Wednesday, May 26, 2021

For colorectal cancer screening, 45 is not the new 50

In 2018, when the American Cancer Society (ACS) recommended lowering the age to start screening for colorectal cancer from 50 to 45, I wrote a Medscape commentary explaining why I thought this decision was "premature at best, and at worst will cause more harm than good." I was not alone in my negative assessment of the new guideline. In the Annals of Internal Medicine, Dr. Michael Bretthauer and colleagues noted the absence of clinical study evidence to support the ACS's assumption "that screening will generate the same benefits for persons younger and older than 50 years," and that the 22% increase in incidence rates of colorectal cancer in persons in their 40s from 2000 to 2013 represented an absolute increase of only 1.3 cases per 100,000 person years. Consequently, he argued, "we need to exercise caution when using models rather than direct clinical data to guide health policy decisions affecting millions." In Gastroenterology, Dr. Peter Liang and colleagues observed that the intended consequences of earlier initiation of screening (reducing colorectal cancer morbidity and mortality in younger persons) could be accompanied by unintended consequences such as diverting resources to a lower-risk population, increasing screening disparities, increasing individual and societal costs, and making it more difficult to study the effectiveness of screening in a younger population.

Unlike the U.S. Preventive Services Task Force (USPSTF) guidelines, American Cancer Society guidelines are not directly linked to insurance coverage for preventive services. Nonetheless, a study found that past-year colorectal cancer screening rates in adults aged 45 to 49 years increased from 4.8% immediately prior to the ACS guideline to 11.7% several months after, suggesting that some physicians and patients had begun following the new guidelines. (My own family physician offered colorectal cancer screening after my 45th birthday, but I declined.)

Our understanding of the pathophysiology of colorectal cancer in younger adults is still evolving. A recent analysis of the rising incidence of early-onset colorectal cancer found that an increasing proportion of tumors are carcinoid tumors, which unlike the more common adenocarcinomas are unlikely to be affected or prevented by screening. As Dr. Bretthauer wrote in an accompanying editorial, "the majority of carcinoid tumors identified by screening represent incidental findings with little health benefit from detection. In fact, many may be characterized as overdiagnosed tumors, which by definition increase the burden and harms of screening without eh balance of additional benefit."

Nonetheless, last week the USPSTF formally recommended lowering the age to start routine colorectal cancer screening to 45, based on a modeling study that suggested 22 to 27 "additional life-years gained" per 1000 persons, assuming 100% adherence. I don't distrust the conclusions of all modeling studies; for example, I support the USPSTF's decision to lower the age to start lung cancer screening from 55 to 50 years based on a model, but in that case there were also significant supporting data from randomized controlled trials in the younger age group, which isn't the case for colorectal cancer and now may never be, at least in the United States. (See screening for prostate cancer for an example of why it's critical to not implement widespread screening in primary care before you study whether or not it actually works.)

The bottom line is that both the ACS and now the USPSTF recommendations to start colorectal cancer screening at age 45 are based on epidemiologic data and decision models with a lot of shaky assumptions - the most shaky being that cancers in younger adults behave the same way as those in older adults. If a young patient wants to get screened for colorectal cancer for individual reasons and/or if a health insurer decides that there are long-term benefits to paying for it, that's one thing, but mandating first-dollar coverage for this preventive service requires stronger evidence than we have.

Tuesday, May 25, 2021

More than half of U.S. adults are fully vaccinated against COVID-19

And, just as impressively, nearly half of the entire U.S. population (including children ages 11 and younger, who aren't even eligible to be vaccinated yet) has received at least one dose of the Pfizer, Moderna, or J&J/Janssen vaccines. It's no wonder that new cases, hospitalizations, and deaths have been plummeting across the country. We're not just flattening the curve, we are absolutely crushing it.

The work isn't done, though. We must continue to urge, encourage, and cajole the unvaccinated to get their shots too. This includes members of several state legislatures that have been rushing to ban mask mandates ...

Monday, May 10, 2021

Understanding and managing long COVID

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 American Family Physician 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 upcoming CDC guidelines on long COVID heed these sensible recommendations remains to be seen.


This post first appeared on the AFP Community Blog.

Tuesday, May 4, 2021

We need childhood vaccination to make COVID-19 as rare as chicken pox or the measles

When I was 16 years old, I contracted the chicken pox from my younger sister, who had inadvertently carried the varicella-zoster virus home from a classmate at her middle school. Her symptoms lasted for a few days and were relatively mild, but I was out of school for two full weeks and was thoroughly miserable for most of that time. I developed blisters in my mouth and throat that made it painful to chew and swallow, and after the full-body rash finally cleared, I was left with several permanent keloids (scars) from scratching, one of which needed to be biopsied several years later to make sure that it wasn't skin cancer. Just three years later, an effective varicella vaccine was introduced in the United States and incorporated into the routine childhood immunization schedule. The Centers for Disease Control and Prevention (CDC) estimates that varicella vaccination prevents 9,000 hospitalizations and 100 deaths in the U.S. each year. Even though my infection was not remotely life-threatening, I absolutely would have gotten the vaccine, had it been available, to avoid the illness that I endured.

During my family medicine residency in Lancaster, PA, I gave a presentation on the rubella vaccine, which is the "R" in the MMR vaccine that nearly all U.S. children have received since the 1970s. I say "nearly all" because the Amish communities that my residency program served had historically declined most vaccinations. Although rubella infection can be asymptomatic and usually causes a few days of mild flu-like symptoms and rash in children and adults, it can cause birth defects if a woman contracts it during pregnancy, particularly during the first trimester. From February through May 1991, a widespread rubella outbreak swept through Lancaster and surrounding counties. The CDC identified 94 Amish women who reported a rubella-like illness or had serologic evidence of acute rubella during their pregnancies. Seven women miscarried; of the 87 live births, 7 had possible congenital rubella syndrome (CRS) and 11 had confirmed CRS:

Clinical abnormalities for the 11 infants with CRS included congenital heart disease (nine), deafness (six), purpura (four), long bone radiolucencies (four), cataracts (three), thrombocytopenia (three), hepatosplenomegaly (two), intracranial calcifications (two), encephalitis (one), microcephaly (one), failure to thrive (one), seizures (one), and disseminated intravascular coagulation (one).

Also in the early 1990s, the health department in nearby Philadelphia battled an outbreak of the measles fueled by a fundamentalist religious group (Faith Tabernacle Congregation) that not only did not believe in providing MMR vaccinations, but in any intervention for sick children other than prayers. Although the overall death rate from measles is no greater than 1 in 1000, tragically, four out of 150 infected children in the congregation died, due to a combination of the infection and delayed medical care. Measles outbreaks don't only incur physical and emotional costs; they cause massive public health, medical care, and productivity costs too. As reported in Pediatrics, a 2019 measles outbreak in Clark County, WA that involved only 72 confirmed cases ended up costing $3.4 million, or $47,479 per case, mostly from the public health response, contact tracing, and the need to quarantine more than 800 unvaccinated or inadequately vaccinated exposed persons.

The U.S. Food and Drug Administration is apparently poised to authorize administering the Pfizer COVID-19 vaccine to 12 to 15 year-olds as early as next week, not a moment too soon, as the success of the adult vaccination campaign has dramatically protected older persons to the extent that nearly a quarter of new infections are now occurring in children. Children and young adults are significantly less vulnerable than middle-aged or older adults; the American Academy of Pediatrics estimates that children make up only 1-3% of hospitalizations, and just over 15,000 children have been hospitalized since the start of the pandemic out of 3.8 million infected. It's worth pointing out, though, that these figures are similar to those from measles and chicken pox in the years before routine MMR and varicella vaccination. Drs. Perri Klass and Adam Ratner recently asserted that the widespread acceptance of MMR vaccination in the U.S. is an apt historical comparison to the "ethical obligation [and] practical necessity" of vaccinating children against today's viral pandemic:

Vaccinating children is likely to have benefits both direct (protecting children against rare severe pediatric cases of Covid-19 and postinfectious conditions such as multisystem inflammatory syndrome in children [MIS-C]) and indirect (protecting others by reducing spread). Those “indirect” benefits also reduce the family toll of parental illness, failing economies, and chronic stress. ... So we need to think creatively and empathically about what motivates parents to accept vaccination for their offspring. How do the conversation and the stakes change when children are not themselves at highest risk?

Former CDC Director Tom Frieden's Resolve to Save Lives Initiative has posted a compelling series of case studies on its website on "Epidemics That Didn't Happen," including several countries that, unlike the U.S. and most Western European nations, were able to successfully blunt the impact of COVID-19. A common thread running through many of the other case studies was early recognition of the outbreak and rapid deployment of an effective vaccine to squash the infectious threat before it spread out of control. Obviously, this strategy wasn't feasible against a novel coronavirus in 2019 and most of 2020, but near-universal vaccination can work now to end the pandemic and stop future local outbreaks when and where they occur.