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; 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.