer heart attacks and strokes and that they had 30% more bleeding into the brain and 50% more bleeding elsewhere. (Note that these are relative differences. The absolute numbers are small: 2/1000 brain bleeds and 9/1000 other bleeds.)

Bleeding risk from use of aspirin goes up with age. Hence, the draft recommendation is that people 60 and up with no known coronary disease not take aspirin as a preventive. For those 40-59, they suggest the decision be individualized.

What is the take-home for you?

1.If you have coronary disease (prior heart attack, angina, a coronary stent or bypass surgery) keep taking your aspirin.

2.If you are a generally healthy person 60 and up, I would not take aspirin as a preventive measure.

3.If you have coronary risk factors such as high cholesterol, diabetes, smoking or a strong family history of coronary disease, discuss the pros and cons of aspirin with your doctor.

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What is a "surrogate outcome"? Why should you care?

The dictionary defines a surrogate as “something that replaces or is used instead of something else.” When the average person thinks of surrogate, the most likely thing that comes to mind is a surrogate parent or child.

Surrogates are widely used in medicine, and often with a less valuable role than a surrogate grandparent.

When a new treatment is proposed, the ideal way it is tested is with a controlled trial. A large group of patients with the condition needing treatment are randomly chosen to receive either the current standard treatment or the proposed new one. They are followed and how each group does is compared. If the new treatment is clearly superior, it will then be recommended for general use.

Controlled trials like this are expensive to prepare and conduct and are generally funded either by the National Institutes of Health or, more often, by the drug company hoping to market its new treatment. If the disease being treated is one that gets worse quickly, and if one of the two remedies is much better, the results may be evident quickly. If the disease normally progresses slowly and/or the difference between the two treatments is small, the trial may have to be conducted for many years. The longer the trial runs, the more it costs the sponsor. Hence, the surrogate outcome.

What do patients expect of a treatment? They want to live longer and feel better. Proving that a new drug accomplishes either of these things better may be difficult when the natural history of the disease plays out over many years or when the new drug is only slightly better. Trial sponsors are thus motivated to find a “surrogate outcome” that may show superiority quicker than outcomes valued by patients are found.

A recent example was the new Biogen drug Aduhelm, that was approved because patients receiving it cleared a marker of Alzheimer’s Disease better than those getting the placebo, even though there was minimal improvement in dementia. Cancer drugs are often approved because a blood marker of cancer or the size of a defect seen on an imaging test improves more than they do on another treatment.

IF these surrogates were proven to be a valid “marker” of feeling better or living longer, their use would allow results to be available sooner and at lower cost. Unfortunately, this is often not the case. Between 2006 and 2018, 62% of the 85 new cancer drugs the FDA approved were approved based on surrogate outcomes. While drug manufacturers are supposed to later provide data on the true outcomes of survival and quality of life, this is often not done. Of approved cancer drugs, only a minority subsequently were shown to improve survival. The FDA should demand that confirmatory trials be reported within a reasonable timeframe, such as 3-4 years after accelerated approval. If such trials were not done or reported, the drugs should no longer be paid for.

When your oncologist or neurologist suggests that a “new and improved” drug be used, ask them to tell you the basis for considering it to be improved. (And don’t forget to ask them how the side effects compare to older drugs as well!)

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What is the scoop on boosters?

Are you feeling confused about Covid vaccination boosters? Join the crowd. So, it appears, is almost everyone in Washington (and everywhere else).

What do we know? What should you do?

We know that the mRNA vaccines remain very effective at preventing serious infection, though it is certainly possible for vaccinated people to catch and spread the virus.

While the Pfizer and Moderna vaccines were in a dead heat (95% vs. 94%) in effectiveness based on the original trials, the Moderna vaccine seems to hold up better. This may be because it uses a higher dose (100 vs. 30 micrograms) and/or because the longer time between doses (4 weeks vs. 3) is better for developing immunity – the longer the better is true for most vaccines.

A study from the CDC found that while both mRNA vaccines offered 90% + protection for the first 4 months after vaccination, this fell to 77% for Pfizer while staying the same for Moderna.

Pfizer has said that antibody levels increased 3-fold in a small (300 subjects) set of volunteers given a booster 5 to 8 months after their initial series. The use of a booster is also supported by data from Israel, where immunity seemed to fade over time but was restored to 95% by a booster in people 60 and older (Israel used almost entirely the Pfizer vaccine).

Finally, the J&J vaccine was less effective than the two mRNA vaccines, but one small study found no drop in antibody levels over 4-6 months, and another found that a booster of the same vaccine made antibody levels rise nine-fold.

There has been no testing of using a different vaccine as a booster to one of the three approved in the U.S., but a study done in Britain found that following the Astra Zeneca vaccine with the Pfizer gave much better protection than using the A-Z vaccine alone (and the A-Z vaccine uses similar technology to the J&J shot). It is unlikely that “mix and match” would be harmful.

The FDA recently approved using the Pfizer vaccine booster for select groups, and the head of the CDC advised broadening the groups eligible.

So… what should you do?

If you got the Pfizer vaccine, had no major side effects and are in a high-risk group, get it. It will be free, and the best evidence we have now says it will improve your protection. The side effects of a third shot were similar to those of the first two. If you are young and healthy, I would not recommend it until we have more data.

If you got the Moderna vaccine, you seem adequately protected. When Moderna’s booster is approved, I would follow the same advice: high-risk (including age) yes, otherwise wait.

If you got the J&J shot, talk to your doctor about possibly using the Pfizer booster “off-label.” Since it is now fully approved, he or she can prescribe it if they feel it is indicated.

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On "Liquid biopsies" and other screening tests

Coming to a mall near you! Or at your doctor’s office or via direct mail: the chance to have a “simple blood test” to detect very early cancer and perhaps save your life. What is the truth behind the hype?

The term “liquid biopsy” refers to the screening of a blood sample for traces of abnormal DNA that are felt to be the markers of a variety of cancers. These tests were approved by the FDA in 2020 for a very limited purpose: to detect DNA markers of specific subtypes of known cancers that meant the cancers would respond to specific treatments. The tests were meant to identify specific cancer-related genetic changes which could influence patients’ treatment choices or make them eligible to participate in clinical trials.

While that is a lucrative market, what has Wall Street salivating is a much larger potential: offering such tests to everyone, with the promise of detecting cancer long before it caused symptoms. We have been conditioned to believe that early detection = greater chance for cure, and in some cancers this is valid. If everyone had regular colonoscopies, the death rate from colon cancer would fall. Early detection of lung cancer in smokers using low-dose CT scanning has been shown to reduce lung cancer death and regular mammograms reduce death from breast cancer, though in neither of these latter cancers is the screening test “dramatically” effective.

Before we start recommending very expensive “liquid biopsies” for widescale use, it is critical to look at what they will accomplish rather than what they might.

The idea behind screening tests is to look for disease in apparently well people with the expectation that finding and treating disease before symptoms develop will lead to better health and/or longer life. In the case of colonoscopy, the theory has been validated, but this is not always the case.

Example 1: screening for atrial fibrillation (AF). We know that AF, a heart rhythm disorder that is very common as we age, is a major cause of stroke, and that by putting patients with AF on blood thinners we can reduce their stroke risk by as much as 80%. A recently published study looked at using small monitors implanted under the skin to detect episodes of AF that would never be found routinely. They did detect three times as many episodes of AF – BUT – when they treated these people with blood thinners, there was no real difference in strokes or deaths compared to the group not screened. It appears the brief asymptomatic episodes of AF that were found may not be as serious as AF found in routine practice.

Example 2: screening for thyroid cancer. In 1999, Korea embarked on an aggressive national cancer screening program. While ultrasound screening of the thyroid was not initially included, it quickly became a widely used study. As a result, by 2011 the rate of thyroid cancer diagnosis increased 15-fold over the rate in 1993. Thyroid cancer is now the most common cancer diagnosed in Korea. At the same time, the death rate from thyroid cancer did not budge. Almost all of these cancers are low-grade and small, and we have known for 70 years that low-grade thyroid cancer is very common and rarely kills. Thyroid surgery is not innocuous: patients can have vocal cord paralysis, accidentally have their parathyroid glands damaged and usually need to take thyroid hormone for life. All for a disease that would never have bothered them if not found.

SO: before the FDA approves “liquid biopsies” for screening use and before you consent to having one done, we need evidence that these tests not only detect cancers not otherwise easily found, but that finding these cancers will let you live a longer and/or healthier life. Otherwise, I fear, we are going to see your health made worse by extensive imaging studies looking for this possible hidden cancer and your life put at risk by having surgery that you do not need.

Let’s not put the cart before the horse.

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