Wednesday, September 30, 2020

The Physical Exam: The next dodo?

Most experts who have looked at the relative value of the medical history, the physical examination and the findings of laboratory tests and imaging studies have come to the same broad conclusion. The medical history is by far the most important contributor to an accurate diagnosis; some 60 to 80% of the time, the history alone leads to the correct diagnosis. The physical exam generally contributes 12-20% of the needed information and laboratory/imaging results 10-20%. Both the physical exam and test results do increase practitioners’ confidence level that their diagnosis is correct.

You would thus expect that physicians would spend a lot of time taking a careful history and devote roughly equal time to doing a comprehensive physical exam and ordering and reviewing lab tests.

Alas, over the last few years my observations while accompanying friends and family members to medical appointments has been just the opposite. History taking is brief and appears to be largely devoted to “checking off” items such as smoking history and medications that are needed to complete the electronic chart. When patients start to tell their stories, the doctor typically interrupts in less than a minute.

As to the physical exam, it is charitable to call most I have witnessed cursory. Well-defined problems do not need a complete physical exam; if you are complaining of a sore throat, the doctor generally needs only check the inside of your mouth and your neck. Less well-defined problems such as weight loss or fatigue may need a classic head-to-toe exam. Even seemingly localized problems may need more than the obvious. Could your sore throat be mono? If so, checking for an enlarged spleen may be very useful.

You would expect hospital admission, reserved for the sickest patients, to require a thorough physical exam, as it was “in the old days.” What seems to pass for a complete physical these days seems to be listening to the heart and lungs and quickly feeling the upper abdomen. Rarely if ever do admitting doctors check the head and neck, and almost never is a breast or rectal exam done.

Instead the focus is on testing: “routine” blood work that gives little information and advanced imaging. The head echocardiography technician at a hospital where I worked once joked to me that the main reason residents ordered echocardiograms was that “the patient has a heart.” When ordered to follow up on a suspected diagnosis, imaging can be very useful; when ordered in a shotgun manner, it is equally likely to produce confusion and misinformation.

Patients, too, place more faith in CT scans and MRIs than in a good “H+P” (history and physical). That faith can be misplaced. Take back pain as a good example. Most people over 40 and almost everyone over 60 will have some abnormality when imaging is done of the spine. This includes people who have never had a backache in their life. All-too-often I have seen patients with muscular or arthritic back pain taken to surgery to fix an abnormality seen on a CT scan, and of course they were not benefitted in the least. A good H+P should strongly suggest the likelihood of a surgically curable source of back pain, and imaging can then confirm it, but the surgeon “who will not see me without a CT scan” is practicing poor quality medicine.

Worried about too much X-ray exposure? A recent study found that if you go to the Emergency Department with pain in your left lower abdomen, a simple combination of findings (absence of vomiting, presence of a fever and tenderness when the doctor presses on your abdomen that is only found in the lower left portion) makes a diagnosis of diverticulitis so accurately that a CT scan is not needed unless the doctor is worried about complications.

Let us not let the clinical exam, and in particular the physical, follow the dodo into extinction. Good history-taking skills and physical exam skills must be taught, and their use rewarded. We will see better results and lower costs.

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Tuesday, September 22, 2020

Fauci and Galileo

On April 12, 1633, the chief inquisitor appointed by Pope Urban VIII began the inquisition of physicist and astronomer Galileo Galilei. Galileo was ordered to turn himself in to the Holy Office to begin trial for holding the belief that the Earth revolves around the sun, which was deemed heretical by the Catholic Church. The Church had decided that the idea that the sun moved around the earth was an absolute fact of scripture that could not be disputed, even though scientists had known for centuries that the Earth was not the center of the universe. On June 22, 1633, the Church handed down the following order: “We pronounce, judge, and declare, that you, the said Galileo… have rendered yourself vehemently suspected by this Holy Office of heresy, that is, of having believed and held the doctrine (which is false and contrary to the Holy and Divine Scriptures) that the sun is the center of the world, and that it does not move from east to west, and that the earth does move, and is not the center of the world.” Galileo agreed not to teach the heresy anymore and spent the rest of his life under house arrest. It took more than 300 years for the Church to admit that Galileo was right and to clear his name of heresy.

Almost 400 years later, are we any better? Any smarter? Or is science still subservient to faith?

Science should be a powerful and positive force in society; it shapes the present, and it can guide our future. Politicians and policy makers should rely on validated research at critical moments of crises and emergencies to help guide their actions. Instead, what we have seen since the start of the Covid-19 crisis is shockingly close to Galileo’s treatment by the Catholic Church of the 17th Century.

By late February, many scientists were predicting hundreds of thousands of American deaths if strong measures were not taken but they were drowned out by Trump’s insistence that the virus would “disappear” mysteriously. The mainstream media deserves condemnation by reporting the fantasies of politicians as having equal weight to the opinions of epidemiologists. Highly opinionated politicians had their rhetoric amplified by social media. Wearing a mask to slow the spread of the virus has become a political stance instead of a scientifically proven way to protect others (and ourselves).

More recently, we have had the spectacle of CDC guidance about testing people exposed to the virus but without symptoms removed (and later restored) because Trump did not want numbers to look bad. This was done despite overwhelming evidence that asymptomatic carriers were a major source of spread. Guidance on how to safely open schools was redacted and edited to push for more school openings regardless of health consequences. The FDA gave “emergency use” approval of hydroxychloroquine to treat Covid-19 based largely on rantings by Trump and Peter Navarro, an economist by training, who insisted he knew more about the science than medical scientists. This was, again, removed when studies showed the drug did no good and might do harm.

The latest blurring of science and faith came when the CDC posted information about respiratory spread of the coronavirus, only to remove the post a day later – clearly because the information in the post did not gibe with large indoor rallies or rapid reopening of all businesses.

Case reporting was taken away from the CDC so that the numbers could be massaged to look better. Most recently we have had Alex Azar, the Secretary of HEW, insisting that he alone could sign off on any new rules, regardless of the opinions of the career scientists who were much more qualified to do this.

Anthony Fauci, America’s most esteemed virologist, who refused to kowtow to every Trump pronouncement, has been subjected to harassment and character assassination by Trump and by his right-wing media enablers.

Science does not have all the answers. Some decisions are inherently political. A 55 MPH national speed limit would probably cut deaths and would cut some greenhouse gases, but it would be widely flouted and may not be politically acceptable. Similarly, a total economic shutdown might be estimated to potentially save X deaths over the rest of the year but might be economically intolerable. What should happen is that politicians take advice from scientists, weigh the competing factors, and decide what is best for the country.

What, alas, is happening is that politicians ignore scientists and make decisions based on what they think will help them be re-elected. Vote for science. The life you save may be your own.

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Saturday, September 12, 2020

Coronavirus vaccines: ready for prime time?

When will we have a vaccine? Can life get back to normal when we have a vaccine? Questions like this have been in the news almost daily. The underlying questions of most interest to the public can be expressed as “when will a safe and effective vaccine be available to me and my family?” and “will the availability of a vaccine allow normal life to resume?”

Vaccine availability will not fail for lack of trying! Vaccine development is usually a back-page issue, and not a high priority to the pharmaceutical industry because profits from sale of vaccines lag well behind those of most pharmaceutical products. With the world’s attention so focused, we now have 38 vaccines against Covid-19 in clinical trials in humans and another 90+ that are in animal trials.

If you are a regular reader of these posts, you know that I consider vaccines to be the most important public health development in medical history. Prevention is always better than treatment, and vaccines have saved many millions of lives over the 225 years since Jenner’s first experiment.
What may be confusing to many is the different approaches that different researchers and companies are taking to making vaccines. Traditionally, vaccination has taken one of two forms: give people a mild illness that is close enough to a serious one that they build up their immunity to the serious one – Jenner’s approach in 1796 – or inject people with killed virus or virus particles that also lead to an immune response without getting sick – the standard approach with influenza vaccines. A major problem with the latter approach is that it is very slow, growing virus in egg cultures before destroying the virus and using it to make vaccines.

Current vaccination research is much more “cutting edge.” Genetic engineering techniques are being used; “viral vectors” are being tested: putting bits of Covid-19 RNA into harmless adenoviruses which infect human cells and produce an antibody response; getting various Covid proteins, including the spike protein, into such vectors. The many approaches taken reflect our inability to know which is most likely to work (as well as companies’ need to have their own unique product!).

As to the “when,” the issue is not developing a candidate but proving that it is both effective and safe. An effective vaccine not only results in recipients developing antibodies, which is easy to measure, but prevents disease in exposed individuals, which is much harder. There is still much we do not know about the body’s response to Covid-19; a clear worry is that people can get repeated colds, many of which are caused by other coronaviruses, so it is not clear that exposure always results in immunity. In my practice, I observed that first or second year teachers seemed to be sick all winter, but that veteran teachers rarely got colds. Perhaps we need repeated exposures to coronaviruses before our immune system can fight them off?

While vaccines in general are very safe (please don’t get me started on the “anti-vax” movement!), vaccines developed and deployed too quickly have been problematic. This can reflect poor manufacturing practices: in the 1950’s a polio vaccine manufactured by Cutter Labs intended to contain inactivated polio virus mistakenly had some batches with live virus.

In the late 1990’s the FDA halted use of a vaccine against rotavirus, a potentially fatal diarrheal illness of children, when it appeared to cause bowel obstruction, and it was eight years before a safe rotavirus vaccine was approved. The complication was rare, and so was only found after the vaccine was in widespread use.

Rushing a vaccine into use is a serious risk. Faced with predictions of a swine flu pandemic in 1976, President Ford launched a huge effort to develop and distribute a vaccine against swine flu, but the flu was less serious than predicted and some 450 people who got the vaccine developed a rare form of paralysis.

How do you develop and test a vaccine to be sure it is both effective and safe? You do not cut corners!

The first step is testing in laboratories, first in cells and then in animals. Initial human testing, Phase 1, is done in small numbers of healthy volunteers to be sure the vaccine results in an immune response and does not have obvious safety issues. In larger, Phase 2 trials, the vaccine is given to hundreds of people, generally including both children, young adults and the elderly, to see if it acts differently in different groups and to watch for obvious safety issues. If these small samples do not raise any concerns, the vaccine moves into Phase 3, in which thousands of volunteers are given either the vaccine or a placebo. These trials must show that many fewer people receiving the vaccine get sick than do those given placebo. They are also watched carefully for any less common side effects that did not appear in the early phase trials.

Only when the results of Phase 3 trials show that a vaccine is both effective and safe should it be approved. The vaccines developed in China and Russia that were rushed into production without results of Phase 3 trials may have serious risks and/or may not work.

My big worry is that a beleaguered FDA, which we have already seen respond to political pressure and approve hydroxychloroquine for Covid-19 only to later rescind that approval, will bow to political pressure and approve a coronavirus vaccine before Phase 3 trials have been completed. Hopefully the manufacturers, wary of lawsuits, will be the regulating force that our regulators should be.

A truly effective and safe Covid-19 vaccine is badly needed and will be welcomed, but “warp speed” is better left to the ships of Star Trek than to public health.

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Monday, September 7, 2020

What is the truth about marijuana?

Other than alcohol, marijuana (cannabis) is the most commonly used drug in the United States. Some 39 million Americans, 12% of the population, use marijuana at least occasionally. While clearly more commonly used by adolescents and young adults, in 2018 4% of adults over 65 admitted to using it within the prior 30 days.

In the United States, the use and possession of marijuana is illegal under federal law for any purpose, by way of the Controlled Substances Act of 1970. Under the CSA, cannabis is classified as a “Schedule I” substance, right up there with heroin and methamphetamine, determined to have a high potential for abuse and no accepted medical use – thereby prohibiting even medical use of the drug. At the state level, however, policies regarding the use of cannabis vary greatly, and in many states conflict significantly with federal law. As of 2020, medical use of marijuana is legal in 33 states and the District of Columbia, and recreational use is legal in 11 more states.

What are the benefits of marijuana? What are the harms? To a large degree, we simply do not know. Marijuana is not a single substance; the plant contains at least 500 chemical substances. The best known and studied are cannabidiol (CBD) which I wrote on recently and delta-9-tetrahydrocannabinol (THC). It is THC that has the CNS (brain) effects. Because of the federal classification of cannabis, much less research has been done than should be, and much of what you read is low quality. Many of the reputed benefits and harms arise from studying people who admit or deny use. Since use was until recently a criminal offense, self-reporting is likely to be unreliable. There is also the confounding factor of whether people who do or do not use marijuana are otherwise the same. Many of the studies claiming adverse effects on intellect are of this variety and not necessarily valid.

Another confounding factor is that the THC content of marijuana, at least that seized by the DEA, the federal Drug Enforcement Agency, has been going steadily and dramatically higher. In 1995, the average concentration of THC in seized products was 4%; in 2014 it was 12% - this is not the pot of the 1960’s!

The human brain has cannabinoid receptors, which mediate the psychoactive effects of cannabis. There are other receptors in immune cells and other tissues that may be more targeted by CBD. Acutely, the effect of THC is the “high:” euphoria, relaxation, altered sensations – and also: decreased processing speed, attention and reality testing. “Tolerance” develops quickly as the receptors are down regulated, so that daily use results in much less response.

Proven benefits of THC are limited. It has some benefit in preventing chemotherapy-related nausea and improves the appetite in many people with wasting disease such as AIDS. While it has been “approved” for pain relief in states where medical marijuana is legal, its benefits beyond those of prescription and OTC pain relievers are modest.

The headlines were dominated in August by a statement from the American Heart Association which stated that cannabis had no cardiovascular benefits but did have adverse CV effects, including arrhythmias and heart attacks. Critics noted that most of the adverse effects were anecdotes and case reports.

Inhaled marijuana products can have the same adverse effects as smoking any product. Before Covid-19, when vaping-relating lung disease was our biggest public health concern, it appeared that vaping cannabis products was particularly dangerous.

Bottom line? Cannabis is not a miracle drug. It is probably no worse than alcohol. (I have never heard of an angry belligerent pot user.) It can clearly impair your ability to safely drive or operate machinery. If you feel it helps your migraine or other painful condition, use it, but use it cautiously, as it is habit-forming.

Until we know more about its effects on the developing brain, I would actively discourage use by adolescents, as I do for alcohol.

More quality scientific study is needed and would be encouraged by moving cannabis out of Schedule I by the DEA.

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