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.

Prescription for Bankruptcy. Buy the book on Amazon

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.

Prescription for Bankruptcy. Buy the book on Amazon

Boosters - Needed? When?

This week saw an announcement from the Biden administration that a 3rd Covid-19 vaccine shot would be recommended for everyone 8 months after their second mRNA (Pfizer or Moderna) shot. Is this a good idea? What does it mean for you?

Since antibodies gradually fade over time, most vaccines are given in multiple doses over an extended time. If you get hepatitis B immunization, you get 3 shots over 6 months. Most childhood vaccines are spread out over years. The current shingles vaccine is given as two shots, 2 to 6 months apart.

The mRNA vaccines were tested (and thus approved for use) using a relatively tight time frame, 3 or 4 weeks apart. I am sure this was because of the urgency of getting these vaccines tested and available. Indirect evidence from Britain, where the second shot was deliberately delayed to permit as many first shots as possible, suggests a longer interval gives even better protection.

Real world evidence shows that these vaccines are extremely effective, even against the Delta variant, with 80%+ prevention of infection and 90%+ prevention of hospitalization out to 6 months. The one group where evidence strongly suggests a third dose is needed are those with depressed immune systems, such as transplant patients.

A recent study found that among nursing home residents, who got the vaccine early, the protection gradually waned, falling as low as 53% 8 months after vaccination. Another, looking at New York residents, found that protection against infection dropped from 92 to 80%, though protection against hospitalization remained over 90%.

A very small recent study, done by Pfizer, found a marked increase in antibodies when a booster dose was given 8-9 months after the second original vaccine.

SO:

1.Yes, a booster is probably a good idea.

2.If you have a depressed immune system, you should get this as soon as possible.

3.If you are otherwise healthy, there is no need to panic and seek one out before you are due.



Prescription for Bankruptcy. Buy the book on Amazon

Has the FDA lost its way?

The FDA failed the U.S. public by approving Biogen’s new Alzheimer’s drug against the recommendation of its expert advisory panel and its own statisticians. That event led me to explore whether this was an aberrancy or part of a pattern, and what I found disturbed me.

The FDA’s origins lie in the Food and Drugs Act, passed by Congress in 1906 and signed into law by President Teddy Roosevelt, which prohibited interstate commerce in misbranded and adulterated foods and medications. Much of the impetus for getting this bill enacted was the revelations by such “muckraking” journalists as Upton Sinclair, whose novel The Jungle exposed unsafe and unsanitary conditions in the meatpacking industry.

Probably the high point of the FDA was in 1961, when Canadian-born Dr. Frances Kelsey refused to allow the sale in the U.S. of thalidomide without further safety data, and her judgement was rewarded when the drug, widely prescribed in Europe for morning sickness, was found to cause serious birth defects.

This episode in turn led to passage of the Kefauver-Harris amendment to the Food and Drugs Act which required that all new drugs demonstrate “substantial evidence” of efficacy as well as safety. This is where the recent FDA decision failed to meet the intent of the law, but it is not the only time.

Under pressure from AIDS activists in the early 1980’s, the FDA developed an accelerated pathway to approve promising new drugs for otherwise poorly treated diseases, with the proviso that on-going studies be done to prove that the drugs fulfilled their promise. A study published this year in the British Medical Journal found that many drugs approved under this accelerated pathway stayed on the market for years or decades without the required studies being done and with major doubts about their efficacy persisting.

I am particularly concerned about the frequent approval of new cancer drugs, most with huge price tags and major side effects, based on “surrogate outcomes:” measures of changes in blood tests or imaging findings that might show the disease is responding, but which do not show meaningful results in terms of prolonging life.

The FDA is also responsible for regulating medical devices such as implants and pacemakers. Here too, as a ProPublica investigative report found, the FDA has often deferred to manufacturers and allowed dangerous products to stay on the market far too long.

How can these problems be improved?

First, as much as possible, the FDA, and the CDC, should be insulated from political pressure. The heads of these agencies should have terms that do not overlap with presidential terms and should be able to be removed only for malfeasance, so that they can make decisions based on science, not politics. Many public health decisions involve trade-offs but improving a president’s reelection odds should not be a factor when it comes to saving lives.

A much more “arms-length” relationship between the regulators at the FDA and the device and pharmaceutical industries must be enforced. No revolving door between agency and industry should color the regulators’ decision making.

The FDA should not be allowed to overrule the decisions of medical experts unless these decisions are close. If a vote is 6-5 with one abstention, there is room for the FDA to decide on approving a new drug based on their judgement. When there is a super majority vote, it should be respected.

Let us demand that the FDA uphold Dr. Kelsey’s standards.

Prescription for Bankruptcy. Buy the book on Amazon

Do I need to wear a mask (AGAIN!)?

The headlines this morning were all about the CDC changing its guidelines about whether vaccinated people need to wear masks. In typically nuanced language, they tried to differentiate between those living in areas with high spread and low vaccination rates and those in areas with fewer cases and better vaccination uptake.

What should YOU do?

A few facts:

The Delta variant is now dominant. Nationally, over 80% of strains tested are Delta. Even in Massachusetts, which has one of the highest vaccination rates and lowest cases/population in the country, Delta now makes up over 50% of Covid cases.

Delta is not more deadly – hospitalizations and deaths from Delta are similar to those caused by the original strain.

Delta IS much more contagious. People infected with the Delta variant carry many more virus particles in their nose and upper airway, and thus are much more likely to transmit the virus to others. This is why case counts are rapidly rising in almost every state.

The m-RNA vaccines, in particular, are very good at protecting you from getting infected and even better at preventing serious illness and death from Delta, but they are not 100%. Even if you are vaccinated, you can catch COVID-19 and pass the virus to others.

So, my advice is:

Avoid travel to Florida and other hotbeds for now until they get their act together.

If you live in a state with low vaccination rates, I would wear a mask any time you are indoors with people you do not know are vaccinated and outdoors when you will be in crowds.

If you live in New England or another region with high vaccination rates, it gets more complicated. Life is never risk-free. Every time you get in a car, you are accepting some risk. At the same time, you do common sense things to lower the risk: you wear a seatbelt and you obey traffic laws.

What seems sensible is to wear a mask when you are indoors in crowded spaces: theatres, grocery stores, houses of worship. I would also wear one outdoors if it is a very crowded space where people are always close such as parades and stadiums. This will both reduce your risk and the risk that you could pick up a mild infection but pass the virus to others. It is thus particularly important if you have friends or relatives with poor immune systems.

Prescription for Bankruptcy. Buy the book on Amazon

Delta dawns

The news media have been filled with stories about the delta variant of the coronavirus, some factual, some scary. What do you need to know?

First, it is a fact of life that many viruses constantly mutate. That is why you get a flu vaccine every fall: not because your immunity from last year has faded, but because the expected influenza virus will be different than the one that circulated last season. Some of the changes in the virus’ genes make them more dangerous to humans, some less. Some mutations make them less easily transmitted, some more. If a variant is more infectious and/or more easily transmitted from one person to another, it eventually becomes the dominant strain.

This appears to be happening in the U.S. with the delta variant. Luckily it does not seem to be more lethal than earlier strains, but it is more easily spread, and is rapidly becoming the most common form of the virus. Along with the appearance of the delta variant, we are seeing a recrudescence of COVID-19 infections. The lifting of restrictions and decreased mask use is almost certainly also playing a role.

I track the virus in Massachusetts and a month ago our average of new cases was down to 57 a day, and the percentage of Covid tests that were positive had fallen to 0.3%. This week, we are seeing 250 new cases daily and 1% of tests are coming back positive.

This is true across the country. The head of the CDC noted on July 16 that the number of new cases had risen 70% from the prior week. Along with rising cases, hospital admissions had gone up 36% and deaths 26%.

The natural immunity acquired after a mild case of COVID-19 does not seem nearly as effective against the delta variant as it is against to original virus strain. The good new is that the available vaccines do seem very effective, and if you are fully vaccinated, you are extremely unlikely to get seriously ill or die.

Virtually all the recent hospitalizations and deaths have been in unvaccinated people.

While being unvaccinated is clearly dangerous to those individuals, it is also dangerous to others. People who get infected are the source of new variants, and the unvaccinated serve as incubators to produce potentially more lethal variants. Lambda anyone? This new variant now rampant in South America is less susceptible to current vaccines.

If you have not been, PLEASE get vaccinated, for your sake and for ours.

Prescription for Bankruptcy. Buy the book on Amazon

Vaccines and the Heart

There has been considerable discussion in the media and medical journals about possible heart damage in young males who received the m-RNA vaccines against COVID-19. While we do not yet know enough to make absolute pronouncements, we are learning quite a bit and can make some informed decisions.

Some facts:

1.Myocarditis, inflammation of the heart, occurs from many causes, including COVID-19 infection itself. Some 1% of athletes who had mild COVID infections had evidence of heart inflammation when carefully studied, though most of them had no symptoms.

2.The “normal” occurrence of myocarditis in the U.S is about 10 cases/100,000 people/year. Based on studies in Israel and the U.S. military, the incidence in young adults receiving 2 doses of the Pfizer or Moderna vaccines was several times higher than would be expected, albeit still rare. In the U.S. military, 23 cases were reported after 2.8 million does had been given. The CDC reported 196 cases among young adults, 16-24, when 27,000,000 vaccine doses had been given to this age group.

3.To date, most of the reported cases have occurred in adolescent or young adult males and almost all were soon (less than a week) after the second dose of vaccine.

4.Symptoms included chest pain, and most had some combination of elevated enzymes showing heart muscle damage, minor ECG abnormalities and abnormal heart scans. Virtually all the reported patients had mild illness, with good recovery in about 4 days with a variety of treatments or with no treatment.

The Advisory Committee on Immunization Practice has strongly advocated that the vaccines’ benefits for adolescent males exceed their risk, and this is probably true. The benefits of vaccination do outweigh the risk, even in this select group, but how vaccination is done can take the myocarditis risk into account.

One could argue that healthy young males might prefer to receive the J&J one-shot vaccine, in which this condition has not been reported. I would also argue that young males who have recovered from COVID-19 could be considered safely immune after a single rather than both doses of the m-RNA vaccine and thus avoid the second dose that seems to be the trigger.

Stay tuned. I am sure we will learn more.

Prescription for Bankruptcy. Buy the book on Amazon