When I started my Internal Medicine residency in 1994 there was an entire floor of AIDS patients. Pharmacology has changed that world and now HIV patients mostly stay away from the hospital. Every now and then a patient will show up not on anti-viral treatment and resemble a mid-1990s AIDS patient but the virus has become an afterthought to most outside of the infectious disease world. The anti-viral therapy for HIV is a clear victory and there is not much debate.
That is not always the case.
One drug that was new in the 1990s was omeprazole. It was the first approved proton pump inhibitor (PPI) and it revolutionized our ability to suppress acid in the stomach. It healed ulcers and treated gastro esophageal reflux effectively. The drug carried a warning about using more than 14 days because there were concerns long term use could lead to gastrinoma tumors. In 1994 it was expensive and if a prescription was needed in the military system you had to track down a gastroenterologist to approve it.
Over the years many different PPIs were approved and the drugs have become one of the most prescribed drug classes in history. They are now widely available over the counter. They have been used chronically by millions of patients and gastrinomas have not exploded across the planet.
The story does not end there. Retrospective studies have suggested long term use could lead to bone fractures, kidney issues, infections, heart attacks, and dementia. It is very difficult to parse out whether some of these risks exist and how big that risk might be.
In 2019, a randomized placebo-controlled study (Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin ) was published in Gastroenterology which showed at three years use of pantoprazole, a PPI, was not associated with any adverse outcomes. There was a trend showing increased risk of enteric infections but far lower than suggested by previous retrospective studies.
This has not laid the issue to rest. You will still see commercials recruiting patients for class action lawsuits mostly related to the chronic kidney disease claims. It is still an issue that needs to be addressed when speaking with colleagues outside of gastroenterology. More importantly, all the negative studies on the PPIs were covered extensively in the media. The 2019 study received almost no attention. That is an ongoing hurdle when a patient has a definitive need for a PPI.
Even with what we know, challenges and questions remain. One excellent study is not a final answer. What happens at five years? Or ten years? Could the pendulum swing yet again on the PPIs? A typical patient would be understandably confused by the information and that is why physicians, and in this case gastroenterologists, exist. Lay out the science and let the patient decide.
So why talk about a long history of a heartburn drug spanning decades?
Science evolves but it also has different degrees of strength. After decades, the science is still evolving on PPIs. And yet somehow people think there can be hard answers on science with COVID-19. That would be 19, as in 2019, the same year a long-term randomized safety trial was finally published on the PPIs.
Early on in the COVID-19 pandemic there were physicians writing themselves hydroxychloroquine prescriptions for future use in case they became infected. Patients were coming in asking for prescriptions as well. The drug was even on hospital algorithms for treatment, including locally. Pharmacies stopped filling the prescriptions so people who needed the medication for other indications could still get it. A lot of the excitement or hysteria was based on studies. And then that was reeled back because of other studies and the drug fell off guidelines (Chloroquine or Hydroxychloroquine and/or Azithromycin | COVID-19 Treatment Guidelines, National Institute of Health).
So what about ivermectin? There is a proposed mechanism of action by which the drug could work (Ivermectin | COVID-19 Treatment Guidelines, National Institute for Health). There have been several studies done on the drug. There is variable quality to the studies and variable outcomes. Some studies show it makes things worse, some say it makes no difference, and some say it may help. None of the studies are high quality. The science does not come down conclusively at this point. The drug has been in guidelines across the world, most notably India, but that country removed it from protocols last month.
There is one widely available over the counter drug with an excellent safety profile that does have a possible mechanism of action against COVID-19 (COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms, National Institute of Health). That drug is famotidine. Famotidine is a histamine-2 blocker and belongs to the class of drugs that preceded PPIs as the mainstay of acid suppression in the stomach. Again, there is no hard science and no consistency to results.
None of these medications have anything close to what science would lead them to be recommended in a clinical guideline. And none of it has ever impressed me.
If I were to become infected with COVID I would not use hydroxychloroquine or ivermectin. Effectiveness and safety are not clear at all. I might consider using famotidine because despite no proven efficacy there is essentially no downside. A more proven therapy like monoclonal antibody treatment (Anti-SARS-CoV-2 Monoclonal Antibodies | COVID-19 Treatment Guidelines, National Institute of Health) is the obvious choice. There are some other promising drugs but those do not spur emotion in the media.
Once or twice a year there is a case in my office where there is no clear diagnosis or standard treatments are not working. COVID-19 is not at that level but our understanding of the disease and its treatment is still in its infancy. There is a lot that is not known and mistakes have been made because we reached ahead of the science out of necessity.
When faced with a tough case one scours the literature for any small study or case report to see if there is anything that can be tried. There often is no answer. Patients can be referred to a major medical center and they will not have an answer. At that point one must try to hypothesize about what may be going on physiologically. If something is tried and works you often do not know if it is placebo or if it was really a solution. At that point it is instinct and experience driving decisions, not science. We have moved past that stage with COVID-19 but it is not exactly diabetes at this point.
There are physicians out there who would recommend ivermectin or hydroxychloroquine. Famotidine has mostly fallen off the radar. They are treating COVID-19 as being a case requiring treatment beyond the hard science.
Physicians are being pillared for using these “discredited” treatments. They are being accused of pushing “misinformation.” The advocates of the drugs are certainly are overstating the evidence. However, it is not accurate to say the treatments have reached a level where they can be completely dismissed.
Vaccines are a slightly different issue. We have excellent randomized clinical data now that confirms safety and efficacy. The only argument that can be made is the benefit may not be all that great in a low-risk population and that is specious. It is a much more bothersome issue.
The question becomes are these physicians snake oil salesmen? And if they are, should there be restrictions placed on them?
Some state medical boards have started threatening the licenses of medical professionals who they state are spreading “misinformation.” There has been a call (Alaska’s medical board needs to act on misinformation, Anchorage Daily News) for Alaska to look into the practice. The three major certification organizations in primary care have also issued a statement (Joint Statement on Dissemination of Misinformation, American Board of Internal Medicine) threatening revocation of status for spreading “misinformation.”
Government intervention is not stopping at information. Nurses in Oregon are being threatened with investigation and possible loss of their license if they do not get a COVID-19 vaccination. (Oregon Nursing Board discusses temp rule over vaccines as protesters gather, MSN).
So what is misinformation? That is a moving target.
The medical world is full of debate. There can be legitimate disagreements. Almost every physician out there has advocated or used a treatment at some point that has less science behind it than much of the COVID-19 literature at this point. And it is not always when we are looking for a Hail Mary.
Those decisions can change as well. I have heard the same expert advocate a treatment one year at a national meeting and unequivocally tell people to never use that treatment the next year. There is no misinformation, just advancing science. That is the only reason Anthony Fauci gets a pass.
The country is in a dangerous place. The word “science” is being used when there really is no quality “science” present. Opinion is quickly becoming hard fact in the name of political agenda. We have journalists who throw around words like “discredited” and “misinformation” in hard news pieces. The same journalists who ran away from taking calculus in college.
In the end people need to be responsible for themselves. It is frustrating when people have “done research.” Research often means they listened to Rachel Maddow or Sean Hannity. And the “appeal to authority” fallacy has got to stop. A specialist is not right just because they are a specialist.
There are limitations to what people outside of medicine can truly evaluate. Data comes in many forms and most laypeople are not trained to know what is good and bad data or how to bring it together coherently. Committees can fight over data for months when developing a guideline.
The media, as pointed out with PPIs, is after sensationalism and not science and exacerbates the problem. It tilts to one side by design based on agenda.
In 2021, my job is to tell people what we know and nuance it appropriately. Then I can tell them what my recommendation is for options in treatment. It is up to the patient at that point to make a decision. That does come down to an issue of trust, many times no different than when I take my car into the mechanic. I generally do not ask MSNBC or FOX or one of their “experts” if my mechanic is right.
People should not ingest drugs without good indication. Physicians should not be anti-vaxxers. This is not a controversial position. At least not to this stomach doctor.
Evidence is the backbone of medicine in the United States. That said, the practice of medicine also requires experience and some instinct. One must occasionally think and act outside the box. Defining when it is okay to step outside those lines is a difficult process. It can occasionally be a disservice to patients to draw those lines.
Patients have to educate themselves. Overcontrolling messages is not going to change the landscape. It will just feed the conspiracy theorists.
If we take away licenses and try to control how people practice their profession, or limit speech, it better be based on solid irrefutable data. Otherwise, we are in dangerous territory.
The irony of course is this is being driven by people who run the media and government. And we all know there is no misinformation being peddled by them. What could possibly go wrong?
Dr. Brian Sweeney has practiced gastroenterology in Anchorage for 21 years, with the first three at JBER. The views presented here are his own and are not made on behalf of any organization.