Monday, May 16, 2022

Mitigating the hidden toll of alcohol use during the pandemic

 - Kenny Lin, MD, MPH

Over the past two years, many of my patients have been drinking more alcohol than in the past, reflecting a troubling national response to COVID-19 pandemic-related stress that Dr. Jennifer Middleton highlighted in a previous AFP Community Blog post. Two recently published studies assessed the increased death toll of unhealthy drinking habits. Alcohol-related deaths occur due to direct effects of alcohol on the body, such as alcoholic hepatitis (severe cases have a 16-30% mortality rate at 28 days and 56% at one year) or via indirect contributions to fatal traffic and nontraffic injuries (e.g., drowning, falls, aspiration, hypothermia, firearm injuries).

The first study used death certificate data from the National Center for Health Statistics to compare numbers and rates of alcohol-related deaths among individuals 16 years or older in 2019 and 2020. Both the absolute number and age-adjusted rate of deaths involving alcohol increased by about 25%, greater than the 16-18% increases in all-cause deaths and death rate during this period. The largest increases (37-40%) were observed in adults aged 25 to 44 years. A second study used data from the National Vital Statistics System to evaluate mortality trends in adults with the diagnosis of alcohol use disorder (AUD) before (2012-2019) and during (2020-2021) the pandemic. Similarly, deaths with AUD listed as a primary or contributing cause during 2020 and 2021 exceeded projected deaths based on pre-pandemic data by 25% and 22%, respectively, with the 25 to 44 year-old age group demonstrating the largest increases (40% and 34%).

For patients who survive alcoholic hepatitis and other alcohol-related life-threatening injuries, it is critical to offer evidence-based medical therapy for AUD, outlined in a 2020 AFP article. Since the effects of AUD may not be clinically evident, the U.S. Preventive Services Task Force recommends screening and brief behavioral counseling interventions in adolescents and adults to reduce unhealthy alcohol use. Managing alcohol withdrawal syndrome and referring patients to Alcoholics Anonymous and other 12-step facilitation programs for AUD are also important mitigation strategies for primary care clinicians.

What about patients who have long been told that having a glass of wine with dinner is good for the heart? Setting aside the question of whether patients underestimate personal alcohol consumption, a large (n=371,463) United Kingdom cohort study recently challenged the theory that light alcohol consumption lowers cardiovascular risk. Investigators found that after adjustment for healthier lifestyles, light alcohol use (up to 1 drink per day) was associated with increased risk for hypertension and coronary artery disease compared to no use. Heavy use (more than 2 drinks per day) was associated with exponentially increasing cardiovascular risks.

Monday, May 9, 2022

Is adenovirus responsible for the hepatitis outbreak in children?

 - Jennifer Middleton, MD, MPH

The cause of the hepatitis outbreak in children across the United States and Europe remains a mystery, with over 100 cases of concern identified in the United States (US). Some cases have been associated with adenovirus infection, and the US Centers for Disease Control and Prevention's (CDC) current health advisory advises physicians to test all children with acute hepatitis of unknown etiology for adenovirus.

The outbreak first came to attention on April 12, 2022, when the European Centre for for Disease Prevention and Control reported 70 cases of "severe acute hepatitis" in previously healthy children under the age of 16, most between the ages of 2 to 5 years, across England and Scotland in the weeks prior. Most children presented with jaundice, though some presented with vomiting. All had significantly elevated liver transaminases (>500 U/L) and negative testing for known hepatitis viruses (hepatitis A, B, C, D, and E). Some (exact figures not provided) had positive SARS-CoV-2 tests, and some had positive adenovirus tests.

A few days later, on April 21, 2022, the US CDC issued a health advisory regarding a cluster of similar hepatitis cases at a children's hospital in Alabama: "Case-finding efforts at this hospital identified...a total of nine patients admitted from October 2021 through February 2022; all five that were sequenced had adenovirus type 41 infection identified." All of these children were previously healthy, all tested negative for hepatitis A, B, and C, and all tested negative for SARS-CoV-2 infection. That same day, the CDC issued a health alert, requesting that physicians "report any suspected cases of hepatitis of unknown origin to their local and state health departments."

A CDC Mortality and Morbidity Weekly Report (MMWR) last week reviewed the details of the 9 cases in Alabama. The children were from different areas of the state and were not otherwise connected:

Elevated transaminases were detected among all patients (alanine aminotransferase [ALT] range = 603–4,696 U/L; aspartate aminotransferase [AST] range = 447–4,000 U/L); total bilirubin ranged from normal to elevated (range = 0.23–13.5 mg/dL, elevated in eight patients). All patients received negative test results for hepatitis viruses A, B, and C, and several other causes of pediatric hepatitis and infections were ruled out including autoimmune hepatitis, Wilson disease, bacteremia, urinary tract infections, and SARS-CoV-2 infection. None of the children had documented history of previous SARS-CoV-2 infection. 

Cases have now been documented in additional European countries as well as Israel. Going forward, the more data the CDC can gather, the greater its chances of solving this puzzle - and, potentially, identifying treatment and/or mitigation measures to benefit patients. Physicians in the US can help by:

  1. Notifying the CDC (ncirddvdgast@cdc.govand/or your state health department "of children <10 years of age with elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) (>500 U/L) who have an unknown etiology for their hepatitis (with or without any adenovirus testing results, independent of the results) since October 1, 2021."
  2. Testing children with hepatitis of unknown etiology for adenovirus 41: "NAAT (e.g. PCR) is preferable and may be done on respiratory specimens, stool or rectal swabs, or blood." 

If you'd like to refresh your knowledge regarding hepatitis, there's an AFP By Topic on Hepatitis (and Other Liver Diseases) that includes comprehensive overviews of diagnosis and treatment.


Monday, May 2, 2022

In patients with heart failure, a low-sodium diet does not improve outcomes

 - Kenny Lin, MD, MPH

A common contributor to acute exacerbations of chronic heart failure is having one or more high-sodium meals prior to the onset of symptoms. It seems reasonable, then, to recommend that patients with heart failure adhere to a low-sodium diet to reduce readmissions and mortality and improve quality of life. But until recently, there was limited evidence to support or refute this line of thinking. In a 2014 editorial, American Family Physician associate editor Barry Weiss, MD discussed several studies showing that a low-sodium (less than 1,800 mg per day) diet produced no benefits and increased mortality compared to a normal diet in heart failure patients in the outpatient and inpatient settings. Consequently, he advised that "based on current evidence and until further studies are completed, patients with heart failure should probably be discouraged from reducing their sodium consumption to less than 2,300 mg per day."

Two subsequent systematic reviews of studies of dietary sodium restriction in heart failure also questioned low-sodium dogma. A 2018 review of 9 randomized trials with 479 participants with heart failure found insufficient data on cardiovascular-associated and all-cause mortality, stroke, and myocardial infarction and conflicting evidence on changes in New York Heart Association functional class. Similarly, a 2021 systematic review and meta-analysis of 10 trials (1011 participants) found that low-sodium diets did not improve quality of life and possibly increased readmission rates and mortality. However, most trials included fewer to 100 participants, leaving open the possibility that a larger trial powered to detect differences in clinical outcomes could still show benefits.

Last month, the Study of Dietary Intervention under 100 mmol in Heart Failure (SODIUM-HF) trial, with 806 participants from 26 sites in Australia, Canada, Chile, Colombia, Mexico, and New Zealand reported its primary findings. All participants in this pragmatic randomized trial were receiving optimally tolerated guideline-directed medical treatment for chronic heart failure. Participants were randomly assigned to usual care or a low sodium diet of <100 mmol/day (<1,500 mg/day). The primary outcome was a composite of cardiovascular-related hospitalization, emergency department visit, and all-cause mortality within 12 months. Median sodium intake decreased in the low-sodium group from 2,286 mg to 1,658 mg/day and in the usual care group from 2,119 mg to 2,073 mg/day by the end of the trial. However, in an intention-to-treat analysis, researchers found no statistical differences between the groups in the composite outcome or in each of the individual outcomes.

As Dr. Weiss cautioned in his AFP editorial, "the possibility that aggressive sodium restriction may lead to unfavorable outcomes in patients with heart failure should not ... be misconstrued as meaning that we should lose our focus on reducing sodium intake in the general population." Indeed, there is good evidence that population-level interventions are effective in preventing cardiovascular disease, including a large Chinese randomized trial of a salt substitute that Dr. Jennifer Middleton discussed in a previous AFP Community Blog post. That's why recent guidance for industry from the U.S. Food and Drug Administration that aims to reduce the average American's daily sodium intake from 3,400 mg to 3,000 mg/day over the next few years could also have a positive public health impact.

Monday, April 25, 2022

Introducing the 2022-23 AFP Jay Siwek Medical Editing Fellow: Dr. Jarrett Sell

 - Jennifer Middleton, MD, MPH

It's my pleasure to introduce our 2022-23 Jay Siwek Medical Editing Fellow, Dr. Jarrett Sell, whose fellowship year will begin June 1. Here are some highlights from a recent interview:

1. Tell us a little about yourself.

I grew up in a rural area of Maryland and entered medical school at the University of Virginia with an interest in practicing family medicine in an area of need. After residency in Phoenix, I was able to return to a small town in Virginia where I practiced traditional family medicine without OB for 8 years. Eleven years ago, I made the switch from private practice to academic medicine and have enjoyed the breadth of teaching, scholarship, and clinical practice which has focused on local community needs and marginalized populations, such as those who identify as LGBTQ+ and those affected by HIV.  


2. What got you interested in medical editing and writing? 


As a life-long reader of fiction, nonfiction, and medical journals, I found that medical editing and writing brings together my natural curiosity and passion for teaching.  The American Family Physician (AFP) journal has personally served as an invaluable resource throughout my career as a student, resident, practicing physician, and clinical educator in its clear presentation of evidence-based approaches to care. I started medical writing as I entered academic medicine and found writing to be a great way to dive deeper into clinical topics of interest with a focus on how the current evidence can inform patient care, particularly for primary care providers. I also found that I enjoyed collaborating with students, residents and other faculty with the goal of improving patient care and advocating for better care for marginalized populations.   


3. What are you hoping to get out of the fellowship? 


I look forward to advancing my skills in medical editing, enriching medical education, collaborating to enhance the journal’s innovation, and improving patient care.  I hope to gain a better understanding of the editing process through collaboration with the diverse and experienced AFP team of editors, and I hope to share some of these skills with other learners.  

 

4. Is there anything else you'd like AFP readers to know about you? 


Outside of work I enjoy live music, reading, time with family, getting outdoors to hike, ski and boat, and I have recently restarted playing tennis after last playing seriously over 20 years ago.   


Welcome to AFP, Dr. Sell!

Monday, April 18, 2022

How did Family Medicine fare in this year's National Resident Match?

 - Kenny Lin, MD, MPH

Well into the fourth year of the America Needs More Family Doctors: 25 X 2030 Collaborative, Match Day 2022 brought some good news: the "largest class of [incoming family medicine] residents ever," according to the American Academy of Family Physicians (AAFP). As Dr. Clif Knight, then the AAFP's Senior Vice President for Education, wrote after the 2020 Match, it was uncertain how the COVID-19 pandemic would affect the number of fourth-year students who matched into family medicine residency programs, even as practicing family physicians were demonstrating their value to health care systems:

The increasingly prominent role of family physicians during the past few months highlights the versatility of family medicine training and competencies. Family physicians have flexed into inpatient, community outreach, and emergency coordination roles. ... The future for family physicians will be promising in the postpandemic era if the opportunities to appropriately reform primary care practice, regulation, and payment are enacted swiftly and with permanence.

A recent commentary in the New England Journal of Medicine pointed out that stable Match rates from year to year can obscure worrisome trends in the residency selection process. For example, the proportion of U.S. MD seniors who match to their top-ranked program has decreased steadily since the mid-2000s, while the proportion who match to their fourth choice or lower has increased. During this time, the number of applications submitted per applicant increased dramatically:

Between 2007 and 2020, ... the number of applications submitted per applicant doubled, with the average U.S. medical school graduate submitting 70 residency applications and the average IMG submitting 139 in 2020. The average internal medicine or general surgery residency program now receives more than 100 applications for every available position. As a consequence, programs interview and rank more applicants than they did in the past. Even though program fill rates are unchanged, there has been a steady increase in the number of applicants that programs must rank to fill each position, from 9.2 in 2002 to 15.4 in 2021. In other words, despite the stability in applicant match rates, program fill rates, and the ratio of PGY-1 positions to applicants, the residency-selection process has grown increasingly stressful, inefficient, and expensive as applicants have applied to more programs.

Delving deeper into the results of the 2022 Match reported by the AAFP provides ample reasons for pessimism. The number of U.S. MD seniors matching into Family Medicine fell from 1,623 in 2021 to 1,555 in 2022, representing only 8.4% of all matched U.S. MD seniors and at 31.5%, their lowest Family Medicine fill rate in history. (In contrast, the 30.3% fill rate of U.S. DO seniors was the highest ever, with 22.4% of all U.S. DO seniors matching to Family Medicine.) Overall, only 12.2% of U.S. medical school graduates will be entering family medicine residency programs in July, less than half of the specialty's 25% X 2030 goal.

In a critical analysis of the past four decades of Match results, Drs. Richard Young and Sophia Tinger observed that Family Medicine interest among U.S. MD graduates has stagnated for the past 10 years, and "there are no indications in the present environment (reimbursement by specialty, legislative mandates, new strategies to increase student interest in family medicine, the COVID-19 pandemic, or anything else) to suggest that the current trends will change over the next 9 years." Or to put it bluntly, "the 25 X 2030 Collaborative will almost certainly fail to reach its goal."

The consequences of an inadequate U.S. primary care workforce to the future health of all Americans could be dire. In a Graham Center Policy One-Pager in the April issue of AFP, Dr. Yalda Jabbarpour and colleagues examined the association of the Community Health Index (CHI; "an average score of public health preparedness, primary care physician supply rates, and the social deprivation index (a proxy for community-level factors such as housing and transportation)") with county-level COVID-19 death rates before and after widespread vaccine availability. Counties with higher CHI scores had lower COVID-19 mortality rates overall, with the number of deaths per 100,000 individuals falling most drastically after vaccination in counties in the highest quintile of CHI scores.

Monday, April 11, 2022

Treating acute asthma symptoms with beclomethasone (instead of albuterol) decreases rate of exacerbations

 - Jennifer Middleton, MD, MPH

The most recent global asthma guidelines advocate against the routine use of short-acting beta agonists (SABAs) for patients with mild asthma, and now a randomized controlled trial (RCT) has found that albuterol (a SABA) was inferior to beclomethasone, an inhaled corticosteroid (ICS), for acute symptom control in persons with asthma regardless of baseline asthma severity.

The researchers only enrolled Black and Latinx patients in this RCT, acknowledging that "guideline recommendations have not been based on studies in these populations." They randomized 1201 outpatients with moderate-to-severe asthma to either albuterol (usual care) or beclomethasone (intervention group) for acute symptom relief and followed them for 15 months. They found that "[t]he annualized rate of severe asthma exacerbations was 0.69 (95% confidence interval [CI], 0.61 to 0.78) in the intervention group and 0.82 (95% CI 0.73 to 0.92) in the usual-care group (hazard ratio, 0.85; 95% CI, 0.72 to 0.999; P=0.048)." Asthma symptoms and missed days of work, both secondary outcome measures in the study, also favored the beclomethasone intervention group.

In 2020, the Global Initiative for Asthma (GINA) guidelines recommended against SABA use as monotherapy for mild asthma, citing data showing increased mortality and exacerbations in patients who only used albuterol for even mild asthma symptoms. The GINA guidelines instead recommend the use of an ICS in combination with formoterol, a long-acting beta agonist (LABA), for acute relief of asthma symptoms in all patients with asthma, regardless of baseline severity. The guidelines do list use of an as-needed SABA as an acceptable option for patients on an ICS already at baseline; this newest study suggests that, even in those patients, SABAs are inferior to ICS for acute symptoms.

Switching from albuterol to either ICS or ICS/LABA inhalers will require substantial changes in the US from both the Food and Drug Administration (FDA) and insurance companies. Symbicort, the only ICS/formoterol product currently FDA-approved in the US, is not FDA-approved for as needed use. Symbicort comes with 60 doses per inhaler; insurance companies in the US do not typically cover  more than 1 inhaler a month, which may be sufficient for patients who do not need treatment daily, but patients with more severe asthma could easily exceed 60 doses in a month using it for both daily control and as needed. Without insurance, Symbicort costs at least $200/month and is not available yet as a generic; even with insurance, many patients pay significant co-pays. Beclomethasone (Qvar) is also quite expensive, costing at least $200 per inhaler.

Advocating for these changes was precisely what the RCT researchers intended, according to the study registry on clinicaltrials.gov:

The investigators have consulted with AA [African American] and H/L [Hispanic/Latinx] patients, health care providers, leaders of professional societies, advocacy groups, health policy leaders, pharmacists, and pharmaceutical manufacturers. All groups have indicated that asthma decision making would be changed if it was demonstrated that implementing PARTICS [Patient Activated Reliever-Triggered Inhaled CorticoSteroid] improves important asthma outcomes such as reducing rates of exacerbations.

The researchers' efforts to partner with patients and advocacy groups is laudable, and hopefully this study helps to spur needed change in asthma inhaler affordability and access. 

If you'd like to read more, this AFP article on "Asthma: Updated Diagnosis and Management Recommendations from GINA" provides a useful overview of the GINA recommendations, which is included in the AFP By Topic on Asthma.

Monday, April 4, 2022

Curbing cascades and low-value care in children

 - Kenny Lin, MD, MPH

Both editorials in the March issue of AFP discussed aspects of the problem of unnecessary health care services. In "Curbing Cascades of Care: What They Are and How to Stop Them," Dr. Ishani Ganguli, whose work in identifying low-value services was featured in a previous AFP Community Blog post, presented the case of a healthy 30-year old man with a heart murmur detected at an annual wellness visit. The physician ordered an echocardiogram that suggested pulmonary hypertension, leading to a cardiology visit and a right heart catheterization which showed normal pressures. Of this "false alarm" and others like it, the author observed:

Such stories are viscerally familiar to most clinicians. This is a cascade of care: a seemingly unstoppable succession of medical services often initiated by an unnecessary test or unexpected result and driven by the desire to avoid even the slightest risk of missing a potentially life-threatening condition. ... Each step in a cascade seems to be a rational progression from the step before. Yet taken together, these cascades can cause substantial harm to patients, including procedural complications, out-of-pocket costs, psychological distress, and stigma from new diagnoses. Clinicians, especially those practicing in rural settings, report anxiety, frustration, and wasted time and effort.

Dr. Ganguli then discussed two health systems strategies to stop cascades of care: avoiding unnecessary services that may trigger cascades (though Choosing Wisely is often easier said than done) and mitigating cascades through providing better point-of-care guidance regarding management of incidentalomas and engaging patients in shared decision-making rather than assuming that they will always prefer more testing in the face of uncertainty.

In a second editorial, Dr. Kao-Ping Chua reviewed "The Importance and Challenges of Reducing Low-Value Care in Children," noting that use of unnecessary services in this population is widespread, harms children and their families, and is costly to families and the health care system. Commenting on a Lown Right Care article in the same issue on the inappropriate use of an electrocardiogram (ECG) in a preparticipation sports examinations, Dr. Chua wrote:

Harms included the temporary exclusion from sports, the direct costs of ECGs and the cardiology visit, and the indirect costs to the family (e.g., costs of transportation to the cardiologist visit, missed school or work). The ECG may have also caused unnecessary emotional stress to the patient and family because it erroneously raised the possibility of a potentially life-threatening cardiac disorder.

On the other end of the age spectrum, a recent report in JAMA Network Open described the development of Evaluating Opportunities to Decrease Low-Value Prescribing (EVOLV-Rx), a tool for detecting 18 low-value prescribing practices in older adults based on scientific validity and clinical usefulness.

Ultimately, EVOLV-Rx, the KIDs List for potentially inappropriate medications in children, and other interventions to reduce low-value care should be evaluated on improvements in patient-oriented and/or reported outcomes (increased benefit, decreased harm, few unintended consequences) rather than reductions in services alone. A 2019 systematic review of more than 100 studies of such interventions found that clinically meaningful measures were often lacking. Nonetheless, individual clinicians can follow the suggestions of Drs. Ganguli and Chua to spend less time handling false alarms and more on concerns and conditions that matter to patients.

Monday, March 28, 2022

Post-op complications increase < 8 weeks after COVID-19 diagnosis

 - Jennifer Middleton, MD, MPH

Health care systems across the world have paused elective surgeries at various points during the COVID-19 pandemic. Numerous asymptomatic patients have also been surprised by a positive pre-op COVID-19 test and had to reschedule their planned surgery. In the health system where I work, once those patients have finished their quarantine, they are free to reschedule their procedures. A new database study suggests that a longer waiting period might reduce post-operative complications; the study reviewed the records of over 5000 persons who had a positive COVID-19 PCR test and had surgery, either in the 4 week period before their positive test or in the weeks after their COVID-19 diagnosis; the study found an increased risk of post-operative complications for patients who had elective surgery within 8 weeks of documented COVID-19 infection.

The study authors used the COVID-19 Research Database, which "includes de-identified and limited datasets from medical and pharmacy claims data, EHR data, mortality data, and consumer data" from across the United States. Over 316 million unique individuals are captured in this database, which the researchers searched to identify persons with positive COVID-19 tests who had undergone elective surgeries in the weeks prior to or following their positive test. The study authors included a wide range of major, but not urgent or emergent, surgeries including mastectomies, colorectal resections, joint replacements, spinal fusions, and coronary artery bypass grafting (CABG). They identified 5479 patients who met study criteria, about half of whom had their surgeries before their COVID-19 diagnosis and about half of whom had their surgeries after their COVID-19 diagnosis. They divided patients into 4 categories: "pre-COVID-19" (control group), "peri-COVID-19" (0-4 weeks after diagnosis), "early-post-COVID-19" (4-8 weeks after diagnosis), and "late-COVID-19" (more than 8 weeks after diagnosis). Less than 2% of included patients had COVID-19 disease considered severe or critical. The researchers found that:

After adjustment for patient characteristics and type of surgery, peri-Covid-19 patients had a significantly higher risk of developing postoperative pneumonia [adjusted odds ratio (aOR), 6.46; 95% confidence interval (CI), 4.06–10.27], respiratory failure (aOR, 3.36; 95% CI, 2.22–5.10), PE (aOR, 2.73; 95% CI, 1.35–5.53) and sepsis (aOR, 3.67; 95% CI, 2.18–6.16) when compared to pre-Covid-19 patients. For most complications, early post-Covid-19 patients did not have a higher risk when compared to pre-Covid-19 patients; however, early post-Covid-19 patients did have a higher risk of developing postoperative pneumonia (aOR, 2.44; 95% CI: 1.20–4.96). 

The study authors appropriately note that "the balance between the risk of postoperative complications and the risk of worse overall survival associated with delayed surgical treatment should be carefully discussed;" for some patients, especially those with cancer, postponing surgery may not be the best balance of benefit and harms. When appropriate, though, discussing this apparent benefit of postponing surgery with our patients - and our surgical colleagues - may help decrease patients' risk of post-operative pneumonia, respiratory failure, and sepsis.

You can find AFP content with the keyword "perioperative care" here, including this article on "Preoperative Testing Before Noncardiac Surgery: Guidelines and Recommendations." The AFP By Topic page on COVID-19 also continues to be regularly updated if you'd like to read more. 

Monday, March 21, 2022

Neurocognitive symptoms in patients with celiac disease and non-celiac gluten sensitivity

- Lilian White, MD

Celiac disease is an autoimmune disorder that results from antibodies to components of gluten. Globally, about 0.7-1.4% of the population has celiac disease. When people with celiac disease eat gluten, their bodies respond by forming antibodies to components of the gluten protein. These antibodies also bind to the villi of intestinal cells, resulting in a variety of signs and symptoms. Classic celiac disease typically presents with localized gastrointestinal (GI) symptoms, including diarrhea, constipation, malabsorption, abdominal pain, bloating, and weight loss. Patients with non-classic celiac disease (which, interestingly, is more common than classic celiac disease) develop symptoms that do not significantly involve the GI tract. These signs and symptoms can include fatigue, joint pain, dermatitis herpetiformis, iron deficiency anemia, migraines, depression, attention deficit disorder, epilepsy, infertility, and low bone density. Some experts prefer to use the terms “intestinal” and “extraintestinal” in place of classic and non-classic celiac disease.

Non-celiac gluten sensitivity is characterized by signs or symptoms associated with gluten ingestion without laboratory findings associated with celiac disease or wheat allergy. Estimates of its prevalence range widely from 0.49% to 14.9%. Symptoms vary and may present in a wide variety of ways, like the intestinal and extraintestinal manifestations of celiac disease.

Neurocognitive symptoms are commonly described by patients with celiac disease; however, there has been little formal study of these symptoms. Neurologic effects of celiac disease have generally been limited to descriptions of neuropathy, epilepsy, and ataxia. A recent survey study of 1396 patients with celiac disease and non-celiac gluten sensitivity was conducted to better understand neurocognitive effects (referred to more informally as “brain fog”) in patients following gluten ingestion. Participants were recruited from the e-mail contact database and social media platforms of the patient advocacy organization Beyond Celiac. 9 in 10 participants reported acute neurocognitive symptoms after gluten ingestion, including forgetfulness, difficulty concentrating, and grogginess. Both groups also noted similar onset and peak of symptoms at 1-2 days, with many continuing to have symptoms 3-5 days later.

While limited by the self-selected population, this study suggests that both patients with celiac disease and non-celiac gluten sensitivity have neurocognitive symptoms following gluten ingestion. The duration of symptoms observed demonstrates the potential to significantly affect patients’ work and/or school performance. It may be helpful for family physicians to ask patients with celiac disease and non-celiac gluten sensitivity if they experience neurocognitive symptoms to better understand how these may be affecting their cognitive functioning and performance.

**

Dr. White, a second-year resident at the Cleveland Clinic Family Medicine Residency Program, is a 2022 AFP Resident Representative.

Monday, March 14, 2022

"Long COVID" symptoms in COVID-19 ICU survivors

 - Jennifer Middleton, MD, MPH

Our understanding of Post-Acute Sequelae of SARS-CoV-2 (PASC), also known as "post-COVID conditions," and/or "long COVID," continues to grow as we pass the 2-year mark of the onset of the COVID pandemic in the United States (US). In the spring of 2021, Dr. Lin reviewed data suggesting that approximately 10% of persons who are infected with COVID experience symptoms for greater than 4 weeks; since then, estimates of PASC have ranged as high as 50% in COVID survivors. A new study sought to identify the prevalence of PASC in persons with COVID-19 infection who required care in the intensive care unit (ICU) and found even higher rates of persistent symptoms, but it's unclear what degree of those symptoms were specifically due to COVID-19.

The symptoms associated with PASC are numerous and include physical, mental, and cognitive concerns, including "cough, breathlessness, fatigue, fever, sore throat, nonspecific chest pains (lung burn), cognitive blunting (brain fog), anxiety, depression, skin rashes, and diarrhea." This study of ICU COVID-19 survivors followed the outcomes of 246 persons in the Netherlands who had been admitted at least one year prior. The researchers sent surveys to these survivors that included several validated symptom scores for physical, mood, and cognitive symptoms following hospitalization. They found that:

At 1 year after ICU treatment for COVID-19, physical symptoms were reported by 182 of 245 patients (74.3% [95% CI, 68.3% to 79.6%]), mental symptoms were reported by 64 of 244 patients (26.2% [95% CI, 20.8% to 32.2%]), and cognitive symptoms were reported by 39 of 241 patients (16.2% [95% CI, 11.8% to 21.5%]).

The study authors appropriately note that these outcomes are quite similar to those published in patients without COVID-19 surviving ICU care. It's difficult to disentangle, at this point, how much of this symptom burden is directly attributable to COVID-19 infection versus just the expected sequelae of illness serious enough to require ICU care - not to mention that the stress of ICU care itself can cause post-traumatic stress disorder (PTSD) (with a prevalence of approximately 10%). It certainly seems plausible, though, that patients with severe COVID-19 infection would also have at least a similar, if not higher, risk of PASC as those patients with COVID-19 who didn't need ICU care. 

Regardless of the exact numbers and/or the degree of contribution of COVID-19 itself, primary care clinicians are likely to provide much of the care to COVID-19 survivors with persistent symptoms. These high prevalence rates should encourage us to ask proactively about PASC/"long COVID" symptoms in our COVID-19 survivors and to validate our patients' frustration and suffering. Though we still have much to learn about PASC, informal guidelines are emerging regarding best treatment practices; this AFP editorial on "Long COVID: A Primer for Clinicians" contains a helpful overview, and look soon for review article on long COVID in an upcoming issue of AFP. The US Centers for Disease Control and Prevention (CDC) also has interim guidance on Post-COVID conditions on its website, and this AFP article on "Post-ICU Care in the Outpatient Setting" provides excellent guidance as well for caring for ICU survivors in general.

Tuesday, March 8, 2022

Debating colorectal cancer screening recommendations: too young, too often?

 - Kenny Lin, MD, MPH

Last year, the U.S. Preventive Services Task Force (USPSTF) updated its colorectal cancer screening recommendations, lowering the starting age for average-risk adults from 50 to 45 years; this change was reflected in the Putting Prevention Into Practice case study in American Family Physician's September 2021 issue. However, after reviewing the USPSTF statement and supporting documents, the American Academy of Family Physicians (AAFP) concluded that the evidence was insufficient to recommend a starting age younger than 50. Two editorials in the February issue of AFP outlined the arguments for and against starting routine screening at 45 years of age.

In the first editorial, Dr. Richard Wender argued that "lowering the starting age is a settled issue," noting that several organizations, including the American Cancer Society, the National Comprehensive Cancer Network, and the American College of Gastroenterology have all independently reviewed the data and come to the same conclusion as the USPSTF. He pointed out that "the incidence of colorectal cancer in 45 year-olds today is ... almost identical to the risk in 50-year-olds in 1979 when colorectal cancer screening was first recommended," and that nearly a quarter of deaths from colorectal cancer in the U.S. occur in individuals diagnosed between 45 and 54 years of age. Four microsimulation models have also concluded that starting screening at 45 years of age is the most efficient strategy to maximize life-years gained per colonoscopy regardless of the initial screening test used (including the multitarget stool DNA test discussed in the same issue of AFP).

The second editorial, by Drs. Corey Lyon, Alexis Vosooney, and Melanie Bird, elaborated on the AAFP's position. The authors noted that "many of the trials used in the modeling studies did not include individuals younger than 50 years or did not provide separate data for this younger age group, decreasing confidence in the data inputs." They also expressed concern about costs to patients and the health care system from implementing the USPSTF recommendation as opposed to optimizing screening in patients age 50 years and older: "Expanding screening to up to 80% of eligible patients 50 to 75 years of age would prevent three times as many colon cancer deaths at one-third of the cost [of routinely screening Americans 45 to 49 years of age]." (A previous AFP Community Blog post by Dr. Jennifer Middleton described two modestly successful outreach strategies to patients who were not up to date on colorectal cancer screening.) Finally, they argued that persistent disparities in colorectal cancer incidence and mortality in Black patients would be more appropriately addressed by improving insurance coverage and access to care in this population rather than lowering the age to start screening. 

While colorectal cancer screening tests remain underused by many patients, studies have also documented that screening colonoscopies are performed more often than necessary - for example, being repeated 9 or fewer years after an initial high-quality colonoscopy showed no significant pathology, in contrast to the American Gastroenterological Association's Choosing Wisely recommendation. A recent systematic review of 6 studies that estimated the rate of overuse of screening colonoscopy in U.S. populations found that it ranged from 17% to 25.7%. Overuse occurs when endoscopists recommend that patients have subsequent colonoscopies at intervals shorter than those supported by guidelines, and primary care physicians (PCPs) defer to subspecialists' recommendations. In an editorial, Drs. Archana Radhakrishnan and Craig Pollack explained the obstacles that PCPs face in going against subspecialist advice but argued that they can still "play an important role in preventing overuse of colorectal cancer screening and surveillance colonoscopies" by directing referrals appropriately and communicating with endoscopists about deviations from evidence-based practices.

Monday, February 28, 2022

What are the best medications for panic disorder?

 - Jennifer Middleton, MD, MPH

The COVID-19 pandemic is continuing to worsen mental health around the world; early studies from 2020 were already showing an increased prevalence of depression, anxiety, and panic disorder, and studies from 2021 demonstrate continued increasing rates of these mental health disorders. With several Food and Drug Administration (FDA) approved medications for panic disorder currently available in the United States, choosing an initial medication for patients with a new diagnosis can feel overwhelming. A newly published systematic review and network meta-analysis sought to identify the most effective medications for panic disorder and found that sertraline and escitalopram had the best balance of benefit and adverse events.

The systematic review and network meta-analysis examined the literature through June 2021 regarding pharmaceutical options for panic disorder. The researchers looked for randomized controlled trials (RCTs) that included adults aged 18 years and older and cited outcomes related to either benefit (remission rates) and/or harm (including somnolence, gastrointestinal problems, and cognitive impairment). They identified 87 studies with a total of 12,800 participants and followed appropriate systematic review methodology to extract and synthesize the data. Most of the studies compared medication treatment to placebo, so the authors conducted a network meta-analysis to compare outcomes among the various medication classes and medications identified in the systematic review:

Our network meta-analysis identified 11 current drug classes for the treatment of panic disorder, highlighting benzodiazepines, tricyclic antidepressants, and SSRIs as the highest ranked treatments for remission based on SUCRA values. Although benzodiazepines were associated with the lowest probability of dropout, they were also associated with the highest risk of adverse events. Overall, SSRIs provided high benefit (remission) with low risk of adverse events. Across individual SSRIs, sertraline and escitalopram were identified as the most efficacious agents with low risk of adverse events.

The researchers also evaluated included studies for risk of bias, and they noted that "[t]he findings were...based on studies of moderate to very low certainty levels of evidence, mostly as a result of within study bias, inconsistency, and imprecision of the findings reported." Nevertheless, this study's comprehensive and rigorous comparisons may still help guide treatment decisions for patients presenting with panic disorder.

Medications are a useful tool for treating panic disorder, but cognitive behavioral therapy is very effective as well (number needed to treat for complete remission of panic after 3-4 months = 2). Accessing support resources can be beneficial; I included a list of mental health resources developed during the pandemic in this blog post from 2020, and I especially like this one from the World Health Organization that emphasizes the importance of simple self-care habits. 

It's also important to precisely diagnose patients to guide treatment recommendations. This 2015 AFP article on "Diagnosis and Management of Generalized Anxiety Disorder and Panic Disorder in Adults" includes diagnostic criteria for both Generalized Anxiety Disorder and panic disorder along with an overview of treatment options - both pharmaceutical and non-pharmaceutical - to discuss with patients. There's also an AFP By Topic on Anxiety Disorders if you'd like to read more. 

Monday, February 21, 2022

Is COVID-19 vaccination beneficial in persons with past infection?

 - Kenny Lin, MD, MPH

Since the first COVID-19 vaccine received authorization for emergency use in December 2020, physicians and the public have vigorously debated whether infection-acquired ("natural") or vaccine-mediated immunity provides better protection against future infection and severe illness. The answer may never be known for certain, as observational studies are limited by confounding and it's hard to imagine a research ethics committee approving a trial that randomizes one group to intentional exposure to a potentially lethal infection. A more important clinical question is: does getting vaccinated after recovery from COVID-19 provide additional benefits? Currently, the Centers for Disease Control and Prevention recommends routine vaccination in all persons aged 5 years or older, regardless of their history of past infection.

Two large cohort studies published last week provided the strongest evidence to date that the answer is yes. The first study used electronic medical records from a health care organization covering more than half of the population of Israel to identify 149,000 patients age 16 years or older who had recovered from documented SARS-CoV-2 infection at least 100 days earlier and had not yet received COVID-19 vaccination as of March 1, 2021. 56% of these persons received at least one dose of BNT162b2 (Pfizer-BioNTech) vaccine by November 26, 2021. 2,168 of those who remained unvaccinated (3.3%) were reinfected during the study, compared to 354 of the vaccinated patients (0.4%). After adjustment for sociodemographic factors and coexisting illnesses, the estimated vaccine effectiveness was 82% for patients aged 64 years or younger and 60% for patients aged 65 years or older. A secondary analysis showed no difference in protection between one or two vaccine doses.

A second study in a highly vaccinated cohort of 35,768 health care workers in the United Kingdom tracked primary infections and reinfections between December 7, 2020 and September 21, 2021. Most participants received two doses of BNT162b2 (Pfizer-BioNTech) vaccine; 8% received the single-dose ChAdOx1 nCoV-19 vaccine (AstraZeneca). In previously uninfected participants who received the second dose of BNT162b2 six weeks or more after the first dose, adjusted vaccine effectiveness was 85% up to 73 days after the second dose but declined to 51% after 200 days. In comparison, adjusted effectiveness of the ChAdOx1 nCoV-19 vaccine was only 58% up to 73 days. In 6,169 participants who had COVID-19 prior to the study, long-term (>1 year) protection against re-infection was 69% in unvaccinated persons but remained high at 94% in persons who received one or two doses of BNT162b2.

Acknowledging some differences between the populations and the predominant variants circulating during the respective study periods, the results support the following conclusions. First, re-infection in unvaccinated persons is relatively uncommon during the first 9 months after a primary infection (1 in 30 in the Israeli study) but becomes more likely after 1 year (per the U.K. study). Similarly, the effectiveness of the initial two doses of BNT162b2 vaccine in preventing COVID-19 declines after 6-7 months, supporting booster doses. However, patients with past infections who subsequently receive one or two doses of BNT162b2 have sustained high levels of protection ("hybrid immunity") against re-infection for at least one year. In an editorial in The Guardian, Dr. Eric Topol recently argued that these and other data support re-defining "fully vaccinated" to include recovery from past infection plus a single dose of an mRNA vaccine.

Monday, February 14, 2022

COVID-19 vaccination in pregnancy may protect infants

 Jennifer Middleton, MD, MPH

COVID-19 vaccination is safe and beneficial in pregnant persons, a group that is especially vulnerable to complications from COVID-19 infection. Emerging research now suggests that these protections may extend to infants through at least the first 6 months of life. Building on earlier studies that demonstrated COVID-19 antibody transmission from mother to infant in utero and in breastmilk, a small study found antibodies against the SARS-CoV-2 spike protein persisted in infants whose mothers received COVID-19 vaccination in pregnancy. 

Researchers at Massachusetts General Hospital followed pregnant persons from their 2nd trimester who either received COVID-19 vaccination or had COVID-19 infection between weeks 20-32 of pregnancy. They chose this time frame because "previous studies have demonstrated superior transplacental transfer of antibodies during this window compared with vaccination closer to delivery." They then measured antibodies against the SARS-CoV-2 spike protein in the enrolled participants' infants for their first 6 months of life. 77 pregnant persons who received COVID-19 vaccination and 12 pregnant persons with symptomatic, documented COVID-19 infection were included in the study:

Vaccinated mothers had significantly higher titers at delivery with a mean (SD) of 2.03 (0.47) optical density (OD450-570) compared with mothers after infection with a mean (SD) of 0.65 (0.76) OD450-570 (P < .001)....Vaccination resulted in significantly greater antibody persistence in infants than infection. At 6 months, 57% (16 of 28) of infants born to vaccinated mothers had detectable antibodies compared with 8% (1 of 12) of infants born to infected mothers (P = .005). 

This study's findings suggest that "natural" immunity from disease is not superior, and may be inferior, to immunity induced by vaccination, though it's important to note that titer levels are a disease-oriented evidence (DOE) outcome. There is no evidence yet that COVID-19 vaccination in pregnancy reduces infants' risk of illness or hospitalization (POEM-level outcomes) compared to COVID-19 infection in pregnancy. Given that other established vaccines have demonstrated a link between infant titers and disease protection, however, this study offers hope that maternal COVID-19 vaccination may offer some protection to infants. 

Protecting infants is important despite conventional wisdom that COVID-19 infection is less severe in children than in adults. Infants appear to be at the highest risk of complications from COVID-19 among children under the age of 18 years. A study from China early in the pandemic (before vaccines were available), found that the prevalence of "severe" or "critical" COVID-19 complications in children under the age of 1 year was 8.8% and 1.9%, respectively. This information is important to share with pregnant persons and parents; yes, overall children have a lower risk of complications from COVID-19 infection, but infants have the highest risk among children under the age of 18 years.

No ongoing or planned COVID-19 vaccination trials include infants under the age of 6 months, so maternal vaccination - along with vaccination of all household members and close contacts - will likely be critical to protecting this age group from COVID-19 infection and its potential complications. Future studies are needed to establish maternal vaccination's benefit for preventing infections, hospitalization, and mortality in infants, but this newest study may inspire future research to answer those questions. In the meantime, we should continue to advise pregnant persons to receive COVID-19 vaccination, and perhaps the potential of benefit for their infant may sway some vaccine-hesitant individuals toward vaccination.

If you'd like to read more, the AFP By Topic on COVID-19 continues to be regularly updated, and this AFP editorial reviewing "Strategies for Addressing and Overcoming Vaccine Hesitancy" has many useful tips.


Tuesday, February 8, 2022

Screening for atrial fibrillation, revisited

 - Kenny Lin, MD, MPH

In 2018, the U.S. Preventive Services Task Force (USPSTF) concluded that there was insufficient evidence to assess the balance of benefits and harms of screening for atrial fibrillation (AF) with electrocardiography. However, the proliferation of wearable devices capable of detecting brief episodes of cardiac arrhythmias raised the question of whether screening high-risk patients outside of the office, analogous to home blood pressure monitoring, might prove beneficial. In a scientific statement, the American Heart Association discussed the knowledge gaps regarding the risk of stroke and benefits and harms of initiating long-term anticoagulation in persons with subclinical AF.

Two randomized screening trials published in 2021 provided a mixed picture. In the LOOP Study, 6004 Danish adults aged 70 to 90 years with stroke risk factors were randomized in a 1:3 ratio to receive an implantable loop recorder (ILR) or routine medical care. ILR participants were contacted if they had atrial fibrillation lasting for at least 6 minutes and recommended to start anticoagulation. Control participants received electrocardiography as needed from their primary care physicians. After a median follow-up of 64.5 months, 32% of patients in the ILR group and 12% of patients in the control group had atrial fibrillation detected, with similar proportions initiating oral anticoagulation. However, there was no significant difference in the primary outcome of stroke or systemic arterial embolism (4.5% of patients in the ILR group vs. 5.6% in the control group). Rates of major bleeding were not statistically different between the groups.

In the STROKESTOP trial, 28,768 Swedish adults aged 75 or 76 years were randomized to receive an invitation to screening with a handheld single-lead electrocardiogram twice daily for 2 weeks or usual care. After nearly 7 years of follow-up, a composite outcome of stroke, systemic embolism, hospitalization for bleeding, or all-cause mortality was slightly less likely to occur in the intervention group (NNT=93), but differences in individual outcomes were not statistically significant.

Reviewing these trial results and additional data, the USPSTF recently updated its 2018 statement and concluded that the evidence remains insufficient to make a recommendation. An accompanying editorial in JAMA Internal Medicine by Drs. John Mandrola and Andrew Foy (who authored a 2019 editorial on the downsides of detecting asymptomatic atrial fibrillation in AFP) noted that despite the potential benefits of widespread cardiac rhythm monitoring on cardiovascular and stroke risk, it "will also lead to misdiagnosis and downstream cascades of care" and that the "work-up of [arrhythmias] can lead to anxiety, iatrogenic harm, and excess health care costs."

Monday, January 31, 2022

Do probiotics reduce the risk of Clostridioides difficile colitis?

 Jennifer Middleton, MD, MPH

"Health Care-Associated Infections: Best Practices for Prevention" published by AFP online ahead of print last week reviews evidence-based recommendations to reduce the risk of hospitalized patients acquiring SARS-CoV-2, catheter-associated urinary tract infections (CAUTIs), central line-associated bloodstream infections (CLABSIs), ventilator-associated pneumonia (VAP), surgical site infections, and Clostridioides difficile (C diff) colitis. Of the authors' key recommendations for practice, the one that might be the most unexpected is the use of probiotics to prevent C diff colitis.

Clostridioides difficile colitis, also referred to as Clostridioides difficile-associated diarrhea (CDAD), caused "an estimated 223,900 cases in hospitalized patients and 12,800 deaths in the United States" in 2017, the latest year for which data is available per the Centers for Disease Control and Prevention (CDC); a 2020 study estimated the incidence of CDAD at 8.3 cases per 10,000 patient-days, increasing the length of hospital stays by at least 3 days and as much as 21.6 days. Given this morbidity and mortality burden, several studies have examined the use of probiotics to reduce the risk of acquiring CDAD, especially in hospitalized patients receiving antibiotics. 

In 2017, a Cochrane meta-analysis assessed the literature to date on the use of probiotics to prevent CDAD. The authors ended up including 39 studies:

 A complete case analysis (i.e. participants who completed the study) among trials investigating CDAD (31 trials, 8672 participants) suggests that probiotics reduce the risk of CDAD by 60%. The incidence of CDAD was 1.5% (70/4525) in the probiotic group compared to 4.0% (164/4147) in the placebo or no treatment control group (RR 0.40, 95% CI 0.30 to 0.52; GRADE = moderate)....However, in a post hoc analysis, we did observe a subgroup effect with respect to baseline risk of developing CDAD. Trials with a baseline CDAD risk of 0% to 2% and 3% to 5% did not show any difference in risk but trials enrolling participants with a baseline risk of > 5% for developing CDAD demonstrated a large 70% risk reduction (interaction P value = 0.01). Among studies with a baseline risk > 5%, the incidence of CDAD in the probiotic group was 3.1% (43/1370) compared to 11.6% (126/1084) in the control group (13 trials, 2454 participants; RR 0.30, 95% CI 0.21 to 0.42; GRADE = moderate). 

The Cochrane authors found a number needed to treat (NNT) of 42 among all study participants, and a NNT among participants at high risk of CDAD of 12. The definitions of "high risk" varied a bit among studies, but most were close to the CDC's parameters of age 65 years and older, hospital or nursing facility admission, immunocompromise, and/or a previous history of CDAD. The Cochrane reviewers acknowledged that, of the 39 included studies, "27 studies were rated as either high or unclear risk of bias."

A 2021 letter in the Journal of the American Board of Family Medicine argues further for the routine use of probiotics for all hospitalized persons receiving antibiotics. In addition to reviewing the 2017 Cochrane review's findings, the authors of this letter also discuss the findings of a 2020 systematic review regarding the cost reduction associated with use of probiotics to reduce CDAD and state that even though "[l]ack of standardization and heterogeneity of treatment remain challenges to implementing probiotic therapies," "the positive results and favorable safety profiles across studies are reassuring." The authors of this AFP article on "Probiotics for Gastrointestinal Conditions: A Summary of the Evidence" also conditionally recommend the use of probiotics to prevent CDAD and other forms of antibiotic-associated diarrhea.

As noted in this 2020 AFP article on "Clostridioides difficile Infection: Update on Management," the Infectious Disease Society of America (IDSA) does not currently recommend the use of probiotics to prevent CDAD, citing the limitations of studies done to date and the potential risks of prescribing probiotics for immunocompromised persons. It remains to be seen when the IDSA might update their 2018 guideline, but one thing the IDSA and the AFP authors agree on is the importance of antibiotic stewardship in reducing CDAD

While we await that guideline update and, hopefully, more robust studies, it may be reasonable to consider patient-centered decision making regarding probiotics' potential risks and benefits for our hospitalized patients who need antibiotics and are at high risk of CDAD. 

Monday, January 24, 2022

Newer glucose-lowering drugs also treat obesity and heart failure

 - Kenny Lin, MD, MPH

Last June, the U.S. Food and Drug Administration (FDA) approved a weekly semaglutide (Wegovy) subcutaneous injection for chronic weight management in adults with obesity or overweight with at least one weight-related condition, based on randomized controlled trial (RCT) evidence that it produces substantial weight loss in persons with a body mass index of 27 or greater without diabetes. A lower dose of semaglutide (Ozempic), a glucagon-like peptide-1 (GLP-1) receptor agonist, had previously been approved by the FDA as a second-line therapy for patients with type 2 diabetes that reduced risk of major adverse cardiac events (MACE) in patients with established cardiovascular disease (CVD).

A 2021 BMJ clinical practice guideline examined the benefits and harms of GLP-1 receptor agonists and sodium-glucose cotransporter 2 (SGLT-2) inhibitors and made recommendations for use of these two drug classes in persons with type 2 diabetes and different levels of CVD risk with and without chronic kidney disease, summarized in Patient-Oriented Evidence That Matters in the January issue of American Family Physician. A related editorial by Dr. Sandy Robertson discussed how evidence can inform when to recommend starting a diabetes drug from one of these two CVD risk-lowering classes:

Current data strongly support a reduction in MACE and all-cause mortality with SGLT-2 inhibitors and GLP-1 agonists in patients who have diabetes with established CVD or kidney disease. These patients should be offered one of these medications in the absence of contraindications, regardless of glucose control. Because there is no significant reduction in cardiovascular outcomes in patients who have diabetes without established CVD, patient-centered shared decision-making about adding an SGLT-2 inhibitor or a GLP-1 agonist for cardiovascular benefit is important and ... based on other established benefits such as weight control (moderate net weight loss for GLP-1 agonists and small weight loss for SGLT-2 inhibitors) against risks of genital infections (SGLT-2 inhibitors) or gastrointestinal disturbances (GLP-1 agonists).

Although GLP-1 agonists are associated with greater weight loss than SGLT-2 inhibitors, a population-based cohort study using Medicare and two U.S. commercial claims data sets found that starting a SGLT-2 inhibitor, compared to starting a GLP-1 agonist, reduced the relative risk of hospitalization for heart failure by about 30 percent in patients with and without CVD. A recent international RCT (622 centers in 23 countries) found that adding the SGLT-2 inhibitor empagliflozin (Jardiance) to usual therapy for patients with heart failure with preserved ejection fraction improved a composite outcome of CVD mortality and hospitalization, regardless of the presence of diabetes (RRR=19%, NNT=31). Similarly, a systematic review and meta-analysis of 8 earlier RCTs found that in heart failure patients without diabetes, SGLT-2 inhibitor treatment reduced the risk of this composite outcome by 20 percent.

Based on this new data, should primary care physicians consider adding a SGLT-2 inhibitor to the standard combination of drug therapies for their patients with heart failure? A qualitative study of Australian general practitioners suggested that knowledge gaps, drug adverse effects, and a preference for subspecialists to initiate SGLT-2 inhibitor therapy may be obstacles to increased prescribing of these drugs, which remain very expensive in the U.S.

Monday, January 17, 2022

"Test-To-Stay" part of the strategy to keep children in schools

 - Jennifer Middleton, MD, MPH

As the COVID-19 pandemic continues to set records for cases and hospitalizations, some schools in the United States (U.S.) are closing schools again - some due to staff and teacher shortages, and some in an attempt to slow COVID-19 spread. Toward the end of last month, the Centers for Disease Control and Prevention (CDC) released new data demonstrating that "Test-To-Stay" can help keep schools open - and children in schools - safely.

The CDC describes its "Test-To-Stay" (TTS) strategy as:

...a practice comprised of contact tracing and serial testing (testing that is sequentially repeated) to allow school-associated close contacts who are not fully vaccinated to continue in-person learning during their quarantine period. While implementation of TTS may vary, contact tracing and testing as well as masking of contacts during their in-school quarantine period are integral to minimize risk of transmission. 

The CDC cites two U.S. studies (Los Angeles, California and Lake County, Illinois) and one study from the United Kingdom to justify TTS. The LA study compared 39 districts using TTS to 39 districts following traditional quarantine guidance and found no difference in COVID-19 case rates. The Lake County study followed 90 schools using TTS and found only a 1.5% rate of secondary transmission. The UK study randomized 86 schools using TTS to 76 schools that followed traditional quarantine guidance and found no difference in COVID-19 cases. The Lake County study estimated that "up to 8,200 in-person learning days" were saved as a result of their TTS protocol. The CDC emphasizes that TTS must be part of a "layered prevention program" that also includes masks and social distancing

TTS is only necessary for unvaccinated children, but vaccination rates for children aged 5-11 years in the U.S. remain quite low. "[J]ust over 17%" of children aged 5-11 years and 54% of children aged 12-17 years are fully vaccinated as of last week. If those numbers do not substantially improve, which is, unfortunately, not expected to happen, TTS may continue to be needed for the forseeable future.

TTS only works with access to rapid tests, which has proved challenging throughout the U.S. As 2 days ago, the Biden administration now requires U.S. health insurance companies to cover the cost of up to 8 rapid COVID-19 tests per person per month. The Biden administration is "strongly incentivizing health plans and insurers to set up a network of convenient locations...where people... will be able to order online or walk in and pick up at-home over-the-counter COVID-19 tests for free." The Centers for Medicare & Medicaid Services (CMS) advises consumers to check with their health insurance plan to see whether they are supporting a "convenient location" or if they will, instead, need to pay up front and then submit for reimbursement. COVIDtests.gov will also begin accepting orders on January 19 and will not require a credit card. Removing the financial and physical access barriers to testing is a must if TTS is to be successfully implemented. 

CMS has a website with answers to questions regarding access to free rapid tests, and you can read the full details of the requirements here if interested. The AFP By Topic on COVID-19 also includes this Cochrane for Clinicians article on "Rapid Point-of-Care Antigen and Molecular Tests for Diagnosis of SARS-CoV-2 Infection" if you'd like to read more.

Tuesday, January 11, 2022

Preventing mumps and COVID-19: don't let perfect be the enemy of good

 - Kenny Lin, MD, MPH

The lower efficacy of COVID-19 vaccines against the SARS-CoV-2 Omicron variant due to viral mutations and waning immunity of the initial series has unfortunately fueled an anti-vaccination narrative that a less-than-perfectly protective vaccine has little clinical value. A comparison to a well-established childhood vaccine exposes the flaw in this argument. According to a 2020 Cochrane review, the effectiveness of measles, mumps, and rubella (MMR) vaccine in preventing mumps is 72% after one dose and 86% after two doses. After the two-dose MMR vaccine was added to the U.S. childhood immunization schedule, though, the number of reported cases of mumps fell from >150,000 in 1968 to 231 in 2003. In the past two decades, outbreaks have occasionally increased the incidence to several thousand reported cases per year. 

A recent study in Pediatrics examined the epidemiology of mumps in U.S. children and adolescents from 2007 to 2019. It found that 87% of children diagnosed with mumps during this period had received at least one dose of MMR vaccine, including most of the 2% of children who required hospitalization. Also, only 2% of cases were associated with international travel. The authors concluded that "clinicians should suspect mumps in patients with parotitis or mumps complications, regardless of age, travel history, and vaccination status."

For family physicians who have never seen a patient with this infection, a 2014 American Family Physician article on salivary gland disorders noted that mumps typically causes bilateral pain and edema of the parotid glands, otalgia, and trismus. Rarely, it can cause meningitis and encephalitis, as illustrated in a recent BMJ case report. Mumps spreads through airborne droplets (salivary, nasal, and urinary secretions) and is highly contagious. The diagnosis should be confirmed with reverse transcriptase-polymerase chain reaction (RT-PCR) or viral culture of a sample obtained with a buccal swab.

In fully vaccinated individuals, giving a third or "booster" dose of MMR vaccine was shown to reduce the risk of mumps during a 2015-16 U.S. college outbreak and 3 separate outbreaks in Queensland, Australia in 2017-18. Based on these studies, in 2018 the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommended that MMR-vaccinated individuals who are "part of a group or population at increased risk for acquiring mumps because of an outbreak" should receive a third dose of MMR vaccine "to improve protection against mumps disease and related complications." Sound familiar? Family physicians should continue to recommend that patients receive authorized COVID-19 vaccines and booster doses and not let the perfect be the enemy of the good.