Wednesday, December 30, 2020

Coffee with that?

Tired of reading about Covid-19? Me too. I will not blog about the novel Coronavirus until there is something new and important to say. (And, no, I do not think that a few serious but very rare allergic reactions fit that description. If they did, we would have to take penicillin and many other important drugs off the market.)

Coffee has a fascinating history. Legend has it that it was discovered by a goat herder in Ethiopia when he noticed that after his goats ate berries from a specific tree, they became so energetic they did not want to sleep at night. From Ethiopia, coffee spread throughout the Arabian peninsula, and coffee houses soon became a staple of social life in the Muslim world. (Based on our travels, this is still true.) European travelers to the Middle East brought back stories of this unusual black beverage, and by the early 17th century, coffee had made its way to Europe. Initially condemned by the clergy as Satanic, coffee got a new lease on life when Pope Clement VIII tasted it, liked it and gave it papal blessing.

While there are numerous chemicals in coffee that lead to differences in aroma, color and taste, the main active ingredient is caffeine. It is caffeine that makes us more energetic and alert (good) and can also make us jittery and unable to sleep (bad). The caffeine in your cup reaches peak levels in your blood some 30 to 60 minutes after you drink it and has a “half-life” of 3 to 5 hours, meaning that some its effect can persist for 10 hours or longer.

In the United States, some 85% of adults consume caffeine daily, most commonly from coffee, but also from tea, chocolate, energy drinks, colas or in tablet form. The estimated average daily consumption of caffeine is 135 mg/day, the amount in about 1.5 8 ounce cups of coffee.

What about health risks and benefits of coffee? The science is less than robust, because most studies are based on comparing differences between people based on their self-reporting of how much coffee they drink. We have, or at least should have, learned that such “observational studies” can suggest possible benefits and harms but cannot prove them. People who drink 2-3 cups of coffee a day may not be like people who do not touch coffee. They may smoke more (or less), exercise more (or less) or may be more (or less) obese. Hence, take everything I say below as hypothesis or conjecture, not Truth.

Caffeine clearly increases alertness, reduces fatigue and reduces reaction time. It improves vigilance in performing tasks that require a long time with minimal stimulation, such as flying aircraft, driving long distances or working on an assembly line. It contributes to pain relief when added to common pain killers such as aspirin or acetaminophen (Tylenol). Caffeine also delays falling asleep and reduces sleep quality. Particularly at higher doses, it can cause or increase anxiety. These effects vary widely between different individuals. I have friends who drink a strong cup of coffee routinely at bedtime and drop off “like a log.” When I eat dinner out (remember those days?), I will ask the server for a cup of decaf “and your phone number, so I know who to call when I am awake at 3 AM.”

What about coffee’s effects on overall health? While consuming pure caffeine chronically has been shown to modestly elevate blood pressure, coffee does not appear to do this. Unfiltered coffee contains a compound that lowers the “good” cholesterol, HDL. This is not true for instant or filtered coffee, so if you are concerned about your lipids, avoid French press or Turkish coffee. There is no evidence that consuming as much as six cups of coffee daily increase the risk of heart attack or stroke.

There have been isolated reports of severe cardiovascular reactions, including sudden death, in people who took very large quantities of “energy drinks,” particularly when taken for weight loss or prior to gym work-outs.

The effects of coffee on cancer are, if anything, beneficial. Many cancers are less frequent in coffee drinkers, including liver, prostate, endometrial, skin and breast. A study published in November of 2020 found a lower risk of progression of metastatic colon cancer in coffee drinkers. Coffee drinkers also have fewer gallstones and kidney stones. Caffeinated (but not decaf) coffee appears to be protective against the development of Parkinson’s disease.

There is controversy about coffee consumption in pregnancy. A study published in the British Medical Journal claimed that maternal caffeine consumption was associated with increased risk of miscarriage and low birth weight. Both the British and American obstetric societies reviewed the study and disagreed with its recommendation that pregnant women avoid caffeine. The best advice seems to be to limit intake to the equivalent of 2 cups of coffee a day.

Several studies have found an association of drinking 2-5 cups of coffee daily with reduced mortality, and none have shown an increase.

A gentle reminder to older readers: caffeine is a diuretic - it will make you go more.

Bottom line: enjoy your morning Cup of Joe, guilt-free, but don’t overdo it.

Prescription for Bankruptcy. Buy the book on Amazon

Thursday, December 17, 2020

Enter Moderna

As you are doubtless aware, the FDA scientific advisory board today voted to recommend approval of Moderna’s Covid-19 vaccine under Emergency Use Authorization, and it is expected that the FDA will grant this on Friday, adding tens of millions of potential vaccine doses to our supply.

What is the difference between the two now-approved vaccines? While there is no peer-reviewed publication for Moderna’s entry as there was for Pfizer’s, the FDA did release the 54- page application the company provided, which I have reviewed. Spoiler alert! Not much.

The Moderna and Pfizer vaccines use almost identical technology: RNA coding for the “spike protein,” in lipid nanoparticles to allow entry into body cells. Both conducted large Phase 3 trials; Pfizer’s was slightly larger, about 18,800 people in each arm of the trial compared to 13,900. Both showed roughly 95% efficacy in preventing symptomatic Covid-19. Both also showed reduction in severe cases, with the edge here perhaps to Moderna. In the Pfizer study, after the first dose, there were 9 severe cases in placebo recipients and 1 in the vaccine group. In the Moderna study, the numbers were 11 and zero.

Side effects were similar in both studies, and I will not repeat these.

One possible advantage to Pfizer was that efficacy seemed similar across all age groups, while the Moderna study showed lower efficacy in subjects over 65: 95.6% in those 18-64, 86.4% in those 65 or older.

An obvious advantage to Moderna is that its vaccine can be stored at less demanding conditions: it should be stored at -13 to 5 degrees F, while Pfizer’s needs temperatures of -70C (-94F). Buy dry ice!!

How about Bell’s palsy, which was in the news? In the Moderna study, there were four cases of this condition, in which there is paralysis on one side of the face, usually (but not always) temporary, 3 in the vaccine group and 1 in the placebo group. To put this in perspective, Bell’s palsy is a common condition. With 30,000 people followed for 2-3 months, you would expect 2-3 cases, so while this needs to be watched for, it is not a major concern. Bottom line: very similar, and either seems both effective and safe.

Prescription for Bankruptcy. Buy the book on Amazon

Monday, December 14, 2020

What do we know about the recently-approved Pfizer vaccine?

As you almost certainly know, the FDA gave emergency use authorization (EUA) late Friday for the Covid-19 vaccine produced by Pfizer and BioNTech, and initial supplies have been shipped. The trial data that persuaded the FDA Advisory Committee to vote in favor of EUA was also published online by the New England Journal of Medicine, giving me and everyone else the opportunity to go beyond the companies’ press release which led to massive hype.

The trial was large enough to be credible. 43,548 volunteers were randomized, and 43,448 received injections. 21,720 got the vaccine and 21,728 got a placebo injection. At the time of the report, 18,556 had gotten both doses of vaccine, 18,530 two doses of placebo and been followed for 2 months.

The two groups were followed for the development of symptoms consistent with Covid-19 and a positive PCR test. There was a clear separation between the two groups beginning at 14 days after the first dose, with many fewer cases in vaccinated people. The pre-defined measure was the difference between vaccine and placebo starting seven days after the second dose, and this was dramatic: 172 cases in the placebo group and 9 in the vaccinated group. This is what led to the widely reported 95% efficacy rate.

Side effects were common, but generally mild. Some 80% of younger vaccine recipients (16-55) had pain at the injection site, as did 68% of those over 55. Fewer than 10% had redness or swelling. Fatigue was seen somewhat more often after the first dose and in over half the subjects after the second. Headache was barely more frequent in vaccine recipients than in the placebo group after the first dose but was 2-3 times more common after the second. Chills and muscle pain were less common but were clearly more common after the vaccine. There were no ”major” adverse events. Two vaccine recipients died, as did four who got placebo, and none of these deaths were felt by independent experts to be vaccine related.

So, over a short period, the vaccine clearly works, and over a short period its side effects are no worse than those for widely accepted vaccines such as the shingles vaccine. What don’t we know? There are still unanswered questions.

First, does it work in children? All study participants were 16 years or older. Studies are now being done in younger adolescents, but not yet in younger children.

Is it safe for pregnant women? Pregnant women were excluded from the trial. The American College of Obstetricians and Gynecologists has offered guidance on vaccinating pregnant and lactating women. The group notes that women should not be required to undergo pregnancy tests before receiving the vaccine and say that vaccines shouldn't be withheld from pregnant women who are eligible for vaccination based on priority groups outlined by the Advisory Committee on Immunization Practices. In addition, vaccination should be offered to lactating women based on their priority group. As with all “expert opinion” that is not supported by data, you must accept this as helpful but inconclusive advice.

How long will immunity last? The study followed patients for a median of two months at the time of reporting. The vaccine used a new technology. A study I referenced in my prior post gave hope that immunity would last, but even that one only had several months’ experience.

What happens if you miss the second dose? As with all clinical trials, this one had a remarkably good follow-up: 98% of those who got dose 1 also got dose 2. In the real world, I would bet house and home that this will not be replicated, though every effort will be expended to try to get people back. It is somewhat reassuring that there was at least some evidence of protection by 14 days after dose 1, a week before the second dose. How much benefit and for how long it lasts are unknown.

Does the vaccine prevent asymptomatic or mild infections? People in the study were only tested if they developed symptoms consistent with Covid-19. We know that even now, many people can carry the virus and pass it to others without being obviously sick. It is certainly possible that vaccinated individuals could catch the virus, not get sick but pass it to others. This is important information that I hope the FDA will demand from on-going studies.

Finally, while the vaccine's safety appears to be acceptable, with mostly annoying side effects, it is too early to declare the vaccine free of serious side effects.

Am I going to get the vaccine? Absolutely, as soon as it is available for me.

Prescription for Bankruptcy. Buy the book on Amazon

Saturday, December 5, 2020

Vaccine for Covid-19: Can I get one? Should I get one?

As regular readers of these posts know, I consider vaccines to be one of, if not THE, major achievements of medical science. Vaccination has literally saved millions of lives over the years. Diseases such as polio, whooping cough and measles that killed children around the world should now be of historic interest only. [Insert drum roll and consign the “anti-vaxxers” to the deepest levels of Hell.] Can they save us from Covid-19?

The traditional approach to vaccination has been a slow process. There are two major ways vaccines have been produced. Measles, mumps and rubella vaccines use a weakened form of the virus – close enough to the real thing that the body builds up defenses against it but so modified as to not cause a serious infection. Flu and polio vaccines and others use killed virus particles that cannot cause infection but which still enable the body’s immune system to later recognize the virus if it tries to infect you and fight it off. New vaccines typically take up to 10 years from conception through wide distribution, with lengthy trials proving that they are both effective and safe. The current pandemic, which has killed millions and damaged economies around the world, did not give us the luxury of many years of development and testing.

National labs and pharmaceutical companies, large and small, have rushed to develop vaccines. As of August 20, a report found 30 vaccines in clinical trials and over 100 at earlier stages of development. As you are probably aware, the two that are furthest along are vaccines from Pfizer (working with a small German biotech firm, BioNTech SE). and Moderna, which has worked closely with the U.S. National Institutes of Health. Both these groups are using a relatively new technology. They are injecting messenger RNA (mRNA) into the body. The mRNA tells the body’s cells to produce a protein, in this case the “spike protein” that is a distinctive part of the coronavirus, which then causes the body to build up an immune response. Note that in one sense this is not that different than the use of weakened live virus: the body’s own cells are tricked into producing a “foreign” substance that induces development of immunity. A different approach has been used by AstraZeneca working with Oxford University. They use a genetically altered adenovirus that carries a Covid-19 protein to develop the immune response. (This technology is also being used by Johnson and Johnson in its attempt and is the basis of the vaccine being distributed in Russia before any testing.)

How well do the Covid-19 vaccines work? A MAJOR WARNING: everything that I and most people know about these vaccines comes not from published peer-reviewed scientific papers but from press releases. The British National Health Service, which hopefully had access to full data, approved the Pfizer vaccine last week for emergency use, and the U.S. FDA is to review their application this week. Moderna is set to apply for emergency use authorization later this month. Based on the data that has been made available, both vaccines are remarkably effective, in the range of 95%. The Moderna/NIH trial enrolled over 30,000 U.S. participants, including 7000 over 65, 5000 under 65 but with high risk chronic diseases, and included 37% black and Hispanic: all high-risk groups. The AstraZeneca trial has been viewed skeptically because of a strange result. Several thousand participants were accidentally given a half dose for their first shot and full dose for their second. After this was noted, all subsequent participants got the intended series of two full doses. The study found that the vaccine seemed 90% effective in the group getting the half dose first shot but only 60% in the rest. This seems biologically implausible and is currently under study.

How safe are the vaccines? This is the $64 question for a substance that may be given to billions of people around the world. The good news is that the preliminary trials have not identified any serious side-effects, though 10-15% did experience soreness at the injection site, fever, chills and muscle aches that last 1-2 days. Whether more important side effects turn up months or years later is at this point not known.

How long will the immunity last? Again, a question impossible to answer. A recent report in the New England Journal of Medicine was encouraging: people enrolled in the very early (Phase 1) trial of the Moderna vaccine still had good levels of immunity in their blood several months after the second dose. A “real life” experiment adds to the optimism. A fishing trawler with a crew of 122 tested all the crew before they went to sea, both by nasal swab and antibodies. Even though all tested negative for the virus, one got sick with Covid and almost the entire crew subsequently fell ill. The only three who did not develop Covid were the three whose earlier antibody tests showed antibodies to the coronavirus.

When will a vaccine be available? Assuming the FDA grants approval, Pfizer and Moderna expect to deliver some 40 million doses by the end of the year. Since all current vaccines require two doses to confer immunity, this means some 20 million people can be vaccinated by late January/early February. The Advisory Committee on Immunization Practices, whose advice is usually followed, said that first priority should go to front-line health care workers, nurses and doctors working with acutely ill patients, some 21 million, and the 3 million residents of long-term care facilities, who have suffered the worst of the effects of the pandemic. Next in line would be those over 75 and such essential workers as teachers, police, fire and EMTs. By May, supplies should be much larger, particularly if vaccines from AstaZeneca and Johnson and Johnson are approved, and the entire population could be vaccinated by the summer.

Will people accept the vaccine? Vaccine skeptics abound, and the politicization of the vaccine development program certainly feeds into these feelings. A recent poll found that more than a third of Massachusetts residents were unlikely to get vaccinated, even though 90% supported requirements to wear masks, 64% were somewhat or very worried about catching Covid-19 and 66% knew someone who had been diagnosed with it. The acceptance rate is critically important, as so-called “herd immunity” will only keep the pandemic at bay if 80-90% of us are immune. Hopefully by the time there is sufficient supply for the general public, enough time will have elapsed from the early use that safety concerns will be addressed. It will also be very important for the doctors, nurses and others giving the vaccine to warn people about the potential for short-term annoying side-effects and reassure them that this shows that the vaccine is working, and ensure they come back for their second shot.

Prescription for Bankruptcy. Buy the book on Amazon