Pulmonology

The use of race/ethnicity in medicine to explain and interpret pulmonary function test (PFT) differences between individuals may contribute to biased medical care and research. Furthermore, it may perpetuate health disparities and structural racism, according to a study published in the journal CHEST®.

Current practices of PFT measurement and interpretation, are imperfect in their ability to accurately describe the relationship between function and health outcomes, according to Nirav R. Bhakta, MD, University of California,San Francisco, and colleagues.

The authors summarized arguments against using race-specific equations, while voicing genuine concerns about removing race from PFT interpretations, and described knowledge gaps and critical questions needing to be addressed for remediation of health disparities.

“Leaving out the perspectives of practicing pulmonologists and physiologists has global relevance for increasingly multicultural communities in which the range of values that represent normal lung function is uncertain,” Dr. Bhakta said in an interview.
 

A lesson in history

Tracing the history of spirometry, the authors stated that observations about vital lung capacity showing differences attributable to height, age, sex, and occupation (e.g., typesetter vs. firefighter) were then extended to include social classes and ultimately race. Whites showed greater average vital capacity for the same sex, height, and age than non-Whites.

While some investigators pointed to environmental sources (such as early life nutrition, respiratory illness, air pollution, exercise, and altitude), research into their mechanisms and magnitudes of effect was not pursued, but rather “a narrative of innate differences took hold,” Dr. Bhakta and colleagues reported.

That sort of narrative risks comparison with those used to uphold slavery and structural racism in the past. More recently, such a narrative was used to deny disability claims of Welsh versus English White miners, and was expanded to interpret algorithms designed to predict expected lung function.
 

Use of standing height questioned

The current practice of using normalized standard height for lung function comparisons misses racial and ethnic differences in the proportion of sitting height to standing height shown in multiple studies, the authors stated. These comparisons may ignore effects on standing height of early-life nutrition, genetics, lung-specific factors such as respiratory infections and exposures to indoor and outdoor pollution, physical activity, and high altitude. Using sitting height instead of standing height reduces lung volume differences up to 50% between White and Black populations, they noted, and socioeconomic variables, such as poverty and immigration status, accounted further for the differences seen. Population differences disappeared by as much as 90% when chest measurements used to estimate surface area or volume were more finely detailed.

The researchers warned, however, that, “because current clinical and policy algorithms rely so heavily on the comparison of an individual’s observed lung function to that which is expected for similar people without typical respiratory disease, an abrupt change to not using race/ethnicity, if not paired with education and a reform of existing algorithms and policies, is also expected to have risks on average to groups of non-White individuals.”

That could lead to potential challenges for some groups ranging from the ability to obtain employment in certain occupations, to being considered for potentially curative lung resections, or having access to home assisted ventilation and rehabilitation programs. “An abrupt change to not using race/ethnicity and taking a society’s overall average as the reference range also has the potential to lead to delayed care, denial of disability benefits, and higher life insurance premiums to White individuals.”
 

Evidence base is limited

“Although evidence demonstrates differences in lung function between racial/ethnic groups, the premise that dividing lung function interpretation up by racial/ethnic background is helpful in the clinical setting is not a proven one.” The authors cited some evidence that lung function interpretation without consideration of race/ethnicity has superior prognostic ability. In addition, research has shown only a weak relationship between lung function and work ability, according to the authors. More appropriate ways of assessing expected lung function for an individual in the absence of a diagnoses are under study.

Offering an alternative

As an alternative to race, Dr. Bhakta and colleagues proposed using a range of values that include individuals across many global populations while still adjusting for sex, age, and height. The resultant value would represent a diverse population average and widen the limits of normal that can be expected in otherwise-healthy people.

The approach would include PFTs with other factors for clinical decision-making, but would allow clinicians and patients to appreciate the limitations of interpretation based on comparison to reference values. However, such an approach may miss pathophysiologically reduced lung function in some individuals, in which case lifesaving therapies, such as chemotherapy, lung cancer resection, and bone marrow transplantation could be withheld. In other instances the consequence would be overtesting and diagnosis, they acknowledged.

The authors further discussed general concerns about the use of race in interpretation of PFTs, addressing limits/considerations as well as knowledge and practice gaps.

For example, one particular concern involves the fact that race does not capture acculturation and mixed ancestry. The limit/consideration is the need to discover mechanisms for differences and to suggest societal interventions, and the knowledge gap pertains to ignorance regarding mechanisms leading to differences in lung function.

For the concern that race is not a proxy for an individual’s genetics, the limit/consideration is that race captures only some genetics and the gap is the need for better genetic information. As an antidote to over reliance on lung function thresholds (without supporting data), they urged outcomes-based standards rather than comparisons with reference populations.
 

New thinking needed

Dr. Bhakta and colleagues pointed out that the forced expiratory volume in 1 second/forced vital capacity ratios important for diagnosis of obstructive lung disease are similar between racial/ethnic categories, underscoring the need for education about limitations of thresholds and reference values with regard to race, particularly as they are used to detect mild disease.

Ignoring race, on the other hand, can lead to unnecessary testing and treatment (with concomitant side effects), and anxiety.

“Reporting through race-based algorithms in the PFT laboratory risks portraying racial disparities as innate and immutable. By anchoring on the improved prediction of lung function from racial/ethnic-specific reference equations, we miss how the significant residual variation still leaves much uncertainty about the expected value for an individual,” the authors concluded. “Given their origin and historical and current use in society, these racial/ethnic labels are better used to identify the effects of structural racism on respiratory health in research and ensure adequate representation in research, rather than in clinical algorithms.”

One of the authors is a speaker for MGC Diagnostics. The others indicated that they had no relevant disclosures.

The use of race/ethnicity in medicine to explain and interpret pulmonary function test (PFT) differences between individuals may contribute to biased medical care and research. Furthermore, it may perpetuate health disparities and structural racism, according to a study published in the journal CHEST®.

Current practices of PFT measurement and interpretation, are imperfect in their ability to accurately describe the relationship between function and health outcomes, according to Nirav R. Bhakta, MD, University of California,San Francisco, and colleagues.

The authors summarized arguments against using race-specific equations, while voicing genuine concerns about removing race from PFT interpretations, and described knowledge gaps and critical questions needing to be addressed for remediation of health disparities.

“Leaving out the perspectives of practicing pulmonologists and physiologists has global relevance for increasingly multicultural communities in which the range of values that represent normal lung function is uncertain,” Dr. Bhakta said in an interview.
 

A lesson in history

Tracing the history of spirometry, the authors stated that observations about vital lung capacity showing differences attributable to height, age, sex, and occupation (e.g., typesetter vs. firefighter) were then extended to include social classes and ultimately race. Whites showed greater average vital capacity for the same sex, height, and age than non-Whites.

While some investigators pointed to environmental sources (such as early life nutrition, respiratory illness, air pollution, exercise, and altitude), research into their mechanisms and magnitudes of effect was not pursued, but rather “a narrative of innate differences took hold,” Dr. Bhakta and colleagues reported.

That sort of narrative risks comparison with those used to uphold slavery and structural racism in the past. More recently, such a narrative was used to deny disability claims of Welsh versus English White miners, and was expanded to interpret algorithms designed to predict expected lung function.
 

Use of standing height questioned

The current practice of using normalized standard height for lung function comparisons misses racial and ethnic differences in the proportion of sitting height to standing height shown in multiple studies, the authors stated. These comparisons may ignore effects on standing height of early-life nutrition, genetics, lung-specific factors such as respiratory infections and exposures to indoor and outdoor pollution, physical activity, and high altitude. Using sitting height instead of standing height reduces lung volume differences up to 50% between White and Black populations, they noted, and socioeconomic variables, such as poverty and immigration status, accounted further for the differences seen. Population differences disappeared by as much as 90% when chest measurements used to estimate surface area or volume were more finely detailed.

The researchers warned, however, that, “because current clinical and policy algorithms rely so heavily on the comparison of an individual’s observed lung function to that which is expected for similar people without typical respiratory disease, an abrupt change to not using race/ethnicity, if not paired with education and a reform of existing algorithms and policies, is also expected to have risks on average to groups of non-White individuals.”

That could lead to potential challenges for some groups ranging from the ability to obtain employment in certain occupations, to being considered for potentially curative lung resections, or having access to home assisted ventilation and rehabilitation programs. “An abrupt change to not using race/ethnicity and taking a society’s overall average as the reference range also has the potential to lead to delayed care, denial of disability benefits, and higher life insurance premiums to White individuals.”
 

Evidence base is limited

“Although evidence demonstrates differences in lung function between racial/ethnic groups, the premise that dividing lung function interpretation up by racial/ethnic background is helpful in the clinical setting is not a proven one.” The authors cited some evidence that lung function interpretation without consideration of race/ethnicity has superior prognostic ability. In addition, research has shown only a weak relationship between lung function and work ability, according to the authors. More appropriate ways of assessing expected lung function for an individual in the absence of a diagnoses are under study.

Offering an alternative

As an alternative to race, Dr. Bhakta and colleagues proposed using a range of values that include individuals across many global populations while still adjusting for sex, age, and height. The resultant value would represent a diverse population average and widen the limits of normal that can be expected in otherwise-healthy people.

The approach would include PFTs with other factors for clinical decision-making, but would allow clinicians and patients to appreciate the limitations of interpretation based on comparison to reference values. However, such an approach may miss pathophysiologically reduced lung function in some individuals, in which case lifesaving therapies, such as chemotherapy, lung cancer resection, and bone marrow transplantation could be withheld. In other instances the consequence would be overtesting and diagnosis, they acknowledged.

The authors further discussed general concerns about the use of race in interpretation of PFTs, addressing limits/considerations as well as knowledge and practice gaps.

For example, one particular concern involves the fact that race does not capture acculturation and mixed ancestry. The limit/consideration is the need to discover mechanisms for differences and to suggest societal interventions, and the knowledge gap pertains to ignorance regarding mechanisms leading to differences in lung function.

For the concern that race is not a proxy for an individual’s genetics, the limit/consideration is that race captures only some genetics and the gap is the need for better genetic information. As an antidote to over reliance on lung function thresholds (without supporting data), they urged outcomes-based standards rather than comparisons with reference populations.
 

New thinking needed

Dr. Bhakta and colleagues pointed out that the forced expiratory volume in 1 second/forced vital capacity ratios important for diagnosis of obstructive lung disease are similar between racial/ethnic categories, underscoring the need for education about limitations of thresholds and reference values with regard to race, particularly as they are used to detect mild disease.

Ignoring race, on the other hand, can lead to unnecessary testing and treatment (with concomitant side effects), and anxiety.

“Reporting through race-based algorithms in the PFT laboratory risks portraying racial disparities as innate and immutable. By anchoring on the improved prediction of lung function from racial/ethnic-specific reference equations, we miss how the significant residual variation still leaves much uncertainty about the expected value for an individual,” the authors concluded. “Given their origin and historical and current use in society, these racial/ethnic labels are better used to identify the effects of structural racism on respiratory health in research and ensure adequate representation in research, rather than in clinical algorithms.”

One of the authors is a speaker for MGC Diagnostics. The others indicated that they had no relevant disclosures.

The use of race/ethnicity in medicine to explain and interpret pulmonary function test (PFT) differences between individuals may contribute to biased medical care and research. Furthermore, it may perpetuate health disparities and structural racism, according to a study published in the journal CHEST®.

Current practices of PFT measurement and interpretation, are imperfect in their ability to accurately describe the relationship between function and health outcomes, according to Nirav R. Bhakta, MD, University of California,San Francisco, and colleagues.

The authors summarized arguments against using race-specific equations, while voicing genuine concerns about removing race from PFT interpretations, and described knowledge gaps and critical questions needing to be addressed for remediation of health disparities.

“Leaving out the perspectives of practicing pulmonologists and physiologists has global relevance for increasingly multicultural communities in which the range of values that represent normal lung function is uncertain,” Dr. Bhakta said in an interview.
 

A lesson in history

Tracing the history of spirometry, the authors stated that observations about vital lung capacity showing differences attributable to height, age, sex, and occupation (e.g., typesetter vs. firefighter) were then extended to include social classes and ultimately race. Whites showed greater average vital capacity for the same sex, height, and age than non-Whites.

While some investigators pointed to environmental sources (such as early life nutrition, respiratory illness, air pollution, exercise, and altitude), research into their mechanisms and magnitudes of effect was not pursued, but rather “a narrative of innate differences took hold,” Dr. Bhakta and colleagues reported.

That sort of narrative risks comparison with those used to uphold slavery and structural racism in the past. More recently, such a narrative was used to deny disability claims of Welsh versus English White miners, and was expanded to interpret algorithms designed to predict expected lung function.
 

Use of standing height questioned

The current practice of using normalized standard height for lung function comparisons misses racial and ethnic differences in the proportion of sitting height to standing height shown in multiple studies, the authors stated. These comparisons may ignore effects on standing height of early-life nutrition, genetics, lung-specific factors such as respiratory infections and exposures to indoor and outdoor pollution, physical activity, and high altitude. Using sitting height instead of standing height reduces lung volume differences up to 50% between White and Black populations, they noted, and socioeconomic variables, such as poverty and immigration status, accounted further for the differences seen. Population differences disappeared by as much as 90% when chest measurements used to estimate surface area or volume were more finely detailed.

The researchers warned, however, that, “because current clinical and policy algorithms rely so heavily on the comparison of an individual’s observed lung function to that which is expected for similar people without typical respiratory disease, an abrupt change to not using race/ethnicity, if not paired with education and a reform of existing algorithms and policies, is also expected to have risks on average to groups of non-White individuals.”

That could lead to potential challenges for some groups ranging from the ability to obtain employment in certain occupations, to being considered for potentially curative lung resections, or having access to home assisted ventilation and rehabilitation programs. “An abrupt change to not using race/ethnicity and taking a society’s overall average as the reference range also has the potential to lead to delayed care, denial of disability benefits, and higher life insurance premiums to White individuals.”
 

Evidence base is limited

“Although evidence demonstrates differences in lung function between racial/ethnic groups, the premise that dividing lung function interpretation up by racial/ethnic background is helpful in the clinical setting is not a proven one.” The authors cited some evidence that lung function interpretation without consideration of race/ethnicity has superior prognostic ability. In addition, research has shown only a weak relationship between lung function and work ability, according to the authors. More appropriate ways of assessing expected lung function for an individual in the absence of a diagnoses are under study.

Offering an alternative

As an alternative to race, Dr. Bhakta and colleagues proposed using a range of values that include individuals across many global populations while still adjusting for sex, age, and height. The resultant value would represent a diverse population average and widen the limits of normal that can be expected in otherwise-healthy people.

The approach would include PFTs with other factors for clinical decision-making, but would allow clinicians and patients to appreciate the limitations of interpretation based on comparison to reference values. However, such an approach may miss pathophysiologically reduced lung function in some individuals, in which case lifesaving therapies, such as chemotherapy, lung cancer resection, and bone marrow transplantation could be withheld. In other instances the consequence would be overtesting and diagnosis, they acknowledged.

The authors further discussed general concerns about the use of race in interpretation of PFTs, addressing limits/considerations as well as knowledge and practice gaps.

For example, one particular concern involves the fact that race does not capture acculturation and mixed ancestry. The limit/consideration is the need to discover mechanisms for differences and to suggest societal interventions, and the knowledge gap pertains to ignorance regarding mechanisms leading to differences in lung function.

For the concern that race is not a proxy for an individual’s genetics, the limit/consideration is that race captures only some genetics and the gap is the need for better genetic information. As an antidote to over reliance on lung function thresholds (without supporting data), they urged outcomes-based standards rather than comparisons with reference populations.
 

New thinking needed

Dr. Bhakta and colleagues pointed out that the forced expiratory volume in 1 second/forced vital capacity ratios important for diagnosis of obstructive lung disease are similar between racial/ethnic categories, underscoring the need for education about limitations of thresholds and reference values with regard to race, particularly as they are used to detect mild disease.

Ignoring race, on the other hand, can lead to unnecessary testing and treatment (with concomitant side effects), and anxiety.

“Reporting through race-based algorithms in the PFT laboratory risks portraying racial disparities as innate and immutable. By anchoring on the improved prediction of lung function from racial/ethnic-specific reference equations, we miss how the significant residual variation still leaves much uncertainty about the expected value for an individual,” the authors concluded. “Given their origin and historical and current use in society, these racial/ethnic labels are better used to identify the effects of structural racism on respiratory health in research and ensure adequate representation in research, rather than in clinical algorithms.”

One of the authors is a speaker for MGC Diagnostics. The others indicated that they had no relevant disclosures.

In May 15, 1976, Family Practice News published its first “Residents’ Viewpoint,” a monthly column the publication established “in an effort to keep established practitioners as well as residents up to date.”

We are currently republishing an installment of this column as part of our continuing celebration of Family Practice News’s 50th anniversary.

MDedge News

Bruce A. Bagley, MD, wrote the first batch of these columns, when he was chief resident in family medicine at St. Joseph’s Hospital, Syracuse, N.Y. Joseph E. Scherger, MD, was the second writer for Family Practice News’s monthly “Residents’ Viewpoint.” At the time Dr. Scher­ger became a columnist, he was a 26-year-old, 2nd-year family practice resident at the Family Medical Center, University Hospital, University of Washington, Seattle.

Dr. Scherger’s first column was published on Feb. 5, 1977. We are republishing his “Residents’ Viewpoint” from June 15, 1977 (see below) and a new column by Victoria Persampiere, DO, who is currently a 2nd-year resident in the family medicine program at Abington Jefferson Health. (See “My experience as a family medicine resident in 2021” after Dr. Scherger’s column.).

We hope you will enjoy comparing and contrasting the experiences of a resident practicing family medicine today to those of a resident practicing family medicine nearly 4½ decades ago.To learn about Dr. Scherger’s current practice and long career, you can read his profile on the cover of the September 2021 issue of Family Practice News or on MDedge.com/FamilyMedicine in our “Family Practice News 50th Anniversary” section.
 

Art of medicine or deception?

Originally published in Family Practice News on June 15, 1977.

The practice of medicine can be divided into the scientific aspects of diagnosis and treatment and the nonscientific aspects of meeting patients’ needs, the art of medicine.

In medical school I learned the science of medicine. There I diligently studied the basic sciences and gained a thorough understanding of the pathophysiology of disease. In the clinical years I learned to apply this knowledge to a wide variety of interesting patients who came to the academic center.

Yet, when I started my family practice residency, I lacked the ability to care for patients. Though I could take a thorough history, perform a complete physical examination, and diagnose and treat specific illnesses, I had little idea how to satisfy patients by meeting their needs.

The art of medicine is the nonscientific part of a successful doctor-patient interaction. For a doctor-patient interaction to be successful, not only must the illness be appropriately addressed, but both patient and physician must be satisfied.

In the university environment, the art of medicine often gets inadequate attention. Indeed, most academic physicians think that only scientific medicine exists and that patients should be satisfied with a sophisticated approach to their problems. Some patients are satisfied, but many are disgruntled. It is not unusual for a patient, after a $1,000 work-up, to go to a family physician or chiropractor for satisfaction.

I was eager to discover the art of medicine at its finest during my rotation away from the university in a rural community. During these 2 months I looked for the pearls of wisdom that allowed community physicians to be so successful. I found that a very explicit technique was used by some physicians to achieve not only satisfaction but adoration from their patients. Unfortunately, this technique is dishonest.

Early in my community experience I was impressed by how often patients told me a doctor had saved them. I heard such statements as “Dr. X saved my leg,” or “Dr. X saved my life.” I know that it does occur, but not as often as I was hearing it.

Investigating these statements I found such stories as, “One day l twisted my ankle very badly, and it became quite swollen. My doctor told me 1 could lose my leg from this but that he would take x-rays, put my leg in an Ace bandage, and give me crutches. In 3 days I was well. I am so thankful he saved my leg.”

And, “One day I had a temperature of 104. All of my muscles ached, my head hurt, and I had a terrible sore throat and cough. My doctor told me l could die from this, but he gave me a medicine and made me stay home. I was sick for about 2 weeks, but I got better. He saved my life.”

Is the art of medicine the art of deception? This horrifying thought actually came to me after hearing several such stories, but I learned that most of the physicians involved in such stories were not well respected by their colleagues.

I learned many honest techniques for successfully caring for patients. The several family physicians with whom I worked, all clinical instructors associated with my residency, were impeccably honest and taught me to combine compassion and efficiency.

Despite learning many positive techniques and having good role models, I left the community experience somewhat saddened by the lack of integrity that can exist in the profession. I was naive in believing that all the nonscientific aspects of medi­cine that made patients happy must be good.

By experiencing deception, I learned why quackery continues to flourish despite the widespread availability of honest medical care. Most significantly, I learned the importance of a sometimes frustrating humility; my patients with sprained ankles and influenza will not believe I saved their lives.

My experience as a family medicine resident in 2021

I graduated medical school in May 2020, right as COVID was taking over the country, and the specter of the virus has hung over every aspect of my residency education thus far.

I did not get a medical school graduation; I was one of the many thousands of newly graduated students who simply left their 4th-year rotation sites one chilly day in March 2020 and just never went back. My medical school education didn’t end with me walking triumphantly across the stage – a first-generation college student finally achieving the greatest dream in her life. Instead, it ended with a Zoom “graduation” and a cross-country move from Georgia to Pennsylvania amidst the greatest pandemic in recent memory. To say my impostor syndrome was bad would be an understatement.
 

Residency in the COVID-19 era

The joy and the draw to family medicine for me has always been the broad scope of conditions that we see and treat. From day 1, however, much of my residency has been devoted to one very small subset of patients – those with COVID-19. At one point, our hospital was so strained that our family medicine program had to run a second inpatient service alongside our usual five-resident service team just to provide care to everybody. Patients were in the hallways. The ER was packed to the gills. We were sleepless, terrified, unvaccinated, and desperate to help our patients survive a disease that was incompletely understood, with very few tools in our toolbox to combat it.

I distinctly remember sitting in the workroom with a coresident of mine, our faces seemingly permanently lined from wearing N95s all shift, and saying to him, “I worry I will be a bad family medicine physician. I worry I haven’t seen enough, other than COVID.” It was midway through my intern year; the days were short, so I was driving to and from the hospital in chilly darkness. My patients, like many around the country, were doing poorly. Vaccines seemed like a promise too good to be true. Worst of all: Those of us who were interns, who had no triumphant podium moment to end our medical school education, were suffering with an intense sense of impostor syndrome, which was strengthened by every “there is nothing else we can offer your loved one at this time” conversation we had. My apprehension about not having seen a wider breadth of medicine during my training is a sentiment still widely shared by COVID-era residents.

Luckily, my coresident was supportive.

“We’re going to be great family medicine physicians,” he said. “We’re learning the hard stuff – the bread and butter of FM – up-front. You’ll see.”

In some ways, I think he was right. Clinical skills, empathy, humility, and forging strong relationships are at the center of every family medicine physician’s heart; my generation has had to learn these skills early and under pressure. Sometimes, there are no answers. Sometimes, the best thing a family doctor can do for a patient is to hear them, understand them, and hold their hand.
 

‘We watched Cinderella together’

Shortly after that conversation with my coresident, I had a particular case which moved me. This gentleman with intellectual disability and COVID had been declining steadily since his admission to the hospital. He was isolated from everybody he knew and loved, but it did not dampen his spirits. He was cheerful to every person who entered his room, clad in their shrouds of PPE, which more often than not felt more like mourning garb than protective wear. I remember very little about this patient’s clinical picture – the COVID, the superimposed pneumonia, the repeated intubations. What I do remember is he loved the Disney classic Cinderella. I knew this because I developed a very close relationship with his family during the course of his hospitalization. Amidst the torrential onslaught of patients, I made sure to call families every day – not because I wanted to, but because my mentors and attendings and coresidents had all drilled into me from day 1 that we are family medicine, and a large part of our role is to advocate for our patients, and to communicate with their loved ones. So I called. I learned a lot about him; his likes, his dislikes, his close bond with his siblings, and of course his lifelong love for Cinderella. On the last week of my ICU rotation, my patient passed peacefully. His nurse and I were bedside. We held his hand. We told him his family loved him. We watched Cinderella together on an iPad encased in protective plastic.

My next rotation was an outpatient one and it looked more like the “bread and butter” of family medicine. But as I whisked in and out of patient rooms, attending to patients with diabetes, with depression, with pain, I could not stop thinking about my hospitalized patients who my coresidents had assumed care of. Each exam room I entered, I rather morbidly thought “this patient could be next on our hospital service.” Without realizing it, I made more of an effort to get to know each patient holistically. I learned who they were as people. I found myself writing small, medically low-yield details in the chart: “Margaret loves to sing in her church choir;” “Katherine is a self-published author.”

I learned from my attendings. As I sat at the precepting table with them, observing their conversations about patients, their collective decades of experience were apparent.

“I’ve been seeing this patient every few weeks since I was a resident,” said one of my attendings.

“I don’t even see my parents that often,” I thought.

The depth of her relationship with, understanding of, and compassion for this patient struck me deeply. This was why I went into family medicine. My attending knew her patients; they were not faceless unknowns in a hospital gown to her. She would have known to play Cinderella for them in the end.

This is a unique time for trainees. We have been challenged, terrified, overwhelmed, and heartbroken. But at no point have we been isolated. We’ve had the generations of doctors before us to lead the way, to teach us the “hard stuff.” We’ve had senior residents to lean on, who have taken us aside and told us, “I can do the goals-of-care talk today; you need a break.” While the plague seems to have passed over our hospital for now, it has left behind a class of family medicine residents who are proud to carry on our specialty’s long tradition of compassionate, empathetic, lifelong care. “We care for all life stages, from cradle to grave,” says every family medicine physician.

My class, for better or for worse, has cared more often for patients in the twilight of their lives, and while it has been hard, I believe it has made us all better doctors. Now, when I hold a newborn in my arms for a well-child check, I am exceptionally grateful – for the opportunities I have been given, for new beginnings amidst so much sadness, and for the great privilege of being a family medicine physician. ■

Dr. Persampiere is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. You can contact her directly at [email protected] or via [email protected].

[email protected]

In May 15, 1976, Family Practice News published its first “Residents’ Viewpoint,” a monthly column the publication established “in an effort to keep established practitioners as well as residents up to date.”

We are currently republishing an installment of this column as part of our continuing celebration of Family Practice News’s 50th anniversary.

MDedge News

Bruce A. Bagley, MD, wrote the first batch of these columns, when he was chief resident in family medicine at St. Joseph’s Hospital, Syracuse, N.Y. Joseph E. Scherger, MD, was the second writer for Family Practice News’s monthly “Residents’ Viewpoint.” At the time Dr. Scher­ger became a columnist, he was a 26-year-old, 2nd-year family practice resident at the Family Medical Center, University Hospital, University of Washington, Seattle.

Dr. Scherger’s first column was published on Feb. 5, 1977. We are republishing his “Residents’ Viewpoint” from June 15, 1977 (see below) and a new column by Victoria Persampiere, DO, who is currently a 2nd-year resident in the family medicine program at Abington Jefferson Health. (See “My experience as a family medicine resident in 2021” after Dr. Scherger’s column.).

We hope you will enjoy comparing and contrasting the experiences of a resident practicing family medicine today to those of a resident practicing family medicine nearly 4½ decades ago.To learn about Dr. Scherger’s current practice and long career, you can read his profile on the cover of the September 2021 issue of Family Practice News or on MDedge.com/FamilyMedicine in our “Family Practice News 50th Anniversary” section.
 

Art of medicine or deception?

Originally published in Family Practice News on June 15, 1977.

The practice of medicine can be divided into the scientific aspects of diagnosis and treatment and the nonscientific aspects of meeting patients’ needs, the art of medicine.

In medical school I learned the science of medicine. There I diligently studied the basic sciences and gained a thorough understanding of the pathophysiology of disease. In the clinical years I learned to apply this knowledge to a wide variety of interesting patients who came to the academic center.

Yet, when I started my family practice residency, I lacked the ability to care for patients. Though I could take a thorough history, perform a complete physical examination, and diagnose and treat specific illnesses, I had little idea how to satisfy patients by meeting their needs.

The art of medicine is the nonscientific part of a successful doctor-patient interaction. For a doctor-patient interaction to be successful, not only must the illness be appropriately addressed, but both patient and physician must be satisfied.

In the university environment, the art of medicine often gets inadequate attention. Indeed, most academic physicians think that only scientific medicine exists and that patients should be satisfied with a sophisticated approach to their problems. Some patients are satisfied, but many are disgruntled. It is not unusual for a patient, after a $1,000 work-up, to go to a family physician or chiropractor for satisfaction.

I was eager to discover the art of medicine at its finest during my rotation away from the university in a rural community. During these 2 months I looked for the pearls of wisdom that allowed community physicians to be so successful. I found that a very explicit technique was used by some physicians to achieve not only satisfaction but adoration from their patients. Unfortunately, this technique is dishonest.

Early in my community experience I was impressed by how often patients told me a doctor had saved them. I heard such statements as “Dr. X saved my leg,” or “Dr. X saved my life.” I know that it does occur, but not as often as I was hearing it.

Investigating these statements I found such stories as, “One day l twisted my ankle very badly, and it became quite swollen. My doctor told me 1 could lose my leg from this but that he would take x-rays, put my leg in an Ace bandage, and give me crutches. In 3 days I was well. I am so thankful he saved my leg.”

And, “One day I had a temperature of 104. All of my muscles ached, my head hurt, and I had a terrible sore throat and cough. My doctor told me l could die from this, but he gave me a medicine and made me stay home. I was sick for about 2 weeks, but I got better. He saved my life.”

Is the art of medicine the art of deception? This horrifying thought actually came to me after hearing several such stories, but I learned that most of the physicians involved in such stories were not well respected by their colleagues.

I learned many honest techniques for successfully caring for patients. The several family physicians with whom I worked, all clinical instructors associated with my residency, were impeccably honest and taught me to combine compassion and efficiency.

Despite learning many positive techniques and having good role models, I left the community experience somewhat saddened by the lack of integrity that can exist in the profession. I was naive in believing that all the nonscientific aspects of medi­cine that made patients happy must be good.

By experiencing deception, I learned why quackery continues to flourish despite the widespread availability of honest medical care. Most significantly, I learned the importance of a sometimes frustrating humility; my patients with sprained ankles and influenza will not believe I saved their lives.

My experience as a family medicine resident in 2021

I graduated medical school in May 2020, right as COVID was taking over the country, and the specter of the virus has hung over every aspect of my residency education thus far.

I did not get a medical school graduation; I was one of the many thousands of newly graduated students who simply left their 4th-year rotation sites one chilly day in March 2020 and just never went back. My medical school education didn’t end with me walking triumphantly across the stage – a first-generation college student finally achieving the greatest dream in her life. Instead, it ended with a Zoom “graduation” and a cross-country move from Georgia to Pennsylvania amidst the greatest pandemic in recent memory. To say my impostor syndrome was bad would be an understatement.
 

Residency in the COVID-19 era

The joy and the draw to family medicine for me has always been the broad scope of conditions that we see and treat. From day 1, however, much of my residency has been devoted to one very small subset of patients – those with COVID-19. At one point, our hospital was so strained that our family medicine program had to run a second inpatient service alongside our usual five-resident service team just to provide care to everybody. Patients were in the hallways. The ER was packed to the gills. We were sleepless, terrified, unvaccinated, and desperate to help our patients survive a disease that was incompletely understood, with very few tools in our toolbox to combat it.

I distinctly remember sitting in the workroom with a coresident of mine, our faces seemingly permanently lined from wearing N95s all shift, and saying to him, “I worry I will be a bad family medicine physician. I worry I haven’t seen enough, other than COVID.” It was midway through my intern year; the days were short, so I was driving to and from the hospital in chilly darkness. My patients, like many around the country, were doing poorly. Vaccines seemed like a promise too good to be true. Worst of all: Those of us who were interns, who had no triumphant podium moment to end our medical school education, were suffering with an intense sense of impostor syndrome, which was strengthened by every “there is nothing else we can offer your loved one at this time” conversation we had. My apprehension about not having seen a wider breadth of medicine during my training is a sentiment still widely shared by COVID-era residents.

Luckily, my coresident was supportive.

“We’re going to be great family medicine physicians,” he said. “We’re learning the hard stuff – the bread and butter of FM – up-front. You’ll see.”

In some ways, I think he was right. Clinical skills, empathy, humility, and forging strong relationships are at the center of every family medicine physician’s heart; my generation has had to learn these skills early and under pressure. Sometimes, there are no answers. Sometimes, the best thing a family doctor can do for a patient is to hear them, understand them, and hold their hand.
 

‘We watched Cinderella together’

Shortly after that conversation with my coresident, I had a particular case which moved me. This gentleman with intellectual disability and COVID had been declining steadily since his admission to the hospital. He was isolated from everybody he knew and loved, but it did not dampen his spirits. He was cheerful to every person who entered his room, clad in their shrouds of PPE, which more often than not felt more like mourning garb than protective wear. I remember very little about this patient’s clinical picture – the COVID, the superimposed pneumonia, the repeated intubations. What I do remember is he loved the Disney classic Cinderella. I knew this because I developed a very close relationship with his family during the course of his hospitalization. Amidst the torrential onslaught of patients, I made sure to call families every day – not because I wanted to, but because my mentors and attendings and coresidents had all drilled into me from day 1 that we are family medicine, and a large part of our role is to advocate for our patients, and to communicate with their loved ones. So I called. I learned a lot about him; his likes, his dislikes, his close bond with his siblings, and of course his lifelong love for Cinderella. On the last week of my ICU rotation, my patient passed peacefully. His nurse and I were bedside. We held his hand. We told him his family loved him. We watched Cinderella together on an iPad encased in protective plastic.

My next rotation was an outpatient one and it looked more like the “bread and butter” of family medicine. But as I whisked in and out of patient rooms, attending to patients with diabetes, with depression, with pain, I could not stop thinking about my hospitalized patients who my coresidents had assumed care of. Each exam room I entered, I rather morbidly thought “this patient could be next on our hospital service.” Without realizing it, I made more of an effort to get to know each patient holistically. I learned who they were as people. I found myself writing small, medically low-yield details in the chart: “Margaret loves to sing in her church choir;” “Katherine is a self-published author.”

I learned from my attendings. As I sat at the precepting table with them, observing their conversations about patients, their collective decades of experience were apparent.

“I’ve been seeing this patient every few weeks since I was a resident,” said one of my attendings.

“I don’t even see my parents that often,” I thought.

The depth of her relationship with, understanding of, and compassion for this patient struck me deeply. This was why I went into family medicine. My attending knew her patients; they were not faceless unknowns in a hospital gown to her. She would have known to play Cinderella for them in the end.

This is a unique time for trainees. We have been challenged, terrified, overwhelmed, and heartbroken. But at no point have we been isolated. We’ve had the generations of doctors before us to lead the way, to teach us the “hard stuff.” We’ve had senior residents to lean on, who have taken us aside and told us, “I can do the goals-of-care talk today; you need a break.” While the plague seems to have passed over our hospital for now, it has left behind a class of family medicine residents who are proud to carry on our specialty’s long tradition of compassionate, empathetic, lifelong care. “We care for all life stages, from cradle to grave,” says every family medicine physician.

My class, for better or for worse, has cared more often for patients in the twilight of their lives, and while it has been hard, I believe it has made us all better doctors. Now, when I hold a newborn in my arms for a well-child check, I am exceptionally grateful – for the opportunities I have been given, for new beginnings amidst so much sadness, and for the great privilege of being a family medicine physician. ■

Dr. Persampiere is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. You can contact her directly at [email protected] or via [email protected].

[email protected]

In May 15, 1976, Family Practice News published its first “Residents’ Viewpoint,” a monthly column the publication established “in an effort to keep established practitioners as well as residents up to date.”

We are currently republishing an installment of this column as part of our continuing celebration of Family Practice News’s 50th anniversary.

MDedge News

Bruce A. Bagley, MD, wrote the first batch of these columns, when he was chief resident in family medicine at St. Joseph’s Hospital, Syracuse, N.Y. Joseph E. Scherger, MD, was the second writer for Family Practice News’s monthly “Residents’ Viewpoint.” At the time Dr. Scher­ger became a columnist, he was a 26-year-old, 2nd-year family practice resident at the Family Medical Center, University Hospital, University of Washington, Seattle.

Dr. Scherger’s first column was published on Feb. 5, 1977. We are republishing his “Residents’ Viewpoint” from June 15, 1977 (see below) and a new column by Victoria Persampiere, DO, who is currently a 2nd-year resident in the family medicine program at Abington Jefferson Health. (See “My experience as a family medicine resident in 2021” after Dr. Scherger’s column.).

We hope you will enjoy comparing and contrasting the experiences of a resident practicing family medicine today to those of a resident practicing family medicine nearly 4½ decades ago.To learn about Dr. Scherger’s current practice and long career, you can read his profile on the cover of the September 2021 issue of Family Practice News or on MDedge.com/FamilyMedicine in our “Family Practice News 50th Anniversary” section.
 

Art of medicine or deception?

Originally published in Family Practice News on June 15, 1977.

The practice of medicine can be divided into the scientific aspects of diagnosis and treatment and the nonscientific aspects of meeting patients’ needs, the art of medicine.

In medical school I learned the science of medicine. There I diligently studied the basic sciences and gained a thorough understanding of the pathophysiology of disease. In the clinical years I learned to apply this knowledge to a wide variety of interesting patients who came to the academic center.

Yet, when I started my family practice residency, I lacked the ability to care for patients. Though I could take a thorough history, perform a complete physical examination, and diagnose and treat specific illnesses, I had little idea how to satisfy patients by meeting their needs.

The art of medicine is the nonscientific part of a successful doctor-patient interaction. For a doctor-patient interaction to be successful, not only must the illness be appropriately addressed, but both patient and physician must be satisfied.

In the university environment, the art of medicine often gets inadequate attention. Indeed, most academic physicians think that only scientific medicine exists and that patients should be satisfied with a sophisticated approach to their problems. Some patients are satisfied, but many are disgruntled. It is not unusual for a patient, after a $1,000 work-up, to go to a family physician or chiropractor for satisfaction.

I was eager to discover the art of medicine at its finest during my rotation away from the university in a rural community. During these 2 months I looked for the pearls of wisdom that allowed community physicians to be so successful. I found that a very explicit technique was used by some physicians to achieve not only satisfaction but adoration from their patients. Unfortunately, this technique is dishonest.

Early in my community experience I was impressed by how often patients told me a doctor had saved them. I heard such statements as “Dr. X saved my leg,” or “Dr. X saved my life.” I know that it does occur, but not as often as I was hearing it.

Investigating these statements I found such stories as, “One day l twisted my ankle very badly, and it became quite swollen. My doctor told me 1 could lose my leg from this but that he would take x-rays, put my leg in an Ace bandage, and give me crutches. In 3 days I was well. I am so thankful he saved my leg.”

And, “One day I had a temperature of 104. All of my muscles ached, my head hurt, and I had a terrible sore throat and cough. My doctor told me l could die from this, but he gave me a medicine and made me stay home. I was sick for about 2 weeks, but I got better. He saved my life.”

Is the art of medicine the art of deception? This horrifying thought actually came to me after hearing several such stories, but I learned that most of the physicians involved in such stories were not well respected by their colleagues.

I learned many honest techniques for successfully caring for patients. The several family physicians with whom I worked, all clinical instructors associated with my residency, were impeccably honest and taught me to combine compassion and efficiency.

Despite learning many positive techniques and having good role models, I left the community experience somewhat saddened by the lack of integrity that can exist in the profession. I was naive in believing that all the nonscientific aspects of medi­cine that made patients happy must be good.

By experiencing deception, I learned why quackery continues to flourish despite the widespread availability of honest medical care. Most significantly, I learned the importance of a sometimes frustrating humility; my patients with sprained ankles and influenza will not believe I saved their lives.

My experience as a family medicine resident in 2021

I graduated medical school in May 2020, right as COVID was taking over the country, and the specter of the virus has hung over every aspect of my residency education thus far.

I did not get a medical school graduation; I was one of the many thousands of newly graduated students who simply left their 4th-year rotation sites one chilly day in March 2020 and just never went back. My medical school education didn’t end with me walking triumphantly across the stage – a first-generation college student finally achieving the greatest dream in her life. Instead, it ended with a Zoom “graduation” and a cross-country move from Georgia to Pennsylvania amidst the greatest pandemic in recent memory. To say my impostor syndrome was bad would be an understatement.
 

Residency in the COVID-19 era

The joy and the draw to family medicine for me has always been the broad scope of conditions that we see and treat. From day 1, however, much of my residency has been devoted to one very small subset of patients – those with COVID-19. At one point, our hospital was so strained that our family medicine program had to run a second inpatient service alongside our usual five-resident service team just to provide care to everybody. Patients were in the hallways. The ER was packed to the gills. We were sleepless, terrified, unvaccinated, and desperate to help our patients survive a disease that was incompletely understood, with very few tools in our toolbox to combat it.

I distinctly remember sitting in the workroom with a coresident of mine, our faces seemingly permanently lined from wearing N95s all shift, and saying to him, “I worry I will be a bad family medicine physician. I worry I haven’t seen enough, other than COVID.” It was midway through my intern year; the days were short, so I was driving to and from the hospital in chilly darkness. My patients, like many around the country, were doing poorly. Vaccines seemed like a promise too good to be true. Worst of all: Those of us who were interns, who had no triumphant podium moment to end our medical school education, were suffering with an intense sense of impostor syndrome, which was strengthened by every “there is nothing else we can offer your loved one at this time” conversation we had. My apprehension about not having seen a wider breadth of medicine during my training is a sentiment still widely shared by COVID-era residents.

Luckily, my coresident was supportive.

“We’re going to be great family medicine physicians,” he said. “We’re learning the hard stuff – the bread and butter of FM – up-front. You’ll see.”

In some ways, I think he was right. Clinical skills, empathy, humility, and forging strong relationships are at the center of every family medicine physician’s heart; my generation has had to learn these skills early and under pressure. Sometimes, there are no answers. Sometimes, the best thing a family doctor can do for a patient is to hear them, understand them, and hold their hand.
 

‘We watched Cinderella together’

Shortly after that conversation with my coresident, I had a particular case which moved me. This gentleman with intellectual disability and COVID had been declining steadily since his admission to the hospital. He was isolated from everybody he knew and loved, but it did not dampen his spirits. He was cheerful to every person who entered his room, clad in their shrouds of PPE, which more often than not felt more like mourning garb than protective wear. I remember very little about this patient’s clinical picture – the COVID, the superimposed pneumonia, the repeated intubations. What I do remember is he loved the Disney classic Cinderella. I knew this because I developed a very close relationship with his family during the course of his hospitalization. Amidst the torrential onslaught of patients, I made sure to call families every day – not because I wanted to, but because my mentors and attendings and coresidents had all drilled into me from day 1 that we are family medicine, and a large part of our role is to advocate for our patients, and to communicate with their loved ones. So I called. I learned a lot about him; his likes, his dislikes, his close bond with his siblings, and of course his lifelong love for Cinderella. On the last week of my ICU rotation, my patient passed peacefully. His nurse and I were bedside. We held his hand. We told him his family loved him. We watched Cinderella together on an iPad encased in protective plastic.

My next rotation was an outpatient one and it looked more like the “bread and butter” of family medicine. But as I whisked in and out of patient rooms, attending to patients with diabetes, with depression, with pain, I could not stop thinking about my hospitalized patients who my coresidents had assumed care of. Each exam room I entered, I rather morbidly thought “this patient could be next on our hospital service.” Without realizing it, I made more of an effort to get to know each patient holistically. I learned who they were as people. I found myself writing small, medically low-yield details in the chart: “Margaret loves to sing in her church choir;” “Katherine is a self-published author.”

I learned from my attendings. As I sat at the precepting table with them, observing their conversations about patients, their collective decades of experience were apparent.

“I’ve been seeing this patient every few weeks since I was a resident,” said one of my attendings.

“I don’t even see my parents that often,” I thought.

The depth of her relationship with, understanding of, and compassion for this patient struck me deeply. This was why I went into family medicine. My attending knew her patients; they were not faceless unknowns in a hospital gown to her. She would have known to play Cinderella for them in the end.

This is a unique time for trainees. We have been challenged, terrified, overwhelmed, and heartbroken. But at no point have we been isolated. We’ve had the generations of doctors before us to lead the way, to teach us the “hard stuff.” We’ve had senior residents to lean on, who have taken us aside and told us, “I can do the goals-of-care talk today; you need a break.” While the plague seems to have passed over our hospital for now, it has left behind a class of family medicine residents who are proud to carry on our specialty’s long tradition of compassionate, empathetic, lifelong care. “We care for all life stages, from cradle to grave,” says every family medicine physician.

My class, for better or for worse, has cared more often for patients in the twilight of their lives, and while it has been hard, I believe it has made us all better doctors. Now, when I hold a newborn in my arms for a well-child check, I am exceptionally grateful – for the opportunities I have been given, for new beginnings amidst so much sadness, and for the great privilege of being a family medicine physician. ■

Dr. Persampiere is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. You can contact her directly at [email protected] or via [email protected].

[email protected]

On Nov. 2, the Centers for Disease Control and Prevention endorsed vaccination with the Pfizer/BioNTech COVID-19 vaccine for children aged 5-11 years. What are some best practices for meeting the challenges of immunizing this younger age group?

This news organization spoke to several pediatric experts to get answers.

More than 6 million children and adolescents (up to age 18 years) in the United States have been infected with SARS-CoV-2. Children represent about 17% of all cases, and an estimated 0.1%-2% of infected children end up hospitalized, according to Oct. 28 data from the American Academy of Pediatrics.

Physicians and other health care practitioners are gearing up for what could be an influx of patients. “Pediatricians are standing by to talk with families about the vaccine and to administer the vaccine to children as soon as possible,” Lee Savio Beers, MD, FAAP, president of the AAP, said in a statement.

In this Q&A, this news organization asked for additional advice from Sara “Sally” Goza, MD, a pediatrician in Fayetteville, Georgia, and immediate past president of the AAP; Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine at Baylor College of Medicine and codirector of the Texas Children’s Hospital Center for Vaccine Development, both in Houston; and Danielle M. Zerr, MD, professor and chief of the division of pediatric infectious disease at the University of Washington, Seattle, and medical director of infection prevention at Seattle Children’s Hospital.
 

Q: How are smaller pediatric practices and solo practitioners going to handle the additional vaccinations?

Dr. Goza: It’s a scheduling challenge with this rollout and all the people who want it and want it right now. They’re going to want it this week.

I’ve actually had some children asking their moms: “When can I get it? When can I get it?” It’s been very interesting – they are chomping at the bit.

If I give the vaccine to a patient this week, in 3 weeks the second dose will be right around Thanksgiving. No one in my office is going to want to be here to give the shot on Thanksgiving, and no patient is going to want to come in on Thanksgiving weekend. So I’m trying to delay those parents – saying, let’s do it next week. That way we’re not messing up a holiday.

Children are going to need two doses, and they won’t be fully protected until 2 weeks after their second dose. So they won’t get full protection for Thanksgiving, but they will have full protection for Christmas.

I know there are a lot of pediatricians who have preordered the vaccine. I know in our office they sent us an email ... to let us know our vaccines are being shipped. So I think a lot of pediatricians are going to have the vaccine.
 

Q: How should pediatricians counsel parents who are fearful or hesitant?

Dr. Hotez: It’s important to emphasize the severity of the 2021 summer Delta epidemic in children. We need to get beyond this false narrative that COVID only produces a mild disease in children. It’s caused thousands of pediatric hospitalizations, not to mention long COVID.

Dr. Zerr: It is key to find out what concerns parents have and then focus on answering their specific questions. It is helpful to emphasize the safety and efficacy of the vaccine and to explain the rigorous processes that the vaccine went through to receive Food and Drug Administration approval.
 

Q: How should pediatricians counter any misinformation/disinformation out there about the COVID-19 vaccines?

Dr. Goza: The most important thing is not to discount what they are saying. Don’t say: “That’s crazy” or “That’s not true.” Don’t roll your eyes and say: “Really, you’re going to believe all that?”

Instead, have a conversation with them about why we think that is not true, or why we know that’s not true. We really have to have that relationship and ask: “Well, what are your concerns?” And then really counter (any misinformation) with facts, with science, and based on your experience.
 

Q: Do the data presented to the FDA and the CDC about the safety and effectiveness of the COVID-19 vaccine for 5- to 11-year-olds seem robust to you?

Dr. Zerr: Yes, and data collection will be ongoing.

Dr. Hotez: I’ve only seen what’s publicly available so far, and it seems to support moving forward with emergency use authorization. The only shortfall is the size, roughly 2,200 children, which would not be of sufficient size to detect a rare safety signal.
 

Q: Do previous controversies around pediatric vaccines (for example, the MMR vaccine and autism) give pediatricians some background and experience so they can address any pushback on the COVID-19 vaccines?

Dr. Goza: Pediatricians have been dealing with vaccine hesitancy for a while now, ever since the MMR and autism controversy started. Even before then, there were certain groups of people who didn’t want vaccines.

We’ve really worked hard at helping teach pediatricians how to deal with the misinformation, how to counter it, and how to help parents understand the vaccines are safe and effective – and that they save lives.

That (experience) will help us in some ways. Unfortunately, there is more misinformation out there – there is almost a concerted effort on misinformation. It’s big.

Pediatricians will do everything we can, but we need help countering it. We need the misinformation to quit getting spread on social media. We can talk one on one with patients and families, but if all they are hearing on social media is the misinformation, it’s really hard.
 

Q: Are pediatricians, especially solo practitioners or pediatricians at smaller practices, going to face challenges with multidose vials and not wasting vaccine product?

Dr. Goza: I’m at a small practice. We have 3.5 FTEs (full-time equivalents) of MDs and three FTEs of nurse practitioners. So we’re not that big – about six providers.

You know, it is a challenge. We’re not going to buy the super-duper freezer, and we’re not going to be able to store these vaccines for a long period of time.

So when we order, we need smaller amounts. For the 12- to 18-year-olds, [maximum storage] was 45 days. Now for the 5- to 11-year-olds, we’re going to be able to store the vaccine in the refrigerator for 10 weeks, which gives us more leeway there.

We try to do all of vaccinations on 1 day, so we know how many people are coming in, and we are not going to waste too many doses.

Our Department of Public Health in Georgia has said: “We want these vaccines in the arms of kids, and if you have to waste some doses, don’t worry about it.” But it’s a 10-dose vial. It’s going to be hard for me to open it up for one child. I just don’t like wasting anything like this.

Our main goal is to get this vaccine in to the arms of children whose parents want it.
 

Q: What are some additional sources of information for pediatricians?

Dr. Zerr: There are a lot of great resources on vaccine hesitancy from reputable sources, including these from the CDC and from the National Academies of Sciences, Engineering, and Medicine:

• Building Confidence With OVID-19 Vaccines
• How to Talk With Parents About COVID-19 Vaccination
• Strategies for Building Confidence in the COVID-19 Vaccines
• Communication Strategies for Building Confidence in COVID-19 Vaccines: Addressing Variants and Childhood Vaccinations

A version of this article first appeared on Medscape.com.

On Nov. 2, the Centers for Disease Control and Prevention endorsed vaccination with the Pfizer/BioNTech COVID-19 vaccine for children aged 5-11 years. What are some best practices for meeting the challenges of immunizing this younger age group?

This news organization spoke to several pediatric experts to get answers.

More than 6 million children and adolescents (up to age 18 years) in the United States have been infected with SARS-CoV-2. Children represent about 17% of all cases, and an estimated 0.1%-2% of infected children end up hospitalized, according to Oct. 28 data from the American Academy of Pediatrics.

Physicians and other health care practitioners are gearing up for what could be an influx of patients. “Pediatricians are standing by to talk with families about the vaccine and to administer the vaccine to children as soon as possible,” Lee Savio Beers, MD, FAAP, president of the AAP, said in a statement.

In this Q&A, this news organization asked for additional advice from Sara “Sally” Goza, MD, a pediatrician in Fayetteville, Georgia, and immediate past president of the AAP; Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine at Baylor College of Medicine and codirector of the Texas Children’s Hospital Center for Vaccine Development, both in Houston; and Danielle M. Zerr, MD, professor and chief of the division of pediatric infectious disease at the University of Washington, Seattle, and medical director of infection prevention at Seattle Children’s Hospital.
 

Q: How are smaller pediatric practices and solo practitioners going to handle the additional vaccinations?

Dr. Goza: It’s a scheduling challenge with this rollout and all the people who want it and want it right now. They’re going to want it this week.

I’ve actually had some children asking their moms: “When can I get it? When can I get it?” It’s been very interesting – they are chomping at the bit.

If I give the vaccine to a patient this week, in 3 weeks the second dose will be right around Thanksgiving. No one in my office is going to want to be here to give the shot on Thanksgiving, and no patient is going to want to come in on Thanksgiving weekend. So I’m trying to delay those parents – saying, let’s do it next week. That way we’re not messing up a holiday.

Children are going to need two doses, and they won’t be fully protected until 2 weeks after their second dose. So they won’t get full protection for Thanksgiving, but they will have full protection for Christmas.

I know there are a lot of pediatricians who have preordered the vaccine. I know in our office they sent us an email ... to let us know our vaccines are being shipped. So I think a lot of pediatricians are going to have the vaccine.
 

Q: How should pediatricians counsel parents who are fearful or hesitant?

Dr. Hotez: It’s important to emphasize the severity of the 2021 summer Delta epidemic in children. We need to get beyond this false narrative that COVID only produces a mild disease in children. It’s caused thousands of pediatric hospitalizations, not to mention long COVID.

Dr. Zerr: It is key to find out what concerns parents have and then focus on answering their specific questions. It is helpful to emphasize the safety and efficacy of the vaccine and to explain the rigorous processes that the vaccine went through to receive Food and Drug Administration approval.
 

Q: How should pediatricians counter any misinformation/disinformation out there about the COVID-19 vaccines?

Dr. Goza: The most important thing is not to discount what they are saying. Don’t say: “That’s crazy” or “That’s not true.” Don’t roll your eyes and say: “Really, you’re going to believe all that?”

Instead, have a conversation with them about why we think that is not true, or why we know that’s not true. We really have to have that relationship and ask: “Well, what are your concerns?” And then really counter (any misinformation) with facts, with science, and based on your experience.
 

Q: Do the data presented to the FDA and the CDC about the safety and effectiveness of the COVID-19 vaccine for 5- to 11-year-olds seem robust to you?

Dr. Zerr: Yes, and data collection will be ongoing.

Dr. Hotez: I’ve only seen what’s publicly available so far, and it seems to support moving forward with emergency use authorization. The only shortfall is the size, roughly 2,200 children, which would not be of sufficient size to detect a rare safety signal.
 

Q: Do previous controversies around pediatric vaccines (for example, the MMR vaccine and autism) give pediatricians some background and experience so they can address any pushback on the COVID-19 vaccines?

Dr. Goza: Pediatricians have been dealing with vaccine hesitancy for a while now, ever since the MMR and autism controversy started. Even before then, there were certain groups of people who didn’t want vaccines.

We’ve really worked hard at helping teach pediatricians how to deal with the misinformation, how to counter it, and how to help parents understand the vaccines are safe and effective – and that they save lives.

That (experience) will help us in some ways. Unfortunately, there is more misinformation out there – there is almost a concerted effort on misinformation. It’s big.

Pediatricians will do everything we can, but we need help countering it. We need the misinformation to quit getting spread on social media. We can talk one on one with patients and families, but if all they are hearing on social media is the misinformation, it’s really hard.
 

Q: Are pediatricians, especially solo practitioners or pediatricians at smaller practices, going to face challenges with multidose vials and not wasting vaccine product?

Dr. Goza: I’m at a small practice. We have 3.5 FTEs (full-time equivalents) of MDs and three FTEs of nurse practitioners. So we’re not that big – about six providers.

You know, it is a challenge. We’re not going to buy the super-duper freezer, and we’re not going to be able to store these vaccines for a long period of time.

So when we order, we need smaller amounts. For the 12- to 18-year-olds, [maximum storage] was 45 days. Now for the 5- to 11-year-olds, we’re going to be able to store the vaccine in the refrigerator for 10 weeks, which gives us more leeway there.

We try to do all of vaccinations on 1 day, so we know how many people are coming in, and we are not going to waste too many doses.

Our Department of Public Health in Georgia has said: “We want these vaccines in the arms of kids, and if you have to waste some doses, don’t worry about it.” But it’s a 10-dose vial. It’s going to be hard for me to open it up for one child. I just don’t like wasting anything like this.

Our main goal is to get this vaccine in to the arms of children whose parents want it.
 

Q: What are some additional sources of information for pediatricians?

Dr. Zerr: There are a lot of great resources on vaccine hesitancy from reputable sources, including these from the CDC and from the National Academies of Sciences, Engineering, and Medicine:

• Building Confidence With OVID-19 Vaccines
• How to Talk With Parents About COVID-19 Vaccination
• Strategies for Building Confidence in the COVID-19 Vaccines
• Communication Strategies for Building Confidence in COVID-19 Vaccines: Addressing Variants and Childhood Vaccinations

A version of this article first appeared on Medscape.com.

On Nov. 2, the Centers for Disease Control and Prevention endorsed vaccination with the Pfizer/BioNTech COVID-19 vaccine for children aged 5-11 years. What are some best practices for meeting the challenges of immunizing this younger age group?

This news organization spoke to several pediatric experts to get answers.

More than 6 million children and adolescents (up to age 18 years) in the United States have been infected with SARS-CoV-2. Children represent about 17% of all cases, and an estimated 0.1%-2% of infected children end up hospitalized, according to Oct. 28 data from the American Academy of Pediatrics.

Physicians and other health care practitioners are gearing up for what could be an influx of patients. “Pediatricians are standing by to talk with families about the vaccine and to administer the vaccine to children as soon as possible,” Lee Savio Beers, MD, FAAP, president of the AAP, said in a statement.

In this Q&A, this news organization asked for additional advice from Sara “Sally” Goza, MD, a pediatrician in Fayetteville, Georgia, and immediate past president of the AAP; Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine at Baylor College of Medicine and codirector of the Texas Children’s Hospital Center for Vaccine Development, both in Houston; and Danielle M. Zerr, MD, professor and chief of the division of pediatric infectious disease at the University of Washington, Seattle, and medical director of infection prevention at Seattle Children’s Hospital.
 

Q: How are smaller pediatric practices and solo practitioners going to handle the additional vaccinations?

Dr. Goza: It’s a scheduling challenge with this rollout and all the people who want it and want it right now. They’re going to want it this week.

I’ve actually had some children asking their moms: “When can I get it? When can I get it?” It’s been very interesting – they are chomping at the bit.

If I give the vaccine to a patient this week, in 3 weeks the second dose will be right around Thanksgiving. No one in my office is going to want to be here to give the shot on Thanksgiving, and no patient is going to want to come in on Thanksgiving weekend. So I’m trying to delay those parents – saying, let’s do it next week. That way we’re not messing up a holiday.

Children are going to need two doses, and they won’t be fully protected until 2 weeks after their second dose. So they won’t get full protection for Thanksgiving, but they will have full protection for Christmas.

I know there are a lot of pediatricians who have preordered the vaccine. I know in our office they sent us an email ... to let us know our vaccines are being shipped. So I think a lot of pediatricians are going to have the vaccine.
 

Q: How should pediatricians counsel parents who are fearful or hesitant?

Dr. Hotez: It’s important to emphasize the severity of the 2021 summer Delta epidemic in children. We need to get beyond this false narrative that COVID only produces a mild disease in children. It’s caused thousands of pediatric hospitalizations, not to mention long COVID.

Dr. Zerr: It is key to find out what concerns parents have and then focus on answering their specific questions. It is helpful to emphasize the safety and efficacy of the vaccine and to explain the rigorous processes that the vaccine went through to receive Food and Drug Administration approval.
 

Q: How should pediatricians counter any misinformation/disinformation out there about the COVID-19 vaccines?

Dr. Goza: The most important thing is not to discount what they are saying. Don’t say: “That’s crazy” or “That’s not true.” Don’t roll your eyes and say: “Really, you’re going to believe all that?”

Instead, have a conversation with them about why we think that is not true, or why we know that’s not true. We really have to have that relationship and ask: “Well, what are your concerns?” And then really counter (any misinformation) with facts, with science, and based on your experience.
 

Q: Do the data presented to the FDA and the CDC about the safety and effectiveness of the COVID-19 vaccine for 5- to 11-year-olds seem robust to you?

Dr. Zerr: Yes, and data collection will be ongoing.

Dr. Hotez: I’ve only seen what’s publicly available so far, and it seems to support moving forward with emergency use authorization. The only shortfall is the size, roughly 2,200 children, which would not be of sufficient size to detect a rare safety signal.
 

Q: Do previous controversies around pediatric vaccines (for example, the MMR vaccine and autism) give pediatricians some background and experience so they can address any pushback on the COVID-19 vaccines?

Dr. Goza: Pediatricians have been dealing with vaccine hesitancy for a while now, ever since the MMR and autism controversy started. Even before then, there were certain groups of people who didn’t want vaccines.

We’ve really worked hard at helping teach pediatricians how to deal with the misinformation, how to counter it, and how to help parents understand the vaccines are safe and effective – and that they save lives.

That (experience) will help us in some ways. Unfortunately, there is more misinformation out there – there is almost a concerted effort on misinformation. It’s big.

Pediatricians will do everything we can, but we need help countering it. We need the misinformation to quit getting spread on social media. We can talk one on one with patients and families, but if all they are hearing on social media is the misinformation, it’s really hard.
 

Q: Are pediatricians, especially solo practitioners or pediatricians at smaller practices, going to face challenges with multidose vials and not wasting vaccine product?

Dr. Goza: I’m at a small practice. We have 3.5 FTEs (full-time equivalents) of MDs and three FTEs of nurse practitioners. So we’re not that big – about six providers.

You know, it is a challenge. We’re not going to buy the super-duper freezer, and we’re not going to be able to store these vaccines for a long period of time.

So when we order, we need smaller amounts. For the 12- to 18-year-olds, [maximum storage] was 45 days. Now for the 5- to 11-year-olds, we’re going to be able to store the vaccine in the refrigerator for 10 weeks, which gives us more leeway there.

We try to do all of vaccinations on 1 day, so we know how many people are coming in, and we are not going to waste too many doses.

Our Department of Public Health in Georgia has said: “We want these vaccines in the arms of kids, and if you have to waste some doses, don’t worry about it.” But it’s a 10-dose vial. It’s going to be hard for me to open it up for one child. I just don’t like wasting anything like this.

Our main goal is to get this vaccine in to the arms of children whose parents want it.
 

Q: What are some additional sources of information for pediatricians?

Dr. Zerr: There are a lot of great resources on vaccine hesitancy from reputable sources, including these from the CDC and from the National Academies of Sciences, Engineering, and Medicine:

• Building Confidence With OVID-19 Vaccines
• How to Talk With Parents About COVID-19 Vaccination
• Strategies for Building Confidence in the COVID-19 Vaccines
• Communication Strategies for Building Confidence in COVID-19 Vaccines: Addressing Variants and Childhood Vaccinations

A version of this article first appeared on Medscape.com.

Influenza infection is linked to a subsequent diagnosis of Parkinson’s disease (PD) more than 10 years later, resurfacing a long-held debate about whether infection increases the risk for movement disorders over the long term.

In a large case-control study, investigators found the odds of PD were elevated by approximately 90% for PD that occurred more than 15 years after influenza infection and by more than 70% for PD occurring more than 10 years after the flu.

“This study is not definitive by any means, but it certainly suggests there are potential long-term consequences from influenza,” study investigator Noelle M. Cocoros, DSc, research scientist at Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, said in an interview.

The study was published online Oct. 25 in JAMA Neurology.

Ongoing debate

The debate about whether influenza is associated with PD has been going on as far back as the 1918 influenza pandemic, when experts documented parkinsonism in affected individuals.

Using data from the Danish patient registry, researchers identified 10,271 subjects diagnosed with PD during a 17-year period (2000-2016). Of these, 38.7% were female, and the mean age was 71.4 years.

They matched these subjects for age and sex to 51,355 controls without PD. Compared with controls, slightly fewer individuals with PD had chronic obstructive pulmonary disease (COPD) or emphysema, but there was a similar distribution of cardiovascular disease and various other conditions.

Researchers collected data on influenza diagnoses from inpatient and outpatient hospital clinics from 1977 to 2016. They plotted these by month and year on a graph, calculated the median number of diagnoses per month, and identified peaks as those with more than threefold the median.

They categorized cases in groups related to the time between the infection and PD: More than 10 years, 10-15 years, and more than 15 years.

The time lapse accounts for a rather long “run-up” to PD, said Dr. Cocoros. There’s a sometimes decades-long preclinical phase before patients develop typical motor signs and a prodromal phase where they may present with nonmotor symptoms such as sleep disorders and constipation.

“We expected there would be at least 10 years between any infection and PD if there was an association present,” said Dr. Cocoros.

Investigators found an association between influenza exposure and PD diagnosis “that held up over time,” she said.

For more than 10 years before PD, the likelihood of a diagnosis for the infected compared with the unexposed was increased 73% (odds ratio [OR] 1.73; 95% confidence interval, 1.11-2.71; P = .02) after adjustment for cardiovascular disease, diabetes, chronic obstructive pulmonary disease, emphysema, lung cancer, Crohn’s disease, and ulcerative colitis.

The odds increased with more time from infection. For more than 15 years, the adjusted OR was 1.91 (95% CI, 1.14 - 3.19; P =.01).

However, for the 10- to 15-year time frame, the point estimate was reduced and the CI nonsignificant (OR, 1.33; 95% CI, 0.54-3.27; P = .53). This “is a little hard to interpret,” but could be a result of the small numbers, exposure misclassification, or because “the longer time interval is what’s meaningful,” said Dr. Cocoros.
 

Potential COVID-19–related PD surge?

In a sensitivity analysis, researchers looked at peak infection activity. “We wanted to increase the likelihood of these diagnoses representing actual infection,” Dr. Cocoros noted.

Here, the OR was still elevated at more than 10 years, but the CI was quite wide and included 1 (OR, 1.52; 95% CI, 0.80-2.89; P = .21). “So the association holds up, but the estimates are quite unstable,” said Dr. Cocoros.

Researchers examined associations with numerous other infection types, but did not see the same trend over time. Some infections – for example, gastrointestinal infections and septicemia – were associated with PD within 5 years, but most associations appeared to be null after more than 10 years.

“There seemed to be associations earlier between the infection and PD, which we interpret to suggest there’s actually not a meaningful association,” said Dr. Cocoros.

An exception might be urinary tract infections (UTIs), where after 10 years, the adjusted OR was 1.19 (95% CI, 1.01-1.40). Research suggests patients with PD often have UTIs and neurogenic bladder.

“It’s possible that UTIs could be an early symptom of PD rather than a causative factor,” said Dr. Cocoros.

It’s unclear how influenza might lead to PD but it could be that the virus gets into the central nervous system, resulting in neuroinflammation. Cytokines generated in response to the influenza infection might damage the brain.

“The infection could be a ‘primer’ or an initial ‘hit’ to the system, maybe setting people up for PD,” said Dr. Cocoros.

As for the current COVID-19 pandemic, some experts are concerned about a potential surge in PD cases in decades to come, and are calling for prospective monitoring of patients with this infection, said Dr. Cocoros.

However, she noted that infections don’t account for all PD cases and that genetic and environmental factors also influence risk.

Many individuals who contract influenza don’t seek medical care or get tested, so it’s possible the study counted those who had the infection as unexposed. Another potential study limitation was that small numbers for some infections, for example, Helicobacter pylori and hepatitis C, limited the ability to interpret results.
 

‘Exciting and important’ findings

Commenting on the research for this news organization, Aparna Wagle Shukla, MD, professor, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, said the results amid the current pandemic are “exciting and important” and “have reinvigorated interest” in the role of infection in PD.

However, the study had some limitations, an important one being lack of accounting for confounding factors, including environmental factors, she said. Exposure to pesticides, living in a rural area, drinking well water, and having had a head injury may increase PD risk, whereas high intake of caffeine, nicotine, alcohol, and nonsteroidal anti-inflammatory drugs might lower the risk.

The researchers did not take into account exposure to multiple microbes or “infection burden,” said Dr. Wagle Shukla, who was not involved in the current study. In addition, as the data are from a single country with exposure to specific influenza strains, application of the findings elsewhere may be limited.

Dr. Wagle Shukla noted that a case-control design “isn’t ideal” from an epidemiological perspective. “Future studies should involve large cohorts followed longitudinally.”

The study was supported by grants from the Lundbeck Foundation and the Augustinus Foundation. Dr. Cocoros has disclosed no relevant financial relationships. Several coauthors have disclosed relationships with industry. The full list can be found with the original article.

A version of this article first appeared on Medscape.com.

Influenza infection is linked to a subsequent diagnosis of Parkinson’s disease (PD) more than 10 years later, resurfacing a long-held debate about whether infection increases the risk for movement disorders over the long term.

In a large case-control study, investigators found the odds of PD were elevated by approximately 90% for PD that occurred more than 15 years after influenza infection and by more than 70% for PD occurring more than 10 years after the flu.

“This study is not definitive by any means, but it certainly suggests there are potential long-term consequences from influenza,” study investigator Noelle M. Cocoros, DSc, research scientist at Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, said in an interview.

The study was published online Oct. 25 in JAMA Neurology.

Ongoing debate

The debate about whether influenza is associated with PD has been going on as far back as the 1918 influenza pandemic, when experts documented parkinsonism in affected individuals.

Using data from the Danish patient registry, researchers identified 10,271 subjects diagnosed with PD during a 17-year period (2000-2016). Of these, 38.7% were female, and the mean age was 71.4 years.

They matched these subjects for age and sex to 51,355 controls without PD. Compared with controls, slightly fewer individuals with PD had chronic obstructive pulmonary disease (COPD) or emphysema, but there was a similar distribution of cardiovascular disease and various other conditions.

Researchers collected data on influenza diagnoses from inpatient and outpatient hospital clinics from 1977 to 2016. They plotted these by month and year on a graph, calculated the median number of diagnoses per month, and identified peaks as those with more than threefold the median.

They categorized cases in groups related to the time between the infection and PD: More than 10 years, 10-15 years, and more than 15 years.

The time lapse accounts for a rather long “run-up” to PD, said Dr. Cocoros. There’s a sometimes decades-long preclinical phase before patients develop typical motor signs and a prodromal phase where they may present with nonmotor symptoms such as sleep disorders and constipation.

“We expected there would be at least 10 years between any infection and PD if there was an association present,” said Dr. Cocoros.

Investigators found an association between influenza exposure and PD diagnosis “that held up over time,” she said.

For more than 10 years before PD, the likelihood of a diagnosis for the infected compared with the unexposed was increased 73% (odds ratio [OR] 1.73; 95% confidence interval, 1.11-2.71; P = .02) after adjustment for cardiovascular disease, diabetes, chronic obstructive pulmonary disease, emphysema, lung cancer, Crohn’s disease, and ulcerative colitis.

The odds increased with more time from infection. For more than 15 years, the adjusted OR was 1.91 (95% CI, 1.14 - 3.19; P =.01).

However, for the 10- to 15-year time frame, the point estimate was reduced and the CI nonsignificant (OR, 1.33; 95% CI, 0.54-3.27; P = .53). This “is a little hard to interpret,” but could be a result of the small numbers, exposure misclassification, or because “the longer time interval is what’s meaningful,” said Dr. Cocoros.
 

Potential COVID-19–related PD surge?

In a sensitivity analysis, researchers looked at peak infection activity. “We wanted to increase the likelihood of these diagnoses representing actual infection,” Dr. Cocoros noted.

Here, the OR was still elevated at more than 10 years, but the CI was quite wide and included 1 (OR, 1.52; 95% CI, 0.80-2.89; P = .21). “So the association holds up, but the estimates are quite unstable,” said Dr. Cocoros.

Researchers examined associations with numerous other infection types, but did not see the same trend over time. Some infections – for example, gastrointestinal infections and septicemia – were associated with PD within 5 years, but most associations appeared to be null after more than 10 years.

“There seemed to be associations earlier between the infection and PD, which we interpret to suggest there’s actually not a meaningful association,” said Dr. Cocoros.

An exception might be urinary tract infections (UTIs), where after 10 years, the adjusted OR was 1.19 (95% CI, 1.01-1.40). Research suggests patients with PD often have UTIs and neurogenic bladder.

“It’s possible that UTIs could be an early symptom of PD rather than a causative factor,” said Dr. Cocoros.

It’s unclear how influenza might lead to PD but it could be that the virus gets into the central nervous system, resulting in neuroinflammation. Cytokines generated in response to the influenza infection might damage the brain.

“The infection could be a ‘primer’ or an initial ‘hit’ to the system, maybe setting people up for PD,” said Dr. Cocoros.

As for the current COVID-19 pandemic, some experts are concerned about a potential surge in PD cases in decades to come, and are calling for prospective monitoring of patients with this infection, said Dr. Cocoros.

However, she noted that infections don’t account for all PD cases and that genetic and environmental factors also influence risk.

Many individuals who contract influenza don’t seek medical care or get tested, so it’s possible the study counted those who had the infection as unexposed. Another potential study limitation was that small numbers for some infections, for example, Helicobacter pylori and hepatitis C, limited the ability to interpret results.
 

‘Exciting and important’ findings

Commenting on the research for this news organization, Aparna Wagle Shukla, MD, professor, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, said the results amid the current pandemic are “exciting and important” and “have reinvigorated interest” in the role of infection in PD.

However, the study had some limitations, an important one being lack of accounting for confounding factors, including environmental factors, she said. Exposure to pesticides, living in a rural area, drinking well water, and having had a head injury may increase PD risk, whereas high intake of caffeine, nicotine, alcohol, and nonsteroidal anti-inflammatory drugs might lower the risk.

The researchers did not take into account exposure to multiple microbes or “infection burden,” said Dr. Wagle Shukla, who was not involved in the current study. In addition, as the data are from a single country with exposure to specific influenza strains, application of the findings elsewhere may be limited.

Dr. Wagle Shukla noted that a case-control design “isn’t ideal” from an epidemiological perspective. “Future studies should involve large cohorts followed longitudinally.”

The study was supported by grants from the Lundbeck Foundation and the Augustinus Foundation. Dr. Cocoros has disclosed no relevant financial relationships. Several coauthors have disclosed relationships with industry. The full list can be found with the original article.

A version of this article first appeared on Medscape.com.

Influenza infection is linked to a subsequent diagnosis of Parkinson’s disease (PD) more than 10 years later, resurfacing a long-held debate about whether infection increases the risk for movement disorders over the long term.

In a large case-control study, investigators found the odds of PD were elevated by approximately 90% for PD that occurred more than 15 years after influenza infection and by more than 70% for PD occurring more than 10 years after the flu.

“This study is not definitive by any means, but it certainly suggests there are potential long-term consequences from influenza,” study investigator Noelle M. Cocoros, DSc, research scientist at Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, said in an interview.

The study was published online Oct. 25 in JAMA Neurology.

Ongoing debate

The debate about whether influenza is associated with PD has been going on as far back as the 1918 influenza pandemic, when experts documented parkinsonism in affected individuals.

Using data from the Danish patient registry, researchers identified 10,271 subjects diagnosed with PD during a 17-year period (2000-2016). Of these, 38.7% were female, and the mean age was 71.4 years.

They matched these subjects for age and sex to 51,355 controls without PD. Compared with controls, slightly fewer individuals with PD had chronic obstructive pulmonary disease (COPD) or emphysema, but there was a similar distribution of cardiovascular disease and various other conditions.

Researchers collected data on influenza diagnoses from inpatient and outpatient hospital clinics from 1977 to 2016. They plotted these by month and year on a graph, calculated the median number of diagnoses per month, and identified peaks as those with more than threefold the median.

They categorized cases in groups related to the time between the infection and PD: More than 10 years, 10-15 years, and more than 15 years.

The time lapse accounts for a rather long “run-up” to PD, said Dr. Cocoros. There’s a sometimes decades-long preclinical phase before patients develop typical motor signs and a prodromal phase where they may present with nonmotor symptoms such as sleep disorders and constipation.

“We expected there would be at least 10 years between any infection and PD if there was an association present,” said Dr. Cocoros.

Investigators found an association between influenza exposure and PD diagnosis “that held up over time,” she said.

For more than 10 years before PD, the likelihood of a diagnosis for the infected compared with the unexposed was increased 73% (odds ratio [OR] 1.73; 95% confidence interval, 1.11-2.71; P = .02) after adjustment for cardiovascular disease, diabetes, chronic obstructive pulmonary disease, emphysema, lung cancer, Crohn’s disease, and ulcerative colitis.

The odds increased with more time from infection. For more than 15 years, the adjusted OR was 1.91 (95% CI, 1.14 - 3.19; P =.01).

However, for the 10- to 15-year time frame, the point estimate was reduced and the CI nonsignificant (OR, 1.33; 95% CI, 0.54-3.27; P = .53). This “is a little hard to interpret,” but could be a result of the small numbers, exposure misclassification, or because “the longer time interval is what’s meaningful,” said Dr. Cocoros.
 

Potential COVID-19–related PD surge?

In a sensitivity analysis, researchers looked at peak infection activity. “We wanted to increase the likelihood of these diagnoses representing actual infection,” Dr. Cocoros noted.

Here, the OR was still elevated at more than 10 years, but the CI was quite wide and included 1 (OR, 1.52; 95% CI, 0.80-2.89; P = .21). “So the association holds up, but the estimates are quite unstable,” said Dr. Cocoros.

Researchers examined associations with numerous other infection types, but did not see the same trend over time. Some infections – for example, gastrointestinal infections and septicemia – were associated with PD within 5 years, but most associations appeared to be null after more than 10 years.

“There seemed to be associations earlier between the infection and PD, which we interpret to suggest there’s actually not a meaningful association,” said Dr. Cocoros.

An exception might be urinary tract infections (UTIs), where after 10 years, the adjusted OR was 1.19 (95% CI, 1.01-1.40). Research suggests patients with PD often have UTIs and neurogenic bladder.

“It’s possible that UTIs could be an early symptom of PD rather than a causative factor,” said Dr. Cocoros.

It’s unclear how influenza might lead to PD but it could be that the virus gets into the central nervous system, resulting in neuroinflammation. Cytokines generated in response to the influenza infection might damage the brain.

“The infection could be a ‘primer’ or an initial ‘hit’ to the system, maybe setting people up for PD,” said Dr. Cocoros.

As for the current COVID-19 pandemic, some experts are concerned about a potential surge in PD cases in decades to come, and are calling for prospective monitoring of patients with this infection, said Dr. Cocoros.

However, she noted that infections don’t account for all PD cases and that genetic and environmental factors also influence risk.

Many individuals who contract influenza don’t seek medical care or get tested, so it’s possible the study counted those who had the infection as unexposed. Another potential study limitation was that small numbers for some infections, for example, Helicobacter pylori and hepatitis C, limited the ability to interpret results.
 

‘Exciting and important’ findings

Commenting on the research for this news organization, Aparna Wagle Shukla, MD, professor, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, said the results amid the current pandemic are “exciting and important” and “have reinvigorated interest” in the role of infection in PD.

However, the study had some limitations, an important one being lack of accounting for confounding factors, including environmental factors, she said. Exposure to pesticides, living in a rural area, drinking well water, and having had a head injury may increase PD risk, whereas high intake of caffeine, nicotine, alcohol, and nonsteroidal anti-inflammatory drugs might lower the risk.

The researchers did not take into account exposure to multiple microbes or “infection burden,” said Dr. Wagle Shukla, who was not involved in the current study. In addition, as the data are from a single country with exposure to specific influenza strains, application of the findings elsewhere may be limited.

Dr. Wagle Shukla noted that a case-control design “isn’t ideal” from an epidemiological perspective. “Future studies should involve large cohorts followed longitudinally.”

The study was supported by grants from the Lundbeck Foundation and the Augustinus Foundation. Dr. Cocoros has disclosed no relevant financial relationships. Several coauthors have disclosed relationships with industry. The full list can be found with the original article.

A version of this article first appeared on Medscape.com.

A number of fatal child poisonings have been linked to common cough and cold medications, according to a report.

The Pediatric Cough and Cold Safety Surveillance System, which tracks fatal child poisonings, has identified 40 such deaths in recent years and raised particular concern about medications containing diphenhydramine, a common antihistamine that can be sedating.

“There is little evidence that cough and cold medicines make children feel better or reduce their symptoms, but there is evidence they can suffer harm,” says Kevin Osterhoudt, MD, medical director of the Poison Control Center at the Children’s Hospital of Philadelphia.

In recent years, the FDA has advised labeling changes and recommended that cough and cold medications not be given to children younger than 2. Drugmakers also voluntarily relabeled these products to state “do not use in children under 4 years of age.”

Compared to older children or adults, young children have a different physiology when they breathe, so any product containing antihistamines can be a danger to little kids, Dr. Osterhoudt says.

But a recent survey shows about half of American parents gave their child cough and cold medication the last time they were ill, Dr. Osterhoudt says. And the findings suggest that cough and cold medications are in homes where children might find them.

Using the new evidence from the national surveillance system, investigators set up an expert panel to review the results. They found that most of the deaths were in children under the age of 2. The results were reported in the October issue of Pediatrics.

In seven instances, death followed the intentional use of medication to sedate the child, reports lead investigator Laurie Seidel Halmo, MD, from Children’s Hospital Colorado, Aurora.

“It’s not uncommon for parents to use sedatives like diphenhydramine to make their child sleepy for activities like air travel,” Dr. Osterhoudt says.

While antihistamines can be sedating, “an overdose of antihistamines like diphenhydramine can paradoxically become a stimulant,” having the opposite effect, he explains.

Adults and teens who take overdoses will sometimes become delirious, hallucinate, and have a racing heart.

But in young children, “if not careful with your dosing, you could actually give too much and create this stimulant activity,” Dr. Osterhoudt says.

In six other cases, the cough and cold medication was given to murder the child, the investigators reported.

The findings are “concerning,” especially with “more than one-half of nontherapeutic intent cases determined to be malicious in nature,” Michele Burns, MD, from Boston Children’s Hospital, and Madeline Renny, MD, from the Grossman School of Medicine in New York, wrote in a commentary with the report.

This important fatality review shows that despite safety efforts, young children remain at risk for death, they report.

The investigators point out that labeling changes do not seem to have protected vulnerable children, and they recommend that doctors educate parents and caregivers about the risk of cough and cold medications.

Dr. Halmo and her team also recommend that the medical community and child welfare advocates be on the lookout for medication use as a source of child abuse.

At home, preventing accidental ingestion could go along with other practices already ingrained in the minds of many, Dr. Osterhoudt says.

“We know to change the clocks in the spring and fall and make sure your smoke detector and carbon monoxide detector has fresh batteries, but maybe it’s also a good time to look at medicines in the house.”

In other words, after you change the clocks, it’s time to take inventory of medications around the house, and if they’re no longer in use, safely dispose of them.

The American Academy of Pediatrics offers guidelines on the safe home storage of medications to keep them out of reach of children and the use of protective caps on drugs.

A version of this article first appeared on WebMD.com.

A number of fatal child poisonings have been linked to common cough and cold medications, according to a report.

The Pediatric Cough and Cold Safety Surveillance System, which tracks fatal child poisonings, has identified 40 such deaths in recent years and raised particular concern about medications containing diphenhydramine, a common antihistamine that can be sedating.

“There is little evidence that cough and cold medicines make children feel better or reduce their symptoms, but there is evidence they can suffer harm,” says Kevin Osterhoudt, MD, medical director of the Poison Control Center at the Children’s Hospital of Philadelphia.

In recent years, the FDA has advised labeling changes and recommended that cough and cold medications not be given to children younger than 2. Drugmakers also voluntarily relabeled these products to state “do not use in children under 4 years of age.”

Compared to older children or adults, young children have a different physiology when they breathe, so any product containing antihistamines can be a danger to little kids, Dr. Osterhoudt says.

But a recent survey shows about half of American parents gave their child cough and cold medication the last time they were ill, Dr. Osterhoudt says. And the findings suggest that cough and cold medications are in homes where children might find them.

Using the new evidence from the national surveillance system, investigators set up an expert panel to review the results. They found that most of the deaths were in children under the age of 2. The results were reported in the October issue of Pediatrics.

In seven instances, death followed the intentional use of medication to sedate the child, reports lead investigator Laurie Seidel Halmo, MD, from Children’s Hospital Colorado, Aurora.

“It’s not uncommon for parents to use sedatives like diphenhydramine to make their child sleepy for activities like air travel,” Dr. Osterhoudt says.

While antihistamines can be sedating, “an overdose of antihistamines like diphenhydramine can paradoxically become a stimulant,” having the opposite effect, he explains.

Adults and teens who take overdoses will sometimes become delirious, hallucinate, and have a racing heart.

But in young children, “if not careful with your dosing, you could actually give too much and create this stimulant activity,” Dr. Osterhoudt says.

In six other cases, the cough and cold medication was given to murder the child, the investigators reported.

The findings are “concerning,” especially with “more than one-half of nontherapeutic intent cases determined to be malicious in nature,” Michele Burns, MD, from Boston Children’s Hospital, and Madeline Renny, MD, from the Grossman School of Medicine in New York, wrote in a commentary with the report.

This important fatality review shows that despite safety efforts, young children remain at risk for death, they report.

The investigators point out that labeling changes do not seem to have protected vulnerable children, and they recommend that doctors educate parents and caregivers about the risk of cough and cold medications.

Dr. Halmo and her team also recommend that the medical community and child welfare advocates be on the lookout for medication use as a source of child abuse.

At home, preventing accidental ingestion could go along with other practices already ingrained in the minds of many, Dr. Osterhoudt says.

“We know to change the clocks in the spring and fall and make sure your smoke detector and carbon monoxide detector has fresh batteries, but maybe it’s also a good time to look at medicines in the house.”

In other words, after you change the clocks, it’s time to take inventory of medications around the house, and if they’re no longer in use, safely dispose of them.

The American Academy of Pediatrics offers guidelines on the safe home storage of medications to keep them out of reach of children and the use of protective caps on drugs.

A version of this article first appeared on WebMD.com.

A number of fatal child poisonings have been linked to common cough and cold medications, according to a report.

The Pediatric Cough and Cold Safety Surveillance System, which tracks fatal child poisonings, has identified 40 such deaths in recent years and raised particular concern about medications containing diphenhydramine, a common antihistamine that can be sedating.

“There is little evidence that cough and cold medicines make children feel better or reduce their symptoms, but there is evidence they can suffer harm,” says Kevin Osterhoudt, MD, medical director of the Poison Control Center at the Children’s Hospital of Philadelphia.

In recent years, the FDA has advised labeling changes and recommended that cough and cold medications not be given to children younger than 2. Drugmakers also voluntarily relabeled these products to state “do not use in children under 4 years of age.”

Compared to older children or adults, young children have a different physiology when they breathe, so any product containing antihistamines can be a danger to little kids, Dr. Osterhoudt says.

But a recent survey shows about half of American parents gave their child cough and cold medication the last time they were ill, Dr. Osterhoudt says. And the findings suggest that cough and cold medications are in homes where children might find them.

Using the new evidence from the national surveillance system, investigators set up an expert panel to review the results. They found that most of the deaths were in children under the age of 2. The results were reported in the October issue of Pediatrics.

In seven instances, death followed the intentional use of medication to sedate the child, reports lead investigator Laurie Seidel Halmo, MD, from Children’s Hospital Colorado, Aurora.

“It’s not uncommon for parents to use sedatives like diphenhydramine to make their child sleepy for activities like air travel,” Dr. Osterhoudt says.

While antihistamines can be sedating, “an overdose of antihistamines like diphenhydramine can paradoxically become a stimulant,” having the opposite effect, he explains.

Adults and teens who take overdoses will sometimes become delirious, hallucinate, and have a racing heart.

But in young children, “if not careful with your dosing, you could actually give too much and create this stimulant activity,” Dr. Osterhoudt says.

In six other cases, the cough and cold medication was given to murder the child, the investigators reported.

The findings are “concerning,” especially with “more than one-half of nontherapeutic intent cases determined to be malicious in nature,” Michele Burns, MD, from Boston Children’s Hospital, and Madeline Renny, MD, from the Grossman School of Medicine in New York, wrote in a commentary with the report.

This important fatality review shows that despite safety efforts, young children remain at risk for death, they report.

The investigators point out that labeling changes do not seem to have protected vulnerable children, and they recommend that doctors educate parents and caregivers about the risk of cough and cold medications.

Dr. Halmo and her team also recommend that the medical community and child welfare advocates be on the lookout for medication use as a source of child abuse.

At home, preventing accidental ingestion could go along with other practices already ingrained in the minds of many, Dr. Osterhoudt says.

“We know to change the clocks in the spring and fall and make sure your smoke detector and carbon monoxide detector has fresh batteries, but maybe it’s also a good time to look at medicines in the house.”

In other words, after you change the clocks, it’s time to take inventory of medications around the house, and if they’re no longer in use, safely dispose of them.

The American Academy of Pediatrics offers guidelines on the safe home storage of medications to keep them out of reach of children and the use of protective caps on drugs.

A version of this article first appeared on WebMD.com.

For patients with moderate to severe asthma, blockade with itepekimab, a new human IgG4P monoclonal antibody against the upstream alarmin interleukin-33, led to a reduction in events that indicate loss of asthma control. Treatment with itepekimab also led to an improvement in lung function compared with placebo, according to results of a phase 2 trial.

However, findings for a subgroup of patients treated with itepekimab in combination with dupilumab, an anti–interleukin-4–receptor alpha subunit and IL-13 monoclonal antibody, were not favorable in comparison with placebo, noted M. E. Wechsler, MD, and colleagues in an article published online in the New England Journal of Medicine.
 

New target

Despite the demonstrated efficacy of available biologic therapies targeting IgE, interleukin-4, interleukin-13, and interleukin-5 for treating moderate to severe type 2 asthma, many patients with type 2 or non–type 2 asthma continue to have symptoms, exacerbations, and reduced lung function. New therapies targeting alternative pathophysiologic pathways are needed.

Genomewide studies show that type 2 and non–type 2 inflammation that contributes to asthma and chronic obstructive pulmonary disease (COPD) are genetically associated with interleukin-33. This inflammation occurs when interleukin-33 binds to its cognate receptor (ST2) and engages the coreceptor interleukin-1 receptor accessory protein to initiate downstream signaling, activating cells of both the innate and adaptive immune systems.
 

Study details

The investigators conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group (four groups), proof-of-concept trial to evaluate the efficacy and safety of the interleukin-33 targeting itepekimab in comparison with placebo for adults with moderate to severe asthma. Dupilumab, which was the active comparator, was administered in combination with itepekimab to evaluate potential additive effects. Dupilumab’s efficacy in this population had been demonstrated previously.

All 296 patients (mean age, 49.1 years; 64% women) were receiving inhaled glucocorticoids plus long-acting beta-agonists (LABAs). They were randomly assigned in a 1:1:1:1 ratio to receive subcutaneous itepekimab (300 mg), itepekimab plus dupilumab (both at 300 mg; combination therapy), dupilumab (300 mg), or placebo every 2 weeks for 12 weeks. LABAs were discontinued at week 4, and inhaled glucocorticoids were tapered over weeks 6 through 9. The primary endpoint was the occurrence of an event indicating the loss of asthma control.
 

Promising results

Primary endpoint analysis at 12 weeks revealed a lower rate of asthma control–loss events in the itepekimab and dupilumab monotherapy groups but not in the combination group, compared with patients who received placebo. Events occurred in 22% of patients in the itepekimab group, in 27% of those in the combination group, in 19% of the dupilumab group, and in 41% of the placebo group. The odds ratios for comparisons with placebo were 0.42 for the itepekimab group (95% confidence interval, 0.20-0.88; P = .02); 0.33 in the dupilumab group (95% CI, 0.15-.70); and 0.52 in the combination group (95% CI, 0.26-1.06; P = .07) .

Following a similar pattern, forced expiratory volume in 1 second before use of a bronchodilator increased with both monotherapies but not with the combination or placebo. Although the trial was not powered to determine differences between itepekimab and dupilumab, the effects of dupilumab therapy were generally greater than those observed with itepekimab, especially for patients with type 2 asthma.

Also, asthma control and quality of life were improved with itepekimab and dupilumab monotherapy in comparison with placebo. There were also greater reductions in the mean blood eosinophil count.

The authors urge further research into the complexities of asthma physiology and encourage researchers to look for predictive biomarkers of anti–interleukin-33 blockade response. They conclude, “In this trial, we found that itepekimab monotherapy led to a lower incidence of events indicating loss of asthma control and to improved lung function, findings that are consistent with a role for interleukin-33 in the pathogenesis of exacerbations and airflow limitation in asthma.”
 

Examining results

In an accompanying editorial, Philip G. Bardin, PhD, and Paul S. Foster, DSc, ask why itepekimab and dupilumab, a combination based on a sound scientific rationale, failed. As monotherapies, both itepekimab and dupilumab are roughly similar in reducing asthma events and improving lung function; thus, is unlikely that inadequate dosing led to the failure of itepekimab.

Interleukin-33 is an attractive target because the cells it promotes secrete cytokines that induce asthma’s pathognomonic features, and biologic agents that target those cytokines (interleukin-5/-5R/-4/-13 axes) have been highly effective. They do not, however, prevent exacerbations after treatment.

Alternative pathways within or outside that paradigm are operant, and other epithelial alarmins, such as interleukin-25 and thymic stromal lymphopoietin, promote type 2 inflammation, Dr. Bardin and Dr. Foster state.

“Combination therapy with itepekimab and dupilumab may have failed because these pathways bypass interleukin-33,” they write. Also, preexisting ILC2 and TH2 cells may have residual capacity to release mediators. The short-term trial design, the editorialists write, may have contributed to the failure of the itepekimab/dupilumab combination; interleukin-33 may be appropriate as a target in a longer-term exacerbation-type trial “in which epithelial infection and other relevant stimuli instigate exacerbated disease. Combination therapy may be capable of lowering exacerbations rather than preventing loss of control in chronic disease.

“Clinical translation of basic science in asthma remains a challenge to be pursued. ... It is imperative to harness scientific insights from translational studies that frustrate our hopeful expectations – so that something can also be gained,” they conclude.
 

The role of interleukin-33

“Our study of itepekimab provides valuable insight into pathophysiology of severe asthma,” said Dr. Wechsler, professor of medicine at the NJH Cohen Family Asthma Institute, Denver, in an interview. “As blocking IL-33 reduced asthma worsening and improved lung function compared to placebo, it suggests that IL-33 plays an important role in asthma pathophysiology and may be a valuable target for a subset of patients with severe asthma,” he stated.

“Since the effect of itepekimab is comparable to that of dupilumab, it is suggested that patients may benefit from blockade of this pathway, but what remains to be seen is identifying which patients are more likely to respond better to one therapy vs. another. The future of blocking IL-33 remains exciting, and studies are being planned to evaluate its efficacy in airways diseases, including COPD,” he concluded.

A version of this article first appeared on Medscape.com.

For patients with moderate to severe asthma, blockade with itepekimab, a new human IgG4P monoclonal antibody against the upstream alarmin interleukin-33, led to a reduction in events that indicate loss of asthma control. Treatment with itepekimab also led to an improvement in lung function compared with placebo, according to results of a phase 2 trial.

However, findings for a subgroup of patients treated with itepekimab in combination with dupilumab, an anti–interleukin-4–receptor alpha subunit and IL-13 monoclonal antibody, were not favorable in comparison with placebo, noted M. E. Wechsler, MD, and colleagues in an article published online in the New England Journal of Medicine.
 

New target

Despite the demonstrated efficacy of available biologic therapies targeting IgE, interleukin-4, interleukin-13, and interleukin-5 for treating moderate to severe type 2 asthma, many patients with type 2 or non–type 2 asthma continue to have symptoms, exacerbations, and reduced lung function. New therapies targeting alternative pathophysiologic pathways are needed.

Genomewide studies show that type 2 and non–type 2 inflammation that contributes to asthma and chronic obstructive pulmonary disease (COPD) are genetically associated with interleukin-33. This inflammation occurs when interleukin-33 binds to its cognate receptor (ST2) and engages the coreceptor interleukin-1 receptor accessory protein to initiate downstream signaling, activating cells of both the innate and adaptive immune systems.
 

Study details

The investigators conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group (four groups), proof-of-concept trial to evaluate the efficacy and safety of the interleukin-33 targeting itepekimab in comparison with placebo for adults with moderate to severe asthma. Dupilumab, which was the active comparator, was administered in combination with itepekimab to evaluate potential additive effects. Dupilumab’s efficacy in this population had been demonstrated previously.

All 296 patients (mean age, 49.1 years; 64% women) were receiving inhaled glucocorticoids plus long-acting beta-agonists (LABAs). They were randomly assigned in a 1:1:1:1 ratio to receive subcutaneous itepekimab (300 mg), itepekimab plus dupilumab (both at 300 mg; combination therapy), dupilumab (300 mg), or placebo every 2 weeks for 12 weeks. LABAs were discontinued at week 4, and inhaled glucocorticoids were tapered over weeks 6 through 9. The primary endpoint was the occurrence of an event indicating the loss of asthma control.
 

Promising results

Primary endpoint analysis at 12 weeks revealed a lower rate of asthma control–loss events in the itepekimab and dupilumab monotherapy groups but not in the combination group, compared with patients who received placebo. Events occurred in 22% of patients in the itepekimab group, in 27% of those in the combination group, in 19% of the dupilumab group, and in 41% of the placebo group. The odds ratios for comparisons with placebo were 0.42 for the itepekimab group (95% confidence interval, 0.20-0.88; P = .02); 0.33 in the dupilumab group (95% CI, 0.15-.70); and 0.52 in the combination group (95% CI, 0.26-1.06; P = .07) .

Following a similar pattern, forced expiratory volume in 1 second before use of a bronchodilator increased with both monotherapies but not with the combination or placebo. Although the trial was not powered to determine differences between itepekimab and dupilumab, the effects of dupilumab therapy were generally greater than those observed with itepekimab, especially for patients with type 2 asthma.

Also, asthma control and quality of life were improved with itepekimab and dupilumab monotherapy in comparison with placebo. There were also greater reductions in the mean blood eosinophil count.

The authors urge further research into the complexities of asthma physiology and encourage researchers to look for predictive biomarkers of anti–interleukin-33 blockade response. They conclude, “In this trial, we found that itepekimab monotherapy led to a lower incidence of events indicating loss of asthma control and to improved lung function, findings that are consistent with a role for interleukin-33 in the pathogenesis of exacerbations and airflow limitation in asthma.”
 

Examining results

In an accompanying editorial, Philip G. Bardin, PhD, and Paul S. Foster, DSc, ask why itepekimab and dupilumab, a combination based on a sound scientific rationale, failed. As monotherapies, both itepekimab and dupilumab are roughly similar in reducing asthma events and improving lung function; thus, is unlikely that inadequate dosing led to the failure of itepekimab.

Interleukin-33 is an attractive target because the cells it promotes secrete cytokines that induce asthma’s pathognomonic features, and biologic agents that target those cytokines (interleukin-5/-5R/-4/-13 axes) have been highly effective. They do not, however, prevent exacerbations after treatment.

Alternative pathways within or outside that paradigm are operant, and other epithelial alarmins, such as interleukin-25 and thymic stromal lymphopoietin, promote type 2 inflammation, Dr. Bardin and Dr. Foster state.

“Combination therapy with itepekimab and dupilumab may have failed because these pathways bypass interleukin-33,” they write. Also, preexisting ILC2 and TH2 cells may have residual capacity to release mediators. The short-term trial design, the editorialists write, may have contributed to the failure of the itepekimab/dupilumab combination; interleukin-33 may be appropriate as a target in a longer-term exacerbation-type trial “in which epithelial infection and other relevant stimuli instigate exacerbated disease. Combination therapy may be capable of lowering exacerbations rather than preventing loss of control in chronic disease.

“Clinical translation of basic science in asthma remains a challenge to be pursued. ... It is imperative to harness scientific insights from translational studies that frustrate our hopeful expectations – so that something can also be gained,” they conclude.
 

The role of interleukin-33

“Our study of itepekimab provides valuable insight into pathophysiology of severe asthma,” said Dr. Wechsler, professor of medicine at the NJH Cohen Family Asthma Institute, Denver, in an interview. “As blocking IL-33 reduced asthma worsening and improved lung function compared to placebo, it suggests that IL-33 plays an important role in asthma pathophysiology and may be a valuable target for a subset of patients with severe asthma,” he stated.

“Since the effect of itepekimab is comparable to that of dupilumab, it is suggested that patients may benefit from blockade of this pathway, but what remains to be seen is identifying which patients are more likely to respond better to one therapy vs. another. The future of blocking IL-33 remains exciting, and studies are being planned to evaluate its efficacy in airways diseases, including COPD,” he concluded.

A version of this article first appeared on Medscape.com.

For patients with moderate to severe asthma, blockade with itepekimab, a new human IgG4P monoclonal antibody against the upstream alarmin interleukin-33, led to a reduction in events that indicate loss of asthma control. Treatment with itepekimab also led to an improvement in lung function compared with placebo, according to results of a phase 2 trial.

However, findings for a subgroup of patients treated with itepekimab in combination with dupilumab, an anti–interleukin-4–receptor alpha subunit and IL-13 monoclonal antibody, were not favorable in comparison with placebo, noted M. E. Wechsler, MD, and colleagues in an article published online in the New England Journal of Medicine.
 

New target

Despite the demonstrated efficacy of available biologic therapies targeting IgE, interleukin-4, interleukin-13, and interleukin-5 for treating moderate to severe type 2 asthma, many patients with type 2 or non–type 2 asthma continue to have symptoms, exacerbations, and reduced lung function. New therapies targeting alternative pathophysiologic pathways are needed.

Genomewide studies show that type 2 and non–type 2 inflammation that contributes to asthma and chronic obstructive pulmonary disease (COPD) are genetically associated with interleukin-33. This inflammation occurs when interleukin-33 binds to its cognate receptor (ST2) and engages the coreceptor interleukin-1 receptor accessory protein to initiate downstream signaling, activating cells of both the innate and adaptive immune systems.
 

Study details

The investigators conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group (four groups), proof-of-concept trial to evaluate the efficacy and safety of the interleukin-33 targeting itepekimab in comparison with placebo for adults with moderate to severe asthma. Dupilumab, which was the active comparator, was administered in combination with itepekimab to evaluate potential additive effects. Dupilumab’s efficacy in this population had been demonstrated previously.

All 296 patients (mean age, 49.1 years; 64% women) were receiving inhaled glucocorticoids plus long-acting beta-agonists (LABAs). They were randomly assigned in a 1:1:1:1 ratio to receive subcutaneous itepekimab (300 mg), itepekimab plus dupilumab (both at 300 mg; combination therapy), dupilumab (300 mg), or placebo every 2 weeks for 12 weeks. LABAs were discontinued at week 4, and inhaled glucocorticoids were tapered over weeks 6 through 9. The primary endpoint was the occurrence of an event indicating the loss of asthma control.
 

Promising results

Primary endpoint analysis at 12 weeks revealed a lower rate of asthma control–loss events in the itepekimab and dupilumab monotherapy groups but not in the combination group, compared with patients who received placebo. Events occurred in 22% of patients in the itepekimab group, in 27% of those in the combination group, in 19% of the dupilumab group, and in 41% of the placebo group. The odds ratios for comparisons with placebo were 0.42 for the itepekimab group (95% confidence interval, 0.20-0.88; P = .02); 0.33 in the dupilumab group (95% CI, 0.15-.70); and 0.52 in the combination group (95% CI, 0.26-1.06; P = .07) .

Following a similar pattern, forced expiratory volume in 1 second before use of a bronchodilator increased with both monotherapies but not with the combination or placebo. Although the trial was not powered to determine differences between itepekimab and dupilumab, the effects of dupilumab therapy were generally greater than those observed with itepekimab, especially for patients with type 2 asthma.

Also, asthma control and quality of life were improved with itepekimab and dupilumab monotherapy in comparison with placebo. There were also greater reductions in the mean blood eosinophil count.

The authors urge further research into the complexities of asthma physiology and encourage researchers to look for predictive biomarkers of anti–interleukin-33 blockade response. They conclude, “In this trial, we found that itepekimab monotherapy led to a lower incidence of events indicating loss of asthma control and to improved lung function, findings that are consistent with a role for interleukin-33 in the pathogenesis of exacerbations and airflow limitation in asthma.”
 

Examining results

In an accompanying editorial, Philip G. Bardin, PhD, and Paul S. Foster, DSc, ask why itepekimab and dupilumab, a combination based on a sound scientific rationale, failed. As monotherapies, both itepekimab and dupilumab are roughly similar in reducing asthma events and improving lung function; thus, is unlikely that inadequate dosing led to the failure of itepekimab.

Interleukin-33 is an attractive target because the cells it promotes secrete cytokines that induce asthma’s pathognomonic features, and biologic agents that target those cytokines (interleukin-5/-5R/-4/-13 axes) have been highly effective. They do not, however, prevent exacerbations after treatment.

Alternative pathways within or outside that paradigm are operant, and other epithelial alarmins, such as interleukin-25 and thymic stromal lymphopoietin, promote type 2 inflammation, Dr. Bardin and Dr. Foster state.

“Combination therapy with itepekimab and dupilumab may have failed because these pathways bypass interleukin-33,” they write. Also, preexisting ILC2 and TH2 cells may have residual capacity to release mediators. The short-term trial design, the editorialists write, may have contributed to the failure of the itepekimab/dupilumab combination; interleukin-33 may be appropriate as a target in a longer-term exacerbation-type trial “in which epithelial infection and other relevant stimuli instigate exacerbated disease. Combination therapy may be capable of lowering exacerbations rather than preventing loss of control in chronic disease.

“Clinical translation of basic science in asthma remains a challenge to be pursued. ... It is imperative to harness scientific insights from translational studies that frustrate our hopeful expectations – so that something can also be gained,” they conclude.
 

The role of interleukin-33

“Our study of itepekimab provides valuable insight into pathophysiology of severe asthma,” said Dr. Wechsler, professor of medicine at the NJH Cohen Family Asthma Institute, Denver, in an interview. “As blocking IL-33 reduced asthma worsening and improved lung function compared to placebo, it suggests that IL-33 plays an important role in asthma pathophysiology and may be a valuable target for a subset of patients with severe asthma,” he stated.

“Since the effect of itepekimab is comparable to that of dupilumab, it is suggested that patients may benefit from blockade of this pathway, but what remains to be seen is identifying which patients are more likely to respond better to one therapy vs. another. The future of blocking IL-33 remains exciting, and studies are being planned to evaluate its efficacy in airways diseases, including COPD,” he concluded.

A version of this article first appeared on Medscape.com.

Placebo treatment was found to be superior to treatment with risankizumab with respect to time to first asthma worsening and annualized rate of asthma worsening for adults with severe persistent asthma in a phase 2a clinical trial.

The randomized, double-blind, 24-week, parallel group, multicenter trial assessed risankizumab efficacy and safety in 214 adults with severe persistent asthma. The results were reported in The New England Journal of Medicine.

Risankizumab is a humanized, monoclonal antibody directed against subunit p19 of interleukin-23. It is approved for the treatment of moderate to severe psoriasis.

Interleukin-23 has been implicated in airway inflammation mediated by type 2 and type 17 cytokines. Noting that inhibition of interleukin-23 is effective in the treatment of psoriasis and Crohn’s disease, Christopher E. Brightling, MD, and colleagues investigated whether targeting interleukin-23 in asthma patients would improve disease control and reduce airway inflammation.
 

Study details

Patients received either 90 mg of risankizumab (subcutaneous) (n = 105) or placebo (n = 109) once every 4 weeks. Time to first asthma worsening was the primary endpoint. Worsening was defined as decline from baseline on 2 or more consecutive days. Deterioration was defined as a decrease of at least 30% in the morning peak expiratory flow or an increase from baseline of at least 50% in rescue medication puffs over 24 hours. In addition, a severe asthma exacerbation or an increase of 0.75 or more points on the five-item Asthma Control Questionnaire (scores range from 0 to 6, with higher scores indicating less control) were considered to be evidence of worsening. Annualized rate of asthma worsening was a secondary endpoint.

The mean age of the patients was 53 years; 66.5% of the patients were women.
 

Disappointing results

In the risankizumab group, median time to first asthma worsening was 40 days, significantly worse than the 86 days reported for the placebo group (hazard ratio, 1.46; 95% confidence interval, 1.05-2.04; P = .03). For annualized asthma worsening, the rate ratio for the comparison of risankizumab with placebo was 1.49 (95% CI, 1.12-1.99).

Among key secondary endpoints, the adjusted mean change in trough forced expiratory volume in 1 second (FEV₁₎ from baseline to week 24 was –0.05 L in the risankizumab group and –0.01 L in the placebo group. The adjusted mean change in FEV₁ after bronchodilator use from baseline to week 24 was –0.10 L in the risankizumab group and –0.03 L in the placebo group. Sputum transcriptomic pathway analysis showed that genes involved in the activation of natural killer cells and cytotoxic T cells and the activation of type 1 helper T and type 17 helper T transcription factors were downregulated by risankizumab. Rates of adverse events were similar among patients receiving risankizumab and those taking placebo.
 

Further trials unwarranted

“The findings not only failed to show benefit for any outcome but also showed asthma worsening occurred earlier and more frequently in those treated with risankizumab versus placebo,” Dr. Brightling, professor in the department of respiratory sciences at University of Leicester, England, said in an interview. “This study does not support any further trials for anti-IL23 in asthma.” Dr. Brightling speculated on the cause of accelerated asthma worsening with risankizumab.

“We found that the gene expression of key molecules involved in our response to infection was decreased in airway samples in those treated with risankizumab versus placebo. It is possible that the increased asthma worsening following risankizumab was related to this suppression of antimicrobial immunity,” he said.

He noted that risankizumab did not affect type-2/eosinophilic inflammation, which is the target for current asthma biologics, or gene expression of T2 molecules. “That suggests that this type of inflammation would have continued in the asthma patients during the trial irrespective of receiving risankizumab or placebo,” he said.
 

Caution with investigating biologicals

Downstream biologic responses to risankizumab were detectable, Philip G. Bardin, PhD, and Paul S. Foster, DSc, observed in an accompanying editorial, but there was no discernible clinical benefit, implying attenuation of apposite pathways. Current understanding of the basic science relevant to asthma, they stated, offers clues to the failure of risankizumab to benefit these patients with severe asthma. Although targeting the interleukin-23 and Th17 axis with risankizumab can reduce development of pathogenic Th17 cells, interleukin-23 is not critical for the development of Th17 cells.

“In contrast to pathways operated by interleukin-5 and interleukin-4R alpha, interleukin-23 has only a limited auxiliary role in amplifying type 2 responses. It is possible that the trial conducted by Brightling and colleagues failed because signaling through alternative disease pathways nullified inhibition of inter-leukin-23,” the editorialists wrote.

Dr. Bardin and Dr. Foster further speculate that because interleukin-23 is vital for effective mucosal immunity, risankizumab may have conferred to patients a predisposition to more severe or more frequent virus-induced exacerbations. They stated that generally, however, the reasons for risankizumab’s poorer outcomes compared to placebo are unclear. “Overall, these findings support a cautious approach in future research investigating biologic therapies in asthma,” they concluded.

The clinical trial was sponsored and funded by BI/AbbVie.

A version of this article first appeared on Medscape.com.

Placebo treatment was found to be superior to treatment with risankizumab with respect to time to first asthma worsening and annualized rate of asthma worsening for adults with severe persistent asthma in a phase 2a clinical trial.

The randomized, double-blind, 24-week, parallel group, multicenter trial assessed risankizumab efficacy and safety in 214 adults with severe persistent asthma. The results were reported in The New England Journal of Medicine.

Risankizumab is a humanized, monoclonal antibody directed against subunit p19 of interleukin-23. It is approved for the treatment of moderate to severe psoriasis.

Interleukin-23 has been implicated in airway inflammation mediated by type 2 and type 17 cytokines. Noting that inhibition of interleukin-23 is effective in the treatment of psoriasis and Crohn’s disease, Christopher E. Brightling, MD, and colleagues investigated whether targeting interleukin-23 in asthma patients would improve disease control and reduce airway inflammation.
 

Study details

Patients received either 90 mg of risankizumab (subcutaneous) (n = 105) or placebo (n = 109) once every 4 weeks. Time to first asthma worsening was the primary endpoint. Worsening was defined as decline from baseline on 2 or more consecutive days. Deterioration was defined as a decrease of at least 30% in the morning peak expiratory flow or an increase from baseline of at least 50% in rescue medication puffs over 24 hours. In addition, a severe asthma exacerbation or an increase of 0.75 or more points on the five-item Asthma Control Questionnaire (scores range from 0 to 6, with higher scores indicating less control) were considered to be evidence of worsening. Annualized rate of asthma worsening was a secondary endpoint.

The mean age of the patients was 53 years; 66.5% of the patients were women.
 

Disappointing results

In the risankizumab group, median time to first asthma worsening was 40 days, significantly worse than the 86 days reported for the placebo group (hazard ratio, 1.46; 95% confidence interval, 1.05-2.04; P = .03). For annualized asthma worsening, the rate ratio for the comparison of risankizumab with placebo was 1.49 (95% CI, 1.12-1.99).

Among key secondary endpoints, the adjusted mean change in trough forced expiratory volume in 1 second (FEV₁₎ from baseline to week 24 was –0.05 L in the risankizumab group and –0.01 L in the placebo group. The adjusted mean change in FEV₁ after bronchodilator use from baseline to week 24 was –0.10 L in the risankizumab group and –0.03 L in the placebo group. Sputum transcriptomic pathway analysis showed that genes involved in the activation of natural killer cells and cytotoxic T cells and the activation of type 1 helper T and type 17 helper T transcription factors were downregulated by risankizumab. Rates of adverse events were similar among patients receiving risankizumab and those taking placebo.
 

Further trials unwarranted

“The findings not only failed to show benefit for any outcome but also showed asthma worsening occurred earlier and more frequently in those treated with risankizumab versus placebo,” Dr. Brightling, professor in the department of respiratory sciences at University of Leicester, England, said in an interview. “This study does not support any further trials for anti-IL23 in asthma.” Dr. Brightling speculated on the cause of accelerated asthma worsening with risankizumab.

“We found that the gene expression of key molecules involved in our response to infection was decreased in airway samples in those treated with risankizumab versus placebo. It is possible that the increased asthma worsening following risankizumab was related to this suppression of antimicrobial immunity,” he said.

He noted that risankizumab did not affect type-2/eosinophilic inflammation, which is the target for current asthma biologics, or gene expression of T2 molecules. “That suggests that this type of inflammation would have continued in the asthma patients during the trial irrespective of receiving risankizumab or placebo,” he said.
 

Caution with investigating biologicals

Downstream biologic responses to risankizumab were detectable, Philip G. Bardin, PhD, and Paul S. Foster, DSc, observed in an accompanying editorial, but there was no discernible clinical benefit, implying attenuation of apposite pathways. Current understanding of the basic science relevant to asthma, they stated, offers clues to the failure of risankizumab to benefit these patients with severe asthma. Although targeting the interleukin-23 and Th17 axis with risankizumab can reduce development of pathogenic Th17 cells, interleukin-23 is not critical for the development of Th17 cells.

“In contrast to pathways operated by interleukin-5 and interleukin-4R alpha, interleukin-23 has only a limited auxiliary role in amplifying type 2 responses. It is possible that the trial conducted by Brightling and colleagues failed because signaling through alternative disease pathways nullified inhibition of inter-leukin-23,” the editorialists wrote.

Dr. Bardin and Dr. Foster further speculate that because interleukin-23 is vital for effective mucosal immunity, risankizumab may have conferred to patients a predisposition to more severe or more frequent virus-induced exacerbations. They stated that generally, however, the reasons for risankizumab’s poorer outcomes compared to placebo are unclear. “Overall, these findings support a cautious approach in future research investigating biologic therapies in asthma,” they concluded.

The clinical trial was sponsored and funded by BI/AbbVie.

A version of this article first appeared on Medscape.com.

Placebo treatment was found to be superior to treatment with risankizumab with respect to time to first asthma worsening and annualized rate of asthma worsening for adults with severe persistent asthma in a phase 2a clinical trial.

The randomized, double-blind, 24-week, parallel group, multicenter trial assessed risankizumab efficacy and safety in 214 adults with severe persistent asthma. The results were reported in The New England Journal of Medicine.

Risankizumab is a humanized, monoclonal antibody directed against subunit p19 of interleukin-23. It is approved for the treatment of moderate to severe psoriasis.

Interleukin-23 has been implicated in airway inflammation mediated by type 2 and type 17 cytokines. Noting that inhibition of interleukin-23 is effective in the treatment of psoriasis and Crohn’s disease, Christopher E. Brightling, MD, and colleagues investigated whether targeting interleukin-23 in asthma patients would improve disease control and reduce airway inflammation.
 

Study details

Patients received either 90 mg of risankizumab (subcutaneous) (n = 105) or placebo (n = 109) once every 4 weeks. Time to first asthma worsening was the primary endpoint. Worsening was defined as decline from baseline on 2 or more consecutive days. Deterioration was defined as a decrease of at least 30% in the morning peak expiratory flow or an increase from baseline of at least 50% in rescue medication puffs over 24 hours. In addition, a severe asthma exacerbation or an increase of 0.75 or more points on the five-item Asthma Control Questionnaire (scores range from 0 to 6, with higher scores indicating less control) were considered to be evidence of worsening. Annualized rate of asthma worsening was a secondary endpoint.

The mean age of the patients was 53 years; 66.5% of the patients were women.
 

Disappointing results

In the risankizumab group, median time to first asthma worsening was 40 days, significantly worse than the 86 days reported for the placebo group (hazard ratio, 1.46; 95% confidence interval, 1.05-2.04; P = .03). For annualized asthma worsening, the rate ratio for the comparison of risankizumab with placebo was 1.49 (95% CI, 1.12-1.99).

Among key secondary endpoints, the adjusted mean change in trough forced expiratory volume in 1 second (FEV₁₎ from baseline to week 24 was –0.05 L in the risankizumab group and –0.01 L in the placebo group. The adjusted mean change in FEV₁ after bronchodilator use from baseline to week 24 was –0.10 L in the risankizumab group and –0.03 L in the placebo group. Sputum transcriptomic pathway analysis showed that genes involved in the activation of natural killer cells and cytotoxic T cells and the activation of type 1 helper T and type 17 helper T transcription factors were downregulated by risankizumab. Rates of adverse events were similar among patients receiving risankizumab and those taking placebo.
 

Further trials unwarranted

“The findings not only failed to show benefit for any outcome but also showed asthma worsening occurred earlier and more frequently in those treated with risankizumab versus placebo,” Dr. Brightling, professor in the department of respiratory sciences at University of Leicester, England, said in an interview. “This study does not support any further trials for anti-IL23 in asthma.” Dr. Brightling speculated on the cause of accelerated asthma worsening with risankizumab.

“We found that the gene expression of key molecules involved in our response to infection was decreased in airway samples in those treated with risankizumab versus placebo. It is possible that the increased asthma worsening following risankizumab was related to this suppression of antimicrobial immunity,” he said.

He noted that risankizumab did not affect type-2/eosinophilic inflammation, which is the target for current asthma biologics, or gene expression of T2 molecules. “That suggests that this type of inflammation would have continued in the asthma patients during the trial irrespective of receiving risankizumab or placebo,” he said.
 

Caution with investigating biologicals

Downstream biologic responses to risankizumab were detectable, Philip G. Bardin, PhD, and Paul S. Foster, DSc, observed in an accompanying editorial, but there was no discernible clinical benefit, implying attenuation of apposite pathways. Current understanding of the basic science relevant to asthma, they stated, offers clues to the failure of risankizumab to benefit these patients with severe asthma. Although targeting the interleukin-23 and Th17 axis with risankizumab can reduce development of pathogenic Th17 cells, interleukin-23 is not critical for the development of Th17 cells.

“In contrast to pathways operated by interleukin-5 and interleukin-4R alpha, interleukin-23 has only a limited auxiliary role in amplifying type 2 responses. It is possible that the trial conducted by Brightling and colleagues failed because signaling through alternative disease pathways nullified inhibition of inter-leukin-23,” the editorialists wrote.

Dr. Bardin and Dr. Foster further speculate that because interleukin-23 is vital for effective mucosal immunity, risankizumab may have conferred to patients a predisposition to more severe or more frequent virus-induced exacerbations. They stated that generally, however, the reasons for risankizumab’s poorer outcomes compared to placebo are unclear. “Overall, these findings support a cautious approach in future research investigating biologic therapies in asthma,” they concluded.

The clinical trial was sponsored and funded by BI/AbbVie.

A version of this article first appeared on Medscape.com.

Oral fluoroquinolone therapy to treat a respiratory infection is associated with an increased risk of sudden cardiac death (SCD) in patients on hemodialysis, particularly those taking other QT-prolonging medications, a large observational study suggests.

However, in many cases, the absolute risk is relatively small, and the antimicrobial benefits of a fluoroquinolone may outweigh the potential cardiac risks, the researchers say.

“Pathogen-directed treatment of respiratory infections is of the utmost importance. Respiratory fluoroquinolones should be prescribed whenever an amoxicillin-based antibiotic offers suboptimal antimicrobial coverage and clinicians should consider electrocardiographic monitoring,” first author Magdalene M. Assimon, PharmD, PhD, University of North Carolina, Chapel Hill, told this news organization.

The study was published online Oct. 20 in JAMA Cardiology (doi: 10.1001/jamacardio.2021.4234).
 

Nearly twofold increased risk 

The QT interval-prolonging potential of fluoroquinolone antibiotics are well known. However, evidence linking respiratory fluoroquinolones to adverse cardiac outcomes in the hemodialysis population is limited.

These new observational findings are based on a total of 626,322 antibiotic treatment episodes among 264,968 adults (mean age, 61 years; 51% men) receiving in-center hemodialysis – with respiratory fluoroquinolone making up 40.2% of treatment episodes and amoxicillin-based antibiotic treatment episodes making up 59.8%.

The rate of SCD within 5 days of outpatient initiation of a study antibiotic was 105.7 per 100,000 people prescribed a respiratory fluoroquinolone (levofloxacin or moxifloxacin) versus with 40.0 per 100,000 prescribed amoxicillin or amoxicillin with clavulanic acid (weighted hazard ratio: 1.95; 95% confidence interval, 1.57-2.41).

The authors estimate that one additional SCD would occur during a 5-day follow-up period for every 2,273 respiratory fluoroquinolone treatment episodes. Consistent associations were seen when follow-up was extended to 7, 10, and 14 days.

“Our data suggest that curtailing respiratory fluoroquinolone prescribing may be one actionable strategy to mitigate SCD risk in the hemodialysis population. However, the associated absolute risk reduction would be relatively small,” wrote the authors.

They noted that the rate of SCD in the hemodialysis population exceeds that of the general population by more than 20-fold. Most patients undergoing hemodialysis have a least one risk factor for drug-induced QT interval prolongation.

In the current study, nearly 20% of hemodialysis patients prescribed a respiratory fluoroquinolone were taking other medications with known risk for torsades de pointes.

“Our results emphasize the importance of performing a thorough medication review and considering pharmacodynamic drug interactions before prescribing new drug therapies for any condition,” Dr. Assimon and colleagues advised.

They suggest that clinicians consider electrocardiographic monitoring before and during fluoroquinolone therapy in hemodialysis patients, especially in high-risk individuals.
 

Valuable study

Reached for comment, Ankur Shah, MD, of the division of kidney diseases and hypertension, Brown University, Providence, R.I., called the analysis “valuable” and said the results are “consistent with the known association of cardiac arrhythmias with respiratory fluoroquinolone use in the general population, postulated to be due to increased risk of torsades de pointes from QTc prolongation. This abnormal heart rhythm can lead to sudden cardiac death.

“Notably, the population receiving respiratory fluoroquinolones had a higher incidence of cardiac disease at baseline, but the risk persisted after adjustment for this increased burden of comorbidity,” Dr. Shah said in an interview. He was not involved in the current research.

Dr. Shah cautioned that observational data such as these should be considered more “hypothesis-generating than practice-changing, as there may be unrecognized confounders or differences in the population that received the respiratory fluoroquinolones.

“A prospective randomized trial would provide a definitive answer, but in the interim, caution should be taken in using respiratory fluoroquinolones when local bacterial resistance patterns or patient-specific data offer another option,” Dr. Shah concluded.  

Dr. Assimon reported receiving grants from the Renal Research Institute (a subsidiary of Fresenius Medical Care), honoraria from the International Society of Nephrology for serving as a statistical reviewer for Kidney International Reports, and honoraria from the American Society of Nephrology for serving as an editorial fellow for the Journal of the American Society of Nephrology. Dr. Shah has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Oral fluoroquinolone therapy to treat a respiratory infection is associated with an increased risk of sudden cardiac death (SCD) in patients on hemodialysis, particularly those taking other QT-prolonging medications, a large observational study suggests.

However, in many cases, the absolute risk is relatively small, and the antimicrobial benefits of a fluoroquinolone may outweigh the potential cardiac risks, the researchers say.

“Pathogen-directed treatment of respiratory infections is of the utmost importance. Respiratory fluoroquinolones should be prescribed whenever an amoxicillin-based antibiotic offers suboptimal antimicrobial coverage and clinicians should consider electrocardiographic monitoring,” first author Magdalene M. Assimon, PharmD, PhD, University of North Carolina, Chapel Hill, told this news organization.

The study was published online Oct. 20 in JAMA Cardiology (doi: 10.1001/jamacardio.2021.4234).
 

Nearly twofold increased risk 

The QT interval-prolonging potential of fluoroquinolone antibiotics are well known. However, evidence linking respiratory fluoroquinolones to adverse cardiac outcomes in the hemodialysis population is limited.

These new observational findings are based on a total of 626,322 antibiotic treatment episodes among 264,968 adults (mean age, 61 years; 51% men) receiving in-center hemodialysis – with respiratory fluoroquinolone making up 40.2% of treatment episodes and amoxicillin-based antibiotic treatment episodes making up 59.8%.

The rate of SCD within 5 days of outpatient initiation of a study antibiotic was 105.7 per 100,000 people prescribed a respiratory fluoroquinolone (levofloxacin or moxifloxacin) versus with 40.0 per 100,000 prescribed amoxicillin or amoxicillin with clavulanic acid (weighted hazard ratio: 1.95; 95% confidence interval, 1.57-2.41).

The authors estimate that one additional SCD would occur during a 5-day follow-up period for every 2,273 respiratory fluoroquinolone treatment episodes. Consistent associations were seen when follow-up was extended to 7, 10, and 14 days.

“Our data suggest that curtailing respiratory fluoroquinolone prescribing may be one actionable strategy to mitigate SCD risk in the hemodialysis population. However, the associated absolute risk reduction would be relatively small,” wrote the authors.

They noted that the rate of SCD in the hemodialysis population exceeds that of the general population by more than 20-fold. Most patients undergoing hemodialysis have a least one risk factor for drug-induced QT interval prolongation.

In the current study, nearly 20% of hemodialysis patients prescribed a respiratory fluoroquinolone were taking other medications with known risk for torsades de pointes.

“Our results emphasize the importance of performing a thorough medication review and considering pharmacodynamic drug interactions before prescribing new drug therapies for any condition,” Dr. Assimon and colleagues advised.

They suggest that clinicians consider electrocardiographic monitoring before and during fluoroquinolone therapy in hemodialysis patients, especially in high-risk individuals.
 

Valuable study

Reached for comment, Ankur Shah, MD, of the division of kidney diseases and hypertension, Brown University, Providence, R.I., called the analysis “valuable” and said the results are “consistent with the known association of cardiac arrhythmias with respiratory fluoroquinolone use in the general population, postulated to be due to increased risk of torsades de pointes from QTc prolongation. This abnormal heart rhythm can lead to sudden cardiac death.

“Notably, the population receiving respiratory fluoroquinolones had a higher incidence of cardiac disease at baseline, but the risk persisted after adjustment for this increased burden of comorbidity,” Dr. Shah said in an interview. He was not involved in the current research.

Dr. Shah cautioned that observational data such as these should be considered more “hypothesis-generating than practice-changing, as there may be unrecognized confounders or differences in the population that received the respiratory fluoroquinolones.

“A prospective randomized trial would provide a definitive answer, but in the interim, caution should be taken in using respiratory fluoroquinolones when local bacterial resistance patterns or patient-specific data offer another option,” Dr. Shah concluded.  

Dr. Assimon reported receiving grants from the Renal Research Institute (a subsidiary of Fresenius Medical Care), honoraria from the International Society of Nephrology for serving as a statistical reviewer for Kidney International Reports, and honoraria from the American Society of Nephrology for serving as an editorial fellow for the Journal of the American Society of Nephrology. Dr. Shah has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Oral fluoroquinolone therapy to treat a respiratory infection is associated with an increased risk of sudden cardiac death (SCD) in patients on hemodialysis, particularly those taking other QT-prolonging medications, a large observational study suggests.

However, in many cases, the absolute risk is relatively small, and the antimicrobial benefits of a fluoroquinolone may outweigh the potential cardiac risks, the researchers say.

“Pathogen-directed treatment of respiratory infections is of the utmost importance. Respiratory fluoroquinolones should be prescribed whenever an amoxicillin-based antibiotic offers suboptimal antimicrobial coverage and clinicians should consider electrocardiographic monitoring,” first author Magdalene M. Assimon, PharmD, PhD, University of North Carolina, Chapel Hill, told this news organization.

The study was published online Oct. 20 in JAMA Cardiology (doi: 10.1001/jamacardio.2021.4234).
 

Nearly twofold increased risk 

The QT interval-prolonging potential of fluoroquinolone antibiotics are well known. However, evidence linking respiratory fluoroquinolones to adverse cardiac outcomes in the hemodialysis population is limited.

These new observational findings are based on a total of 626,322 antibiotic treatment episodes among 264,968 adults (mean age, 61 years; 51% men) receiving in-center hemodialysis – with respiratory fluoroquinolone making up 40.2% of treatment episodes and amoxicillin-based antibiotic treatment episodes making up 59.8%.

The rate of SCD within 5 days of outpatient initiation of a study antibiotic was 105.7 per 100,000 people prescribed a respiratory fluoroquinolone (levofloxacin or moxifloxacin) versus with 40.0 per 100,000 prescribed amoxicillin or amoxicillin with clavulanic acid (weighted hazard ratio: 1.95; 95% confidence interval, 1.57-2.41).

The authors estimate that one additional SCD would occur during a 5-day follow-up period for every 2,273 respiratory fluoroquinolone treatment episodes. Consistent associations were seen when follow-up was extended to 7, 10, and 14 days.

“Our data suggest that curtailing respiratory fluoroquinolone prescribing may be one actionable strategy to mitigate SCD risk in the hemodialysis population. However, the associated absolute risk reduction would be relatively small,” wrote the authors.

They noted that the rate of SCD in the hemodialysis population exceeds that of the general population by more than 20-fold. Most patients undergoing hemodialysis have a least one risk factor for drug-induced QT interval prolongation.

In the current study, nearly 20% of hemodialysis patients prescribed a respiratory fluoroquinolone were taking other medications with known risk for torsades de pointes.

“Our results emphasize the importance of performing a thorough medication review and considering pharmacodynamic drug interactions before prescribing new drug therapies for any condition,” Dr. Assimon and colleagues advised.

They suggest that clinicians consider electrocardiographic monitoring before and during fluoroquinolone therapy in hemodialysis patients, especially in high-risk individuals.
 

Valuable study

Reached for comment, Ankur Shah, MD, of the division of kidney diseases and hypertension, Brown University, Providence, R.I., called the analysis “valuable” and said the results are “consistent with the known association of cardiac arrhythmias with respiratory fluoroquinolone use in the general population, postulated to be due to increased risk of torsades de pointes from QTc prolongation. This abnormal heart rhythm can lead to sudden cardiac death.

“Notably, the population receiving respiratory fluoroquinolones had a higher incidence of cardiac disease at baseline, but the risk persisted after adjustment for this increased burden of comorbidity,” Dr. Shah said in an interview. He was not involved in the current research.

Dr. Shah cautioned that observational data such as these should be considered more “hypothesis-generating than practice-changing, as there may be unrecognized confounders or differences in the population that received the respiratory fluoroquinolones.

“A prospective randomized trial would provide a definitive answer, but in the interim, caution should be taken in using respiratory fluoroquinolones when local bacterial resistance patterns or patient-specific data offer another option,” Dr. Shah concluded.  

Dr. Assimon reported receiving grants from the Renal Research Institute (a subsidiary of Fresenius Medical Care), honoraria from the International Society of Nephrology for serving as a statistical reviewer for Kidney International Reports, and honoraria from the American Society of Nephrology for serving as an editorial fellow for the Journal of the American Society of Nephrology. Dr. Shah has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

I graduated medical school in May 2020, right as COVID was taking over the country, and the specter of the virus has hung over every aspect of my residency education thus far.

I did not get a medical school graduation; I was one of the many thousands of newly graduated students who simply left their 4th-year rotation sites one chilly day in March 2020 and just never went back. My medical school education didn’t end with me walking triumphantly across the stage – a first-generation college student finally achieving the greatest dream in her life. Instead, it ended with a Zoom “graduation” and a cross-country move from Georgia to Pennsylvania amidst the greatest pandemic in recent memory. To say my impostor syndrome was bad would be an understatement.
 

Residency in the COVID-19-era

The joy and the draw to family medicine for me has always been the broad scope of conditions that we see and treat. From day 1, however, much of my residency has been devoted to one very small subset of patients – those with COVID-19. At one point, our hospital was so strained that our family medicine program had to run a second inpatient service alongside our usual five-resident service team just to provide care to everybody. Patients were in the hallways. The ER was packed to the gills. We were sleepless, terrified, unvaccinated, and desperate to help our patients survive a disease that was incompletely understood, with very few tools in our toolbox to combat it.

I distinctly remember sitting in the workroom with a coresident of mine, our faces seemingly permanently lined from wearing N95s all shift, and saying to him, “I worry I will be a bad family medicine physician. I worry I haven’t seen enough, other than COVID.” It was midway through my intern year; the days were short, so I was driving to and from the hospital in chilly darkness. My patients, like many around the country, were doing poorly. Vaccines seemed like a promise too good to be true. Worst of all: Those of us who were interns, who had no triumphant podium moment to end our medical school education, were suffering with an intense sense of impostor syndrome which was strengthened by every “there is nothing else we can offer your loved one at this time,” conversation we had. My apprehension about not having seen a wider breadth of medicine during my training is a sentiment still widely shared by COVID-era residents.

Luckily, my coresident was supportive.

“We’re going to be great family medicine physicians,” he said. “We’re learning the hard stuff – the bread and butter of FM – up-front. You’ll see.”

In some ways, I think he was right. Clinical skills, empathy, humility, and forging strong relationships are at the center of every family medicine physician’s heart; my generation has had to learn these skills early and under pressure. Sometimes, there are no answers. Sometimes, the best thing a family doctor can do for a patient is to hear them, understand them, and hold their hand.
 

‘We watched Cinderella together’

Shortly after that conversation with my coresident, I had a particular case which moved me. This gentleman with intellectual disability and COVID had been declining steadily since his admission to the hospital. He was isolated from everybody he knew and loved, but it did not dampen his spirits. He was cheerful to every person who entered his room, clad in their shrouds of PPE, which more often than not felt more like mourning garb than protective wear. I remember very little about this patient’s clinical picture – the COVID, the superimposed pneumonia, the repeated intubations. What I do remember is he loved the Disney classic, Cinderella. I knew this because I developed a very close relationship with his family during the course of his hospitalization. Amidst the torrential onslaught of patients, I made sure to call families every day – not because I wanted to, but because my mentors and attendings and coresidents had all drilled into me from day 1 that we are family medicine, and a large part of our role is to advocate for our patients, and to communicate with their loved ones. So I called. I learned a lot about him; his likes, his dislikes, his close bond with his siblings, and of course his lifelong love for Cinderella. On the last week of my ICU rotation, my patient passed peacefully. His nurse and I were bedside. We held his hand. We told him his family loved him. We watched Cinderella together on an iPad encased in protective plastic.

My next rotation was an outpatient one and it looked more like the “bread and butter” of family medicine. But as I whisked in and out of patient rooms, attending to patients with diabetes, with depression, with pain, I could not stop thinking about my hospitalized patients who my coresidents had assumed care of. Each exam room I entered, I rather morbidly thought “this patient could be next on our hospital service.” Without realizing it, I made more of an effort to get to know each patient holistically. I learned who they were as people. I found myself writing small, medically low-yield details in the chart: “Margaret loves to sing in her church choir;” “Katherine is a self-published author.”

I learned from my attendings. As I sat at the precepting table with them, observing their conversations about patients, their collective decades of experience were apparent.

“I’ve been seeing this patient every few weeks since I was a resident,” said one of my attendings.

“I don’t even see my parents that often,” I thought.

The depth of her relationship with, understanding of, and compassion for this patient struck me deeply. This was why I went into family medicine. My attending knew her patients; they were not faceless unknowns in a hospital gown to her. She would have known to play Cinderella for them in the end.

This is a unique time for trainees. We have been challenged, terrified, overwhelmed, and heartbroken. But at no point have we been isolated. We’ve had the generations of doctors before us to lead the way, to teach us the “hard stuff.” We’ve had senior residents to lean on, who have taken us aside and told us, “I can do the goals-of-care talk today, you need a break.” While the plague seems to have passed over our hospital for now, it has left behind a class of family medicine residents who are proud to carry on our specialty’s long tradition of compassionate, empathetic, lifelong care. “We care for all life stages, from cradle to grave,” says every family medicine physician.

My class, for better or for worse, has cared more often for patients in the twilight of their lives, and while it has been hard, I believe it has made us all better doctors. Now, when I hold a newborn in my arms for a well-child check, I am exceptionally grateful – for the opportunities I have been given, for new beginnings amidst so much sadness, and for the great privilege of being a family medicine physician.
 

Dr. Persampiere is a 2nd-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. You can contact her directly at [email protected] or via [email protected].

I graduated medical school in May 2020, right as COVID was taking over the country, and the specter of the virus has hung over every aspect of my residency education thus far.

I did not get a medical school graduation; I was one of the many thousands of newly graduated students who simply left their 4th-year rotation sites one chilly day in March 2020 and just never went back. My medical school education didn’t end with me walking triumphantly across the stage – a first-generation college student finally achieving the greatest dream in her life. Instead, it ended with a Zoom “graduation” and a cross-country move from Georgia to Pennsylvania amidst the greatest pandemic in recent memory. To say my impostor syndrome was bad would be an understatement.
 

Residency in the COVID-19-era

The joy and the draw to family medicine for me has always been the broad scope of conditions that we see and treat. From day 1, however, much of my residency has been devoted to one very small subset of patients – those with COVID-19. At one point, our hospital was so strained that our family medicine program had to run a second inpatient service alongside our usual five-resident service team just to provide care to everybody. Patients were in the hallways. The ER was packed to the gills. We were sleepless, terrified, unvaccinated, and desperate to help our patients survive a disease that was incompletely understood, with very few tools in our toolbox to combat it.

I distinctly remember sitting in the workroom with a coresident of mine, our faces seemingly permanently lined from wearing N95s all shift, and saying to him, “I worry I will be a bad family medicine physician. I worry I haven’t seen enough, other than COVID.” It was midway through my intern year; the days were short, so I was driving to and from the hospital in chilly darkness. My patients, like many around the country, were doing poorly. Vaccines seemed like a promise too good to be true. Worst of all: Those of us who were interns, who had no triumphant podium moment to end our medical school education, were suffering with an intense sense of impostor syndrome which was strengthened by every “there is nothing else we can offer your loved one at this time,” conversation we had. My apprehension about not having seen a wider breadth of medicine during my training is a sentiment still widely shared by COVID-era residents.

Luckily, my coresident was supportive.

“We’re going to be great family medicine physicians,” he said. “We’re learning the hard stuff – the bread and butter of FM – up-front. You’ll see.”

In some ways, I think he was right. Clinical skills, empathy, humility, and forging strong relationships are at the center of every family medicine physician’s heart; my generation has had to learn these skills early and under pressure. Sometimes, there are no answers. Sometimes, the best thing a family doctor can do for a patient is to hear them, understand them, and hold their hand.
 

‘We watched Cinderella together’

Shortly after that conversation with my coresident, I had a particular case which moved me. This gentleman with intellectual disability and COVID had been declining steadily since his admission to the hospital. He was isolated from everybody he knew and loved, but it did not dampen his spirits. He was cheerful to every person who entered his room, clad in their shrouds of PPE, which more often than not felt more like mourning garb than protective wear. I remember very little about this patient’s clinical picture – the COVID, the superimposed pneumonia, the repeated intubations. What I do remember is he loved the Disney classic, Cinderella. I knew this because I developed a very close relationship with his family during the course of his hospitalization. Amidst the torrential onslaught of patients, I made sure to call families every day – not because I wanted to, but because my mentors and attendings and coresidents had all drilled into me from day 1 that we are family medicine, and a large part of our role is to advocate for our patients, and to communicate with their loved ones. So I called. I learned a lot about him; his likes, his dislikes, his close bond with his siblings, and of course his lifelong love for Cinderella. On the last week of my ICU rotation, my patient passed peacefully. His nurse and I were bedside. We held his hand. We told him his family loved him. We watched Cinderella together on an iPad encased in protective plastic.

My next rotation was an outpatient one and it looked more like the “bread and butter” of family medicine. But as I whisked in and out of patient rooms, attending to patients with diabetes, with depression, with pain, I could not stop thinking about my hospitalized patients who my coresidents had assumed care of. Each exam room I entered, I rather morbidly thought “this patient could be next on our hospital service.” Without realizing it, I made more of an effort to get to know each patient holistically. I learned who they were as people. I found myself writing small, medically low-yield details in the chart: “Margaret loves to sing in her church choir;” “Katherine is a self-published author.”

I learned from my attendings. As I sat at the precepting table with them, observing their conversations about patients, their collective decades of experience were apparent.

“I’ve been seeing this patient every few weeks since I was a resident,” said one of my attendings.

“I don’t even see my parents that often,” I thought.

The depth of her relationship with, understanding of, and compassion for this patient struck me deeply. This was why I went into family medicine. My attending knew her patients; they were not faceless unknowns in a hospital gown to her. She would have known to play Cinderella for them in the end.

This is a unique time for trainees. We have been challenged, terrified, overwhelmed, and heartbroken. But at no point have we been isolated. We’ve had the generations of doctors before us to lead the way, to teach us the “hard stuff.” We’ve had senior residents to lean on, who have taken us aside and told us, “I can do the goals-of-care talk today, you need a break.” While the plague seems to have passed over our hospital for now, it has left behind a class of family medicine residents who are proud to carry on our specialty’s long tradition of compassionate, empathetic, lifelong care. “We care for all life stages, from cradle to grave,” says every family medicine physician.

My class, for better or for worse, has cared more often for patients in the twilight of their lives, and while it has been hard, I believe it has made us all better doctors. Now, when I hold a newborn in my arms for a well-child check, I am exceptionally grateful – for the opportunities I have been given, for new beginnings amidst so much sadness, and for the great privilege of being a family medicine physician.
 

Dr. Persampiere is a 2nd-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. You can contact her directly at [email protected] or via [email protected].

I graduated medical school in May 2020, right as COVID was taking over the country, and the specter of the virus has hung over every aspect of my residency education thus far.

I did not get a medical school graduation; I was one of the many thousands of newly graduated students who simply left their 4th-year rotation sites one chilly day in March 2020 and just never went back. My medical school education didn’t end with me walking triumphantly across the stage – a first-generation college student finally achieving the greatest dream in her life. Instead, it ended with a Zoom “graduation” and a cross-country move from Georgia to Pennsylvania amidst the greatest pandemic in recent memory. To say my impostor syndrome was bad would be an understatement.
 

Residency in the COVID-19-era

The joy and the draw to family medicine for me has always been the broad scope of conditions that we see and treat. From day 1, however, much of my residency has been devoted to one very small subset of patients – those with COVID-19. At one point, our hospital was so strained that our family medicine program had to run a second inpatient service alongside our usual five-resident service team just to provide care to everybody. Patients were in the hallways. The ER was packed to the gills. We were sleepless, terrified, unvaccinated, and desperate to help our patients survive a disease that was incompletely understood, with very few tools in our toolbox to combat it.

I distinctly remember sitting in the workroom with a coresident of mine, our faces seemingly permanently lined from wearing N95s all shift, and saying to him, “I worry I will be a bad family medicine physician. I worry I haven’t seen enough, other than COVID.” It was midway through my intern year; the days were short, so I was driving to and from the hospital in chilly darkness. My patients, like many around the country, were doing poorly. Vaccines seemed like a promise too good to be true. Worst of all: Those of us who were interns, who had no triumphant podium moment to end our medical school education, were suffering with an intense sense of impostor syndrome which was strengthened by every “there is nothing else we can offer your loved one at this time,” conversation we had. My apprehension about not having seen a wider breadth of medicine during my training is a sentiment still widely shared by COVID-era residents.

Luckily, my coresident was supportive.

“We’re going to be great family medicine physicians,” he said. “We’re learning the hard stuff – the bread and butter of FM – up-front. You’ll see.”

In some ways, I think he was right. Clinical skills, empathy, humility, and forging strong relationships are at the center of every family medicine physician’s heart; my generation has had to learn these skills early and under pressure. Sometimes, there are no answers. Sometimes, the best thing a family doctor can do for a patient is to hear them, understand them, and hold their hand.
 

‘We watched Cinderella together’

Shortly after that conversation with my coresident, I had a particular case which moved me. This gentleman with intellectual disability and COVID had been declining steadily since his admission to the hospital. He was isolated from everybody he knew and loved, but it did not dampen his spirits. He was cheerful to every person who entered his room, clad in their shrouds of PPE, which more often than not felt more like mourning garb than protective wear. I remember very little about this patient’s clinical picture – the COVID, the superimposed pneumonia, the repeated intubations. What I do remember is he loved the Disney classic, Cinderella. I knew this because I developed a very close relationship with his family during the course of his hospitalization. Amidst the torrential onslaught of patients, I made sure to call families every day – not because I wanted to, but because my mentors and attendings and coresidents had all drilled into me from day 1 that we are family medicine, and a large part of our role is to advocate for our patients, and to communicate with their loved ones. So I called. I learned a lot about him; his likes, his dislikes, his close bond with his siblings, and of course his lifelong love for Cinderella. On the last week of my ICU rotation, my patient passed peacefully. His nurse and I were bedside. We held his hand. We told him his family loved him. We watched Cinderella together on an iPad encased in protective plastic.

My next rotation was an outpatient one and it looked more like the “bread and butter” of family medicine. But as I whisked in and out of patient rooms, attending to patients with diabetes, with depression, with pain, I could not stop thinking about my hospitalized patients who my coresidents had assumed care of. Each exam room I entered, I rather morbidly thought “this patient could be next on our hospital service.” Without realizing it, I made more of an effort to get to know each patient holistically. I learned who they were as people. I found myself writing small, medically low-yield details in the chart: “Margaret loves to sing in her church choir;” “Katherine is a self-published author.”

I learned from my attendings. As I sat at the precepting table with them, observing their conversations about patients, their collective decades of experience were apparent.

“I’ve been seeing this patient every few weeks since I was a resident,” said one of my attendings.

“I don’t even see my parents that often,” I thought.

The depth of her relationship with, understanding of, and compassion for this patient struck me deeply. This was why I went into family medicine. My attending knew her patients; they were not faceless unknowns in a hospital gown to her. She would have known to play Cinderella for them in the end.

This is a unique time for trainees. We have been challenged, terrified, overwhelmed, and heartbroken. But at no point have we been isolated. We’ve had the generations of doctors before us to lead the way, to teach us the “hard stuff.” We’ve had senior residents to lean on, who have taken us aside and told us, “I can do the goals-of-care talk today, you need a break.” While the plague seems to have passed over our hospital for now, it has left behind a class of family medicine residents who are proud to carry on our specialty’s long tradition of compassionate, empathetic, lifelong care. “We care for all life stages, from cradle to grave,” says every family medicine physician.

My class, for better or for worse, has cared more often for patients in the twilight of their lives, and while it has been hard, I believe it has made us all better doctors. Now, when I hold a newborn in my arms for a well-child check, I am exceptionally grateful – for the opportunities I have been given, for new beginnings amidst so much sadness, and for the great privilege of being a family medicine physician.
 

Dr. Persampiere is a 2nd-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. You can contact her directly at [email protected] or via [email protected].

Antithrombotic therapy in clinically stable, nonhospitalized COVID-19 patients does not offer protection against adverse cardiovascular or pulmonary events, new randomized clinical trial results suggest.

Bruce Jancin/MDedge News

Antithrombotic therapy has proven useful in acutely ill inpatients with COVID-19, but in this study, treatment with aspirin or apixaban (Eliquis) did not reduce the rate of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary causes in patients ill with COVID-19 but who were not hospitalized.

“Among symptomatic, clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome,” the authors conclude. “However, the study was terminated after enrollment of 9% of participants because of a primary event rate lower than anticipated.”

The study, which was led by Jean M. Connors, MD, Brigham and Women’s Hospital, Boston, was published online October 11 in JAMA.

The ACTIV-4B Outpatient Thrombosis Prevention Trial was a randomized, adaptive, double-blind, placebo-controlled trial that sought to compare anticoagulant and antiplatelet therapy among 7,000 symptomatic but clinically stable outpatients with COVID-19.

The trial was conducted at 52 sites in the U.S. between Sept. 2020 and June 2021, with final follow-up this past August 5, and involved minimal face-to-face interactions with study participants.

Patients were randomized in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164 patients), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days.

The primary endpoint was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause.

The trial was terminated early this past June by the independent data monitoring committee because of lower than anticipated event rates. At the time, just 657 symptomatic outpatients with COVID-19 had been enrolled.

The median age of the study participants was 54 years (Interquartile Range [IQR] 46-59); 59% were women.

The median time from diagnosis to randomization was 7 days, and the median time from randomization to initiation of study medications was 3 days.

The trial’s primary efficacy and safety analyses were restricted to patients who received at least one dose of trial medication, for a final number of 558 patients.

Among these patients, the primary endpoint occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5 mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group.

The researchers found that the absolute risk reductions compared with placebo for the primary outcome were 0.0% (95% confidence interval not calculable) in the aspirin group, 0.7% (95% confidence interval, -2.1% to 4.1%) in the prophylactic-dose apixaban group, and 1.4% (95% CI, -1.5% to 5%) in the therapeutic-dose apixaban group.

No major bleeding events were reported.

The absolute risk differences compared with placebo for clinically relevant nonmajor bleeding events were 2% (95% CI, -2.7% to 6.8%) in the aspirin group, 4.5% (95% CI, -0.7% to 10.2%) in the prophylactic-dose apixaban group, and 6.9% (95% CI, 1.4% to 12.9%) in the therapeutic-dose apixaban group.

Safety and efficacy results were similar in all randomly assigned patients.

The researchers speculated that a combination of two demographic shifts over time may have led to the lower than anticipated rate of events in ACTIV-4B.

“First, the threshold for hospital admission has markedly declined since the beginning of the pandemic, such that hospitalization is no longer limited almost exclusively to those with severe pulmonary distress likely to require mechanical ventilation,” they write. “As a result, the severity of illness among individuals with COVID-19 and destined for outpatient care has declined.”

“Second, at least within the U.S., where the trial was conducted, individuals currently being infected with SARS-CoV-2 tend to be younger and have fewer comorbidities when compared with individuals with incident infection at the onset of the pandemic,” they add.

Further, COVID-19 testing was quite limited early in the pandemic, they note, “and it is possible that the anticipated event rates based on data from registries available at that time were overestimated because the denominator (that is, the number of infected individuals overall) was essentially unknown.”
 

Robust evidence

“The ACTIV-4B trial is the first randomized trial to generate robust evidence about the effects of antithrombotic therapy in outpatients with COVID-19,” Otavio Berwanger, MD, PhD, director of the Academic Research Organization, Hospital Israelita Albert Einstein, Sao Paulo-SP, Brazil, told this news organization.

“It should be noted that this was a well-designed trial with low risk of bias. On the other hand, the main limitation is the low number of events and, consequently, the limited statistical power,” said Dr. Berwanger, who wrote an accompanying editorial.

The ACTIV-4B trial has immediate implications for clinical practice, he added.

“In this sense, considering the neutral results for major cardiopulmonary outcomes, the use of aspirin or apixaban for the management of outpatients with COVID-19 should not be recommended.”

ACTIV-4B also provides useful information for the steering committees of other ongoing trials of antithrombotic therapy for patients with COVID-19 who are not hospitalized, Dr. Berwanger added.

“In this sense, probably issues like statistical power, outcome choices, recruitment feasibility, and even futility would need to be revisited. And finally, lessons learned from the implementation of an innovative, pragmatic, and decentralized trial design represent an important legacy for future trials in cardiovascular diseases and other common conditions,” he said.

The study was funded by the National Institutes of Health, and the National Heart, Lung, and Blood Institute. Dr. Connors reports financial relationships with Bristol-Myers Squibb, Pfizer, Abbott, Alnylam, Takeda, Roche, and Sanofi. Dr. Berwanger reports financial relationships with AstraZeneca, Amgen, Servier, Bristol-Myers Squibb, Bayer, Novartis, Pfizer, and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

Antithrombotic therapy in clinically stable, nonhospitalized COVID-19 patients does not offer protection against adverse cardiovascular or pulmonary events, new randomized clinical trial results suggest.

Bruce Jancin/MDedge News

Antithrombotic therapy has proven useful in acutely ill inpatients with COVID-19, but in this study, treatment with aspirin or apixaban (Eliquis) did not reduce the rate of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary causes in patients ill with COVID-19 but who were not hospitalized.

“Among symptomatic, clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome,” the authors conclude. “However, the study was terminated after enrollment of 9% of participants because of a primary event rate lower than anticipated.”

The study, which was led by Jean M. Connors, MD, Brigham and Women’s Hospital, Boston, was published online October 11 in JAMA.

The ACTIV-4B Outpatient Thrombosis Prevention Trial was a randomized, adaptive, double-blind, placebo-controlled trial that sought to compare anticoagulant and antiplatelet therapy among 7,000 symptomatic but clinically stable outpatients with COVID-19.

The trial was conducted at 52 sites in the U.S. between Sept. 2020 and June 2021, with final follow-up this past August 5, and involved minimal face-to-face interactions with study participants.

Patients were randomized in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164 patients), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days.

The primary endpoint was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause.

The trial was terminated early this past June by the independent data monitoring committee because of lower than anticipated event rates. At the time, just 657 symptomatic outpatients with COVID-19 had been enrolled.

The median age of the study participants was 54 years (Interquartile Range [IQR] 46-59); 59% were women.

The median time from diagnosis to randomization was 7 days, and the median time from randomization to initiation of study medications was 3 days.

The trial’s primary efficacy and safety analyses were restricted to patients who received at least one dose of trial medication, for a final number of 558 patients.

Among these patients, the primary endpoint occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5 mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group.

The researchers found that the absolute risk reductions compared with placebo for the primary outcome were 0.0% (95% confidence interval not calculable) in the aspirin group, 0.7% (95% confidence interval, -2.1% to 4.1%) in the prophylactic-dose apixaban group, and 1.4% (95% CI, -1.5% to 5%) in the therapeutic-dose apixaban group.

No major bleeding events were reported.

The absolute risk differences compared with placebo for clinically relevant nonmajor bleeding events were 2% (95% CI, -2.7% to 6.8%) in the aspirin group, 4.5% (95% CI, -0.7% to 10.2%) in the prophylactic-dose apixaban group, and 6.9% (95% CI, 1.4% to 12.9%) in the therapeutic-dose apixaban group.

Safety and efficacy results were similar in all randomly assigned patients.

The researchers speculated that a combination of two demographic shifts over time may have led to the lower than anticipated rate of events in ACTIV-4B.

“First, the threshold for hospital admission has markedly declined since the beginning of the pandemic, such that hospitalization is no longer limited almost exclusively to those with severe pulmonary distress likely to require mechanical ventilation,” they write. “As a result, the severity of illness among individuals with COVID-19 and destined for outpatient care has declined.”

“Second, at least within the U.S., where the trial was conducted, individuals currently being infected with SARS-CoV-2 tend to be younger and have fewer comorbidities when compared with individuals with incident infection at the onset of the pandemic,” they add.

Further, COVID-19 testing was quite limited early in the pandemic, they note, “and it is possible that the anticipated event rates based on data from registries available at that time were overestimated because the denominator (that is, the number of infected individuals overall) was essentially unknown.”
 

Robust evidence

“The ACTIV-4B trial is the first randomized trial to generate robust evidence about the effects of antithrombotic therapy in outpatients with COVID-19,” Otavio Berwanger, MD, PhD, director of the Academic Research Organization, Hospital Israelita Albert Einstein, Sao Paulo-SP, Brazil, told this news organization.

“It should be noted that this was a well-designed trial with low risk of bias. On the other hand, the main limitation is the low number of events and, consequently, the limited statistical power,” said Dr. Berwanger, who wrote an accompanying editorial.

The ACTIV-4B trial has immediate implications for clinical practice, he added.

“In this sense, considering the neutral results for major cardiopulmonary outcomes, the use of aspirin or apixaban for the management of outpatients with COVID-19 should not be recommended.”

ACTIV-4B also provides useful information for the steering committees of other ongoing trials of antithrombotic therapy for patients with COVID-19 who are not hospitalized, Dr. Berwanger added.

“In this sense, probably issues like statistical power, outcome choices, recruitment feasibility, and even futility would need to be revisited. And finally, lessons learned from the implementation of an innovative, pragmatic, and decentralized trial design represent an important legacy for future trials in cardiovascular diseases and other common conditions,” he said.

The study was funded by the National Institutes of Health, and the National Heart, Lung, and Blood Institute. Dr. Connors reports financial relationships with Bristol-Myers Squibb, Pfizer, Abbott, Alnylam, Takeda, Roche, and Sanofi. Dr. Berwanger reports financial relationships with AstraZeneca, Amgen, Servier, Bristol-Myers Squibb, Bayer, Novartis, Pfizer, and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

Antithrombotic therapy in clinically stable, nonhospitalized COVID-19 patients does not offer protection against adverse cardiovascular or pulmonary events, new randomized clinical trial results suggest.

Bruce Jancin/MDedge News

Antithrombotic therapy has proven useful in acutely ill inpatients with COVID-19, but in this study, treatment with aspirin or apixaban (Eliquis) did not reduce the rate of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary causes in patients ill with COVID-19 but who were not hospitalized.

“Among symptomatic, clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome,” the authors conclude. “However, the study was terminated after enrollment of 9% of participants because of a primary event rate lower than anticipated.”

The study, which was led by Jean M. Connors, MD, Brigham and Women’s Hospital, Boston, was published online October 11 in JAMA.

The ACTIV-4B Outpatient Thrombosis Prevention Trial was a randomized, adaptive, double-blind, placebo-controlled trial that sought to compare anticoagulant and antiplatelet therapy among 7,000 symptomatic but clinically stable outpatients with COVID-19.

The trial was conducted at 52 sites in the U.S. between Sept. 2020 and June 2021, with final follow-up this past August 5, and involved minimal face-to-face interactions with study participants.

Patients were randomized in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164 patients), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days.

The primary endpoint was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause.

The trial was terminated early this past June by the independent data monitoring committee because of lower than anticipated event rates. At the time, just 657 symptomatic outpatients with COVID-19 had been enrolled.

The median age of the study participants was 54 years (Interquartile Range [IQR] 46-59); 59% were women.

The median time from diagnosis to randomization was 7 days, and the median time from randomization to initiation of study medications was 3 days.

The trial’s primary efficacy and safety analyses were restricted to patients who received at least one dose of trial medication, for a final number of 558 patients.

Among these patients, the primary endpoint occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5 mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group.

The researchers found that the absolute risk reductions compared with placebo for the primary outcome were 0.0% (95% confidence interval not calculable) in the aspirin group, 0.7% (95% confidence interval, -2.1% to 4.1%) in the prophylactic-dose apixaban group, and 1.4% (95% CI, -1.5% to 5%) in the therapeutic-dose apixaban group.

No major bleeding events were reported.

The absolute risk differences compared with placebo for clinically relevant nonmajor bleeding events were 2% (95% CI, -2.7% to 6.8%) in the aspirin group, 4.5% (95% CI, -0.7% to 10.2%) in the prophylactic-dose apixaban group, and 6.9% (95% CI, 1.4% to 12.9%) in the therapeutic-dose apixaban group.

Safety and efficacy results were similar in all randomly assigned patients.

The researchers speculated that a combination of two demographic shifts over time may have led to the lower than anticipated rate of events in ACTIV-4B.

“First, the threshold for hospital admission has markedly declined since the beginning of the pandemic, such that hospitalization is no longer limited almost exclusively to those with severe pulmonary distress likely to require mechanical ventilation,” they write. “As a result, the severity of illness among individuals with COVID-19 and destined for outpatient care has declined.”

“Second, at least within the U.S., where the trial was conducted, individuals currently being infected with SARS-CoV-2 tend to be younger and have fewer comorbidities when compared with individuals with incident infection at the onset of the pandemic,” they add.

Further, COVID-19 testing was quite limited early in the pandemic, they note, “and it is possible that the anticipated event rates based on data from registries available at that time were overestimated because the denominator (that is, the number of infected individuals overall) was essentially unknown.”
 

Robust evidence

“The ACTIV-4B trial is the first randomized trial to generate robust evidence about the effects of antithrombotic therapy in outpatients with COVID-19,” Otavio Berwanger, MD, PhD, director of the Academic Research Organization, Hospital Israelita Albert Einstein, Sao Paulo-SP, Brazil, told this news organization.

“It should be noted that this was a well-designed trial with low risk of bias. On the other hand, the main limitation is the low number of events and, consequently, the limited statistical power,” said Dr. Berwanger, who wrote an accompanying editorial.

The ACTIV-4B trial has immediate implications for clinical practice, he added.

“In this sense, considering the neutral results for major cardiopulmonary outcomes, the use of aspirin or apixaban for the management of outpatients with COVID-19 should not be recommended.”

ACTIV-4B also provides useful information for the steering committees of other ongoing trials of antithrombotic therapy for patients with COVID-19 who are not hospitalized, Dr. Berwanger added.

“In this sense, probably issues like statistical power, outcome choices, recruitment feasibility, and even futility would need to be revisited. And finally, lessons learned from the implementation of an innovative, pragmatic, and decentralized trial design represent an important legacy for future trials in cardiovascular diseases and other common conditions,” he said.

The study was funded by the National Institutes of Health, and the National Heart, Lung, and Blood Institute. Dr. Connors reports financial relationships with Bristol-Myers Squibb, Pfizer, Abbott, Alnylam, Takeda, Roche, and Sanofi. Dr. Berwanger reports financial relationships with AstraZeneca, Amgen, Servier, Bristol-Myers Squibb, Bayer, Novartis, Pfizer, and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.