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FUO, pneumonia often distinguishes influenza from RSV in hospitalized young children
LJUBLJANA, SLOVENIA – as the cause of hospitalization in infants and young children, Cihan Papan, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
Dr. Papan, a pediatrician at University Children’s Hospital Mannheim (Germany) and Heidelberg (Germany) University, presented a retrospective single-center study of all 573 children aged under 2 years hospitalized over the course of several seasons for respiratory syncytial virus (RSV) or influenza as confirmed by rapid antigen testing. Even though these are two of the leading causes of hospitalization among young children, there is surprisingly sparse data comparing the two in terms of disease severity and hospital resource utilization, including antibiotic consumption. That information gap provided the basis for this study.
There were 476 children with confirmed RSV, 96 with influenza, and 1 RSV/influenza coinfection. Notably, even though the RSV group had lower temperatures and C-reactive protein levels, they were nevertheless more likely to be treated with antibiotics, by a margin of 29% to 23%.
“These findings open new possibilities for antimicrobial stewardship in these groups of virally infected children,” observed Dr. Papan.
Fever of unknown origin was present in 68.8% of the influenza-positive patients, compared with just 0.2% of the RSV-positive children. In contrast, 50.2% of the RSV group had pneumonia and 49.6% had bronchitis or bronchiolitis, versus just 22.9% and 6.3% of the influenza patients, respectively. A larger proportion of the young children with RSV infection presented in a severely ill–looking condition. Children with RSV infection also were significantly younger.
Dr. Papan reported having no financial conflicts regarding his study.
LJUBLJANA, SLOVENIA – as the cause of hospitalization in infants and young children, Cihan Papan, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
Dr. Papan, a pediatrician at University Children’s Hospital Mannheim (Germany) and Heidelberg (Germany) University, presented a retrospective single-center study of all 573 children aged under 2 years hospitalized over the course of several seasons for respiratory syncytial virus (RSV) or influenza as confirmed by rapid antigen testing. Even though these are two of the leading causes of hospitalization among young children, there is surprisingly sparse data comparing the two in terms of disease severity and hospital resource utilization, including antibiotic consumption. That information gap provided the basis for this study.
There were 476 children with confirmed RSV, 96 with influenza, and 1 RSV/influenza coinfection. Notably, even though the RSV group had lower temperatures and C-reactive protein levels, they were nevertheless more likely to be treated with antibiotics, by a margin of 29% to 23%.
“These findings open new possibilities for antimicrobial stewardship in these groups of virally infected children,” observed Dr. Papan.
Fever of unknown origin was present in 68.8% of the influenza-positive patients, compared with just 0.2% of the RSV-positive children. In contrast, 50.2% of the RSV group had pneumonia and 49.6% had bronchitis or bronchiolitis, versus just 22.9% and 6.3% of the influenza patients, respectively. A larger proportion of the young children with RSV infection presented in a severely ill–looking condition. Children with RSV infection also were significantly younger.
Dr. Papan reported having no financial conflicts regarding his study.
LJUBLJANA, SLOVENIA – as the cause of hospitalization in infants and young children, Cihan Papan, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
Dr. Papan, a pediatrician at University Children’s Hospital Mannheim (Germany) and Heidelberg (Germany) University, presented a retrospective single-center study of all 573 children aged under 2 years hospitalized over the course of several seasons for respiratory syncytial virus (RSV) or influenza as confirmed by rapid antigen testing. Even though these are two of the leading causes of hospitalization among young children, there is surprisingly sparse data comparing the two in terms of disease severity and hospital resource utilization, including antibiotic consumption. That information gap provided the basis for this study.
There were 476 children with confirmed RSV, 96 with influenza, and 1 RSV/influenza coinfection. Notably, even though the RSV group had lower temperatures and C-reactive protein levels, they were nevertheless more likely to be treated with antibiotics, by a margin of 29% to 23%.
“These findings open new possibilities for antimicrobial stewardship in these groups of virally infected children,” observed Dr. Papan.
Fever of unknown origin was present in 68.8% of the influenza-positive patients, compared with just 0.2% of the RSV-positive children. In contrast, 50.2% of the RSV group had pneumonia and 49.6% had bronchitis or bronchiolitis, versus just 22.9% and 6.3% of the influenza patients, respectively. A larger proportion of the young children with RSV infection presented in a severely ill–looking condition. Children with RSV infection also were significantly younger.
Dr. Papan reported having no financial conflicts regarding his study.
REPORTING FROM ESPID 2019
Green thumbnail
The patient was given a diagnosis of green nail syndrome (GNS), an infection of the nail bed caused by Pseudomonas aeruginosa. These bacteria produce pyocyanin, a blue-green pigment that discolors the nail. GNS often occurs in patients with prior nail problems, such as onychomycosis, onycholysis, trauma, chronic paronychia, or psoriasis.
Nail disease disrupts the integumentary barrier and allows a portal of entry for bacteria. Scanning electron microscopy of patients with GNS has shown that fungal infections create tunnel-like structures in the nail keratin, and P aeruginosa can grow in these spaces. Nails with prior nail disease that are chronically exposed to moisture are at greatest risk of developing GNS, and it is typical for only one nail to be involved.
It’s likely that this patient’s earlier nail problem had been a case of onycholysis, based on her description of a “spongy” nail bed and loose nail. This created a favorable environment for an infection by allowing moisture and bacteria to infiltrate the space. The patient also acknowledged that she washed dishes by hand and bathed her young children. This frequent soaking of her hands likely helped to provide a moist environment in which P aeruginosa could thrive. In addition, onycholysis is associated with hypothyroidism, which the patient also had.
GNS can be diagnosed by clinical observation and characteristic pigmentation along with an appropriate patient history. Nail discoloration, or chromonychia, can present in a variety of colors. Nail findings may represent an isolated disease or provide an important clinical clue to other systemic diseases. The specific shade of discoloration helps to differentiate the underlying pathology. Culture of the nail bed may be helpful if bacterial resistance or co-infection with fungal organisms is suspected. GNS is often painless, but may be accompanied by mild tenderness of the nail.
The patient was prescribed ciprofloxacin 500 mg twice a day for 10 days, plus bleach soaks (1 part bleach to 4 parts water) twice a day. She also was advised to wear gloves for household tasks that involved immersing her hands in water, and to dry her finger with a hair dryer after bathing.
This case was adapted from: Gish D, Romero BJ. Green fingernail. J Fam Pract. 2017;66:E7-E9.
The patient was given a diagnosis of green nail syndrome (GNS), an infection of the nail bed caused by Pseudomonas aeruginosa. These bacteria produce pyocyanin, a blue-green pigment that discolors the nail. GNS often occurs in patients with prior nail problems, such as onychomycosis, onycholysis, trauma, chronic paronychia, or psoriasis.
Nail disease disrupts the integumentary barrier and allows a portal of entry for bacteria. Scanning electron microscopy of patients with GNS has shown that fungal infections create tunnel-like structures in the nail keratin, and P aeruginosa can grow in these spaces. Nails with prior nail disease that are chronically exposed to moisture are at greatest risk of developing GNS, and it is typical for only one nail to be involved.
It’s likely that this patient’s earlier nail problem had been a case of onycholysis, based on her description of a “spongy” nail bed and loose nail. This created a favorable environment for an infection by allowing moisture and bacteria to infiltrate the space. The patient also acknowledged that she washed dishes by hand and bathed her young children. This frequent soaking of her hands likely helped to provide a moist environment in which P aeruginosa could thrive. In addition, onycholysis is associated with hypothyroidism, which the patient also had.
GNS can be diagnosed by clinical observation and characteristic pigmentation along with an appropriate patient history. Nail discoloration, or chromonychia, can present in a variety of colors. Nail findings may represent an isolated disease or provide an important clinical clue to other systemic diseases. The specific shade of discoloration helps to differentiate the underlying pathology. Culture of the nail bed may be helpful if bacterial resistance or co-infection with fungal organisms is suspected. GNS is often painless, but may be accompanied by mild tenderness of the nail.
The patient was prescribed ciprofloxacin 500 mg twice a day for 10 days, plus bleach soaks (1 part bleach to 4 parts water) twice a day. She also was advised to wear gloves for household tasks that involved immersing her hands in water, and to dry her finger with a hair dryer after bathing.
This case was adapted from: Gish D, Romero BJ. Green fingernail. J Fam Pract. 2017;66:E7-E9.
The patient was given a diagnosis of green nail syndrome (GNS), an infection of the nail bed caused by Pseudomonas aeruginosa. These bacteria produce pyocyanin, a blue-green pigment that discolors the nail. GNS often occurs in patients with prior nail problems, such as onychomycosis, onycholysis, trauma, chronic paronychia, or psoriasis.
Nail disease disrupts the integumentary barrier and allows a portal of entry for bacteria. Scanning electron microscopy of patients with GNS has shown that fungal infections create tunnel-like structures in the nail keratin, and P aeruginosa can grow in these spaces. Nails with prior nail disease that are chronically exposed to moisture are at greatest risk of developing GNS, and it is typical for only one nail to be involved.
It’s likely that this patient’s earlier nail problem had been a case of onycholysis, based on her description of a “spongy” nail bed and loose nail. This created a favorable environment for an infection by allowing moisture and bacteria to infiltrate the space. The patient also acknowledged that she washed dishes by hand and bathed her young children. This frequent soaking of her hands likely helped to provide a moist environment in which P aeruginosa could thrive. In addition, onycholysis is associated with hypothyroidism, which the patient also had.
GNS can be diagnosed by clinical observation and characteristic pigmentation along with an appropriate patient history. Nail discoloration, or chromonychia, can present in a variety of colors. Nail findings may represent an isolated disease or provide an important clinical clue to other systemic diseases. The specific shade of discoloration helps to differentiate the underlying pathology. Culture of the nail bed may be helpful if bacterial resistance or co-infection with fungal organisms is suspected. GNS is often painless, but may be accompanied by mild tenderness of the nail.
The patient was prescribed ciprofloxacin 500 mg twice a day for 10 days, plus bleach soaks (1 part bleach to 4 parts water) twice a day. She also was advised to wear gloves for household tasks that involved immersing her hands in water, and to dry her finger with a hair dryer after bathing.
This case was adapted from: Gish D, Romero BJ. Green fingernail. J Fam Pract. 2017;66:E7-E9.
Impact of climate change on mortality underlined by global study
Regardless of where people live in the world, air pollution is linked to increased rates of cardiovascular disease, respiratory problems, and all-cause mortality, according to one of the largest studies ever to assess the effects of inhalable particulate matter (PM), published Aug. 21 in the New England Journal of Medicine.
“These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies,” reported Cong Liu of the Huazhong University of Science and Technology in Wuhan, China, and an international team of researchers.
“Many people are experiencing worse allergy and asthma symptoms in the setting of increased heat and worse air quality,” Caren G. Solomon, MD, of Harvard Medical School, Boston, said in an interview. “It is often not appreciated that these are complications of climate change.”
Other such complications include heat-related illnesses and severe weather events, as well as the less visible manifestations, such as shifts in the epidemiology of vector-borne infectious disease, Dr. Solomon and colleagues wrote in an editorial accompanying Mr. Liu’s study.
“The stark reality is that high levels of greenhouse gases caused by the combustion of fossil fuels – and the resulting rise in temperature and sea levels and intensification of extreme weather – are having profound consequences for human health and health systems,” Dr. Solomon and colleagues wrote (N Engl J Med. 2019;381:773-4.).
In the new air pollution study, Mr. Liu and colleagues analyzed 59.6 million deaths from 652 cities across 24 countries, “thereby greatly increasing the generalizability of the association and decreasing the likelihood that the reported associations are subject to confounding bias,” wrote John R. Balmes, MD, of the University of California, San Francisco, and the University of California, Berkeley, in an editorial about the study (N Engl J Med. 2019;381:774-6).
The researchers compared air pollution data from 1986-2015 from the Multi-City Multi-Country (MCC) Collaborative Research Network to mortality data reported from individual countries. They assessed PM with an aerodynamic diameter of 10 mcg or less (PM10; n = 598 cities) and PM with an aerodynamic diameter of 2.5 mcg or less (PM2.5; n=499 cities).
Mr. Liu’s team used a time-series analysis – a standard upon which the majority of air pollution research relies. These studies “include daily measures of health events (e.g., daily mortality), regressed against concentrations of PM (e.g., 24-hour average PM2.5) and weather variables (e.g., daily average temperature) for a given geographic area,” Dr. Balmes wrote. “The population serves as its own control, and confounding by population characteristics is negligible because these are stable over short time frames.”
The researchers found a 0.44% increase in daily all-cause mortality for each 10-mcg/m3 increase in the 2-day moving average (current and previous day) of PM10. The same increase was linked to a 0.36% increase in daily cardiovascular mortality and a 0.47% increase in daily respiratory mortality. Similarly, a 10-mcg/m3 increase in the PM2.5 average was linked to 0.68% increase in all-cause mortality, a 0.55% increase in cardiovascular mortality, and 0.74% increase in respiratory mortality.
Locations with higher annual mean temperatures showed stronger associations, and all these associations remained statistically significant after the researchers adjusted for gaseous pollutants.
Although the majority of countries and cities included in the study came from the northern hemisphere, the researchers noted that the magnitude of effect they found, particularly for PM10 concentrations, matched up with that seen in previous studies of multiple cities or countries.
Still, they found “significant evidence of spatial heterogeneity in the associations between PM concentration and daily mortality across countries and regions.” Among the factors that could contribute to those variations are “different PM components, long-term air pollution levels, population susceptibility, and different lengths of study periods,” they speculated.
What makes this study remarkable – despite decades of previous similar studies – is its size and the implications of a curvilinear shape in its concentration-response relation, according to Dr. Balmes.
“The current study of PM data from many regions around the world provides the strongest evidence to date that higher levels of exposure may be associated with a lower per-unit risk,” Dr. Balmes wrote. “Regions that have lower exposures had a higher per-unit risk. This finding has profound policy implications, especially given that no threshold of effect was found. Even high-income countries, such as the United States, with relatively good air quality could still see public health benefits from further reduction of ambient PM concentrations.”
The policy implications, however, extend well beyond clean air regulations because the findings represent just one aspect of climate change’s negative effects on health, which are “frighteningly broad,” Dr. Solomon and colleagues wrote.
“As climate change continues to alter disease patterns and disrupt health systems, its effects on human health will become harder to ignore,” they wrote. “We, as a medical community, have the responsibility and the opportunity to mobilize the urgent, large-scale climate action required to protect health – as well as the ingenuity to develop novel and bold interventions to avert the most catastrophic outcomes.”
The new research and associated commentary marked the introduction of a new NEJM topic on climate change effects on health and health systems.
SOURCE: Liu C et al. N Engl J Med. 2019;381:705-15.
This article was updated 8/22/19.
The negative effects of climate change on global public health are already playing out around us, but scientific research shows that they will only get worse – unless we begin addressing the issue in earnest now.
At the macro level nationally, effective policy is actually being stripped away right now. “[While] scientists tell us we have little time to wait if we hope to avoid the most devastating effects of climate change, leaders in Washington, D.C., are attacking science and rolling back Obama-era rules from the Environmental Protection Agency,” such as working to weaken vehicle fuel-efficiency standards, relaxing methane emissions rules, ending mercury emissions regulation and taking other actions that will only increase air pollution.
“If these EPA rollbacks are successful, they will diminish our ability to mitigate health effects and diseases related to the burning of fossil fuels and the immense toll they take on our families. ... If we stop supporting and listening to the best available science, if we allow more pollution to be emitted, and if we start limiting the EPA’s ability to monitor and enforce pollution standards, then we put at risk everyone’s health – and especially the health and future of our children.”
Engaging in advocacy and communicating to our representatives that we want stronger regulations is one way people can personally take action, but we can take immediate actions in our everyday lives too. Rather than dwelling on the despair of helplessness and hopelessness that grips many people when it comes to climate change, this moment can be reframed as an opportunity for people to make decisions that immediately begin improving their health — and also happen to be good for the planet.
“To me, the most urgent challenge when it comes to health and climate change is the reality that, when climate change comes up, in the U.S. audience, the first thing that should come into people’s minds is that we need to do this now because we need to protect our children’s health. ... Too many people either don’t get that it matters to health at all, or they don’t get that the actions we need to take are exactly what we need to do to address the health problems that have been nearly impossible to deal with.”
For example, problems like rising child obesity and type 2 diabetes rates have plagued public health, yet people can make changes that reduce obesity and diabetes risk that also decrease their carbon footprints, he said. “One of the best ways to deal with obesity is to eat more plants, and it turns out that’s really good for the climate” Additionally, getting people out of cars and walking and cycling can reduce individuals’ risk of diabetes – while simultaneously decreasing air pollution. “We need to be doing these things regardless of climate change, and if parents and children understood that the pathway to a healthier future was through tackling climate change, we would see a transformation.”
The value of local policy actions should be emphasized, such as ones that call for a reduction in a city’s use of concrete – which increases localized heat – and constructing more efficient buildings. Healthcare providers have an opportunity – and responsibility – not only to recognize this reality but to help their patients recognize it too.
“We can also use our roles as trusted advisers to inform and motivate actions that are increasingly necessary to protect the health of the communities we serve.” They also need to be vigilant about conditions that will worsen as the planet heats up: For example, medications such as diuretics carry more risks in higher temperatures, and patients taking them need to know that.
The need to address climate change matters because we face the challenge of protecting the world’s most vulnerable people.
“One of the great things about climate change is if it causes us to rethink about what we need to do to protect the future, it’s going to help our health today. ... If we can use that as the motivator, then maybe we can stop arguing and start thinking about climate as a positive issue, as a more personal issue we can all participate in and be willing to invest in.”
Gina McCarthy, MS, was administrator of the Environmental Protection Agency during 2013-2017, and Aaron Bernstein, MD, MPH, is a pediatrician at Boston Children’s Hospital. Both are from the Center for Climate, Health, and the Global Environment (Harvard C-CHANGE) at the Harvard T.H. Chan School of Public Health in Boston. Their comments came from their perspective (N Engl J Med. 2019 Aug 22. doi: 10.1056/NEJMp1909643) published in NEJM along with this article and editorial and a phone interview. They reported not having any disclosures.
The negative effects of climate change on global public health are already playing out around us, but scientific research shows that they will only get worse – unless we begin addressing the issue in earnest now.
At the macro level nationally, effective policy is actually being stripped away right now. “[While] scientists tell us we have little time to wait if we hope to avoid the most devastating effects of climate change, leaders in Washington, D.C., are attacking science and rolling back Obama-era rules from the Environmental Protection Agency,” such as working to weaken vehicle fuel-efficiency standards, relaxing methane emissions rules, ending mercury emissions regulation and taking other actions that will only increase air pollution.
“If these EPA rollbacks are successful, they will diminish our ability to mitigate health effects and diseases related to the burning of fossil fuels and the immense toll they take on our families. ... If we stop supporting and listening to the best available science, if we allow more pollution to be emitted, and if we start limiting the EPA’s ability to monitor and enforce pollution standards, then we put at risk everyone’s health – and especially the health and future of our children.”
Engaging in advocacy and communicating to our representatives that we want stronger regulations is one way people can personally take action, but we can take immediate actions in our everyday lives too. Rather than dwelling on the despair of helplessness and hopelessness that grips many people when it comes to climate change, this moment can be reframed as an opportunity for people to make decisions that immediately begin improving their health — and also happen to be good for the planet.
“To me, the most urgent challenge when it comes to health and climate change is the reality that, when climate change comes up, in the U.S. audience, the first thing that should come into people’s minds is that we need to do this now because we need to protect our children’s health. ... Too many people either don’t get that it matters to health at all, or they don’t get that the actions we need to take are exactly what we need to do to address the health problems that have been nearly impossible to deal with.”
For example, problems like rising child obesity and type 2 diabetes rates have plagued public health, yet people can make changes that reduce obesity and diabetes risk that also decrease their carbon footprints, he said. “One of the best ways to deal with obesity is to eat more plants, and it turns out that’s really good for the climate” Additionally, getting people out of cars and walking and cycling can reduce individuals’ risk of diabetes – while simultaneously decreasing air pollution. “We need to be doing these things regardless of climate change, and if parents and children understood that the pathway to a healthier future was through tackling climate change, we would see a transformation.”
The value of local policy actions should be emphasized, such as ones that call for a reduction in a city’s use of concrete – which increases localized heat – and constructing more efficient buildings. Healthcare providers have an opportunity – and responsibility – not only to recognize this reality but to help their patients recognize it too.
“We can also use our roles as trusted advisers to inform and motivate actions that are increasingly necessary to protect the health of the communities we serve.” They also need to be vigilant about conditions that will worsen as the planet heats up: For example, medications such as diuretics carry more risks in higher temperatures, and patients taking them need to know that.
The need to address climate change matters because we face the challenge of protecting the world’s most vulnerable people.
“One of the great things about climate change is if it causes us to rethink about what we need to do to protect the future, it’s going to help our health today. ... If we can use that as the motivator, then maybe we can stop arguing and start thinking about climate as a positive issue, as a more personal issue we can all participate in and be willing to invest in.”
Gina McCarthy, MS, was administrator of the Environmental Protection Agency during 2013-2017, and Aaron Bernstein, MD, MPH, is a pediatrician at Boston Children’s Hospital. Both are from the Center for Climate, Health, and the Global Environment (Harvard C-CHANGE) at the Harvard T.H. Chan School of Public Health in Boston. Their comments came from their perspective (N Engl J Med. 2019 Aug 22. doi: 10.1056/NEJMp1909643) published in NEJM along with this article and editorial and a phone interview. They reported not having any disclosures.
The negative effects of climate change on global public health are already playing out around us, but scientific research shows that they will only get worse – unless we begin addressing the issue in earnest now.
At the macro level nationally, effective policy is actually being stripped away right now. “[While] scientists tell us we have little time to wait if we hope to avoid the most devastating effects of climate change, leaders in Washington, D.C., are attacking science and rolling back Obama-era rules from the Environmental Protection Agency,” such as working to weaken vehicle fuel-efficiency standards, relaxing methane emissions rules, ending mercury emissions regulation and taking other actions that will only increase air pollution.
“If these EPA rollbacks are successful, they will diminish our ability to mitigate health effects and diseases related to the burning of fossil fuels and the immense toll they take on our families. ... If we stop supporting and listening to the best available science, if we allow more pollution to be emitted, and if we start limiting the EPA’s ability to monitor and enforce pollution standards, then we put at risk everyone’s health – and especially the health and future of our children.”
Engaging in advocacy and communicating to our representatives that we want stronger regulations is one way people can personally take action, but we can take immediate actions in our everyday lives too. Rather than dwelling on the despair of helplessness and hopelessness that grips many people when it comes to climate change, this moment can be reframed as an opportunity for people to make decisions that immediately begin improving their health — and also happen to be good for the planet.
“To me, the most urgent challenge when it comes to health and climate change is the reality that, when climate change comes up, in the U.S. audience, the first thing that should come into people’s minds is that we need to do this now because we need to protect our children’s health. ... Too many people either don’t get that it matters to health at all, or they don’t get that the actions we need to take are exactly what we need to do to address the health problems that have been nearly impossible to deal with.”
For example, problems like rising child obesity and type 2 diabetes rates have plagued public health, yet people can make changes that reduce obesity and diabetes risk that also decrease their carbon footprints, he said. “One of the best ways to deal with obesity is to eat more plants, and it turns out that’s really good for the climate” Additionally, getting people out of cars and walking and cycling can reduce individuals’ risk of diabetes – while simultaneously decreasing air pollution. “We need to be doing these things regardless of climate change, and if parents and children understood that the pathway to a healthier future was through tackling climate change, we would see a transformation.”
The value of local policy actions should be emphasized, such as ones that call for a reduction in a city’s use of concrete – which increases localized heat – and constructing more efficient buildings. Healthcare providers have an opportunity – and responsibility – not only to recognize this reality but to help their patients recognize it too.
“We can also use our roles as trusted advisers to inform and motivate actions that are increasingly necessary to protect the health of the communities we serve.” They also need to be vigilant about conditions that will worsen as the planet heats up: For example, medications such as diuretics carry more risks in higher temperatures, and patients taking them need to know that.
The need to address climate change matters because we face the challenge of protecting the world’s most vulnerable people.
“One of the great things about climate change is if it causes us to rethink about what we need to do to protect the future, it’s going to help our health today. ... If we can use that as the motivator, then maybe we can stop arguing and start thinking about climate as a positive issue, as a more personal issue we can all participate in and be willing to invest in.”
Gina McCarthy, MS, was administrator of the Environmental Protection Agency during 2013-2017, and Aaron Bernstein, MD, MPH, is a pediatrician at Boston Children’s Hospital. Both are from the Center for Climate, Health, and the Global Environment (Harvard C-CHANGE) at the Harvard T.H. Chan School of Public Health in Boston. Their comments came from their perspective (N Engl J Med. 2019 Aug 22. doi: 10.1056/NEJMp1909643) published in NEJM along with this article and editorial and a phone interview. They reported not having any disclosures.
Regardless of where people live in the world, air pollution is linked to increased rates of cardiovascular disease, respiratory problems, and all-cause mortality, according to one of the largest studies ever to assess the effects of inhalable particulate matter (PM), published Aug. 21 in the New England Journal of Medicine.
“These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies,” reported Cong Liu of the Huazhong University of Science and Technology in Wuhan, China, and an international team of researchers.
“Many people are experiencing worse allergy and asthma symptoms in the setting of increased heat and worse air quality,” Caren G. Solomon, MD, of Harvard Medical School, Boston, said in an interview. “It is often not appreciated that these are complications of climate change.”
Other such complications include heat-related illnesses and severe weather events, as well as the less visible manifestations, such as shifts in the epidemiology of vector-borne infectious disease, Dr. Solomon and colleagues wrote in an editorial accompanying Mr. Liu’s study.
“The stark reality is that high levels of greenhouse gases caused by the combustion of fossil fuels – and the resulting rise in temperature and sea levels and intensification of extreme weather – are having profound consequences for human health and health systems,” Dr. Solomon and colleagues wrote (N Engl J Med. 2019;381:773-4.).
In the new air pollution study, Mr. Liu and colleagues analyzed 59.6 million deaths from 652 cities across 24 countries, “thereby greatly increasing the generalizability of the association and decreasing the likelihood that the reported associations are subject to confounding bias,” wrote John R. Balmes, MD, of the University of California, San Francisco, and the University of California, Berkeley, in an editorial about the study (N Engl J Med. 2019;381:774-6).
The researchers compared air pollution data from 1986-2015 from the Multi-City Multi-Country (MCC) Collaborative Research Network to mortality data reported from individual countries. They assessed PM with an aerodynamic diameter of 10 mcg or less (PM10; n = 598 cities) and PM with an aerodynamic diameter of 2.5 mcg or less (PM2.5; n=499 cities).
Mr. Liu’s team used a time-series analysis – a standard upon which the majority of air pollution research relies. These studies “include daily measures of health events (e.g., daily mortality), regressed against concentrations of PM (e.g., 24-hour average PM2.5) and weather variables (e.g., daily average temperature) for a given geographic area,” Dr. Balmes wrote. “The population serves as its own control, and confounding by population characteristics is negligible because these are stable over short time frames.”
The researchers found a 0.44% increase in daily all-cause mortality for each 10-mcg/m3 increase in the 2-day moving average (current and previous day) of PM10. The same increase was linked to a 0.36% increase in daily cardiovascular mortality and a 0.47% increase in daily respiratory mortality. Similarly, a 10-mcg/m3 increase in the PM2.5 average was linked to 0.68% increase in all-cause mortality, a 0.55% increase in cardiovascular mortality, and 0.74% increase in respiratory mortality.
Locations with higher annual mean temperatures showed stronger associations, and all these associations remained statistically significant after the researchers adjusted for gaseous pollutants.
Although the majority of countries and cities included in the study came from the northern hemisphere, the researchers noted that the magnitude of effect they found, particularly for PM10 concentrations, matched up with that seen in previous studies of multiple cities or countries.
Still, they found “significant evidence of spatial heterogeneity in the associations between PM concentration and daily mortality across countries and regions.” Among the factors that could contribute to those variations are “different PM components, long-term air pollution levels, population susceptibility, and different lengths of study periods,” they speculated.
What makes this study remarkable – despite decades of previous similar studies – is its size and the implications of a curvilinear shape in its concentration-response relation, according to Dr. Balmes.
“The current study of PM data from many regions around the world provides the strongest evidence to date that higher levels of exposure may be associated with a lower per-unit risk,” Dr. Balmes wrote. “Regions that have lower exposures had a higher per-unit risk. This finding has profound policy implications, especially given that no threshold of effect was found. Even high-income countries, such as the United States, with relatively good air quality could still see public health benefits from further reduction of ambient PM concentrations.”
The policy implications, however, extend well beyond clean air regulations because the findings represent just one aspect of climate change’s negative effects on health, which are “frighteningly broad,” Dr. Solomon and colleagues wrote.
“As climate change continues to alter disease patterns and disrupt health systems, its effects on human health will become harder to ignore,” they wrote. “We, as a medical community, have the responsibility and the opportunity to mobilize the urgent, large-scale climate action required to protect health – as well as the ingenuity to develop novel and bold interventions to avert the most catastrophic outcomes.”
The new research and associated commentary marked the introduction of a new NEJM topic on climate change effects on health and health systems.
SOURCE: Liu C et al. N Engl J Med. 2019;381:705-15.
This article was updated 8/22/19.
Regardless of where people live in the world, air pollution is linked to increased rates of cardiovascular disease, respiratory problems, and all-cause mortality, according to one of the largest studies ever to assess the effects of inhalable particulate matter (PM), published Aug. 21 in the New England Journal of Medicine.
“These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies,” reported Cong Liu of the Huazhong University of Science and Technology in Wuhan, China, and an international team of researchers.
“Many people are experiencing worse allergy and asthma symptoms in the setting of increased heat and worse air quality,” Caren G. Solomon, MD, of Harvard Medical School, Boston, said in an interview. “It is often not appreciated that these are complications of climate change.”
Other such complications include heat-related illnesses and severe weather events, as well as the less visible manifestations, such as shifts in the epidemiology of vector-borne infectious disease, Dr. Solomon and colleagues wrote in an editorial accompanying Mr. Liu’s study.
“The stark reality is that high levels of greenhouse gases caused by the combustion of fossil fuels – and the resulting rise in temperature and sea levels and intensification of extreme weather – are having profound consequences for human health and health systems,” Dr. Solomon and colleagues wrote (N Engl J Med. 2019;381:773-4.).
In the new air pollution study, Mr. Liu and colleagues analyzed 59.6 million deaths from 652 cities across 24 countries, “thereby greatly increasing the generalizability of the association and decreasing the likelihood that the reported associations are subject to confounding bias,” wrote John R. Balmes, MD, of the University of California, San Francisco, and the University of California, Berkeley, in an editorial about the study (N Engl J Med. 2019;381:774-6).
The researchers compared air pollution data from 1986-2015 from the Multi-City Multi-Country (MCC) Collaborative Research Network to mortality data reported from individual countries. They assessed PM with an aerodynamic diameter of 10 mcg or less (PM10; n = 598 cities) and PM with an aerodynamic diameter of 2.5 mcg or less (PM2.5; n=499 cities).
Mr. Liu’s team used a time-series analysis – a standard upon which the majority of air pollution research relies. These studies “include daily measures of health events (e.g., daily mortality), regressed against concentrations of PM (e.g., 24-hour average PM2.5) and weather variables (e.g., daily average temperature) for a given geographic area,” Dr. Balmes wrote. “The population serves as its own control, and confounding by population characteristics is negligible because these are stable over short time frames.”
The researchers found a 0.44% increase in daily all-cause mortality for each 10-mcg/m3 increase in the 2-day moving average (current and previous day) of PM10. The same increase was linked to a 0.36% increase in daily cardiovascular mortality and a 0.47% increase in daily respiratory mortality. Similarly, a 10-mcg/m3 increase in the PM2.5 average was linked to 0.68% increase in all-cause mortality, a 0.55% increase in cardiovascular mortality, and 0.74% increase in respiratory mortality.
Locations with higher annual mean temperatures showed stronger associations, and all these associations remained statistically significant after the researchers adjusted for gaseous pollutants.
Although the majority of countries and cities included in the study came from the northern hemisphere, the researchers noted that the magnitude of effect they found, particularly for PM10 concentrations, matched up with that seen in previous studies of multiple cities or countries.
Still, they found “significant evidence of spatial heterogeneity in the associations between PM concentration and daily mortality across countries and regions.” Among the factors that could contribute to those variations are “different PM components, long-term air pollution levels, population susceptibility, and different lengths of study periods,” they speculated.
What makes this study remarkable – despite decades of previous similar studies – is its size and the implications of a curvilinear shape in its concentration-response relation, according to Dr. Balmes.
“The current study of PM data from many regions around the world provides the strongest evidence to date that higher levels of exposure may be associated with a lower per-unit risk,” Dr. Balmes wrote. “Regions that have lower exposures had a higher per-unit risk. This finding has profound policy implications, especially given that no threshold of effect was found. Even high-income countries, such as the United States, with relatively good air quality could still see public health benefits from further reduction of ambient PM concentrations.”
The policy implications, however, extend well beyond clean air regulations because the findings represent just one aspect of climate change’s negative effects on health, which are “frighteningly broad,” Dr. Solomon and colleagues wrote.
“As climate change continues to alter disease patterns and disrupt health systems, its effects on human health will become harder to ignore,” they wrote. “We, as a medical community, have the responsibility and the opportunity to mobilize the urgent, large-scale climate action required to protect health – as well as the ingenuity to develop novel and bold interventions to avert the most catastrophic outcomes.”
The new research and associated commentary marked the introduction of a new NEJM topic on climate change effects on health and health systems.
SOURCE: Liu C et al. N Engl J Med. 2019;381:705-15.
This article was updated 8/22/19.
FROM NEJM
HCV coinfection adds to cardiovascular risk in HIV-infected patients
Hepatitis C virus (HCV) coinfection, as well as an accumulation of viral and bacterial infections, was independently associated with the risk of developing a cardiovascular event in HIV-infected patients, according to the results of a large retrospective analysis.
The study comprised 823 patients at a single institution during 1982-2018. The researchers assessed those patients who had at least two visits to the HIV clinic, data concerning herpes varicella zoster virus (VZV) reactivation, and bacterial infections. Data on HCV coinfection status (as determined by HCV antibodies and qualitative HCV-PCR) were also available, according to Miguel Genebat, MD, of Virgen del Rocío University Hospital, Seville, Spain, and colleagues.
During the observational period, 58 patients (7%) experienced a cardiovascular event at a median age of 47 years. Most of these patients (50, 86%) had effective HIV treatment, with their viral load being persistently undetectable.
In terms of standard cardiovascular disease (CVD) risk factors, hypercholesterolemia was present in 31 patients (53%) and only 11 subjects (19%) had diabetes. This left 24 “low-risk” subjects, 5 of whom (21%) developed recurrent CVD and 8 of whom (33%) died after the development of cardiovascular disease.
The most frequent cardiovascular event was acute coronary syndrome (ACS), developed by 38 patients, with 14 (24%) of these individuals having recurrent CVD events. Among the 58 patients who experienced a cardiovascular event, 21 (36%) died, 17 from cardiovascular disease, 2 from cancer, and 2 each from acute bacterial infection and end-stage liver disease.
The researchers examined other variables potentially associated with the development of cardiovascular disease. They performed a multivariate analysis considering the added burden of infections and found that advanced age at HIV-1 diagnosis (OR, 1.07), a T-CD4 nadir of less than 200 cells/mcL (OR, 2.01), a diagnosis of HIV prior to combined antiretroviral therapy availability in 1996 (OR, 2.35), and cumulative infections greater than 2 (OR, 3.63), were all significantly and independently associated with the risk of developing a cardiovascular event.
They also found that HCV coinfection (OR, 2.84) on its own in simple multivariate analysis increased the risk of developing a CVD event in HIV-infected subjects. There was insufficient power to tease out the individual risk of other infections, such as herpes zoster virus and bacterial infections, hence the use of cumulative infections reported above.
The researchers concluded that potential strategies to minimize cardiovascular risk in these subjects could be treating HCV coinfection in all subjects independently of liver fibrosis stage, starting cART as soon as possible, and immunizing for those infections for which effective vaccine are available.
The authors reported that they had no conflicts of interest.
SOURCE: Genebat M. et al. Antiviral Res. 2019 Sep;169:104527.
Hepatitis C virus (HCV) coinfection, as well as an accumulation of viral and bacterial infections, was independently associated with the risk of developing a cardiovascular event in HIV-infected patients, according to the results of a large retrospective analysis.
The study comprised 823 patients at a single institution during 1982-2018. The researchers assessed those patients who had at least two visits to the HIV clinic, data concerning herpes varicella zoster virus (VZV) reactivation, and bacterial infections. Data on HCV coinfection status (as determined by HCV antibodies and qualitative HCV-PCR) were also available, according to Miguel Genebat, MD, of Virgen del Rocío University Hospital, Seville, Spain, and colleagues.
During the observational period, 58 patients (7%) experienced a cardiovascular event at a median age of 47 years. Most of these patients (50, 86%) had effective HIV treatment, with their viral load being persistently undetectable.
In terms of standard cardiovascular disease (CVD) risk factors, hypercholesterolemia was present in 31 patients (53%) and only 11 subjects (19%) had diabetes. This left 24 “low-risk” subjects, 5 of whom (21%) developed recurrent CVD and 8 of whom (33%) died after the development of cardiovascular disease.
The most frequent cardiovascular event was acute coronary syndrome (ACS), developed by 38 patients, with 14 (24%) of these individuals having recurrent CVD events. Among the 58 patients who experienced a cardiovascular event, 21 (36%) died, 17 from cardiovascular disease, 2 from cancer, and 2 each from acute bacterial infection and end-stage liver disease.
The researchers examined other variables potentially associated with the development of cardiovascular disease. They performed a multivariate analysis considering the added burden of infections and found that advanced age at HIV-1 diagnosis (OR, 1.07), a T-CD4 nadir of less than 200 cells/mcL (OR, 2.01), a diagnosis of HIV prior to combined antiretroviral therapy availability in 1996 (OR, 2.35), and cumulative infections greater than 2 (OR, 3.63), were all significantly and independently associated with the risk of developing a cardiovascular event.
They also found that HCV coinfection (OR, 2.84) on its own in simple multivariate analysis increased the risk of developing a CVD event in HIV-infected subjects. There was insufficient power to tease out the individual risk of other infections, such as herpes zoster virus and bacterial infections, hence the use of cumulative infections reported above.
The researchers concluded that potential strategies to minimize cardiovascular risk in these subjects could be treating HCV coinfection in all subjects independently of liver fibrosis stage, starting cART as soon as possible, and immunizing for those infections for which effective vaccine are available.
The authors reported that they had no conflicts of interest.
SOURCE: Genebat M. et al. Antiviral Res. 2019 Sep;169:104527.
Hepatitis C virus (HCV) coinfection, as well as an accumulation of viral and bacterial infections, was independently associated with the risk of developing a cardiovascular event in HIV-infected patients, according to the results of a large retrospective analysis.
The study comprised 823 patients at a single institution during 1982-2018. The researchers assessed those patients who had at least two visits to the HIV clinic, data concerning herpes varicella zoster virus (VZV) reactivation, and bacterial infections. Data on HCV coinfection status (as determined by HCV antibodies and qualitative HCV-PCR) were also available, according to Miguel Genebat, MD, of Virgen del Rocío University Hospital, Seville, Spain, and colleagues.
During the observational period, 58 patients (7%) experienced a cardiovascular event at a median age of 47 years. Most of these patients (50, 86%) had effective HIV treatment, with their viral load being persistently undetectable.
In terms of standard cardiovascular disease (CVD) risk factors, hypercholesterolemia was present in 31 patients (53%) and only 11 subjects (19%) had diabetes. This left 24 “low-risk” subjects, 5 of whom (21%) developed recurrent CVD and 8 of whom (33%) died after the development of cardiovascular disease.
The most frequent cardiovascular event was acute coronary syndrome (ACS), developed by 38 patients, with 14 (24%) of these individuals having recurrent CVD events. Among the 58 patients who experienced a cardiovascular event, 21 (36%) died, 17 from cardiovascular disease, 2 from cancer, and 2 each from acute bacterial infection and end-stage liver disease.
The researchers examined other variables potentially associated with the development of cardiovascular disease. They performed a multivariate analysis considering the added burden of infections and found that advanced age at HIV-1 diagnosis (OR, 1.07), a T-CD4 nadir of less than 200 cells/mcL (OR, 2.01), a diagnosis of HIV prior to combined antiretroviral therapy availability in 1996 (OR, 2.35), and cumulative infections greater than 2 (OR, 3.63), were all significantly and independently associated with the risk of developing a cardiovascular event.
They also found that HCV coinfection (OR, 2.84) on its own in simple multivariate analysis increased the risk of developing a CVD event in HIV-infected subjects. There was insufficient power to tease out the individual risk of other infections, such as herpes zoster virus and bacterial infections, hence the use of cumulative infections reported above.
The researchers concluded that potential strategies to minimize cardiovascular risk in these subjects could be treating HCV coinfection in all subjects independently of liver fibrosis stage, starting cART as soon as possible, and immunizing for those infections for which effective vaccine are available.
The authors reported that they had no conflicts of interest.
SOURCE: Genebat M. et al. Antiviral Res. 2019 Sep;169:104527.
FROM ANTIVIRAL RESEARCH
FDA approves Xenleta for community-acquired bacterial pneumonia treatment
The Food and Drug Administration has announced its approval of lefamulin (Xenleta) for the treatment of community-acquired bacterial pneumonia in adults.
Approval was based on results of two clinical trials assessing a total of 1,289 people with community-acquired bacterial pneumonia. In these trials, lefamulin was compared with moxifloxacin with and without linezolid. Patients who received lefamulin had similar rates of treatment success as those taking moxifloxacin alone or moxifloxacin plus linezolid.
The most common adverse reactions associated with lefamulin include diarrhea, nausea, reactions at the injection site, elevated liver enzymes, and vomiting. Patients with prolonged QT interval, patients with arrhythmias, patients receiving treatment with antiarrhythmic agents, and patients receiving other drugs that prolong the QT interval are contraindicated. In addition, because of evidence of fetal harm in animal studies, pregnant women should be advised of potential risks before receiving lefamulin.
“This new drug provides another option for the treatment of patients with community-acquired bacterial pneumonia, a serious disease. For managing this serious disease, it is important for physicians and patients to have treatment options,” Ed Cox, MD, MPH, director of the FDA’s Office of Antimicrobial Products, said in the press release.
The Food and Drug Administration has announced its approval of lefamulin (Xenleta) for the treatment of community-acquired bacterial pneumonia in adults.
Approval was based on results of two clinical trials assessing a total of 1,289 people with community-acquired bacterial pneumonia. In these trials, lefamulin was compared with moxifloxacin with and without linezolid. Patients who received lefamulin had similar rates of treatment success as those taking moxifloxacin alone or moxifloxacin plus linezolid.
The most common adverse reactions associated with lefamulin include diarrhea, nausea, reactions at the injection site, elevated liver enzymes, and vomiting. Patients with prolonged QT interval, patients with arrhythmias, patients receiving treatment with antiarrhythmic agents, and patients receiving other drugs that prolong the QT interval are contraindicated. In addition, because of evidence of fetal harm in animal studies, pregnant women should be advised of potential risks before receiving lefamulin.
“This new drug provides another option for the treatment of patients with community-acquired bacterial pneumonia, a serious disease. For managing this serious disease, it is important for physicians and patients to have treatment options,” Ed Cox, MD, MPH, director of the FDA’s Office of Antimicrobial Products, said in the press release.
The Food and Drug Administration has announced its approval of lefamulin (Xenleta) for the treatment of community-acquired bacterial pneumonia in adults.
Approval was based on results of two clinical trials assessing a total of 1,289 people with community-acquired bacterial pneumonia. In these trials, lefamulin was compared with moxifloxacin with and without linezolid. Patients who received lefamulin had similar rates of treatment success as those taking moxifloxacin alone or moxifloxacin plus linezolid.
The most common adverse reactions associated with lefamulin include diarrhea, nausea, reactions at the injection site, elevated liver enzymes, and vomiting. Patients with prolonged QT interval, patients with arrhythmias, patients receiving treatment with antiarrhythmic agents, and patients receiving other drugs that prolong the QT interval are contraindicated. In addition, because of evidence of fetal harm in animal studies, pregnant women should be advised of potential risks before receiving lefamulin.
“This new drug provides another option for the treatment of patients with community-acquired bacterial pneumonia, a serious disease. For managing this serious disease, it is important for physicians and patients to have treatment options,” Ed Cox, MD, MPH, director of the FDA’s Office of Antimicrobial Products, said in the press release.
Short-term parenteral antibiotics effective for bacteremic UTI in young infants
according to a study.
While previous studies have shown short-term parenteral antibiotic therapy to be safe and equally effective in uncomplicated urinary tract infections (UTIs), short-term therapy safety in bacteremic UTI had not been established, Sanyukta Desai, MD, of the University of Cincinnati and Cincinnati Children’s Hospital and associates wrote in Pediatrics.
“As a result, infants with bacteremic UTI often receive prolonged courses of parenteral antibiotics, which can lead to long hospitalizations and increased costs,” they said.
In a multicenter, retrospective cohort study, Dr. Desai and associates analyzed a group of 115 infants aged 60 days or younger who were admitted to a group of 11 participating EDs between July 1, 2011, and June 30, 2016, if they had a UTI caused by a bacterial pathogen. Half of the infants were administered parenteral antibiotics for 7 days or less before being switched to oral antibiotics, and the rest were given parenteral antibiotics for more than 7 days before switching to oral. Infants were more likely to receive long-term parenteral treatment if they were ill appearing and had growth of a non–Escherichia coli organism.
Six infants (two in the short-term group, four in the long-term group) had a recurrent UTI, each one diagnosed between 15 and 30 days after discharge; the adjusted risk difference between the two groups was 3% (95% confidence interval, –5.8 to 12.7). Two of the infants in the long-term group with a recurrent UTI had a different organism than during the index infection. When comparing only the infants with growth of the same pathogen that caused the index UTI, the adjusted risk difference between the two groups was 0.2% (95% CI, –7.8 to 8.3).
A total of 15 infants (6 in the short-term group, 9 in the long-term group) had 30-day all-cause reutilization, with no significant difference between groups (adjusted risk difference, 3%; 95% CI, –14.6 to 20.4).
Mean length of stay was significantly longer in the long-term treatment group, compared with the short-term group (11 days vs. 5 days; adjusted mean difference, 6 days; 95% CI, 4.0-8.8).
No infants experienced a serious adverse event such as ICU readmission, need for mechanical ventilation or vasopressor use, or signs of neurologic sequelae within 30 days of discharge from the index hospitalization, the investigators noted. Peripherally inserted central catheters were required in 13 infants; of these, 1 infant had to revisit an ED because of a related mechanical complication.
“Researchers in future prospective studies should seek to establish the bioavailability and optimal dosing of oral antibiotics in young infants and assess if there are particular subpopulations of infants with bacteremic UTI who may benefit from longer courses of parenteral antibiotic therapy,” Dr. Desai and associates concluded.
In a related editorial, Natalia V. Leva, MD, and Hillary L. Copp, MD, of the University of California, San Francisco, noted that the study represents a “critical piece of a complicated puzzle that not only includes minimum duration of parenteral antibiotic treatment but also involves bioavailability of antimicrobial agents in infants and total treatment duration, which includes parenteral and oral antibiotic therapy.”
The question that remains is how long a duration of parenteral antibiotic is necessary, Dr. Leva and Dr. Copp wrote. “Desai et al. used a relatively arbitrary cutoff of 7 days on the basis of the distribution of antibiotic course among their patient population; however, this is likely more a reflection of clinical practice than it is evidence based.” They concluded that this study provided evidence that a “short course of parenteral antibiotics in infants [aged 60 days or younger] with bacteremic UTI is safe and effective. Although the current study does not address total duration of antibiotics [parenteral and oral], it does shine a light on where we should focus future research endeavors.”
The study authors reported that they had no conflicts of interest. The study was supported in part by a National Center for Advancing Translational Sciences grant and an Agency for Healthcare Research and Quality grant. The editorialists had no relevant conflicts of interest and received no external funding.
SOURCEs: Desai S et al. Pediatrics. 2019 Aug 20. doi: 10.1542/peds.2018-3844; Leva et al. 2019 Aug 20. doi: 10.1542/peds.2019-1611.
according to a study.
While previous studies have shown short-term parenteral antibiotic therapy to be safe and equally effective in uncomplicated urinary tract infections (UTIs), short-term therapy safety in bacteremic UTI had not been established, Sanyukta Desai, MD, of the University of Cincinnati and Cincinnati Children’s Hospital and associates wrote in Pediatrics.
“As a result, infants with bacteremic UTI often receive prolonged courses of parenteral antibiotics, which can lead to long hospitalizations and increased costs,” they said.
In a multicenter, retrospective cohort study, Dr. Desai and associates analyzed a group of 115 infants aged 60 days or younger who were admitted to a group of 11 participating EDs between July 1, 2011, and June 30, 2016, if they had a UTI caused by a bacterial pathogen. Half of the infants were administered parenteral antibiotics for 7 days or less before being switched to oral antibiotics, and the rest were given parenteral antibiotics for more than 7 days before switching to oral. Infants were more likely to receive long-term parenteral treatment if they were ill appearing and had growth of a non–Escherichia coli organism.
Six infants (two in the short-term group, four in the long-term group) had a recurrent UTI, each one diagnosed between 15 and 30 days after discharge; the adjusted risk difference between the two groups was 3% (95% confidence interval, –5.8 to 12.7). Two of the infants in the long-term group with a recurrent UTI had a different organism than during the index infection. When comparing only the infants with growth of the same pathogen that caused the index UTI, the adjusted risk difference between the two groups was 0.2% (95% CI, –7.8 to 8.3).
A total of 15 infants (6 in the short-term group, 9 in the long-term group) had 30-day all-cause reutilization, with no significant difference between groups (adjusted risk difference, 3%; 95% CI, –14.6 to 20.4).
Mean length of stay was significantly longer in the long-term treatment group, compared with the short-term group (11 days vs. 5 days; adjusted mean difference, 6 days; 95% CI, 4.0-8.8).
No infants experienced a serious adverse event such as ICU readmission, need for mechanical ventilation or vasopressor use, or signs of neurologic sequelae within 30 days of discharge from the index hospitalization, the investigators noted. Peripherally inserted central catheters were required in 13 infants; of these, 1 infant had to revisit an ED because of a related mechanical complication.
“Researchers in future prospective studies should seek to establish the bioavailability and optimal dosing of oral antibiotics in young infants and assess if there are particular subpopulations of infants with bacteremic UTI who may benefit from longer courses of parenteral antibiotic therapy,” Dr. Desai and associates concluded.
In a related editorial, Natalia V. Leva, MD, and Hillary L. Copp, MD, of the University of California, San Francisco, noted that the study represents a “critical piece of a complicated puzzle that not only includes minimum duration of parenteral antibiotic treatment but also involves bioavailability of antimicrobial agents in infants and total treatment duration, which includes parenteral and oral antibiotic therapy.”
The question that remains is how long a duration of parenteral antibiotic is necessary, Dr. Leva and Dr. Copp wrote. “Desai et al. used a relatively arbitrary cutoff of 7 days on the basis of the distribution of antibiotic course among their patient population; however, this is likely more a reflection of clinical practice than it is evidence based.” They concluded that this study provided evidence that a “short course of parenteral antibiotics in infants [aged 60 days or younger] with bacteremic UTI is safe and effective. Although the current study does not address total duration of antibiotics [parenteral and oral], it does shine a light on where we should focus future research endeavors.”
The study authors reported that they had no conflicts of interest. The study was supported in part by a National Center for Advancing Translational Sciences grant and an Agency for Healthcare Research and Quality grant. The editorialists had no relevant conflicts of interest and received no external funding.
SOURCEs: Desai S et al. Pediatrics. 2019 Aug 20. doi: 10.1542/peds.2018-3844; Leva et al. 2019 Aug 20. doi: 10.1542/peds.2019-1611.
according to a study.
While previous studies have shown short-term parenteral antibiotic therapy to be safe and equally effective in uncomplicated urinary tract infections (UTIs), short-term therapy safety in bacteremic UTI had not been established, Sanyukta Desai, MD, of the University of Cincinnati and Cincinnati Children’s Hospital and associates wrote in Pediatrics.
“As a result, infants with bacteremic UTI often receive prolonged courses of parenteral antibiotics, which can lead to long hospitalizations and increased costs,” they said.
In a multicenter, retrospective cohort study, Dr. Desai and associates analyzed a group of 115 infants aged 60 days or younger who were admitted to a group of 11 participating EDs between July 1, 2011, and June 30, 2016, if they had a UTI caused by a bacterial pathogen. Half of the infants were administered parenteral antibiotics for 7 days or less before being switched to oral antibiotics, and the rest were given parenteral antibiotics for more than 7 days before switching to oral. Infants were more likely to receive long-term parenteral treatment if they were ill appearing and had growth of a non–Escherichia coli organism.
Six infants (two in the short-term group, four in the long-term group) had a recurrent UTI, each one diagnosed between 15 and 30 days after discharge; the adjusted risk difference between the two groups was 3% (95% confidence interval, –5.8 to 12.7). Two of the infants in the long-term group with a recurrent UTI had a different organism than during the index infection. When comparing only the infants with growth of the same pathogen that caused the index UTI, the adjusted risk difference between the two groups was 0.2% (95% CI, –7.8 to 8.3).
A total of 15 infants (6 in the short-term group, 9 in the long-term group) had 30-day all-cause reutilization, with no significant difference between groups (adjusted risk difference, 3%; 95% CI, –14.6 to 20.4).
Mean length of stay was significantly longer in the long-term treatment group, compared with the short-term group (11 days vs. 5 days; adjusted mean difference, 6 days; 95% CI, 4.0-8.8).
No infants experienced a serious adverse event such as ICU readmission, need for mechanical ventilation or vasopressor use, or signs of neurologic sequelae within 30 days of discharge from the index hospitalization, the investigators noted. Peripherally inserted central catheters were required in 13 infants; of these, 1 infant had to revisit an ED because of a related mechanical complication.
“Researchers in future prospective studies should seek to establish the bioavailability and optimal dosing of oral antibiotics in young infants and assess if there are particular subpopulations of infants with bacteremic UTI who may benefit from longer courses of parenteral antibiotic therapy,” Dr. Desai and associates concluded.
In a related editorial, Natalia V. Leva, MD, and Hillary L. Copp, MD, of the University of California, San Francisco, noted that the study represents a “critical piece of a complicated puzzle that not only includes minimum duration of parenteral antibiotic treatment but also involves bioavailability of antimicrobial agents in infants and total treatment duration, which includes parenteral and oral antibiotic therapy.”
The question that remains is how long a duration of parenteral antibiotic is necessary, Dr. Leva and Dr. Copp wrote. “Desai et al. used a relatively arbitrary cutoff of 7 days on the basis of the distribution of antibiotic course among their patient population; however, this is likely more a reflection of clinical practice than it is evidence based.” They concluded that this study provided evidence that a “short course of parenteral antibiotics in infants [aged 60 days or younger] with bacteremic UTI is safe and effective. Although the current study does not address total duration of antibiotics [parenteral and oral], it does shine a light on where we should focus future research endeavors.”
The study authors reported that they had no conflicts of interest. The study was supported in part by a National Center for Advancing Translational Sciences grant and an Agency for Healthcare Research and Quality grant. The editorialists had no relevant conflicts of interest and received no external funding.
SOURCEs: Desai S et al. Pediatrics. 2019 Aug 20. doi: 10.1542/peds.2018-3844; Leva et al. 2019 Aug 20. doi: 10.1542/peds.2019-1611.
FROM PEDIATRICS
Key clinical point: Urinary tract infection (UTI) recurrence and hospital reutilization was similar in infants with bacteremic UTIs, regardless of parenteral antibiotic treatment duration of 7 days or less or greater than 7 days prior to oral antibiotics.
Major finding: The adjusted risk difference for both infection recurrence and hospital reutilization was 3% and was nonsignificant in both cases.
Study details: A group of 115 infants aged 60 days or younger who were admitted to an ED with a bacteremic UTI.
Disclosures: The study authors reported that they had no conflicts of interest. The funding of the study was supported in part by a National Center for Advancing Translational Sciences grant and an Agency for Healthcare Research and Quality grant.
Source: Desai S et al. Pediatrics. 2019 Aug 20. doi: 10.1542/peds.2018-3844.
New measles outbreak reported in western N.Y.
A new measles outbreak in western New York has affected five people within a Mennonite community, according to the New York State Department of Health.
The five cases in Wyoming County, located east of Buffalo, were reported Aug. 8 and no further cases have been confirmed as of Aug. 16, the county health department said on its website.
Those five cases, along with six new cases in Rockland County, N.Y., and 10 more around the country, brought the total for the Centers for Disease Control and Prevention’s latest reporting week to 21 and the total for the year to 1,203, the CDC said Aug. 19.
Along with Wyoming County and Rockland County (296 cases since Sept. 2018), the CDC currently is tracking outbreaks in New York City (653 cases since Sept. 2018), Washington state (85 cases in 2019; 13 in the current outbreak), California (65 cases in 2019; 5 in the current outbreak), and Texas (21 cases in 2019; 6 in the current outbreak).
“More than 75% of the cases this year are linked to outbreaks in New York and New York City,” the CDC said on its website, while also noting that “124 of the people who got measles this year were hospitalized, and 64 reported having complications, including pneumonia and encephalitis.”
A new measles outbreak in western New York has affected five people within a Mennonite community, according to the New York State Department of Health.
The five cases in Wyoming County, located east of Buffalo, were reported Aug. 8 and no further cases have been confirmed as of Aug. 16, the county health department said on its website.
Those five cases, along with six new cases in Rockland County, N.Y., and 10 more around the country, brought the total for the Centers for Disease Control and Prevention’s latest reporting week to 21 and the total for the year to 1,203, the CDC said Aug. 19.
Along with Wyoming County and Rockland County (296 cases since Sept. 2018), the CDC currently is tracking outbreaks in New York City (653 cases since Sept. 2018), Washington state (85 cases in 2019; 13 in the current outbreak), California (65 cases in 2019; 5 in the current outbreak), and Texas (21 cases in 2019; 6 in the current outbreak).
“More than 75% of the cases this year are linked to outbreaks in New York and New York City,” the CDC said on its website, while also noting that “124 of the people who got measles this year were hospitalized, and 64 reported having complications, including pneumonia and encephalitis.”
A new measles outbreak in western New York has affected five people within a Mennonite community, according to the New York State Department of Health.
The five cases in Wyoming County, located east of Buffalo, were reported Aug. 8 and no further cases have been confirmed as of Aug. 16, the county health department said on its website.
Those five cases, along with six new cases in Rockland County, N.Y., and 10 more around the country, brought the total for the Centers for Disease Control and Prevention’s latest reporting week to 21 and the total for the year to 1,203, the CDC said Aug. 19.
Along with Wyoming County and Rockland County (296 cases since Sept. 2018), the CDC currently is tracking outbreaks in New York City (653 cases since Sept. 2018), Washington state (85 cases in 2019; 13 in the current outbreak), California (65 cases in 2019; 5 in the current outbreak), and Texas (21 cases in 2019; 6 in the current outbreak).
“More than 75% of the cases this year are linked to outbreaks in New York and New York City,” the CDC said on its website, while also noting that “124 of the people who got measles this year were hospitalized, and 64 reported having complications, including pneumonia and encephalitis.”
Statins hamper hepatocellular carcinoma in viral hepatitis patients
Lipophilic statin therapy significantly reduced the incidence and mortality of hepatocellular carcinoma in adults with viral hepatitis, based on data from 16,668 patients.
The mortality rates for hepatocellular carcinoma in the United States and Europe have been on the rise for decades, and the risk may persist in severe cases despite the use of hepatitis B virus suppression or hepatitis C virus eradication, wrote Tracey G. Simon, MD, of Harvard Medical School, Boston, and colleagues. Previous studies suggest that statins might reduce HCC risk in viral hepatitis patients, but evidence supporting one type of statin over another for HCC prevention is limited, they said.
In a study published in the Annals of Internal Medicine, the researchers reviewed data from a national registry of hepatitis patients in Sweden to assess the effect of lipophilic or hydrophilic statin use on HCC incidence and mortality.
They found a significant reduction in 10-year HCC risk for lipophilic statin users, compared with nonusers (8.1% vs. 3.3%. However, the difference was not significant for hydrophilic statin users vs. nonusers (8.0% vs. 6.8%). The effect of lipophilic statin use was dose dependent; the largest effect on reduction in HCC risk occurred with 600 or more lipophilic statin cumulative daily doses in users, compared with nonusers (8.4% vs. 2.5%).
The study population included 6,554 lipophilic statin users and 1,780 hydrophilic statin users, matched with 8,334 nonusers. Patient demographics were similar between both types of statin user and nonuser groups.
In addition, 10-year mortality was significantly lower for lipophilic statin users compared with nonusers (15.2% vs. 7.3%) and also for hydrophilic statin users, compared with nonusers (16.0% vs. 11.5%).
In a small number of patients with liver disease (462), liver-specific mortality was significantly reduced in lipophilic statin users, compared with nonusers (adjusted hazard ratio, 0.76 vs. 0.98).
“Of note, our findings were robust across several sensitivity analyses and were similar in all predefined subgroups, including among men and women and persons with and without cirrhosis or antiviral therapy use,” the researchers noted.
The study findings were limited by several factors including the potential confounding from variables such as smoking, hepatitis B viral DNA, hepatitis C virus eradication, stage of fibrosis, and HCC screening, as well as a lack of laboratory data to assess cholesterol levels’ impact on statin use, the researchers said. In addition, the study did not compare lipophilic and hydrophilic statins.
However, the results suggest potential distinct benefits of lipophilic statins to reduce HCC risk and support the need for further research, the researchers concluded.
Dr. Simon had no financial conflicts to disclose, but disclosed support from a North American Training Grant from the American College of Gastroenterology. Several coauthors disclosed relationships with multiple companies including AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck Sharp & Dohme. The study was supported in part by the American College of Gastroenterology, the American Association for the Study of Liver Diseases, the Boston Nutrition Obesity Research Center, the National Institutes of Health, Nyckelfonden, Region Orebro (Sweden) County, and the Karolinska Institutet.
SOURCE: Simon TG et al. Ann Intern Med. 2019 Aug 19. doi: 10.7326/M18-2753.
Lipophilic statin therapy significantly reduced the incidence and mortality of hepatocellular carcinoma in adults with viral hepatitis, based on data from 16,668 patients.
The mortality rates for hepatocellular carcinoma in the United States and Europe have been on the rise for decades, and the risk may persist in severe cases despite the use of hepatitis B virus suppression or hepatitis C virus eradication, wrote Tracey G. Simon, MD, of Harvard Medical School, Boston, and colleagues. Previous studies suggest that statins might reduce HCC risk in viral hepatitis patients, but evidence supporting one type of statin over another for HCC prevention is limited, they said.
In a study published in the Annals of Internal Medicine, the researchers reviewed data from a national registry of hepatitis patients in Sweden to assess the effect of lipophilic or hydrophilic statin use on HCC incidence and mortality.
They found a significant reduction in 10-year HCC risk for lipophilic statin users, compared with nonusers (8.1% vs. 3.3%. However, the difference was not significant for hydrophilic statin users vs. nonusers (8.0% vs. 6.8%). The effect of lipophilic statin use was dose dependent; the largest effect on reduction in HCC risk occurred with 600 or more lipophilic statin cumulative daily doses in users, compared with nonusers (8.4% vs. 2.5%).
The study population included 6,554 lipophilic statin users and 1,780 hydrophilic statin users, matched with 8,334 nonusers. Patient demographics were similar between both types of statin user and nonuser groups.
In addition, 10-year mortality was significantly lower for lipophilic statin users compared with nonusers (15.2% vs. 7.3%) and also for hydrophilic statin users, compared with nonusers (16.0% vs. 11.5%).
In a small number of patients with liver disease (462), liver-specific mortality was significantly reduced in lipophilic statin users, compared with nonusers (adjusted hazard ratio, 0.76 vs. 0.98).
“Of note, our findings were robust across several sensitivity analyses and were similar in all predefined subgroups, including among men and women and persons with and without cirrhosis or antiviral therapy use,” the researchers noted.
The study findings were limited by several factors including the potential confounding from variables such as smoking, hepatitis B viral DNA, hepatitis C virus eradication, stage of fibrosis, and HCC screening, as well as a lack of laboratory data to assess cholesterol levels’ impact on statin use, the researchers said. In addition, the study did not compare lipophilic and hydrophilic statins.
However, the results suggest potential distinct benefits of lipophilic statins to reduce HCC risk and support the need for further research, the researchers concluded.
Dr. Simon had no financial conflicts to disclose, but disclosed support from a North American Training Grant from the American College of Gastroenterology. Several coauthors disclosed relationships with multiple companies including AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck Sharp & Dohme. The study was supported in part by the American College of Gastroenterology, the American Association for the Study of Liver Diseases, the Boston Nutrition Obesity Research Center, the National Institutes of Health, Nyckelfonden, Region Orebro (Sweden) County, and the Karolinska Institutet.
SOURCE: Simon TG et al. Ann Intern Med. 2019 Aug 19. doi: 10.7326/M18-2753.
Lipophilic statin therapy significantly reduced the incidence and mortality of hepatocellular carcinoma in adults with viral hepatitis, based on data from 16,668 patients.
The mortality rates for hepatocellular carcinoma in the United States and Europe have been on the rise for decades, and the risk may persist in severe cases despite the use of hepatitis B virus suppression or hepatitis C virus eradication, wrote Tracey G. Simon, MD, of Harvard Medical School, Boston, and colleagues. Previous studies suggest that statins might reduce HCC risk in viral hepatitis patients, but evidence supporting one type of statin over another for HCC prevention is limited, they said.
In a study published in the Annals of Internal Medicine, the researchers reviewed data from a national registry of hepatitis patients in Sweden to assess the effect of lipophilic or hydrophilic statin use on HCC incidence and mortality.
They found a significant reduction in 10-year HCC risk for lipophilic statin users, compared with nonusers (8.1% vs. 3.3%. However, the difference was not significant for hydrophilic statin users vs. nonusers (8.0% vs. 6.8%). The effect of lipophilic statin use was dose dependent; the largest effect on reduction in HCC risk occurred with 600 or more lipophilic statin cumulative daily doses in users, compared with nonusers (8.4% vs. 2.5%).
The study population included 6,554 lipophilic statin users and 1,780 hydrophilic statin users, matched with 8,334 nonusers. Patient demographics were similar between both types of statin user and nonuser groups.
In addition, 10-year mortality was significantly lower for lipophilic statin users compared with nonusers (15.2% vs. 7.3%) and also for hydrophilic statin users, compared with nonusers (16.0% vs. 11.5%).
In a small number of patients with liver disease (462), liver-specific mortality was significantly reduced in lipophilic statin users, compared with nonusers (adjusted hazard ratio, 0.76 vs. 0.98).
“Of note, our findings were robust across several sensitivity analyses and were similar in all predefined subgroups, including among men and women and persons with and without cirrhosis or antiviral therapy use,” the researchers noted.
The study findings were limited by several factors including the potential confounding from variables such as smoking, hepatitis B viral DNA, hepatitis C virus eradication, stage of fibrosis, and HCC screening, as well as a lack of laboratory data to assess cholesterol levels’ impact on statin use, the researchers said. In addition, the study did not compare lipophilic and hydrophilic statins.
However, the results suggest potential distinct benefits of lipophilic statins to reduce HCC risk and support the need for further research, the researchers concluded.
Dr. Simon had no financial conflicts to disclose, but disclosed support from a North American Training Grant from the American College of Gastroenterology. Several coauthors disclosed relationships with multiple companies including AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck Sharp & Dohme. The study was supported in part by the American College of Gastroenterology, the American Association for the Study of Liver Diseases, the Boston Nutrition Obesity Research Center, the National Institutes of Health, Nyckelfonden, Region Orebro (Sweden) County, and the Karolinska Institutet.
SOURCE: Simon TG et al. Ann Intern Med. 2019 Aug 19. doi: 10.7326/M18-2753.
FROM THE ANNALS OF INTERNAL MEDICINE
Key clinical point: Use of lipophilic statins significantly reduced incidence and mortality of hepatocellular cancer in adults with viral hepatitis.
Major finding: The 10-year risk of HCC was 8.1% among patients taking lipophilic statins, compared with 3.3% among those not on statins.
Study details: The data come from a population-based cohort study of 16,668 adult with viral hepatitis from a national registry in Sweden.
Disclosures: Dr. Simon had no financial conflicts to disclose, but disclosed support from a North American Training Grant from the American College of Gastroenterology. Several coauthors disclosed relationships with multiple companies including AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and MSD.
Source: Simon TG et al. Ann Intern Med. 2019 Aug 19. doi: 10.7326/M18-2753.
Differential monocytic HLA-DR expression prognostically useful in PICU
LJUBLJANA, SLOVENIA – During their first 4 days in the pediatric ICU, critically ill children have significantly reduced human leukocyte antigen (HLA)–DR expression within all three major subsets of monocytes. The reductions are seen regardless of whether the children were admitted for sepsis, trauma, or after surgery, Navin Boeddha, MD, PhD, reported in his PIDJ Award Lecture at the annual meeting of the European Society for Paediatric Infectious Diseases.
The PIDJ Award is given annually by the editors of the Pediatric Infectious Disease Journal in recognition of what they deem the most important study published in the journal during the prior year. This one stood out because it identified promising potential laboratory markers that have been sought as a prerequisite to developing immunostimulatory therapies aimed at improving outcomes in severely immunosuppressed children.
Researchers are particularly eager to explore this investigative treatment strategy because the mortality and long-term morbidity of pediatric sepsis, in particular, remain unacceptably high. The hope now is that HLA-DR expression on monocyte subsets will be helpful in directing granulocyte-macrophage colony-stimulating factor, interferon-gamma, and other immunostimulatory therapies to the pediatric ICU patients with the most favorable benefit/risk ratio, according to Dr. Boeddha of Sophia Children’s Hospital and Erasmus University, Rotterdam, the Netherlands.
He reported on 37 critically ill children admitted to a pediatric ICU – 12 for sepsis, 11 post surgery, 10 for trauma, and 4 for other reasons – as well as 37 healthy controls. HLA-DR expression on monocyte subsets was measured by flow cytometry upon admission and again on each of the following 3 days.
The impetus for this study is that severe infection, major surgery, and severe trauma are often associated with immunosuppression. And while prior work in septic adults has concluded that decreased monocytic HLA-DR expression is a marker for immunosuppression – and that the lower the level of such expression, the greater the risk of nosocomial infection and death – this phenomenon hasn’t been well studied in critically ill children, he explained.
Dr. Boeddha and coinvestigators found that monocytic HLA-DR expression, which plays a major role in presenting antigens to T cells, decreased over time during the critically ill children’s first 4 days in the pediatric ICU. Moreover, it was lower than in controls at all four time points. This was true both for the percentage of HLA-DR–expressing monocytes of all subsets, as well as for HLA-DR mean fluorescence intensity.
In the critically ill study population as a whole, the percentage of classical monocytes – that is, CD14++ CD16– monocytes – was significantly greater at admission than in healthy controls by margins of 95% and 87%, while the percentage of nonclassical CD14+/-CD16++ monocytes was markedly lower at 2% than the 9% figure in controls.
The biggest discrepancy in monocyte subset distribution was seen in patients admitted for sepsis. Their percentage of classical monocytes was lower than in controls by a margin of 82% versus 87%; however, their proportion of intermediate monocytes (CD14++ CD16+) upon admission was twice that of controls, and it climbed further to 14% on day 2.
Among the key findings in the Rotterdam study: 13 of 37 critically ill patients experienced at least one nosocomial infection while in the pediatric ICU. Their day 2 percentage of HLA-DR–expressing classical monocytes was 42%, strikingly lower than the 78% figure in patients who didn’t develop an infection. Also, the 6 patients who died had only a 33% rate of HLA-DR–expressing classical monocytes on day 3 after pediatric ICU admission versus a 63% rate in survivors of their critical illness.
Thus, low HLA-DR expression on classical monocytes early during the course of a pediatric ICU stay may be the sought-after biomarker that identifies a particularly high-risk subgroup of critically ill children in whom immunostimulatory therapies should be studied. However, future confirmatory studies should monitor monocytic HLA-DR expression in a larger critically ill patient population for a longer period in order to establish the time to recovery of low expression and its impact on long-term complications, the physician said.
Dr. Boeddha reported having no financial conflicts regarding the award-winning study, supported by the European Union and Erasmus University.
SOURCE: Boeddha NP et al. Pediatr Infect Dis J. 2018 Oct;37(10):1034-40.
LJUBLJANA, SLOVENIA – During their first 4 days in the pediatric ICU, critically ill children have significantly reduced human leukocyte antigen (HLA)–DR expression within all three major subsets of monocytes. The reductions are seen regardless of whether the children were admitted for sepsis, trauma, or after surgery, Navin Boeddha, MD, PhD, reported in his PIDJ Award Lecture at the annual meeting of the European Society for Paediatric Infectious Diseases.
The PIDJ Award is given annually by the editors of the Pediatric Infectious Disease Journal in recognition of what they deem the most important study published in the journal during the prior year. This one stood out because it identified promising potential laboratory markers that have been sought as a prerequisite to developing immunostimulatory therapies aimed at improving outcomes in severely immunosuppressed children.
Researchers are particularly eager to explore this investigative treatment strategy because the mortality and long-term morbidity of pediatric sepsis, in particular, remain unacceptably high. The hope now is that HLA-DR expression on monocyte subsets will be helpful in directing granulocyte-macrophage colony-stimulating factor, interferon-gamma, and other immunostimulatory therapies to the pediatric ICU patients with the most favorable benefit/risk ratio, according to Dr. Boeddha of Sophia Children’s Hospital and Erasmus University, Rotterdam, the Netherlands.
He reported on 37 critically ill children admitted to a pediatric ICU – 12 for sepsis, 11 post surgery, 10 for trauma, and 4 for other reasons – as well as 37 healthy controls. HLA-DR expression on monocyte subsets was measured by flow cytometry upon admission and again on each of the following 3 days.
The impetus for this study is that severe infection, major surgery, and severe trauma are often associated with immunosuppression. And while prior work in septic adults has concluded that decreased monocytic HLA-DR expression is a marker for immunosuppression – and that the lower the level of such expression, the greater the risk of nosocomial infection and death – this phenomenon hasn’t been well studied in critically ill children, he explained.
Dr. Boeddha and coinvestigators found that monocytic HLA-DR expression, which plays a major role in presenting antigens to T cells, decreased over time during the critically ill children’s first 4 days in the pediatric ICU. Moreover, it was lower than in controls at all four time points. This was true both for the percentage of HLA-DR–expressing monocytes of all subsets, as well as for HLA-DR mean fluorescence intensity.
In the critically ill study population as a whole, the percentage of classical monocytes – that is, CD14++ CD16– monocytes – was significantly greater at admission than in healthy controls by margins of 95% and 87%, while the percentage of nonclassical CD14+/-CD16++ monocytes was markedly lower at 2% than the 9% figure in controls.
The biggest discrepancy in monocyte subset distribution was seen in patients admitted for sepsis. Their percentage of classical monocytes was lower than in controls by a margin of 82% versus 87%; however, their proportion of intermediate monocytes (CD14++ CD16+) upon admission was twice that of controls, and it climbed further to 14% on day 2.
Among the key findings in the Rotterdam study: 13 of 37 critically ill patients experienced at least one nosocomial infection while in the pediatric ICU. Their day 2 percentage of HLA-DR–expressing classical monocytes was 42%, strikingly lower than the 78% figure in patients who didn’t develop an infection. Also, the 6 patients who died had only a 33% rate of HLA-DR–expressing classical monocytes on day 3 after pediatric ICU admission versus a 63% rate in survivors of their critical illness.
Thus, low HLA-DR expression on classical monocytes early during the course of a pediatric ICU stay may be the sought-after biomarker that identifies a particularly high-risk subgroup of critically ill children in whom immunostimulatory therapies should be studied. However, future confirmatory studies should monitor monocytic HLA-DR expression in a larger critically ill patient population for a longer period in order to establish the time to recovery of low expression and its impact on long-term complications, the physician said.
Dr. Boeddha reported having no financial conflicts regarding the award-winning study, supported by the European Union and Erasmus University.
SOURCE: Boeddha NP et al. Pediatr Infect Dis J. 2018 Oct;37(10):1034-40.
LJUBLJANA, SLOVENIA – During their first 4 days in the pediatric ICU, critically ill children have significantly reduced human leukocyte antigen (HLA)–DR expression within all three major subsets of monocytes. The reductions are seen regardless of whether the children were admitted for sepsis, trauma, or after surgery, Navin Boeddha, MD, PhD, reported in his PIDJ Award Lecture at the annual meeting of the European Society for Paediatric Infectious Diseases.
The PIDJ Award is given annually by the editors of the Pediatric Infectious Disease Journal in recognition of what they deem the most important study published in the journal during the prior year. This one stood out because it identified promising potential laboratory markers that have been sought as a prerequisite to developing immunostimulatory therapies aimed at improving outcomes in severely immunosuppressed children.
Researchers are particularly eager to explore this investigative treatment strategy because the mortality and long-term morbidity of pediatric sepsis, in particular, remain unacceptably high. The hope now is that HLA-DR expression on monocyte subsets will be helpful in directing granulocyte-macrophage colony-stimulating factor, interferon-gamma, and other immunostimulatory therapies to the pediatric ICU patients with the most favorable benefit/risk ratio, according to Dr. Boeddha of Sophia Children’s Hospital and Erasmus University, Rotterdam, the Netherlands.
He reported on 37 critically ill children admitted to a pediatric ICU – 12 for sepsis, 11 post surgery, 10 for trauma, and 4 for other reasons – as well as 37 healthy controls. HLA-DR expression on monocyte subsets was measured by flow cytometry upon admission and again on each of the following 3 days.
The impetus for this study is that severe infection, major surgery, and severe trauma are often associated with immunosuppression. And while prior work in septic adults has concluded that decreased monocytic HLA-DR expression is a marker for immunosuppression – and that the lower the level of such expression, the greater the risk of nosocomial infection and death – this phenomenon hasn’t been well studied in critically ill children, he explained.
Dr. Boeddha and coinvestigators found that monocytic HLA-DR expression, which plays a major role in presenting antigens to T cells, decreased over time during the critically ill children’s first 4 days in the pediatric ICU. Moreover, it was lower than in controls at all four time points. This was true both for the percentage of HLA-DR–expressing monocytes of all subsets, as well as for HLA-DR mean fluorescence intensity.
In the critically ill study population as a whole, the percentage of classical monocytes – that is, CD14++ CD16– monocytes – was significantly greater at admission than in healthy controls by margins of 95% and 87%, while the percentage of nonclassical CD14+/-CD16++ monocytes was markedly lower at 2% than the 9% figure in controls.
The biggest discrepancy in monocyte subset distribution was seen in patients admitted for sepsis. Their percentage of classical monocytes was lower than in controls by a margin of 82% versus 87%; however, their proportion of intermediate monocytes (CD14++ CD16+) upon admission was twice that of controls, and it climbed further to 14% on day 2.
Among the key findings in the Rotterdam study: 13 of 37 critically ill patients experienced at least one nosocomial infection while in the pediatric ICU. Their day 2 percentage of HLA-DR–expressing classical monocytes was 42%, strikingly lower than the 78% figure in patients who didn’t develop an infection. Also, the 6 patients who died had only a 33% rate of HLA-DR–expressing classical monocytes on day 3 after pediatric ICU admission versus a 63% rate in survivors of their critical illness.
Thus, low HLA-DR expression on classical monocytes early during the course of a pediatric ICU stay may be the sought-after biomarker that identifies a particularly high-risk subgroup of critically ill children in whom immunostimulatory therapies should be studied. However, future confirmatory studies should monitor monocytic HLA-DR expression in a larger critically ill patient population for a longer period in order to establish the time to recovery of low expression and its impact on long-term complications, the physician said.
Dr. Boeddha reported having no financial conflicts regarding the award-winning study, supported by the European Union and Erasmus University.
SOURCE: Boeddha NP et al. Pediatr Infect Dis J. 2018 Oct;37(10):1034-40.
REPORTING FROM ESPID 2019
Presepsin can rule out invasive bacterial infection in infants
LJUBLJANA, SLOVENIA – A point-of-care presepsin measurement in the emergency department displayed powerful accuracy for early rule-out of invasive bacterial infection in infants less than 3 months old presenting with fever without a source, based on results of a phase 3 multicenter Italian study.
“P-SEP [presepsin] is a promising new biomarker. P-SEP accuracy for invasive bacterial infection is comparable to procalcitonin, even though P-SEP, like procalcitonin, is probably not accurate enough to be used as a stand-alone marker to rule-in an invasive bacterial infection,” Luca Pierantoni, MD, said in presenting the preliminary study results at the annual meeting of the European Society for Paediatric Infectious Diseases.
The presepsin test is a rapid point-of-care test well-suited for the ED setting, with a cost equal to that of point-of-care procalcitonin.
Presepsin is a form of soluble CD14 that is released from the surface of macrophages, monocytes, and neutrophils when these immune cells are stimulated by pathogens. “We think it may be a reliable diagnostic and prognostic marker of sepsis in adults and neonates,” explained Dr. Pierantoni of the University of Bologna, Italy.
Indeed, studies in adults suggest presepsin has better sensitivity and specificity than other biomarkers for early diagnosis of sepsis, and that it provides useful information on severity and prognosis as well. But, Dr. Pierantoni and his coworkers wondered, how does it perform in febrile young infants?
The Italian study was designed to address an unmet need: Fever accounts for about one-third of ED visits in infants up to age 3 months, 20% of whom are initially categorized as having fever without source. Yet ultimately 10%-20% of those youngsters having fever without source are found to have an invasive bacterial infection – that is, sepsis or meningitis – or a severe bacterial infection such as pneumonia, a urinary tract infection, or an infected umbilical cord. The sooner these infants can be identified and appropriately treated, the better.
The study enrolled 284 children less than 3 months old who had fever without cause of a mean 10.5 hours duration and presented to the emergency departments of six Italian medical centers. Children were eligible for the study regardless of whether they appeared toxic or well. Presepsin, procalcitonin, and C-reactive protein levels were immediately measured in all participants. Ultimately, 5.6% of subjects were diagnosed with an invasive bacterial infection, and another 21.2% had a severe bacterial infection.
Using a cutoff value of 449 pg/mL, P-SEP had good diagnostic accuracy for invasive bacterial infection, with an area under the receiver operating characteristics curve of 0.81, essentially the same as the 0.82 value for procalcitonin. P-SEP had a sensitivity and specificity of 87% and 75%, respectively, placing it in the same ballpark as the 82% and 86% values for procalcitonin. The strong point for P-SEP was its 99% negative predictive value, as compared to 91% for procalcitonin. The positive predictive values were 17% for P-SEP and 20% for procalcitonin.
In response to an audience question, Dr. Pierantoni speculated that the best use for P-SEP in the setting of fever of unknown origin may be in combination with procalcitonin rather than as a replacement for it. The research team is now in the process of analyzing their study data to see if that is indeed the case.
He reported having no financial conflicts regarding his study, conducted free of commercial support.
LJUBLJANA, SLOVENIA – A point-of-care presepsin measurement in the emergency department displayed powerful accuracy for early rule-out of invasive bacterial infection in infants less than 3 months old presenting with fever without a source, based on results of a phase 3 multicenter Italian study.
“P-SEP [presepsin] is a promising new biomarker. P-SEP accuracy for invasive bacterial infection is comparable to procalcitonin, even though P-SEP, like procalcitonin, is probably not accurate enough to be used as a stand-alone marker to rule-in an invasive bacterial infection,” Luca Pierantoni, MD, said in presenting the preliminary study results at the annual meeting of the European Society for Paediatric Infectious Diseases.
The presepsin test is a rapid point-of-care test well-suited for the ED setting, with a cost equal to that of point-of-care procalcitonin.
Presepsin is a form of soluble CD14 that is released from the surface of macrophages, monocytes, and neutrophils when these immune cells are stimulated by pathogens. “We think it may be a reliable diagnostic and prognostic marker of sepsis in adults and neonates,” explained Dr. Pierantoni of the University of Bologna, Italy.
Indeed, studies in adults suggest presepsin has better sensitivity and specificity than other biomarkers for early diagnosis of sepsis, and that it provides useful information on severity and prognosis as well. But, Dr. Pierantoni and his coworkers wondered, how does it perform in febrile young infants?
The Italian study was designed to address an unmet need: Fever accounts for about one-third of ED visits in infants up to age 3 months, 20% of whom are initially categorized as having fever without source. Yet ultimately 10%-20% of those youngsters having fever without source are found to have an invasive bacterial infection – that is, sepsis or meningitis – or a severe bacterial infection such as pneumonia, a urinary tract infection, or an infected umbilical cord. The sooner these infants can be identified and appropriately treated, the better.
The study enrolled 284 children less than 3 months old who had fever without cause of a mean 10.5 hours duration and presented to the emergency departments of six Italian medical centers. Children were eligible for the study regardless of whether they appeared toxic or well. Presepsin, procalcitonin, and C-reactive protein levels were immediately measured in all participants. Ultimately, 5.6% of subjects were diagnosed with an invasive bacterial infection, and another 21.2% had a severe bacterial infection.
Using a cutoff value of 449 pg/mL, P-SEP had good diagnostic accuracy for invasive bacterial infection, with an area under the receiver operating characteristics curve of 0.81, essentially the same as the 0.82 value for procalcitonin. P-SEP had a sensitivity and specificity of 87% and 75%, respectively, placing it in the same ballpark as the 82% and 86% values for procalcitonin. The strong point for P-SEP was its 99% negative predictive value, as compared to 91% for procalcitonin. The positive predictive values were 17% for P-SEP and 20% for procalcitonin.
In response to an audience question, Dr. Pierantoni speculated that the best use for P-SEP in the setting of fever of unknown origin may be in combination with procalcitonin rather than as a replacement for it. The research team is now in the process of analyzing their study data to see if that is indeed the case.
He reported having no financial conflicts regarding his study, conducted free of commercial support.
LJUBLJANA, SLOVENIA – A point-of-care presepsin measurement in the emergency department displayed powerful accuracy for early rule-out of invasive bacterial infection in infants less than 3 months old presenting with fever without a source, based on results of a phase 3 multicenter Italian study.
“P-SEP [presepsin] is a promising new biomarker. P-SEP accuracy for invasive bacterial infection is comparable to procalcitonin, even though P-SEP, like procalcitonin, is probably not accurate enough to be used as a stand-alone marker to rule-in an invasive bacterial infection,” Luca Pierantoni, MD, said in presenting the preliminary study results at the annual meeting of the European Society for Paediatric Infectious Diseases.
The presepsin test is a rapid point-of-care test well-suited for the ED setting, with a cost equal to that of point-of-care procalcitonin.
Presepsin is a form of soluble CD14 that is released from the surface of macrophages, monocytes, and neutrophils when these immune cells are stimulated by pathogens. “We think it may be a reliable diagnostic and prognostic marker of sepsis in adults and neonates,” explained Dr. Pierantoni of the University of Bologna, Italy.
Indeed, studies in adults suggest presepsin has better sensitivity and specificity than other biomarkers for early diagnosis of sepsis, and that it provides useful information on severity and prognosis as well. But, Dr. Pierantoni and his coworkers wondered, how does it perform in febrile young infants?
The Italian study was designed to address an unmet need: Fever accounts for about one-third of ED visits in infants up to age 3 months, 20% of whom are initially categorized as having fever without source. Yet ultimately 10%-20% of those youngsters having fever without source are found to have an invasive bacterial infection – that is, sepsis or meningitis – or a severe bacterial infection such as pneumonia, a urinary tract infection, or an infected umbilical cord. The sooner these infants can be identified and appropriately treated, the better.
The study enrolled 284 children less than 3 months old who had fever without cause of a mean 10.5 hours duration and presented to the emergency departments of six Italian medical centers. Children were eligible for the study regardless of whether they appeared toxic or well. Presepsin, procalcitonin, and C-reactive protein levels were immediately measured in all participants. Ultimately, 5.6% of subjects were diagnosed with an invasive bacterial infection, and another 21.2% had a severe bacterial infection.
Using a cutoff value of 449 pg/mL, P-SEP had good diagnostic accuracy for invasive bacterial infection, with an area under the receiver operating characteristics curve of 0.81, essentially the same as the 0.82 value for procalcitonin. P-SEP had a sensitivity and specificity of 87% and 75%, respectively, placing it in the same ballpark as the 82% and 86% values for procalcitonin. The strong point for P-SEP was its 99% negative predictive value, as compared to 91% for procalcitonin. The positive predictive values were 17% for P-SEP and 20% for procalcitonin.
In response to an audience question, Dr. Pierantoni speculated that the best use for P-SEP in the setting of fever of unknown origin may be in combination with procalcitonin rather than as a replacement for it. The research team is now in the process of analyzing their study data to see if that is indeed the case.
He reported having no financial conflicts regarding his study, conducted free of commercial support.
REPORTING FROM ESPID 2019
Key clinical point: A rapid point-of-care measurement of presepsin in the ED can rule out invasive bacterial infection with 99% accuracy in young infants with fever of unknown source.
Major finding: The negative predictive value of a presepsin level below the cutoff value of 449 pg/mL was 99%.
Study details: This was a multicenter Italian observational study of 284 infants less than 3 months old who presented to emergency departments with fever without source.
Disclosures: The presenter reported having no financial conflicts regarding his study, conducted free of commercial support.