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. 

Increasing clarity about benefits and harms of screening for diabetes

 - Kenny Lin, MD, MPH

Affecting about 6 percent of pregnancies in the United States, gestational diabetes increases risks of preeclampsia, shoulder dystocia, and macrosomia, and is associated with a 10-fold greater risk of developing type 2 diabetes mellitus in later life. In a recent draft statement, the U.S. Preventive Services Task Force (USPSTF) affirmed its previous recommendation to screen pregnant persons for gestational diabetes at or after 24 weeks of gestation. Historically, there have been two screening options: a non-fasting 50 gram oral glucose challenge test followed by a fasting 100 gram glucose tolerance test if the first test result exceeds a threshold value (typically 130-140 mg/dL), or a single fasting 75 gram glucose tolerance test. Although two-step screening is more commonly used in the U.S., until recently the comparative outcomes of these approaches were uncertain. This evidence gap is important because the diagnosis is associated with increased psychological and emotional burden; labeling more persons as having gestational diabetes with the one-step screening approach would only be justified if doing so resulted in better pregnancy outcomes than the two-step approach.

A pragmatic, randomized trial recently compared the one-step and two-step approaches in more than 23,000 women who received prenatal care at Kaiser Permanente Northwest and Kaiser Permanente Hawaii. Researchers evaluated five primary outcomes: "diagnosis of gestational diabetes, large-for-gestational-age infants, a perinatal composite outcome (stillbirth, neonatal death, shoulder dystocia, bone fracture, or any arm or hand nerve palsy related to birth injury), gestational hypertension or preeclampsia, and primary cesarean section." As expected, a diagnosis of gestational diabetes was more common in participants who underwent one-step screening (16.5%) compared to the two-step approach (8.5%). However, intention-to-treat analyses found no statistically significant differences in any perinatal or maternal complications. Although the trial was not designed to measure potential long-term benefits of post-pregnancy risk-reduction strategies to prevent type 2 diabetes, the results suggest that the two-step approach produces equivalent benefits, and fewer harms, than the one-step approach.

The USPSTF is also updating its recommendation on screening for prediabetes and type 2 diabetes in nonpregnant adults. Compared to its 2015 statement, which recommends screening overweight or obese adults between the ages of 40 and 70, the updated draft statement lowers the age range to include persons aged 35 to 39 years. Although the focus of the Task Force's old and new diabetes screening guidelines is identifying persons with prediabetes in order to prevent them from developing diabetes and its complications, the utility of the term "prediabetes" is controversial, as Dr. Jennifer Middleton discussed in a previous AFP Community Blog post. In older adults, prediabetes is extremely common. In a prospective cohort study of community-dwelling adults aged 71 to 90 years, 73 percent met one or both of the diagnostic criteria for prediabetes (hemoglobin A1c level of 5.7% to 6.4%, impaired fasting glucose of 100-125 mg/dL). After 6.5 years of follow-up, persons with prediabetes at baseline were substantially more likely to revert to normoglycemia or to die than to progress to diabetes. Based on these findings, stopping diabetes screening after age 70 will avoid overdiagnosis and unnecessary treatment.

Subduing influenza in the age of COVID-19

 - Jennifer Middleton, MD, MPH

The 2020-2021 influenza season has been historically mild, which public health experts have attributed to the behaviors surrounding COVID-19 prevention: mask-wearing, social distancing, and self-quarantining. While we are hopefully past the point of lockdowns, perhaps the COVID-19 pandemic does have lessons to offer regarding future influenza seasons.

The Centers for Disease Control and Prevention (CDC) notes that influenza activity remains "unusually low" across the United States (US). All 50 states are currently reporting "minimal" levels of influenza activity in contrast to this time last year, when over half of states reported "high" levels of influenza activity:

The Influenza Hospitalization Surveillance Network (FluSurv-NET) conducts population-based surveillance for laboratory-confirmed influenza-related hospitalizations in select counties in 14 states and represents approximately 9% of the U.S. population.... Between October 1, 2020, and March 6, 2021, FluSurv-NET sites...reported...an overall cumulative hospitalization rate of 0.7 per 100,000 population. This is much lower than average for this point in the season and lower than rates for any season since routine data collection began in 2005, including the low severity 2011-12 season.  

Fears of a COVID-19 and influenza "twindemic" overwhelming the US healthcare system have, thankfully, not materialized. (Sadly, though, COVID-19 proved to be more than capable of overwhelming healthcare systems on its own.) It's likely that the same behaviors instituted to decrease SARS-CoV-2 transmission were even more effective at curtailing the far less contagious influenza viruses. 

Continued mask-wearing could dampen the severity of future influenza seasons, but, post-COVID-19-pandemic, will people still be willing to wear masks? It's not entirely implausible:

Part of why it’s possible that masks could become a more long-term fixture in the U.S. is because elsewhere in the world, previous pandemics had the same effect. In 2003, the SARS outbreaks in parts of Asia, including China, Taiwan and South Korea, required mask-wearing....In between the pandemics, consistent mask-wearing in parts of Asia evolved into an occasional polite choice someone might make if they had a cold or cough and were out in public. 

Wearing a mask and keeping 6 feet away from others would be reasonable behaviors for all people to continue who need to leave home when ill, not only to decrease the burden from endemic COVID-19 but also influenza. Whether those behaviors persist, and precisely how they might affect the 2021-2022 influenza season, remains to be seen.

We'll continue to regularly update the AFP By Topics on both Influenza and Coronavirus Disease 2019 (COVID-19) as the 2020-2021 influenza season, and hopefully the COVID-19 pandemic, begin to wind down.

Can Choosing Wisely prevent acute low back pain from becoming chronic?

 - Kenny Lin, MD, MPH

More than a dozen Choosing Wisely campaign recommendations concern what not to do for patients with acute low back pain. Based on a clinical practice guideline from the American College of Physicians, the American Society of Anesthesiologists and several other groups recommend avoiding imaging studies within the first six weeks in patients without red flags or specific clinical indications. The American Academy of Orthopedic Surgeons and the American Academy of Physical Medicine and Rehabilitation (AAPMR) advise avoiding opioids for these patients unless other alternatives have not provided pain relief. The AAPMR and the North American Spine Society discourage bed rest as treatment for acute low back pain. These recommendations are intended to reduce downstream harms and costs: for example, a spurious finding on MRI could lead to unnecessary surgery; use of opioids could lead to physical dependence and opioid use disorder; bed rest and avoidance of physical activity could increase the risk of long-term disability.

Can guideline-discordant care for patients with acute low back pain increase the risk of progression to chronic low back pain? In an inception cohort study published in JAMA Network Open, researchers enrolled 5233 adults with acute low back pain from 77 U.S. primary care practices, assessed their baseline risk of transition to chronic pain using the Subgroups for Targeted Treatment (STarT) Back prognostic tool, and followed them for 6 months. 32% of participants met clinical criteria for chronic low back pain at the study's end. Characteristics associated with transition to chronic pain included obesity (adjusted odds ratio, 1.52), tobacco use (aOR, 1.56), severe baseline disability (aOR, 1.82), and a depression and/or anxiety diagnosis (aOR, 1.66). Researchers also examined associations between chronic low back pain and inappropriate care processes within 21 days of the initial visit: 1) any opioid prescriptions, or benzodiazepines or systemic steroids prescribed without an NSAID or skeletal muscle relaxant; 2) diagnostic imaging; 3) medical subspecialty referral for back pain. Compared to the 52% of participants who received none of these, patients with 1, 2, or 3 inappropriate care processes were 1.39, 1.88, and 2.16 times more likely to develop chronic low back pain after controlling for clinical characteristics.

Although adherence to Choosing Wisely recommendations was associated with a lower risk of patients developing chronic low back pain in this study, it is disappointing that almost half of them received at least some inappropriate care. Is care for back pain an outlier, or does it reflect national trends? A recent cross-sectional study examined the use of 32 low-value health services in Medicare fee-for-service beneficiaries. The study found modest progress from 2014 to 2018 in the percentage of persons receiving any low-value service (declined from 36.3% to 33.6%), number of low-value services per 1000 persons (declined from 678 to 633), and spending per 1000 persons on low-value care (declined from $52,766 to $46,922). Three services comprised about two-thirds of low-value care: preoperative laboratory testing, opioids for back pain, and antibiotics for upper respiratory infections. While preoperative testing decreased during the study period, opioid and antibiotic prescribing both increased.

Since the campaign's inception in 2012, Choosing Wisely recommendations have been widely disseminated in AFP, FPM (formerly Family Practice Management), and other family medicine journals. The American Academy of Family Physicians periodically updates and adds new "don't do" recommendations, most recently in 2018. Other studies have recognized that clinicians in underserved or "safety net" practices are as likely to provide low-value care as clinicians in better resourced settings. A 2018 AFP editorial by Dr. Jennifer Middleton recognized that increasing awareness of best practices is necessary but not sufficient to drive implementation: "For meaningful change to occur, the workflows and systems we operate within must change so that new habits become routine." The Medicare study suggests that workflows and systems have not changed enough in the past decade to undo entrenched low-value practices.

Nutrition disparities during the COVID-19 pandemic

 - Jennifer Middleton, MD, MPH

A large, multi-year study of nutrition habits in France is yielding interesting findings during the COVID-19 pandemic. Behaviors related to nutrition are no exception to the deep-seated health inequities COVID-19 continues to expose.

The Nutri-Net Sante study began in 2009. Study researchers monitor participants using a sophisticated online survey:

[D]ietary intakes are assessed every 6 months as part of the usual cohort follow-up using three non-consecutive 24 [hour] dietary records randomly assigned over two weeks and including two weekdays and one weekend day. These web-based 24 [hour] dietary records have been validated against dietary records filled during an interview with a dietitian and against biomarkers.

In April 2020, during France's nationwide lockdown, the researchers collected data from participants regarding changes in lifestyle habits. While some participants increased their snacking frequency (an otherwise rarity in French culture) and decreased their physical activity, others instead increased their home cooking of nutritious meals and increased their physical activity. The less healthy behaviors correlated with lower socio-economic status (SES), while the more healthy behaviors correlated with higher SES.

Although these findings have yet to be formally peer-reviewed and published, they are consistent with similar studies across the globe (Italy, Poland, China, Latin America). The Centers for Disease Control and Prevention (CDC) recommends "good nutrition" to build resilience during the pandemic; they acknowledge, however, that achieving this aim is challenging for many by also listing resources regarding food insecurity. Google searches related to food insecurity ("food bank," "free food") have increased world-wide since March 2020. "The health disparities in nutrition and obesity correlate closely with the alarming racial and ethnic disparities related to Covid-19." 

During the COVID-19 pandemic, it's more critical than ever that we systematically and universally screen our patients for food insecurity along with other social determinants of health. Several simple screening tools exist, including the AAFP's EveryONE Project's Social Needs Screening Tool. The EveryONE Project website also includes guidance for connecting patients with community resources. This 2018 AFP editorial on "Food Insecurity: How You Can Help Your Patients" also includes a comprehensive list of online tools and resources. 

Post-pandemic, we must support improvements in our social environment that will mitigate long-standing racial biases and provide equitable health for all; this equity cannot be achieved without access to affordable and high-quality nutrition for all persons. The COVID-19 pandemic is a powerful reminder that efforts to improve our patients' health and well-being will always be incomplete if we confine them to the interiors of hospitals, health centers, and physicians' offices.