The top ten AFP Community Blog posts of 2021

 - Kenny Lin, MD, MPH

Two years into the pandemic, our most popular blog posts continue to focus on prevention or treatment of COVID-19. As you are hopefully enjoying time with family and friends over the holidays, here is an opportunity to catch up on the top 10 most-read AFP Community Blog posts of 2021.

1. Patient-centered discussion of COVID-19 infection and mRNA vaccines (June 1) - 2188 views

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.

2. Can Choosing Wisely prevent acute low back pain from becoming chronic? (March 8) - 1142 views

Can guideline-discordant care for patients with acute low back pain increase the risk of progression to chronic low back pain? In an 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, and followed them for 6 months.

3. Discussing COVID-19 vaccine risks with patients (July 6) - 861 views

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.

4. COVID vaccine boosters: now, later, or never? (August 2) - 816 views

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.

5. COVID vaccine update: new data and new vaccines (February 1) - 807 views

Assuming supply and distribution challenges are eventually overcome, vaccine hesitancy may pose another threat to decreasing SARS-CoV-2 transmission, which is critical to slowing the development of additional COVID variants.

6. New (old) treatments for COVID: inhaled budesonide and the -umabs (February 15) - 796 views

Researchers have identified two classes of medications that may benefit patients with symptomatic COVID-19, both well-known medications already in use for other conditions.

7. Interpretation and use of COVID-19 diagnostic tests: key resources (April 20) - 746 views

A analysis in the Annals of Internal Medicine estimated that a weekly home-based antigen testing program could avert 2.8 million infections and 15,700 deaths in the U.S. over a 60-day time frame, at a cost of less than $8000 per infection averted.

8. Understanding and managing long COVID (May 3) - 725 views

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.

9. Should we choose ARBs over ACEis for hypertension? (October 25) - 703 views

There was no statistically significant difference between the ACEi and the ARB groups regarding risk of CVD events, but ACEi patients had more adverse medication reactions.

10. Pharmacogenetic testing's promise, problems and pitfalls (July 27) - 673 views

Though pharmacogenetic testing holds promise for improving clinical decision-making, 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.

Studying sildenafil's potential to prevent Alzheimer's disease

 - Jennifer Middleton, MD, MPH

As the controversy over aducanumab's FDA approval for Alzheimer's disease continues, another potential treatment for Alzheimer's has been garnering attention. Using a complex gene-mapping technique, a team of U.S. researchers identified sildenafil (Viagra, Revatio), out of a group of more than 1,600 FDA approved medications, as having the potential to target both amyloid and tau protein formation. Further case-control analysis demonstrated a decreased risk of Alzheimer's among individuals who had received a sildenafil prescription compared to those who had not.

The researchers began with the hypothesis that an effective Alzheimer's medication should target both amyloid and tau, given the failure to date of attempts to create effective, separate anti-amyloid and anti-tau therapies:

“Recent studies show that the interplay between amyloid and tau is a greater contributor to Alzheimer’s than either by itself,” said Dr. Cheng [the study's lead investigator]. “Therefore, we hypothesized that drugs targeting the molecular network intersection of amyloid and tau endophenotypes should have the greatest potential for success.”

The researchers then used a "large gene-mapping network" which "integrated genetic and other biologic data" and scored each medication based on its effect on amyloid and tau, with higher scores for medications that targeted both. When sildenafil received the top score, the researchers then analyzed over 7 million insurance claims records and found that "sildenafil usage was significantly associated with a 69% reduced risk of AD (hazard ratio 0.31, 95% confidence interval 0.25–0.39, P < 1.0 × 10–8)." The study team correctly notes that "[t]he association between sildenafil use and decreased incidence of AD does not establish causality, which will require a randomized controlled trial," which the study team is currently planning.

The implications of this "big data" approach to identifying novel treatments among approved FDA medications ("drug repurposing") is tantalizing, and the sildenafil/Alzheimer's research team is reportedly already investigating applying this approach to Parkinson's disease and amyotrophic lateral sclerosis. Perhaps this study portends a new wave of research to benefit patients with diseases that, to date, have limited therapeutic options. 

None of the study researchers is advising the use of sildenafil yet for Alzheimer's disease, though you can find an overview of currently approved treatment options (minus aducanumab, which was not yet available at the time of publication) in this AFP article on "Alzheimer Disease: Pharmacologic and Nonpharmacologic Therapies for Cognitive and Functional Symptoms." There's also an AFP By Topic on Dementia if you'd like a more in-depth review.

Mitigating the impact of substance use disorders on family members

- Kento Sonoda, MD, AAHIVS

In the United States, the estimated number of overdose deaths between May 2020 and April 2021 surpassed 100,000, even worse than a record 93,000 last year. As 20.4 million people age 12 years or older were diagnosed with a substance use disorder (SUD) in 2019, the number of the impacted family members is likely 50 million or more. Numerous studies have examined the negative health impacts on individuals with SUD, but studies about the effects of addiction on family members are limited. SUD can negatively affect family members’ health, especially mental health, along with their quality of life, work, and finances. Barriers such as stigma, limited support services, hopelessness, and feeling undervalued deter affected family members from seeking help. Sacrificing their time and money for loved ones who are suffering from SUD can lead family members to neglect their own chronic medical conditions.

For instance, I cared for a woman in her early 50s whose husband struggles with alcohol use disorder, which caused him to lose his job. She developed new heart failure with reduced ejection fraction secondary to uncontrolled hypertension, likely from stopping all of her antihypertensive medications due to financial burden and self-neglect. She disclosed that she does not have enough time and energy to take care of herself. She had not asked for help or received medical care because of stigma and isolation until she could not tolerate her symptoms any more.

As the number of patients with SUD has been increasing, family physicians play a central role in taking care of these patients and their family members. Additionally, the COVID-19 pandemic has worsened mental conditions and potentially exacerbated the negative consequences for family members. When uncontrolled chronic conditions or mental illnesses are identified in the outpatient setting, screening for family members with SUD can be considered as a means to better understand the full situation and provide support and helpful resources as needed.

The following resources are available for family members and loved ones of individuals with substance use disorders: Adult Children of Alcoholics World Service Organization (a 12-step, 12-tradition program of people who grew up in dysfunctional homes due to substance use disorder), Al-Anon (a mutual support program for people whose lives have been affected by someone else’s drinking), Alateen (a part of the Al-Anon Family Groups for young people), Family Anonymous (a 12-step fellowship for the family and friends of those individuals with substance-related issues), Nar-Anon (a 12-step program for family and friends with SUD), and National Association for Children of Addiction (the only national membership organization focusing on the children of parents struggling with SUD).

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Dr. Sonoda is an Addiction Medicine Fellow at the University of Pittsburgh Medical Center and the 2021 AFP Resident Representative.

Will COVID antivirals help end the pandemic?

 - Jennifer Middleton, MD, MPH

The U.S. Food and Drug Administration (FDA)'s advisory committee voted last week in favor of approving molnupiravir, Merck's oral antiviral medication for COVID-19. The FDA is expected to follow the committee's recommendation and authorize use of the drug this week under an Emergency Use Authorization (EUA). Pfizer is also preparing an EUA application for its antiviral medication, ritonavir. While the development of additional treatments to combat COVID-19 is cause for some optimism, it may be too early to celebrate given the limited, preliminary nature of both medications' efficacy to date.

Data from molnupiravir's phase 2a trial has not yet been peer reviewed; outcomes demonstrated reasonable tolerability and a substantial reduction of viral load. Merck also announced phase 3 data demonstrating a nearly 50% reduction in death and hospitalization for outpatients with laboratory-confirmed COVID-19 infection who began taking it within 5 days of symptom onset. This data came from an interim analysis of 775 trial participants with "mild to moderate COVID-19" and "one risk factor associated with poor disease outcome." The trial's independent data review committee recommended terminating the trial early given these findings, but continued follow-up of study participants has demonstrated a lower efficacy of about 30%. That trial's data is not yet available for public review but was reportedly considered by the FDA advisory committee. The advisory committee vote was close (13-10); committee members who voted "yes" despite molnupiravir's modest efficacy cited the lack of other antiviral treatments available, with some suggesting that approval could be later rescinded if better treatments are developed. Members voting "no" raised concerns about the drug's risk of teratogenesis as well as its potential to induce dangerous mutations into the SARS-CoV-2 virus:

“Even if the probability is very low, 1 in 10,000 or 100,000, that this drug would induce an escape mutant from which the vaccines we have do not cover, that could be catastrophic...” Dr. James Hildreth, CEO of Meharry Medical College in Nashville, Tenn., told the panel.

Pfizer's ritonavir has had more promising results. Its phase 2/3 trial enrolled just over 1200 "non-hospitalized adults aged 18 and older with confirmed COVID-19 who are at increased risk of progressing to severe illness" who were randomized to either receive placebo or ritonavir within 5 days of laboratory-confirmed COVID-19 infection. Pfizer reported an 85% reduction in the risk of hospitalization or death in enrolled participants with a no significant difference of adverse events between groups (21% placebo vs 19% ritonavir). This study was also stopped early due its positive interim findings; it remains to be see whether these positive findings will persist with further analysis.

While oral antiviral medications may be "another tool in our toolbox" as touted by U.S. President Biden, vaccination remains the most critical element to stem the development of new SARS-CoV-2 mutations as well as the pandemic. The worldwide vaccine supply is adequate to meet the World Health Organization's ambitious vaccination goals if "distributed equitably."

In the meantime, the AFP By Topic on COVID-19 continues to be regularly updated, with sections on Prevention (including this Lown Right Care article on "Helping Ambivalent Patients Make Healthy Decisions About COVID-19") and Treatment.

Dietary and nutrition guidance for the holidays and beyond

 - Kenny Lin, MD, MPH

Still feeling the aftereffects of Thanksgiving dinner? You're hardly alone. As the days get shorter and people look forward to holiday celebrations, three recent dietary and nutrition guidelines provide practical advice for physicians and patients.

The 2020-2025 Dietary Guidelines for Americans, summarized in Practice Guidelines in the November issue of AFP, are the latest iteration of a scientific collaboration between the U.S. Departments of Agriculture (USDA) and Health and Human Services dating back to 1980. The current report provides guidance for healthy eating across a person's lifespan, emphasizing dietary patterns with nutrient-dense foods and beverages:

At least one-half of food eaten should be fruits and vegetables, especially whole fruits and vegetables of a variety of colors. The core elements of the other half of food that should be eaten include grains, dairy, protein, and oils with lower saturated fat. At least one-half of grain servings should be whole grains. Minimize alcohol use and consumption of foods with added sugar, saturated fat, and sodium.

In an accompanying editorial, Drs. Amy Locke and Rachel Goossen observed that "although many of the recommendations are widely accepted, ... criticisms revolve around the authors' reported financial ties to the food industry and the discrepancies between the published guidelines and the recommendations submitted to the authors by the scientific advisory committee." Examples of such discrepancies include the Dietary Guidelines' overemphasis on consuming dairy and animal-based proteins and insufficient limits on alcohol use. Drs. Locke and Goossen suggested that "the most accessible way to use the information included in the report is through the USDA's MyPlate website and app" that organize advice by food groups and subgroups.

Recognizing that nearly 9 in 10 adults consume more sodium than the National Academy of Medicine's Chronic Disease Risk Reduction (CDRR) intake of 2,300 mg/day, the U.S. Food and Drug Administration recently finalized voluntary guidance for industry that aims to reduce the average American's daily sodium intake by 12% (from 3,400 to 3,000 mg/day) over the next two and a half years. Industry cooperation is critical because more than 70% of sodium intake comes from packaged food and food prepared away from home. Whether these goals will be achieved in the absence of an enforcement mechanism is unclear, as the sodium content of popular commercially processed and restaurant foods has changed little over the past decade.

Finally, the U.S. Preventive Services Task Force reiterated its 2014 recommendation that found insufficient evidence to assess the benefits and harms of screening for vitamin D deficiency in asymptomatic adults. In a Putting Prevention into Practice case study in AFP, Drs. Howard Tracer and Robert West noted that due to individual variability, "no one serum vitamin D level cutoff point defines deficiency, and no consensus exists regarding the precise serum levels of vitamin D that represent optimal health or sufficiency." In a previous editorial, I observed that frequent measurement of vitamin D levels in clinical practice is inconsistent with the evidence. As for supplementation, "family physicians should also counsel patients on the recommended dietary allowance for vitamin D (600 IU per day in adults 70 years and younger, and 800 IU per day in adults older than 70 years), and discourage most patients from using supplements, especially in dosages near or above the tolerable upper limit of 4,000 IU per day."

Do the benefits of medical cannabinoids outweigh the harms?

 - Jennifer Middleton, MD, MPH

A recent systematic review and accompanying BMJ Clinical Practice Guideline have been creating media buzz regarding medical marijuana and cannabinoids. The systematic review authors comprehensively searched a broad range of databases for randomized controlled trials of at least 20 participants with chronic pain who were followed for a minimum of 1 month. They identified 32 trials with a total of nearly 5200 participants to include in the systematic review. Study durations ranged from 1.0-5.5 months, and most (28) studied non-cancer-related chronic pain. Most studies (29) compared medical cannabis and/or cannabinoids with placebo. After analyzing the data, the authors concluded that:

Compared with placebo, non-inhaled medical cannabis probably results in a small increase in the proportion of patients experiencing at least the minimally important difference (MID) of 1 cm (on a 10 cm visual analogue scale (VAS)) in pain relief (modelled risk difference (RD) of 10% (95% confidence interval 5% to 15%), based on a weighted mean difference (WMD) of −0.50 cm (95% CI −0.75 to −0.25 cm, moderate certainty)). Medical cannabis taken orally results in a very small improvement in physical functioning (4% modelled RD (0.1% to 8%) for achieving at least the MID of 10 points on the 100-point SF-36 physical functioning scale, WMD of 1.67 points (0.03 to 3.31, high certainty)), and a small improvement in sleep quality (6% modelled RD (2% to 9%) for achieving at least the MID of 1 cm on a 10 cm VAS, WMD of −0.35 cm (−0.55 to −0.14 cm, high certainty)). 

The authors interpreted these findings as "moderate to high certainty evidence" that the use of medical cannabis and cannabinoids was associated with a "small to very small" improvement in pain, functioning, and sleep. They also reported on adverse events that occurred more frequently in the medical cannabis and cannabinoids patients, including cognitive impairment and nausea/vomiting. 

This systematic review's findings informed an accompanying Clinical Practice Guideline in the same issue of BMJ, in which the guideline authors issued "a weak recommendation to offer a trial of non-inhaled medical cannabis or cannabinoids, in addition to standard care and management (if not sufficient), for people living with chronic cancer or non-cancer pain." The guideline development panel included three of the authors of the above systematic review, patients, and "clinicians with content expertise," who acknowledge that their recommendation "reflects a high value placed on small to very small improvements in self reported pain intensity, physical functioning, and sleep quality, and willingness to accept a small to modest risk of mostly self limited and transient harms." They acknowledge that their guideline contradicts previous guidelines issued by NICE, the American Society of Clinical Oncology, and Canadian Family Physician, arguing that those guidelines were limited by an overly "selective review of the evidence" and a "failure to consider patient values and preferences."

These conflicting guidelines attest to the continued controversy regarding the use of marijuana and/or cannabinoids in medicine. Currently, 36 US states and 4 US territories permit their use. As this recent JAMA editorial attests, "[t]his heterogeneous approach to policy making can directly affect patients and clinicians because they are left to interpret mixed messages from lawmakers about the safety and efficacy of medical cannabis use." The AAFP's position paper on "Marijuana and Cannabinoids: Health, Research, and Regulatory Considerations" acknowledges the burgeoning evidence base regarding these substances' potential medical benefit while also cautioning against their established harms. A 2015 AFP editorial, "Effectiveness, Adverse Events, and Safety of Medical Marijuana," affirms both benefits and harms while calling for reclassification of cannabis as a schedule II drug by the US Food and Drug Administration (FDA) to permit more rigorous outcomes-based research. 

Patients will doubtless continue to inquire about medical cannabis and cannabinoids while we await more definitive evidence; for those clinicians practicing in states where they are an option, discussing the balance of known benefits and harms can help patients make an informed decision. This AFP By Topic on Chronic Pain provides overviews of additional therapeutic options to consider, and stay tuned for "Cannabis Essentials: Tools for Clinical Practice," coming in next month's issue of AFP.

Reassessing race-based clinical prediction tools

 - Kenny Lin, MD, MPH

Five months ago, AFP published Dr. Bonzo Reddick's editorial "Fallacies and Dangers of Practicing Race-Based Medicine." In this editorial, Dr. Reddick reviewed the limitations of several commonly used clinical prediction tools that employ race as a biologic variable rather than recognizing it as a social construct. For example, he pointed out that the American College of Cardiology / American Heart Association Pooled Cohort Equations (PCE) predict that "a 40-year-old White male smoker has a lower cardiovascular risk than a 40-year-old Black male nonsmoker," or put more bluntly, "being a Black man is more dangerous than smoking." Since then, researchers and policy makers have made considerable progress in addressing the inappropriate use of race in medical decision making.

A Curbside Consultation in the September issue introduced a multiracial patient who is confused by the need to identify as African American, White, or Other so that his clinician can evaluate the appropriateness of statin therapy. If White, his estimated 10-year cardiovascular disease (CVD) risk would be 5.8%; if African American, it would be 17.7%. Similarly, a preprint study using thousands of hypothetical and actual patients concluded that large differences in PCE estimates in Black versus White persons with identical risk factor profiles would have the practical effect of "introduc[ing] race-related variations in clinical recommendations for CVD prevention." Until new cardiovascular risk prediction models are developed that omit race, Drs. Mara Gordon and Isha Marina Di Bartolo suggested that physicians exercise caution when using race as a marker of genetic ancestry; consider alternative approaches to risk stratification; and use social determinants of health as an alternative to demographics.

Turning from the heart to the kidneys, including race in the estimation of glomerular filtration rate (eGFR) has the effect of increasing a Black person's eGFR relative to a White person's with the same serum creatinine level. Consequently, Black patients with chronic kidney disease become eligible for kidney transplants nearly two years later than their White counterparts. Underlying this point, Glenda Roberts, a patient representative to a National Kidney Foundation and American Society of Nephrology Task Force that recommended implementing a refitted eGFR calculation that does not include race, observed in a recent opinion piece that though she self-identifies as Black, learning from a DNA analysis that her ancestry was only 48% African (making her, technically, White) would have gotten her on the transplant list sooner! The Chronic Kidney Disease Epidemiology Collaboration has published new eGFR equations that omit race and incorporate serum creatinine and cystatin C.

A 2007 calculator for predicting the likelihood of a successful vaginal birth after cesarean (VBAC) delivery that includes race-based correction factors for African American and Hispanic women was later challenged for promoting disparities in cesarean rates. Earlier this year, researchers from the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network unveiled a new VBAC calculator without race variables that has excellent calibration and a similar area under the receiver operating characteristic curve as the previous calculator.

Further work remains to be done. The Agency for Healthcare Research and Quality (AHRQ) posted draft Key Questions for a future systematic evidence report on the impact of clinical algorithms on racial disparities in health and health care. Another AHRQ-funded methods report on racism and health inequities in clinical preventive services and guideline development supported the U.S. Preventive Services Task Force's proposed changes to its recommendation processes to mitigate the effects of systemic racism.

How common is remission of type 2 diabetes?

 - Jennifer Middleton, MD, MPH

Perhaps your patients with type 2 diabetes have also asked you if it's possible to "cure" their diabetes. The only method with an evidence base of doing so to date has been bariatric surgery, but a new study suggests that achieving remission from type 2 diabetes may be more common than previously thought. Using a national registry that included 99% of all persons in Scotland with a type 2 diabetes diagnosis, this study's authors examined hemoglobin A1c values throughout the 2019 calendar year and found that 4.8% decreased their A1c below 6.5%.

In this cohort of over 162,000 persons, the study authors identified several differences between the persons who achieved remission and those who did not:

Key differences in characteristics of people in remission in 2019 compared to people who were not in remission in 2019 were older age (70% of people in remission were aged ≥65, compared to 54% of people not in remission); greater weight loss between diagnosis of diabetes and 2019; lower proportions with previous prescriptions of GLT [glucose lowering therapy] (25% of people in remission had been prescribed GLT compared to 84% of people not in remission); lower mean HbA1c at diagnosis...; and higher prevalence of previous history of bariatric surgery (although overall numbers of people with a history of bariatric surgery were small). 

The authors hypothesize that "[i]t is possible that older people were diagnosed with diabetes with HbA1c values closer to diagnostic thresholds or after minor weight gain, and, therefore, only minor decreases in HbA1c or minor weight loss might be more likely to result in remission than among younger people." It's not surprising that patients who were able to lose weight (those in remission lost an average of 6.5 kg, or about 14 pounds) and/or who had lower A1cs to begin with were more likely to achieve remission. The lower prescriptions of glucose-lowering medications in the remission group likely relates to their overall lower A1cs to begin with. Bariatric surgery has already been demonstrated to help persons with type 2 diabetes achieve remission; a 2020 study found that nearly half of persons with type 2 diabetes achieved sustained remission after gastric bypass, though only 488 persons in the 2019 Scottish cohort had a history of bariatric surgery. 

The American Diabetes Association (ADA) released guidelines last month defining "remission" as an A1c < 6.5% "measured at least 3 months after cessation of glucose-lowering pharmacotherapy." They further recommend that:

• A1c testing occur at least annually to confirm continued remission
• Continued regular screening for retinal disease
• Continued regular screening for kidney disease
• Continued assessment and treatment of cardiovascular disease risk factors

Little patient-oriented outcomes that matter (POEM) data exists to back these recommendations. The guideline authors do cite this study demonstrating worsening of diabetic retinopathy in persons who achieved diabetes remission after bariatric surgery, though it's unclear whether the abrupt drop in blood glucose levels after surgery contributed to this worsening as compared to just continued retinopathy disease progression.

This Scottish study provides at least some sense regarding those persons more likely to achieve type 2 diabetes remission: older age, lower A1c to begin with, and able to sustain at least 6.5 kg of weight loss. You can read more at the AFP By Topic on Diabetes: Type 2, which includes a wealth of information on screening, prevention, and treatment.

Neonatal abstinence syndrome is on the rise

 - Kenny Lin, MD, MPH

The opioid epidemic accelerated during the COVID-19 pandemic, with the Centers for Disease Control and Prevention estimating that more than 93,000 people died from opioid-related overdoses in 2020, a 30 percent increase over 2019. As more pregnant patients have been using opioids, rates of neonatal abstinence syndrome (NAS) have also been on the rise, nearly doubling between 2010 and 2017. Family physicians who care for newborns will increasingly be called on to manage this syndrome. In an editorial in the September issue of AFP, Drs. Roschanak Mossabeb and Kevin Sowti reviewed key points in treatment of NAS, including a low-stimulation environment, skin-to-skin contact, frequent breastfeeding, and opioid therapy when indicated. They emphasized that involving the mother in the care plan is essential to achieving the best outcomes:

Mothers should be viewed as medicine for their infants; by spending time together, infants will likely need less pharmacologic treatment, hence a shorter hospital stay and decreased hospital costs. In addition, strengthening the mother-infant bond may reduce postpartum depression and improve maternal stress response.

Unfortunately, for a variety of reasons mothers and newborns with NAS are often separated after being discharged home. A recent county-level analysis in Health Affairs found that national increases in NAS are associated with increases in placement of infants in foster care: "every one diagnosis ... per ten births was associated with a 41 percent higher rate of infant foster care entry." Infants residing in rural counties were more likely to be placed in foster care than those residing in urban counties.

A quality improvement collaborative in Colorado hospitals aimed to standardize care of opioid-exposed newborns by implementing the Eat, Sleep, Console model. Study results showed that while hospital length of stay and pharmacologic therapy use decreased for all mother-infant dyads during the study period, these positive effects were delayed in mothers who self-identified as being of Hispanic ethnicity. Racial differences in treatment and outcomes have also been observed in studies comparing Black and and White newborns with NAS. However, a critique of two of these studies cautioned physicians against conflating racial disparities with genetic differences in treatment requirements, noting that implicit bias and racism is more likely to explain the disparities than biologically-based explanations.

Should we choose ARBs over ACEis for hypertension?

 - Jennifer Middleton, MD, MPH

Angiotensin-converting enzyme inhibitors (ACEis) have been a first-line medication for hypertension for decades, with well-established mortality and morbidity benefits.  Although newer on the block, angiotensin II receptor blockers (ARBs) have demonstrated many of these same benefits for patients and were included in the Eight Joint National Committee (JNC 8) guideline as another reasonable first-line option for treating hypertension. Initially cost-prohibitive for many patients, most ARBs are now available generic and at similar cost to ACEis, and data has been emerging that their tolerability profile is better than ACEis without sacrificing those all-important patient-oriented outcomes that matter (POEM) benefits. A large cohort study now adds to this evidence base, potentially furthering the case for choosing ARBs over ACEis for patients with hypertension.

The study authors reviewed 8 databases from across the United States, South Korea, and Germany that included over 3 million patients. They identified patients who were started on either an ACEi or an ARB for primary hypertension and noted outcomes related to both cardiovascular disease (CVD) events and adverse medication reactions. They used propensity score models to "adjust for potential confounding and improve balance between the ACE inhibitor and ARB patient cohorts...which included "tens of thousands of measured baseline covariates including: demographics, diagnoses,... [and] comorbidity or risk scores." There was no statistically significant difference between the ACEi and the ARB groups regarding risk of CVD events, but ACEi patients had more adverse medication reactions:

We found no statistically significant difference in the primary outcomes of acute myocardial infarction (hazard ratio, 1.11 for ACE versus ARB [95% CI, 0.95–1.32]), heart failure (hazard ratio, 1.03 [0.87–1.24]), stroke (hazard ratio, 1.07 [0.91–1.27]), or composite cardiovascular events (hazard ratio, 1.06 [0.90–1.25]). Across secondary and safety outcomes, patients on ARBs had significantly lower risk of angioedema, cough, pancreatitis, and GI bleeding.

Specifically, patients receiving ACEis were more likely to experience acute pancreatitis (hazard ratio [HR] 1.32 [95% CI 1.04-1.70]), angioedema (HR 3.31 [95% CI 2.55-4.51]), cough (HR 1.32 [95% CI 1.11-1.59]), and GI bleed (HR 1.18 [95% CI 1.01-1.41]). 

It's important to note that this study was not a randomized controlled trial (RCT); patients were not prospectively divided into randomized groups to rigorously assess for differences between treatments. Its impossible to completely adjust for potential confounders, no matter how rigorous the propensity score models are. Then again, an RCT on this scale would be a sizable undertaking, and cohort study data can still provide useful information. This study is consistent with the findings of an earlier meta-analysis of head-to-head, ACEi versus ARB, RCTs that found no difference in CVD outcomes but increased patient drop-out in the ACEi group, presumably due to side effects. 

This study also would not apply to patients already receiving appropriate treatment for hypertension that is effective and well-tolerated; that is, switching patients to an ARB from an ACEi who are already doing well isn't necessarily warranted. For those patients with a new hypertension diagnosis, though, and/or those patients whose blood pressure control is inadequate and need an additional agent, it may make sense to consider ARBs over ACEis. If you'd like to read more, there's an AFP By Topic on Hypertension which includes sections on Treatment, Improving Practice, and also resources from FPM.  

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.

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.

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.

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.

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.

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.

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.

**

Leaders of the the United Kingdom Health Alliance on Climate Change have published a follow-up document about the accomplishments and shortcomings of the United Nations Climate Change Conference (COP26) in Glasgow.

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 dysfunction 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.

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) protocol. Unfortunately, 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.

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.

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.