Despite the rigors of evidence-based medicine, some ill-informed medical axioms die hard.
“There aren't too many things that are pure myths in medicine, but there are definitely things that we were taught that were pure dogma,” said Douglas S. Paauw, MD, MACP, in April at Internal Medicine Meeting 2019 in Philadelphia.
Medical myths persist for many reasons, including physiologic assumptions, case reports, and tradition, he said. This last one in particular has a strong hold on practice. “Tradition is very powerful, and remember, it's only really in the last 100 years or so that we've really had a strong attempt to have strong evidence for things,” said Dr. Paauw, professor of medicine at the University of Washington School of Medicine in Seattle.
During his talk, “Busting Medical Myths: When Dogma Is for the Dogs,” he debunked many common medical misconceptions. Below are 10 of the top tenets internists may want to be more tentative about.
Myth No. 1: Avoid the influenza vaccine in patients with egg allergy. This idea is based on the fear that administering a vaccine that was grown in eggs might cause anaphylaxis due to minute amounts of egg protein. “This was, I think, well intentioned and reasonable,” said Dr. Paauw. “But in the last few years, we've actually had some data to look at, and we find that this generally doesn't happen.” One review, published in the August 2014 Expert Review of Vaccines, found that in 28 studies of 4,315 patients with egg allergy (656 with a history of anaphylaxis), no patients developed a serious reaction after receiving an egg-based influenza vaccine.
Recommendations from the CDC and the American Academy of Allergy, Asthma, & Immunology agree: Patients with egg allergy of any severity should receive the influenza vaccine annually, with no special waiting periods after vaccination. Even so, Dr. Paauw said his clinic still asks patients about egg allergies. “If we're going to give it anyway, why are we asking? … This should not be an excuse that patients give us for avoiding the influenza vaccine,” he said.
Myth No. 2: Avoid the influenza vaccine, and possibly other vaccines, in patients with a history of Guillain-Barré syndrome due to the potential increased risk of relapse. “The 1976 swine flu vaccine had probably the largest number of cases, but this has always been a concern,” said Dr. Paauw. “For many years, I did not vaccinate my Guillain-Barré patients because I thought, ‘Well, that makes sense.’”
There aren't a ton of data on this, but the existing literature is convincing, he said. One study, published in the March 2012 Clinical Infectious Diseases, assessed 279 patients with previous Guillain-Barré syndrome who received a total of 989 vaccinations, including 405 trivalent influenza vaccinations. No cases of recurrent Guillain-Barré occurred. The GBS/CIDP Foundation recommends avoiding immunizations that caused initial symptoms within six weeks of administration. “I think that's fair enough,” Dr. Paauw said. “The vast majority of our Guillain-Barré syndrome patients, that's not the case, so they should be fine and ready to get vaccinated, and I've changed my practice.”
However, he warned that physicians who want to vaccinate may encounter strong feelings from patients. “As we change things that we've done for a while with our patients, sometimes there's a lot of pushback, and there's a lot of emotion with it too,” Dr. Paauw said. For an easier transition, try to suggest vaccination at first and allow patients to decide on their own time, he recommended.
Myth No. 3: “Sinus” headaches require antibiotic therapy. Many patients will come in two or three times a year, reporting sinus headaches and congestion and adding that once they take antibiotics, they feel better in a day or two. In fact, these generally are not sinus headaches, but migraine headaches, Dr. Paauw said. “This is a really important variant of migraine headaches that has been poorly understood. … In all of our practices, they've been labeled as sinus headaches for a long time,” he said. One study, published in the December 2013 Journal of Headache and Pain, found that of 130 patients with migraine and a history of sinusitis, about 82% were misdiagnosed as having sinusitis, with an average time to migraine diagnosis of almost eight years.
The confusion is partly due to symptoms. In a study of 100 patients who believed they had sinus headaches (about 75% of whom had a final diagnosis of migraine or probable migraine), 76% of patients had repeated pain in the distribution of the second division of the trigeminal nerve, and 62% experienced bilateral forehead and maxillary pain with their headaches, according to results published in February 2007 by Headache. “This is what pushes us away from thinking about migraine in these patients. They say, ‘I hurt right here, I think it's my sinuses,’” Dr. Paauw said. “In this variant, two-thirds of them can have bilateral pain. That's very atypical for what we usually think about migraine.” With or without antibiotics or decongestants, these patients will usually get better within 12 to 48 hours, he said.
Myth No. 4: Antimicrobial prophylaxis is necessary for dental work in patients with any kind of prosthetics in the body. “This is one of the stranger myths,” Dr. Paauw said. “We thought we were done with this back in the 1990s.” Then, in 2009, the American Academy of Orthopaedic Surgeons came out with a new statement, saying clinicians should consider antibiotic prophylaxis prior to any invasive procedure performed on all patients with total knee or hip replacements. The statement was a 180-degree turn from a 1997 joint statement from the group and the American Dental Association. Curiously, both statements referenced the same paper, which said that late prosthetic joint infections are not associated with infective endocarditis, he said. “They had it right in 1997, nothing new happened, and in 2009 they said it should be considered. … I am just flabbergasted by it,” Dr. Paauw said.
Although the statement was retired in December 2012, he said this myth is “still out there.” When Dr. Paauw asked attendees how many had received in the past year a request for antibiotic prophylaxis from a patient, dentist, or orthopedic surgeon, hands shot up throughout the room. Now there is new evidence to show that antibiotics aren't necessary in these patients. A study of 6,513 matched pairs of Taiwanese patients who had total knee or hip arthroplasty and had dental treatment found that there was no significant difference in infection risk between those who took antibiotics and those who didn't, according to results published in the February 2017 Infection Control & Hospital Epidemiology. “[That] is what we thought it would be, because the organisms that cause prosthetic joint infection are not dental organisms, by and large, so it never made any sense,” said Dr. Paauw, adding that he keeps fact sheets and articles handy to dispel this myth in practice. “Instead of a prescription, I just fax them to the dentist or orthopedic surgeon,” he said. 
Myth No. 5: Docusate is the go-to treatment for constipation. “It is still one of most commonly used drugs for constipation, especially on the surgery side when people are discharged on narcotics … but it probably doesn't do much in the way of softening stool,” said Dr. Paauw. One systematic review, published in the February 2000 Journal of Pain and Symptom Management, concluded that the drug's use in palliative care has been based on inadequate experimental evidence.
More recently, the Canadian Agency for Drugs and Technologies in Health concluded in June 2014 that “[T]he available evidence suggests that docusate is no more effective than placebo in the prevention or management of constipation.” Dr. Paauw recommended sticking to constipation treatments that have “some real efficacy,” such as psyllium and polyethylene glycol.
Myth No. 6: Metronidazole and alcohol don't mix. For years, physicians have told patients that they might get a disulfiram-like reaction if they combine alcohol with metronidazole, Dr. Paauw noted. “On every pill bottle of metronidazole you prescribe, there's a little martini glass with a slash through it,” he said. This myth mainly comes from case reports. “A theory that this reaction occurred was in many of the pharmacology textbooks from the '50s and '60s, and so the case reports followed,” said Dr. Paauw.
One review, published in the February 2000 Annals of Pharmacotherapy, analyzed six case reports from 1969 to 1982 that allegedly showed this reaction and found that none produced any evidence that it exists. Four of eight patients in the reports had serious adverse events, including one death. However, “They didn't have evidence of increased acetaldehyde levels … and then the death, they didn't even have a prescription for metronidazole. They did some bloodwork and they said, ‘We found evidence of metronidazole in the bloodstream,’ but there are many drugs that cross-react with metronidazole,” he noted.
With the case reports potentially in question, Dr. Paauw looked for other data and found a study in rats that showed increased intracolonic (but not blood) acetaldehyde levels with ethanol and metronidazole. “So what do we need? A human study. Where do you get volunteers? Medical school,” he said. A double-blind trial randomized 12 healthy medical students to receive alcohol plus either placebo or metronidazole three times a day for five days. There was no difference between groups in blood acetaldehyde levels, vital signs, or symptoms, according to results published in the June 2002 Annals of Pharmacotherapy.
“For healthy adults, we have a small study that it seemed to be OK,” Dr. Paauw concluded. “But we don't know what the deal is with most of the people we take care of,” such as patients with renal disease or end-stage liver disease, who could have problems with just the alcohol alone. “Certainly [if] the issue comes up for the young healthy adult, I think the risk is very, very low,” he said.
Myth No. 7: Iron must be dosed multiple times a day to treat iron deficiency. “I was certainly taught to give iron three times a day, and that was certainly what the tagline was in the 1980s, and that continued through the '90s,” said Dr. Paauw. As an attending in 2000 with the thought that three-times-daily dosing might be overkill, he challenged his trainees to an experiment: Take iron three times a day for a week. One by one, they all felt sick and quit. An intern was done with it in one day, a resident lasted two days, Dr. Paauw lasted three days, and one medical student with an iron will lasted five days.
In terms of the data, he said, one of the best studies on once-daily iron was published in the October 2005 American Journal of Medicine and randomized 90 hospitalized elderly patients with iron-deficiency anemia to receive elemental iron as 15 mg or 50 mg of liquid ferrous gluconate, or 150 mg of ferrous calcium citrate. At 60 days, there was no difference between groups in the rise of hemoglobin or ferritin levels, but there was a significant difference in side effects, with fewer patients in the low-dose group reporting abdominal discomfort compared to the other groups. In addition, some newer data suggest that dosing iron every other day might lead to better absorption, Dr. Paauw noted.
Myth No. 8: Vitamin B12 injections are necessary to treat pernicious anemia. This myth comes from studies in the '40s and '50s that gave tiny doses of oral B12 with animal intrinsic factor based on the idea that intrinsic factor was necessary for absorption, Dr. Paauw said. However, there's a second physiologic mechanism at play with bigger doses (e.g., 1,000 µg), mass action, which allows B12 to cross into the bloodstream, he explained. “That was not known with these early studies … so these all failed because they got antibodies and they gave tiny doses, so it was ‘proven’ that oral treatment didn't work,” Dr. Paauw said.
Now, low-quality evidence shows that oral and intramuscular B12 have similar effects in terms of normalizing serum B12 levels, but oral B12 costs less, a March 2018 Cochrane review concluded. “They graded it low-quality because of the numbers,” as the available studies on daily dosing were small, Dr. Paauw noted. “We don't have a huge study, but it works, and it's a lot easier for patients to take oral B12.”
Myth No. 9: Beta-blockers increase the risk of depression. This myth comes from a case series published in 1967 in which the major symptom reported was fatigue, he said. “We do know that beta-blockers can be associated with fatigue,” Dr. Paauw said, but everyone latched onto the idea that the association with depression was a strong one.
Several studies have failed to find a powerful association. Most recently, a propensity-matched study in the April 2016 American Heart Journal found that beta-blocker therapy was not associated with an increase in depressive symptoms up to 12 months after acute MI. “I think it's still controversial, but if an effect exists, it's small, and certainly it shouldn't stop us from using beta-blockers when the beta-blocker indication is really a strong one,” Dr. Paauw concluded. 
Myth No. 10: Medications are no good past their expiration date. The expiration date is the date when the manufacturer still guarantees 90% potency, and companies have very little motivation to extend it, he explained. One group that does have a vested interest in doing so is the U.S. military. An analysis of data from the federal Shelf Life Extension Program, published in May 2006 by the Journal of Pharmaceutical Sciences, found that 88% of 122 drugs from 3,005 lots had 90% or more potency one year past the expiration date, with an average extension of more than five years.
Another study, published in November 2012 by Archives of Internal Medicine, assessed medications (mostly compound drugs) that were sealed in boxes and had expired 28 to 40 years prior. Overall, 12 of 14 compounds had retained 90% or more potency, and medications that stood the test of time included codeine, hydrocodone, and acetaminophen. “The only one that broke down was aspirin. The aspirin was only at 1% of what was supposed to be in it,” said Dr. Paauw.
One medication of extra financial and safety-related importance is epinephrine injection, which was found to be sterile and detectably pure more than 2.5 years after expiration in a study published in January 2018 by Prehospital Emergency Care. Another study of 40 EpiPens that were one to 50 months past expiration found that all had 80% or more of their labeled concentrations, according to results published in June 2017 by Annals of Internal Medicine. But because of the high morbidity of a failed injection, Dr. Paauw said this is not enough information to rely on expired pens (the pens will not cause toxicity, but they may be ineffective). Nonetheless, he recalled a patient who did not use epinephrine when needed and proceeded to get very sick. “When I asked why, they said because it had expired,” Dr. Paauw said, adding that he tells patients to keep expired pens as backup. “It's better to have something there than nothing.”