Monday, October 18, 2021

Measuring and minimizing low-value care

 - Kenny Lin, MD, MPH

Hospitals and health systems have often needed to restrict nonemergent care during COVID-19 surges, with mixed effects on patients. Some patients may experience worse outcomes when necessary treatment or surgery is postponed, while others may avoid receiving unnecessary and potentially harmful (low-value) care. Of course, relying on a pandemic to reduce low-value care is not a strategy; at best, it's a blunt instrument that will be discarded when the public health emergency ends. Recent studies of pre-pandemic low-value care have further demonstrated the need for sustainable interventions.

Dr. Ishani Ganguli and colleagues described the use of 41 low-value medical services in a retrospective cohort of more than 11 million Medicare beneficiaries across 556 health systems. They found that the most common services were preoperative laboratory testing, prostate-specific antigen testing in men older than 70 years, and antipsychotic medications in patients with dementia. Characteristics of health systems associated with greater low-value care (based on a composite measure of the 28 most common services) were having a smaller proportion of primary care physicians, a larger proportion of patients of color, no teaching hospital, higher health care spending, and headquarters in the Southern or Western U.S.

Another recent study of Medicare claims data examined the prevalence and costs of hospital-acquired conditions and patient safety indicator events associated with a selection of low-value inpatient procedures. The investigators identified 231 hospital-acquired conditions and 1,764 patient safety indicator events associated with these procedures from 2016 to 2018, resulting in $3.16 million and $26.7 million in additional health care costs, respectively. For example, hospital-acquired conditions occurring during an admission for percutaneous coronary intervention extended length of stay by an average of 17.5 days and increased the cost of hospitalization by $22,000.

The Cochrane Library has created a special collection of systematic reviews on resource-intensive interventions "for which there is high or moderate certainty evidence that they confer clinically small or no effects, and for which there is some evidence of harm to patients." Examples include preoperative testing for cataract surgery, percutaneous vertebroplasty for vertebral compression fractures, and intensive follow-up strategies after treatment of non-metastatic colorectal cancer.

As Dr. Jennifer Middleton pointed out in a previous AFP editorial, changing physician behavior to minimize low-value care requires creating new workflows and systems of care. A systematic review of 131 articles on Choosing Wisely interventions in the U.S. through June 2019 found that the most effective interventions target clinicians rather than patients, are active rather than passive, and include multiple components. The type of low-value service targeted did not affect outcomes. Components of effective clinician-focused interventions included behavioral nudges, feedback / report cards, clinical decision support, electronic health record enhancements, clinician champions, education and academic detailing, and creating new clinical pathways.

Monday, October 11, 2021

The malaria vaccine's lessons for COVID-19

 - Jennifer Middleton, MD, MPH

Last week, the World Health Organization (WHO) endorsed the use of RTS,S (Mosquirix), a vaccine against malaria which targets Plasmodium falciparum in its sporozite phase. Mosquirix, given in 4 doses between ages 5 months and 3 years, is the first vaccine ever developed against a parasite. Plasmodium falciparum's range is limited to Africa, and the distribution of RTS,S will be appropriately prioritized to areas of greatest need there

RTS,S decreases the risk of severe malaria by 50% in the first year, though its effectiveness wanes to near zero after 3-4 years. Combining RTS,S with seasonal chemoprophylaxis further improves outcomes:

There were 305 events of uncomplicated clinical malaria per 1000 person-years at risk in the chemoprevention-alone group, 278 events per 1000 person-years in the vaccine-alone group, and 113 events per 1000 person-years in the combination group. The hazard ratio for the protective efficacy of RTS,S/AS01E as compared with chemoprevention was 0.92 (95% confidence interval [CI], 0.84 to 1.01), which excluded the prespecified noninferiority margin of 1.20.

Worldwide, malaria afflicts over 220 million people a year; in Africa, it kills an estimated 400,000 persons a year. Children bear its brunt, with 67% of malaria deaths occurring in children under the age of 5 years, and it causes profound morbidity in those who survive (and are often repeatedly reinfected). RTS,S will not singlehandedly eliminate malaria, but, in combination with bed nets and chemoprophylaxis, it could help prevent over 5 million cases of malaria - and over 23,000 child deaths - a year. 

RTS,S and the COVID-19 vaccine share some interesting parallels. The COVID-19 vaccines are also not 100% effective at preventing COVID-19 disease, but they have still saved hundreds of thousands of lives since their introduction as well as reducing the morbidities associated with COVID-19 infection. In combination with face masks and social distancing, the COVID-19 vaccines can provide a path out of the pandemic. Prioritizing COVID-19 vaccine supply to regions of the world still waiting for their first doses (instead of focusing on boosters for those already vaccinated) could maximize their life-saving capacity and reduce the risk of further viral mutation. Viewing these infectious diseases as complex, global challenges that require a multifactorial approach could lead to more effective collaboration, cohesive solutions, and more lives saved. 

In the meantime, we need to keep recommending COVID-19 vaccination as well as discuss preventive measures with patients planning travel to malaria-endemic regions. This AFP article on "Prevention of Malaria in Travelers" provides an overview of medications, insect repellents, and bed nets, and the Centers for Disease Control and Prevention (CDC) has additional information on malaria diagnosis and treatment. The AFP By Topic on Travel Medicine also includes this article on pretravel consultation along with a wealth of patient education handouts.

Monday, October 4, 2021

What we now know about multisystem inflammatory syndrome in children

 - Kenny Lin, MD, MPH

In May 2020, a previous AFP Community Blog post described an emerging COVID-19 associated, Kawasaki disease-like syndrome that became known as multisystem inflammatory syndrome in children (MIS-C). (The Centers for Disease Control and Prevention later identified a similar inflammatory syndrome in adults, MIS-A.) Over the past year, as family physicians, pediatricians, and children's hospitals have gained experience with treating patients with MIS-C, we now know more about differentiating it from Kawasaki disease and managing its major complications. A review article by Drs. John Darby and Jennifer Jackson in the September issue of AFP provided an overview and comparison of Kawasaki disease and MIS-C. Although Kawasaki disease primarily occurs in toddlers, MIS-C has been observed in patients from one week to 20 years of age, with a median age of 7 to 9 years. In the U.S., Hispanic and non-Hispanic Black children have been disproportionately affected by MIS-C, comprising 62% of all cases. Vomiting, diarrhea, and abdominal pain occur in 80% of patients, while neurocognitive symptoms affect about 20%. Additional symptoms of MIS-C can include hypotension secondary to cardiac dysfunction and systemic vasodilation.

Two observational studies of patients with MIS-C published in June 2021 added to the knowledge base but did not definitively identify the most appropriate treatment. A propensity-score matched analysis of 518 patients admitted to U.S. hospitals for MIS-C between March 15 and October 31, 2020 found that initial treatment with intravenous immune globulin (IVIG) plus glucocorticoids, compared to IVIG alone, was associated with a reduced risk of new or persistent cardiovascular dysfunction (a composite outcome of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2 of admission. In contrast, an international cohort study of 614 children with suspected MIS-C from 32 countries treated from June 2020 through February 2021 found no differences in a composite outcome of inotropic support or mechanical ventilation by day 2 or later between children who received IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone.

A longitudinal cohort study of 50 patients admitted to a single U.S. medical center between April and June 2020 reported outcomes of MIS-C at 6 months. 31 patients required intensive care, and 33 developed left ventricular dysfunction, coronary dilation, or aneurysms. The mean length of stay was 5 days. After two weeks, only 9 patients had persistent ventricular dysfunction or other coronary abnormalities, though nearly half reported fatigue with ordinary activities. All 25 patients who presented for a 6-month follow-up visit were asymptomatic, with a single patient having left ventricular diastolic dysfunction. Although the rapid resolution of symptoms and cardiac abnormalities seen in this study is good news, it is unclear if these outcomes will persist given the much greater number of children with COVID-19 infections who were hospitalized during the summer of 2021. The best approach to preventing MIS-C remains reducing the risk of SARS-CoV-2 infection through vaccinating adolescents and - pending regulatory approval in the next few weeks - younger children.

Monday, September 27, 2021

Is the pandemic worsening childhood obesity rates?

 - Jennifer Middleton, MD, MPH

The COVID-19 pandemic is correlating with worsening health measures in adults (obesity and alcohol consumption, for starters), and new evidence demonstrates concern with increasing rates of childhood obesity as well. 

Centers for Disease Control and Prevention (CDC) researchers examined data from IQVIA's electronic records, including over 432,000 children and teens aged 2-19 years from across the United States (US). Among this relatively diverse cohort (34.3% non-white), they found that:

Between the prepandemic and pandemic periods, the rate of BMI increase approximately doubled, from 0.052 (95% confidence interval [CI] = 0.051–0.052) to 0.100 (95% CI = 0.098–0.101) kg/m2/month (ratio = 1.93 [95% CI = 1.90–1.96]). Persons aged 2–19 years with overweight or obesity during the prepandemic period experienced significantly higher rates of BMI increase during the pandemic period than did those with healthy weight. 

The rate change was most dramatic for children aged 5-11 years (0.09 kg/m2/month or 3 oz/m2/month which is 2.5 times higher than during the prepandemic time period.). The CDC authors posit that school interruptions are a likely contributor to these changes which makes sense given that school is, for many children, an essential source of nutritious meals and physical activity

A somewhat smaller study of 191,000 US children published last month using Kaiser Permanente data from Southern California had similar findings, with statistically significant differences in weight gain among children aged 5-11 years ("a mean gain among 5- through 11-year-olds of 2.30 kg (95% CI, 2.24-2.36 kg) more during the pandemic than during the reference period"). These researchers provided more information about the diversity of their cohort, with "10.4% Asian and Pacific Islander, 50.4% Hispanic, 7.0% non-Hispanic Black, and 25.3% non-Hispanic White."

Ensuring access to nutritious meals and physical activity are necessary components of a healthy school environment. A bill is currently pending in the US Congress to fund universal free meals in all US schools. Studies show that providing time for physical education does not harm children's educational gains. Additionally important is creating a healthy psychological environment, as weight-based bullying in school is very common, with both peers and educators as perpetrators. Family physicians can support children by letting their US congressperson know of their support for the Universal School Meals Act, by encouraging school leaders to allow time for physical activity during the school day, and by educating ourselves about our conscious or subconscious biases about overweight persons. We can then work with families to have nonjudgmental conversations about behavior modifications to limit or reverse weight gain. 

If you'd like to read more, check out this AFP article on "Evaluation and Treatment of Childhood Obesity" and this AFP Cochrane review on "Interventions for Reducing Childhood Obesity." These AFP patient education handouts on "Helping Your Child Keep a Healthy Weight" and "Helping Your Child Lose Weight" contain several practical tips to discuss with families as well.

Monday, September 20, 2021

The challenge of correctly diagnosing hypertension in adults

 - Kenny Lin, MD, MPH

Screening for high blood pressure in adults can be straightforward or quite complex. The U.S. Preventive Services Task Force (USPSTF) recently reaffirmed its longstanding recommendation to screen for hypertension with office blood pressure measurement but advises confirming the diagnosis with measurements outside of the clinical setting. The diagnostic standard for out-of-office measurement is 24-hour ambulatory blood pressure monitoring (ABPM), but ABPM is often unavailable, not covered by insurance, or inconvenient for patients.

A more accessible alternative, reviewed by Dr. Jeffrey Weinfeld and colleagues in the September issue of AFP, is home blood pressure monitoring (HBPM). In addition to confirming a hypertension diagnosis, HBPM can be used to identify white coat hypertension (elevated readings in the office but normal readings at home) and masked hypertension (elevated readings at home but normal readings in the office). Patients can purchase a clinically validated blood pressure monitor for $37 to $100 without insurance, and this expense may be reimbursed from a health care flexible spending account. The downside of HBPM is that patients sometimes forget to check their blood pressures at home or forget to record and bring in the readings. 

What is the role of automated oscillometric office blood pressure (AOBP) devices such as those used in the Systolic Blood Pressure Intervention Trial (SPRINT)? A systematic review and meta-analysis previously summarized in AFP found that AOBP systolic measurements were on average 14.5 mm Hg lower than manual blood pressures in patients with hypertension and better aligned with values obtained with ABPM. In a Letter to the Editor in the August issue, Dr. Lenard Lesser argued that the USPSTF "missed an opportunity to promote AOBP measurements as an easier-to-implement alternative to ambulatory blood pressure monitoring." Dr. Lesser pointed out that the only randomized trial of hypertension screening cited by the USPSTF that reported improvements in clinically meaningful outcomes actually used AOBP.

In the latest entry in JAMA's Rational Clinical Examination series, Dr. Anthony Viera and colleagues systematically reviewed studies that addressed the question, "Does This Adult Patient Have Hypertension?" Comparing AOBP with HBPM, they found that 

The thresholds for defining hypertension and the prevalence of hypertension were similar in office BP measurement and home BP measurement studies, and the estimated predictive values of office oscillometric BP measures and HBPM were numerically nearly identical. ... The combination of results from office BP measurement and HBPM has better diagnostic accuracy than the independent results alone, and when concordant, is likely sufficient for diagnosis. However, 24-hour ABPM should be considered when results are discordant, especially for patients with a higher pretest probability of hypertension.

Monday, September 13, 2021

Do salt substitutes improve mortality in persons at high risk of CVD?

 - Jennifer Middleton, MD, MPH

The current Dietary Guidelines for Americans recommend limiting daily sodium intake to 2,300 mg or less, but 90% of Americans aged 2 years and older consume more salt than this amount daily. The best evidence to date recommends lowering sodium intake to reduce the risk of cardiovascular disease (CVD), but given the pervasiveness of sodium in the American diet, lowering salt intake can be challenging. Replacing table salt with a lower-sodium product could be a more feasible change, and a large randomized controlled trial now suggests that doing so may decrease mortality from CVD in those persons at higher risk. 

The study researchers enrolled nearly 21,000 participants from 600 villages in rural China. The researchers randomized villages to either continued usual salt use or use of a provided salt substitute (75% sodium chloride and 25% potassium chloride). Participants either had a history of stroke or were at least 60 years of age with hypertension:

The mean duration of follow-up was 4.74 years. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1000 person-years; rate ratio, 0.86; 95% confidence interval [CI], 0.77 to 0.96; P=0.006), as were the rates of major cardiovascular events (49.09 events vs. 56.29 events per 1000 person-years; rate ratio, 0.87; 95% CI, 0.80 to 0.94; P<0.001) and death (39.28 events vs. 44.61 events per 1000 person-years; rate ratio, 0.88; 95% CI, 0.82 to 0.95; P<0.001).  

The difference in adverse events due to hyperkalemia was not statistically significant between groups. 

Generalizing the results of this study may be risky; I would presume that most Americans, for example, consume more processed foods and foods prepared outside of the home than the rural Chinese participants in this study. Since "[m]ost sodium consumed in the United States comes from salt added during commercial food processing and preparation, including foods prepared at restaurants," simply decreasing sodium intake in foods prepared at home may not have as great of an effect among persons eating the standard American diet. Then again, even a small benefit could have a sizable effect on population outcomes, and salt substitutes are inexpensive and simple to incorporate into home cooking. Given the minimal harms associated with the salt substitute product in this study, recommending a salt substitute for home use still seems like a reasonable recommendation for our patients at higher risk of CVD.

Taking the time to discuss these recommendations with patients is worthwhile; the United States Preventive Services Task Force (USPSTF) gives a "B" grade to "Behavioral Counseling Interventions to Promote a Healthy Diet and Physical Activity for CVD Prevention in Adults with Cardiovascular Risk Factors." As with all behavior change, tailoring strategies to each patient's circumstances increases the likelihood of success. In addition to recommending salt substitutes, we can teach our patients to read food labels for sodium content, recommend low salt recipes, and discourage frequent restaurant meals. For patients having difficulty making changes, this 2018 AFP article on "Diets for Health: Goals and Guidelines" includes this table with suggestions for overcoming common barriers to eating a healthier diet.

Monday, September 6, 2021

Alliance of international health journals calls for emergency action to limit climate change

 - Kenny Lin, MD, MPH

Today, one week ahead of the 76th session of the United Nations General Assembly, more than 200 health journals worldwide have simultaneously published an editorial calling on health professionals, policy makers, and governments to support emergency actions to limit average global temperature increases to below 1.5 degrees Celsius. Asserting that increases above that level would "risk catastrophic harm to health that will be impossible to reverse," the editorial's authors advocate for "fundamental and equitable changes to societies" to alter the world's current catastrophic temperature trajectory:

Equity must be at the center of the global response. Contributing a fair share to the global effort means that reduction commitments must account for the cumulative, historical contribution each country has made to emissions, as well as its current emissions and capacity to respond. Wealthier countries will have to cut emissions more quickly, making reductions by 2030 beyond those currently proposed and reaching net-zero emissions before 2050.

Last month, a landmark report from the Intergovernmental Panel on Climate Change (IPCC) concluded that human activities since 1850, primarily burning of fossil fuels, have already warmed the planet by 1.1 degrees Celsius. At 1.5 degrees, the IPCC warned, extreme weather patterns would become more frequent, and rising sea levels, vector-borne diseases, life-threatening heat waves, and severe droughts would affect billions of people worldwide. Currently, the 10 countries with the greatest greenhouse gas emissions (China, the U.S., the European Union, India, Russia, Japan, Brazil, Indonesia, Iran, and Canada) account for more than two-thirds of global emissions.

American Family Physician strongly supports this global effort to prevent future environmental catastrophes. Our first full-length clinical review article about the health impacts of global warming appeared in 2011. An accompanying editorial highlighted the physician's role in efforts to slow global warming, including reducing the carbon footprints of hospitals and health care facilities. In 2016, Associate Deputy Editor Caroline Wellbery, MD, PhD observed that the 2015-2020 Dietary Guidelines for Americans' "heart-healthy recommendations align with ... environmental concerns," making eating less meat a healthy and environmentally responsible dietary choice.

A 2019 update on managing health impacts of climate change discussed ways that clinicians can mitigate "morbidity and mortality from worsening cardiopulmonary health, worsening allergies, and greater risk of infectious disease and mental illness, including anxiety, depression, and posttraumatic stress disorder from extreme weather events." Health professionals must recognize how their workplaces directly contribute to making climates less healthy: "The U.S. health care sector is responsible for 10% of all greenhouse gas emissions, 10% of smog formation, 12% of air pollution emissions, and smaller but significant amounts of ozone-depleting substances and other air toxicants." The article also suggested counseling patients on the personal and environmental benefits of utilizing active transport and a consuming plant-based diets.

Physicians' lack of training in climate science and global warming's negative impacts on health may be an obstacle to leveraging the collective authority of the medical profession to address the climate crisis. This gap is closing, though, as recent editorials in Academic Medicine have called for critical curricular reforms in medical school and residency education, and in some cases, medical students themselves have been leading these educational efforts.

Monday, August 30, 2021

Supporting patients with stomas

 - Jennifer Middleton, MD, MPH

Family physicians are likely to care for patients with colostomies and ileostomies, so comfort with both the basics of stoma care and the common psychosocial challenges of managing a stoma are a must. Patients may have temporary colostomies for several reasons, including the need to divert stool away from the perineum for surgical procedures and with bowel resections for diverticular disease or malignancy. Patients with cancer, severe fecal incontinence, inflammatory bowel disease, and/or recurrent diverticular disease may have permanent colostomies or ileostomies. 

Patients should receive instructions from their colorectal care team about the frequency of emptying and changing their stoma bags. Some patients will be advised to empty their stoma bag 1-3 times a day and will then replace the bag every 2-4 days; some patients will be advised to simply replace the bag when full every 1-2 days. The odor of stool from a stoma can be more intense than with usual defecation, and patients may want to choose an air freshener product to keep handy during bag emptying and changing. Patients should be prepared for the potential of bag leaking by either carrying or keeping nearby an extra set of supplies (new ostomy bag, adhesive remover, new adhesive, small trash bag/plastic bag for disposal).

There are different types of ostomy bag systems and a wide variety of products to protect the skin around the stoma (including powders and barrier wipes). Although colorectal care providers usually manage product recommendations and orders, keeping track of the products your patients are using will help if they ever need you to reorder them. Familiarity with these supplies and general management of ostomy bags can also lead to more meaningful conversations with patients about ostomy management. This 5-minute video gives an overview of emptying and changing ostomy bags. Healthy stomas are pink or red and often have a somewhat raw or abraded appearance. Skin care around the stoma site is important, and patients should be checking the skin around the stoma with every bag change. If patients are experiencing skin irritation, encourage them to should reach out to their colorectal team to discuss skin care product options; if their stoma is blue, purple, or tender, urge patients to reach out to their colorectal care team immediately for evaluation.

Having provided care for a family member with a stoma, I can personally relate to the challenges of adapting to a colostomy or ileostomy. Talking about stool and bowel problems is often stigmatized, and, consequently, patients may not feel that they can discuss the challenges of dealing with a stoma with friends and family. It's not surprising that persons with a stoma have higher rates of depression and social isolation compared to the general population. Dyspareunia and erectile function are also more common in patients with stomas. This article contains several pragmatic tips for managing situations such as returning to work, traveling, and intimacy. Patients can also find positive depictions of life with a stoma on social media and connect with both local and online support groups for "ostomates." 

Although stomas may seem intimidating at first, family physicians are more than capable of learning the basics of stoma care and supporting patients with stomas throughout their experience.

Monday, August 16, 2021

What are the risks of tapering chronic opioids?

 - Jennifer Middleton, MD, MPH

The Centers for Disease Control and Prevention (CDC) recommends tapering chronic opioid doses when patients do not have meaningful pain benefit and/or show signs of a substance use disorder. Despite increased opioid tapering by physicians in the last few years, however, deaths from opioid use continue to escalate. A new study suggests that tapering long-term opioid doses may be contributing to this increased mortality by increasing affected patients' risks for mental health crisis and/or opioid overdose.

This retrospective cohort study of a national database included over 113,000 participants' records from 2008-2019. The study authors defined tapering as a "at least 15% relative reduction in mean daily dose during any of 6 overlapping 60-day windows within a 7-month follow-up period." Their main outcomes were emergency department and/or hospital visit for drug overdose, drug withdrawal, and/or mental health crisis. Patients with tapered opioid doses were more likely to present with drug overdose or withdrawal in the subsequent 12 months than patients maintained on their chronic opioid regimen (9.3 overdose events per 100 person-years compared with 5.5 events per 100 person-years), and patients with tapered opioid doses were also more likely to present with mental health crisis (depression, anxiety, and/or suicide) than patients maintained on their chronic opioid regimen (7.6 mental health crisis events per 100 person-years compared with 3.3 events per 100 person-years). The confidence intervals for both absolute risk differences were statistically significant (adjusted incidence rate difference, 3.8 per 100 person-years [95% CI, 3.0-4.6] and adjusted incidence rate difference, 4.3 per 100 person-years [95% CI, 3.2-5.3], respectively). 

This study's observational design can only determine correlation, not causation, though the authors cite earlier published studies demonstrating the "potential hazards of rapid dose reduction, including withdrawal, transition to illicit opioids, and psychological distress." They recommend "more gradual dose reductions" (the CDC recommends reducing doses by no more than 10% a month for patients taking chronic opioids) to reduce the risk of adverse events and call for further research to better define optimal patient selection and dose reduction protocols for opioid tapering. A 2020 AFP Curbside Consultation provides an overview of one current tool to manage opioid tapering, the BRAVO (Broaching the subject, Risk-benefit calculation, Addiction, Velocity and validation, Other strategies) protocolUnfortunately, some patients with chronic opioid use develop opioid use disorder, and these patients require additional treatment beyond tapering off opioids. The AFP By Topic on the Opioid Epidemic - Key Resources provides articles to guide diagnosis and management, including this overview of "Opioid Use Disorder: Medical Treatment Options." 

The COVID-19 pandemic is accelerating opioid-related mortality; as we await further research, tapering chronic opioid doses, when appropriate, remains a useful tool if we proceed slowly and engage in thoughtful patient-centered decision making regarding its potential risks.

Tuesday, August 10, 2021

Should risk calculators be used in lung cancer screening decisions?

 - Kenny Lin, MD, MPH

The American Academy of Family Physicians recently endorsed the U.S. Preventive Services Task Force (USPSTF)'s 2021 recommendation to offer annual lung cancer screening with low-dose computed tomography (LDCT) to adults aged 50 to 80 years with at least a 20 pack-year smoking history who have smoked within the past 15 years. Although a meta-analysis of 8 randomized controlled trials found that people screened with LDCT are 19% less likely to die from lung cancer (NNS = 250), it also concluded that about 20% of tumors are overdiagnosed, in line with a previous report from the U.S. National Lung Screening Trial. Unfortunately, doctors do not often discuss harms of lung cancer screening such as overdiagnosis, overtreatment, and complications of diagnostic procedures performed for positive tests.

Deciding if the potential benefits outweigh the harms of lung cancer screening for an individual patient requires a way to personalize estimates of benefit based on patients' risk factors. In a Letter to the Editor regarding a 2019 American Family Physician article on the pros and cons of lung cancer screening, Dr. Abbie Begnaud and colleagues suggested:

If an eligible patient is reasonably healthy, clinicians could consider calculating individualized lung cancer risk using one of several well-validated risk models. We and others have developed web-based tools to help clinicians incorporate individualized risk calculations into decision-making. Individualized risk assessment can be helpful because patients at higher risk of developing lung cancer are also more likely to benefit from early detection through screening. When lung cancer risk increases, uncertainty about whether to recommend screening decreases when the person has a reasonable life expectancy.

Unlike risk prediction tools for cardiovascular disease and breast cancer, however, there is no consensus on which lung cancer risk calculator should be used. A systematic review published earlier this year in the Journal of General Internal Medicine identified 10 publicly available risk calculators and assessed their performance in 16 hypothetical patients across the continuum of lung cancer risk. The calculators used varying inputs (demographic factors, cancer history, smoking status, and personal and environmental factors) to generate lung cancer risk estimates; unsurprisingly, there were substantial differences in risk estimates for 10 of the 16 hypothetical patients. The authors concluded that the lack of standardization of lung cancer risk factors and consistency in risk estimates from web-based calculators may be an obstacle to shared decision making.

Notably, the USPSTF statement "recommends using age and smoking history to determine screening eligibility rather than more elaborate risk prediction models because there is insufficient evidence to assess whether risk prediction model–based screening would improve outcomes relative to using the risk factors of age and smoking history for broad implementation in primary care." In a Putting Prevention Into Practice case study in the July issue of AFP, Drs. Howard Tracer and James Pierre explained how to apply the Task Force recommendations in clinical practice.

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 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.