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Osteoporosis risk rises with air pollution levels
COPENHAGEN – Chronic exposure to high levels of particulate matter (PM) air pollution 2.5 mcm (PM2.5) or larger, and 10 mcm (PM10) or larger, in size is associated with a significantly higher likelihood of having osteoporosis, according to research presented at the annual European Congress of Rheumatology.
The results of the 7-year longitudinal study carried out across Italy from 2013 to 2019 dovetail with other recent published accounts from the same team of Italian researchers, led by Giovanni Adami, MD, of the rheumatology unit at the University of Verona (Italy). In addition to the current report presented at EULAR 2022, Dr. Adami and associates have reported an increased risk of flares of both rheumatoid arthritis and psoriasis following periods of elevated pollution, as well as an overall elevated risk for autoimmune diseases with higher concentrations of PM2.5 and PM10.
The pathogenesis of osteoporosis is thought to involve both genetic and environmental input, such as smoking, which is itself environmental air pollution, Dr. Adami said. The biological rationale for why air pollution might contribute to risk for osteoporosis comes from studies showing that exposure to indoor air pollution from biomass combustion raises serum levels of RANKL (receptor activator of nuclear factor-kappa ligand 1) but lowers serum osteoprotegerin – suggesting an increased risk of bone resorption – and that toxic metals such as lead, cadmium, mercury, and aluminum accumulate in the skeleton and negatively affect bone health.
In their study, Dr. Adami and colleagues found that, overall, the average exposure during the period 2013-2019 across Italy was 16.0 mcg/m3 for PM2.5 and 25.0 mcg/m3 for PM10.
“I can tell you that [25.0 mcg/m3 for PM10] is a very high exposure. It’s not very good for your health,” Dr. Adami said.
Data on more than 59,000 Italian women
Dr. Adami and colleagues used clinical characteristics and densitometric data from Italy’s osteoporosis fracture risk and osteoporosis screening reimbursement tool known as DeFRAcalc79, which has amassed variables from more than 59,000 women across the country. They used long-term average PM concentrations across Italy during 2013-2019 that were obtained from the Italian Institute for Environmental Protection and Research’s 617 air quality stations in 110 Italian provinces. The researchers linked individuals to a PM exposure value determined from the average concentration of urban, rural, and near-traffic stations in each person’s province of residence.
For 59,950 women across Italy who were at high risk for fracture, the researchers found 64.5% with bone mineral density that was defined as osteoporotic. At PM10 concentrations of 30 mcg/m3 or greater, there was a significantly higher likelihood of osteoporosis at both the femoral neck (odds ratio, 1.15) and lumbar spine (OR, 1.17).
The likelihood of osteoporosis was slightly greater with PM2.5 at concentrations of 25 mcg/m3 or more at the femoral neck (OR, 1.22) and lumbar spine (OR, 1.18). These comparisons were adjusted for age, body mass index (BMI), presence of prevalent fragility fractures, family history of osteoporosis, menopause, glucocorticoid use, comorbidities, and for residency in northern, central, or southern Italy.
Both thresholds of PM10 > 30 mcg/m3 and PM2.5 > 25 mcg/m3 “are considered safe … by the World Health Organization,” Dr. Adami pointed out.
“If you live in a place where the chronic exposure is less than 30 mcg/m3, you probably have slightly lower risk of osteoporosis as compared to those who live in a highly industrialized, polluted zone,” he explained.
“The cortical bone – femoral neck – seemed to be more susceptible, compared to trabecular bone, which is the lumbar spine. We have no idea why this is true, but we might speculate that somehow chronic inflammation like the [kind] seen in rheumatoid arthritis might be responsible for cortical bone impairment and not trabecular bone impairment,” Dr. Adami said.
One audience member, Kenneth Poole, BM, PhD, senior lecturer and honorary consultant in Metabolic Bone Disease and Rheumatology at the University of Cambridge (England), asked whether it was possible to account for the possibility of confounding caused by areas with dense housing in places where the particulate matter would be highest, and where residents may be less active and use stairs less often.
Dr. Adami noted that confounding is indeed a possibility, but he said Italy is unique in that its most polluted area – the Po River valley – is also its most wealthy area and in general has less crowded living situations with a healthier population, which could have attenuated, rather than reinforced, the results.
Does air pollution have an immunologic effect?
In interviews with this news organization, session comoderators Filipe Araújo, MD, and Irene Bultink, MD, PhD, said that the growth in evidence for the impact of air pollution on risk for, and severity of, various diseases suggests air pollution might have an immunologic effect.
“I think it’s very important to point this out. I also think it’s very hard to rule out confounding, because when you’re living in a city with crowded housing you may not walk or ride your bike but instead go by car or metro, and [the lifestyle is different],” said Dr. Bultink of Amsterdam University Medical Centers.
“It stresses that these diseases [that are associated with air pollution] although they are different in their pathophysiology, it points toward the systemic nature of rheumatic diseases, including osteoporosis,” said Dr. Araújo of Hospital Cuf Cascais (Portugal) and Hospital Ortopédico de Sant’Ana, Parede, Portugal.
The study was independently supported.Dr. Adami disclosed being a shareholder of Galapagos and Theramex.
A version of this article first appeared on Medscape.com.
COPENHAGEN – Chronic exposure to high levels of particulate matter (PM) air pollution 2.5 mcm (PM2.5) or larger, and 10 mcm (PM10) or larger, in size is associated with a significantly higher likelihood of having osteoporosis, according to research presented at the annual European Congress of Rheumatology.
The results of the 7-year longitudinal study carried out across Italy from 2013 to 2019 dovetail with other recent published accounts from the same team of Italian researchers, led by Giovanni Adami, MD, of the rheumatology unit at the University of Verona (Italy). In addition to the current report presented at EULAR 2022, Dr. Adami and associates have reported an increased risk of flares of both rheumatoid arthritis and psoriasis following periods of elevated pollution, as well as an overall elevated risk for autoimmune diseases with higher concentrations of PM2.5 and PM10.
The pathogenesis of osteoporosis is thought to involve both genetic and environmental input, such as smoking, which is itself environmental air pollution, Dr. Adami said. The biological rationale for why air pollution might contribute to risk for osteoporosis comes from studies showing that exposure to indoor air pollution from biomass combustion raises serum levels of RANKL (receptor activator of nuclear factor-kappa ligand 1) but lowers serum osteoprotegerin – suggesting an increased risk of bone resorption – and that toxic metals such as lead, cadmium, mercury, and aluminum accumulate in the skeleton and negatively affect bone health.
In their study, Dr. Adami and colleagues found that, overall, the average exposure during the period 2013-2019 across Italy was 16.0 mcg/m3 for PM2.5 and 25.0 mcg/m3 for PM10.
“I can tell you that [25.0 mcg/m3 for PM10] is a very high exposure. It’s not very good for your health,” Dr. Adami said.
Data on more than 59,000 Italian women
Dr. Adami and colleagues used clinical characteristics and densitometric data from Italy’s osteoporosis fracture risk and osteoporosis screening reimbursement tool known as DeFRAcalc79, which has amassed variables from more than 59,000 women across the country. They used long-term average PM concentrations across Italy during 2013-2019 that were obtained from the Italian Institute for Environmental Protection and Research’s 617 air quality stations in 110 Italian provinces. The researchers linked individuals to a PM exposure value determined from the average concentration of urban, rural, and near-traffic stations in each person’s province of residence.
For 59,950 women across Italy who were at high risk for fracture, the researchers found 64.5% with bone mineral density that was defined as osteoporotic. At PM10 concentrations of 30 mcg/m3 or greater, there was a significantly higher likelihood of osteoporosis at both the femoral neck (odds ratio, 1.15) and lumbar spine (OR, 1.17).
The likelihood of osteoporosis was slightly greater with PM2.5 at concentrations of 25 mcg/m3 or more at the femoral neck (OR, 1.22) and lumbar spine (OR, 1.18). These comparisons were adjusted for age, body mass index (BMI), presence of prevalent fragility fractures, family history of osteoporosis, menopause, glucocorticoid use, comorbidities, and for residency in northern, central, or southern Italy.
Both thresholds of PM10 > 30 mcg/m3 and PM2.5 > 25 mcg/m3 “are considered safe … by the World Health Organization,” Dr. Adami pointed out.
“If you live in a place where the chronic exposure is less than 30 mcg/m3, you probably have slightly lower risk of osteoporosis as compared to those who live in a highly industrialized, polluted zone,” he explained.
“The cortical bone – femoral neck – seemed to be more susceptible, compared to trabecular bone, which is the lumbar spine. We have no idea why this is true, but we might speculate that somehow chronic inflammation like the [kind] seen in rheumatoid arthritis might be responsible for cortical bone impairment and not trabecular bone impairment,” Dr. Adami said.
One audience member, Kenneth Poole, BM, PhD, senior lecturer and honorary consultant in Metabolic Bone Disease and Rheumatology at the University of Cambridge (England), asked whether it was possible to account for the possibility of confounding caused by areas with dense housing in places where the particulate matter would be highest, and where residents may be less active and use stairs less often.
Dr. Adami noted that confounding is indeed a possibility, but he said Italy is unique in that its most polluted area – the Po River valley – is also its most wealthy area and in general has less crowded living situations with a healthier population, which could have attenuated, rather than reinforced, the results.
Does air pollution have an immunologic effect?
In interviews with this news organization, session comoderators Filipe Araújo, MD, and Irene Bultink, MD, PhD, said that the growth in evidence for the impact of air pollution on risk for, and severity of, various diseases suggests air pollution might have an immunologic effect.
“I think it’s very important to point this out. I also think it’s very hard to rule out confounding, because when you’re living in a city with crowded housing you may not walk or ride your bike but instead go by car or metro, and [the lifestyle is different],” said Dr. Bultink of Amsterdam University Medical Centers.
“It stresses that these diseases [that are associated with air pollution] although they are different in their pathophysiology, it points toward the systemic nature of rheumatic diseases, including osteoporosis,” said Dr. Araújo of Hospital Cuf Cascais (Portugal) and Hospital Ortopédico de Sant’Ana, Parede, Portugal.
The study was independently supported.Dr. Adami disclosed being a shareholder of Galapagos and Theramex.
A version of this article first appeared on Medscape.com.
COPENHAGEN – Chronic exposure to high levels of particulate matter (PM) air pollution 2.5 mcm (PM2.5) or larger, and 10 mcm (PM10) or larger, in size is associated with a significantly higher likelihood of having osteoporosis, according to research presented at the annual European Congress of Rheumatology.
The results of the 7-year longitudinal study carried out across Italy from 2013 to 2019 dovetail with other recent published accounts from the same team of Italian researchers, led by Giovanni Adami, MD, of the rheumatology unit at the University of Verona (Italy). In addition to the current report presented at EULAR 2022, Dr. Adami and associates have reported an increased risk of flares of both rheumatoid arthritis and psoriasis following periods of elevated pollution, as well as an overall elevated risk for autoimmune diseases with higher concentrations of PM2.5 and PM10.
The pathogenesis of osteoporosis is thought to involve both genetic and environmental input, such as smoking, which is itself environmental air pollution, Dr. Adami said. The biological rationale for why air pollution might contribute to risk for osteoporosis comes from studies showing that exposure to indoor air pollution from biomass combustion raises serum levels of RANKL (receptor activator of nuclear factor-kappa ligand 1) but lowers serum osteoprotegerin – suggesting an increased risk of bone resorption – and that toxic metals such as lead, cadmium, mercury, and aluminum accumulate in the skeleton and negatively affect bone health.
In their study, Dr. Adami and colleagues found that, overall, the average exposure during the period 2013-2019 across Italy was 16.0 mcg/m3 for PM2.5 and 25.0 mcg/m3 for PM10.
“I can tell you that [25.0 mcg/m3 for PM10] is a very high exposure. It’s not very good for your health,” Dr. Adami said.
Data on more than 59,000 Italian women
Dr. Adami and colleagues used clinical characteristics and densitometric data from Italy’s osteoporosis fracture risk and osteoporosis screening reimbursement tool known as DeFRAcalc79, which has amassed variables from more than 59,000 women across the country. They used long-term average PM concentrations across Italy during 2013-2019 that were obtained from the Italian Institute for Environmental Protection and Research’s 617 air quality stations in 110 Italian provinces. The researchers linked individuals to a PM exposure value determined from the average concentration of urban, rural, and near-traffic stations in each person’s province of residence.
For 59,950 women across Italy who were at high risk for fracture, the researchers found 64.5% with bone mineral density that was defined as osteoporotic. At PM10 concentrations of 30 mcg/m3 or greater, there was a significantly higher likelihood of osteoporosis at both the femoral neck (odds ratio, 1.15) and lumbar spine (OR, 1.17).
The likelihood of osteoporosis was slightly greater with PM2.5 at concentrations of 25 mcg/m3 or more at the femoral neck (OR, 1.22) and lumbar spine (OR, 1.18). These comparisons were adjusted for age, body mass index (BMI), presence of prevalent fragility fractures, family history of osteoporosis, menopause, glucocorticoid use, comorbidities, and for residency in northern, central, or southern Italy.
Both thresholds of PM10 > 30 mcg/m3 and PM2.5 > 25 mcg/m3 “are considered safe … by the World Health Organization,” Dr. Adami pointed out.
“If you live in a place where the chronic exposure is less than 30 mcg/m3, you probably have slightly lower risk of osteoporosis as compared to those who live in a highly industrialized, polluted zone,” he explained.
“The cortical bone – femoral neck – seemed to be more susceptible, compared to trabecular bone, which is the lumbar spine. We have no idea why this is true, but we might speculate that somehow chronic inflammation like the [kind] seen in rheumatoid arthritis might be responsible for cortical bone impairment and not trabecular bone impairment,” Dr. Adami said.
One audience member, Kenneth Poole, BM, PhD, senior lecturer and honorary consultant in Metabolic Bone Disease and Rheumatology at the University of Cambridge (England), asked whether it was possible to account for the possibility of confounding caused by areas with dense housing in places where the particulate matter would be highest, and where residents may be less active and use stairs less often.
Dr. Adami noted that confounding is indeed a possibility, but he said Italy is unique in that its most polluted area – the Po River valley – is also its most wealthy area and in general has less crowded living situations with a healthier population, which could have attenuated, rather than reinforced, the results.
Does air pollution have an immunologic effect?
In interviews with this news organization, session comoderators Filipe Araújo, MD, and Irene Bultink, MD, PhD, said that the growth in evidence for the impact of air pollution on risk for, and severity of, various diseases suggests air pollution might have an immunologic effect.
“I think it’s very important to point this out. I also think it’s very hard to rule out confounding, because when you’re living in a city with crowded housing you may not walk or ride your bike but instead go by car or metro, and [the lifestyle is different],” said Dr. Bultink of Amsterdam University Medical Centers.
“It stresses that these diseases [that are associated with air pollution] although they are different in their pathophysiology, it points toward the systemic nature of rheumatic diseases, including osteoporosis,” said Dr. Araújo of Hospital Cuf Cascais (Portugal) and Hospital Ortopédico de Sant’Ana, Parede, Portugal.
The study was independently supported.Dr. Adami disclosed being a shareholder of Galapagos and Theramex.
A version of this article first appeared on Medscape.com.
AT THE EULAR 2022 CONGRESS
What are the signs of post–acute infection syndromes?
The long-term health consequences of COVID-19 have refocused our attention on post–acute infection syndromes (PAIS), starting a discussion on the need for a complete understanding of multisystemic pathophysiology, clinical indicators, and the epidemiology of these syndromes, representing a significant blind spot in the field of medicine. A better understanding of these persistent symptom profiles, not only for post-acute sequelae of SARS-CoV-2 infection (PASC), better known as long COVID, but also for other diseases with unexplainable post-acute sequelae, would allow doctors to fine tune the diagnostic criteria. Having a clear definition and better understanding of post–acute infection symptoms is a necessary step toward developing an evidence-based, multidisciplinary management approach.
PAIS, PASC, or long COVID
The observation of unexplained chronic sequelae after SARS-CoV-2 is known as PASC or long COVID.
Long COVID has been reported as a syndrome in survivors of serious and critical disease, but the effects also persist over time for subjects who experienced a mild infection that did not require admission to hospital. This means that PASC, especially when occurring after a mild or moderate COVID-19 infection, shares many of the same characteristics as chronic diseases triggered by other pathogenic organisms, many of which have not been sufficiently clarified.
PAIS are characterized by a set of core symptoms centering on the following:
- Exertion intolerance
- Disproportionate levels of fatigue
- Neurocognitive and sensory impairment
- Flu-like symptoms
- Unrefreshing sleep
- Myalgia/arthralgia
A plethora of nonspecific symptoms are often present to various degrees.
These similarities suggest a unifying pathophysiology that needs to be elucidated to properly understand and manage postinfectious chronic disability.
Overview of PAIS
A detailed revision on what is currently known about PAIS was published in Nature Medicine. It provided various useful pieces of information to assist with the poor recognition of these conditions in clinical practice, a result of which is that patients might experience delayed or a complete lack of clinical care.
The following consolidated postinfection sequelae are mentioned:
- Q fever fatigue syndrome, which follows infection by the intracellular bacterium Coxiella burnetii
- Post-dengue fatigue syndrome, which can follow infection by the mosquito-borne dengue virus
- Fatiguing and rheumatic symptoms in a subset of individuals infected with chikungunya virus, a mosquito-borne virus that causes fever and joint pain in the acute phase
- Post-polio syndrome, which can emerge as many as 15-40 years after an initial poliomyelitis attack (similarly, some other neurotropic microbes, such as West Nile virus, might lead to persistent effects)
- Prolonged, debilitating, chronic symptoms have long been reported in a subset of patients after common and typically nonserious infections. For example, after mononucleosis, a condition generally caused by Epstein-Barr virus (EBV), and after an outbreak of Giardia lamblia, an intestinal parasite that usually causes acute intestinal illness. In fact, several studies identified the association of this outbreak of giardiasis with chronic fatigue, irritable bowel syndrome (IBS), and fibromyalgia persisting for many years.
- Views expressed in the literature regarding the frequency and the validity of posttreatment Lyme disease syndrome are divided. Although substantial evidence points to persistence of arthralgia, fatigue, and subjective neurocognitive impairments in a minority of patients with Lyme disease after the recommended antibiotic treatment, some of the early studies have failed to characterize the initial Lyme disease episode with sufficient rigor.
Symptoms and signs
The symptoms and signs which, based on the evidence available, are seen more frequently in health care checks may be characterized as the following:
- Exertion intolerance, fatigue
- Flu-like and ‘sickness behavior’ symptoms: fever, feverishness, muscle pain, feeling sick, malaise, sweating, irritability
- Neurological/neurocognitive symptoms: brain fog, impaired concentration or memory, trouble finding words
- Rheumatologic symptoms: chronic or recurrent joint pain
- Trigger-specific symptoms: for example, eye problems post Ebola, IBS post Giardia, anosmia and ageusia post COVID-19, motor disturbances post polio and post West Nile virus
Myalgic encephalomyelitis/chronic fatigue syndrome
Patients with this disorder experience worsening of symptoms following physical, cognitive, or emotional exertion above their (very low) tolerated limit. Other prominent features frequently observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are neurocognitive impairments (colloquially referred to as brain fog), unrefreshing sleep, pain, sensory disturbances, gastrointestinal issues, and various forms of dysautonomia. Up to 75% of ME/CFS cases report an infection-like episode preceding the onset of their illness. Postinfectious and postviral fatigue syndromes were originally postulated as subsets of chronic fatigue syndrome. However, there appears to be no clear consensus at present about whether these terms should be considered synonymous to the ME/CFS label or any of its subsets, or include a wider range of postinfectious fatigue conditions.
Practical diagnostic criteria
From a revision of the available criteria, it emerges that the diagnostic criteria for a PAIS should include not only the presence of symptoms, but ideally also the intensity, course, and constellation of symptoms within an individual, as the individual symptoms and symptom trajectories of PAIS vary over time, rendering a mere comparison of symptom presence at a single time point misleading. Furthermore, when a diagnosis of ME/CFS is made, attention should be given to the choice of diagnostic criteria, with preference given to the more conservative criteria, so as not to run the risk of overestimating the syndrome.
Asthenia is the cornerstone symptom for most epidemiological studies on PAIS, but it would be reductive to concentrate only on this rather than the other characteristics, such as the exacerbation of symptoms following exertion, together with other characteristic symptoms and signs that may allow for better identification of the overall, observable clinical picture in these postinfection syndromes, which have significant impacts on a patient’s quality of life.
This article was translated from Univadis Italy. A version of this article appeared on Medscape.com.
The long-term health consequences of COVID-19 have refocused our attention on post–acute infection syndromes (PAIS), starting a discussion on the need for a complete understanding of multisystemic pathophysiology, clinical indicators, and the epidemiology of these syndromes, representing a significant blind spot in the field of medicine. A better understanding of these persistent symptom profiles, not only for post-acute sequelae of SARS-CoV-2 infection (PASC), better known as long COVID, but also for other diseases with unexplainable post-acute sequelae, would allow doctors to fine tune the diagnostic criteria. Having a clear definition and better understanding of post–acute infection symptoms is a necessary step toward developing an evidence-based, multidisciplinary management approach.
PAIS, PASC, or long COVID
The observation of unexplained chronic sequelae after SARS-CoV-2 is known as PASC or long COVID.
Long COVID has been reported as a syndrome in survivors of serious and critical disease, but the effects also persist over time for subjects who experienced a mild infection that did not require admission to hospital. This means that PASC, especially when occurring after a mild or moderate COVID-19 infection, shares many of the same characteristics as chronic diseases triggered by other pathogenic organisms, many of which have not been sufficiently clarified.
PAIS are characterized by a set of core symptoms centering on the following:
- Exertion intolerance
- Disproportionate levels of fatigue
- Neurocognitive and sensory impairment
- Flu-like symptoms
- Unrefreshing sleep
- Myalgia/arthralgia
A plethora of nonspecific symptoms are often present to various degrees.
These similarities suggest a unifying pathophysiology that needs to be elucidated to properly understand and manage postinfectious chronic disability.
Overview of PAIS
A detailed revision on what is currently known about PAIS was published in Nature Medicine. It provided various useful pieces of information to assist with the poor recognition of these conditions in clinical practice, a result of which is that patients might experience delayed or a complete lack of clinical care.
The following consolidated postinfection sequelae are mentioned:
- Q fever fatigue syndrome, which follows infection by the intracellular bacterium Coxiella burnetii
- Post-dengue fatigue syndrome, which can follow infection by the mosquito-borne dengue virus
- Fatiguing and rheumatic symptoms in a subset of individuals infected with chikungunya virus, a mosquito-borne virus that causes fever and joint pain in the acute phase
- Post-polio syndrome, which can emerge as many as 15-40 years after an initial poliomyelitis attack (similarly, some other neurotropic microbes, such as West Nile virus, might lead to persistent effects)
- Prolonged, debilitating, chronic symptoms have long been reported in a subset of patients after common and typically nonserious infections. For example, after mononucleosis, a condition generally caused by Epstein-Barr virus (EBV), and after an outbreak of Giardia lamblia, an intestinal parasite that usually causes acute intestinal illness. In fact, several studies identified the association of this outbreak of giardiasis with chronic fatigue, irritable bowel syndrome (IBS), and fibromyalgia persisting for many years.
- Views expressed in the literature regarding the frequency and the validity of posttreatment Lyme disease syndrome are divided. Although substantial evidence points to persistence of arthralgia, fatigue, and subjective neurocognitive impairments in a minority of patients with Lyme disease after the recommended antibiotic treatment, some of the early studies have failed to characterize the initial Lyme disease episode with sufficient rigor.
Symptoms and signs
The symptoms and signs which, based on the evidence available, are seen more frequently in health care checks may be characterized as the following:
- Exertion intolerance, fatigue
- Flu-like and ‘sickness behavior’ symptoms: fever, feverishness, muscle pain, feeling sick, malaise, sweating, irritability
- Neurological/neurocognitive symptoms: brain fog, impaired concentration or memory, trouble finding words
- Rheumatologic symptoms: chronic or recurrent joint pain
- Trigger-specific symptoms: for example, eye problems post Ebola, IBS post Giardia, anosmia and ageusia post COVID-19, motor disturbances post polio and post West Nile virus
Myalgic encephalomyelitis/chronic fatigue syndrome
Patients with this disorder experience worsening of symptoms following physical, cognitive, or emotional exertion above their (very low) tolerated limit. Other prominent features frequently observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are neurocognitive impairments (colloquially referred to as brain fog), unrefreshing sleep, pain, sensory disturbances, gastrointestinal issues, and various forms of dysautonomia. Up to 75% of ME/CFS cases report an infection-like episode preceding the onset of their illness. Postinfectious and postviral fatigue syndromes were originally postulated as subsets of chronic fatigue syndrome. However, there appears to be no clear consensus at present about whether these terms should be considered synonymous to the ME/CFS label or any of its subsets, or include a wider range of postinfectious fatigue conditions.
Practical diagnostic criteria
From a revision of the available criteria, it emerges that the diagnostic criteria for a PAIS should include not only the presence of symptoms, but ideally also the intensity, course, and constellation of symptoms within an individual, as the individual symptoms and symptom trajectories of PAIS vary over time, rendering a mere comparison of symptom presence at a single time point misleading. Furthermore, when a diagnosis of ME/CFS is made, attention should be given to the choice of diagnostic criteria, with preference given to the more conservative criteria, so as not to run the risk of overestimating the syndrome.
Asthenia is the cornerstone symptom for most epidemiological studies on PAIS, but it would be reductive to concentrate only on this rather than the other characteristics, such as the exacerbation of symptoms following exertion, together with other characteristic symptoms and signs that may allow for better identification of the overall, observable clinical picture in these postinfection syndromes, which have significant impacts on a patient’s quality of life.
This article was translated from Univadis Italy. A version of this article appeared on Medscape.com.
The long-term health consequences of COVID-19 have refocused our attention on post–acute infection syndromes (PAIS), starting a discussion on the need for a complete understanding of multisystemic pathophysiology, clinical indicators, and the epidemiology of these syndromes, representing a significant blind spot in the field of medicine. A better understanding of these persistent symptom profiles, not only for post-acute sequelae of SARS-CoV-2 infection (PASC), better known as long COVID, but also for other diseases with unexplainable post-acute sequelae, would allow doctors to fine tune the diagnostic criteria. Having a clear definition and better understanding of post–acute infection symptoms is a necessary step toward developing an evidence-based, multidisciplinary management approach.
PAIS, PASC, or long COVID
The observation of unexplained chronic sequelae after SARS-CoV-2 is known as PASC or long COVID.
Long COVID has been reported as a syndrome in survivors of serious and critical disease, but the effects also persist over time for subjects who experienced a mild infection that did not require admission to hospital. This means that PASC, especially when occurring after a mild or moderate COVID-19 infection, shares many of the same characteristics as chronic diseases triggered by other pathogenic organisms, many of which have not been sufficiently clarified.
PAIS are characterized by a set of core symptoms centering on the following:
- Exertion intolerance
- Disproportionate levels of fatigue
- Neurocognitive and sensory impairment
- Flu-like symptoms
- Unrefreshing sleep
- Myalgia/arthralgia
A plethora of nonspecific symptoms are often present to various degrees.
These similarities suggest a unifying pathophysiology that needs to be elucidated to properly understand and manage postinfectious chronic disability.
Overview of PAIS
A detailed revision on what is currently known about PAIS was published in Nature Medicine. It provided various useful pieces of information to assist with the poor recognition of these conditions in clinical practice, a result of which is that patients might experience delayed or a complete lack of clinical care.
The following consolidated postinfection sequelae are mentioned:
- Q fever fatigue syndrome, which follows infection by the intracellular bacterium Coxiella burnetii
- Post-dengue fatigue syndrome, which can follow infection by the mosquito-borne dengue virus
- Fatiguing and rheumatic symptoms in a subset of individuals infected with chikungunya virus, a mosquito-borne virus that causes fever and joint pain in the acute phase
- Post-polio syndrome, which can emerge as many as 15-40 years after an initial poliomyelitis attack (similarly, some other neurotropic microbes, such as West Nile virus, might lead to persistent effects)
- Prolonged, debilitating, chronic symptoms have long been reported in a subset of patients after common and typically nonserious infections. For example, after mononucleosis, a condition generally caused by Epstein-Barr virus (EBV), and after an outbreak of Giardia lamblia, an intestinal parasite that usually causes acute intestinal illness. In fact, several studies identified the association of this outbreak of giardiasis with chronic fatigue, irritable bowel syndrome (IBS), and fibromyalgia persisting for many years.
- Views expressed in the literature regarding the frequency and the validity of posttreatment Lyme disease syndrome are divided. Although substantial evidence points to persistence of arthralgia, fatigue, and subjective neurocognitive impairments in a minority of patients with Lyme disease after the recommended antibiotic treatment, some of the early studies have failed to characterize the initial Lyme disease episode with sufficient rigor.
Symptoms and signs
The symptoms and signs which, based on the evidence available, are seen more frequently in health care checks may be characterized as the following:
- Exertion intolerance, fatigue
- Flu-like and ‘sickness behavior’ symptoms: fever, feverishness, muscle pain, feeling sick, malaise, sweating, irritability
- Neurological/neurocognitive symptoms: brain fog, impaired concentration or memory, trouble finding words
- Rheumatologic symptoms: chronic or recurrent joint pain
- Trigger-specific symptoms: for example, eye problems post Ebola, IBS post Giardia, anosmia and ageusia post COVID-19, motor disturbances post polio and post West Nile virus
Myalgic encephalomyelitis/chronic fatigue syndrome
Patients with this disorder experience worsening of symptoms following physical, cognitive, or emotional exertion above their (very low) tolerated limit. Other prominent features frequently observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are neurocognitive impairments (colloquially referred to as brain fog), unrefreshing sleep, pain, sensory disturbances, gastrointestinal issues, and various forms of dysautonomia. Up to 75% of ME/CFS cases report an infection-like episode preceding the onset of their illness. Postinfectious and postviral fatigue syndromes were originally postulated as subsets of chronic fatigue syndrome. However, there appears to be no clear consensus at present about whether these terms should be considered synonymous to the ME/CFS label or any of its subsets, or include a wider range of postinfectious fatigue conditions.
Practical diagnostic criteria
From a revision of the available criteria, it emerges that the diagnostic criteria for a PAIS should include not only the presence of symptoms, but ideally also the intensity, course, and constellation of symptoms within an individual, as the individual symptoms and symptom trajectories of PAIS vary over time, rendering a mere comparison of symptom presence at a single time point misleading. Furthermore, when a diagnosis of ME/CFS is made, attention should be given to the choice of diagnostic criteria, with preference given to the more conservative criteria, so as not to run the risk of overestimating the syndrome.
Asthenia is the cornerstone symptom for most epidemiological studies on PAIS, but it would be reductive to concentrate only on this rather than the other characteristics, such as the exacerbation of symptoms following exertion, together with other characteristic symptoms and signs that may allow for better identification of the overall, observable clinical picture in these postinfection syndromes, which have significant impacts on a patient’s quality of life.
This article was translated from Univadis Italy. A version of this article appeared on Medscape.com.
HPV vaccination with Cervarix ‘unmasks’ cervical lesions from non-vax strains
Vaccines against human papillomavirus have been hailed as a success: they have been shown to decrease the incidence of cervical lesions associated with the HPV types that are in the vaccine.
However,
An expert not involved in the research said the new data “tell us to be a little bit careful.” Although the HPV types not included in the vaccine are rarer and less aggressive, they can still cause cancer.
The data come from the Costa Rica HPV Vaccine Trial, which involved more than 10,000 women aged 18-25 years. The HPV vaccine used in the trial was Cervarix, from GlaxoSmithKline. It covers the two leading causes of cervical cancer, HPV-16 and -18, and provides partial protection against three other genotypes.
After a follow-up of 11 years, among vaccinated women, there was an excess of precancerous cervical lesions caused by genotypes not included in the vaccine, resulting in negative vaccine efficacy for those HPV variants.
The increase wasn’t enough to offset the overall benefit of vaccination when all genotypes were considered, said the researchers, led by Jaimie Shing, PhD, a postdoctoral research fellow at the National Cancer Institute in Bethesda, Md.
Vaccinated women “still had long-term absolute reductions in high-grade lesions,” they pointed out.
The net protection “remained considerable, emphasizing the importance of HPV vaccination for cervical cancer prevention,” the team concluded.
The findings were published online in The Lancet Oncology.
The results are likely the first evidence to date of “clinical unmasking” with HPV vaccination, meaning that protection against the strains covered by the vaccine leaves women more prone to attack from other carcinogenic HPV variants.
This phenomenon “could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programs,” the investigators commented.
Highlighting a need for caution
The take-home message from the trial is that “we have to be careful,” said Marc Steben, MD, co-President of HPV Global Action and a professor at the University of Montreal.
He noted that the Cervarix HPV vaccine used in the trial is not the vaccine that is used now in developed nations.
The current standard HPV vaccine is Gardasil 9 (Merck), which offers broader coverage against nine HPV types (types 6, 11, 16, 18, 31, 33, 45, 52, and 58).
There are 12 main carcinogenic HPV genotypes, so unmasking of other strains is still possible with Gardasil 9, he said.
There is another issue, Dr. Steben added. The success of HPV vaccinations - a nearly 90% reduction in invasive cervical cancer in women who are vaccinated at a young age – has led to questions about the future role of routine cervical cancer screening.
“Some people are saying that if we achieve 90% coverage, we might” eliminate community transmission and no longer need to screen, he said.
These trial results “tell us to be a little bit careful,” Dr. Steben continued. Those HPV types that are less aggressive and rarer than HPV-16 and -18 “can still cause cancer and might be there and surprise us. It could take more time than we thought” to get to the point where screening can be eliminated.
“There might be a little problem if we stop too early,” he said.
Study details
During the period 2004-2005, the investigators randomly assigned 3,727 women aged 18-25 years to receive Cervarix and 3,739 to a control group that received the hepatitis A vaccine; after 4 years, the control group also received Cervarix and exited the study. They were replaced by an unvaccinated control group of 2,836 women. The new control group and the original HPV vaccine group were followed for an additional 7 years.
In years 7-11 of the trial, the investigators found 9.2 additional cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) from HPV types not covered by Cervarix per 1,000 vaccinated women in comparison with unvaccinated participants. This corresponds to –71.2% negative vaccine efficacy against CIN2+ lesions of HPV types not covered by the vaccine.
There were 8.3 additional CIN3+ lesions from nontargeted HPV strains per 1,000 vaccinated women in comparison with unvaccinated participants, which corresponds to –135% negative vaccine efficacy.
Overall, however, there was a net benefit of vaccination, with 27 fewer CIN2+ lesions when all HPV genotypes – vaccine covered or not – were considered per 1,000 vaccinated women over the entire 11 years of follow-up.
There were also 8.7 fewer CIN3+ lesions across all genotypes per 1,000 vaccinated women, but the benefit was not statistically significant.
Among the study limits, the team was unable to evaluate the effect of clinical unmasking on cervical cancer, because women were treated for high-grade cervical lesions before cases could progress to cervical cancer.
The trial was funded by the National Cancer Institute and the National Institutes of Health Office of Research on Women’s Health. GlaxoSmithKline provided the Cervarix vaccine and supported aspects of the trial. Two authors are named inventors on U.S. government–owned HPV vaccine patents with expired licenses to GlaxoSmithKline and Merck. Dr. Steben is an adviser/speaker for many companies, including GlaxoSmithKline and Merck.
A version of this article first appeared on Medscape.com.
Vaccines against human papillomavirus have been hailed as a success: they have been shown to decrease the incidence of cervical lesions associated with the HPV types that are in the vaccine.
However,
An expert not involved in the research said the new data “tell us to be a little bit careful.” Although the HPV types not included in the vaccine are rarer and less aggressive, they can still cause cancer.
The data come from the Costa Rica HPV Vaccine Trial, which involved more than 10,000 women aged 18-25 years. The HPV vaccine used in the trial was Cervarix, from GlaxoSmithKline. It covers the two leading causes of cervical cancer, HPV-16 and -18, and provides partial protection against three other genotypes.
After a follow-up of 11 years, among vaccinated women, there was an excess of precancerous cervical lesions caused by genotypes not included in the vaccine, resulting in negative vaccine efficacy for those HPV variants.
The increase wasn’t enough to offset the overall benefit of vaccination when all genotypes were considered, said the researchers, led by Jaimie Shing, PhD, a postdoctoral research fellow at the National Cancer Institute in Bethesda, Md.
Vaccinated women “still had long-term absolute reductions in high-grade lesions,” they pointed out.
The net protection “remained considerable, emphasizing the importance of HPV vaccination for cervical cancer prevention,” the team concluded.
The findings were published online in The Lancet Oncology.
The results are likely the first evidence to date of “clinical unmasking” with HPV vaccination, meaning that protection against the strains covered by the vaccine leaves women more prone to attack from other carcinogenic HPV variants.
This phenomenon “could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programs,” the investigators commented.
Highlighting a need for caution
The take-home message from the trial is that “we have to be careful,” said Marc Steben, MD, co-President of HPV Global Action and a professor at the University of Montreal.
He noted that the Cervarix HPV vaccine used in the trial is not the vaccine that is used now in developed nations.
The current standard HPV vaccine is Gardasil 9 (Merck), which offers broader coverage against nine HPV types (types 6, 11, 16, 18, 31, 33, 45, 52, and 58).
There are 12 main carcinogenic HPV genotypes, so unmasking of other strains is still possible with Gardasil 9, he said.
There is another issue, Dr. Steben added. The success of HPV vaccinations - a nearly 90% reduction in invasive cervical cancer in women who are vaccinated at a young age – has led to questions about the future role of routine cervical cancer screening.
“Some people are saying that if we achieve 90% coverage, we might” eliminate community transmission and no longer need to screen, he said.
These trial results “tell us to be a little bit careful,” Dr. Steben continued. Those HPV types that are less aggressive and rarer than HPV-16 and -18 “can still cause cancer and might be there and surprise us. It could take more time than we thought” to get to the point where screening can be eliminated.
“There might be a little problem if we stop too early,” he said.
Study details
During the period 2004-2005, the investigators randomly assigned 3,727 women aged 18-25 years to receive Cervarix and 3,739 to a control group that received the hepatitis A vaccine; after 4 years, the control group also received Cervarix and exited the study. They were replaced by an unvaccinated control group of 2,836 women. The new control group and the original HPV vaccine group were followed for an additional 7 years.
In years 7-11 of the trial, the investigators found 9.2 additional cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) from HPV types not covered by Cervarix per 1,000 vaccinated women in comparison with unvaccinated participants. This corresponds to –71.2% negative vaccine efficacy against CIN2+ lesions of HPV types not covered by the vaccine.
There were 8.3 additional CIN3+ lesions from nontargeted HPV strains per 1,000 vaccinated women in comparison with unvaccinated participants, which corresponds to –135% negative vaccine efficacy.
Overall, however, there was a net benefit of vaccination, with 27 fewer CIN2+ lesions when all HPV genotypes – vaccine covered or not – were considered per 1,000 vaccinated women over the entire 11 years of follow-up.
There were also 8.7 fewer CIN3+ lesions across all genotypes per 1,000 vaccinated women, but the benefit was not statistically significant.
Among the study limits, the team was unable to evaluate the effect of clinical unmasking on cervical cancer, because women were treated for high-grade cervical lesions before cases could progress to cervical cancer.
The trial was funded by the National Cancer Institute and the National Institutes of Health Office of Research on Women’s Health. GlaxoSmithKline provided the Cervarix vaccine and supported aspects of the trial. Two authors are named inventors on U.S. government–owned HPV vaccine patents with expired licenses to GlaxoSmithKline and Merck. Dr. Steben is an adviser/speaker for many companies, including GlaxoSmithKline and Merck.
A version of this article first appeared on Medscape.com.
Vaccines against human papillomavirus have been hailed as a success: they have been shown to decrease the incidence of cervical lesions associated with the HPV types that are in the vaccine.
However,
An expert not involved in the research said the new data “tell us to be a little bit careful.” Although the HPV types not included in the vaccine are rarer and less aggressive, they can still cause cancer.
The data come from the Costa Rica HPV Vaccine Trial, which involved more than 10,000 women aged 18-25 years. The HPV vaccine used in the trial was Cervarix, from GlaxoSmithKline. It covers the two leading causes of cervical cancer, HPV-16 and -18, and provides partial protection against three other genotypes.
After a follow-up of 11 years, among vaccinated women, there was an excess of precancerous cervical lesions caused by genotypes not included in the vaccine, resulting in negative vaccine efficacy for those HPV variants.
The increase wasn’t enough to offset the overall benefit of vaccination when all genotypes were considered, said the researchers, led by Jaimie Shing, PhD, a postdoctoral research fellow at the National Cancer Institute in Bethesda, Md.
Vaccinated women “still had long-term absolute reductions in high-grade lesions,” they pointed out.
The net protection “remained considerable, emphasizing the importance of HPV vaccination for cervical cancer prevention,” the team concluded.
The findings were published online in The Lancet Oncology.
The results are likely the first evidence to date of “clinical unmasking” with HPV vaccination, meaning that protection against the strains covered by the vaccine leaves women more prone to attack from other carcinogenic HPV variants.
This phenomenon “could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programs,” the investigators commented.
Highlighting a need for caution
The take-home message from the trial is that “we have to be careful,” said Marc Steben, MD, co-President of HPV Global Action and a professor at the University of Montreal.
He noted that the Cervarix HPV vaccine used in the trial is not the vaccine that is used now in developed nations.
The current standard HPV vaccine is Gardasil 9 (Merck), which offers broader coverage against nine HPV types (types 6, 11, 16, 18, 31, 33, 45, 52, and 58).
There are 12 main carcinogenic HPV genotypes, so unmasking of other strains is still possible with Gardasil 9, he said.
There is another issue, Dr. Steben added. The success of HPV vaccinations - a nearly 90% reduction in invasive cervical cancer in women who are vaccinated at a young age – has led to questions about the future role of routine cervical cancer screening.
“Some people are saying that if we achieve 90% coverage, we might” eliminate community transmission and no longer need to screen, he said.
These trial results “tell us to be a little bit careful,” Dr. Steben continued. Those HPV types that are less aggressive and rarer than HPV-16 and -18 “can still cause cancer and might be there and surprise us. It could take more time than we thought” to get to the point where screening can be eliminated.
“There might be a little problem if we stop too early,” he said.
Study details
During the period 2004-2005, the investigators randomly assigned 3,727 women aged 18-25 years to receive Cervarix and 3,739 to a control group that received the hepatitis A vaccine; after 4 years, the control group also received Cervarix and exited the study. They were replaced by an unvaccinated control group of 2,836 women. The new control group and the original HPV vaccine group were followed for an additional 7 years.
In years 7-11 of the trial, the investigators found 9.2 additional cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) from HPV types not covered by Cervarix per 1,000 vaccinated women in comparison with unvaccinated participants. This corresponds to –71.2% negative vaccine efficacy against CIN2+ lesions of HPV types not covered by the vaccine.
There were 8.3 additional CIN3+ lesions from nontargeted HPV strains per 1,000 vaccinated women in comparison with unvaccinated participants, which corresponds to –135% negative vaccine efficacy.
Overall, however, there was a net benefit of vaccination, with 27 fewer CIN2+ lesions when all HPV genotypes – vaccine covered or not – were considered per 1,000 vaccinated women over the entire 11 years of follow-up.
There were also 8.7 fewer CIN3+ lesions across all genotypes per 1,000 vaccinated women, but the benefit was not statistically significant.
Among the study limits, the team was unable to evaluate the effect of clinical unmasking on cervical cancer, because women were treated for high-grade cervical lesions before cases could progress to cervical cancer.
The trial was funded by the National Cancer Institute and the National Institutes of Health Office of Research on Women’s Health. GlaxoSmithKline provided the Cervarix vaccine and supported aspects of the trial. Two authors are named inventors on U.S. government–owned HPV vaccine patents with expired licenses to GlaxoSmithKline and Merck. Dr. Steben is an adviser/speaker for many companies, including GlaxoSmithKline and Merck.
A version of this article first appeared on Medscape.com.
FROM THE LANCET ONCOLOGY
Could a type 2 diabetes drug tackle kidney stones?
than patients who received placebo during a median 1.5 years of treatment.
These findings are from an analysis of pooled data from phase 1-4 clinical trials of empagliflozin for blood glucose control in 15,081 patients with type 2 diabetes.
Priyadarshini Balasubramanian, MD, presented the study as a poster at the annual meeting of the Endocrine Society; the study also was published online in the Journal of Clinical Endocrinology & Metabolism.
The researchers acknowledge this was a retrospective, post-hoc analysis and that urolithiasis – a stone in the urinary tract, which includes nephrolithiasis, a kidney stone – was an adverse event, not a primary or secondary outcome.
Also, the stone composition, which might help explain how the drug may affect stone formation, is unknown.
Therefore, “dedicated randomized prospective clinical trials are needed to confirm these initial observations in patients both with and without type 2 diabetes,” said Dr. Balasubramanian, a clinical fellow in the section of endocrinology & metabolism, department of internal medicine at Yale University, New Haven, Conn.
However, “if this association is proven, empagliflozin may be used to decrease the risk of kidney stones at least in those with type 2 diabetes, but maybe also in those without diabetes,” Dr. Balasubramanian said in an interview.
Further trials are also needed to determine if this is a class effect, which is likely, she speculated, and to unravel the potential mechanism.
This is important because of the prevalence of kidney stones, which affect up to 15% of the general population and 15%-20% of patients with diabetes, she explained.
‘Provocative’ earlier findings
The current study was prompted by a recent observational study by Kasper B. Kristensen, MD, PhD, and colleagues.
Because SGLT2 inhibitors increase urinary glucose excretion through reduced renal reabsorption of glucose leading to osmotic diuresis and increased urinary flow, they hypothesized that these therapies “may reduce the risk of upper urinary tract stones (nephrolithiasis) by reducing the concentration of lithogenic substances in urine.”
Using data from Danish Health registries, they matched 12,325 individuals newly prescribed an SGLT2 inhibitor 1:1 with patients newly prescribed a glucagonlike peptide-1 (GLP1) agonist, another new class of drugs for treating type 2 diabetes.
They found a hazard ratio of 0.51 (95% confidence interval, 0.37-0.71) for incident nephrolithiasis and a hazard ratio of 0.68 (95% CI, 0.48-0.97) for recurrent nephrolithiasis for patients taking SGLT2 inhibitors versus GLP-1 agonists.
These findings are “striking,” according to Dr. Balasubramanian and colleagues. However, “these data, while provocative, were entirely retrospective and therefore possibly prone to bias,” they add.
Pooled data from 20 trials
The current study analyzed data from 20 randomized controlled trials of glycemic control in type 2 diabetes, in which 10,177 patients had received empagliflozin 10 mg or 25 mg and 4,904 patients had received placebo.
Most patients (46.5%) had participated in the EMPA-REG OUTCOMES trial, which also had the longest follow-up (2.6 years).
The researchers identified patients with a new stone from the urinary tract (including the kidney, ureter, and urethra). Patients had received either the study drug for a median of 543 days or placebo for a median of 549 days.
During treatment, 104 of 10,177 patients in the pooled empagliflozin groups and 79 of 4,904 patients in the pooled placebo groups developed a stone in the urinary tract.
This was equivalent to 0.63 new urinary-tract stones per 100 patient-years in the pooled empagliflozin groups versus 1.01 new urinary-tract stones per 100 patient-years in the pooled placebo groups.
The incidence rate ratio was 0.64 (95% CI, 0.48-0.86), in favor of empagliflozin.
When the analysis was restricted to new kidney stones, the results were similar: 75 of 10,177 patients in the pooled empagliflozin groups and 57 of 4,904 patients in the pooled placebo groups developed a kidney stone.
This was equivalent to 0.45 new kidney stones per 100 patient-years in the pooled empagliflozin groups versus 0.72 new kidney stones per 100 patient-years in the pooled placebo groups.
The IRR was 0.65 (95% CI, 0.46-0.92), in favor of empagliflozin.
Upcoming small RCT in adults without diabetes
Invited to comment on the new study, Dr. Kristensen said: “The reduced risk of SGLT2 inhibitors towards nephrolithiasis is now reported in at least two studies with different methodology, different populations, and different exposure and outcome definitions.”
“I agree that randomized clinical trials designed specifically to confirm these findings appear warranted,” added Dr. Kristensen, from the Institute of Public Health, Clinical Pharmacology, Pharmacy, and Environmental Medicine, University of Southern Denmark in Odense.
There is a need for studies in patients with and without diabetes, he added, especially ones that focus on prevention of nephrolithiasis in patients with kidney stone disease.
A new trial should shed further light on this.
Results are expected by the end of 2022 for SWEETSTONE (Impact of the SGLT2 Inhibitor Empagliflozin on Urinary Supersaturations in Kidney Stone Formers), a randomized, double-blind crossover exploratory study in 46 patients without diabetes.
This should provide preliminary data to “establish the relevance for larger trials assessing the prophylactic potential of empagliflozin in kidney stone disease,” according to an article on the trial protocol recently published in BMJ.
The trials included in the pooled dataset were funded by Boehringer Ingelheim or the Boehringer Ingelheim and Eli Lilly Diabetes Alliance. Dr. Balasubramanian has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
than patients who received placebo during a median 1.5 years of treatment.
These findings are from an analysis of pooled data from phase 1-4 clinical trials of empagliflozin for blood glucose control in 15,081 patients with type 2 diabetes.
Priyadarshini Balasubramanian, MD, presented the study as a poster at the annual meeting of the Endocrine Society; the study also was published online in the Journal of Clinical Endocrinology & Metabolism.
The researchers acknowledge this was a retrospective, post-hoc analysis and that urolithiasis – a stone in the urinary tract, which includes nephrolithiasis, a kidney stone – was an adverse event, not a primary or secondary outcome.
Also, the stone composition, which might help explain how the drug may affect stone formation, is unknown.
Therefore, “dedicated randomized prospective clinical trials are needed to confirm these initial observations in patients both with and without type 2 diabetes,” said Dr. Balasubramanian, a clinical fellow in the section of endocrinology & metabolism, department of internal medicine at Yale University, New Haven, Conn.
However, “if this association is proven, empagliflozin may be used to decrease the risk of kidney stones at least in those with type 2 diabetes, but maybe also in those without diabetes,” Dr. Balasubramanian said in an interview.
Further trials are also needed to determine if this is a class effect, which is likely, she speculated, and to unravel the potential mechanism.
This is important because of the prevalence of kidney stones, which affect up to 15% of the general population and 15%-20% of patients with diabetes, she explained.
‘Provocative’ earlier findings
The current study was prompted by a recent observational study by Kasper B. Kristensen, MD, PhD, and colleagues.
Because SGLT2 inhibitors increase urinary glucose excretion through reduced renal reabsorption of glucose leading to osmotic diuresis and increased urinary flow, they hypothesized that these therapies “may reduce the risk of upper urinary tract stones (nephrolithiasis) by reducing the concentration of lithogenic substances in urine.”
Using data from Danish Health registries, they matched 12,325 individuals newly prescribed an SGLT2 inhibitor 1:1 with patients newly prescribed a glucagonlike peptide-1 (GLP1) agonist, another new class of drugs for treating type 2 diabetes.
They found a hazard ratio of 0.51 (95% confidence interval, 0.37-0.71) for incident nephrolithiasis and a hazard ratio of 0.68 (95% CI, 0.48-0.97) for recurrent nephrolithiasis for patients taking SGLT2 inhibitors versus GLP-1 agonists.
These findings are “striking,” according to Dr. Balasubramanian and colleagues. However, “these data, while provocative, were entirely retrospective and therefore possibly prone to bias,” they add.
Pooled data from 20 trials
The current study analyzed data from 20 randomized controlled trials of glycemic control in type 2 diabetes, in which 10,177 patients had received empagliflozin 10 mg or 25 mg and 4,904 patients had received placebo.
Most patients (46.5%) had participated in the EMPA-REG OUTCOMES trial, which also had the longest follow-up (2.6 years).
The researchers identified patients with a new stone from the urinary tract (including the kidney, ureter, and urethra). Patients had received either the study drug for a median of 543 days or placebo for a median of 549 days.
During treatment, 104 of 10,177 patients in the pooled empagliflozin groups and 79 of 4,904 patients in the pooled placebo groups developed a stone in the urinary tract.
This was equivalent to 0.63 new urinary-tract stones per 100 patient-years in the pooled empagliflozin groups versus 1.01 new urinary-tract stones per 100 patient-years in the pooled placebo groups.
The incidence rate ratio was 0.64 (95% CI, 0.48-0.86), in favor of empagliflozin.
When the analysis was restricted to new kidney stones, the results were similar: 75 of 10,177 patients in the pooled empagliflozin groups and 57 of 4,904 patients in the pooled placebo groups developed a kidney stone.
This was equivalent to 0.45 new kidney stones per 100 patient-years in the pooled empagliflozin groups versus 0.72 new kidney stones per 100 patient-years in the pooled placebo groups.
The IRR was 0.65 (95% CI, 0.46-0.92), in favor of empagliflozin.
Upcoming small RCT in adults without diabetes
Invited to comment on the new study, Dr. Kristensen said: “The reduced risk of SGLT2 inhibitors towards nephrolithiasis is now reported in at least two studies with different methodology, different populations, and different exposure and outcome definitions.”
“I agree that randomized clinical trials designed specifically to confirm these findings appear warranted,” added Dr. Kristensen, from the Institute of Public Health, Clinical Pharmacology, Pharmacy, and Environmental Medicine, University of Southern Denmark in Odense.
There is a need for studies in patients with and without diabetes, he added, especially ones that focus on prevention of nephrolithiasis in patients with kidney stone disease.
A new trial should shed further light on this.
Results are expected by the end of 2022 for SWEETSTONE (Impact of the SGLT2 Inhibitor Empagliflozin on Urinary Supersaturations in Kidney Stone Formers), a randomized, double-blind crossover exploratory study in 46 patients without diabetes.
This should provide preliminary data to “establish the relevance for larger trials assessing the prophylactic potential of empagliflozin in kidney stone disease,” according to an article on the trial protocol recently published in BMJ.
The trials included in the pooled dataset were funded by Boehringer Ingelheim or the Boehringer Ingelheim and Eli Lilly Diabetes Alliance. Dr. Balasubramanian has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
than patients who received placebo during a median 1.5 years of treatment.
These findings are from an analysis of pooled data from phase 1-4 clinical trials of empagliflozin for blood glucose control in 15,081 patients with type 2 diabetes.
Priyadarshini Balasubramanian, MD, presented the study as a poster at the annual meeting of the Endocrine Society; the study also was published online in the Journal of Clinical Endocrinology & Metabolism.
The researchers acknowledge this was a retrospective, post-hoc analysis and that urolithiasis – a stone in the urinary tract, which includes nephrolithiasis, a kidney stone – was an adverse event, not a primary or secondary outcome.
Also, the stone composition, which might help explain how the drug may affect stone formation, is unknown.
Therefore, “dedicated randomized prospective clinical trials are needed to confirm these initial observations in patients both with and without type 2 diabetes,” said Dr. Balasubramanian, a clinical fellow in the section of endocrinology & metabolism, department of internal medicine at Yale University, New Haven, Conn.
However, “if this association is proven, empagliflozin may be used to decrease the risk of kidney stones at least in those with type 2 diabetes, but maybe also in those without diabetes,” Dr. Balasubramanian said in an interview.
Further trials are also needed to determine if this is a class effect, which is likely, she speculated, and to unravel the potential mechanism.
This is important because of the prevalence of kidney stones, which affect up to 15% of the general population and 15%-20% of patients with diabetes, she explained.
‘Provocative’ earlier findings
The current study was prompted by a recent observational study by Kasper B. Kristensen, MD, PhD, and colleagues.
Because SGLT2 inhibitors increase urinary glucose excretion through reduced renal reabsorption of glucose leading to osmotic diuresis and increased urinary flow, they hypothesized that these therapies “may reduce the risk of upper urinary tract stones (nephrolithiasis) by reducing the concentration of lithogenic substances in urine.”
Using data from Danish Health registries, they matched 12,325 individuals newly prescribed an SGLT2 inhibitor 1:1 with patients newly prescribed a glucagonlike peptide-1 (GLP1) agonist, another new class of drugs for treating type 2 diabetes.
They found a hazard ratio of 0.51 (95% confidence interval, 0.37-0.71) for incident nephrolithiasis and a hazard ratio of 0.68 (95% CI, 0.48-0.97) for recurrent nephrolithiasis for patients taking SGLT2 inhibitors versus GLP-1 agonists.
These findings are “striking,” according to Dr. Balasubramanian and colleagues. However, “these data, while provocative, were entirely retrospective and therefore possibly prone to bias,” they add.
Pooled data from 20 trials
The current study analyzed data from 20 randomized controlled trials of glycemic control in type 2 diabetes, in which 10,177 patients had received empagliflozin 10 mg or 25 mg and 4,904 patients had received placebo.
Most patients (46.5%) had participated in the EMPA-REG OUTCOMES trial, which also had the longest follow-up (2.6 years).
The researchers identified patients with a new stone from the urinary tract (including the kidney, ureter, and urethra). Patients had received either the study drug for a median of 543 days or placebo for a median of 549 days.
During treatment, 104 of 10,177 patients in the pooled empagliflozin groups and 79 of 4,904 patients in the pooled placebo groups developed a stone in the urinary tract.
This was equivalent to 0.63 new urinary-tract stones per 100 patient-years in the pooled empagliflozin groups versus 1.01 new urinary-tract stones per 100 patient-years in the pooled placebo groups.
The incidence rate ratio was 0.64 (95% CI, 0.48-0.86), in favor of empagliflozin.
When the analysis was restricted to new kidney stones, the results were similar: 75 of 10,177 patients in the pooled empagliflozin groups and 57 of 4,904 patients in the pooled placebo groups developed a kidney stone.
This was equivalent to 0.45 new kidney stones per 100 patient-years in the pooled empagliflozin groups versus 0.72 new kidney stones per 100 patient-years in the pooled placebo groups.
The IRR was 0.65 (95% CI, 0.46-0.92), in favor of empagliflozin.
Upcoming small RCT in adults without diabetes
Invited to comment on the new study, Dr. Kristensen said: “The reduced risk of SGLT2 inhibitors towards nephrolithiasis is now reported in at least two studies with different methodology, different populations, and different exposure and outcome definitions.”
“I agree that randomized clinical trials designed specifically to confirm these findings appear warranted,” added Dr. Kristensen, from the Institute of Public Health, Clinical Pharmacology, Pharmacy, and Environmental Medicine, University of Southern Denmark in Odense.
There is a need for studies in patients with and without diabetes, he added, especially ones that focus on prevention of nephrolithiasis in patients with kidney stone disease.
A new trial should shed further light on this.
Results are expected by the end of 2022 for SWEETSTONE (Impact of the SGLT2 Inhibitor Empagliflozin on Urinary Supersaturations in Kidney Stone Formers), a randomized, double-blind crossover exploratory study in 46 patients without diabetes.
This should provide preliminary data to “establish the relevance for larger trials assessing the prophylactic potential of empagliflozin in kidney stone disease,” according to an article on the trial protocol recently published in BMJ.
The trials included in the pooled dataset were funded by Boehringer Ingelheim or the Boehringer Ingelheim and Eli Lilly Diabetes Alliance. Dr. Balasubramanian has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ENDO 2022
What’s the best time of day to exercise? It depends on your goals
For most of us, the “best” time of day to work out is simple: When we can.
Maybe that’s before or after work. Or when the gym offers free daycare. Or when our favorite instructor teaches our favorite class.
That’s why we call it a “routine.” And if the results are the same, it’s hard to imagine changing it up.
But what if the results aren’t the same?
They may not be, according to a new study from a research team at Skidmore College in Saratoga Springs, N.Y.
Women who worked out in the morning lost more fat, while those who trained in the evening gained more upper-body strength and power. As for men, the performance improvements were similar no matter when they exercised. But those who did so in the evening had a significant drop in blood pressure, among other benefits.
The study is part of a growing body of research showing different results for different times of day among different populations. As it turns out, when you exercise can ultimately have a big effect, not just on strength and fat loss, but also heart health, mood, and quality of sleep.
An accidental discovery
The original goal of the Skidmore study was to test a unique fitness program with a group of healthy, fit, and extremely active adults in early middle age.
The program includes four workouts a week, each with a different focus: strength, steady-pace endurance, high-intensity intervals, and flexibility (traditional stretching combined with yoga and Pilates exercises).
But because the group was so large – 27 women and 20 men completed the 3-month program – they had to split them into morning and evening workout groups.
It wasn’t until researchers looked at the results that they saw the differences between morning and evening exercise, says lead author Paul Arciero, PhD.
Dr. Arciero stressed that participants in every group got leaner and stronger. But the women who worked out in the morning got much bigger reductions in body fat and body-fat percentage than the evening group. Meanwhile, women in the evening group got much bigger gains in upper-body strength, power, and muscular endurance than their morning counterparts.
Among the men, the evening group had significantly larger improvements in blood pressure, cholesterol levels, and the percentage of fat they burned for energy, along with a bigger drop in feelings of fatigue.
Strategic timing for powerful results
Some of these findings are consistent with previous research. For example, a study published in 2021 showed that the ability to exert high effort and express strength and power peaks in the late afternoon, about the same time that your core body temperature is at its highest point.
On the other hand, you’ll probably perform better in the morning when the activity requires a lot of skill and coordination or depends on strategic decision-making.
The findings apply to both men and women.
Performance aside, exercise timing might offer strong health benefits for men with type 2 diabetes, or at high risk for it.
A study showed that men who exercised between 3 p.m. and 6 p.m. saw dramatic improvements in blood sugar management and insulin sensitivity, compared to a group that worked out between 8 a.m. and 10 a.m.
They also lost more fat during the 12-week program, even though they were doing the exact same workouts.
Train consistently, sleep well
When you exercise can affect your sleep quality in many ways, said neuroscientist Jennifer Heisz, PhD, of McMaster University, Hamilton, Ont.
First, she said, “exercise helps you fall asleep faster and sleep deeper at night.” (The only exception is if you exercise so intensely or so close to bedtime that your heart rate is still elevated.)
Second, “exercising at a consistent time every day helps regulate the body’s circadian rhythms.” It doesn’t matter if the exercise is in the morning, evening, or anywhere in between. As long as it’s predictable, it will help you fall asleep and wake up at the same times.
Outdoor exercise is even better, she said. The sun is the most powerful regulator of the circadian clock and works in tandem with physical activity.
Third, exercising at specific times can help you overcome jet lag or adjust to an earlier or later shift at work.
“Exercising at 7 a.m. or between 1 and 4 p.m. helps your circadian clock to ‘fall back’ in time, making it easier to wake up earlier,” Dr. Heisz said. If you need to train your body to wake up later in the morning, try working out between 7 p.m. and 10 p.m.
All exercise is good, but the right timing can make it even better
“The best time to exercise is when you can fit it in,” Dr. Arciero said. “You’ve got to choose the time that fits your lifestyle best.”
But context matters, he noted.
“For someone needing to achieve an improvement in their risk for cardiometabolic disease,” his study shows an advantage to working out later in the day, especially for men. If you’re more focused on building upper-body strength and power, you’ll probably get better results from training in the afternoon or evening.
And for fat loss, the Skidmore study shows better results for women who did morning workouts.
And if you’re still not sure? Try sleeping on it – preferably after your workout.
A version of this article first appeared on WebMD.com.
For most of us, the “best” time of day to work out is simple: When we can.
Maybe that’s before or after work. Or when the gym offers free daycare. Or when our favorite instructor teaches our favorite class.
That’s why we call it a “routine.” And if the results are the same, it’s hard to imagine changing it up.
But what if the results aren’t the same?
They may not be, according to a new study from a research team at Skidmore College in Saratoga Springs, N.Y.
Women who worked out in the morning lost more fat, while those who trained in the evening gained more upper-body strength and power. As for men, the performance improvements were similar no matter when they exercised. But those who did so in the evening had a significant drop in blood pressure, among other benefits.
The study is part of a growing body of research showing different results for different times of day among different populations. As it turns out, when you exercise can ultimately have a big effect, not just on strength and fat loss, but also heart health, mood, and quality of sleep.
An accidental discovery
The original goal of the Skidmore study was to test a unique fitness program with a group of healthy, fit, and extremely active adults in early middle age.
The program includes four workouts a week, each with a different focus: strength, steady-pace endurance, high-intensity intervals, and flexibility (traditional stretching combined with yoga and Pilates exercises).
But because the group was so large – 27 women and 20 men completed the 3-month program – they had to split them into morning and evening workout groups.
It wasn’t until researchers looked at the results that they saw the differences between morning and evening exercise, says lead author Paul Arciero, PhD.
Dr. Arciero stressed that participants in every group got leaner and stronger. But the women who worked out in the morning got much bigger reductions in body fat and body-fat percentage than the evening group. Meanwhile, women in the evening group got much bigger gains in upper-body strength, power, and muscular endurance than their morning counterparts.
Among the men, the evening group had significantly larger improvements in blood pressure, cholesterol levels, and the percentage of fat they burned for energy, along with a bigger drop in feelings of fatigue.
Strategic timing for powerful results
Some of these findings are consistent with previous research. For example, a study published in 2021 showed that the ability to exert high effort and express strength and power peaks in the late afternoon, about the same time that your core body temperature is at its highest point.
On the other hand, you’ll probably perform better in the morning when the activity requires a lot of skill and coordination or depends on strategic decision-making.
The findings apply to both men and women.
Performance aside, exercise timing might offer strong health benefits for men with type 2 diabetes, or at high risk for it.
A study showed that men who exercised between 3 p.m. and 6 p.m. saw dramatic improvements in blood sugar management and insulin sensitivity, compared to a group that worked out between 8 a.m. and 10 a.m.
They also lost more fat during the 12-week program, even though they were doing the exact same workouts.
Train consistently, sleep well
When you exercise can affect your sleep quality in many ways, said neuroscientist Jennifer Heisz, PhD, of McMaster University, Hamilton, Ont.
First, she said, “exercise helps you fall asleep faster and sleep deeper at night.” (The only exception is if you exercise so intensely or so close to bedtime that your heart rate is still elevated.)
Second, “exercising at a consistent time every day helps regulate the body’s circadian rhythms.” It doesn’t matter if the exercise is in the morning, evening, or anywhere in between. As long as it’s predictable, it will help you fall asleep and wake up at the same times.
Outdoor exercise is even better, she said. The sun is the most powerful regulator of the circadian clock and works in tandem with physical activity.
Third, exercising at specific times can help you overcome jet lag or adjust to an earlier or later shift at work.
“Exercising at 7 a.m. or between 1 and 4 p.m. helps your circadian clock to ‘fall back’ in time, making it easier to wake up earlier,” Dr. Heisz said. If you need to train your body to wake up later in the morning, try working out between 7 p.m. and 10 p.m.
All exercise is good, but the right timing can make it even better
“The best time to exercise is when you can fit it in,” Dr. Arciero said. “You’ve got to choose the time that fits your lifestyle best.”
But context matters, he noted.
“For someone needing to achieve an improvement in their risk for cardiometabolic disease,” his study shows an advantage to working out later in the day, especially for men. If you’re more focused on building upper-body strength and power, you’ll probably get better results from training in the afternoon or evening.
And for fat loss, the Skidmore study shows better results for women who did morning workouts.
And if you’re still not sure? Try sleeping on it – preferably after your workout.
A version of this article first appeared on WebMD.com.
For most of us, the “best” time of day to work out is simple: When we can.
Maybe that’s before or after work. Or when the gym offers free daycare. Or when our favorite instructor teaches our favorite class.
That’s why we call it a “routine.” And if the results are the same, it’s hard to imagine changing it up.
But what if the results aren’t the same?
They may not be, according to a new study from a research team at Skidmore College in Saratoga Springs, N.Y.
Women who worked out in the morning lost more fat, while those who trained in the evening gained more upper-body strength and power. As for men, the performance improvements were similar no matter when they exercised. But those who did so in the evening had a significant drop in blood pressure, among other benefits.
The study is part of a growing body of research showing different results for different times of day among different populations. As it turns out, when you exercise can ultimately have a big effect, not just on strength and fat loss, but also heart health, mood, and quality of sleep.
An accidental discovery
The original goal of the Skidmore study was to test a unique fitness program with a group of healthy, fit, and extremely active adults in early middle age.
The program includes four workouts a week, each with a different focus: strength, steady-pace endurance, high-intensity intervals, and flexibility (traditional stretching combined with yoga and Pilates exercises).
But because the group was so large – 27 women and 20 men completed the 3-month program – they had to split them into morning and evening workout groups.
It wasn’t until researchers looked at the results that they saw the differences between morning and evening exercise, says lead author Paul Arciero, PhD.
Dr. Arciero stressed that participants in every group got leaner and stronger. But the women who worked out in the morning got much bigger reductions in body fat and body-fat percentage than the evening group. Meanwhile, women in the evening group got much bigger gains in upper-body strength, power, and muscular endurance than their morning counterparts.
Among the men, the evening group had significantly larger improvements in blood pressure, cholesterol levels, and the percentage of fat they burned for energy, along with a bigger drop in feelings of fatigue.
Strategic timing for powerful results
Some of these findings are consistent with previous research. For example, a study published in 2021 showed that the ability to exert high effort and express strength and power peaks in the late afternoon, about the same time that your core body temperature is at its highest point.
On the other hand, you’ll probably perform better in the morning when the activity requires a lot of skill and coordination or depends on strategic decision-making.
The findings apply to both men and women.
Performance aside, exercise timing might offer strong health benefits for men with type 2 diabetes, or at high risk for it.
A study showed that men who exercised between 3 p.m. and 6 p.m. saw dramatic improvements in blood sugar management and insulin sensitivity, compared to a group that worked out between 8 a.m. and 10 a.m.
They also lost more fat during the 12-week program, even though they were doing the exact same workouts.
Train consistently, sleep well
When you exercise can affect your sleep quality in many ways, said neuroscientist Jennifer Heisz, PhD, of McMaster University, Hamilton, Ont.
First, she said, “exercise helps you fall asleep faster and sleep deeper at night.” (The only exception is if you exercise so intensely or so close to bedtime that your heart rate is still elevated.)
Second, “exercising at a consistent time every day helps regulate the body’s circadian rhythms.” It doesn’t matter if the exercise is in the morning, evening, or anywhere in between. As long as it’s predictable, it will help you fall asleep and wake up at the same times.
Outdoor exercise is even better, she said. The sun is the most powerful regulator of the circadian clock and works in tandem with physical activity.
Third, exercising at specific times can help you overcome jet lag or adjust to an earlier or later shift at work.
“Exercising at 7 a.m. or between 1 and 4 p.m. helps your circadian clock to ‘fall back’ in time, making it easier to wake up earlier,” Dr. Heisz said. If you need to train your body to wake up later in the morning, try working out between 7 p.m. and 10 p.m.
All exercise is good, but the right timing can make it even better
“The best time to exercise is when you can fit it in,” Dr. Arciero said. “You’ve got to choose the time that fits your lifestyle best.”
But context matters, he noted.
“For someone needing to achieve an improvement in their risk for cardiometabolic disease,” his study shows an advantage to working out later in the day, especially for men. If you’re more focused on building upper-body strength and power, you’ll probably get better results from training in the afternoon or evening.
And for fat loss, the Skidmore study shows better results for women who did morning workouts.
And if you’re still not sure? Try sleeping on it – preferably after your workout.
A version of this article first appeared on WebMD.com.
FROM FRONTIERS IN PHYSIOLOGY
Breast cancer less common in Black women, so why do more die?
Although breast cancer occurs less frequently in Black women, compared with White women, they have a much higher risk of dying from the disease.
In the United States, age-adjusted breast cancer mortality between 2014 and 2018 was approximately 40% higher among Black women than among non-Hispanic White women.
This mortality gap likely reflects the fact that Black women face substantial barriers to obtaining timely, high-quality medical care, compared with White women, lead author Ismail Jatoi, MD, PhD, University of Texas Health Science Center, San Antonio, and colleagues suggest in a recent opinion piece.
The article was published online in The New England Journal of Medicine.
When the team examined the statistics for breast cancer mortality, they found a surprise: The mortality gap between races only dates back to 1980.
Prior to 1980, mortality from breast cancer among Black women was slightly lower than White women, Dr. Jatoi and colleagues point out.
That year was a turning point in breast cancer management, as in 1980, both mammography screening and adjuvant endocrine therapy became available.
This was also when the mortality gap between the races started to show up.
It was disparities in access to the two new interventions that precipitated the divergence, as the authors suggest. Why this occurred is fairly self-evident, they comment.
“Black women are more likely than White women to lack health insurance or to have inadequate coverage, which has limited their access to mammography screening and adversely affected therapeutic decisionmaking,” researchers point out.
Moreover, both mammography screening and endocrine therapy primarily benefit patients with hormone receptor (HR)-positive breast cancer, which is equally common in Black and White patients. However, Black women have a 65% higher rate of HR-negative cancers than White women – and HR-negative tumors are often detected during the interval between mammography screening exams as palpable cancers.
Black women also have an 81% higher rate of triple-negative breast cancer, so they have benefited less from mammography screening and adjuvant endocrine therapy, both of which favor the detection and treatment of HR-positive breast cancer, the authors emphasize.
Some have suggested that the excess HR-negative breast cancer in Black women might be explained by hereditary factors. Yet as Dr. Jatoi and colleagues point out, the incidence of HR-negative breast cancer has actually been falling across all races in the United States since 1992.
However, the declines have been slower among Black women, and reductions in its incidence have been smaller among White women living in less affluent regions of the United States compared with White women from more affluent regions.
These patterns suggest that social determinants of health influence not only access to and quality of health care but also the development of HR-negative breast cancers, as the authors observe.
“If all people with breast cancer benefited equally from effective medical interventions, racial differences in mortality for individual tumor subtypes would largely reflect differences in incidence,” Dr. Jatoi and colleagues continue.
Yet the statistics show that the substantial racial disparities in mortality for both HR-positive and HR-negative cancers between Black and White women cannot be explained by differences in the incidence of either tumor alone, they write.
For example, mortality for HR-positive breast cancer is 19% higher among Black women than among White women, yet the incidence of HR-positive breast cancer is 22% lower among Black women.
Similarly, mortality from HR-negative breast cancer is over twice as high among Black women as it is among White women – a substantially larger disparity, compared with the 65% relative difference in the incidence of HR-negative breast cancer between the two races.
“Universal health care coverage could reduce disparities in treatment for cancers of all subtypes, including triple-negative breast cancer,” Dr. Jatoi and colleagues emphasize.
“Ensuring universal access to high-quality medical care can substantially narrow the racial disparity in U.S. breast-cancer mortality,” they conclude.
The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Although breast cancer occurs less frequently in Black women, compared with White women, they have a much higher risk of dying from the disease.
In the United States, age-adjusted breast cancer mortality between 2014 and 2018 was approximately 40% higher among Black women than among non-Hispanic White women.
This mortality gap likely reflects the fact that Black women face substantial barriers to obtaining timely, high-quality medical care, compared with White women, lead author Ismail Jatoi, MD, PhD, University of Texas Health Science Center, San Antonio, and colleagues suggest in a recent opinion piece.
The article was published online in The New England Journal of Medicine.
When the team examined the statistics for breast cancer mortality, they found a surprise: The mortality gap between races only dates back to 1980.
Prior to 1980, mortality from breast cancer among Black women was slightly lower than White women, Dr. Jatoi and colleagues point out.
That year was a turning point in breast cancer management, as in 1980, both mammography screening and adjuvant endocrine therapy became available.
This was also when the mortality gap between the races started to show up.
It was disparities in access to the two new interventions that precipitated the divergence, as the authors suggest. Why this occurred is fairly self-evident, they comment.
“Black women are more likely than White women to lack health insurance or to have inadequate coverage, which has limited their access to mammography screening and adversely affected therapeutic decisionmaking,” researchers point out.
Moreover, both mammography screening and endocrine therapy primarily benefit patients with hormone receptor (HR)-positive breast cancer, which is equally common in Black and White patients. However, Black women have a 65% higher rate of HR-negative cancers than White women – and HR-negative tumors are often detected during the interval between mammography screening exams as palpable cancers.
Black women also have an 81% higher rate of triple-negative breast cancer, so they have benefited less from mammography screening and adjuvant endocrine therapy, both of which favor the detection and treatment of HR-positive breast cancer, the authors emphasize.
Some have suggested that the excess HR-negative breast cancer in Black women might be explained by hereditary factors. Yet as Dr. Jatoi and colleagues point out, the incidence of HR-negative breast cancer has actually been falling across all races in the United States since 1992.
However, the declines have been slower among Black women, and reductions in its incidence have been smaller among White women living in less affluent regions of the United States compared with White women from more affluent regions.
These patterns suggest that social determinants of health influence not only access to and quality of health care but also the development of HR-negative breast cancers, as the authors observe.
“If all people with breast cancer benefited equally from effective medical interventions, racial differences in mortality for individual tumor subtypes would largely reflect differences in incidence,” Dr. Jatoi and colleagues continue.
Yet the statistics show that the substantial racial disparities in mortality for both HR-positive and HR-negative cancers between Black and White women cannot be explained by differences in the incidence of either tumor alone, they write.
For example, mortality for HR-positive breast cancer is 19% higher among Black women than among White women, yet the incidence of HR-positive breast cancer is 22% lower among Black women.
Similarly, mortality from HR-negative breast cancer is over twice as high among Black women as it is among White women – a substantially larger disparity, compared with the 65% relative difference in the incidence of HR-negative breast cancer between the two races.
“Universal health care coverage could reduce disparities in treatment for cancers of all subtypes, including triple-negative breast cancer,” Dr. Jatoi and colleagues emphasize.
“Ensuring universal access to high-quality medical care can substantially narrow the racial disparity in U.S. breast-cancer mortality,” they conclude.
The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Although breast cancer occurs less frequently in Black women, compared with White women, they have a much higher risk of dying from the disease.
In the United States, age-adjusted breast cancer mortality between 2014 and 2018 was approximately 40% higher among Black women than among non-Hispanic White women.
This mortality gap likely reflects the fact that Black women face substantial barriers to obtaining timely, high-quality medical care, compared with White women, lead author Ismail Jatoi, MD, PhD, University of Texas Health Science Center, San Antonio, and colleagues suggest in a recent opinion piece.
The article was published online in The New England Journal of Medicine.
When the team examined the statistics for breast cancer mortality, they found a surprise: The mortality gap between races only dates back to 1980.
Prior to 1980, mortality from breast cancer among Black women was slightly lower than White women, Dr. Jatoi and colleagues point out.
That year was a turning point in breast cancer management, as in 1980, both mammography screening and adjuvant endocrine therapy became available.
This was also when the mortality gap between the races started to show up.
It was disparities in access to the two new interventions that precipitated the divergence, as the authors suggest. Why this occurred is fairly self-evident, they comment.
“Black women are more likely than White women to lack health insurance or to have inadequate coverage, which has limited their access to mammography screening and adversely affected therapeutic decisionmaking,” researchers point out.
Moreover, both mammography screening and endocrine therapy primarily benefit patients with hormone receptor (HR)-positive breast cancer, which is equally common in Black and White patients. However, Black women have a 65% higher rate of HR-negative cancers than White women – and HR-negative tumors are often detected during the interval between mammography screening exams as palpable cancers.
Black women also have an 81% higher rate of triple-negative breast cancer, so they have benefited less from mammography screening and adjuvant endocrine therapy, both of which favor the detection and treatment of HR-positive breast cancer, the authors emphasize.
Some have suggested that the excess HR-negative breast cancer in Black women might be explained by hereditary factors. Yet as Dr. Jatoi and colleagues point out, the incidence of HR-negative breast cancer has actually been falling across all races in the United States since 1992.
However, the declines have been slower among Black women, and reductions in its incidence have been smaller among White women living in less affluent regions of the United States compared with White women from more affluent regions.
These patterns suggest that social determinants of health influence not only access to and quality of health care but also the development of HR-negative breast cancers, as the authors observe.
“If all people with breast cancer benefited equally from effective medical interventions, racial differences in mortality for individual tumor subtypes would largely reflect differences in incidence,” Dr. Jatoi and colleagues continue.
Yet the statistics show that the substantial racial disparities in mortality for both HR-positive and HR-negative cancers between Black and White women cannot be explained by differences in the incidence of either tumor alone, they write.
For example, mortality for HR-positive breast cancer is 19% higher among Black women than among White women, yet the incidence of HR-positive breast cancer is 22% lower among Black women.
Similarly, mortality from HR-negative breast cancer is over twice as high among Black women as it is among White women – a substantially larger disparity, compared with the 65% relative difference in the incidence of HR-negative breast cancer between the two races.
“Universal health care coverage could reduce disparities in treatment for cancers of all subtypes, including triple-negative breast cancer,” Dr. Jatoi and colleagues emphasize.
“Ensuring universal access to high-quality medical care can substantially narrow the racial disparity in U.S. breast-cancer mortality,” they conclude.
The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
To predict mortality, you need a leg to stand on
Storks everywhere, rejoice.
According to the findings, people in middle age and older who couldn’t perform the 10-second standing test were nearly four times as likely to die of any cause – heart attacks, strokes, cancer, and more – in the coming years than those who could, well, stand the test of time.
Claudio Gil Araújo, MD, PhD, research director of the Exercise Medicine Clinic-CLINIMEX in Rio de Janeiro, who led the study, called the results “awesome!”
“As a physician who has worked with cardiac patients for over 4 decades, I was very impressed in finding out that, for those between 51 and 75 years of age, it is riskier for survival to not complete the 10-second one-leg standing test than to have been diagnosed as having coronary artery disease or in being hypertensive” or having abnormal cholesterol, Dr. Araújo said in an interview.
The findings appeared in the British Journal of Sports Medicine.
Researchers have known for at least a half century that balance and mortality are connected. One reason is falls: Worldwide, nearly 700,000 people each year die as a result of a fall, according to the World Health Organization, and more than 37 million falls annually require medical attention. But as the new study indicates, falls aren’t the only problem.
Dr. Araújo and colleagues have been working on ways to improve balance and strength as people age. In addition to the one-legged standing test, they have previously shown that the ability to rise from a sitting position on the floor is also a strong predictor of longevity.
For the new study, the researchers assessed 1,702 people in Brazil (68% men) aged 51-75 years who had been participating in an ongoing exercise study that began there in 1994.
Three tries to succeed
Starting in 2008, the team introduced the standing test, which involves balancing on one leg and placing the other foot at the back weight-bearing limb for support. People get three tries to maintain that posture for at least 10 seconds.
Not surprisingly, the ability to perform the test dropped with age. Although 20% of people in the study overall were unable to stand on one leg for 10 seconds, that figure rose to about 70% for those aged 76-80 years, and nearly 90% for those aged 81-85, according to the researchers. Of the two dozen 85-year-olds in the study, only two were able to complete the standing test, Dr. Araújo told this news organization.
At roughly age 70, half of people could not complete the 10-second test.
Over an average of 7 years of follow-up, 17.5% of people who could not manage the 10-second stand had died, compared with 4.5% of those who could last that long, the study found.
After accounting for age and many other risk factors, such as diabetes, body mass index, and a history of heart disease, people who were unable to complete the standing test were 84% more likely to die from any cause over the study period than their peers with better one-legged static balance (95% confidence interval, 1.23-2.78; P < .001).
The researchers said their study was limited by its lack of diversity – all the participants were relatively affluent Brazilians – and the inability to control for a history of falls and physical activity. But they said the size of the cohort, the long follow-up period, and their use of sophistical statistical methods helped mitigate the shortcomings.
Although low aerobic fitness is a marker of poor health, much less attention has been paid to nonaerobic fitness – things like balance, flexibility, and muscle strength and power, Dr. Araújo said.
“We are accumulating evidence that these three components of nonaerobic physical fitness are potentially relevant for good health and even more relevant for survival in older subjects,” Dr. Araújo said. Poor nonaerobic fitness, which is normally but not always associated with a sedentary lifestyle, “is the background of most cases of frailty, and being frail is strongly associated with a poor quality of life, less physical activity and exercise, and so on. It’s a bad circle.”
Dr. Araújo’s group has been using the standing test in their clinic for more than a dozen years and have seen gains in their patients. “Patients are often unaware that they are unable to sustain 10 seconds standing one legged. After this simple evaluation, they are much more prone to engage in balance training,” he said.
For now, the researchers don’t have data to show that improving static balance or performance on the standing test can affect survival, a “quite attractive” possibility, he added. But balance can be substantially improved through training.
“After only a few sessions, an improvement can be perceived, and this influences quality of life,” Dr. Araújo said. “And this is exactly what we do with the patients that we evaluated and for those that are attending our medically supervised exercise program.”
George A. Kuchel, MD, CM, FRCP, professor and Travelers Chair in Geriatrics and Gerontology at the University of Connecticut, Farmington, called the research “well done” and said the results “make perfect sense, since we have known for a long time that muscle strength is an important determinant of health, independence, and survival.”
Identifying frail patients quickly, simply, and reliably in the clinical setting is a pressing need, Dr. Kuchel, director of the UConn Center on Aging, said in an interview. The 10-second test “has considerable appeal” for this purpose.
“This could be, or rather should be, of great interest to all busy clinicians who see older adults in primary care or consultative capacities,” Dr. Kuchel added. “I hate to be nihilistic as regards what is possible in the context of really busy clinical practices, but even the minute or so that this takes to do may very well be too much for busy clinicians to do.”
Dr. Araújo and Dr. Kuchel reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Storks everywhere, rejoice.
According to the findings, people in middle age and older who couldn’t perform the 10-second standing test were nearly four times as likely to die of any cause – heart attacks, strokes, cancer, and more – in the coming years than those who could, well, stand the test of time.
Claudio Gil Araújo, MD, PhD, research director of the Exercise Medicine Clinic-CLINIMEX in Rio de Janeiro, who led the study, called the results “awesome!”
“As a physician who has worked with cardiac patients for over 4 decades, I was very impressed in finding out that, for those between 51 and 75 years of age, it is riskier for survival to not complete the 10-second one-leg standing test than to have been diagnosed as having coronary artery disease or in being hypertensive” or having abnormal cholesterol, Dr. Araújo said in an interview.
The findings appeared in the British Journal of Sports Medicine.
Researchers have known for at least a half century that balance and mortality are connected. One reason is falls: Worldwide, nearly 700,000 people each year die as a result of a fall, according to the World Health Organization, and more than 37 million falls annually require medical attention. But as the new study indicates, falls aren’t the only problem.
Dr. Araújo and colleagues have been working on ways to improve balance and strength as people age. In addition to the one-legged standing test, they have previously shown that the ability to rise from a sitting position on the floor is also a strong predictor of longevity.
For the new study, the researchers assessed 1,702 people in Brazil (68% men) aged 51-75 years who had been participating in an ongoing exercise study that began there in 1994.
Three tries to succeed
Starting in 2008, the team introduced the standing test, which involves balancing on one leg and placing the other foot at the back weight-bearing limb for support. People get three tries to maintain that posture for at least 10 seconds.
Not surprisingly, the ability to perform the test dropped with age. Although 20% of people in the study overall were unable to stand on one leg for 10 seconds, that figure rose to about 70% for those aged 76-80 years, and nearly 90% for those aged 81-85, according to the researchers. Of the two dozen 85-year-olds in the study, only two were able to complete the standing test, Dr. Araújo told this news organization.
At roughly age 70, half of people could not complete the 10-second test.
Over an average of 7 years of follow-up, 17.5% of people who could not manage the 10-second stand had died, compared with 4.5% of those who could last that long, the study found.
After accounting for age and many other risk factors, such as diabetes, body mass index, and a history of heart disease, people who were unable to complete the standing test were 84% more likely to die from any cause over the study period than their peers with better one-legged static balance (95% confidence interval, 1.23-2.78; P < .001).
The researchers said their study was limited by its lack of diversity – all the participants were relatively affluent Brazilians – and the inability to control for a history of falls and physical activity. But they said the size of the cohort, the long follow-up period, and their use of sophistical statistical methods helped mitigate the shortcomings.
Although low aerobic fitness is a marker of poor health, much less attention has been paid to nonaerobic fitness – things like balance, flexibility, and muscle strength and power, Dr. Araújo said.
“We are accumulating evidence that these three components of nonaerobic physical fitness are potentially relevant for good health and even more relevant for survival in older subjects,” Dr. Araújo said. Poor nonaerobic fitness, which is normally but not always associated with a sedentary lifestyle, “is the background of most cases of frailty, and being frail is strongly associated with a poor quality of life, less physical activity and exercise, and so on. It’s a bad circle.”
Dr. Araújo’s group has been using the standing test in their clinic for more than a dozen years and have seen gains in their patients. “Patients are often unaware that they are unable to sustain 10 seconds standing one legged. After this simple evaluation, they are much more prone to engage in balance training,” he said.
For now, the researchers don’t have data to show that improving static balance or performance on the standing test can affect survival, a “quite attractive” possibility, he added. But balance can be substantially improved through training.
“After only a few sessions, an improvement can be perceived, and this influences quality of life,” Dr. Araújo said. “And this is exactly what we do with the patients that we evaluated and for those that are attending our medically supervised exercise program.”
George A. Kuchel, MD, CM, FRCP, professor and Travelers Chair in Geriatrics and Gerontology at the University of Connecticut, Farmington, called the research “well done” and said the results “make perfect sense, since we have known for a long time that muscle strength is an important determinant of health, independence, and survival.”
Identifying frail patients quickly, simply, and reliably in the clinical setting is a pressing need, Dr. Kuchel, director of the UConn Center on Aging, said in an interview. The 10-second test “has considerable appeal” for this purpose.
“This could be, or rather should be, of great interest to all busy clinicians who see older adults in primary care or consultative capacities,” Dr. Kuchel added. “I hate to be nihilistic as regards what is possible in the context of really busy clinical practices, but even the minute or so that this takes to do may very well be too much for busy clinicians to do.”
Dr. Araújo and Dr. Kuchel reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Storks everywhere, rejoice.
According to the findings, people in middle age and older who couldn’t perform the 10-second standing test were nearly four times as likely to die of any cause – heart attacks, strokes, cancer, and more – in the coming years than those who could, well, stand the test of time.
Claudio Gil Araújo, MD, PhD, research director of the Exercise Medicine Clinic-CLINIMEX in Rio de Janeiro, who led the study, called the results “awesome!”
“As a physician who has worked with cardiac patients for over 4 decades, I was very impressed in finding out that, for those between 51 and 75 years of age, it is riskier for survival to not complete the 10-second one-leg standing test than to have been diagnosed as having coronary artery disease or in being hypertensive” or having abnormal cholesterol, Dr. Araújo said in an interview.
The findings appeared in the British Journal of Sports Medicine.
Researchers have known for at least a half century that balance and mortality are connected. One reason is falls: Worldwide, nearly 700,000 people each year die as a result of a fall, according to the World Health Organization, and more than 37 million falls annually require medical attention. But as the new study indicates, falls aren’t the only problem.
Dr. Araújo and colleagues have been working on ways to improve balance and strength as people age. In addition to the one-legged standing test, they have previously shown that the ability to rise from a sitting position on the floor is also a strong predictor of longevity.
For the new study, the researchers assessed 1,702 people in Brazil (68% men) aged 51-75 years who had been participating in an ongoing exercise study that began there in 1994.
Three tries to succeed
Starting in 2008, the team introduced the standing test, which involves balancing on one leg and placing the other foot at the back weight-bearing limb for support. People get three tries to maintain that posture for at least 10 seconds.
Not surprisingly, the ability to perform the test dropped with age. Although 20% of people in the study overall were unable to stand on one leg for 10 seconds, that figure rose to about 70% for those aged 76-80 years, and nearly 90% for those aged 81-85, according to the researchers. Of the two dozen 85-year-olds in the study, only two were able to complete the standing test, Dr. Araújo told this news organization.
At roughly age 70, half of people could not complete the 10-second test.
Over an average of 7 years of follow-up, 17.5% of people who could not manage the 10-second stand had died, compared with 4.5% of those who could last that long, the study found.
After accounting for age and many other risk factors, such as diabetes, body mass index, and a history of heart disease, people who were unable to complete the standing test were 84% more likely to die from any cause over the study period than their peers with better one-legged static balance (95% confidence interval, 1.23-2.78; P < .001).
The researchers said their study was limited by its lack of diversity – all the participants were relatively affluent Brazilians – and the inability to control for a history of falls and physical activity. But they said the size of the cohort, the long follow-up period, and their use of sophistical statistical methods helped mitigate the shortcomings.
Although low aerobic fitness is a marker of poor health, much less attention has been paid to nonaerobic fitness – things like balance, flexibility, and muscle strength and power, Dr. Araújo said.
“We are accumulating evidence that these three components of nonaerobic physical fitness are potentially relevant for good health and even more relevant for survival in older subjects,” Dr. Araújo said. Poor nonaerobic fitness, which is normally but not always associated with a sedentary lifestyle, “is the background of most cases of frailty, and being frail is strongly associated with a poor quality of life, less physical activity and exercise, and so on. It’s a bad circle.”
Dr. Araújo’s group has been using the standing test in their clinic for more than a dozen years and have seen gains in their patients. “Patients are often unaware that they are unable to sustain 10 seconds standing one legged. After this simple evaluation, they are much more prone to engage in balance training,” he said.
For now, the researchers don’t have data to show that improving static balance or performance on the standing test can affect survival, a “quite attractive” possibility, he added. But balance can be substantially improved through training.
“After only a few sessions, an improvement can be perceived, and this influences quality of life,” Dr. Araújo said. “And this is exactly what we do with the patients that we evaluated and for those that are attending our medically supervised exercise program.”
George A. Kuchel, MD, CM, FRCP, professor and Travelers Chair in Geriatrics and Gerontology at the University of Connecticut, Farmington, called the research “well done” and said the results “make perfect sense, since we have known for a long time that muscle strength is an important determinant of health, independence, and survival.”
Identifying frail patients quickly, simply, and reliably in the clinical setting is a pressing need, Dr. Kuchel, director of the UConn Center on Aging, said in an interview. The 10-second test “has considerable appeal” for this purpose.
“This could be, or rather should be, of great interest to all busy clinicians who see older adults in primary care or consultative capacities,” Dr. Kuchel added. “I hate to be nihilistic as regards what is possible in the context of really busy clinical practices, but even the minute or so that this takes to do may very well be too much for busy clinicians to do.”
Dr. Araújo and Dr. Kuchel reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE BRITISH JOURNAL OF SPORTS MEDICINE
Moderate activity versus sweat equity
It’s no secret that the fitness level of all age groups in our country is poor. A recent study in Pediatrics sharpens the focus on the question of how we might address the problem in the teenage population. Based in England, the investigators placed wrist accelerometers on their 13- and 14-year-old subjects who were then assessed using shuttle runs at progressively faster speeds.
The researchers found that the participants’ cardiorespiratory fitness improved as the subjects’ time doing vigorous activity increased up to 20 minutes and then plateaued. The study authors could not prove that the vigorous activity caused the increased in fitness. However, they were impressed by the plateau phenomenon and suggest that this might suggest a change in the recommendations by the World Health Organization and U.S. Department of Health & Human Services which currently call for 60 minutes of moderate to vigorous physical activity per day for adolescents
At first blush a shift down to 20 minutes of vigorous activity would appear to be workable and achievable. This would be particularly true for public school systems that are already struggling to get any kind of activity shoehorned into their schedules that are already crammed in an attempt to address mandated academic achievement goals. Freeing up an additional 40 minutes of the school day and yielding improved cardiorespiratory fitness sounds like a win-win.
But, let’s take a deep breath and for a few moments return to the world of reality. First, how many school systems are providing that 60 minutes of moderate activity (let’s forget the vigorous piece for the moment) included in the current WHO/HHS recommendations? Next, let’s take a look at what “vigorous” activity means. There are variety of definitions but in general they include sweating, flushing, and dyspnea to the point of having difficulty speaking.
Let’s just focus on the “sweating” part. To me that sounds like an activity that would require some wardrobe alteration at a minimum and very likely a locker room and a shower. Those can be fightin’ words for many teenagers. Even if a school can provide adequate locker room and shower infrastructure change-ups and showers are time-gobbling activities. And, more realistically, what are the chances of getting body image–challenged adolescents to willingly take advantage of them? You don’t have to talk to very many adults before you will hear stories of discomfort and embarrassment resulting from forced locker room and shower experiences. When I was a teenager the only way you could flunk physical education was to refuse to go in the locker room and “change up.” I think or at least hope that physical educators are more sensitive to the fragility of their adolescents students. But, the bottom line is that creating a curriculum that will improve cardiorespiratory fitness is fraught with challenges most school systems can’t address. It’s sad but true.
So, where does that leave us? This new study from England may be helpful for families who are caught in a time crunch and looking improve their fitness or for the physical educator who would like to help his/her motivated students get on a healthier track. But, this study should not prompt us to throw up our hands and toss out the current recommendations of an hour of moderate activity. As unrealistic as it may be for most school systems it allows for the injection of physical activity into academic settings where creative educators can offer things like walking lectures and field trips. It all boils down to the fact that some activity is better than none at all with or without the sweat equity.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
It’s no secret that the fitness level of all age groups in our country is poor. A recent study in Pediatrics sharpens the focus on the question of how we might address the problem in the teenage population. Based in England, the investigators placed wrist accelerometers on their 13- and 14-year-old subjects who were then assessed using shuttle runs at progressively faster speeds.
The researchers found that the participants’ cardiorespiratory fitness improved as the subjects’ time doing vigorous activity increased up to 20 minutes and then plateaued. The study authors could not prove that the vigorous activity caused the increased in fitness. However, they were impressed by the plateau phenomenon and suggest that this might suggest a change in the recommendations by the World Health Organization and U.S. Department of Health & Human Services which currently call for 60 minutes of moderate to vigorous physical activity per day for adolescents
At first blush a shift down to 20 minutes of vigorous activity would appear to be workable and achievable. This would be particularly true for public school systems that are already struggling to get any kind of activity shoehorned into their schedules that are already crammed in an attempt to address mandated academic achievement goals. Freeing up an additional 40 minutes of the school day and yielding improved cardiorespiratory fitness sounds like a win-win.
But, let’s take a deep breath and for a few moments return to the world of reality. First, how many school systems are providing that 60 minutes of moderate activity (let’s forget the vigorous piece for the moment) included in the current WHO/HHS recommendations? Next, let’s take a look at what “vigorous” activity means. There are variety of definitions but in general they include sweating, flushing, and dyspnea to the point of having difficulty speaking.
Let’s just focus on the “sweating” part. To me that sounds like an activity that would require some wardrobe alteration at a minimum and very likely a locker room and a shower. Those can be fightin’ words for many teenagers. Even if a school can provide adequate locker room and shower infrastructure change-ups and showers are time-gobbling activities. And, more realistically, what are the chances of getting body image–challenged adolescents to willingly take advantage of them? You don’t have to talk to very many adults before you will hear stories of discomfort and embarrassment resulting from forced locker room and shower experiences. When I was a teenager the only way you could flunk physical education was to refuse to go in the locker room and “change up.” I think or at least hope that physical educators are more sensitive to the fragility of their adolescents students. But, the bottom line is that creating a curriculum that will improve cardiorespiratory fitness is fraught with challenges most school systems can’t address. It’s sad but true.
So, where does that leave us? This new study from England may be helpful for families who are caught in a time crunch and looking improve their fitness or for the physical educator who would like to help his/her motivated students get on a healthier track. But, this study should not prompt us to throw up our hands and toss out the current recommendations of an hour of moderate activity. As unrealistic as it may be for most school systems it allows for the injection of physical activity into academic settings where creative educators can offer things like walking lectures and field trips. It all boils down to the fact that some activity is better than none at all with or without the sweat equity.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
It’s no secret that the fitness level of all age groups in our country is poor. A recent study in Pediatrics sharpens the focus on the question of how we might address the problem in the teenage population. Based in England, the investigators placed wrist accelerometers on their 13- and 14-year-old subjects who were then assessed using shuttle runs at progressively faster speeds.
The researchers found that the participants’ cardiorespiratory fitness improved as the subjects’ time doing vigorous activity increased up to 20 minutes and then plateaued. The study authors could not prove that the vigorous activity caused the increased in fitness. However, they were impressed by the plateau phenomenon and suggest that this might suggest a change in the recommendations by the World Health Organization and U.S. Department of Health & Human Services which currently call for 60 minutes of moderate to vigorous physical activity per day for adolescents
At first blush a shift down to 20 minutes of vigorous activity would appear to be workable and achievable. This would be particularly true for public school systems that are already struggling to get any kind of activity shoehorned into their schedules that are already crammed in an attempt to address mandated academic achievement goals. Freeing up an additional 40 minutes of the school day and yielding improved cardiorespiratory fitness sounds like a win-win.
But, let’s take a deep breath and for a few moments return to the world of reality. First, how many school systems are providing that 60 minutes of moderate activity (let’s forget the vigorous piece for the moment) included in the current WHO/HHS recommendations? Next, let’s take a look at what “vigorous” activity means. There are variety of definitions but in general they include sweating, flushing, and dyspnea to the point of having difficulty speaking.
Let’s just focus on the “sweating” part. To me that sounds like an activity that would require some wardrobe alteration at a minimum and very likely a locker room and a shower. Those can be fightin’ words for many teenagers. Even if a school can provide adequate locker room and shower infrastructure change-ups and showers are time-gobbling activities. And, more realistically, what are the chances of getting body image–challenged adolescents to willingly take advantage of them? You don’t have to talk to very many adults before you will hear stories of discomfort and embarrassment resulting from forced locker room and shower experiences. When I was a teenager the only way you could flunk physical education was to refuse to go in the locker room and “change up.” I think or at least hope that physical educators are more sensitive to the fragility of their adolescents students. But, the bottom line is that creating a curriculum that will improve cardiorespiratory fitness is fraught with challenges most school systems can’t address. It’s sad but true.
So, where does that leave us? This new study from England may be helpful for families who are caught in a time crunch and looking improve their fitness or for the physical educator who would like to help his/her motivated students get on a healthier track. But, this study should not prompt us to throw up our hands and toss out the current recommendations of an hour of moderate activity. As unrealistic as it may be for most school systems it allows for the injection of physical activity into academic settings where creative educators can offer things like walking lectures and field trips. It all boils down to the fact that some activity is better than none at all with or without the sweat equity.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
This breast tumor subtype disproportionately affects Black women
That finding, suggested by transcriptomic analyses of a racially diverse cohort that identified racial disparities in the proportion of HR-positive basal tumors, underscores a need for diverse racial representation in clinical trials, researchers recently reported at the annual meeting of the American Society of Clinical Oncology.
The leading cause of cancer-associated death among Black women is breast cancer, and compared with White women, Black women are 41% more likely to die from breast cancer, said Sonya A. Reid, MD, MPH, a medical oncologist with the Vanderbilt-Ingram Cancer Center, Nashville, Tenn., and the study author.
Few studies, Dr. Reid said, have evaluated if tumor biology differences contribute to the racial outcome disparity. Hormone receptor-positive tumors classified as basal-type with Blueprint genomic analysis (HR+/Basal) are overrepresented among Black women. These tumors are thought to be similar to triple negative breast cancer tumors (TNBC) which are more aggressive and tend to have worse outcomes.
TNBC, Dr. Reid said, is associated with low ACKR1 expression, which encodes the Duffy antigen and correlates with worse breast cancer outcomes. Given the overrepresentation and worse outcomes among Black women with HR-positive basal tumors, Dr. Reid and colleagues compared differentially expressed genes (DEGs) by race and subtype.
Their analysis of data from 2,657 women with stage 1, 2, and 3 breast cancer, showed that among 455 Black women, 315 had luminal (HR-positive luminal) and 140 had basal tumors (66 HR-positive basal and 74 HR-negative basal). Among White women included as a reference group (n = 2,202), tumors were were HR-positive luminal in 1,825 and HR-positive basal or HR-negative basal in 158 and 219, respectively. The proportion of Black women with HR-positive basal tumors was significantly higher, compared with White women (15% versus 7%; P <0.001) as was the proportion of Black women with HR-negative basal tumors, compared with White women (16% versus 10%; P <0.001).
Women included in the study were participants in the ongoing BEST study (5R01CA204819) at Vanderbilt University Medical Center, Nashvlile, Tenn., or FLEX study (NCT03053193). In a multidimensional scaling analysis, HR-positive basal tumors clustered with TNBC rather than with HR-positive luminal tumors. While a differential gene expression analysis comparing HR-positive basal with HR-positive luminal tumors resulted in over 700 differently expressed genes in Black women, no such genes were identified when comparing HR-positive basal tumors with TNBC. ACKR1 expression in HR-positive basal tumors was comparable to TNBC in Black women (P = 0.81) and White women (P = 0.46). In contrast, HR-positive basal tumors had significantly lower ACKR1 expression than HR-positive luminal tumors in Black (P < 0.01) and White women (P < 0.01).
The findings highlight the importance of further genomic classification for patients with HR-positive tumors, Dr. Reid said.
“Molecular subtype classification is not standard of care for patients with localized breast cancer. However, the current analysis suggests that genomic classification could have important clinical implications. Women with HR-positive basal tumors should not be treated uniformly with HR-poisitive luminal tumors. Our data suggest that HR-positive basal tumors are transcriptomically similar to TNBC tumors and should potentially be treated similar to TNBC,” she said.
There are several genomic tests that are widely available clinically to guide treatment decisions and are covered by insurance, Dr. Reid said. Prior studies have shown racial disparity in the omission of genomic tests to guide treatment decisions, however. “Increasing access [to] and awareness of genomic testing will improve guideline-adherent care for all patients. We must intentionally recruit minority patients into clinical trials, knowing that Black women are more likely to die of their breast cancer,” she said.
A further impediment lies in the fact that while most minority patients receive their care in the community, most clinical trials are offered at large academic centers, Dr. Reid said. Future trials, she urged, should include a predetermined percentage of racial/ethnic groups in the clinical trial design to reflect the breast cancer population.
Limitations of the study included that race was self-reported. She noted further that the data for survival are not yet mature. She added, “We will also be evaluating the association of different systemic treatment options across the different molecular subtypes.”
Dr. Reid reported no relevant disclosures.
That finding, suggested by transcriptomic analyses of a racially diverse cohort that identified racial disparities in the proportion of HR-positive basal tumors, underscores a need for diverse racial representation in clinical trials, researchers recently reported at the annual meeting of the American Society of Clinical Oncology.
The leading cause of cancer-associated death among Black women is breast cancer, and compared with White women, Black women are 41% more likely to die from breast cancer, said Sonya A. Reid, MD, MPH, a medical oncologist with the Vanderbilt-Ingram Cancer Center, Nashville, Tenn., and the study author.
Few studies, Dr. Reid said, have evaluated if tumor biology differences contribute to the racial outcome disparity. Hormone receptor-positive tumors classified as basal-type with Blueprint genomic analysis (HR+/Basal) are overrepresented among Black women. These tumors are thought to be similar to triple negative breast cancer tumors (TNBC) which are more aggressive and tend to have worse outcomes.
TNBC, Dr. Reid said, is associated with low ACKR1 expression, which encodes the Duffy antigen and correlates with worse breast cancer outcomes. Given the overrepresentation and worse outcomes among Black women with HR-positive basal tumors, Dr. Reid and colleagues compared differentially expressed genes (DEGs) by race and subtype.
Their analysis of data from 2,657 women with stage 1, 2, and 3 breast cancer, showed that among 455 Black women, 315 had luminal (HR-positive luminal) and 140 had basal tumors (66 HR-positive basal and 74 HR-negative basal). Among White women included as a reference group (n = 2,202), tumors were were HR-positive luminal in 1,825 and HR-positive basal or HR-negative basal in 158 and 219, respectively. The proportion of Black women with HR-positive basal tumors was significantly higher, compared with White women (15% versus 7%; P <0.001) as was the proportion of Black women with HR-negative basal tumors, compared with White women (16% versus 10%; P <0.001).
Women included in the study were participants in the ongoing BEST study (5R01CA204819) at Vanderbilt University Medical Center, Nashvlile, Tenn., or FLEX study (NCT03053193). In a multidimensional scaling analysis, HR-positive basal tumors clustered with TNBC rather than with HR-positive luminal tumors. While a differential gene expression analysis comparing HR-positive basal with HR-positive luminal tumors resulted in over 700 differently expressed genes in Black women, no such genes were identified when comparing HR-positive basal tumors with TNBC. ACKR1 expression in HR-positive basal tumors was comparable to TNBC in Black women (P = 0.81) and White women (P = 0.46). In contrast, HR-positive basal tumors had significantly lower ACKR1 expression than HR-positive luminal tumors in Black (P < 0.01) and White women (P < 0.01).
The findings highlight the importance of further genomic classification for patients with HR-positive tumors, Dr. Reid said.
“Molecular subtype classification is not standard of care for patients with localized breast cancer. However, the current analysis suggests that genomic classification could have important clinical implications. Women with HR-positive basal tumors should not be treated uniformly with HR-poisitive luminal tumors. Our data suggest that HR-positive basal tumors are transcriptomically similar to TNBC tumors and should potentially be treated similar to TNBC,” she said.
There are several genomic tests that are widely available clinically to guide treatment decisions and are covered by insurance, Dr. Reid said. Prior studies have shown racial disparity in the omission of genomic tests to guide treatment decisions, however. “Increasing access [to] and awareness of genomic testing will improve guideline-adherent care for all patients. We must intentionally recruit minority patients into clinical trials, knowing that Black women are more likely to die of their breast cancer,” she said.
A further impediment lies in the fact that while most minority patients receive their care in the community, most clinical trials are offered at large academic centers, Dr. Reid said. Future trials, she urged, should include a predetermined percentage of racial/ethnic groups in the clinical trial design to reflect the breast cancer population.
Limitations of the study included that race was self-reported. She noted further that the data for survival are not yet mature. She added, “We will also be evaluating the association of different systemic treatment options across the different molecular subtypes.”
Dr. Reid reported no relevant disclosures.
That finding, suggested by transcriptomic analyses of a racially diverse cohort that identified racial disparities in the proportion of HR-positive basal tumors, underscores a need for diverse racial representation in clinical trials, researchers recently reported at the annual meeting of the American Society of Clinical Oncology.
The leading cause of cancer-associated death among Black women is breast cancer, and compared with White women, Black women are 41% more likely to die from breast cancer, said Sonya A. Reid, MD, MPH, a medical oncologist with the Vanderbilt-Ingram Cancer Center, Nashville, Tenn., and the study author.
Few studies, Dr. Reid said, have evaluated if tumor biology differences contribute to the racial outcome disparity. Hormone receptor-positive tumors classified as basal-type with Blueprint genomic analysis (HR+/Basal) are overrepresented among Black women. These tumors are thought to be similar to triple negative breast cancer tumors (TNBC) which are more aggressive and tend to have worse outcomes.
TNBC, Dr. Reid said, is associated with low ACKR1 expression, which encodes the Duffy antigen and correlates with worse breast cancer outcomes. Given the overrepresentation and worse outcomes among Black women with HR-positive basal tumors, Dr. Reid and colleagues compared differentially expressed genes (DEGs) by race and subtype.
Their analysis of data from 2,657 women with stage 1, 2, and 3 breast cancer, showed that among 455 Black women, 315 had luminal (HR-positive luminal) and 140 had basal tumors (66 HR-positive basal and 74 HR-negative basal). Among White women included as a reference group (n = 2,202), tumors were were HR-positive luminal in 1,825 and HR-positive basal or HR-negative basal in 158 and 219, respectively. The proportion of Black women with HR-positive basal tumors was significantly higher, compared with White women (15% versus 7%; P <0.001) as was the proportion of Black women with HR-negative basal tumors, compared with White women (16% versus 10%; P <0.001).
Women included in the study were participants in the ongoing BEST study (5R01CA204819) at Vanderbilt University Medical Center, Nashvlile, Tenn., or FLEX study (NCT03053193). In a multidimensional scaling analysis, HR-positive basal tumors clustered with TNBC rather than with HR-positive luminal tumors. While a differential gene expression analysis comparing HR-positive basal with HR-positive luminal tumors resulted in over 700 differently expressed genes in Black women, no such genes were identified when comparing HR-positive basal tumors with TNBC. ACKR1 expression in HR-positive basal tumors was comparable to TNBC in Black women (P = 0.81) and White women (P = 0.46). In contrast, HR-positive basal tumors had significantly lower ACKR1 expression than HR-positive luminal tumors in Black (P < 0.01) and White women (P < 0.01).
The findings highlight the importance of further genomic classification for patients with HR-positive tumors, Dr. Reid said.
“Molecular subtype classification is not standard of care for patients with localized breast cancer. However, the current analysis suggests that genomic classification could have important clinical implications. Women with HR-positive basal tumors should not be treated uniformly with HR-poisitive luminal tumors. Our data suggest that HR-positive basal tumors are transcriptomically similar to TNBC tumors and should potentially be treated similar to TNBC,” she said.
There are several genomic tests that are widely available clinically to guide treatment decisions and are covered by insurance, Dr. Reid said. Prior studies have shown racial disparity in the omission of genomic tests to guide treatment decisions, however. “Increasing access [to] and awareness of genomic testing will improve guideline-adherent care for all patients. We must intentionally recruit minority patients into clinical trials, knowing that Black women are more likely to die of their breast cancer,” she said.
A further impediment lies in the fact that while most minority patients receive their care in the community, most clinical trials are offered at large academic centers, Dr. Reid said. Future trials, she urged, should include a predetermined percentage of racial/ethnic groups in the clinical trial design to reflect the breast cancer population.
Limitations of the study included that race was self-reported. She noted further that the data for survival are not yet mature. She added, “We will also be evaluating the association of different systemic treatment options across the different molecular subtypes.”
Dr. Reid reported no relevant disclosures.
FROM ASCO 2022
IL-6 antibody mitigates mucus hypersecretion in COPD
Treatment with an interleukin-6 neutralizing antibody significantly reduced airway mucus hypersecretion (AMH) in chronic obstructive pulmonary disease (COPD), based on data from human and mouse cells in a human organoid model.
AMH plays a large part in aggravating airway obstruction in patients with COPD, Yuan-Yuan Wei, MD, of First Affiliated Hospital of Anhui Medical University, Hefei, China, and colleagues wrote.
Current pharmacotherapies relieve COPD symptoms and improve exercise tolerance, but have not proven effective for relieving the airflow limitations caused by mucus accumulation that “leads to irreversible structural damage and an unfavorable prognosis,” the researchers said. Although reducing AMH could help manage COPD, the molecular mechanisms of action have not been fully explored.
In a study published in Biomedicine & Pharmacotherapy , the researchers examined the relationship between IL-6 and AMH. Since IL-6 has been shown to cause overexpression of the mucin-type protein known as Muc5ac, they hypothesized that IL-6 antibodies (IL-6Ab) might block this protein elevation.
The researchers recruited 30 adults with COPD and 30 controls from a single center. Bronchial epithelial cells were isolated from the participants and measured the levels of Muc5ac protein and mRNA in the lung tissue. Compared with controls, COPD patients had elevated Muc5ac positively correlated with IL-6.
The researchers then created an organoid model of a trachea for COPD patients and controls. In the model, Muc5ac was similarly elevated in COPD patients, compared with controls. “Furthermore, IL-6 significantly induced excessive secretion of mucus in the organoid model of trachea in COPD patients as observed under electron microscope, and IL-6Ab attenuated these effects,” they noted.
IL-6 significantly increased both Muc5ac mRNA and protein expression in the organoid model of trachea (P < .0001 and P < .005, respectively), but both of these significantly decreased when treated with IL-6Ab (P < .0001 and P < .05, respectively).
The researchers also examined human and mouse cells to explore the mechanism of action of IL-6Ab. Using high-throughput sequencing, they found that the IL-6Ab induced nuclear translocation of the Nrt2 gene in COPD patients, and that this action promoted the effect of IL-6Ab on excessive mucus secretion.
The study findings were limited by the relatively small study population from a single center, the researchers noted.
However, the results support the potential of IL-6Ab as “a novel therapeutic strategy in the treatment of IL-6–induced hypersecretion of airway mucus so as to improve airflow limitations in COPD,” they concluded.
The study was supported by supported by the National Natural Science Foundation of China and the Scientific Research Project of Education Department of Anhui Province. The researchers had no financial conflicts to disclose.
Treatment with an interleukin-6 neutralizing antibody significantly reduced airway mucus hypersecretion (AMH) in chronic obstructive pulmonary disease (COPD), based on data from human and mouse cells in a human organoid model.
AMH plays a large part in aggravating airway obstruction in patients with COPD, Yuan-Yuan Wei, MD, of First Affiliated Hospital of Anhui Medical University, Hefei, China, and colleagues wrote.
Current pharmacotherapies relieve COPD symptoms and improve exercise tolerance, but have not proven effective for relieving the airflow limitations caused by mucus accumulation that “leads to irreversible structural damage and an unfavorable prognosis,” the researchers said. Although reducing AMH could help manage COPD, the molecular mechanisms of action have not been fully explored.
In a study published in Biomedicine & Pharmacotherapy , the researchers examined the relationship between IL-6 and AMH. Since IL-6 has been shown to cause overexpression of the mucin-type protein known as Muc5ac, they hypothesized that IL-6 antibodies (IL-6Ab) might block this protein elevation.
The researchers recruited 30 adults with COPD and 30 controls from a single center. Bronchial epithelial cells were isolated from the participants and measured the levels of Muc5ac protein and mRNA in the lung tissue. Compared with controls, COPD patients had elevated Muc5ac positively correlated with IL-6.
The researchers then created an organoid model of a trachea for COPD patients and controls. In the model, Muc5ac was similarly elevated in COPD patients, compared with controls. “Furthermore, IL-6 significantly induced excessive secretion of mucus in the organoid model of trachea in COPD patients as observed under electron microscope, and IL-6Ab attenuated these effects,” they noted.
IL-6 significantly increased both Muc5ac mRNA and protein expression in the organoid model of trachea (P < .0001 and P < .005, respectively), but both of these significantly decreased when treated with IL-6Ab (P < .0001 and P < .05, respectively).
The researchers also examined human and mouse cells to explore the mechanism of action of IL-6Ab. Using high-throughput sequencing, they found that the IL-6Ab induced nuclear translocation of the Nrt2 gene in COPD patients, and that this action promoted the effect of IL-6Ab on excessive mucus secretion.
The study findings were limited by the relatively small study population from a single center, the researchers noted.
However, the results support the potential of IL-6Ab as “a novel therapeutic strategy in the treatment of IL-6–induced hypersecretion of airway mucus so as to improve airflow limitations in COPD,” they concluded.
The study was supported by supported by the National Natural Science Foundation of China and the Scientific Research Project of Education Department of Anhui Province. The researchers had no financial conflicts to disclose.
Treatment with an interleukin-6 neutralizing antibody significantly reduced airway mucus hypersecretion (AMH) in chronic obstructive pulmonary disease (COPD), based on data from human and mouse cells in a human organoid model.
AMH plays a large part in aggravating airway obstruction in patients with COPD, Yuan-Yuan Wei, MD, of First Affiliated Hospital of Anhui Medical University, Hefei, China, and colleagues wrote.
Current pharmacotherapies relieve COPD symptoms and improve exercise tolerance, but have not proven effective for relieving the airflow limitations caused by mucus accumulation that “leads to irreversible structural damage and an unfavorable prognosis,” the researchers said. Although reducing AMH could help manage COPD, the molecular mechanisms of action have not been fully explored.
In a study published in Biomedicine & Pharmacotherapy , the researchers examined the relationship between IL-6 and AMH. Since IL-6 has been shown to cause overexpression of the mucin-type protein known as Muc5ac, they hypothesized that IL-6 antibodies (IL-6Ab) might block this protein elevation.
The researchers recruited 30 adults with COPD and 30 controls from a single center. Bronchial epithelial cells were isolated from the participants and measured the levels of Muc5ac protein and mRNA in the lung tissue. Compared with controls, COPD patients had elevated Muc5ac positively correlated with IL-6.
The researchers then created an organoid model of a trachea for COPD patients and controls. In the model, Muc5ac was similarly elevated in COPD patients, compared with controls. “Furthermore, IL-6 significantly induced excessive secretion of mucus in the organoid model of trachea in COPD patients as observed under electron microscope, and IL-6Ab attenuated these effects,” they noted.
IL-6 significantly increased both Muc5ac mRNA and protein expression in the organoid model of trachea (P < .0001 and P < .005, respectively), but both of these significantly decreased when treated with IL-6Ab (P < .0001 and P < .05, respectively).
The researchers also examined human and mouse cells to explore the mechanism of action of IL-6Ab. Using high-throughput sequencing, they found that the IL-6Ab induced nuclear translocation of the Nrt2 gene in COPD patients, and that this action promoted the effect of IL-6Ab on excessive mucus secretion.
The study findings were limited by the relatively small study population from a single center, the researchers noted.
However, the results support the potential of IL-6Ab as “a novel therapeutic strategy in the treatment of IL-6–induced hypersecretion of airway mucus so as to improve airflow limitations in COPD,” they concluded.
The study was supported by supported by the National Natural Science Foundation of China and the Scientific Research Project of Education Department of Anhui Province. The researchers had no financial conflicts to disclose.
FROM BIOMEDICINE & PHARMACOTHERAPY