Monday, August 2, 2021

COVID vaccine boosters: now, later, or never?

 Jennifer Middleton, MD, MPH

As COVID-19 infection numbers continue to rise, and with continued breakthrough cases in persons who have been fully vaccinated, questions about booster shots are circulating. The delta variant is wreaking havoc in many places across the world, especially in pockets of the US with low vaccination rates including Missouri, Arkansas, Louisiana, and Florida. Reports of breakthrough infections in persons fully vaccinated have contributed to many alarming headlines, though public health experts have been quick to emphasize that the vast majority of severe infections are occurring in unvaccinated persons.

Data from Israel, which has vaccinated 60% of its population against COVID-19, is fueling fears as well. Estimates that the vaccine was just 39% effective at preventing infection in the last couple of months there have been heavily publicized, though Israeli researchers have been quick to point out that the vaccine has consistently remained highly effective (>90%) at preventing severe COVID-19 infection:

Experts suggested several possible explanations for the seeming decline, including the possible waning of immune protection in people vaccinated early in the year....[b]ut it's also possible that the apparent decline is a mathematical fluke. Case numbers are much lower in Israel now that they were earlier in the year..."I think that data should be taken very cautiously because of small numbers," [according to] Eran Segal, a biologist at the Weizmann Institute of Science.

With these concerns swirling, Pfizer announced preliminary results regarding its investigation into the efficacy of a 3rd COVID-19 vaccine dose, finding "[p]ost dose 3 [antibody] titers vs. the Delta variant are >5-fold post dose 2 titers in 18-55 [year-olds] & >11-fold post dose 2 titers in 65-85 [year-olds]." These numbers sound impressive, but this antibody titer study was only conducted in 23 individuals, and it's unclear precisely how antibody titers correlate with more important patient-oriented outcomes such as severe illness and death. In a joint statement issued earlier this month, the FDA and the CDC asserted that "Americans who have been fully vaccinated do not need a booster shot at this time....We are prepared for booster doses if and when the science demonstrates that they are needed." The stark inequity of worldwide vaccine distribution also raises ethical concerns regarding devoting more vaccine product to the US when most of the world's population still does not have access to even a first COVID-19 vaccine dose.

The Advisory Committee of Immunization Practices (ACIP) has been discussing the possible benefit of a booster dose for immunocompromised persons, though ACIP declined to make any recommendations at its meeting last week. While we wait for more data and possible recommendations on boosters, the CDC is now advising all Americans, even those who have been fully vaccinated, to mask indoors if they are in areas of high COVID-19 transmission (which is most of the US as of this writing), especially if they live with persons unable to be vaccinated and/or at higher risk of complications from COVID-19 disease. We should still continue to advise our patients, even our vaccinated ones, to exercise caution and thoughtfulness as the delta variant continues to spread.

Tuesday, July 27, 2021

Pharmacogenetic testing's promise, problems, and pitfalls

 - Kenny Lin, MD, MPH

In 2019, Dr. Carl Bryce wrote a Diagnostic Tests review in American Family Physician about the allopurinol hypersensitivity assay, "a blood test to detect the presence of a human leukocyte antigen B [HLA-B] genetic variant that increases the risk of life-threatening, severe cutaneous reactions in patients taking allopurinol." According to this article and a rapid evidence review of gout, testing was recommended for Korean adults with stage 3 or higher chronic kidney disease and all adults of Han Chinese or Thai descent, who have a higher frequency of the variant, prior to initiating allopurinol. In 2020, the American College of Rheumatology (ACR) simplified and broadened this testing recommendation to "people of Southeast Asian and African American descent."

Though pharmacogenetic testing holds promise for improving clinical decision-making, a recent JAMA Viewpoint contended that race-based testing recommendations are problematic. Even a racially homogenous European country such as Switzerland exhibits wide genetic diversity in the frequency of the HLA-B*58:01 allele, with one city (Basel) actually having a higher frequency than the U.S. African American population. Further examination of the ACR's race-based guidance reveals additional complexities and contradictions:

The ACR guideline cites Han Chinese, Korean, and Thai as examples of Southeast Asian descent, even though China and Korea are not typically considered Southeast Asian countries. The guideline then states that screening is cost-effective in Asian populations generally. However, Japan is in Asia, but the allele frequency of HLA-B*5801 in Japan is even lower than that of White individuals in the US, who are not recommended for screening. In addition, the recommendation to screen all African American patients in the US before prescribing allopurinol belies wide-ranging HLA-B*5801 variation across Africa, where reported HLA-B*5801 frequencies, based on small sample sizes, range from 1% (comparable with White individuals in the US) to 10% (comparable with Thailand).

In an AFP editorial published online last month, Dr. Bonzo Reddick took aim at a related issue: the use of diagnostic and clinical prediction tools that, like pharmacogenetic tests, incorrectly utilize race as a proxy for genetic differences. These include the atherosclerotic cardiovascular disease (ASCVD) Pooled Cohort risk calculator, equations for glomerular filtration rate (GFR), a calculator for predicting the likelihood of a successful vaginal birth after cesarean delivery, and pulmonary function testing "correction factors" for Black and Asian patients.

Recognizing that "claims about pharmacogenetic testing ... are inconsistently supported by scientific evidence, and most tests have not been examined by the U.S. Food and Drug Administration [FDA]," Drs. Wendy Rubinstein and Michael Pacanowski shared the FDA's perspective on what clinicians need to know in the July issue of AFP. In a table of selected pharmacogenetic associations, they summarized known and potential gene-drug interactions and recommendations for clinical practice, when applicable. In a Diagnostic Tests review in the same issue, Dr. Natasha Pyzocha evaluated GeneSight Psychotropic, an expensive test panel that analyses 12 genes with possible interactions with 57 neuropsychiatric medications. Dr. Pyzocha concluded that while this test may help patients who have had multiple unsuccessful trials of therapy, "because only a small population of patients are expected to have genetic phenotypes that would necessitate medication changes, ... routine genetic testing is not recommended," and "choosing antidepressants based on health history and symptoms should still be the standard initial approach."

Monday, July 19, 2021

Should the FDA have approved aducanumab?

- Jennifer Middleton, MD, MPH

The US Food and Drug Administration (FDA) recently approved  aducanumab (Aduhelm), "a first-of-its-kind treatment....that targets the fundamental pathophysiology" of Alzheimer's disease. Pharmacologic treatment options for Alzheimer's disease have previously only targeted symptoms, but aducanumab purports to attack the amyloid plaques "that result in loss of neurons and their connections." Aducanumab's approval, however, has been met with criticism from both the medical community and members of the FDA themselves.

The FDA approved aducanumab via its accelerated approval pathway, intended for "drugs for serious conditions that fill an unmet medical need." The accelerated approval pathway permits drug makers to present less rigorous (and less time consuming) outcomes than the traditional approval process:

A surrogate endpoint used for accelerated approval is a marker - a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit, but is not itself a measure of clinical benefit. Likewise, an intermediate clinical endpoint is a measure of a therapeutic effect that is considered reasonably likely to predict the clinical benefit of a drug, such as an effect on irreversible morbidity and mortality (IMM).

The two phase III trials that aducanumab's manufacturers presented to the FDA had identical study designs; each enrolled adults worldwide aged 50-85 with symptoms consistent with early Alzheimer's disease and randomized them into 3 groups: placebo, low-dose aducanumab, and high-dose aducanumab (all administered every 4 weeks intravenously). Their primary endpoint was the Clinical Dementia Rating - Sum of Boxes (CDR-SB), administered at participant enrollment and again after 78 weeks of treatment.  Neither study found benefit for low-dose aducanumab; one study's results suggested potential for high-dose aducanumab, while the other study did not.

Perhaps not unsurprisingly, 10 of the 11 FDA advisory committee members voted against aducanumab's approval in November of 2020 after reviewing the results of these 2 studies. Yet on June 7, 2021, the FDA approved aducanumab, citing trial data demonstrating that "[p]atients receiving the treatment had significant dose-and time-dependent reduction of amyloid beta plaque, while patients in the control arm of the studies had no reduction of amyloid beta plaque." It's notable that the FDA justified its decision using one of the trials' secondary outcome measures and not the primary outcome measure, CDR-SB, that had inconsistent results. Three physicians resigned from the FDA advisory committee in protest, including Dr. Aaron Kesselheim, who has since publicly aired his concerns regarding the drug's questionable safety, unproven efficacy, monitoring requirements, and steep price tag ($56,000/year). Allegations of improper communications between aducanumab's manufacturers and the FDA have also emerged, casting more doubt on the propriety of aducanumab's approval.

Patient advocacy groups are cheering aducanumab's approval, though, and understandably so; the devastation Alzheimer's disease wreaks on patients and families is profound, and the potential to ameliorate that suffering with a completely new drug is tantalizing. The FDA is requiring aducanumab's manufacturers to continue gathering data regarding its safety and efficacy, so time will tell whether the FDA's approval decision will prove to be a rash or sound one.

You can read more about Alzheimer's disease, and other dementia disorders, at the AFP By Topic on Dementia, which includes this 2017 AFP overview of "Alzheimer Disease: Pharmacologic and Nonpharmacologic Therapies for Cognitive and Functional Symptoms." 

Monday, July 12, 2021

Which U.S. hospitals are providing Right Care to their communities?

 - Kenny Lin, MD, MPH

The Lown Institute, which has partnered with AFP since 2018 on a series of Right Care articles addressing clinical scenarios of overuse and underuse in primary care, recently released the second edition of its Hospitals Index. Unlike traditional metrics that are primarily based on a hospital's revenue and reputation, the Lown Institute Hospitals Index ranks U.S. hospitals by equity, value, and outcomes nationally and by state. This year, Lown produced separate rankings of hospitals by overuse of low-value tests and procedures, racial inclusivity, and community benefit.

A key finding of this year's community benefit ranking is that more than 7 in 10 private nonprofit hospitals spend less on charity care and community investment than they receive in tax breaks (what Lown terms a "fair share deficit"). These hospitals' collective fair share deficit was $17 billion, with the bottom ten hospitals representing $1.8 billion of that national total. Although pre-2010 data are not available for comparison, the size of this deficit seems to suggest that the Affordable Care Act's requirement for nonprofit hospitals to conduct community health needs assessments (CHNAs) every 3 years hasn't led to greater investments in community health. However, New York State's Prevention Agenda legislatively required nonprofit hospitals to collaborate with local health departments on CHNAs starting in 2013. A recent analysis of IRS data found that compared to a control group of hospitals in the other 49 states and District of Columbia, New York hospitals increased their mean spending on population health improvement by $393,000-$786,000.

More information on the Lown Institute Hospitals Index methodology is available in a JAMA Network Open article and in recorded webinars and explanatory videosU.S. News & World Report has announced that its 2021-22 Best Hospitals ranking will incorporate Lown's metric for overuse of spinal fusion. In an editorial in the May 15 issue of AFP, Drs. Alan Roth and Andy Lazris pointed out that a silver lining of the COVID-19 pandemic is that many patients avoided unnecessary spinal fusions and other interventions of questionable benefit, such as electrocardiograms in asymptomatic, low-risk adults. Whether these gains in Choosing Wisely will be preserved post-pandemic is unclear. Finally, in a June 15 Lown Right Care article, Drs. Roth and Lazris joined AFP Patient Partners Helen Haskell and John James in highlighting the negative health consequences of poor physician-patient communication.

Tuesday, July 6, 2021

Discussing COVID-19 vaccine risks with patients

- Jennifer Middleton, MD, MPH

Data continues to emerge regarding the safety of COVID-19 vaccination in pregnant and younger persons. 

When my pregnant sister asked me a few months ago if she should get vaccinated against COVID-19, I didn't hesitate to advise "yes." We now have published data suggesting that vaccination does not alter pregnancy outcomes. Researchers reviewed two-and-a-half months of data from vaccine safety surveillance systems, including over 35,000 pregnant persons, and found rates of preterm birth and miscarriage comparable to established rates pre-pandemic. Given that pregnancy confers a higher risk of COVID-19 complications, it seems reasonable to continue to advise vaccination for pregnant persons while we await more definitive, long-term data. 

Concerns about post-vaccination myocarditis have also been making headlines. A case series published last week examined myocarditis incidence in members of the United States military. 23 male patients were diagnosed with myocarditis after an evaluation for acute chest pain within 12 to 96 hours after receiving a COVID-19 vaccine. Most cases occurred after the 2nd vaccine (and all of the individuals with myocarditis after their 1st vaccine dose had previously diagnosed COVID-19). The US military administered over 3 million doses of COVID-19 vaccines; their described rate of post-vaccination myocarditis is higher than the rate of myocarditis expected in the general population, but the study authors correctly point out that this risk is still quite small compared to the risks of COVID-19 disease:
[I]t is important to frame concerns about potential vaccine-associated myocarditis within the context of the current pandemic. Infection with SARS-CoV-2 is a clear cause of serious cardiac injury in many patients....Prevalence of cardiac injury may be as high as 60%.... Given that COVID-19 vaccines are remarkably effective at preventing infection, any risk of rare adverse events following immunization must be carefully weighed against the very substantial benefit of vaccination. 
Discussing risk with patients in a meaningful way can be challenging. An 2018 FPM article on communicating risk with patients during shared decision making recommends being honest with patients about potential risks, "[u]sing frequencies with the smallest numbers possible (but not “1 in X” [as patients may worry that they'll be that 1])," and avoiding descriptive language (such as "low" or "high" risk). For example, the risk from the above study of myocarditis after COVID-19 vaccination was 19 cases per 100,000 person-years, but the risk of heart problems with COVID-19 infection is as high as 6 in 10. Family physicians are in the perfect position to have these conversations, especially since a recommendation from a trusted physician has historically been the strongest predictor of receipt of any vaccine

Even though the US didn't quite meet President Biden's goal of vaccinating 70% of the adult population by July 4, 20 US states and the District of Columbia did meet or surpass that goal. COVID-19 vaccine hesitancy also appears to be decreasing as 2021 progresses, so it's definitely worth continuing to have these conversations with our patients. If you'd like to learn more, the AAFP regularly updates its "COVID-19 Safety and Efficacy Data Overview" website, and this AFP editorial on "Strategies for Addressing and Overcoming Vaccine Hesitancy" contains many useful tips. The blog recently featured this guest post on "Patient-centered discussion of COVID-19 infection and mRNA vaccines" as well.

Monday, June 28, 2021

Are continuous glucose monitors overrated and overused?

- Kenny Lin, MD, MPH

The popularity of continuous glucose monitoring (CGM) is surging in the U.S., but whether patients are being helped is unclear. Not only is CGM currently being used by 2 million patients with type 2 diabetes, but start-ups promote them as biofeedback "wellness tools" for people without diabetes even though there is no evidence that CGM improves dietary choices, weight loss, or other outcomes in persons with obesity or prediabetes. Arguing in an American Family Physician editorial a year ago that "Continuous Glucose Monitoring in Type 2 Diabetes Is Not Ready for Widespread Adoption," Dr. Sandy Robertson and colleagues pointed out that no long-term studies had demonstrated that CGM improved patient-oriented outcomes in this population compared to finger-stick or no self-glucose monitoring, and that "unnecessary monitoring not only wastes money but can negatively impact quality of life." I've also written on this blog before that patients with type 2 diabetes who are not using insulin do not benefit from self-monitoring.

In this context, two articles in the June 1 issue of AFP emphasized the relatively narrow evidence-based indications for considering CGM. A POEM (Patient-Oriented Evidence That Matters) reported on a systematic review and meta-analysis that found little benefit except in "patients using intensive insulin therapy" who are insensitive to extreme hyperglycemia or hypoglycemia; and a Diagnostic Tests review of the FreeStyle Libre 14-Day "flash" CGM system reported "convenience, possible cost savings, and improvement in treatment satisfaction" for selected patients, but noted that "in adults with insulin-treated type 2 diabetes, there is conflicting evidence whether it reduces [hemoglobin] A1c levels and hypoglycemic time and events."

Two recent studies in JAMA shed additional light on the effects of CGM on glycemic control in patients with insulin-treated type 2 diabetes. In the first study, a multicenter randomized, controlled trial of 175 adults using basal-only insulin with a mean hemoglobin A1c level of 9.1%, participants assigned to the CGM group spent more time in the normal glucose range (70 to 180 mg/dL) and had a lower average hemoglobin A1c at 8 months of follow-up (8.0% vs. 8.4%) than participants in the traditional glucose monitoring group. Severe hypoglycemic events were rare in both groups. In the second study, a retrospective cohort of more than 40,000 patients with type 1 and insulin-treated type 2 diabetes at Kaiser Permanente California, those who initiated CGM "had significant improvements in hemoglobin A1c and reductions in emergency department visits and hospitalizations for hypoglycemia" compared to those who did not initiate CGM. Though the study authors attempted to control for the many baseline differences between the two groups (for example, CGM initiators were "more likely White and English-language speakers and less likely living in a deprived neighborhood"), unmeasured residual confounding may still have affected the results.

Financial conflicts of interest complicate interpretation of the evidence regarding the effectiveness of CGM. A "summary review of recent real-world evidence" on flash CGM published last year in the American Diabetes Association's Clinical Diabetes journal not only was funded by Abbott Diabetes Care (which makes the FreeStyle Libre system) and acknowledged the assistance of a medical communications company in writing the manuscript, but both authors also served on Abbott's advisory board. At AFP, such close ties to a manufacturer of CGM devices would disqualify authors from writing a review article on diabetes or related topics, as we recognize that disclosure is not enough to mitigate biases introduced by these conflicts.

Monday, June 21, 2021

Do ACE-Is and ARBs benefit patients with advanced CKD?

 - Jennifer Middleton, MD, MPH

Many prescribers discontinue patients' angiotension-converting enzyme inhibitors (ACE-Is) or angiotension receptor blockers (ARBs) as their estimated glomerular filtration rate (eGFR) worsens due to concerns about hyperkalemia, hypotension, and/or worsening chronic kidney disease (CKD). Slightly less than half of all persons with CKD stage 4 or 5 in the United States (US) are not currently prescribed an ACE-I or ARB. Two recent studies, however, demonstrate potential benefits of ACE-I and ARB use in patients with advanced CKD. 

The first study reviewed the medical records in a large US health system of nearly 4,000 patients with CKD who were prescribed an ACE inhibitor or an ARB and whose CKD eventually worsened to an eGFR below 30 mL/min/1.73m2. Cohorts were divided into patients whose ACE-Is or ARBs were discontinued when their eGFR dropped below 30 mL/min/1.73m2 and those patients whose ACE-Is or ARBs were continued despite this lower eGFR. Researchers then tracked participants' outcomes for 5 years. They found that persons who had their ACE-I/ARB discontinued had a higher mortality risk than those whose ACE-Is/ARBs were continued (hazard ratio [HR] 1.39; 95% CI 1.20-1.60). The risk of adverse cardiac events was higher in persons who had stopped their ACE-I/ARB (HR 1.37; 95% CI 1.20-1.56). There was no difference in the rate of CKD progression to end-stage kidney disease (ESKD) between groups (HR 1.19; 95% CI 0.86-1.65).

The second study reviewed the medical records of nearly 5000 patients in Sweden with an eGFR below 30 mL/min/1.73m2 (but not receiving dialysis) who received a new prescription for either an ACE-I/ARB or a calcium channel blocker (CCB). After a median of 4.1 years, persons who received an ACE-I/ARB had a lower risk of needing to initiate dialysis compared to the persons who received a CCB (adjusted HR, 0.79 [95% CI, 0.69-0.89]). Mortality and risk of adverse cardiac events were similar in both groups (adjusted HR, 0.97 [95% CI, 0.88-1.07] and adjusted HR, 1.00 [95% CI, 0.88-1.15]), respectively). 

These two studies examined different nuances of patients with advancing CKD: the first, persons whose previous ACE-I/ARB was continued despite worsening eGFR, the second, persons receiving new prescriptions for ACE-I/ARB at a lower eGFR. These differences may explain the studies' differing findings regarding mortality benefit of these medication classes (only found in the first study), adverse cardiac events benefit (the first study), and lowered risk of advancement to ESKD (the second study).

Cohort studies can only demonstrate correlation. Both studies' authors acknowledge the potential for unrecognized confounding factors; for example, it's possible that the persons in both studies who didn't receive ACE-Is/ARBs were somehow more ill than those who did. Until we see randomized controlled trials comparing these approaches, though, these current studies are the best evidence we have to date, and they suggest that continuing ACE-I/ARBs in persons with advanced CKD is likely safe and may have benefits.

If you'd like to read more, check out the AFP By Topic on Kidney Disease, which includes this article on "Chronic Kidney Disease: Detection and Evaluation" and this Cochrane for Clinicians on "ACE Inhibitors vs. ARBs for Patients with Diabetic Kidney Disease." 

Monday, June 14, 2021

Reexamining prenatal care and planned community birth

 - Kenny Lin, MD, MPH

The need to restrict in-person office visits in 2020 to slow the spread of the COVID-19 pandemic affected prenatal care, as some in-person visits were transitioned to virtual or visit intervals were extended. But how did the traditional U.S. prenatal visit schedule - monthly until 28 weeks, biweekly until 36 weeks, and weekly until delivery - become established in the first place? According to a recent review article in the American Journal of Obstetrics & Gynecology, the present-day schedule of 12-14 visits over the course of one's pregnancy was codified in 1930 in a booklet published by the Federal Children's Bureau, during an era when the majority of births occurred in the home. In the intervening century, the only major effort to change the frequency of prenatal appointments came in 1989, when an expert panel commissioned by the Department of Health and Human Services recommended a flexible, risk-based schedule:

Their proposed schedule included 7 visits for low-risk multiparous patients and 9 visits for low-risk nulliparous patients, with additional visits added as needed for high-risk patients based on medical and social risk factors. Interestingly, they suggested a phone visit for multiparous patients at 10 week's gestation, perhaps a first step toward what we now see as telemedicine for prenatal care.

The American College of Obstetricians and Gynecologists (ACOG) decided to reject the new schedule based on insufficient supporting evidence, even though "these recommendations implied maintaining an existing visit structure that was also not evidence-based." Then, as now, supporting evidence for prenatal interventions was limited. For example, though long endorsed by ACOG, counseling for healthy weight and weight gain in pregnancy was not officially recognized by the U.S. Preventive Services Task Force as a beneficial preventive service until last month.

A research study of the Google Trends database suggested that interest in planned community birth in the U.S. and the United Kingdom rose during the pandemic: the frequency of online search queries related to home birth increased by 239% and 53%, respectively, from March through November 2020 compared to the preceding year. According to an article by Dr. Gregory Lang and colleagues in the June 1 issue of American Family Physician, out-of-hospital births increased by 75% from 2004 to 2017, and in 2018 one out of every 61 newborns was delivered outside of a hospital. Planned community births are associated with a lower risk of obstetric interventions, including cesarean delivery, and, in "low-risk, vertex, singleton, term pregnancies in patients who have not had a previous cesarean delivery," neonatal outcomes may be similar to those in hospital settings.

In an accompanying editorial, Drs. Lawrence Leeman and Jessica Goldstein discussed ways to promote safety in community-based birth settings, including "adequate birth attendant training, access to emergency obstetric care, and careful risk assessment throughout the prenatal and intrapartum periods." The authors noted that regardless of whether they personally provide maternity care services, "family physicians play an important role in improving the safety of community birthing by offering counseling on the choice of birth setting, consultation, and collaboration during prenatal care, and by facilitating the process of maternal or newborn transfer [to the hospital] when necessary."

Monday, June 7, 2021

USPSTF updates colorectal cancer screening recommendations

 - Jennifer Middleton, MD, MPH

The United States Preventive Services Task Force (USPSTF) updated its recommendations for colorectal cancer (CRC) screening last month; it is now a B recommendation for adults aged 45-49 to be screened. (The previous A recommendation for adults aged 50-75 is unchanged.)  An increasing prevalence of CRC in younger adults, along with more outcome data from screening younger adults, led to the new recommendation for adults aged 45-49:

[T]he USPSTF determined that beginning screening at age 45 years and continuing to the age of 75 years, for the following screening strategies, yielded a reasonable balance of benefits (life-years gained) and burdens or harms (number of colonoscopies): annual FIT, sDNA-FIT every 1 to 3 years, CT colonography or flexible sigmoidoscopy every 5 years, colonoscopy every 10 years, or flexible sigmoidoscopy every 10 years with annual FIT. 

The USPSTF's statement was supported by a systematic review and a modeling study. The systematic review sought to answer: 1) how effective is CRC screening to lower rates of CRC cancer and/or mortality, 2) how accurate are the available screening modalities, and 3) what are the harms of CRC screening. The researchers found that 1) screening via the modalities listed above* decreases cancer rates and improves mortality, 2) several modalities* have reasonable data to support their use, and 3) most harms are due to colonoscopy; since persons with a positive screening test then require colonoscopy, colonoscopy's harms were applied by researchers to the other testing modalities (the article's Table 4 reviews these in-depth). The modeling study used three sophisticated microsimulation models and found that "screening for colorectal cancer with stool tests, endoscopic tests, or computed tomography colonography starting at age 45 years provides an efficient balance of colonoscopy burden and life-years gained."

The studies cited by the systematic review did not separately analyze their data for adults aged 45-49, and the modeling study is limited by the assumptions entered into the model by researchers. Criticism of the new recommendation for adults aged 45-49 centers around the lack of randomized controlled trials specifically examining this population. The capacity to accommodate this additional population segment is also of concern: "[r]eliance on colonoscopy for screening among individuals aged 45 to 49 years might crowd out approximately one-third of individuals aged 50 to 75 years whose [colorectal cancer] screening is not up-to-date, given limited endoscopy capacity in some communities." The new recommendations are also not an endorsement to ignore patients with concerning symptoms under the age of 45, since "[n]early half of patients with early onset CRC are diagnosed before age 45 years...as was the case for the actor Chadwick Boseman, who died from CRC at age 43 years. Symptoms of CRC...should be evaluated promptly with appropriate diagnostic tests."

As family physicians, we should both discuss the new recommendation with patients and also provide guidance regarding the choice of screening modality when appropriate. Although these 2020 AFP Practice Guidelines from the BMJ and the ACP refer to the 2016 USPSTF recommendation statement, their overviews of CRC screening options remain relevant and useful. The USPSTF's website also has this table reviewing the evidence base behind each screening modality

If you'd like to read more, there's an AFP By Topic on Health Maintenance and Counseling and also this section on Colorectal Cancer Screening in the AFP By Topic on Cancer.

* recommended screening modalities are annual Fecal Immunochemical Test (FIT), stool DNA-Fecal Immunochemical Test (sDNA-FIT) every 1-3 years, CT colonography or flexible sigmoidoscopy every 5 years, colonoscopy every 10 years, or flexible sigmoidoscopy every 10 years with annual FIT.

Tuesday, June 1, 2021

Guest Post: Patient-centered discussion of COVID-19 infection and mRNA vaccines

- Matthew R. Porter, MD, FAAFP, CAQHPM

Few patients understand what the SARS-CoV-2 virus does to the human body or how a COVID-19 messenger RNA (mRNA) vaccine works. The following patient-centered explanation utilizes readily understood metaphors and two clear, simple illustrations that you may use in your vaccine counseling visits. When patients understand how the virus infects cells and how an mRNA vaccine works, most anti-vaccine myths are neutralized and vaccine hesitancy decreases.

Here is a sample conversation I've used to help persuade vaccine-hesitant and vaccine-resistant patients of the safety of the COVID-19 mRNA vaccines:

"Ms. Smith, can I explain to you how the COVID virus infects our body?

Here is a picture of the virus. You can see the spike proteins on the outside. These are like suction cups. They help the virus attach to the cells in our lungs. Inside the virus is RNA, which functions like a DVD because it stores all the information needed to make another virus. For this reason I've made it look like a DVD.


After the virus attaches to a cell, it injects all of the RNA into the cell. The DVD goes to a photocopier in the cell and prints out all the information it has. This stack of pages I've drawn here represents all that information, like a stack of messages. Messenger RNA, mRNA for short, is just copies of all the messages.

The mRNA then goes to the part of the cell that makes proteins. But instead of making a single COVID virus, the mRNA tricks the cell into making thousands of copies of the virus. This overwhelms the cell, causing it to explode, releasing all of those viruses to attack other lung cells. This process occurs until our immune system gets the outbreak under control. By then, in some patients with risk factors, too much damage has been done to the lungs, causing respiratory failure.

Now let me compare this to how an mRNA vaccine works. Imagine this book is the entire COVID RNA. To make the vaccine, a single page of this book with instructions for how to make a spike protein was photocopied. That information is all that is in the vaccine. When it gets inside a cell, the body sees it and says "Hey, these are instructions for making a protein!" Then the spike protein is made. At this point, the cell looks at the spike protein and says "Hey, you don't have ID!" Antibodies are made that fit the shape of the spike protein. The protein is quickly destroyed, as was the single page of mRNA instructions. So all you have left at this point are the antibodies against the spike protein, ready to attack the actual COVID virus.


You can see from this explanation that all of the mRNA in the COVID vaccine is actually present in a COVID infection. But instead of making cells explode, it just prepares the body to fight off the infection. So it makes no sense to downplay the risk of a COVID infection and exaggerate the risk of the mRNA vaccine when the complete set of COVID RNA and mRNA enter your body when you get infected. Every other time in your life you had a viral infection, your body had no problem getting rid of virus proteins and virus mRNA. It is no different with the mRNA of the COVID vaccines."

**

Dr. Porter is a staff physician at Waco Family Medicine in Waco, Texas.

Monday, May 24, 2021

Ovarian cancer screening (still) doesn't save lives

 - Jennifer Middleton, MD, MPH

Five years ago, I wrote about the pitfalls of advertising ovarian cancer screening (specifically, the ROCA test) to post-menopausal persons given the dearth of evidence supporting a mortality or morbidity benefit. The primary study that I cited, the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), released preliminary data in 2016. While they offered the tantalizing suggestion that ovarian and tubal cancer screening may offer a small benefit, they also acknowledged that the mortality of its participant groups did not appear markedly different. Now, after following these 200,000+ participants for a median of 16.3 years, the UKCTOCS researchers are definitively reporting no difference in mortality rates among those who were screened for ovarian and tubal cancer compared to those who were not. 

The UKCTOCS enrolled participants who were post-menopausal from across the United Kingdom and randomized them into three groups: annual multimodal screening (MMS) using ROCA, annual transvaginal ultrasound screening (USS), or no screening. The completed study, published earlier this month, found that:

Compared with no screening, there was a 47·2% (95% CI 19·7 to 81·1) increase in stage I and 24·5% (−41·8 to –2·0) decrease in stage IV disease incidence in the MMS group. Overall the incidence of stage I or II disease was 39·2% (95% CI 16·1 to 66·9) higher in the MMS group than in the no screening group, whereas the incidence of stage III or IV disease was 10·2% (−21·3 to 2·4) lower. 1206 women died of the disease: 296 (0·6%) of 50 625 in the MMS group, 291 (0·6%) of 50 623 in the USS group, and 619 (0·6%) of 101 314 in the no screening group. No significant reduction in ovarian and tubal cancer deaths was observed in the MMS (p=0·58) or USS (p=0·36) groups compared with the no screening group.

Although the MMS identified more cancers at an earlier stage, this early identification did not translate into a mortality benefit. In 2016, the UKCTOCS researchers responsibly advised caution regarding the risk of lead time bias in judging MMS' early detection ability; their assertion then that "follow-up is needed to assess the extent of the mortality reduction before firm conclusions can be reached on the long-term efficacy...of ovarian cancer screening" presciently predicted their final findings.

The United States Preventive Services Task Force (USPSTF) continues to recommend against ovarian cancer screening, and their rationale includes the important caveat that "screening for ovarian cancer can result in...many false-positive results, which can lead to unnecessary surgical interventions in women who do not have cancer." The Choosing Wisely campaign similarly advises against ovarian cancer screening in average risk, asymptomatic persons. As I wrote in 2016we should continue to focus our preventive care on interventions that are proven to decrease mortalityThis AFP article on "Diagnosis and Management of Ovarian Cancer" includes links to editorials that provide additional context regarding screening if you'd like to read more. 

Thursday, May 20, 2021

Guest Post: Thinking about loss in medicine

 - Jason Kurland, MD

Seven years into my medical career and one year into COVID, I've been thinking a lot about loss. Thinking about the primary care patients I lost during COVID and those who died in years prior to the pandemic. I don't find myself missing every patient who has died months later, but I do think of the ones who saw me in clinic regularly every 3 months, then every 2, sometimes every 2 to 4 weeks when their health worsened. The ones I squeezed into an urgent care shift because they needed to be seen by someone familiar with their history. The ones I recognized immediately from my colleague's texts: "admitted your 67 y/o patient with CHF" or "recurrent GIB" or "decompensated cirrhosis." Since I practice full spectrum family medicine in a rural hospital, I may see some patients in clinic one week and in the Emergency Department (ED) or on the medical ward the next. On occasion, I might deliver their granddaughter’s child.

I recall the night over a year ago when we coded a 92 year-old woman, found down at home, only to hear a second ambulance arrive as I called the code. The new patient was her son, my primary care patient. I ended up diagnosing him with yet another myocardial infarction that night; he had five stents already. He survived another year and had many more clinic and virtual visits. Last spring, he was found pulseless on the bathroom floor at home. I walked past our single negative pressure ED room where my colleagues were struggling to restart his heart, unaware that it was him until a screener in the hall outside told me. I poked my masked and shielded head in the door to confirm his Do Not Resuscitate order, ending the code. I then broke the news by phone to his wife who was waiting outside the hospital, per our stringent pandemic visitor policies.

After all of those visits, the setbacks and the improbable upturns, my patient is gone. My role now is to comfort the family, help them process the loss. I feel a grim sense of pride in doing a good job of death care.

My patient no longer pops up reliably in my schedule. I have no reason to open the chart. The time I spent reading about one of their complications or discussing their care with a specialist who ultimately agrees "that's hard, there's no simple answer" no longer keeps me after clinic. I lose the pleasure of checking in with a patient whom I also happened to have liked as a person. I lose the moments when I tell a colleague who is taking care of my patient in our urgent care, "so, the history on that is...."

Of course it makes sense that patients who have an outsized presence in my professional life can, sometimes, have an outsized presence in my emotional life. On good days, it feels like what I do really matters. Even when I have nothing medical to offer, I sense my longtime patients appreciate a familiar voice. But my patients and I inevitably share an asymmetric intimacy. I learn secrets about them, and I am present at their moments of extreme vulnerability. I might share a fact about me or show them a picture of my daughter being goofy. I can drop a detail into our visit that humanizes me or connects with something in their life. But ultimately, I am there for them.

My profession doesn't have a custom or a process for my grieving. Twice in the last year, I had to stifle the impulse to ask a terminally ill patient I’ve known for years for a selfie with them. I recognized, even as the thought occurred, that the request was inappropriate, that it blurred a line. Reflecting since, I realize I just wanted something by which to remember them, to recall our connection, shared jokes and disappointments, our relationship.

**

Dr. Kurland is Director of the Emergency Department at Zuni Comprehensive Community Health Center in New Mexico.

Monday, May 17, 2021

AAFP updates recommendations on lung cancer screening

- Sarah Coles, MD and Alexis Vosooney, MD

Recently the U.S. Preventive Services Task Force (USPSTF) updated its recommendation statement on lung cancer screening, lowering the age to start screening and pack year eligibility. The USPSTF now recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 50 to 80 years who have at least a 20 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should stop once a person has not smoked for 15 years or has health issues that limit life expectancy or the ability and desire to have curative lung surgery.

The American Academy of Family Physicians (AAFP) disagreed with the previous (2013) USPSTF recommendation, which was based predominantly on a single trial, the National Lung Screening Trial (NLST). At that time, the AAFP concluded there was insufficient evidence to recommend for or against LDCT lung cancer screening. The AAFP had concerns about the generalizability of the trial (conducted in a large, academic medical center with a population that was younger and more likely to be current smokers than in the general population), the uncertain magnitude of benefit and the potential for harm, overdiagnosis, and uncertainty about optimal screening intervals. Championing the science, the AAFP highlighted concerns about this recommendation and called for additional research, and that challenge was met.

The new evidence review commissioned by the USPSTF includes seven randomized clinical trials (RCTs) of lung cancer screening with LDCT. NLST and the NELSON trial were the largest and the only trials powered to detect lung cancer mortality benefits to screening. Screening resulted in a difference in lung cancer specific mortality of 0.46%. The relative risk reduction for lung cancer mortality is 16-20%. The NELSON trial demonstrated a number needed to screen (NNS) to prevent one lung cancer death of 130 over 10 years of follow up. These improvements in cancer specific mortality are comparable or greater than other recommended screening tests such as breast cancer screening. A modeling study was also performed comparing screening strategies with different starting and stopping ages, frequency, and eligibility criteria. This analysis suggested that the 2021 USPSTF recommendation would result in more benefit than the 2013 recommendation.

Among studies conducted in the US, rates of overdiagnosis and false positives varied widely, with false positives generally declining with each screening round. In NLST, false positives led to invasive procedures and complications were rare. Use of current nodule management strategies such as Lung-RADS can reduce false positive rates and decrease unnecessary invasive procedures and improve the balance of benefit and harms.

After a robust discussion that included the strength of evidence, the risk of harm, the likelihood and magnitude of benefit, and the impact on health equity, the AAFP’s Commission on Health of the Public and Science agreed that there was sufficient data from clinical trials and observational studies to recommend screening and supported the USPSTF recommendation.

Further research is needed into harms of screening, particularly rates and consequences of overdiagnosis, unnecessary procedures, and barriers to implementation in community settings. None of the included studies in the USPSTF systematic review provided estimates for the lifetime risk of radiation-induced cancers or fatal cancers from continuing annual screening up to age 80. The general population is less likely to benefit than the study participants in NSLT and NELSON trials because of higher risks of other causes of death, such as heart disease. These trials were mainly conducted at large, academic medical centers with access to case management, specialized radiologists, and surgical expertise. Community based practices may not have the same resources to navigate positive results and follow up needs. The studies had poor racial and gender diversity, and the impact of screening on health equity for communities of color is unknown.

As with all screening recommendations, family physicians should discuss the potential benefits and risks of harm with each patient when considering lung cancer screening. The National Cancer Institute has developed resources to help clinicians with these discussions. While lung cancer screening does appear to help, smoking cessation remains key to reducing lung cancer deaths.

Monday, May 10, 2021

Introducing the 2021-2022 AFP Jay Siwek Medical Editing Fellow: Dr. Jorge Finke

 - Jennifer Middleton, MD, MPH

It's my pleasure to introduce our 2021-2022 Jay Siwek Medical Editing Fellow, Dr. Jorge Finke, whose fellowship year will begin June 1. Here are some highlights from a recent interview:

1. Tell us a little about yourself. 

I was born in the Dominican Republic and moved to the U.S. at the age of four. I grew up in a small working-class city north of Boston, which inspired me to focus my medical career on community medicine. I graduated from college and medical school in Massachusetts and decided to stay for family medicine residency at UMass. As a new attending, I’ve been working at a community health center in Boston which provides care to underserved patients. I love teaching and mentoring students at all stages of their education, so I hope I can continue integrating those opportunities in my career. 

 2. What got you interested in medical writing and editing? 

My residency program placed a strong emphasis on the practice of evidence-based medicine. I had the realization that much of what we we learn and are trained to do in medical school is not always founded in evidence, and that evidence is always changing. This inspired me to continually ask questions about the “why” and think more critically about how we practice. It led me to read more journal articles and have active conversations with my colleagues around practice-changing information I would find. A faculty member offered me the opportunity to write a “Cochrane for Clinicians” article for American Family Physician, which gave me a taste of medical writing, and I’ve been looking for more ways to get involved ever since. 

 3. What are you hoping to get out of the fellowship? 

I’m excited to be a part of the editorial team. Working with experienced editors will help me learn to better evaluate and appraise manuscripts, which will hopefully, in turn, make me a better editor and writer. I’ll be constantly exposed to new advances in clinical practice that will help me both in my day-to-day care of patients but also allow me to share these insights with my colleagues. Through this fellowship, I hope to learn and grow as both a clinician and teacher, which will give me greater career range and help me become a more well-rounded physician. 

 4. Is there anything else you'd like AFP readers to know about you? 

Outside of work, I’m always looking to try new things and pick up new hobbies. I enjoy the creativity of trying new recipes and cooking for my wife who is my personal taste-tester. I enjoy sailing in Boston during the summers. I visit my family in the Dominican Republic when I can and enjoy relaxing at the beaches there. Within my work, I am passionate about caring for underserved populations, addiction medicine, and medical education.

Monday, May 3, 2021

Understanding and managing long COVID

 - Kenny Lin, MD, MPH

Although 90% of non-hospitalized patents with acute COVID-19 have complete symptom resolution by 21 days, the rest suffer from a wide range of nonspecific symptoms for weeks to months, collectively known as post-acute sequelae of SARS-CoV-2 (PASC) or long COVID. An AFP editorial on long COVID published last December advised that family physicians perform limited testing in these patients guided by the clinical assessment; for those with normal results, "recommended management ... consists of emotional support, ongoing monitoring, symptomatic treatment (e.g., acetaminophen for fever), and attention to comorbidities." A virtual workshop convened that month by the National Institutes of Health (NIH) noted that long COVID symptoms "have been reported among persons of all ages," including children, and that this syndrome potentially represents an enormous chronic health burden; since at least 32 million people have had COVID-19 in the U.S. alone, 3 million or more could be affected. 

Evidence gaps highlighted by workshop speakers included the epidemiology, clinical spectrum, and natural history, and pathophysiology of long COVID. In January, Dr. Francis Collins announced that the NIH would use a Congressional appropriation of $1.15 billion over four years to fund a PASC Initiative to support "a combination of ongoing and new research studies and the creation of core resources ... to help us understand the long-term effects of SARS-CoV-2 infection, and how we may be able to prevent and treat these effects moving forward." 

Two recent electronic health record studies have advanced our understanding of long COVID in the U.S. A cohort study of more than 73,000 non-hospitalized COVID-19 survivors in the Veterans Health Administration (VHA) found that compared to non-hospitalized VHA users who did not have COVID-19, the former group had an increased risk of death beyond the first 30 days of illness (HR 1.59, 95% CI 1.46-1.73) and were more likely to seek outpatient care and have more frequent visits. In addition, the study found an excess burden of respiratory conditions, nervous system conditions, mental health disorders, metabolic disorders, cardiovascular conditions, and gastrointestinal disorders in the COVID-19 cohort at 6 months of follow-up. Similarly, a Centers for Disease Control and Prevention (CDC) study of 3,171 non-hospitalized adults at Kaiser Permanente Georgia who had a positive SARS-CoV-2 polymerase chain reaction result from April to September 2020 found that 69% attended one or more outpatient visits 28 to 180 days after their COVID-19 diagnosis. 68% of these patients had visits for a new primary diagnosis; although most visits were with primary care clinicians, 38% visited with a new specialist. The volume of visits for symptoms potentially related to COVID-19 (throat or chest pain, shortness of breath, malaise and fatigue) declined after 60 days, but some continued through 120 to 180 days.

In a perspective paper in The Milbank Quarterly, Dr. Zackary Berger and colleagues observed that primary care clinicians will play important roles in providing and coordinating care for vulnerable patients with long COVID. The racial health disparities seen in acute COVID-19 will likely translate into similar disparities in long COVID, exacerbated by structural barriers to health and care access (economic, geographical, housing and segregation, and occupational) that could impede recovery. The authors recommended boosting health system resources devoted to primary care and addressing the root causes of inequity though actions to mitigate the social determinants of health. Whether the upcoming CDC guidelines on long COVID heed these sensible recommendations remains to be seen.

Monday, April 26, 2021

What is the connection between eczema and learning disabilities?

 - Jennifer Middleton, MD, MPH

A cross-sectional study of over 2000 children with eczema in the United States found that their self-reported severity of eczema correlated with the diagnosis of a learning disability.

This study's researchers reviewed data from the Pediatric Eczema Elective Registry (PEER) of over 2000 children with eczema who had been enrolled for at least 10 years. PEER was initially designed as a post-marketing study to assess the long-term risk of malignancy in children who received pimecrolimus to treat their eczema. While these children were followed in the registry, data on multiple other factors, including school functioning and additional diagnoses, were collected. The average age of eczema diagnosis among participants was 9 months, the average age at 10-year follow-up was 16.1 years, and 53.8% of participants were girls. 44.9% of participants identified as Black, and 53.8% of participants identified as white. Severity of eczema/atopic dermatitis (AD) was determined according to the Patient-Oriented Eczema Measure (POEM). The researchers found that: 

In multivariable logistic regression models adjusted for sex, age, race/ethnicity, annual household income, age of AD onset, family history of AD, and comorbid conditions, participants with mild AD (odds ratio [OR], 1.72; 95% CI, 1.11-2.67), moderate AD (OR, 2.09; 95% CI, 1.32-3.30), and severe to very severe AD (OR, 3.10; 95% CI, 1.55-6.19) on the POEM were all significantly more likely to have reported [a diagnosed] LD than those with clear or almost clear skin.

The authors are quick to point out that "causality cannot be inferred from the findings of the present study," though it's also not implausible. The itching and scaling from chronic eczema can decrease quality of life for both adults and children. Since difficulties with focusing attention can be a component of learning disabilities, it's possible that children distracted by their eczema symptoms might more easily meet criteria for an LD diagnosis. It may also be only correlation, since both learning disabilities and eczema are diagnosed more often in children of lower socioeconomic status. And, no study to date has assessed whether successful treatment for eczema improves LD symptoms.

Despite these unanswered questions, taking the time to assess how our young patients' eczema is impacting their quality of life (QOL) seems reasonable. Educating families about eczema management may improve pediatric patients' QOL, and following QOL scores may provide another metric to track the degree of treatment success. Since early diagnosis of learning disabilities leads to improved outcomes, remaining vigilant for signs of an LD in children with eczema may be beneficial. 

If you'd like to read more, this 2020 article provides an overview on "Atopic Dermatitis: Diagnosis and Treatment," and this 2019 article reviews "Specific Learning Disabilities: The Family Physician's Role."

Tuesday, April 20, 2021

Interpretation and use of COVID-19 diagnostic tests: key resources

 - Kenny Lin, MD, MPH

Despite the recent decision by U.S. health agencies to pause administration of the Johnson & Johnson vaccine to investigate rare blood clots in several young women, the pace of vaccinations against SARS-CoV-2 is accelerating. The Centers for Disease Control and Prevention reports that more than half of U.S. adults have now received at least one dose, and 33% are fully vaccinated. (In patients age 65 years and older, the respective percentages are 80% and 65%.) However, with more than 50,000 new cases being reported every day, including a small number of breakthrough infections, the need for COVID-19 testing is not going to go away any time soon.

A few weeks ago, the U.S. Food and Drug Administration announced that it had authorized several COVID-19 tests for over-the-counter use for serial screening of asymptomatic persons. Soon to arrive in national chain pharmacies and other stores, these tests and others - mostly of the rapid antigen variety - will cost between $10 and $110. A clinical and cost-effectiveness analysis in the Annals of Internal Medicine estimated that a weekly home-based antigen testing program could avert 2.8 million infections and 15,700 deaths in the U.S. over a 60-day time frame, at a cost of less than $8000 per infection averted. Not only could frequent testing make residences and workplaces safer, it could also improve the safety of in-person K-12 schooling and summer camps, since children younger than age 16 are not yet eligible to receive any of the vaccines.

The April 15 issue of AFP includes an article by Dr. William Nettleton that discusses several common questions and answers about SARS-CoV-2 diagnostic test interpretation

How Do Test Characteristics Such as Sensitivity, Specificity, and Percent Agreement Inform SARS-CoV-2 Diagnostic Test Interpretation?

How Should Clinicians Counsel Patients about Serologic SARS-CoV-2 Test Results?

In addition to describing key features of molecular and antigen diagnostic tests, the article includes a useful leaf plot figure that allows clinicians to translate pretest to posttest probability of COVID-19 infection based on a positive or negative test result and the test's sensitivity and specificity.

Family physicians who need a quick refresher on clinical probability formulas and related conceptual issues can read a recent article in BMJ Evidence-Based Medicine. Those seeking a more in-depth discussion of COVID-19 test use and clinical scenarios may consult an evidence-based review that I co-authored in the Journal of the American Board of Family Medicine. Notably, we observed: "Often lost when testing is encouraged is that testing does not by itself confer health benefits. Rather, testing is useful to the extent it forms a critical link to subsequent medical or public health interventions." Although access to COVID-19 testing is absolutely necessary for an effective pandemic response, it is not sufficient in the absence of equitable interventions to support behaviors that prevent viral transmission (e.g., paid leave to support self-isolation and quarantine, laws requiring mask use in crowded indoor spaces). Finally, the American Academy of Family Physicians has a comprehensive guide to COVID-19 testing on its website.

Monday, April 12, 2021

Physician losses during COVID-19: necessary next steps

 - Jennifer Middleton, MD, MPH

As we pass the one-year mark of the COVID-19 pandemic, let us pause to grieve the colleagues and teammates we have lost. 

Over 3,600 healthcare workers in the United States have died from COVID-19 according to "Lost on the Frontline," a year-long investigation by The Guardian and Kaiser Health Network (KHN). Dr. Lin tweeted last week about this project, which identified 17% of these deaths as physicians. Those lost included Dr. Frank Gabrin, an Emergency Medicine physician in New York City, and Dr. Susan Moore, a pediatrician in Carmel, Indiana. Dr. Moore, who was Black, highlighted in her final days the endemic racism in healthcare that she, too, experienced; the pandemic's greater toll among Black and brown communities is reflected in the "Lost on the Frontline" statistics. Also unsurprisingly,

[t]he yearlong series of investigative reports found that many of these deaths could have been prevented. Widespread shortages of masks and other personal protective gear, a lack of covid testing, weak contact tracing, inconsistent mask guidance by politicians, missteps by employers and lax enforcement of workplace safety rules by government regulators all contributed to the increased risk faced by health care workers. Studies show that health care workers were more than three times as likely to contract covid as the general public.

These failures have further compounded the mental health burden carried by many physicians during the pandemic. These burdens have claimed some of our peers' lives. The "Lost on the Frontline" project's numbers do not include physicians who have completed suicide, such as Dr. Lorna Breen; given pre-pandemic estimates that one physician a day commits suicide in the United States, at least another 300-400 physician lives need to be added to the "Lost on the Frontline" tally.

The April 1 issue of AFP includes this article on "The Suicidal Patient: Evaluation and Management," and its tenets apply equally to caring for our physician-patients. As family physicians, our colleagues are often also our patients, and we owe them compassionate, discreet, accessible mental health care. With our generalist approach, we can be leaders in advocating for physician wellness in our health systems and training centers. We can contribute to an environment that recognizes and honors our struggles instead of silencing and stigmatizing them. 

The AAFP has a website for COVID-19: Physician Well-Being with resources relevant to all specialties. The American Psychiatric Association's Physician Wellbeing Resources site includes both personal and organizational mental health interventions. The American Medical Association also has a site with several resources to help promote physician wellness. Let's lead the way, family physicians, in building systems and relationships that care for each other the way we all deserve.

If you or someone you know is considering suicide, call Doctor Lifeline (1-888-409-0141), the National Suicide Prevention Lifeline (1-800-273-8255); en Espanol (1-888-628-9454); TTY users, use your prefered services or dial 711 then 1-800-273-8255; go to https://suicidepreventionlifeline.org; or text HOME to 741741.

Monday, April 5, 2021

Premature adoption of 3D mammography threatens study that aims to prove its value

 - Kenny Lin, MD, MPH

Although digital breast tomosynthesis (DBT; 3D mammography) was approved by the U.S. Food and Drug Administration a decade ago and has since been rapidly adopted by breast imaging centers, no studies have shown that it is more beneficial or less harmful for breast cancer screening than traditional digital mammography. In a Diagnostic Tests review in the April 1 issue of AFP, Drs. Kathleen Barry and Chelsea Evans noted that DBT offers a "modestly increased cancer detection rate" and lower recall rate, but also costs about 40% more per test and exposes patients to a higher dose of radiation. It is unclear if additional cancers detected by DBT would have eventually become symptomatic, and "no studies have evaluated mortality as an outcome in women screened with DBT compared with digital mammography."

To address these important questions, in 2017 the U.S. National Cancer Institute (NCI) and the Canadian Cancer Trials Group launched a $100 million randomized trial, TMIST (Tomosynthesis Mammographic Imaging Screening Trial). With a planned enrollment of 165,000 women at 100 North American clinical sites, TMIST was designed to compare the incidence of advanced breast cancer after 4.5 years of follow up in women receiving either digital mammography or DBT. However, by early 2020, investigators had managed to enroll fewer than 23,000 women and were forced to expand to include overseas sites in Asia and Europe. The reason, according to an article in Medscape: already convinced that DBT was a superior technology, large numbers of U.S. and Canadian radiologists were declining to participate. Then the COVID-19 pandemic hit, further hindering recruitment efforts.

Meanwhile, a national study of Breast Cancer Surveillance Consortium sites found substantial racial and ethnic disparities in DBT access, with Black, Asian, and Hispanic women significantly less likely than White women to be screened at a facility with DBT or to receive DBT if the facility offered both DBT and digital mammography. If DBT is truly superior to digital mammography, this apparent disadvantage may worsen existing disparities in breast cancer outcomes. If it isn't, then widespread DBT use is unnecessary and wasteful.

After the NCI director suggested in the fall of 2020 that the "feasibility and relevance" of TMIST was in jeopardy, a working group was formed to reevaluate the trial. In its report released last month, the group recommended that the trial continue, but with protocol revisions that included reducing the sample size to 102,000 and developing specific targets for enrolling women from racial and ethnic minority groups. Unlike European trials that are also evaluating DBT, the group noted, TMIST is the only study that is representative of the U.S. population, includes women younger than age 50, and includes multiple rounds of screening.

In a 2019 commentary, Drs. Joy Melnikow and Joshua Fenton observed of DBT:

Diffusion of medical technology ahead of definitive evidence is common in the United States. ... Societal attitudes that place high value on innovation and technology create a fertile environment for the rapid adoption of novel but unproven interventions. ... When the evidence from randomized clinical trials catches up, interventions shown to add little value to previous approaches are often already embedded in practice, widely covered by health insurance (sometimes by mandate), and difficult to withdraw.

Initial findings from TMIST will be available in 2027 at the earliest if investigators can reach its lower enrollment goal. As radiology facilities across the country continue to "upgrade" from digital mammography to DBT and more states mandate insurance coverage of the newer but unproven technology, it remains to be seen whether this study's findings will have any effects on clinical practice.

Monday, March 29, 2021

Answering questions about AstraZeneca's COVID-19 vaccine

 - Jennifer Middleton, MD, MPH

The recent stream of headlines regarding the AstraZeneca COVID-19 vaccine may prompt your patients to ask about its safety and availability.

 A week ago, AstraZeneca reported that its COVID-19 vaccine, after interim analysis of United States (US) trial data, was 79% effective at preventing symptomatic COVID-19 and 100% effective at preventing COVID-19-related hospitalizations and death. This statement was met with skepticism, however, by the US National Institute of Allergy and Infectious Diseases (NIAID), which released a statement that it had "expressed concern" with AstraZeneca regarding the veracity of their data. NIAID reportedly also sent a private letter to AstraZeneca accusing them of "cherry-picking" their data and criticizing them for risking its credibility. The next day, AstraZeneca released updated "primary analysis" data from its US trials demonstrating 76% effectiveness at preventing symptomatic COVID-19 and 100% effectiveness at preventing COVID-19-related hospitalizations and death. 

It's unclear why AstraZeneca publicly reported interim data, "when final results were so close;" it's also unclear why the NIAID made their concerns public when, typically, these "back and forth" concerns are shared "behind the curtain." The NY Times reported late last week that "the brushback from federal officials appeared to reflect high levels of distrust between American regulators and AstraZeneca." 

AstraZeneca vaccine's reputation problems precede this latest incident. Its multinational phase 2 and 3 trials last year were plagued by dosing discrepancies and communication failures with the US Food and Drug Administration (FDA). Recent reports of thrombocytopenia, disseminated intravascular coagulation (DIC), and cerebral venous sinus thrombosis (CVST) following vaccination in Europe, although rare, led some countries to temporarily halt its distribution until the World Health Organization (WHO) and the European Medicines Agency (EMA) asserted its overall safety earlier this month. 

Despite evidence that this vaccine is safe and effective, along with its successful use around the world, lay press coverage of these events may be lowering our patients' willingness to get vaccinated. Family physicians can expect their patients to ask about this controversy and, potentially, express concerns about getting vaccinated. Being prepared to listen to our patients' concerns and address them without judgment may help reduce vaccine hesitancy. For those patients in the US with continued reservations about the AstraZeneca vaccine, it may also help to inform them that they are unlikely to receive it; sufficient COVID-19 vaccine supply from Pfizer, Moderna, and Johnson & Johnson has already been procured to vaccinate the entire US population by late spring. 

If you'd like to read more, the AFP By Topic collection on Coronavirus Disease 2019 (COVID-19) continues to be regularly updated, and the Centers for Disease Control and Prevention (CDC) website includes regularly updated information regarding all of the COVID-19 vaccines currently available in the US.