Categories
Outpatient Practice

Physicians Should Promote Over-The-Counter Influenza Testing

When the COVID history books are written, one of the good things to come out of the pandemic is the public’s successful use of home antigen testing for viruses. Forty years ago, if you wanted any kind of diagnostic medical test, you had to go to a doctor. The U.S. Food and Drug Administration (FDA) took the position that the general public was just not sophisticated enough to perform any kind of home testing. Then, in 1976, the FDA made a ground-breaking approval of e.p.t. – the Early Pregnancy Test which became the first over-the-counter pregnancy test that anyone could do. By 1988, 33% women of child-bearing potential had used a home pregnancy test. Today, global annual sales of home pregnancy tests are $705 million and they are well-accepted for their ability to accurately identify pregnancy as early as a week after conception.

Home glucose testing followed a similar timeline. The first glucose test strip, Dextrostix, was developed in 1965 and for the next fifteen years, the use of test strips was limited to physician offices. In 1980, the Dextrometer was launched and home glucose testing rapidly became the standard of care.

But it wasn’t until the COVID pandemic that home testing for an infection became available. Indeed, the home tests for COVID became one of public health’s most valuable tools to identify infections early in order to isolate contagious persons and slow the infection rate in communities. I can remember the earliest COVID home tests that required a person to use a camera on a phone or computer to link with a person trained in proctoring the steps in testing and in interpretation of the results. Those test kits gave way to tests that anyone could do on their own, without telemedicine proctoring. It turned out that the general public was more sophisticated than the health community had thought and were able to correctly perform and interpret these tests without proctoring.

Labcorp’s Pixel test can diagnose RSV and influenza infection in addition to COVID. Anyone can buy an over-the-counter Pixel test and do the nasal swab themself at home; however, it must be mailed to Labcorp for analysis and the results can take 2 days to come back. This delay of 2 days to make a diagnosis renders Pixel of limited use since rapid influenza tests can be performed in a doctor’s office in a matter of minutes. Thus, if a person is worried that they have influenza, it is far more expedient to go to their doctor, an urgent care center, or an emergency department for a rapid flu test.

Last year, in February 2023, the FDA approved Lucira, a home test for both COVID and influenza. This test, produced by Pfizer, correctly identified 90% of positive influenza A samples and 99.3% of negative influenza A samples. Lucira also detects influenza B but there were few cases of influenza B circulating at the time that Lucira was tested for accuracy. Unlike Pixel, Lucira tests are done by having the person do their own nasal swab and then perform testing and test interpretation themselves. The test requires a battery-powered device to analyze the specimens (the device and batteries are included in the Lucira kit). The total amount of time to perform the nasal swab and run the test through the device is about 35 minutes. Lucira is available through Amazon and costs $50 for one test kit. You can read the full kit instructions here, at the FDA’s website.

Why aren’t more people using Lucira tests?

Lucira has been a major breakthrough – a home influenza test that anyone can do and get immediate results. Diagnosing influenza early is crucial for infection control and treatment efficacy. You get influenza by being exposed to an infected person’s respiratory droplets. Thus, early diagnosis permits isolation of an infected person so as to reduce the chance of spreading influenza to family members, co-workers, or classmates. We have a very effective treatment for influenza – oseltamivir (Tamiflu), made by Genentech. However, for oseltamivir to be effective, it should be started within 2 days of the onset of influenza symptoms. This limits the usefulness of the Pixel tests since by the time the results get back, it is often too late to start Tamiflu. For these reasons, you would think that Lucira would be flying off the shelves but the reality is that few Americans (including doctors) have even heard of it. So why is it being so woefully underutilized?

  • It is only available through Amazon. In larger communities, Amazon can deliver a Lucira test kit the same day it is ordered. But in some areas of the country, it can take longer. Most people would prefer to stop by their local pharmacy to buy a test kit on-demand when they first develop flu symptoms but you can’t buy Lucira at a CVS or Walgreens. By limiting sales through Amazon, there is an access and time barrier to obtaining a test kit.
  • It is expensive. Personally, I would be more than willing to pay $50 to find out as early as possible if my fever and cough are due to influenza or not. But $50 can be a cost barrier to many people, especially since a COVID-only test kit costs less than $20 (for 2 tests in a kit) at your local pharmacy.
  • It is not being marketed. The American public is inundated with TV commercials for drugs. That’s because there is money to be made when pharmaceutical companies sell more of those drugs. Pfizer has relatively little to gain by selling its Lucira test kits. If Genentech produced an influenza home test kit, it would have an enormous financial incentive in the form of greater sales of Tamiflu from all of those early influenza diagnoses. Pfizer lacks an incentive to put money into advertising Lucira or to reduce the price of Lucira.
  • The public has COVID fatigue. Let’s face it, we’re all tired of COVID and just want it to go away. And the truth is that COVID hospitalizations were lower last week than any week since June 2023. We are also at the end of influenza season and flu cases are dwindling. If you get flu-like symptoms today, it is statistically more likely to be some other respiratory virus that there is no treatment for, anyway. COVID and influenza are out-of-sight, out-of-mind in the American public’s consciousness.

So, what can we do?

I’ve seen many people die from influenza during my career. As a pulmonologist, I know that the best way to reduce the chance that my patients will die from influenza is to diagnose it as early as possible. But I also know that it can be difficult for patients to get in to see a doctor within 48 hours of onset of flu-like symptoms. Patients will often call their doctor or message their doctor through their electronic medical record patient portal when they have flu-like symptoms but most doctors will not prescribe Tamiflu unless they have confidence that the patient actually has influenza as opposed to some other respiratory virus. So, what can we do to improve the use of home influenza testing?

  1. Make it more widely available. Don’t get me wrong, I buy a lot of stuff through Amazon. I’m surprised that Jeff Bezos doesn’t send me a fruit basket every Christmas in gratitude. But by limiting distribution to Amazon, the test kits are just not readily available to many (or most) Americans. Physicians should ask Pfizer to sell Lucira at brick and mortar pharmacies.
  2. Increase competition. Adam Smith, the father of supply and demand economics, identified that the best way to improve the quality and availability of a good or service as well as reduce the price of that good or service is through competition. Right now, Pfizer has a monopoly on the home influenza test kit market and is not incentivized to reduce the cost of test kits or to improve those kits. The FDA needs to authorize home influenza test kits from other manufacturers. It’s industrial competition that makes America great.
  3. Physicians need to educate themselves. We are influenced the greatest when a trusted peer advocates a new test or treatment. This can be through formal educational programs, such as grand rounds, or through informal settings such as department meetings or medical staff meetings. We need to spread the word about the availability of home influenza testing – not only among ourselves but also among our patients.
  4. A perfect opportunity for telemedicine. My inbasket in our electronic medical record was always the bane of my existence. I would tediously clear out all of the test results and patient messages every evening but by the next day, that inbasket would be full again. Physicians don’t like providing health advice or treatment via a patient portal or phone call because it takes up a lot of time and they don’t get paid (or if they do, they get paid very little). But with the expansion of telemedicine reimbursement during the COVID pandemic, a doctor can get paid for their time and expertise while improving the health of their patient expediently. Home influenza testing creates an ideal opportunity to utilize telemedicine – the doctor can observe the patient’s general condition and look at the test result via the video link. If the test is positive, a prescription for Tamiflu can be sent to the pharmacy without the patient having to come to the doctor’s office (and potentially infect patients in the waiting room, the office staff, or the doctor him/herself). Ideally, medical practices should make same-day telemedicine encounters available for any patient with a positive home influenza test. Every hour faster that we can prescribe Tamiflu is better for our patients.

At age 65-years-old, I recognize that I am at higher risk of death or serious illness from either COVID or influenza. Even if the infection doesn’t make me sick enough to be admitted to the hospital, those infections will still make me feel pretty crappy for several days and I don’t particularly like to feel crappy. I’m financially secure enough (and value my health enough) that next fall, when influenza season starts, I’ll spend the $50 and buy a Lucira kit through Amazon and leave it in my medicine cabinet for a year in case I develop symptoms. But I think that we can do better – and by we, I mean doctors, the FDA, and kit manufacturers. I’m hoping that like e.p.t. paved the way for other home pregnancy tests, Lucira will pave the way for other home influenza test kits that are easier to use, more accurate, more available, and less expensive.

April 25, 2024

Categories
Outpatient Practice

Your Hospital Needs Palliative Care Telemedicine

One of the good things to come out of the COVID pandemic was the expanded use of telemedicine. It allowed us to provide on-going care to our patients during lock-down periods early in the pandemic and later allowed us to care for patients who were uncomfortable coming into a place where they could potentially become infected. It became clear from the beginning that some specialties were more amenable to telemedicine than others. Telemedicine was less useful for those visits that require a more detailed physical exam or required in-office procedures. Telemedicine was more useful for those visits that were mainly for counseling. A recent study in JAMA demonstrated the value of telemedicine in palliative care for non-cancer diseases.

The study involved 306 patients two Veteran’s Administration health systems between October 2016 and April 2020. Patients all had either COPD, interstitial lung disease, or heart failure. Patients were randomly assigned to either usual care or a telehealth group that received 6 phone calls from a nurse and 6 phone calls from a social worker. Patients were evaluated with a multi-domain quality of life survey (the FACT-G score) and disease-specific quality of life scores. After 6-months, the telehealth group reported significantly better quality of life than the usual care group. There are several important conclusions we can make about palliative medicine telehealth based on this study:

  1. It does not require expensive specialists. The RN and social worker who performed the telephone calls had 10 hours of training. Physicians who have completed palliative medicine fellowships are in short supply and there are not enough of them to provide telehealth services for all hospitals. Registered nurses and social workers are much more widely available (and less expensive) than board-certified palliative medicine physicians. This study shows that at least some of palliative care telehealth can be provided by RNs and social workers with a minimum of training. This would free up palliative medicine physicians (and nurse practitioners) to provide programatic oversight and to provide selective telehealth encounters when the RN or social worker identified need for advanced care and decision-making.
  2. It works for patients with non-cancer diagnoses. In many hospitals, palliative medicine is largely relegated to the care of patients with cancer. Furthermore, palliative medicine is often funded by the hospital’s cancer program. This study shows that the quality of life of patients with COPD, interstitial lung disease, and heart failure improve with palliative medicine telehealth.
  3. It overcomes transportation and mobility barriers. Patients with advanced COPD, interstitial lung disease, or heart failure generally have limiting dyspnea with exertion and are often on supplemental oxygen. This creates a barrier to traveling to an outpatient clinic site with the result that many patients who could benefit by palliative medicine do not receive it. This is especially true of patients who live a great distance from the palliative medicine clinic location.
  4. It did not affect hospitalization rates. The total number of patients in the study was small with only 154 patients randomized to palliative care telehealth and 152 patients randomized to usual care. The primary outcome for which the study was powered was for quality of life scores and a secondary outcome was hospitalization. At the end of 1 year, 109 of the palliative care group and 119 of the usual care group had been hospitalized, a difference that was not statistically significant. There was also no statistical difference in mortality at 1 year: 6 patients in the palliative care group and 5 patients in the usual care group died. Healthcare utilization, in terms of annual total healthcare costs, was not reported so it is unknown if palliative care telehealth reduced healthcare expenditures.
  5. The population studied was limited to Veterans Administration patients. Care at VA medical centers is very different than care at other healthcare facilities. There is easy access to inpatient and outpatient care. Co-pays and deductibles for medical care are relatively low or waived. Additionally, medications are free or available with a relatively low co-pay. In this study, most patients were male and Hispanic. It is unknown if the results can be extrapolated to a more diverse group of patients or patients at non-VA hospitals.

Advantages of palliative medicine telehealth

Any physician who has ever performed a home visit will tell you that you get important information by seeing the patient in their own home environment that you cannot get when seeing the patient in a clinic exam room. During a video-telehealth visit, you can often get a good idea of the patient’s environment that can clue you into home health needs. Assessment of entry ways, stairs, and bathrooms can indicate measures that can be taken to reduce falls. Assessment of home oxygen equipment can ensure adequate (and safe) oxygenation. The need for durable medical equipment can be identified.

The advantages of using telehealth to reach patients who have mobility, transportation, or geographic distance barriers cannot be overstated. Some physicians will argue that in-person visits for palliative care are superior to telemedicine visits; however, a telemedicine visit is vastly superior to no visit if the patient is unable to come to the physician’s office. This is particularly true for patients with conditions such as end-stage renal disease who are bound to their locality three days a week for dialysis, those who are wheelchair-dependent, and those who have limiting dyspnea on exertion.

During COVID, it quickly became clear that telemedicine was more effective for some specialties than others. Diseases that require the patient to undergo regular testing (blood tests, EKGs, pulmonary function tests, etc.) are not as amenable to telemedicine since the patient must come to the clinic for the tests, anyway. Similarly, diseases that require an in-person physical examination for regular assessment are not as amenable to telemedicine compared to those diseases that only require counseling. Palliative medicine is primarily counseling and generally does not require regular testing or procedures. Thus, palliative medicine is in many ways the ideal specialty to utilize telemedicine.

Telehealth has the potential to reduce palliative medicine outpatient no-show rates. When a patient cancels an outpatient appointment on short notice, there is no bill generated and no income to cover the overhead expense of the clinic or the physician’s salary for that period of time. Even if a patient is feeling too unwell to travel on the day of their office appointment or if their transportation is unexpectedly unavailable, that patient can still have a billable telehealth visit which can reduce or eliminate the financial loss of a late cancellation or no-show.

Paying for it

The recent study does not address cost of care. A disadvantage of using a registered nurse to perform palliative care telehealth is that those encounters are generally not billable. Thus, the funding must come from other sources. Alternatively, telehealth can be performed by a physician, nurse practitioner, or physician assistant who can generate revenue by making it a billable telemedicine encounter. Future studies are needed to determine if per-person annual healthcare costs are lowered by palliative medicine telehealth in non-cancer diseases. If so, then managed care programs and insurance companies could be approached for funding. Similarly, health systems participating in value-based-purchasing models and bundled-care payment models could internally fund palliative care telehealth if it is shown to be reduce hospitalizations or annual cost of care.

Palliative medicine is rarely financially self-sufficient. In most hospitals, palliative care is heavily subsidized by the hospital since it is not possible to cover the salary of palliative medicine physicians or advance practice providers on professional revenue billing alone. This study has shown that palliative medicine telehealth improves patient quality of life. However, the current U.S. healthcare system does not pay hospitals to improve quality of life. Hospitals get paid by outpatient testing, surgeries, and inpatient admissions. They use the profits from these services to cover the cost of services that they lose money on. Palliative care has to compete with a myriad other hospital services for funding. In deciding which of these services to monetarily support, hospital leaders rely on clinical research studies and publications to guide them. This recent study will help to provide needed justification for expansion of palliative care telemedicine services. Indeed, palliative medicine and telemedicine are perfect for each other.

March 8, 2024

Categories
Epidemiology Outpatient Practice

Is It Dangerous To Vaccinate Pregnant Women And Children Against COVID?

Last fall, I was hiking and birdwatching in a nature preserve in coastal North Carolina. A woman walked by talking on her cell phone loudly enough for me to overhear her conversation 50 feet away. She spoke about her outrage that children were being vaccinated against COVID and that her internet research from the Children’s Health Defense organization indicated to her that COVID was a hoax propagated by Bill Gates and that COVID vaccines cause autism. I rolled my eyes, kept my mouth shut, and went back to watching egrets.

It reminded me of another conversation that I had with one of our family medicine physicians about 15 years ago. It was October and she was pregnant. I had arranged an influenza vaccination station in the hospital physician lounge and told her about it so that she could get vaccinated. She said that she wasn’t going to get a flu shot because she believed that flu shots in pregnant women cause autism in their children. I tried to convince her otherwise but she was firm in her beliefs. That winter, when she delivered her baby, she had active influenza. Her newborn ended up in the neonatal ICU at Nationwide Children’s Hospital with an intracranial hemorrhage.

The lesson is that misinformation abounds, even among intelligent and educated people. The main defense against misinformation is scientific research. In the short-run, misinformation can persist but in the long-run, science eventually prevails. Beliefs such as the sun revolves around the earth, the earth is flat, and smoking cigarettes is beneficial to your health were all held as incontrovertible truths in the past but eventually were dispelled by science to all except the most gullible. This week, two new scientific studies were published that will help to dispel misinformation about COVID vaccines and children.

The first was a study in JAMA that looked at all newborns in Sweden and Norway between June 2021 and January 2023; in total, 196,470 infants. 48% of the infants were born of mothers who were vaccinated against COVID during pregnancy and 52% were born of unvaccinated mothers. The results are striking. The babies born from unvaccinated mothers were twice as likely to have intracranial hemorrhage compared to babies born from mothers who were vaccinated during pregnancy. In addition, compared to babies whose mothers got vaccinated, the babies of unvaccinated mothers were twice as likely to die and 50% more likely to have hypoxic encephalopathy. The benefits of maternal vaccination did not stop there. Newborns of unvaccinated mothers were also more likely to have anemia, bleeding, thombosis, lower birth weight, septicemia, seizures, heart failure, feeding problems, and necrotizing enterocolitis. This was a study that involved a huge number of subjects and made all the stronger because all children born in the two countries for a year and a half were included in the analysis.

The second study was also published in JAMA and looked at 2,959 children between ages 5-17 at 6 U.S. study sites in Texas, Arizona, Oregon, Michigan, Utah, and Washington. 25% of the children received a bivalent COVID vaccine and 75% were not vaccinated with a bivalent COVID vaccine. The results were not surprising – the unvaccinated children were more likely to get both asymptomatic COVID infections and symptomatic COVID infections compared to the vaccinated children.

These two studies will not convince all anti-vaxxers but they will hopefully loosen the hold of misinformation on some of them. For some people, beliefs are just too hard to break – there are still those among us who believe that there are bands of bigfoot roaming rural Ohio, stealing chickens and throwing rocks at passing cars. Similarly, like the woman at the North Carolina nature preserve, there are those who are ardent believers of Robert F. Kennedy, Jr. (the founder of the Children’s Health Defense organization) who publicly stated about COVID vaccines: “It is criminal medical malpractice to give a child one of these vaccines”. In 1887, Abraham Lincoln famously said “You can fool all of the people some of time; you can fool some of the people all of the time, but you can’t fool all the people all the time.” Kennedy has made millions of dollars for himself by fooling some of the people all of the time.

But physicians can now tell their pregnant patients with confidence that getting a COVID vaccination will improve their chances of having a healthy baby and improve the chances that their baby will live through its first month after birth. COVID vaccines do not provide 100% protection against the infection. But then neither do kevlar vests provide 100% protection in a mass shooting. However, wearing a kevlar vest will improve your chances of surviving and improve your chances of avoiding major injury. COVID vaccines are like wearing a kevlar vest against the virus for pregnant women and for children.

February 7, 2024

Categories
Epidemiology Outpatient Practice

Why Your Practice Needs An Outpatient Antibiotic Stewardship Program

When physicians hear the words “antibiotic stewardship”, they think of inpatient programs to control antibiotic use. However, more than 80% of antibiotics are prescribed in the outpatient setting. The Joint Commission mandates that hospitals have an inpatient antibiotic stewardship program but there is no national requirement in the outpatient setting and consequently, better stewardship of outpatient antibiotic use is essential to control multi-drug resistant bacteria.

Emergence of drug-resistant bacteria

Charles Darwin

The story of drug-resistant bacteria is the story of evolutionary biology and that story dates back more than 2 centuries ago.

It was the fall of 1827 and Charles Darwin was bored. He was in his second year of medical school at the University of Edinburgh but was neglecting his medical studies as he was more interested in studying the biology of oysters than of humans. So, his father sent him to Cambridge to study to become a county parson instead. There, he was more interested in studying entomology than religion. However, he did manage to graduate in 1831. But with no employment opportunities that interested him, he decided to sign on as a naturalist on a 5-year expedition to chart the coast of South America on the HMS Beagle. His observations of during the voyage served as the foundation for his theory of natural selection that later became the central tenet of evolutionary biology.

Alexander Fleming

Perhaps nowhere has natural selection been more easily observed than in the emergence of antibiotic resistant bacteria over the past 80 years. In 1928, Alexander Fleming discovered penicillin, purely by accident. In 1941, police constable Albert Alexander became the first person treated with penicillin when he scratched his face with a rose thorn and developed a flesh-consuming infection caused by Staph aureus. After 5 days of treatment with the new drug, his infection was under control but he then relapsed when his doctors exhausted their supply of penicillin. When penicillin was initially rolled out, it killed essentially all Staph aureus bacteria. But by 1942, penicillin-resistant Staph were identified and by 1946, 12.5% of all Staph aureus isolates were resistant to penicillin. One year later, the incidence of penicillin resistant staph had tripled even further.

Methicillin-resistant Staph aureus

To fight the rapidly emerging resistance of Staph aureus to penicillin, a new semi-synthetic penicillin derivative was created in 1959 called methicillin. It was first marketed in September 1960 but only one month later, a public health lab in London identified isolates of Staph that were resistant to the new antibiotic and these were called methicillin resistant Staph aureus, or MRSA. Thirty years ago, 2% of all Staph infections were due to MRSA. Today, in the United States, most staph infections are caused by MRSA and one-third of all healthy Americans are colonized with MRSA in their noses. To treat MRSA infections, the medical community turned to vancomycin. But in 2002, the first case of vancomycin-resistant Staph aureus was identified in a diabetic patient in Michigan. Today, vancomycin-resistant Staph aureus has replaced MRSA as the bacterial bogyman in our nation’s hospitals.

Currently in the United States, there are 2.8 million infections caused by drug-resistant infections and 35,000 deaths due to antibiotic resistance every year. There are additionally 12,800 deaths each year due to Clostridium difficile that arises as a complication of antibiotic use. Antibiotic overuse and misuse is fertilizer for antimicrobial resistance. To slow the emergence of drug-resistant pathogens, it is necessary to more judiciously prescribe antibiotics, especially in the outpatient setting.

The problem of outpatient antibiotic use

In the U.S., three are 211 million outpatient antibiotic prescriptions written every year. The CDC estimates that 72% of these are necessary but 28% are unnecessary. Even when antibiotic prescriptions are necessary, we have opportunities to improve drug selection, improve drug dosing, and shorten the duration of administration. Taking all of this into consideration, about half of all outpatient antibiotics are either unnecessary or prescribed incorrectly.

All of us who practice outpatient medicine have been guilty of antibiotic misuse at one time or another. A patient comes to the office with a viral upper respiratory infection and the doctor prescribes an antibiotic that was never needed in the first place. Maybe the doctor was not aware of clinical practice guidelines for managing upper respiratory infections. Maybe the doctor wanted to make the patient happy by prescribing an antibiotic. Maybe the doctor was afraid of complications of the URI. Maybe the doctor figured he or she could bill a higher level of service for the office visit by prescribing an antibiotic. Maybe the doctor thought that it would be faster to prescribe an antibiotic than to explain why an antibiotic was not necessary. Regardless of the reason, the next time that the patient has a cold, that patient will believe that an antibiotic is necessary and expect the physician to prescribe one. This results in a vicious cycle of antibiotic misuse.

The 4 components of outpatient antibiotic stewardship

The Centers for Disease Control has an excellent on-line resource for outpatient antibiotic stewardship. This resource identifies four key components that can be incorporated into any outpatient practice: commitment, action, tracking, and education.

Commitment

Not only must the physician be committed to appropriate antibiotic use but the entire office staff must be committed. This implies that a consistent message will be given to patients, from the nurses, from the schedulers, from the medical assistants, and from the physicians. For example, when a patient calls in with a sore throat, the nurses can set the stage for antibiotic stewardship by saying “The doctor needs to evaluate you in person to determine if an antibiotic is necessary” rather than simply calling in an antibiotic prescription. The schedulers can help by telling the patient that the office has the ability to do on-site rapid strep screens during the patient’s office visit. The medical assistants can reinforce the message by telling the patient that a negative rapid strep test means that the sore throat is not caused by a bacteria.

Ideally, each medical practice should have a leader for the practice’s antibiotic stewardship program. This could be a pharmacist, nurse or medical assistant. This individual would be responsible for ensuring that all of the office staff know their roles in antibiotic stewardship and that the office’s commitment to antibiotic stewardship is communicated to patients. A simple way of doing this is with posters in the waiting room or in the examination rooms stating the practice’s commitment. The CDC has a down-loadable poster that can be used by any medical office. A 2014 study found that inappropriate antibiotic prescriptions were reduced by 19.7% simply by hanging commitment posters in exam rooms.

Action

Incorporation of evidence-based guidelines for management of common outpatient infections can help ensure that the right antibiotic is prescribed for the right duration of time for any given bacterial infection. Guidelines can also help ensure that antibacterial antibiotics are not prescribed for viral infections. One of the challenges with use of evidence-based guidelines is that many national organizations publish their own guidelines for any given infection and these guidelines can differ depending on the decisions of different guideline writing committees and how long in the past the guidelines were written. Large medical centers can develop their own practice guidelines based on distillation of available literature. In smaller outpatient practices, it is best for all of the providers to agree on the use of one guideline or another – it can be confusing to staff and patients if different providers in the practice utilize different clinical guidelines. When possible, the power of the electronic medical record should be harnessed to prompt clinicians regarding test ordering or antibiotic prescriptions for any given infection based on the ICD-10 diagnoses.

A useful action plan is the use of the “over-the-counter prescription pad” to use for common viral infections – essentially a printed checklist of non-antibiotic recommendations by the provider for such items as acetaminophen, NSAIDs, decongestant nose sprays, guaifenesin, dextromethorphan, etc. Often, a printed paper to given to the patient that is customized to include the patient’s name, date, and diagnosis can be a powerful way to reinforce that antibiotics are not necessary and that the physician is invested in treating the patient (just not with an antibiotic).

Tracking

For hospital-employed physicians, most compensation plans incorporate some kind of quality metric into each physician’s annual bonus. In our medical center, over the years these have included metrics such as percent of patients getting mammograms or colonoscopies, percent of patients getting influenza vaccinations, and patient satisfaction scores. Antibiotic stewardship is in many ways an ideal quality metric for outpatient and ER practices. This is because appropriate antibiotic prescription is a physician behavior whereas when a patient refuses a flu shot, is a no-show for their scheduled colonoscopy, or writes a bad patient satisfaction survey, it is a patient behavior. As a result, using these latter types of metrics for physician bonuses tends to financially reward physicians who have a “desirable” patient panel as opposed to those physicians who care for a lot of uninsured, lower income, or lower education level patients. By using a physician behavior in the bonus equation, the practice can avoid penalizing physicians for patient behaviors that are beyond the physicians’ control.

The electronic medical record can be utilized to track and report antibiotic stewardship quality metrics such as use of order sets derived from the organization’s clinical practice guidelines, use of rapid strep testing in patients given antibiotics for pharyngitis, and appropriate duration of antibiotics for uncomplicated urinary tract infections.

Education

This requires both education of physicians and education of patients. Physician education can take the form of grand rounds and other CME events about antibiotic stewardship. But on a smaller scale, can include distribution of the organization’s clinical practice guidelines for common infections. Successful distribution can be a challenge, however – many hospitals that maintain a “clinical practice guideline” website on the hospital’s intranet find that physicians rarely access the website. Successful adoption of guidelines usually is most effectively done on a local basis, such as at medical staff meetings, at department meetings, or by incorporation of the guideline into the electronic medical record.

Patients need to be educated about the difference between viral and bacterial infections and why viral infections do not require an antibacterial antibiotic. They also need to be educated about the risks of antibiotics, including costs, side effects, development of drug-resistant bacteria, and C. difficile. Patient education materials can again include posters for the examination rooms but can also include text pasted into the patient’s after visit summary. Whenever possible, after visit summaries should be printed and handed to the patient at the end of their office visit rather than simply loaded onto the patient portal in the electronic medical record – few patient actually open up their patient portal after they leave the office but a piece of paper will tend to stick around until the patient actually reads it.

The Centers for Disease control has several excellent patient education handouts that can be printed as posters for the office’s exam rooms or as paper handouts to be given to patients. These are available in both English and Spanish language versions. These can be downloaded from the CDC’s website or you can click on the images below for the English language handouts.

 

 

 

 

 

 

Penicillin allergy deserves a special mention. Fully 10% of patients report having an allergy to penicillin but only 1% of the population actually has penicillin allergy when tested for IgE-mediated reactions. In other words, 9 out of 10 patients who think they have a penicillin allergy do not actually have an allergy.  One of the reasons for this is that 80% of patients who truly have a penicillin allergy lose their IgE responsiveness after 10 years. But presumption of penicillin allergy drives the use of more broad-spectrum antibiotics and the development of drug-resistant bacteria. Patients reporting penicillin allergy should be asked about the specific symptoms they had when taking penicillin in the past. When uncertainty exists, patients should undergo penicillin skin testing. In the past, this required consulting an allergist but now there are easy-to-perform penicillin allergy skin tests that can be done in the primary care office. Importantly, if the test is negative, then not only does the patient need to be informed that they are not allergic, but penicillin allergy should be removed from their electronic medical record.

The special case of dentistry

Dentists account for 10% of all outpatient antibiotic prescriptions. But dental practices generally fall outside of the purview of our nation’s hospitals. As a consequence, dental practices are largely on their own when it comes to antibiotic stewardship support. Physicians can help by participating in dental continuing education programs and by sharing effective programs and practices with local dentistry colleagues. One of the important changes over the past 20 years has been a move away from indiscriminate use of prophylactic antibiotics prior to dental procedures in patients with heart murmurs and limiting prophylactic antibiotics to only those cardiac patients that truly benefit from them. There are also CDC guidelines for when to prescribe antibiotics for common oral infections such as pulpitis, periodontitis, and pulp necrosis.

An ounce of prevention

The most effective way to reduce antibiotic misuse and development of drug-resistant pathogens is to never get infected in the first place. Keeping patients up to date with vaccinations is essential. Chief among these for bacterial infections is pneumococcal pneumonia – the new PCV20 vaccine should be given to all adults over age 65. Similarly, viral infection can mimic bacterial infections or lead to secondary bacterial infections that can result in antibiotic prescriptions. Preventing these common viral infections can thus reduce antibiotic use. All Americans should receive an annual influenza vaccine and COVID update vaccine. All people over age 60 and all pregnant women should be vaccinated against RSV.

We are fortunate to be living in an era when we have more effective vaccines for deadly diseases than ever before. Vaccine recommendations change frequently as new vaccines are developed. The CDC lists the current vaccination recommendations on their website. You can also click on the images below for the 2024 child and adult vaccine schedules.

 

 

 

We don’t have to lose the war…

I have watched patients die of bacterial infections that were untreatable with any known antibiotic. I have taken care of patients with such extensive drug allergies that there was only one or two antibiotics that I could use for any infection they came down with. I have taken care of patients who were admitted to our ICU with overwhelming Clostridium difficile due to taking an unnecessary antibiotic or due to taking a necessary antibiotic for longer than indicated. In all of these cases, antibiotic misuse and drug-resistant bacteria were the root causes.

The good news is that initiatives to reduce antibiotic misuse are effective. Since 2013, the CDC reports that there has been  a decrease in hospital-acquired infections caused by vancomycin-resistant enterococcal, multi-drug-resistant Pseudomonas, methicillin-resistant Staph aureus, carbapenem-resistant acinetobacter, and drug-resistant Candida. However, other outpatient-acquired drug-resistant pathogens are now on the rise including erythromycin-resistant group A Strep, drug-resistant Neisseria gonorrhoeae, and ESBL-producing Enterobacteriaceae. Outpatient stewardship efforts in our physician offices, urgent care centers, and emergency departments can and will make a difference. To view an OSU MedNet-21 webcast for more information on outpatient antibiotic stewardship, click on this link.

November 22, 2023

Categories
Outpatient Practice

The History Of Idiopathic Pulmonary Fibrosis Treatments

Next year will be the 80th anniversary of the first description of idiopathic pulmonary fibrosis (IPF). It will also mark 40 years since I graduated from medical school. I spent most of those 40 years specializing in the management of patients with IPF and there have been enormous strides forward in those 40 years. This post will look back on where we have been, where we are now, and where we are going with respect to treating IPF.

First, some definitions.

Interstitial lung diseases are characterized by the accumulation of inflammation or scar or both in the lungs. There are at least 140 different interstitial lung diseases. Pulmonary fibrosis means accumulation of scar in the lungs and many of the interstitial lung diseases can result in pulmonary fibrosis. For most of these, the cause is known, such as rheumatoid arthritis-associated pulmonary fibrosis, radiation-induced pulmonary fibrosis, and asbestosis. Idiopathic pulmonary fibrosis (IPF) is when pulmonary fibrosis occurs without any known underlying cause (“idiopathic” means no obvious cause).

Usual interstitial pneumonitis (UIP) is a pattern of findings on either a chest CT scan or a lung biopsy that is typically seen in idiopathic pulmonary fibrosis. However, the UIP pattern can also be seen in other interstitial lung diseases. For this reason, the radiologist and the pathologist generally do not diagnose idiopathic pulmonary fibrosis – it is up to the pulmonologist who is seeing the patient to diagnose idiopathic pulmonary fibrosis by taking the radiologist’s or pathologist’s finding of UIP in the context of the patient’s history, physical exam, and laboratory test results.

The historical timeline of IPF

There is no one person who discovered idiopathic pulmonary fibrosis. Instead, there has been an evolution of thought about IPF over the past century. Some of the more important points in the timeline of IPF are:

  • 1944. The first clinical description of idiopathic pulmonary fibrosis is credited to Drs. Hamman and Rich from Johns Hopkins in 1944 in their description of 4 patients with interstitial lung disease of uncertain cause. Although the term “Hamman-Rich syndrome” became used as a catch-all term for many interstitial lung diseases (including idiopathic pulmonary fibrosis), their 4 patients likely had acute interstitial pneumonitis, which is a different disease.
  • 1962. Dr. Gross suggested that there were two forms of Hamman-Rich syndrome: an acute form and a chronic form. This article laid the foundation for IPF as a distinct disease (the chronic form).
  • 1964. Dr. Scadding from the United Kingdom proposed using the term cryptogenic fibrosing alveolitis for the chronic form of Hamman-Rich syndrome. For many years, cryptogenic fibrosing alveolitis was synonymous with idiopathic pulmonary fibrosis.
  • 1969. Drs. Leibow and Carrington described 5 histologic subgroups of “chronic idiopathic interstitial pneumonia”, one of which was usual interstitial pneumonitis (UIP).
  • 1976. Researchers at the National Institutes of Health, led by Dr. Crystal, proposed that idiopathic pulmonary fibrosis initiates as inflammation in the alveoli of the lungs that later progresses to fibrosis. The basis of this proposed mechanism was the findings of increased inflammatory cells in bronchoalveolar lavage fluid obtained from bronchoscopies performed on patients with IPF.
  • 1998. Drs. Katzenstein and Myers proposed that usual interstitial pneumonitis is the lung biopsy finding that occurs in idiopathic pulmonary fibrosis. They determined that the disease is due to excessive fibrosis (scar) and that there is little inflammation.
  • 2001. Dr. Hunninghake and colleagues determined that IPF can be often be diagnosed by the finding of usual interstitial pneumonitis on the chest CT scan, allowing some patients to avoid undergoing a lung biopsy.

What causes idiopathic pulmonary fibrosis?

In 2023, idiopathic pulmonary fibrosis is less idiopathic than it was in the past. IPF can be currently thought of as an auto-fibrotic lung disease due to a combination of inherited genes and environmental factors. An “auto-immune” disease occurs when the body’s immune system turns against itself, such as in systemic lupus erythematosis. An “auto-inflammatory” disease occurs when the body’s inflammatory system turns against itself, such as in the VEXAS syndrome. An “auto-fibrotic” disease is when the body’s scarring system turns against itself. Scar results when wounds heal and as such, auto-fibrotic diseases can be thought of as disorders of uncontrolled wound healing.

There is not one single gene that is responsible for idiopathic pulmonary fibrosis but rather there are many genes that can predispose a person to develop IPF. These genes vary in terms of how strongly they predispose IPF. For example, people with abnormal telomerase genes have a very high risk for developing IPF whereas those with an abnormal MUC5B gene have an increased risk of developing IPF that is not as great as with abnormal telomerase genes. For all of these genes, environmental injury to the lungs significantly increases the chance that a person will ultimately develop IPF. The most common cause of environmental injury is tobacco smoking but respiratory viruses, work-related dust inhalation, air pollution, and chronic gastroesophageal reflux can also increase the chance that a person with an abnormal gene will develop IPF.

How do we know if a drug for IPF works?

The only way to know if a drug against any disease works is by scientific research. But some types of scientific research are more convincing than others. Here are the common categories of research that physicians look at when determining a drug’s effectiveness.

  • Case reports. These are usually publications of one or two patients who appeared to respond to some type of treatment. Case reports are the weakest evidence of a drug’s effectiveness but they can be the justification for doing additional future research about a drug.
  • Case series. These are publications of numerous patients treated with a drug. Although they can provide stronger evidence than a case reports, they are still overall fairly weak. These are often called “retrospective reviews” meaning that a physician is looking back (retrospective) over a group of patients that the physician has managed in the past.
  • Open-label clinical trial. This is when a researcher deliberately gives a group of patients a drug and tracks how they respond to it. There will generally be a specific test that the researcher performs to see if the drug has an impact, for example, by performing pulmonary function tests. When a clinical trial is “open-label”, it means that the researcher and the patients know whether or not they are getting the drug. However, this knowledge can lead to bias by either the patients or the researcher who may want to think that the drug is working, even if it is not.
  • Randomized, double-blind, placebo-controlled clinical trial. These provide the strongest evidence that a drug is effective. Patients are randomly assigned to either receive the drug or a placebo and neither the patients nor the researchers know if a particular patient got the drug or got the placebo. In order for these studies to be statistically significant, the studies have to have a large number of patients, typically in the hundreds or thousands.

There are three “phases” of clinical trials of new drugs. The FDA will grant approval if the final phase of a clinical trial shows a statistically significant benefit of the drug without severe side effects.

  • Phase 1 trials. These involve a small number of patients and are usually open-label and of short duration. The researchers are primarily interested in drug safety and side effects. Several doses of the drug will be tested in order to find the safest doses and how frequently the drug should be given.
  • Phase 2 trials. These involve a larger number of patients who are randomized to receive either the drug or a placebo. During phase 2, the researchers will determine if the drug holds the possibility of being effective and will determine the best dose of the drug to use in the next phase.
  • Phase 3 trials. These involve very large numbers of patients – IPF trials typically require more than a thousand subjects. There are usually many hospitals (study sites) involved from multiple states and often from multiple countries. Patients are randomized to receive placebo or the drug and are tested regularly to determine if the drug is effective compared to placebo. Most IPF phase 3 trials require each subject to participate for 1 – 2 years.

IPF treatment over the years

Prior to 2014, there were no drugs that were approved by the FDA to treat idiopathic pulmonary fibrosis. Therefore, physicians used drugs that were approved for other diseases that were already available on the market. This is called “off-label” use of these drugs. Over time, researchers performed clinical trials to determine if these off-label drugs were actually effective and pharmaceutical companies developed new drugs to test in clinical trials. Clinical trials are expensive to perform and most of the clinical trials involving off-label drugs were funded by federal grants from the National Institutes of Health. Clinical trials of newly created drugs are generally funded by pharmaceutical companies. There has been a steady evolution in the treatment of IPF:

  • 1970’s – The prevailing belief about the cause of IPF was abnormal inflammation resulting in alveolitis. Thus, the drugs most commonly used to treat IPF were anti-inflammatory drugs, such as the corticosteroid, prednisone. There were no clinical trials to determine the best dose or whether corticosteroids even worked at all.
  • 1980’s – After years of watching patients fail to improve with corticosteroids, physicians turned to a more powerful anti-inflammatory drug, cyclophosphamide (Cytoxan) based on case reports and retrospective case series. Cytoxan was largely used as a chemotherapy drug to treat cancer but was also being used to treat auto-immune diseases such as systemic lupus erythematosus (aka, SLE)  and granulomatosis with angiitis (aka, Wegener’s granulomatosis). A problem with Cytoxan is that it was very toxic and patients frequently developed low white blood cell counts, bladder hemorrhaging, and bladder cancer.
  • 1990’s – After years of dealing with Cytoxan’s side effects, physicians looked to a different drug that was slightly less powerful as an anti-inflammatory drug but had much fewer complications. That drug was azathioprine, or Imuran. This was often given along with the corticosteroid, prednisone. A third drug as also frequently added: N-acetylcysteine (NAC). Because NAC has very few side effects and is available over-the-counter, it was seen as being fairly innocuous and possibly beneficial due to it’s anti-oxidant properties.
  • 2000’s – A phase 3 study of azathioprine, prednisone, and NAC found that these drugs were not helpful in IPF and if anything, patients who took them did worse than patients who got the placebo. A small study suggested that gamma interferon might be beneficial and so physicians turned to the off-label use of gamma interferon that was already approved by the FDA for use in a rare condition called chronic granulomatous disease.
  • 2010’s – A phase 3 study of gamma interferon showed that it was ineffective in IPF and thus physicians stopped using it. In 2014, large phase 3 trials found that the anti-fibrotic drugs pirfenidone and nintedanib were both effective in IPF, resulting in the FDA approving their use. Presently, these are the only drugs approved for IPF in the U.S. and are considered the current standard of care.

The past 3 decades are littered with drugs that initially held promise but were shown in clinical trials to be ineffective in IPF. A list of the most prominent of these drugs is below:

Current IPF treatment

Pirfenidone and nintedanib have both been shown to slow the progression of IPF compared to placebo, however they do not stop or cure the disease. Think of them as slowing the progression of IPF from 60 miles per hour down to 30 miles per hour. The patients will still ultimately get worse but just more slowly. There has not been a head-to-head comparison of the two drugs but the available evidence suggests that both are equally effective. The choice of which drug to prescribe is generally based on the personal preference of the physician and the patient. These preferences are most commonly based on the differing side effect profiles of the two drugs: pirfenidone cause cause skin rash and sun-sensitivity, nintedanib can cause diarrhea. The drugs also differ in drug-drug interactions – for example, nintedanib interacts with anticoagulants whereas pirfenidone interacts with ciprofloxacin.

Lung transplant is the only curative treatment for IPF. In the U.S., IPF is now the most common indication for lung transplant, accounting for 37%. Not all patients with IPF are eligible for transplant, however. The decision of eligibility is made by each hospital’s transplant team and limiting factors can include active tobacco use, obesity, older age, deconditioning, and presence of other concurrent diseases. Moreover, transplant comes with it’s own risks – 15% of patients with IPF die in the first 12 months after transplant and of those who survive the first 12 months, only 67% are still alive 5 years after transplant. However, post-transplant care is improving and survival rates are expected to improve in the future.

In addition to anti-fibrotic medications and lung transplant, there are other interventions that have been shown to be useful in patients with idiopathic pulmonary fibrosis. Oxygen is effective in improving the quality of life of patients with IPF. It can reduce shortness of breath, improve ability to exercise, and facilitate travel. Pulmonary rehabilitation is also effective in improving quality of life and should be considered for all IPF patients with shortness of breath or exercise limitation. Patients with IPF are at increased risk of obstructive sleep apnea and physicians should have a low threshold for performing sleep studies and prescribing CPAP when indicated. Although treating asymptomatic patients with proton pump inhibitors is ineffective in IPF, whose with symptoms of gastroesphageal reflux should be treated in order to reduce on-going lung injury. Patients with large hiatal hernias may benefit by surgical repair if they are able to tolerate surgery. Smoking cessation is essential to stop on-going lung injury, improve quality of life, and make patients eligible for lung transplant. All patients with IPF should be vaccinated to prevent pneumococcal pneumonia, influenza, respiratory syncytial virus (RSV) and COVID. Patients with IPF are at higher risk of death from respiratory infections and even if they survive the infection, it can result in additional lung injury that can accelerate the progression of IPF. During the first 12 months of the pandemic, 5% of my outpatients with interstitial lung disease died from a COVID infection due to their greater susceptibility.

Although cure of IPF is not yet possible (other than with transplant), it appears that our current treatment approach is making a difference. A recent study from Italy compared patients with IPF over a 15-year period from 2002 to 2016. Over this time, there was an increase in life expectancy, decrease in the rate of hospitalization, and decrease in the rate of acute exacerbations. Correlated with these improved outcomes was an increase in the use of anti-fibrotic drugs (pirfenidone and nintedanib), decrease in the use of anti-inflammatory drugs (corticosteroids, cyclophosphamide, and azathioprine), and increase in the use of bronchoscopic cryobiopsies as opposed to the more invasive surgical lung biopsies.

The future of IPF treatment

Prior to the FDA approval of pirfenidone and nintedanib, most IPF clinical trials compared a promising drug to placebo. Now that pirfenidone and nintedanib are the accepted standard of care, future trials have to either compare new drugs to pirfenidone and nintedanib or have to compare new drugs to placebo in patients who are already taking pirfenidone or nintedanib. Performing clinical trials in IPF is complicated for a number of reasons:

  • The heterogeneity of IPF makes trial design difficult. Given that there are multiple predisposing genes involved in IPF and given that there are multiple environmental risks for IPF, no two patients with IPF are exactly alike and treatments that work for one patient may not work for another.
  • Mortality cannot be used as an endpoint. The current average survival of a patient with IPF is 5.5 years based on the Italian study. If researchers were to use death as the endpoint in a clinical trial, that trial would have to last for a decade or more in order to recruit a sufficient number of patients and follow them until death. This is too long of a length of time to realistically perform a clinical trial.
  • Pulmonary function tests are currently the best outcome measure for IPF clinical trials. We use change in the forced vital capacity and diffusing capacity as markers of the progression of IPF. Although this is appealing from a logical standpoint, PFT changes may not necessarily correlate with life expectancy. But for now, PFTs are the best that we have.
  • To be statistically significant, trials must include hundreds of patients. The CAPACITY and ASCEND studies that led to approval of pirfenidone enrolled 1,247 subjects. The IMPULSIS studies that led to the approval of nintedanib enrolled 1,066 subjects. To recruit this many subjects, many study sites are required – the IMPULSIS studies required 205 hospital locations in 24 countries, the CAPACITY studies required 110 hospital locations in 13 countries, and the ASCEND study required 127 hospital locations in 9 countries.  Because future trials will need to incorporate multiple treatment arms including those taking pirfenidone, those taking nintedanib, and those taking neither, the number of subjects in future trials will need to be even larger than in previous IPF trials.
  • Clinical trials are costly. The average cost to bring a new drug to market, from initial drug discovery to FDA approval is $2.3 billion. Consequently, for pharmaceutical companies to recoup their drug development costs, any new drug is expensive and IPF drugs are no exception. The retail price of pirfenidone is $16,000 per month ($2,200 per month if using coupons such as GoodRx) and the retail price of nintedanib is similar.

There are a number of new drugs currently in phase 1 and phase 2 trials and several of these hold early promise to add to our treatment options for IPF patients. Some of the questions likely to be answered in future IPF treatment research include:

  • Is combination therapy more effective than mono therapy? Currently, patients receive either pirfenidone or nintedanib but not both. We do not know if the combination of the two be better than either one alone. The same holds for any new drug that is developed – whether it should be given alone or in combination with one of the two currently approved drugs.
  • Is inhaled therapy better than oral therapy? Giving drugs to treat lung disease by inhalation is attractive – it offers the possibility of giving relatively high concentrations of the drug directly to the airways with lower concentrations in the blood. This has the potential to reduce systemic side effects while boosting the effect in the lungs.
  • What are the chemical pathways involved in fibrosis? At present, it appears that transforming growth factor-β (TGF-β) is a key player in fibrosis development. Drugs that specifically target TGF-β may be effective in slowing fibrosis. Because TGF-β is secreted as inactive form that is converted to an active form by αvβ6 integrin, this molecule is another attractive target for future treatments. We need to identify the other proteins in the body that are involved in fibrosis.
  • Are there biomarkers of IPF that would be better to use in clinical trials than changes in pulmonary function tests? In atherosclerosis, we have a great biomarker in the cholesterol level that allows us to determine if a drug is working without having to wait to see whether or not a patient develops a heart attack or stroke. Measurement of biomarkers that are involved in the chemical pathways of fibrosis would allow us to more quickly tell if a drug is working for a particular patient without having to wait months or years to see if there are changes in pulmonary function tests.
  • Can genetics direct treatment? The different genes involved in idiopathic pulmonary fibrosis affect different proteins in the body and each of these proteins has a different role in the development of fibrosis. In lung cancer, we use the genetics of a person’s cancer to choose which chemotherapy will be most effective. As we learn more about the genetics of IPF, it is likely that a person’s specific genetic make-up will help us pick the best treatment for that particular individual.
  • What is the role of gene therapy? Gene editing is in its infancy in medicine but is already showing great promise in muscular dystrophy and sickle cell anemia. As we learn more about the genes involved in IPF, we may be able to edit those genes, not only in patients with IPF but also potentially in their relatives with the hope of preventing the onset of IPF in the first place. Because IPF only affects the lungs, it is possible that only the genes of lung tissues would need to be edited, for example, by inhalational techniques.

When I first started specializing in treating IPF 35 years ago, it was my hope to see effective treatments arise during my career. Not only do we now have effective treatments but we also know which medications can actually make patients worse. For these reasons, our management of IPF is much better today than ever before. The treatment will be even better yet in the future with translational research that results in taking the word “idiopathic” out of idiopathic pulmonary fibrosis and clinical research to bring us more effective therapies for patients with IPF.

November 14, 2023

Categories
Outpatient Practice

Pelvic Floor Dysfunction Is The Epidemic You Didn’t Know Existed

One out of every two women will develop a pelvic floor disorder at some point in their life. These disorders usually require physical therapy and often require surgery. So, why don’t we hear more about pelvic floor dysfunction?

The pelvic floor is a hammock-like group of muscles and ligaments that drape across the pelvis and support all of the pelvic organs. If these muscles and ligaments become damaged, then they cannot hold organs in the pelvis (resulting in prolapse) and cannot maintain sphincter control (resulting in incontinence). The most common cause of dysfunction of these muscles and ligaments is pregnancy and childbirth. During pregnancy, the weight of the gravid uterus plus changes in intra-abdominal pressure can stretch the components of the pelvic floor. During delivery, the levator ani muscle, pubococcygeus muscle, and pudendal nerve are all susceptible to stretch injury. In addition, more than half of vaginal deliveries result in vaginal lacerations which can involve the pelvic floor muscles and sphincters.

The frequency of these disorders is shockingly common. At one year after vaginal delivery, 41% of women experience stress urinary incontinence, 32% experience nocturia, 23% experience flatus incontinence, and 9% have some degree of prolapse. Age also affects the pelvic floor with loss of muscle and ligament integrity, particularly after menopause. The Women’s Health Initiative study found that 41% of older women with a uterus have some degree of prolapse.

So, why don’t we hear about it?

Pelvic floor dysfunction is a silent epidemic because all too often, women do not bring it up when seeing their doctor and their doctor does not ask the right questions.

Assumption of normal. Many women just assume that symptomatic pelvic floor dysfunction is just a normal and expected consequence of “everything getting stretched out” during labor and delivery. Because of this assumption of normal, women frequently do not discuss postpartum urinary incontinence, anal incontinence, or vaginal bulges with their doctor.

Patient embarrassment. Many women have a hard time bringing up issues regarding their urination or bowel movements, even with their physician. Some women don’t know enough about normal female pelvic anatomy to tell when their pelvic structures are not quite right.

Doctors do not ask the right questions. Obstetricians are generally good at asking about pelvic floor dysfunction symptoms but primary care physicians and other non-obstetricians frequently are not. Sometimes it is because the primary care physician just assumes that the obstetrician will take care of any problems resulting from pregnancy and sometimes it is because of lack of familiarity with the clinical manifestations of pelvic floor dysfunction. When asking women about pelvic floor dysfunction, we should remember the 3 “B’s”: Bladder, Bowel, and Bulge.

Pelvic floor dysfunction symptoms

The most common serious consequences of pelvic floor dysfunction are incontinence and prolapse. Types of urinary incontinence include stress urinary incontinence, urgency urinary incontinence, and mixed urinary incontinence. Bowel control issues include fecal incontinence, flatus incontinence, and fecal urgency.

Prolapse occurs when a pelvic organ herniates. A cystocele is when the bladder herniates into the anterior vaginal wall. A rectocele is when the rectum herniates into the posterior vaginal wall. And a uterovaginal prolapse is when the cervix and uterus descends into the lower vagina. Prolapse can result in urinary incontinence, constipation, pelvic discomfort, and pain during sexual intercourse.

What can be done about it?

Pelvic floor physical therapy. Fortunately, there are effective treatments that can significantly improve the quality of a woman’s life. This generally starts with pelvic floor physical therapy. This is performed by a specially-trained physical therapist who can teach women exercises to strengthen the pelvic muscles and help restore normal pelvic function. Most notably are Kegel exercises when the pelvic muscles are contracted and then relaxed.

A bit of history about Kegel exercises. If I was to then ask you who invented Kegel exercises, you might say American gynecologist Arnold Henry Kegel who published an article about exercises to strengthen the pelvic floor in the Annals of Western Medicine and Surgery in 1948. But that wouldn’t be exactly right. Instead, we have to go back 12 years earlier when a book was published by a professional dancer named Margaret Morris. She was born in 1891 and began her career as a child actress and ballet dancer. By age 19, she was an internationally known choreographer and theater producer. In her 30’s she opened a dance school and became interested in how movement and posture affected health. So, in 1925, she went to London’s St. Thomas Hospital to study physiotherapy. She further developed her ideas about exercises and health that culminated in her 1936 book titled “Maternity and Post-Operative Exercises”. In her book, she outlined 21 exercises for women to perform that could improve urinary incontinence and other consequences of childbirth. Her book was reviewed in JAMA in 1937 where the reviewer stated that he was: “..satisfied with the soundness of Miss Morris’s scheme and believe that their application will yield most beneficial results.” Dr. Kegel then wrote about her exercises more than a decade later and he now gets all of the credit for Margaret Morris’s pelvic floor exercises.

Other non-surgical treatments. When symptoms persist despite pelvic floor physical therapy, there are other treatment options. Diet and lifestyle measures to reduce urinary incontinence include weight loss, avoidance of excessively large fluid ingestions, and avoiding drinking fluids shortly before bedtime. Pessaries and over-the-counter vaginal inserts can also be useful. Measures to reduce fecal incontinence include dietary soluble fiber (but avoid insoluble fiber), ritualization of bowel movements, and over-the-counter loperamide. Avoidance of caffeine and avoidance of vigorous exercising after meals can also reduce fecal incontinence.

Surgical options. When these measures are ineffective, there are a variety of surgical options. There have been many recent developments in surgical procedures for pelvic floor dysfunction. For example, in the past, uterine prolapse was primarily treated with hysterectomy; however, now there are many uterine-sparing procedures that can be performed. Other new techniques include sacroneuromodulation for fecal incontinence and onobotulinum toxin for urinary urgency incontinence. This is where a urogynecologist can be an invaluable resource. Many larger medical centers have comprehensive subspecialty peripartum pelvic floor disorder clinics overseen by a urogynecologist. Physicians at smaller hospitals that cannot support a full subspecialty clinic should be familiar with regional pelvic floor disorder clinics for referral.

The bottom line: talk with your patients

Given the frequency of pelvic floor dysfunction, it is incumbent on every primary care physician to be familiar with the symptoms and to be willing to speak openly about them with patients. If your hospital has a labor and delivery unit, then it needs a pelvic floor physical therapist. As an emeritus faculty, I’ve been doing some pro bono teaching at the Ohio State University and recently guest-moderated an OSU MedNet webcast on pelvic floor disorders by Dr. Lisa Hickman. This webcast is a great resource for physicians, nurse practitioners, nurse midwives, and physician assistants who need to brush up on the diagnosis and management of pelvic floor dysfunction. You can view the webcast by clicking on this link.

September 20, 2023

Categories
Emergency Department Inpatient Practice Outpatient Practice

Does NP + AI = MD?

Artificial intelligence (AI) is causing a paradigm shift in the education, business, and legal professions. But AI is also poised to irreversibly change the way medicine is practiced. Jobs that traditionally relied on extensive training by memorization may be able to be performed as well (or better) by AI than by humans. Jobs that have relied on image analysis or sound pattern analysis are also at risk of being displaced by AI.

Let me give you an example from my hobby of birdwatching. In the past, bird species identification relied on comparing a bird that you saw in a tree to a drawing or photograph in a bird identification book. To become an expert birder, you needed thousands of hours of birding to identify birds by their calls and by their seasonal plumage. But now, we have the Merlin app. When birding, I can turn on my phone’s microphone and Merlin will identify bird species by bird calls. I can take a photograph of a bird, upload it to the app, and Merlin will tell me what bird I saw. With Merlin, even a novice birder like me can identify birds like a seasoned expert.

So, what if we have the Merlin app equivalent to identify heart sounds by auscultation? Or diagnose a rash by a photograph? Or interpret CT scan images? Or read cytology specimens on microscopic slides? Like it or not, artificial intelligence is coming to medicine and it will make many skills traditionally requiring hundreds of hours of training, obsolete.

Artificial intelligence and advance practice providers

To become a primary care physician (general internist, general pediatrician, or family physician) requires 11 years of education and training after high school. To become a nurse practitioner (NP) or physician assistant (PA) only requires 6 years of training after high school. As a result, it is far less expensive to become an NP or PA than to become a primary care physician but the trade-off is that NPs and PAs generally have a  lower annual income than physicians. However, if the salary of an NP and a primary care physician was the same, most hospitals would prefer to hire the physician under the presumption that additional 5 years of training to be a primary care physician would translate to greater skill and knowledge than the NP or PA. On the other hand, if the skillset and knowledge of an NP or PA was the same as that of a primary care physician, most hospitals would prefer to hire the NP or PA because they are cheaper.

Artificial intelligence now offers the possibility of eliminating the need to acquire many of the skills and much of the knowledge currently required to become a physician. This offers a future where an NP armed with a few AI apps may be able to perform many of the tasks currently relegated to physicians.

Need to diagnose a child with a fever and a rash? There’s going to be an app for that. Need to decide the best blood pressure medication to prescribe for a patient with newly diagnosed hypertension? There’s going to be an app for that. Need to recommend follow-up of a pulmonary nodule given a patient’s age and smoking history? There’s going to be an app for that.

The FDA and medical devices

At first glance, it would seem logical to embed artificial intelligence into electronic medical record (EMR) software programs. After all, the EMR is the database of all information about a patient – their blood pressure, their family history, their medication list, etc. However, a barrier to incorporating AI into the electronic medical record is that the U.S. Food and Drug Administration considers AI to be a medical device whereas the electronic medical record is just considered a documentation tool. Medical devices are regulated differently than documentation tools. Medical devices require extensive clinical trials and then FDA approval; documentation tools do not. Clinical trials and FDA regulation are very expensive and can pose a barrier to regular EMR software upgrades. For these reasons, the major electronic medical record companies have been reluctant to incorporate artificial intelligence algorithms into their EMR programs.

For the most part, this makes sense. You don’t want to have an artificial intelligence program to recommend a chemotherapy regimen for advanced lung cancer unless it has been shown in clinical trials to be accurate and has been approved by the FDA. The fear of the electronic medical record companies is that if their EMRs become classified as medical devices, then they will have to get FDA approval every time they want to change the font size in their blood chemistry test results in the EMR. So, at least for now, the electronic medical record and artificial intelligence programs will need to be separated, and that means that there will have to be a human to do a history and physical examination and then to interface between the EMR and the AI. But in many situations, that human can be an NP or a PA, rather than a physician.

Artificial intelligence and primary care

Much of primary care is based on clinical practice guidelines. The U.S. Preventative Services Taskforce has guidelines for everything from colon cancer screening to pre-exposure prophylaxis to prevent HIV. The American College of Cardiology has a hypertension diagnosis and management guideline. The Advisory Committee on Immunization Practices has guidelines for childhood and adult vaccination schedules. And the American Diabetes Association has a guideline for the prevention, diagnosis, and treatment of diabetes. If you roll all of these clinical practice guidelines into one artificial intelligence program, then you have the majority of primary care medicine routine visits covered.

As a medical student, I spent hours memorizing vaccination schedules, hypertension treatment algorithms, diabetes medication drug interactions, and the staging systems for various cancers. And guess what? An artificial intelligence program can do all of these things better than my memory allows me to do. In other words, AI eliminates the need for much of the education and training that we currently require in medical school and residency. Artificial intelligence will allow a practitioner with lesser training (such as an NP or PA) to be just as good as a physician when it comes to preventative care medicine and algorithm-based management of most common medical conditions.

However, artificial intelligence is not infallible

Artificial intelligence is actually not new in medicine. I’ve been using simple forms of AI for decades. Every EKG and pulmonary function test that I have ordered in the past 30 years that comes with a computer interpretation has incorporated rudimentary AI into those interpretations. These interpretations programs are fairly good at identifying normal but invariably come up with an incorrect diagnosis in a substantial percentage of those tests that are abnormal. So, before I am willing to allow an AI program to diagnosis breast cancer from a histopathology slide and before I am willing to allow an AI program to diagnose idiopathic pulmonary fibrosis from a chest CT scan, these programs are going to have to get very, very good. Until then, the use of artificial intelligence for more complex pathologic and radiologic diagnoses will supplement rather than replace a physician.

And then there is legal liability…

If a radiologist misses a lung cancer on a chest X-ray, the radiologist is named in a medical malpractice lawsuit. If a patient dies of sepsis when a hospitalist made an incorrect antibiotic choice for the patient’s pneumonia, the hospitalist is named in the malpractice suit. But if an artificial intelligence program misses the lung cancer or selects the wrong antibiotic, who gets named in the malpractice case? The company that created the AI program? The hospital that purchased the AI program? The FDA that approved the program? The physician who entered the patient’s clinical data into the program? All four of them?

Currently, a physician in primary care practice will pay about $12,000 per year in malpractice insurance premiums whereas a primary care nurse practitioner pays about $1,200. The reason for the 10-fold difference is that in most situations, a nurse practitioner is understood to be working under the supervision of a physician and that physician is ultimately responsible or at least shares responsibility for the management of patients seen by the nurse practitioner.  Artificial intelligence is likely to be similar – if it is considered to be a medical device then that device will need to be used by a licensed medical practitioner who will have the greater burden of malpractice liability. Clearly, laws will need to be written to clarify liability before artificial intelligence can be autonomously implemented in clinical practice.

Who will AI benefit the most – nurse practitioners or physicians?

A recent study from MIT researchers found that artificial intelligence has the greatest impact on the least skilled workers. Workers who were new or had low skills were helped more by AI than highly skilled workers. In other words, AI allows those with less training to be “upskilled” much more than those with advanced training.

Extrapolating from this study, it is likely that nurse practitioners and physician assistants will derive greater benefit from artificial intelligence than physicians. Artificial intelligence can make up for the fewer years of training that it takes to become an NP or PA.

Which physicians are most vulnerable to being displaced by artificial intelligence?

Although artificial intelligence has received a lot of press about its potential in radiology, I would argue that primary care physicians are most vulnerable to being displaced by artificial intelligence. Notice that I used the word “displaced” rather than “replaced”. That is because artificial intelligence is likely to be used to supplement a practitioner rather than become a practitioner, at least in the foreseeable future. In this regard, an NP or PA using an artificial intelligence program can replicate much of the skillset of a primary care practitioner. Thus the combination of an NP or PA plus an artificial intelligence program will together displace the primary care physician.

Physicians who are the least vulnerable are those who perform procedures such as surgeons and interventional cardiologists. Although this could change in the future, for now, no AI program or nurse practitioner is capable of independently performing a hip replacement surgery or a coronary artery stent placement. In primary care practice, the office procedures are far less complex – cerumen removal, IUD placement, and laceration suturing can be performed by an NP or PA and do not require a physician.

Also less vulnerable are physicians who are highly specialized. For example, an artificial intelligence program for brain MRI imaging will need to be used under the supervision of a practitioner who can confirm or contradict the AI’s findings. This will require a practitioner who is already an expert in brain MRI image interpretation, in other words, a physician specializing in neuroradiology. Artificial intelligence can still benefit the neuroradiologist, however, by serving in a capacity similar to that of a radiology resident who performs a preliminary read of the MRI that is then over-read and confirmed by the attending neuroradiogist.

“I’m a medical student, should artificial intelligence affect my career choice?”

The answer is… maybe. Fully implemented artificial intelligence in medicine is still a long way off. There will have to be significant improvements in software, significant legal liability questions resolved, and supervision requirements defined. However, if AI can replace certain medical specialists at a lower cost, then economic theory indicates that it eventually will. General internists, general pediatricians, and family physicians may be more vulnerable to displacement than other specialties, especially if the field of medical artificial intelligence matures coincident with an increase in the number of nurse practitioners and physician assistants. However, when it comes to cajoling a cardiologist to add in a patient with chest pain to their already full Friday afternoon schedule, an AI program simply cannot replace a persuasive family physician. The primary care physician may become more of a manager: coordinating care and overseeing a group of nurse practitioners who each have access to the artificial intelligence program.

Things are about to get interesting…

Change in medicine is inevitable but initial resistance to change is also inevitable. When electronic medical records were initially implemented, physicians universally hated them and many refused to use them. Now, no physician in his or her right mind would want to return to an era of paper records kept in manila folders. Ten years ago, the idea of driverless vehicles was met with skepticism but today, you can order a driverless Waymo taxi in San Francisco and you can buy a driverless John Deere tractor to plow your farm.

Artificial intelligence is coming in medicine and its widespread implementation is unavoidable. The question is whether it will augment physicians or displace physicians. I believe that it will do both, depending on the specialty.  From my vantage point, primary care physicians may be the most vulnerable to displacement. And employment opportunities for NPs and PAs are looking bright.

August 30, 2023

Categories
Emergency Department Inpatient Practice Medical Education Outpatient Practice

The New DEA Opioid Education Requirements For Physicians

In March 2023, the U.S. Drug Enforcement Agency (DEA) announced new education requirements for all physicians applying for new or renewal DEA licenses. This was the result of provisions in the Consolidated Appropriations Act of 2023 that enacted a one-time requirement of 8 hours of continuing medical education (CME) on the treatment and management of patients with opioid or other substance use disorders. The requirement went into effect on June 27, 2023. Because DEA licenses are renewed on a rolling 3-year basis, all physicians with DEA licenses must meet this requirement sometime in the next 3 years.

Another provision of the Consolidated Appropriations Act of 2023 was to eliminate the DATA-Waiver (X-Waiver) Program that was previously required for physicians to prescribe buprenorphine. In the past, hospitalists, emergency medicine physicians, and other practitioners needed to obtain an X-Waiver to initiate buprenorphine when patients with opioid use disorder were admitted to the hospital or seen in the emergency department. Because only a small number of physicians took the time and effort to obtain an X-Waiver, the requirement was seen as a barrier to getting patients started on treatment. Now, any practitioner with a current Drug Enforcement Administration (DEA) registration may prescribe buprenorphine for opioid use disorder (if permitted by state law). The trade-off for elimination of the X-Waiver was the requirement that all practitioners with a DEA license be trained in the treatment of opioid use disorder, including the use of buprenorphine.

Who does this affect?

Any practitioner with a DEA registration must meet this requirement. This includes physicians, dentists, nurse practitioners, and physician assistants. However, only practitioners who prescribe controlled substances need to register with the DEA and obtain a DEA number. Although the majority of U.S. physicians have DEA numbers, some physicians do not, either by nature of their practice (for example, pathologists and researchers) or by choice (for example, general practitioners who do not want the hassle of prescribing opioids and other controlled substances).

To obtain a DEA number, a physician must apply to the DEA and pay an $888 fee. DEA numbers are valid for 3 years at which time the physician must re-apply. The DEA waives the fee for certain physicians including those who work in the military, for U.S. government hospitals or institutions, and for state government hospitals or institutions. As an employee of the Ohio State University (a state government institution), my DEA fees were waived. However, even if the fee is waived, the practitioner must still apply for and obtain a DEA number and the practitioner must still meet the new education requirements.

Certain practitioners are exempt from the new educational requirement including veterinarians, physicians board-certified in addiction medicine, and practitioners who have graduated from their professional school within the past 5 years. The latter means that most residents in training are exempt.

What are the specifics of the requirement?

When applying for a new or renewal DEA number, physicians (and other practitioners) must check a box attesting to having completed 8 hours of training on treatment and management of patients with opioid or other substance use disorders. This is a fairly broad topic area and it is up to physicians to maintain their own documentation of completion of education in the event of an audit. In addition, if the physician faces legal action (such as a medical malpractice lawsuit), documentation of completion may be necessary to establish physician competency. The details of the requirement are as follows:

  • The 8 hours of education do not need to occur in one session and (for example) can be 8 individual 1-hour CME events.
  • This is a one-time requirement and will not need to be repeated every three years when re-applying for a DEA number.
  • Education can take the form of grand rounds, classroom sessions, on-line materials, or professional society meetings.
  • Education hours obtained prior to the new requirement also count. For example, attending a grand rounds on buprenorphine in past years can count; just be sure that you have documentation of participation or attendance. Physicians with an X-Waiver can count the training hours from their original X-Waiver application.
  • The education can come from any organization accredited to provide CME credits by the Accreditation Council for Continuing Medical Education.

What do hospitals need to do?

Although the DEA requirement is left to the responsibility of the individual practitioner applying for a DEA number, hospitals do have an obligation to facilitate education. First, if practitioners fail to get the required 8 hours of training and are unable to obtain a DEA number, the hospital’s ability to dispense controlled substances or manage patients requiring controlled substances will be compromised. Second, in the event of a medical malpractice lawsuit involving a practitioner on the medical staff who lacks documentation of completion of the educational requirements, the hospital could be accused of being complicit by not confirming that their practitioners were appropriately trained. Specific steps that hospitals should take now include:

  • Make sure that all members of the medical staff are aware of the new DEA requirements.
  • Inventory practitioners’ DEA license expiration dates and remind practitioners at least 6 months in advance of that date that they must fulfill the educational requirements prior to the renewing their DEA number.
  • Require practitioners with DEA numbers to submit documentation of completion of the educational requirements and then maintain that documentation in each practitioner’s employment record.
  • Require any new practitioners to include documentation of completion of substance abuse treatment CME as part of their application to the medical staff. Those lacking documentation should be required to complete training during their provisional/probational appointment period.
  • Schedule grand rounds or other CME events covering treating and managing patients with opioid or other substance use disorders.
  • Provide practitioners with links to on-line CME resources. For nearly a quarter of a century, I moderated the CME webcast, OSU MedNet-21. We produced many CME webcasts on substance abuse disorders and these webcasts are available to anyone. A recent example is:
  • Many professional societies have included sessions on substance abuse disorders as part of their annual meetings or have prepared on-line CME sessions to help fulfill the requirements. Examples of on-line education programs include:
  • The Centers for Disease Control offers a free on-line 1-hour CME activity about substance abuse disorders
  • Journal subscription materials can count. Practitioners with subscriptions to resources such as UpToDate, JAMA, and the New England Journal of Medicine can obtain CME credit by reading relevant articles and then applying for CME hours.

Why has Congress required this?

The primary impetus for the new requirement is a directive of the U.S. Congress to address the opioid epidemic. Eliminating the X-Waiver program was seen as a way of improving access to treatment for patients with opioid use disorder. But to justify elimination of the X-Waivers, Congress needed a mechanism to ensure that all practitioners were knowledgable in initiating treatment for opioid use disorder.

In 2021, a total of 106,699 Americans died of a drug overdose. Although street-purchased fentanyl was the most common drug implicated, prescription opioids accounted for 16,706 of the overdose deaths in 2021. In fact, the number of deaths from prescription opioids exceeded the number of deaths from heroin (9,173).

Drug overdose deaths are particularly high in Appalachian states. West Virginia has the highest overdose death rate at 90.9 per 100,000 population, followed by Kentucky and Tennessee (each 56.6 per 100,000 population) and Louisiana (55.9 per 100,000 population). My state of Ohio ranks 7th highest at 48.1 per 100,000 population. Nebraska comes in lowest at 11.4 per 100,000 population.

To put these numbers in perspective, last year, the U.S. COVID death rate was 61.3 per 100,000 population. Opioids are abused by more than 10 million Americans each year (3.8% of Americans) and 2.7 million Americans have an opioid use disorder. About half of those who become addicted to opioids first use opioids in the form of prescription pain medications. An estimated 3% – 19% of people who take prescription opioid pain medications will become addicted to opioids. Addiction can occur with only 3-5 days of prescription opioid use.

The good news is that there are effective treatments for opioid use disorder including buprenorphine (often combined with naloxone), methadone, and naltrexone. In addition, the FDA has now approved naloxone to be sold over-the-counter to treat opioid overdose. The goal of the DEA education requirements is that any practitioner in the U.S. who is licensed to prescribe opioids is also trained in identifying and treating opioid abuse.

A quarter of a century of change

In the 25 years since the American Pain Society advocated that physicians adopt “pain as the 5th vital sign” and since Purdue Pharmaceuticals falsely promoted OxyContin as a non-addictive opioid, physicians have become much more aware of the role that we have played in catalyzing the current opioid epidemic. The new DEA education requirements were created as one step in remedying the epidemic. By helping our physicians meet these new requirements, hospitals can help reduce the number of Americans who become addicted and help increase the number of Americans who get their addiction treated.

August 28, 2023

Categories
Emergency Department Outpatient Practice

Over The Counter Oral Contraceptives: An Opportunity For Hospitals

Last week, the U.S. FDA approved Opill, the first over-the-counter birth control pill. It contains 0.075 mg progesterone and must be taken every day, at the same time of day. Opill now gives hospitals a new opportunity to reduce unwanted pregnancies by counseling women in the emergency departments, inpatient settings, and outpatient clinics.

How effective is Opill?

Most currently available prescription oral contraceptives are combination estrogen/progestin pills. The estrogen component poses risks of deep venous thrombosis, pulmonary embolism, hypertension, myocardial infarction, and stroke. For this reason, it is likely that combination estrogen/progestin oral contraceptives will remain only available by prescription in the future. Since progestin-only pills lack estrogen, they are generally safer than combination birth control pills. Opill contains norgestrel, a form of progestin. The amount of progestin in Opill (0.075 mg) is much lower than the amount of progestin in most combination pills (typically about 1.0 mg) and less than currently available progestin-only prescription birth control pills (0.35 mg). Because it only contains progestin and only in a very low dose, it is sometimes called a birth control “mini-pill”. 

Opill (norgestrel) works by thickening cervical mucus, creating a barrier to prevent sperm from entering the cervix and uterus. In addition, norgestrel slows the passage of ova through the fallopian tubes and alters the endometrium to impede ova attachment. In about half of women, norgestrel also prevents ovulation. Norgestrel blood levels peak approximately 2 hours after ingestion and the drug is completely eliminated from the body by 24 hours. These pharmacokinetics are why rigid adherence to the dosing schedule at the same time every day is required.

The effectiveness of any form of contraception is often measured by the “Pearl index”, named after biologist, Raymond Pearl. This index is the number of pregnancies per 100 women using that form of contraception for one year. In a 2022 review of the literature in the journal Contraception, the average Pearl index for progestin-only oral contraceptives is about 2. This means that if 100 women use progestin-only pills for a year, 2 of them will become pregnant. However, in real life, the Pearl index is almost never as high as it is in clinical trials where researchers make every effort to ensure that women do not miss doses. It is just too easy to take a dose more than 3 hours late in the day or to forget to take a daily dose altogether. For this reason, it is likely that in regular clinical use, the Pearl index for Opill will likely be closer to the Pearl index of combination estrogen-progestin birth control pills, or around 7 pregnancies per 100 women per year. This puts Opill in an intermediately effective form of contraception: better than condoms but not as effective as IUDs or implants.

However, even with a Pearl index of 4 – 7 pregnancies per 100 women per year, Opill will now be the most effective over-the-counter contraception method available and far more effective than condoms.

Advantages and disadvantages of Opill

Advantages:

  • No physician visit required for a prescription. The wait for a routine return appointment at my own PCP is 4 months. This is too long for most people to wait to get access to contraception.
  • Good option for women/girls who do not want their healthcare provider to know about their sexual activity. This is particularly useful for minors who do not want their parents to know that they are sexually active.
  • Useful for women who frequently travel or occasionally lose medications. It can be difficult to get an emergency refill of a prescription oral contraceptive, particularly when out of state or on weekends. Women can get a refill of their Opill anytime at any pharmacy in the country.
  • Fewer side effects than prescription combination estrogen/progestin birth control pills.
  • Unlike condoms and diaphragms, it is not necessary to interrupt sex to use Opill.

Disadvantages:

  • No physician visit required for a prescription. This can be a missed opportunity to counsel women/girls about all of the various contraception options.
  • Does not prevent sexually transmitted diseases.
  • Should not be used in women with a history of breast cancer, women with undiagnosed vaginal bleeding, and women with liver disease.
  • Can result in irregular vaginal bleeding.
  • Other common side effects may include nausea, breast tenderness, and headaches.
  • Must be taken every day and within 3 hours of the regular hour of the day that it is normally taken. If a dose is missed, delayed, or there is vomiting after taking a dose, alternative contraception must be used for at least 48 hours.
  • Even with perfect use, 1 out of every 50 women will get pregnant every year.
  • Possibly less effective in obese women/girls.
  • Drug interactions with phenytoin, carbamazepine, barbiturates, rifampin, efavirenz, bosentan and St. John’s Wort. These drugs can render Opill ineffective.
  • Not tested in girls younger than 15 years old.

An opportunity to counsel ER patients

One of the more common diagnoses we make in women in U.S. emergency departments is pregnancy. A 1994 study found that 6.3% of women of childbearing potential presenting to the ER had unsuspected pregnancies. The incidence of pregnancy in women presenting with abdominal pain is even higher at 13%. When women suspect that they may be pregnant, many will present to the emergency department for pregnancy testing rather than their primary care provider. This has become particularly true in states that have time restrictions on abortions. Because women often do not realize that they are pregnant until they miss a menstrual period, they are often 4 – 5 weeks pregnant when they begin to suspect pregnancy. In states where abortion is illegal after 6 weeks gestation, a delay in pregnancy testing of even a few days while waiting to see a primary care provider can result in exceeding the legal gestational time for an abortion. A trip to the ER is often the fastest way for a women to find out whether or not she is pregnant.

As a rule, emergency medicine physicians do not prescribe maintenance medications, including birth control pills. Consequently, until now, all that an ER provider could recommend to women who had came to the emergency department for pregnancy testing and had a negative test was to see their primary care provider for contraception counseling and prescriptions. Unfortunately, many women do not have a  regular primary care provider. Furthermore, many adolescents do not want to speak to their pediatricians about contraception for fear that their parents will find out. Many unmarried adult women do not want to admit to their primary care provider that they are sexually active or do not want that information to be recorded in an electronic medical record that any healthcare worker might get access to.

But now, our ER providers have the ability to recommend reasonably effective non-prescription contraception to any woman. But how should the information be provided and which women should get that information? It is ineffective to simply ask women if they are sexually active in the ER because they are frequently not forthcoming about their sexual history. Indeed, a 1989 study found that 7% of women ER patients who stated that there was no chance that they were pregnant were, in fact, pregnant. Sometimes it is because there is a relative or friend in the ER room with them and they don’t want that individual to know about their sexual history. Sometimes, they don’t want to risk their sexual history being recorded in the electronic medical record. Sometimes they don’t even want the ER provider to know that they are sexually active because it would acknowledge violation of cultural or religious doctrines. The most effective strategy is to provide information about contraception to all women of childbearing potential. But what is the best way to provide that information?

Unfortunately, there are insurmountable barriers to printing up information about Opill on the ER after visit summary for every female patient between the ages of 11 and 50. Twelve-year-olds can and do get pregnant but handing out information about contraception to every 12-year-old who comes to the ER with a sprained ankle will infuriate many parents who in turn will write scathing reviews of the hospital on Yelp that will then infuriate hospital administrators and board members. Although the FDA does not expressly state the youngest age that Opill is indicated for, in clinical trials, it was not used in girls younger than age 15 so hospitals could potentially face legal liability if it is perceived that they were recommending Opill for girls younger than 15. In addition, some women and girls may be offended if this information is printed on their after visit summary. This could include women with previous tubal ligation or hysterectomy, widows, lesbians, Catholics, and the celibate. One compromise would be to just include information about Opill on the after visit summary for female patients between ages 18 and 50 or between ages 15 and 50. This option is less likely to offend parents but can still offend other girls and women. Another compromise would be to only include after visit summary information for patients who had a pregnancy test or a test for sexually transmitted disease in the ER. This would target those women and girls who are presumably at a higher risk of becoming pregnant but because most ER visits do not result in pregnancy or STD testing, most women and girls will not receive any information. Alternatively, information about Opill could be posted in public areas such as posters in examination rooms, posters in waiting rooms, or screen displays on public video/TV monitors. This is the least intrusive and least likely to offend anyone. However, it may be less impactful since there is no printed information for girls and women to take with them. Information does not need to be excessively detailed. For example, a wall poster or after visit summary could simply say something like “Over the counter birth control pills are now available; to learn more, go to this website…”.

Opill and Catholic hospitals

These informational tactics will only be applicable for the nation’s non-Catholic hospitals. Currently, 16% of all U.S. hospitals are affiliated with the Catholic Church. In many communities, a Catholic hospital is the only available healthcare facility. Because of the church’s doctrine prohibiting contraception, these hospitals would face opposition to providing information about Opill from the church. This is particularly unfortunate since a primary mission of many Catholic hospitals is to provide care to the underserved, a population of women who are less likely to have regular primary care providers and thus have less access to prescription contraception. Although 99.0% of Catholic women have used some form of contraception at some time of their lives (despite church doctrine), this is less than women with no religious affiliation (99.6%), mainline Protestants (99.4%), and evangelical Protestants (99.3%). This barrier to contraception access for Catholic women is reflected in the religious demographics of American women undergoing abortion – Catholic women are more likely to have an abortion than women belonging to other religions in the United States. Data from the Guttmacher Institute indicates that 24% of American women undergoing abortion identify as Catholic but only 22% of the American population as a whole is Catholic.

On the other hand, Opill provides a new opportunity for physicians employed by Catholic hospitals – including primary care providers at hospital-owned outpatient clinics. Many such hospitals and clinics prohibit their physicians from prescribing contraception, inserting IUDs, or even performing tubal ligation or vasectomy for the purpose of contraception. Many physicians at these hospitals are not even willing to include documentation of discussions about contraception in the electronic medical record for fear of being identified by hospital officials as providing forbidden services during medical record audits. Now, however, physicians and other providers at Catholic hospitals, emergency departments, and clinics can verbally recommend over-the-counter Opill to their patients interested in contraception without creating an incriminating documentation trail in the electronic medical record that could result in job termination.

Reducing unwanted pregnancies

Abortion legislation is currently one of the most controversial socio-political issues in the U.S. The most effective way to reduce abortion is not by making abortion illegal but instead by preventing unwanted pregnancies in the first place. As Americans, we waste way too much emotional energy arguing about abortion laws while often ignoring tactics to reduce unwanted pregnancies. The availability of Opill now gives us a new opportunity to reduce these unwanted pregnancies by increasing the availability of reasonably effective contraception to women who otherwise have barriers to obtaining prescription contraception. 

We do not yet know how Opill will be priced. Most prescription oral contraceptives currently cost $10 – $50 per month without insurance and presumably, Opill will be in this general price range. Health insurance policies typically only cover prescription medications and generally do not cover over the counter medications. It is unclear if health insurance companies and Medicaid will cover Opill. The cost of Opill for a year is far, far less than the cost of a pregnancy. The Kaiser Family Foundation estimates that the total cost of pregnancy, child birth, and postpartum care is $18,865. In addition, the average healthcare costs per child is $2,966 per year which adds up to $53,388 from birth to age 18. This means that the total healthcare cost of an unintended pregnancy is $72,253. In addition, the average cost of $4 per child per day for SNAP (Supplemental Nutrition Assistance Program, aka food stamps) adds another $26,280 charged to taxpayers over 18 years for every unwanted pregnancy to a low-income woman. Even at a cost of $50 per month, insurance companies and Medicaid programs would be financially foolish to not cover Opill. Indeed, by preventing unwanted pregnancies, Opill could reduce health insurance premiums and reduce taxpayer costs of Medicaid and SNAP.

Not perfect, but…

Opill is not the most effective form of contraception, nor is it for all women and girls. But it is a well-needed addition to the current contraception options and holds the promise of reducing unwanted pregnancies and abortions. Hospitals, and especially emergency departments, can play an important role in educating women and girls about Opill. Each hospital should decide for itself what the best method of patient education is in its own facilities.

July 17, 2023

Categories
Emergency Department Epidemiology Outpatient Practice

It’s Back! Malaria In The United States

Last week, I was hiking and birdwatching in Fort Macon State Park in North Carolina. I got a few good bird photos but I got a lot of mosquito bites. In North Carolina, they are a nuisance but in Florida or Texas, they can be deadly. Locally transmitted malaria is now present for the first time in 20 years in the U.S. Many physicians are unfamiliar with its presentation and many hospitals are not prepared to perform diagnostic testing.

Worldwide, malaria affects 241 million people each year and and causes over a half a million deaths per year. It is caused by five species of the protozoan parasite Plasmodium (P. falciparum, P. vivax, P. malariae, P. ovale, and P. knowlesi) which are transmitted by the bite of a female Anopheles mosquito. It primarily occurs in equatorial regions, particularly in central African nations.

In the past, it was also endemic in the United States but was largely eradicated by public health efforts at mosquito control. In 2018, there were 1,823 cases of malaria diagnosed in the U.S., all in foreign travelers who became infected elsewhere. Until this year, the last cases of endemic malaria in the U.S. were in Palm Beach, Florida in 2003 when 8 persons were infected with Plasmodium vivax. 

The recent outbreaks occurred in Sarasota County, Florida (4 cases on May 26, 2023) and Cameron County, Texas (1 case on June 23, 2023). In both areas, the species was Plasmodium vivax. Because of rising temperatures from climate change, southern areas of the United States may see more cases of endemic malaria in the future. Because these are locations that many Americans travel to for vacations, physicians in all states need to include malaria not only in the differential diagnosis of patients presenting with fever who have traveled to endemic countries but also in patients traveling to south Texas or south Florida. It has been nearly 3 decades since I last encountered a case of malaria and much has changed in the diagnosis and management since that time. So, this post is to update practitioners and hospitals on what they need to know.

Clinical presentation

After the initial mosquito bite, patients are asymptomatic during the incubation period and symptom onset is generally 1 – 5 weeks after the initial infection. Symptoms are non-specific and most commonly include fever, chills, headache, myalgias, and fatigue. Less commonly, patients can present with GI symptoms such as nausea, vomiting, and diarrhea. If not diagnosed and treated early, patients can become critically ill with mental status changes, seizures, renal failure, acute respiratory distress syndrome, liver failure, and coma. Pregnant women are at particularly high risk for developing severe disease and death. Others at high risk include immunocompromised patients, those with splenectomy, and children less than 5 years of age. Different Plasmodium species cause different severities of infection: P. falciparum and P. knowlesi infections can cause rapidly progressive severe illness or death, whereas P. vivax (the species causing the recent Florida and Texas cases) is less likely to cause severe disease.

Routine laboratory findings are also non-specific and can include anemia, thrombocytopenia, and elevated liver function tests. Patients presenting with thrombocytopenia are more likely to develop severe disease. Because malaria can progress extremely rapidly, it is essential that diagnosis be made immediately. The clinical suspicion of malaria should be considered a medical emergency – this is not a disease that you discharge patients with from the emergency room to follow-up with their PCP the next day.

Diagnosis and treatment

P. vivax on thin blood smear

Malaria should be considered in any patient with fever and recent travel to endemic areas (now including the southern most areas of the United States). The diagnosis is confirmed by thin and thick blood smears for visual identification of the Plasmodium parasite. A new rapid diagnostic test for malaria has also been developed. The BinaxNOW Malaria test is approved by the FDA and has a sensitivity of 94% and specificity of 84%. The BinaxNOW Malaria test can be used to make a quick presumptive diagnosis but because both false positive and false negative results can occur, it should always be followed by thin and thick blood smear evaluation. PCR tests for malaria are very sensitive and are available through the CDC but the time required for specimen transport and test completion makes PCR impractical for clinical decision making.

The treatment of malaria depends on the specific species involved, the geographic location of travel, and the severity of infection. A summary table is available on the CDC’s malaria diagnosis and treatment for U.S. clinicians website. Uncomplicated infections with P. vivax, P. ovale, P. malariae, and P. knowlesi are generally treated with either chloroquine or artemisinin combination therapy. Uncomplicated infection with P. falciparum is generally treated with artemisinin combination therapy. Severe malaria infections are treated with intravenous artesunate. Most hospital pharmacies do not stock arteunate but it can be obtained in an emergency by having the pharmacist call 1-855-526-4827 to identify the closest distributor.

What hospitals should do now

With international travel picking up post-COVID and now that P. vivax malaria has been identified in the United States, hospitals should evaluate their malaria preparation. Specific steps include:

  • Consider stocking the BinaxNOW Malaria rapid diagnostic test.
  • Ensure that laboratory technicians are educated and competent in performing thin and thick blood smears. The CDC has on-line guidelines.
  • Ensure that laboratory technicians and pathologists are educated and competent in the microscopic identification of malaria trophozoites. The CDC has an on-line resource for identification of malaria and other parasites that includes photomicrographs of trophozoites of the various Plasmodium species on both thick and thin blood smears.
  • Educate medical staff about malaria presentation and diagnosis with particular attention to emergency department providers, hospitalists, critical care practitioners, and primary care providers. Patients with suspected or newly diagnosed malaria should either be admitted or kept overnight in observation status.
  • Ensure that the pharmacy has a process in place for obtaining intravenous artesunate in an emergency.
  • Educate primary care providers and travel clinics about current malaria prophylaxis measures for patients traveling to high-risk areas.

Mosquito bites can be more than just an itch

A mosquito is like a flying syringe that goes from animal to animal and person to person. Like a contaminated syringe, mosquitos can transmit a wide variety of blood-borne diseases including malaria, yellow fever, dengue fever, chikungunya, filariasis, West Nile virus, various forms of encephalitis, and Zika virus. The best way to prevent these infections is to prevent mosquito bites in the first place. This is particularly true for people traveling to locations where any of these various infections are endemic. Here are recommendations we can give to all of our patients:

  • Wear loose-fitting long sleeve clothing. As I learned from my recent outing last week, when shirts get soaked with sweat and stick to the skin, they offer no protection from mosquitos.
  • Use effective insect repellant. The most effective is DEET in 25 – 30% concentrations. OLE (oil of lemon eucalyptus) and picaridin are less-effective alternatives to DEET.
  • For those who work outside or spend a lot of time outside, treat clothing with permethrin. Some outdoor gear can be purchased already treated with permethrin but you can also buy permethrin spray and treat clothing yourself. Just be sure to follow clothing washing instructions to prevent the permethrin from being washed away.
  • Skip the citronella candles, sonic repellant devices, and wearable repellant devices. These are nowhere near as effective as DEET.
  • Inspect window screens. Although keeping doors and windows closed is the best way to keep mosquitos from getting into the house, this is not always an option, especially for homes without air conditioning. Be sure that screens fit tightly into window frames and that there are no holes in the screens.
  • Eliminate stagnant water. For property owners, eliminating places where water accumulates can prevent mosquitos from laying eggs and prevent eggs from hatching. These can include bird baths, gutters, old tires, toys, and other open containers.
  • Where stagnant water cannot be drained, encourage community mosquito control spraying programs.
  • When traveling to areas where sleeping outdoors or in unscreened buildings is necessary, mosquito nets can be effective.

It is too early to say whether or not malaria will become regularly transmitted in the United States in the future. But the recent Florida and Texas cases are a reminder that malaria is still with us. International travel makes the world an increasingly small place with endemic areas just a few hours away from every city in the U.S.

June 30, 2023