Heidi Splete

Physical activity mitigated the impact of high body mass index (BMI) on cardiovascular risk factors, but not overall cardiovascular disease risk, according to an observational study of half a million individuals.

Despite the historically high rates of overweight and obesity worldwide, some evidence suggests that cardiorespiratory fitness could reduce the effects of excess weight on cardiovascular disease risk, wrote Pedro L. Valenzuela, PhD, of the University of Alcalá, Madrid, and colleagues.

“To clarify the existence of the ‘fat-but-fit’ [or ‘elevated BMI but active’] paradox, in this observational study, we assessed the joint association between different BMI categories and physical activity levels, respectively, and the prevalence of major CVD risk factors,” they said.

In a population-based cohort study published in the European Journal of Preventive Cardiology, the researchers identified 527,662 adults aged 18-64 years who were insured by an occupational risk–prevention company and underwent annual medical exams as part of their coverage. The average age of the participants was 42 years, 32% were women, and the average BMI was 26.2 kg/m².

The participants were categorized as normal weight (42%), overweight (41%), and obese (18%), and their activity levels were categorized as inactive (64%), insufficiently active (12%), and regularly active (24%). In addition, 30% had hypercholesterolemia, 15% had hypertension, and 3% had diabetes.

Overall, compared with inactivity, insufficient activity or regular activity reduced CVD risk factors within each BMI category, and subgroups. “However, regular/insufficient PA did not compensate for the negative effects of overweight/obesity, as individuals with overweight/obesity were at greater CVD risk than their peers with normal weight, irrespective of PA levels,” the researchers said. Compared with active normal-weight men, the odds ratios for hypertension in active overweight men and active obese men were 1.98 and 4.93, respectively; the odds ratios for hypercholesterolemia were 1.61 and 2.03, respectively, and the odds ratios for diabetes were 1.33 and 3.62, respectively (P < .001 for all). Trends were similar for women.

The study results were limited by the cross-sectional design; inability to control for participants’ diet, and the reliance of self-reports of leisure-time physical activity. However, the findings were strengthened by the large sample size and “refute the notion that a physically active lifestyle can completely negate the deleterious effects of overweight/obesity,” the researchers said.

Although increasing physical activity should remain a priority for health policies, “weight loss per se should remain a primary target for health policies aimed at reducing CVD risk in people with overweight/obesity,” they concluded.
 

Interpret findings with caution

“With the ever-increasing public health problem of overweight and obesity, it is useful to assess any measure or measures that can have a favorable or adverse effect on cardiometabolic risk factors and the risk of CVD” Prakash Deedwania, MD, of the University of California, San Francisco, said in an interview.

Dr. Deedwania said he was not entirely surprised by the study findings. “The investigators have correlated only the self-reported level of physical activity (which is not always reliable) to the presence of three cardiac risk factors: hypertension, hypercholesterolemia, and diabetes.”

The study “is not comparable to prior reports that had shown a favorable impact of carefully assessed cardiorespiratory fitness with the risk of CVD,” Dr. Deedwania noted. “However, this is one of the largest population-wide surveillance studies of more than a half million active workers across Spain, and it does show that, despite self-reported physical activity, overweight and obesity are associated with higher risks of hypertension, diabetes, and hypercholesterolemia,” he explained.

“The main message of these findings is that, although physical activity does have a dose-dependent favorable impact on CV risk, the main public health intervention to reduce the risk of CV risk should focus on weight loss in overweight and obese individuals,” Dr. Deedwania emphasized.

“Future studies should focus on comparing various levels of daily activities and routine exercise such as walking, bicycling, etc., with the beneficial impact on cardiometabolic risk factors in overweight and obese individuals,” he said.

Dr. Valenzuela disclosed support from the University of Alcalá. Research by corresponding author Dr. Lucia was funded by grants from Spanish Ministry of Science and Innovation and Fondos FEDER. Dr. Deedwania had no financial conflicts to disclose.

Physical activity mitigated the impact of high body mass index (BMI) on cardiovascular risk factors, but not overall cardiovascular disease risk, according to an observational study of half a million individuals.

Despite the historically high rates of overweight and obesity worldwide, some evidence suggests that cardiorespiratory fitness could reduce the effects of excess weight on cardiovascular disease risk, wrote Pedro L. Valenzuela, PhD, of the University of Alcalá, Madrid, and colleagues.

“To clarify the existence of the ‘fat-but-fit’ [or ‘elevated BMI but active’] paradox, in this observational study, we assessed the joint association between different BMI categories and physical activity levels, respectively, and the prevalence of major CVD risk factors,” they said.

In a population-based cohort study published in the European Journal of Preventive Cardiology, the researchers identified 527,662 adults aged 18-64 years who were insured by an occupational risk–prevention company and underwent annual medical exams as part of their coverage. The average age of the participants was 42 years, 32% were women, and the average BMI was 26.2 kg/m².

The participants were categorized as normal weight (42%), overweight (41%), and obese (18%), and their activity levels were categorized as inactive (64%), insufficiently active (12%), and regularly active (24%). In addition, 30% had hypercholesterolemia, 15% had hypertension, and 3% had diabetes.

Overall, compared with inactivity, insufficient activity or regular activity reduced CVD risk factors within each BMI category, and subgroups. “However, regular/insufficient PA did not compensate for the negative effects of overweight/obesity, as individuals with overweight/obesity were at greater CVD risk than their peers with normal weight, irrespective of PA levels,” the researchers said. Compared with active normal-weight men, the odds ratios for hypertension in active overweight men and active obese men were 1.98 and 4.93, respectively; the odds ratios for hypercholesterolemia were 1.61 and 2.03, respectively, and the odds ratios for diabetes were 1.33 and 3.62, respectively (P < .001 for all). Trends were similar for women.

The study results were limited by the cross-sectional design; inability to control for participants’ diet, and the reliance of self-reports of leisure-time physical activity. However, the findings were strengthened by the large sample size and “refute the notion that a physically active lifestyle can completely negate the deleterious effects of overweight/obesity,” the researchers said.

Although increasing physical activity should remain a priority for health policies, “weight loss per se should remain a primary target for health policies aimed at reducing CVD risk in people with overweight/obesity,” they concluded.
 

Interpret findings with caution

“With the ever-increasing public health problem of overweight and obesity, it is useful to assess any measure or measures that can have a favorable or adverse effect on cardiometabolic risk factors and the risk of CVD” Prakash Deedwania, MD, of the University of California, San Francisco, said in an interview.

Dr. Deedwania said he was not entirely surprised by the study findings. “The investigators have correlated only the self-reported level of physical activity (which is not always reliable) to the presence of three cardiac risk factors: hypertension, hypercholesterolemia, and diabetes.”

The study “is not comparable to prior reports that had shown a favorable impact of carefully assessed cardiorespiratory fitness with the risk of CVD,” Dr. Deedwania noted. “However, this is one of the largest population-wide surveillance studies of more than a half million active workers across Spain, and it does show that, despite self-reported physical activity, overweight and obesity are associated with higher risks of hypertension, diabetes, and hypercholesterolemia,” he explained.

“The main message of these findings is that, although physical activity does have a dose-dependent favorable impact on CV risk, the main public health intervention to reduce the risk of CV risk should focus on weight loss in overweight and obese individuals,” Dr. Deedwania emphasized.

“Future studies should focus on comparing various levels of daily activities and routine exercise such as walking, bicycling, etc., with the beneficial impact on cardiometabolic risk factors in overweight and obese individuals,” he said.

Dr. Valenzuela disclosed support from the University of Alcalá. Research by corresponding author Dr. Lucia was funded by grants from Spanish Ministry of Science and Innovation and Fondos FEDER. Dr. Deedwania had no financial conflicts to disclose.

Physical activity mitigated the impact of high body mass index (BMI) on cardiovascular risk factors, but not overall cardiovascular disease risk, according to an observational study of half a million individuals.

Despite the historically high rates of overweight and obesity worldwide, some evidence suggests that cardiorespiratory fitness could reduce the effects of excess weight on cardiovascular disease risk, wrote Pedro L. Valenzuela, PhD, of the University of Alcalá, Madrid, and colleagues.

“To clarify the existence of the ‘fat-but-fit’ [or ‘elevated BMI but active’] paradox, in this observational study, we assessed the joint association between different BMI categories and physical activity levels, respectively, and the prevalence of major CVD risk factors,” they said.

In a population-based cohort study published in the European Journal of Preventive Cardiology, the researchers identified 527,662 adults aged 18-64 years who were insured by an occupational risk–prevention company and underwent annual medical exams as part of their coverage. The average age of the participants was 42 years, 32% were women, and the average BMI was 26.2 kg/m².

The participants were categorized as normal weight (42%), overweight (41%), and obese (18%), and their activity levels were categorized as inactive (64%), insufficiently active (12%), and regularly active (24%). In addition, 30% had hypercholesterolemia, 15% had hypertension, and 3% had diabetes.

Overall, compared with inactivity, insufficient activity or regular activity reduced CVD risk factors within each BMI category, and subgroups. “However, regular/insufficient PA did not compensate for the negative effects of overweight/obesity, as individuals with overweight/obesity were at greater CVD risk than their peers with normal weight, irrespective of PA levels,” the researchers said. Compared with active normal-weight men, the odds ratios for hypertension in active overweight men and active obese men were 1.98 and 4.93, respectively; the odds ratios for hypercholesterolemia were 1.61 and 2.03, respectively, and the odds ratios for diabetes were 1.33 and 3.62, respectively (P < .001 for all). Trends were similar for women.

The study results were limited by the cross-sectional design; inability to control for participants’ diet, and the reliance of self-reports of leisure-time physical activity. However, the findings were strengthened by the large sample size and “refute the notion that a physically active lifestyle can completely negate the deleterious effects of overweight/obesity,” the researchers said.

Although increasing physical activity should remain a priority for health policies, “weight loss per se should remain a primary target for health policies aimed at reducing CVD risk in people with overweight/obesity,” they concluded.
 

Interpret findings with caution

“With the ever-increasing public health problem of overweight and obesity, it is useful to assess any measure or measures that can have a favorable or adverse effect on cardiometabolic risk factors and the risk of CVD” Prakash Deedwania, MD, of the University of California, San Francisco, said in an interview.

Dr. Deedwania said he was not entirely surprised by the study findings. “The investigators have correlated only the self-reported level of physical activity (which is not always reliable) to the presence of three cardiac risk factors: hypertension, hypercholesterolemia, and diabetes.”

The study “is not comparable to prior reports that had shown a favorable impact of carefully assessed cardiorespiratory fitness with the risk of CVD,” Dr. Deedwania noted. “However, this is one of the largest population-wide surveillance studies of more than a half million active workers across Spain, and it does show that, despite self-reported physical activity, overweight and obesity are associated with higher risks of hypertension, diabetes, and hypercholesterolemia,” he explained.

“The main message of these findings is that, although physical activity does have a dose-dependent favorable impact on CV risk, the main public health intervention to reduce the risk of CV risk should focus on weight loss in overweight and obese individuals,” Dr. Deedwania emphasized.

“Future studies should focus on comparing various levels of daily activities and routine exercise such as walking, bicycling, etc., with the beneficial impact on cardiometabolic risk factors in overweight and obese individuals,” he said.

Dr. Valenzuela disclosed support from the University of Alcalá. Research by corresponding author Dr. Lucia was funded by grants from Spanish Ministry of Science and Innovation and Fondos FEDER. Dr. Deedwania had no financial conflicts to disclose.

COVID-19 infection altered the gut microbiota of adult patients and caused depletion of several types of bacteria with known immunomodulatory properties, based on data from a cohort study of 100 patients with confirmed COVID-19 infections from two hospitals.

“As the GI tract is the largest immunological organ in the body and its resident microbiota are known to modulate host immune responses, we hypothesized that the gut microbiota is associated with host inflammatory immune responses in COVID19,” wrote Yun Kit Yeoh, PhD, of the Chinese University of Hong Kong, and colleagues.

In a study published in Gut, the researchers investigated patient microbiota by collecting blood, stool, and patient records between February and May 2020 from 100 confirmed SARS-CoV-2–infected patients in Hong Kong during hospitalization, as well as follow-up stool samples from 27 patients up to 30 days after they cleared the COVID-19 virus; these observations were compared with 78 non–COVID-19 controls.

Overall, 274 stool samples were sequenced. Samples collected from patients during hospitalization for COVID-19 were compared with non–COVID-19 controls. The presence of phylum Bacteroidetes was significantly higher in COVID-19 patients compared with controls (23.9% vs. 12.8%; P < .001), as were Actinobacteria (26.1% vs. 19.0%; P < .001).

After controlling for antibiotics, the investigators found that “differences between cohorts were primarily linked to enrichment of taxa such as Parabacteroides, Sutterella wadsworthensis, and Bacteroides caccae and depletion of Adlercreutzia equolifaciens, Dorea formicigenerans, and Clostridium leptum in COVID-19 relative to non-COVID-19” (P < .05). In addition, Faecalibacterium prausnitzii and Bifidobacterium bifidum were negatively correlated with COVID-19 severity after investigators controlled for patient age and antibiotic use (P < .05).

The researchers also examined bacteria in COVID-19 patients and controls in the context of cytokines and other inflammatory markers. “We hypothesized that these compositional changes play a role in exacerbating disease by contributing to dysregulation of the immune response,” they said.

In fact, species depleted in COVID-19 patients including included B. adolescentis, E. rectale, and F. prausnitzii were negatively correlated with inflammatory markers including CXCL10, IL-10, TNF-alpha, and CCL2.

In addition, 42 stool samples from 27 patients showed significantly distinct gut microbiota from controls up to 30 days (median, 6 days) after virus clearance, regardless of antibiotics use (P < .05), the researchers said.
 

Long-term data needed

The study findings were limited by several factors, including the potential confounding of microbial signatures associated with COVID-19 because of heterogeneous patient management in the clinical setting and the potential that gut microbiota reflects a patient’s health with no impact on disease severity, as well as lack of data on the role of antibiotics for severe and critical patients, the researchers noted. In addition, “gut microbiota composition is highly heterogeneous across human populations and changes in compositions reported here may not necessarily be reflected in patients with COVID-19 from other biogeographies,” they wrote.

The “longer follow-up of patients with COVID-19 (e.g., 3 months to 1 year after clearing the virus) is needed to address questions related to the duration of gut microbiota dysbiosis post recovery, link between microbiota dysbiosis and long-term persistent symptoms, and whether the dysbiosis or enrichment/depletion of specific gut microorganisms predisposes recovered individuals to future health problems,” they wrote.

However, the results suggest a likely role for gut microorganisms in host inflammatory responses to COVID-19 infection, and “underscore an urgent need to understand the specific roles of gut microorganisms in human immune function and systemic inflammation,” they concluded.
 

More than infectious

“A growing body of evidence suggests that severity of illness from COVID-19 is largely determined by the patient’s aberrant immune response to the virus,” Jatin Roper, MD, of Duke University, Durham, N.C., said in an interview. “Therefore, a critical question is: What patient factors determine this immune response? The gut microbiota closely interact with the host immune system and are altered in many immunological diseases,” he said. “Furthermore, the SARS-CoV-2 virus infects enterocytes in the intestine and causes symptomatic gastrointestinal disease in a subset of patients. Therefore, understanding a possible association between gut microbiota and COVID-19 may reveal microbial species involved in disease pathogenesis,” he emphasized.   

In the current study, “I was surprised to find that COVID-19 infection is associated with depletion of immunomodulatory gut bacteria,” said Dr. Roper. “An open question is whether these changes are caused by the SARS-CoV-2 virus and then result in altered immune response. Alternatively, the changes in gut microbiota may be a result of the immune response or other changes associated with the disease,” he said.

“COVID-19 is an immunological disease, not just an infectious disease,” explained Dr. Roper. “The gut microbiota may play an important role in the pathogenesis of the disease. Thus, specific gut microbes could one day be analyzed to risk stratify patients, or even modified to treat the disease,” he noted.
 

Beyond COVID-19

“Given the impact of the gut microbiota on health and disease, as well as the impact of diseases on the microbiota, I am not at all surprised to find that there were significant changes in the microbiota of COVID-19 patients and that these changes are associated with inflammatory cytokines, chemokines, and blood markers of tissue damage,” said Anthony Sung, MD, also of Duke University.

According to Dr. Sung, researchers have already been investigating possible connections between gut microbiota and other conditions such as Alzheimer’s disease, and it’s been hypothesized that these connections are mediated by interactions between the gut microbiota and the immune system.

“While this is an important paper in our understanding of COVID-19, and highlights the microbiome as a potential therapeutic target, we need to conduct clinical trials of microbiota-based interventions before we can fully realize the clinical implications of these findings,” he said.

The study was supported by the Health and Medical Research Fund, the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region, and donations from Hui Hoy & Chow Sin Lan Charity Fund Limited, Pine and Crane Company Limited, Mr. Hui Ming, and The D.H. Chen Foundation. The researchers had no financial conflicts to disclose. Dr. Roper and Dr. Sung had no financial conflicts to disclose.

COVID-19 infection altered the gut microbiota of adult patients and caused depletion of several types of bacteria with known immunomodulatory properties, based on data from a cohort study of 100 patients with confirmed COVID-19 infections from two hospitals.

“As the GI tract is the largest immunological organ in the body and its resident microbiota are known to modulate host immune responses, we hypothesized that the gut microbiota is associated with host inflammatory immune responses in COVID19,” wrote Yun Kit Yeoh, PhD, of the Chinese University of Hong Kong, and colleagues.

In a study published in Gut, the researchers investigated patient microbiota by collecting blood, stool, and patient records between February and May 2020 from 100 confirmed SARS-CoV-2–infected patients in Hong Kong during hospitalization, as well as follow-up stool samples from 27 patients up to 30 days after they cleared the COVID-19 virus; these observations were compared with 78 non–COVID-19 controls.

Overall, 274 stool samples were sequenced. Samples collected from patients during hospitalization for COVID-19 were compared with non–COVID-19 controls. The presence of phylum Bacteroidetes was significantly higher in COVID-19 patients compared with controls (23.9% vs. 12.8%; P < .001), as were Actinobacteria (26.1% vs. 19.0%; P < .001).

After controlling for antibiotics, the investigators found that “differences between cohorts were primarily linked to enrichment of taxa such as Parabacteroides, Sutterella wadsworthensis, and Bacteroides caccae and depletion of Adlercreutzia equolifaciens, Dorea formicigenerans, and Clostridium leptum in COVID-19 relative to non-COVID-19” (P < .05). In addition, Faecalibacterium prausnitzii and Bifidobacterium bifidum were negatively correlated with COVID-19 severity after investigators controlled for patient age and antibiotic use (P < .05).

The researchers also examined bacteria in COVID-19 patients and controls in the context of cytokines and other inflammatory markers. “We hypothesized that these compositional changes play a role in exacerbating disease by contributing to dysregulation of the immune response,” they said.

In fact, species depleted in COVID-19 patients including included B. adolescentis, E. rectale, and F. prausnitzii were negatively correlated with inflammatory markers including CXCL10, IL-10, TNF-alpha, and CCL2.

In addition, 42 stool samples from 27 patients showed significantly distinct gut microbiota from controls up to 30 days (median, 6 days) after virus clearance, regardless of antibiotics use (P < .05), the researchers said.
 

Long-term data needed

The study findings were limited by several factors, including the potential confounding of microbial signatures associated with COVID-19 because of heterogeneous patient management in the clinical setting and the potential that gut microbiota reflects a patient’s health with no impact on disease severity, as well as lack of data on the role of antibiotics for severe and critical patients, the researchers noted. In addition, “gut microbiota composition is highly heterogeneous across human populations and changes in compositions reported here may not necessarily be reflected in patients with COVID-19 from other biogeographies,” they wrote.

The “longer follow-up of patients with COVID-19 (e.g., 3 months to 1 year after clearing the virus) is needed to address questions related to the duration of gut microbiota dysbiosis post recovery, link between microbiota dysbiosis and long-term persistent symptoms, and whether the dysbiosis or enrichment/depletion of specific gut microorganisms predisposes recovered individuals to future health problems,” they wrote.

However, the results suggest a likely role for gut microorganisms in host inflammatory responses to COVID-19 infection, and “underscore an urgent need to understand the specific roles of gut microorganisms in human immune function and systemic inflammation,” they concluded.
 

More than infectious

“A growing body of evidence suggests that severity of illness from COVID-19 is largely determined by the patient’s aberrant immune response to the virus,” Jatin Roper, MD, of Duke University, Durham, N.C., said in an interview. “Therefore, a critical question is: What patient factors determine this immune response? The gut microbiota closely interact with the host immune system and are altered in many immunological diseases,” he said. “Furthermore, the SARS-CoV-2 virus infects enterocytes in the intestine and causes symptomatic gastrointestinal disease in a subset of patients. Therefore, understanding a possible association between gut microbiota and COVID-19 may reveal microbial species involved in disease pathogenesis,” he emphasized.   

In the current study, “I was surprised to find that COVID-19 infection is associated with depletion of immunomodulatory gut bacteria,” said Dr. Roper. “An open question is whether these changes are caused by the SARS-CoV-2 virus and then result in altered immune response. Alternatively, the changes in gut microbiota may be a result of the immune response or other changes associated with the disease,” he said.

“COVID-19 is an immunological disease, not just an infectious disease,” explained Dr. Roper. “The gut microbiota may play an important role in the pathogenesis of the disease. Thus, specific gut microbes could one day be analyzed to risk stratify patients, or even modified to treat the disease,” he noted.
 

Beyond COVID-19

“Given the impact of the gut microbiota on health and disease, as well as the impact of diseases on the microbiota, I am not at all surprised to find that there were significant changes in the microbiota of COVID-19 patients and that these changes are associated with inflammatory cytokines, chemokines, and blood markers of tissue damage,” said Anthony Sung, MD, also of Duke University.

According to Dr. Sung, researchers have already been investigating possible connections between gut microbiota and other conditions such as Alzheimer’s disease, and it’s been hypothesized that these connections are mediated by interactions between the gut microbiota and the immune system.

“While this is an important paper in our understanding of COVID-19, and highlights the microbiome as a potential therapeutic target, we need to conduct clinical trials of microbiota-based interventions before we can fully realize the clinical implications of these findings,” he said.

The study was supported by the Health and Medical Research Fund, the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region, and donations from Hui Hoy & Chow Sin Lan Charity Fund Limited, Pine and Crane Company Limited, Mr. Hui Ming, and The D.H. Chen Foundation. The researchers had no financial conflicts to disclose. Dr. Roper and Dr. Sung had no financial conflicts to disclose.

COVID-19 infection altered the gut microbiota of adult patients and caused depletion of several types of bacteria with known immunomodulatory properties, based on data from a cohort study of 100 patients with confirmed COVID-19 infections from two hospitals.

“As the GI tract is the largest immunological organ in the body and its resident microbiota are known to modulate host immune responses, we hypothesized that the gut microbiota is associated with host inflammatory immune responses in COVID19,” wrote Yun Kit Yeoh, PhD, of the Chinese University of Hong Kong, and colleagues.

In a study published in Gut, the researchers investigated patient microbiota by collecting blood, stool, and patient records between February and May 2020 from 100 confirmed SARS-CoV-2–infected patients in Hong Kong during hospitalization, as well as follow-up stool samples from 27 patients up to 30 days after they cleared the COVID-19 virus; these observations were compared with 78 non–COVID-19 controls.

Overall, 274 stool samples were sequenced. Samples collected from patients during hospitalization for COVID-19 were compared with non–COVID-19 controls. The presence of phylum Bacteroidetes was significantly higher in COVID-19 patients compared with controls (23.9% vs. 12.8%; P < .001), as were Actinobacteria (26.1% vs. 19.0%; P < .001).

After controlling for antibiotics, the investigators found that “differences between cohorts were primarily linked to enrichment of taxa such as Parabacteroides, Sutterella wadsworthensis, and Bacteroides caccae and depletion of Adlercreutzia equolifaciens, Dorea formicigenerans, and Clostridium leptum in COVID-19 relative to non-COVID-19” (P < .05). In addition, Faecalibacterium prausnitzii and Bifidobacterium bifidum were negatively correlated with COVID-19 severity after investigators controlled for patient age and antibiotic use (P < .05).

The researchers also examined bacteria in COVID-19 patients and controls in the context of cytokines and other inflammatory markers. “We hypothesized that these compositional changes play a role in exacerbating disease by contributing to dysregulation of the immune response,” they said.

In fact, species depleted in COVID-19 patients including included B. adolescentis, E. rectale, and F. prausnitzii were negatively correlated with inflammatory markers including CXCL10, IL-10, TNF-alpha, and CCL2.

In addition, 42 stool samples from 27 patients showed significantly distinct gut microbiota from controls up to 30 days (median, 6 days) after virus clearance, regardless of antibiotics use (P < .05), the researchers said.
 

Long-term data needed

The study findings were limited by several factors, including the potential confounding of microbial signatures associated with COVID-19 because of heterogeneous patient management in the clinical setting and the potential that gut microbiota reflects a patient’s health with no impact on disease severity, as well as lack of data on the role of antibiotics for severe and critical patients, the researchers noted. In addition, “gut microbiota composition is highly heterogeneous across human populations and changes in compositions reported here may not necessarily be reflected in patients with COVID-19 from other biogeographies,” they wrote.

The “longer follow-up of patients with COVID-19 (e.g., 3 months to 1 year after clearing the virus) is needed to address questions related to the duration of gut microbiota dysbiosis post recovery, link between microbiota dysbiosis and long-term persistent symptoms, and whether the dysbiosis or enrichment/depletion of specific gut microorganisms predisposes recovered individuals to future health problems,” they wrote.

However, the results suggest a likely role for gut microorganisms in host inflammatory responses to COVID-19 infection, and “underscore an urgent need to understand the specific roles of gut microorganisms in human immune function and systemic inflammation,” they concluded.
 

More than infectious

“A growing body of evidence suggests that severity of illness from COVID-19 is largely determined by the patient’s aberrant immune response to the virus,” Jatin Roper, MD, of Duke University, Durham, N.C., said in an interview. “Therefore, a critical question is: What patient factors determine this immune response? The gut microbiota closely interact with the host immune system and are altered in many immunological diseases,” he said. “Furthermore, the SARS-CoV-2 virus infects enterocytes in the intestine and causes symptomatic gastrointestinal disease in a subset of patients. Therefore, understanding a possible association between gut microbiota and COVID-19 may reveal microbial species involved in disease pathogenesis,” he emphasized.   

In the current study, “I was surprised to find that COVID-19 infection is associated with depletion of immunomodulatory gut bacteria,” said Dr. Roper. “An open question is whether these changes are caused by the SARS-CoV-2 virus and then result in altered immune response. Alternatively, the changes in gut microbiota may be a result of the immune response or other changes associated with the disease,” he said.

“COVID-19 is an immunological disease, not just an infectious disease,” explained Dr. Roper. “The gut microbiota may play an important role in the pathogenesis of the disease. Thus, specific gut microbes could one day be analyzed to risk stratify patients, or even modified to treat the disease,” he noted.
 

Beyond COVID-19

“Given the impact of the gut microbiota on health and disease, as well as the impact of diseases on the microbiota, I am not at all surprised to find that there were significant changes in the microbiota of COVID-19 patients and that these changes are associated with inflammatory cytokines, chemokines, and blood markers of tissue damage,” said Anthony Sung, MD, also of Duke University.

According to Dr. Sung, researchers have already been investigating possible connections between gut microbiota and other conditions such as Alzheimer’s disease, and it’s been hypothesized that these connections are mediated by interactions between the gut microbiota and the immune system.

“While this is an important paper in our understanding of COVID-19, and highlights the microbiome as a potential therapeutic target, we need to conduct clinical trials of microbiota-based interventions before we can fully realize the clinical implications of these findings,” he said.

The study was supported by the Health and Medical Research Fund, the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region, and donations from Hui Hoy & Chow Sin Lan Charity Fund Limited, Pine and Crane Company Limited, Mr. Hui Ming, and The D.H. Chen Foundation. The researchers had no financial conflicts to disclose. Dr. Roper and Dr. Sung had no financial conflicts to disclose.

Women who experienced severe complications during pregnancy were more than twice as likely to die at any time after their last pregnancy, including post partum and beyond, based on data from more than 1 million women.

“Current data suggest that up to 88% of maternal deaths are preceded by severe maternal morbidity,” but the long-term risk of mortality and the effect of severe maternal morbidity has not been well studied, wrote U. Vivian Ukah, MPH, PhD, of McGill University, Montreal, and colleagues.

In a longitudinal cohort study published in Obstetrics & Gynecology, the researchers identified 1,229,306 pregnant women who delivered in Quebec between 1989 and 2016.

The primary outcome of in-hospital mortality after the last pregnancy, either post partum (within 42 days of delivery) or long term (43 days to 29 years after delivery).

Overall, 2.9% of the study population experienced severe maternal morbidity, with an associated mortality rate of 0.86 per 1,000 person-years versus 0.41 per 1,000 person-years in women without severe maternal morbidity. The median time to death for women with severe maternal mortality was 6.8 years, compared with 151 years for those without severe maternal morbidity.

The death rate at any time after delivery, post partum and beyond, was twice as high among women with severe maternal morbidity. The morbidities most often associated with long-term mortality after 42 days were severe cardiac complications (hazard ratio, 7.00), acute renal failure (HR, 4.35), and cerebrovascular accidents (HR, 4.03).

However, the mortality risk following severe maternal morbidity decreased over time, the researchers noted. Severe maternal morbidity was associated with 6.73 times the mortality risk, compared with no morbidity, during the period from 43 days to 11 months, but this difference dropped to 1.91, 1.77, and 1.18 times the risk, compared with no comorbidity, at 1-4 years, 5-9 years, and 10-29 years, respectively.

The study findings were limited by several factors, including the inability to prove causality, the use of only in-hospital mortality data, and the potential for missed cases that fell outside the Canadian Perinatal Surveillance System definition of severe maternal morbidity, the researchers noted.

However, the results suggest that identifying severe maternal morbidity may help identify women at risk for postpartum and long-term premature mortality. “Women with severe maternal morbidity may benefit from continued surveillance and preventative interventions to reduce the risk of premature mortality,” they concluded.

Increased morbidity rates drive need for research

“In this retrospective longitudinal cohort study of over 1.2 million women delivering in Quebec between 1989 and 2016, Dr. Ukah and her colleagues demonstrated the association between severe maternal morbidity [SMM] and an accelerated risk of mortality beyond the postpartum period, compared with women who do not experience SMM,” Rachel Humphrey, MD, a maternal-fetal medicine specialist at Advent Health in Orlando, said in an interview. “This study is important as there has been a steady increase in SMM in recent years. In the United States, the CDC reports that SMM affected more than 50,000 women in 2014 alone. Across multiple countries the decline in overall health of women giving birth is felt to contribute to SMM. As the rates of preexisting conditions such as maternal obesity, hypertension, diabetes, and advanced age increases, we can assume that SMM will increase as well. This study clearly depicts the association between SMM and maternal death at 43 days to years after the complicated delivery. We can assume that, as SMM increases, so will the risk of mortality beyond the postpartum period for these women who initially survive their serious pregnancy complication.”

Dr. Humphrey said that, in some respects, the study results are to be expected. “It is logical to assume that a patient with a life-threatening issue at delivery such as severe cardiac complications, acute renal failure and cerebrovascular accident would be at higher risk for long-term morbidity and mortality. This study also adds to the large body of evidence linking socioeconomic deprivation with SMM. But there were unexpected findings in this study. I did not expect certain types of SMM to be associated with an increased risk of death years after the event.For example, hysterectomy at delivery carried a hazard ratio of 3.54 for death at 5-9 years after the event. The association between severe hemorrhage and fully adjusted hazard ratio was similarly increased at 2.96 [2.37-3.71].”

 

More screening and prospective studies needed

“Recognizing the association between SMM and accelerated long-term risk of mortality is a first step in determining what interventions might improve health and longevity in women who experience SMM,” said Dr. Humphrey. “With the absence of prospective studies, it still is logical to assume that close medical follow-up and lifestyle interventions are appropriate in this population. Screening for and actively managing chronic conditions such as diabetes, dyslipidemia, and hypertension seems appropriate for these patients.”

As for further research, “I am interested to know through prospective clinical trials if specific health maintenance screens and interventions would have a positive impact on the life expectancy of survivors of SMM,” said Dr. Humphrey. “I applaud this team for providing data up to 27 years after an obstetric complication, and I am interested to see if Dr. Ukah and her team will continue their research to determine if there is a ‘second peak’ in mortality in the survivors of SMM when they are elderly. Finally, I would be interested to see more detailed data from this team on the associations between socioeconomic deprivation and short- and long-term mortality for women in their study. This information may help further fuel the movement toward social changes to maximize the health of the women and families we serve.”

The study was supported by the Heart & Stroke Foundation of Canada and awards to the lead author and others from the Fonds de recherche du Québec-Santé. The researchers and Dr. Humphrey had no financial conflicts to disclose.

Women who experienced severe complications during pregnancy were more than twice as likely to die at any time after their last pregnancy, including post partum and beyond, based on data from more than 1 million women.

“Current data suggest that up to 88% of maternal deaths are preceded by severe maternal morbidity,” but the long-term risk of mortality and the effect of severe maternal morbidity has not been well studied, wrote U. Vivian Ukah, MPH, PhD, of McGill University, Montreal, and colleagues.

In a longitudinal cohort study published in Obstetrics & Gynecology, the researchers identified 1,229,306 pregnant women who delivered in Quebec between 1989 and 2016.

The primary outcome of in-hospital mortality after the last pregnancy, either post partum (within 42 days of delivery) or long term (43 days to 29 years after delivery).

Overall, 2.9% of the study population experienced severe maternal morbidity, with an associated mortality rate of 0.86 per 1,000 person-years versus 0.41 per 1,000 person-years in women without severe maternal morbidity. The median time to death for women with severe maternal mortality was 6.8 years, compared with 151 years for those without severe maternal morbidity.

The death rate at any time after delivery, post partum and beyond, was twice as high among women with severe maternal morbidity. The morbidities most often associated with long-term mortality after 42 days were severe cardiac complications (hazard ratio, 7.00), acute renal failure (HR, 4.35), and cerebrovascular accidents (HR, 4.03).

However, the mortality risk following severe maternal morbidity decreased over time, the researchers noted. Severe maternal morbidity was associated with 6.73 times the mortality risk, compared with no morbidity, during the period from 43 days to 11 months, but this difference dropped to 1.91, 1.77, and 1.18 times the risk, compared with no comorbidity, at 1-4 years, 5-9 years, and 10-29 years, respectively.

The study findings were limited by several factors, including the inability to prove causality, the use of only in-hospital mortality data, and the potential for missed cases that fell outside the Canadian Perinatal Surveillance System definition of severe maternal morbidity, the researchers noted.

However, the results suggest that identifying severe maternal morbidity may help identify women at risk for postpartum and long-term premature mortality. “Women with severe maternal morbidity may benefit from continued surveillance and preventative interventions to reduce the risk of premature mortality,” they concluded.

Increased morbidity rates drive need for research

“In this retrospective longitudinal cohort study of over 1.2 million women delivering in Quebec between 1989 and 2016, Dr. Ukah and her colleagues demonstrated the association between severe maternal morbidity [SMM] and an accelerated risk of mortality beyond the postpartum period, compared with women who do not experience SMM,” Rachel Humphrey, MD, a maternal-fetal medicine specialist at Advent Health in Orlando, said in an interview. “This study is important as there has been a steady increase in SMM in recent years. In the United States, the CDC reports that SMM affected more than 50,000 women in 2014 alone. Across multiple countries the decline in overall health of women giving birth is felt to contribute to SMM. As the rates of preexisting conditions such as maternal obesity, hypertension, diabetes, and advanced age increases, we can assume that SMM will increase as well. This study clearly depicts the association between SMM and maternal death at 43 days to years after the complicated delivery. We can assume that, as SMM increases, so will the risk of mortality beyond the postpartum period for these women who initially survive their serious pregnancy complication.”

Dr. Humphrey said that, in some respects, the study results are to be expected. “It is logical to assume that a patient with a life-threatening issue at delivery such as severe cardiac complications, acute renal failure and cerebrovascular accident would be at higher risk for long-term morbidity and mortality. This study also adds to the large body of evidence linking socioeconomic deprivation with SMM. But there were unexpected findings in this study. I did not expect certain types of SMM to be associated with an increased risk of death years after the event.For example, hysterectomy at delivery carried a hazard ratio of 3.54 for death at 5-9 years after the event. The association between severe hemorrhage and fully adjusted hazard ratio was similarly increased at 2.96 [2.37-3.71].”

 

More screening and prospective studies needed

“Recognizing the association between SMM and accelerated long-term risk of mortality is a first step in determining what interventions might improve health and longevity in women who experience SMM,” said Dr. Humphrey. “With the absence of prospective studies, it still is logical to assume that close medical follow-up and lifestyle interventions are appropriate in this population. Screening for and actively managing chronic conditions such as diabetes, dyslipidemia, and hypertension seems appropriate for these patients.”

As for further research, “I am interested to know through prospective clinical trials if specific health maintenance screens and interventions would have a positive impact on the life expectancy of survivors of SMM,” said Dr. Humphrey. “I applaud this team for providing data up to 27 years after an obstetric complication, and I am interested to see if Dr. Ukah and her team will continue their research to determine if there is a ‘second peak’ in mortality in the survivors of SMM when they are elderly. Finally, I would be interested to see more detailed data from this team on the associations between socioeconomic deprivation and short- and long-term mortality for women in their study. This information may help further fuel the movement toward social changes to maximize the health of the women and families we serve.”

The study was supported by the Heart & Stroke Foundation of Canada and awards to the lead author and others from the Fonds de recherche du Québec-Santé. The researchers and Dr. Humphrey had no financial conflicts to disclose.

Women who experienced severe complications during pregnancy were more than twice as likely to die at any time after their last pregnancy, including post partum and beyond, based on data from more than 1 million women.

“Current data suggest that up to 88% of maternal deaths are preceded by severe maternal morbidity,” but the long-term risk of mortality and the effect of severe maternal morbidity has not been well studied, wrote U. Vivian Ukah, MPH, PhD, of McGill University, Montreal, and colleagues.

In a longitudinal cohort study published in Obstetrics & Gynecology, the researchers identified 1,229,306 pregnant women who delivered in Quebec between 1989 and 2016.

The primary outcome of in-hospital mortality after the last pregnancy, either post partum (within 42 days of delivery) or long term (43 days to 29 years after delivery).

Overall, 2.9% of the study population experienced severe maternal morbidity, with an associated mortality rate of 0.86 per 1,000 person-years versus 0.41 per 1,000 person-years in women without severe maternal morbidity. The median time to death for women with severe maternal mortality was 6.8 years, compared with 151 years for those without severe maternal morbidity.

The death rate at any time after delivery, post partum and beyond, was twice as high among women with severe maternal morbidity. The morbidities most often associated with long-term mortality after 42 days were severe cardiac complications (hazard ratio, 7.00), acute renal failure (HR, 4.35), and cerebrovascular accidents (HR, 4.03).

However, the mortality risk following severe maternal morbidity decreased over time, the researchers noted. Severe maternal morbidity was associated with 6.73 times the mortality risk, compared with no morbidity, during the period from 43 days to 11 months, but this difference dropped to 1.91, 1.77, and 1.18 times the risk, compared with no comorbidity, at 1-4 years, 5-9 years, and 10-29 years, respectively.

The study findings were limited by several factors, including the inability to prove causality, the use of only in-hospital mortality data, and the potential for missed cases that fell outside the Canadian Perinatal Surveillance System definition of severe maternal morbidity, the researchers noted.

However, the results suggest that identifying severe maternal morbidity may help identify women at risk for postpartum and long-term premature mortality. “Women with severe maternal morbidity may benefit from continued surveillance and preventative interventions to reduce the risk of premature mortality,” they concluded.

Increased morbidity rates drive need for research

“In this retrospective longitudinal cohort study of over 1.2 million women delivering in Quebec between 1989 and 2016, Dr. Ukah and her colleagues demonstrated the association between severe maternal morbidity [SMM] and an accelerated risk of mortality beyond the postpartum period, compared with women who do not experience SMM,” Rachel Humphrey, MD, a maternal-fetal medicine specialist at Advent Health in Orlando, said in an interview. “This study is important as there has been a steady increase in SMM in recent years. In the United States, the CDC reports that SMM affected more than 50,000 women in 2014 alone. Across multiple countries the decline in overall health of women giving birth is felt to contribute to SMM. As the rates of preexisting conditions such as maternal obesity, hypertension, diabetes, and advanced age increases, we can assume that SMM will increase as well. This study clearly depicts the association between SMM and maternal death at 43 days to years after the complicated delivery. We can assume that, as SMM increases, so will the risk of mortality beyond the postpartum period for these women who initially survive their serious pregnancy complication.”

Dr. Humphrey said that, in some respects, the study results are to be expected. “It is logical to assume that a patient with a life-threatening issue at delivery such as severe cardiac complications, acute renal failure and cerebrovascular accident would be at higher risk for long-term morbidity and mortality. This study also adds to the large body of evidence linking socioeconomic deprivation with SMM. But there were unexpected findings in this study. I did not expect certain types of SMM to be associated with an increased risk of death years after the event.For example, hysterectomy at delivery carried a hazard ratio of 3.54 for death at 5-9 years after the event. The association between severe hemorrhage and fully adjusted hazard ratio was similarly increased at 2.96 [2.37-3.71].”

 

More screening and prospective studies needed

“Recognizing the association between SMM and accelerated long-term risk of mortality is a first step in determining what interventions might improve health and longevity in women who experience SMM,” said Dr. Humphrey. “With the absence of prospective studies, it still is logical to assume that close medical follow-up and lifestyle interventions are appropriate in this population. Screening for and actively managing chronic conditions such as diabetes, dyslipidemia, and hypertension seems appropriate for these patients.”

As for further research, “I am interested to know through prospective clinical trials if specific health maintenance screens and interventions would have a positive impact on the life expectancy of survivors of SMM,” said Dr. Humphrey. “I applaud this team for providing data up to 27 years after an obstetric complication, and I am interested to see if Dr. Ukah and her team will continue their research to determine if there is a ‘second peak’ in mortality in the survivors of SMM when they are elderly. Finally, I would be interested to see more detailed data from this team on the associations between socioeconomic deprivation and short- and long-term mortality for women in their study. This information may help further fuel the movement toward social changes to maximize the health of the women and families we serve.”

The study was supported by the Heart & Stroke Foundation of Canada and awards to the lead author and others from the Fonds de recherche du Québec-Santé. The researchers and Dr. Humphrey had no financial conflicts to disclose.

All-cause mortality in patients with COPD over 10 years of follow-up was accurately predicted by a newly developed model based on a point system incorporating imaging-derived variables.

decade3d/Thinkstock

Identifying risk factors is important to develop treatments and preventive strategies, but the role of imaging variables in COPD mortality among smokers has not been well studied, wrote investigator Matthew Strand, PhD, of National Jewish Health in Denver, and colleagues.

An established risk model is the body mass index–airflow Obstruction-Dyspnea-Exercise capacity (BODE) index, developed to predict mortality in COPD patients over a 4-year period. The investigators noted that while models such as BODE provide useful information about predictors of mortality in COPD, they were developed using participants in the Global initiative for obstructive Lung Disease (GOLD) spirometry grades 1-4, and have been largely constructed without quantitative computed tomography (CT) imaging variables until recently.

“The BODE index was created as a simple point scoring system to predict risk of all-cause mortality within 4 years, and is based on FEV_{1 [forced expiratory volume at 1 second]}, [6-minute walk test], dyspnea and BMI, a subset of predictors we considered in our model,” the investigators noted. The new model includes data from pulmonary function tests and volumetric CT scans.

In a study published in Chronic Obstructive Pulmonary Diseases, the researchers identified 9,074 current and past smokers in the COPD Genetic Epidemiology study (COPDGene) for whom complete data were available. They developed a point system to determine mortality risk in current and former smokers after controlling for multiple risk factors. The average age of the study population was 60 years. All participants were current or former smokers with a smoking history of at least 10 pack-years.

Assessments of the study participants included a medical history, pre- and post-bronchodilator spirometry, a 6-minute walk distance test, and inspiratory and expiratory CT scans. The researchers analyzed mortality risk in the context of Global Initiative for Obstructive Lung Disease (GOLD) classifications of patients in the sample.

Overall, the average 10-year mortality risk was 18% for women and 25% for men. Performance on the 6-minute walk test (distances less than 500 feet), FEV₁ (less than 20), and older age (80 years and older) were the strongest predictors of mortality.

The model showed strong predictive accuracy, with an area under the receiver operating characteristic curve averaging 0.797 that was validated in an external cohort, the researchers said.

The study findings were limited by the observational design that does not allow for estimating the causal effects of such modifiable factors as smoking cessation, that might impact the walking test and FEV₁ values, the researchers noted. In addition, the model did not allow for testing the effects of smoking vs. not smoking.

However, the model developed in the study “will allow physicians and patients to better understand factors affecting risk of an adverse event, some of which may be modifiable,” the researchers said. “The risk estimates can be used to target groups of individuals for future clinical trials, including those not currently classified as having COPD based on GOLD criteria,” they said.

The study was supported by the National Heart, Lung, and Blood Institute and by the COPD Foundation through contributions to an industry advisory committee including AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion.

All-cause mortality in patients with COPD over 10 years of follow-up was accurately predicted by a newly developed model based on a point system incorporating imaging-derived variables.

decade3d/Thinkstock

Identifying risk factors is important to develop treatments and preventive strategies, but the role of imaging variables in COPD mortality among smokers has not been well studied, wrote investigator Matthew Strand, PhD, of National Jewish Health in Denver, and colleagues.

An established risk model is the body mass index–airflow Obstruction-Dyspnea-Exercise capacity (BODE) index, developed to predict mortality in COPD patients over a 4-year period. The investigators noted that while models such as BODE provide useful information about predictors of mortality in COPD, they were developed using participants in the Global initiative for obstructive Lung Disease (GOLD) spirometry grades 1-4, and have been largely constructed without quantitative computed tomography (CT) imaging variables until recently.

“The BODE index was created as a simple point scoring system to predict risk of all-cause mortality within 4 years, and is based on FEV_{1 [forced expiratory volume at 1 second]}, [6-minute walk test], dyspnea and BMI, a subset of predictors we considered in our model,” the investigators noted. The new model includes data from pulmonary function tests and volumetric CT scans.

In a study published in Chronic Obstructive Pulmonary Diseases, the researchers identified 9,074 current and past smokers in the COPD Genetic Epidemiology study (COPDGene) for whom complete data were available. They developed a point system to determine mortality risk in current and former smokers after controlling for multiple risk factors. The average age of the study population was 60 years. All participants were current or former smokers with a smoking history of at least 10 pack-years.

Assessments of the study participants included a medical history, pre- and post-bronchodilator spirometry, a 6-minute walk distance test, and inspiratory and expiratory CT scans. The researchers analyzed mortality risk in the context of Global Initiative for Obstructive Lung Disease (GOLD) classifications of patients in the sample.

Overall, the average 10-year mortality risk was 18% for women and 25% for men. Performance on the 6-minute walk test (distances less than 500 feet), FEV₁ (less than 20), and older age (80 years and older) were the strongest predictors of mortality.

The model showed strong predictive accuracy, with an area under the receiver operating characteristic curve averaging 0.797 that was validated in an external cohort, the researchers said.

The study findings were limited by the observational design that does not allow for estimating the causal effects of such modifiable factors as smoking cessation, that might impact the walking test and FEV₁ values, the researchers noted. In addition, the model did not allow for testing the effects of smoking vs. not smoking.

However, the model developed in the study “will allow physicians and patients to better understand factors affecting risk of an adverse event, some of which may be modifiable,” the researchers said. “The risk estimates can be used to target groups of individuals for future clinical trials, including those not currently classified as having COPD based on GOLD criteria,” they said.

The study was supported by the National Heart, Lung, and Blood Institute and by the COPD Foundation through contributions to an industry advisory committee including AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion.

All-cause mortality in patients with COPD over 10 years of follow-up was accurately predicted by a newly developed model based on a point system incorporating imaging-derived variables.

decade3d/Thinkstock

Identifying risk factors is important to develop treatments and preventive strategies, but the role of imaging variables in COPD mortality among smokers has not been well studied, wrote investigator Matthew Strand, PhD, of National Jewish Health in Denver, and colleagues.

An established risk model is the body mass index–airflow Obstruction-Dyspnea-Exercise capacity (BODE) index, developed to predict mortality in COPD patients over a 4-year period. The investigators noted that while models such as BODE provide useful information about predictors of mortality in COPD, they were developed using participants in the Global initiative for obstructive Lung Disease (GOLD) spirometry grades 1-4, and have been largely constructed without quantitative computed tomography (CT) imaging variables until recently.

“The BODE index was created as a simple point scoring system to predict risk of all-cause mortality within 4 years, and is based on FEV_{1 [forced expiratory volume at 1 second]}, [6-minute walk test], dyspnea and BMI, a subset of predictors we considered in our model,” the investigators noted. The new model includes data from pulmonary function tests and volumetric CT scans.

In a study published in Chronic Obstructive Pulmonary Diseases, the researchers identified 9,074 current and past smokers in the COPD Genetic Epidemiology study (COPDGene) for whom complete data were available. They developed a point system to determine mortality risk in current and former smokers after controlling for multiple risk factors. The average age of the study population was 60 years. All participants were current or former smokers with a smoking history of at least 10 pack-years.

Assessments of the study participants included a medical history, pre- and post-bronchodilator spirometry, a 6-minute walk distance test, and inspiratory and expiratory CT scans. The researchers analyzed mortality risk in the context of Global Initiative for Obstructive Lung Disease (GOLD) classifications of patients in the sample.

Overall, the average 10-year mortality risk was 18% for women and 25% for men. Performance on the 6-minute walk test (distances less than 500 feet), FEV₁ (less than 20), and older age (80 years and older) were the strongest predictors of mortality.

The model showed strong predictive accuracy, with an area under the receiver operating characteristic curve averaging 0.797 that was validated in an external cohort, the researchers said.

The study findings were limited by the observational design that does not allow for estimating the causal effects of such modifiable factors as smoking cessation, that might impact the walking test and FEV₁ values, the researchers noted. In addition, the model did not allow for testing the effects of smoking vs. not smoking.

However, the model developed in the study “will allow physicians and patients to better understand factors affecting risk of an adverse event, some of which may be modifiable,” the researchers said. “The risk estimates can be used to target groups of individuals for future clinical trials, including those not currently classified as having COPD based on GOLD criteria,” they said.

The study was supported by the National Heart, Lung, and Blood Institute and by the COPD Foundation through contributions to an industry advisory committee including AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion.

Patients with rheumatoid arthritis–associated interstitial lung disease showed increases in overall mortality, respiratory mortality, and cancer mortality, compared with RA patients without interstitial lung disease, based on data from more than 500,000 patients in a nationwide cohort study.

RA-associated interstitial lung disease (RA-ILD) has been associated with worse survival rates as well as reduced quality of life, functional impairment, and increased health care use and costs, wrote Jeffrey A. Sparks, MD, of Brigham and Women’s Hospital, Boston, and colleagues. However, data on the incidence and prevalence of RA-ILD have been inconsistent and large studies are lacking.

In a study published online in Rheumatology, the researchers identified 509,787 RA patients aged 65 years and older from Medicare claims data. The average age of the patients was 72.6 years, and 76.2% were women.

At baseline, 10,306 (2%) of the study population had RA-ILD, and 13,372 (2.7%) developed RA-ILD over an average of 3.8 years’ follow-up per person (total of 1,873,127 person-years of follow-up). The overall incidence of RA-ILD was 7.14 per 1,000 person-years.

Overall mortality was significantly higher among RA-ILD patients than in those with RA alone in a multivariate analysis (38.7% vs. 20.7%; hazard ratio, 1.66).

In addition, RA-ILD was associated with an increased risk of respiratory mortality (HR, 4.39) and cancer mortality (HR, 1.56), compared with RA without ILD. For these hazard regression analyses, the researchers used Fine and Gray subdistribution HRs “to handle competing risks of alternative causes of mortality. For example, the risk of respiratory mortality for patients with RA-ILD, compared with RA without ILD also accounted for the competing risk of cardiovascular, cancer, infection and other types of mortality.”

Case courtesy A.Prof Frank Gaillard, Radiopaedia.org, rID: 12274

In another multivariate analysis, male gender, smoking, asthma, chronic obstructive pulmonary disorder, and medication use (specifically biologic disease-modifying antirheumatic drugs, targeted synthetic DMARDs, and glucocorticoids) were independently associated with increased incident RA-ILD at baseline. However, “the associations of RA-related medications with incident RA-ILD risk should be interpreted with caution since they may be explained by unmeasured factors, including RA disease activity, severity, comorbidities, and prior or concomitant medication use,” the researchers noted.

The study findings were limited by several factors, including the lack of data on disease activity, disease duration, disease severity, and RA-related autoantibodies, the researchers noted. However, the results support data from previous studies and were strengthened by the large sample size and data on demographics and health care use.

“Ours is the first to study the epidemiology and mortality outcomes of RA-ILD using a validated claims algorithm to identify RA and RA-ILD,” and “to quantify the mortality burden of RA-ILD and to identify a potentially novel association of RA-ILD with cancer mortality,” they noted.

The study was supported by an investigator-initiated grant from Bristol-Myers Squibb. Lead author Dr. Sparks disclosed support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund. Dr. Sparks also disclosed serving as a consultant to Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer for work unrelated to the current study. Other authors reported research funding from Bristol-Myers Squibb, involvement in a clinical trial funded by Genentech and Bristol-Myers Squibb, and receiving research support to Brigham and Women’s Hospital for other studies from AbbVie, Bayer, Bristol-Myers Squibb, Novartis, Pfizer, Roche, and Vertex.

Patients with rheumatoid arthritis–associated interstitial lung disease showed increases in overall mortality, respiratory mortality, and cancer mortality, compared with RA patients without interstitial lung disease, based on data from more than 500,000 patients in a nationwide cohort study.

RA-associated interstitial lung disease (RA-ILD) has been associated with worse survival rates as well as reduced quality of life, functional impairment, and increased health care use and costs, wrote Jeffrey A. Sparks, MD, of Brigham and Women’s Hospital, Boston, and colleagues. However, data on the incidence and prevalence of RA-ILD have been inconsistent and large studies are lacking.

In a study published online in Rheumatology, the researchers identified 509,787 RA patients aged 65 years and older from Medicare claims data. The average age of the patients was 72.6 years, and 76.2% were women.

At baseline, 10,306 (2%) of the study population had RA-ILD, and 13,372 (2.7%) developed RA-ILD over an average of 3.8 years’ follow-up per person (total of 1,873,127 person-years of follow-up). The overall incidence of RA-ILD was 7.14 per 1,000 person-years.

Overall mortality was significantly higher among RA-ILD patients than in those with RA alone in a multivariate analysis (38.7% vs. 20.7%; hazard ratio, 1.66).

In addition, RA-ILD was associated with an increased risk of respiratory mortality (HR, 4.39) and cancer mortality (HR, 1.56), compared with RA without ILD. For these hazard regression analyses, the researchers used Fine and Gray subdistribution HRs “to handle competing risks of alternative causes of mortality. For example, the risk of respiratory mortality for patients with RA-ILD, compared with RA without ILD also accounted for the competing risk of cardiovascular, cancer, infection and other types of mortality.”

Case courtesy A.Prof Frank Gaillard, Radiopaedia.org, rID: 12274

In another multivariate analysis, male gender, smoking, asthma, chronic obstructive pulmonary disorder, and medication use (specifically biologic disease-modifying antirheumatic drugs, targeted synthetic DMARDs, and glucocorticoids) were independently associated with increased incident RA-ILD at baseline. However, “the associations of RA-related medications with incident RA-ILD risk should be interpreted with caution since they may be explained by unmeasured factors, including RA disease activity, severity, comorbidities, and prior or concomitant medication use,” the researchers noted.

The study findings were limited by several factors, including the lack of data on disease activity, disease duration, disease severity, and RA-related autoantibodies, the researchers noted. However, the results support data from previous studies and were strengthened by the large sample size and data on demographics and health care use.

“Ours is the first to study the epidemiology and mortality outcomes of RA-ILD using a validated claims algorithm to identify RA and RA-ILD,” and “to quantify the mortality burden of RA-ILD and to identify a potentially novel association of RA-ILD with cancer mortality,” they noted.

The study was supported by an investigator-initiated grant from Bristol-Myers Squibb. Lead author Dr. Sparks disclosed support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund. Dr. Sparks also disclosed serving as a consultant to Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer for work unrelated to the current study. Other authors reported research funding from Bristol-Myers Squibb, involvement in a clinical trial funded by Genentech and Bristol-Myers Squibb, and receiving research support to Brigham and Women’s Hospital for other studies from AbbVie, Bayer, Bristol-Myers Squibb, Novartis, Pfizer, Roche, and Vertex.

Patients with rheumatoid arthritis–associated interstitial lung disease showed increases in overall mortality, respiratory mortality, and cancer mortality, compared with RA patients without interstitial lung disease, based on data from more than 500,000 patients in a nationwide cohort study.

RA-associated interstitial lung disease (RA-ILD) has been associated with worse survival rates as well as reduced quality of life, functional impairment, and increased health care use and costs, wrote Jeffrey A. Sparks, MD, of Brigham and Women’s Hospital, Boston, and colleagues. However, data on the incidence and prevalence of RA-ILD have been inconsistent and large studies are lacking.

In a study published online in Rheumatology, the researchers identified 509,787 RA patients aged 65 years and older from Medicare claims data. The average age of the patients was 72.6 years, and 76.2% were women.

At baseline, 10,306 (2%) of the study population had RA-ILD, and 13,372 (2.7%) developed RA-ILD over an average of 3.8 years’ follow-up per person (total of 1,873,127 person-years of follow-up). The overall incidence of RA-ILD was 7.14 per 1,000 person-years.

Overall mortality was significantly higher among RA-ILD patients than in those with RA alone in a multivariate analysis (38.7% vs. 20.7%; hazard ratio, 1.66).

In addition, RA-ILD was associated with an increased risk of respiratory mortality (HR, 4.39) and cancer mortality (HR, 1.56), compared with RA without ILD. For these hazard regression analyses, the researchers used Fine and Gray subdistribution HRs “to handle competing risks of alternative causes of mortality. For example, the risk of respiratory mortality for patients with RA-ILD, compared with RA without ILD also accounted for the competing risk of cardiovascular, cancer, infection and other types of mortality.”

Case courtesy A.Prof Frank Gaillard, Radiopaedia.org, rID: 12274

In another multivariate analysis, male gender, smoking, asthma, chronic obstructive pulmonary disorder, and medication use (specifically biologic disease-modifying antirheumatic drugs, targeted synthetic DMARDs, and glucocorticoids) were independently associated with increased incident RA-ILD at baseline. However, “the associations of RA-related medications with incident RA-ILD risk should be interpreted with caution since they may be explained by unmeasured factors, including RA disease activity, severity, comorbidities, and prior or concomitant medication use,” the researchers noted.

The study findings were limited by several factors, including the lack of data on disease activity, disease duration, disease severity, and RA-related autoantibodies, the researchers noted. However, the results support data from previous studies and were strengthened by the large sample size and data on demographics and health care use.

“Ours is the first to study the epidemiology and mortality outcomes of RA-ILD using a validated claims algorithm to identify RA and RA-ILD,” and “to quantify the mortality burden of RA-ILD and to identify a potentially novel association of RA-ILD with cancer mortality,” they noted.

The study was supported by an investigator-initiated grant from Bristol-Myers Squibb. Lead author Dr. Sparks disclosed support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund. Dr. Sparks also disclosed serving as a consultant to Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer for work unrelated to the current study. Other authors reported research funding from Bristol-Myers Squibb, involvement in a clinical trial funded by Genentech and Bristol-Myers Squibb, and receiving research support to Brigham and Women’s Hospital for other studies from AbbVie, Bayer, Bristol-Myers Squibb, Novartis, Pfizer, Roche, and Vertex.

Palliative care referrals for inpatients with pulmonary arterial hypertension averaged 2%, a retrospective study of more than 30,000 hospital admissions has found.

“Specialty palliative care services (PCS) are present in the vast majority of hospitals with more than 300 beds, and PCS use for patients who are facing serious illness with potentially life-limiting prognoses increasingly is becoming the standard of care,” wrote Vidhu Anand, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. But despite experts recommending PCS in pulmonary arterial hypertension (PAH), data on the use of palliative care referrals for PAH patients are limited, they added.

In a study published in Chest, the researchers used the National (Nationwide) Inpatient Sample to identify 30,495 admissions with a primary diagnosis of PAH between 2001 through 2017. The primary outcome was the use of PCS in these patients.

Overall, inpatient use of PCS was 2.2%, but that figure increased from 0.5% in 2001 to 7.6% in 2017, representing a fivefold increase over the study period, with a significant increase after 2009. The reason for this notable increase remains unclear; however, “it may be related to recognition of palliative care and hospice as a medical subspecialty with board certification in 2008 or identification of palliative care by the National Priorities Partnership as one of six priority areas in 2008,” the researchers said.
 

Incorporating palliative care in a treatment strategy

The perception of PCS as an element of treatment plans for patients with severe lung disease, and not only as end-of-life care, has certainly increased in recent years, Sachin Gupta, MD, FCCP, said in an interview.

Dr. Gupta is a pulmonologist practicing in the San Francisco Bay area, and he did not take part in the study. He recommended early integration of PCS treating patients with PAH. “I have frequently asked PCS to aid early on during inpatient admission with PAH patients for pain management, as well as for aiding in POLST [Physician Orders for Life-Sustaining Treatment] paperwork to be completed. Increased age and comorbidities are certainly risk factors themselves for a longer hospital course and worse outcomes; in addition, in center-based PAH care there are more means available by which to give a patient with right heart failure that ‘one last shot’ – an opportunity for a longer life. I truly think it is a relationship with the patient, built from the outpatient pulmonary hypertension clinic, that allows the treating physician to have a better sense of a patient’s quality of life longitudinally, and to have the candid conversation when things begin to decline.”

Which patients receive PCS?

The study found that socioeconomic factors, and the severity of illness, are the drivers of PCS referrals. In a multivariate analysis, independent predictors of PCS use included white race, private insurance, and higher socioeconomic status. Additional independent predictors of PCS use included increased comorbidities, admission to an urban hospital, admission to a small hospital, presence of heart failure and cardiogenic shock, acute noncardiac organ failure, and use of extracorporeal membrane oxygenation and noninvasive mechanical ventilation, the researchers noted.

Patients who received PCS consultation were significantly more likely than those not receiving PCS to have DNR status (46.2% vs. 1.8%), longer length of hospital stay (12.9 days vs. 7.2 days), higher hospitalization costs $130,434 vs. $56,499), and higher in-hospital mortality (52.8% vs. 6.4%; P < .001 for all).

Some patients refuse PCS and others are not offered PCS. Dr. Gupta noted that it should be no surprise that not all patients are comfortable with the idea of a PCS referral. “Fear, misunderstanding, and cultural beliefs may be individually or together at the root of resistance to PCS. Their reluctance may be due to a ‘false narrative’ of the purpose of palliative care. The conception of PCS being for end-of-life care may be the result of personal experiences or experience with loved ones. Occasionally, a patient equates PCS with access to narcotics (‘knock me out’), which they may or may not want. I try to reassure patients that there will be no coercion for anything they do not want, and at the end of the day, the medical team is the main driver of their care, not the palliative service.”

Actively drug-abusing PAH patients are a particular challenge, said Dr. Gupta. These patients often refuse palliative care referral both as inpatients and outpatients. “Such patients are an enigma for many PAH-treating physicians as they may survive to discharge, despite a terrible prognosis predicted by their testing.”

In addition, patients in whom organ transplantation is being pursued may not receive timely PCS, he said. “It can be an absolute challenge to bring such patients to the finish line (transplantation), and the timing of PCS referral is often deferred. Arguably, for better or worse, such patients refuse, or more often are not offered, PCS as inpatients while there is still a chance organ transplantation is a viable option for them.”

The use of PCS in less than 10% of PAH admissions is similar to previous studies showing low use of PCS for patients with acute myocardial infarction, heart failure, and COPD, the researchers noted. However, “Given the high morbidity and mortality associated with PAH even after hospitalization, hospital admissions without PCS use represent a missed opportunity,” the investigators wrote.
 

Early warning on the need for PCS

Increasing PCS referrals for PAH patients requires clinicians to be proactive, Dr. Gupta stressed. “Pulmonologists, especially those managing pulmonary hypertension outpatients without the aid of a PAH center, should remain vigilant at all routine visits to calculate a patient’s risk score (i.e. REVEAL 2.0 risk calculator) to stratify their risk of 1-year mortality. Based on this assessment, shared decision making can help guide next steps including early outpatient PCS involvement for those at high risk. I also calculate a patient’s risk score, based on the data I have, when PAH patients are admitted to the hospital. Occasionally, a patient who I initially think is moderate risk turns out to be high risk when I calculate their risk score. In such high-risk patients, PCS consultation should certainly be considered early on.”

The study findings were limited by several factors including the possible coding errors associated with use of discharge diagnosis, lack of data on medication and the cause of PAH, and lack of information on the reasons for PCS referrals, the researchers noted. However, the results “addressed an important knowledge gap highlighting the national use of PCS in PAH,” they said. Further research is needed to address disparities and the integration of PCS into PAH care protocols, they added.

The researchers had no financial conflicts to disclose. The study received no outside funding; one coauthor disclosed support from the National Center for Advancing Translational Sciences Clinical and Translational Science.

Palliative care referrals for inpatients with pulmonary arterial hypertension averaged 2%, a retrospective study of more than 30,000 hospital admissions has found.

“Specialty palliative care services (PCS) are present in the vast majority of hospitals with more than 300 beds, and PCS use for patients who are facing serious illness with potentially life-limiting prognoses increasingly is becoming the standard of care,” wrote Vidhu Anand, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. But despite experts recommending PCS in pulmonary arterial hypertension (PAH), data on the use of palliative care referrals for PAH patients are limited, they added.

In a study published in Chest, the researchers used the National (Nationwide) Inpatient Sample to identify 30,495 admissions with a primary diagnosis of PAH between 2001 through 2017. The primary outcome was the use of PCS in these patients.

Overall, inpatient use of PCS was 2.2%, but that figure increased from 0.5% in 2001 to 7.6% in 2017, representing a fivefold increase over the study period, with a significant increase after 2009. The reason for this notable increase remains unclear; however, “it may be related to recognition of palliative care and hospice as a medical subspecialty with board certification in 2008 or identification of palliative care by the National Priorities Partnership as one of six priority areas in 2008,” the researchers said.
 

Incorporating palliative care in a treatment strategy

The perception of PCS as an element of treatment plans for patients with severe lung disease, and not only as end-of-life care, has certainly increased in recent years, Sachin Gupta, MD, FCCP, said in an interview.

Dr. Gupta is a pulmonologist practicing in the San Francisco Bay area, and he did not take part in the study. He recommended early integration of PCS treating patients with PAH. “I have frequently asked PCS to aid early on during inpatient admission with PAH patients for pain management, as well as for aiding in POLST [Physician Orders for Life-Sustaining Treatment] paperwork to be completed. Increased age and comorbidities are certainly risk factors themselves for a longer hospital course and worse outcomes; in addition, in center-based PAH care there are more means available by which to give a patient with right heart failure that ‘one last shot’ – an opportunity for a longer life. I truly think it is a relationship with the patient, built from the outpatient pulmonary hypertension clinic, that allows the treating physician to have a better sense of a patient’s quality of life longitudinally, and to have the candid conversation when things begin to decline.”

Which patients receive PCS?

The study found that socioeconomic factors, and the severity of illness, are the drivers of PCS referrals. In a multivariate analysis, independent predictors of PCS use included white race, private insurance, and higher socioeconomic status. Additional independent predictors of PCS use included increased comorbidities, admission to an urban hospital, admission to a small hospital, presence of heart failure and cardiogenic shock, acute noncardiac organ failure, and use of extracorporeal membrane oxygenation and noninvasive mechanical ventilation, the researchers noted.

Patients who received PCS consultation were significantly more likely than those not receiving PCS to have DNR status (46.2% vs. 1.8%), longer length of hospital stay (12.9 days vs. 7.2 days), higher hospitalization costs $130,434 vs. $56,499), and higher in-hospital mortality (52.8% vs. 6.4%; P < .001 for all).

Some patients refuse PCS and others are not offered PCS. Dr. Gupta noted that it should be no surprise that not all patients are comfortable with the idea of a PCS referral. “Fear, misunderstanding, and cultural beliefs may be individually or together at the root of resistance to PCS. Their reluctance may be due to a ‘false narrative’ of the purpose of palliative care. The conception of PCS being for end-of-life care may be the result of personal experiences or experience with loved ones. Occasionally, a patient equates PCS with access to narcotics (‘knock me out’), which they may or may not want. I try to reassure patients that there will be no coercion for anything they do not want, and at the end of the day, the medical team is the main driver of their care, not the palliative service.”

Actively drug-abusing PAH patients are a particular challenge, said Dr. Gupta. These patients often refuse palliative care referral both as inpatients and outpatients. “Such patients are an enigma for many PAH-treating physicians as they may survive to discharge, despite a terrible prognosis predicted by their testing.”

In addition, patients in whom organ transplantation is being pursued may not receive timely PCS, he said. “It can be an absolute challenge to bring such patients to the finish line (transplantation), and the timing of PCS referral is often deferred. Arguably, for better or worse, such patients refuse, or more often are not offered, PCS as inpatients while there is still a chance organ transplantation is a viable option for them.”

The use of PCS in less than 10% of PAH admissions is similar to previous studies showing low use of PCS for patients with acute myocardial infarction, heart failure, and COPD, the researchers noted. However, “Given the high morbidity and mortality associated with PAH even after hospitalization, hospital admissions without PCS use represent a missed opportunity,” the investigators wrote.
 

Early warning on the need for PCS

Increasing PCS referrals for PAH patients requires clinicians to be proactive, Dr. Gupta stressed. “Pulmonologists, especially those managing pulmonary hypertension outpatients without the aid of a PAH center, should remain vigilant at all routine visits to calculate a patient’s risk score (i.e. REVEAL 2.0 risk calculator) to stratify their risk of 1-year mortality. Based on this assessment, shared decision making can help guide next steps including early outpatient PCS involvement for those at high risk. I also calculate a patient’s risk score, based on the data I have, when PAH patients are admitted to the hospital. Occasionally, a patient who I initially think is moderate risk turns out to be high risk when I calculate their risk score. In such high-risk patients, PCS consultation should certainly be considered early on.”

The study findings were limited by several factors including the possible coding errors associated with use of discharge diagnosis, lack of data on medication and the cause of PAH, and lack of information on the reasons for PCS referrals, the researchers noted. However, the results “addressed an important knowledge gap highlighting the national use of PCS in PAH,” they said. Further research is needed to address disparities and the integration of PCS into PAH care protocols, they added.

The researchers had no financial conflicts to disclose. The study received no outside funding; one coauthor disclosed support from the National Center for Advancing Translational Sciences Clinical and Translational Science.

Palliative care referrals for inpatients with pulmonary arterial hypertension averaged 2%, a retrospective study of more than 30,000 hospital admissions has found.

“Specialty palliative care services (PCS) are present in the vast majority of hospitals with more than 300 beds, and PCS use for patients who are facing serious illness with potentially life-limiting prognoses increasingly is becoming the standard of care,” wrote Vidhu Anand, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. But despite experts recommending PCS in pulmonary arterial hypertension (PAH), data on the use of palliative care referrals for PAH patients are limited, they added.

In a study published in Chest, the researchers used the National (Nationwide) Inpatient Sample to identify 30,495 admissions with a primary diagnosis of PAH between 2001 through 2017. The primary outcome was the use of PCS in these patients.

Overall, inpatient use of PCS was 2.2%, but that figure increased from 0.5% in 2001 to 7.6% in 2017, representing a fivefold increase over the study period, with a significant increase after 2009. The reason for this notable increase remains unclear; however, “it may be related to recognition of palliative care and hospice as a medical subspecialty with board certification in 2008 or identification of palliative care by the National Priorities Partnership as one of six priority areas in 2008,” the researchers said.
 

Incorporating palliative care in a treatment strategy

The perception of PCS as an element of treatment plans for patients with severe lung disease, and not only as end-of-life care, has certainly increased in recent years, Sachin Gupta, MD, FCCP, said in an interview.

Dr. Gupta is a pulmonologist practicing in the San Francisco Bay area, and he did not take part in the study. He recommended early integration of PCS treating patients with PAH. “I have frequently asked PCS to aid early on during inpatient admission with PAH patients for pain management, as well as for aiding in POLST [Physician Orders for Life-Sustaining Treatment] paperwork to be completed. Increased age and comorbidities are certainly risk factors themselves for a longer hospital course and worse outcomes; in addition, in center-based PAH care there are more means available by which to give a patient with right heart failure that ‘one last shot’ – an opportunity for a longer life. I truly think it is a relationship with the patient, built from the outpatient pulmonary hypertension clinic, that allows the treating physician to have a better sense of a patient’s quality of life longitudinally, and to have the candid conversation when things begin to decline.”

Which patients receive PCS?

The study found that socioeconomic factors, and the severity of illness, are the drivers of PCS referrals. In a multivariate analysis, independent predictors of PCS use included white race, private insurance, and higher socioeconomic status. Additional independent predictors of PCS use included increased comorbidities, admission to an urban hospital, admission to a small hospital, presence of heart failure and cardiogenic shock, acute noncardiac organ failure, and use of extracorporeal membrane oxygenation and noninvasive mechanical ventilation, the researchers noted.

Patients who received PCS consultation were significantly more likely than those not receiving PCS to have DNR status (46.2% vs. 1.8%), longer length of hospital stay (12.9 days vs. 7.2 days), higher hospitalization costs $130,434 vs. $56,499), and higher in-hospital mortality (52.8% vs. 6.4%; P < .001 for all).

Some patients refuse PCS and others are not offered PCS. Dr. Gupta noted that it should be no surprise that not all patients are comfortable with the idea of a PCS referral. “Fear, misunderstanding, and cultural beliefs may be individually or together at the root of resistance to PCS. Their reluctance may be due to a ‘false narrative’ of the purpose of palliative care. The conception of PCS being for end-of-life care may be the result of personal experiences or experience with loved ones. Occasionally, a patient equates PCS with access to narcotics (‘knock me out’), which they may or may not want. I try to reassure patients that there will be no coercion for anything they do not want, and at the end of the day, the medical team is the main driver of their care, not the palliative service.”

Actively drug-abusing PAH patients are a particular challenge, said Dr. Gupta. These patients often refuse palliative care referral both as inpatients and outpatients. “Such patients are an enigma for many PAH-treating physicians as they may survive to discharge, despite a terrible prognosis predicted by their testing.”

In addition, patients in whom organ transplantation is being pursued may not receive timely PCS, he said. “It can be an absolute challenge to bring such patients to the finish line (transplantation), and the timing of PCS referral is often deferred. Arguably, for better or worse, such patients refuse, or more often are not offered, PCS as inpatients while there is still a chance organ transplantation is a viable option for them.”

The use of PCS in less than 10% of PAH admissions is similar to previous studies showing low use of PCS for patients with acute myocardial infarction, heart failure, and COPD, the researchers noted. However, “Given the high morbidity and mortality associated with PAH even after hospitalization, hospital admissions without PCS use represent a missed opportunity,” the investigators wrote.
 

Early warning on the need for PCS

Increasing PCS referrals for PAH patients requires clinicians to be proactive, Dr. Gupta stressed. “Pulmonologists, especially those managing pulmonary hypertension outpatients without the aid of a PAH center, should remain vigilant at all routine visits to calculate a patient’s risk score (i.e. REVEAL 2.0 risk calculator) to stratify their risk of 1-year mortality. Based on this assessment, shared decision making can help guide next steps including early outpatient PCS involvement for those at high risk. I also calculate a patient’s risk score, based on the data I have, when PAH patients are admitted to the hospital. Occasionally, a patient who I initially think is moderate risk turns out to be high risk when I calculate their risk score. In such high-risk patients, PCS consultation should certainly be considered early on.”

The study findings were limited by several factors including the possible coding errors associated with use of discharge diagnosis, lack of data on medication and the cause of PAH, and lack of information on the reasons for PCS referrals, the researchers noted. However, the results “addressed an important knowledge gap highlighting the national use of PCS in PAH,” they said. Further research is needed to address disparities and the integration of PCS into PAH care protocols, they added.

The researchers had no financial conflicts to disclose. The study received no outside funding; one coauthor disclosed support from the National Center for Advancing Translational Sciences Clinical and Translational Science.

The Food and Drug Administration has approved voclosporin (Lupkynis) for the treatment of lupus nephritis, according to a Jan. 22 press release from manufacturer Aurinia Pharmaceuticals.

Lupkynis is a calcineurin-inhibitor immunosuppressant, and is the first oral medication to show effectiveness in lupus nephritis, according to the company. The drug is indicated for the treatment of adult patients with active lupus nephritis in combination with a background immunosuppressive therapy regimen, according to the drug label, which also has a boxed warning describing the increased risk of infections and malignancies, including lymphoma.

The approval of voclosporin was based on data from two studies, the AURORA phase 3 study and the AURA-LV phase 2 study. The studies included 533 adults with lupus nephritis who were randomized to 23.7 mg or placebo of voclosporin twice daily in the form of oral capsules, or placebo capsules, in addition to standard of care (mycophenolate mofetil plus low-dose glucocorticoids).

In the AURORA phase 3 study of 357 patients, close to twice as many patients in the treatment group showed a complete renal response, compared with the placebo group after 1 year (40.8% vs. 22.5%). In addition, patients treated with voclosporin more quickly achieved a significant reduction in urine protein to creatinine ratio, compared with the placebo patients (169 days vs. 372 days).

Severe adverse events were similar between the groups, including the most common complication of infection (10.1% and 11.2% for voclosporin and control groups, respectively). Other adverse reactions reported in at least 3% of the study participants included a decrease in glomerular filtration rate, hypertension, diarrhea, headache, anemia, cough, urinary tract infection, upper abdominal pain, dyspepsia, alopecia, renal impairment, abdominal pain, mouth ulceration, fatigue, tremor, acute kidney injury, and decreased appetite, according to the company press release.

Full clinical trial information for the AURORA study is available here.

The Food and Drug Administration has approved voclosporin (Lupkynis) for the treatment of lupus nephritis, according to a Jan. 22 press release from manufacturer Aurinia Pharmaceuticals.

Lupkynis is a calcineurin-inhibitor immunosuppressant, and is the first oral medication to show effectiveness in lupus nephritis, according to the company. The drug is indicated for the treatment of adult patients with active lupus nephritis in combination with a background immunosuppressive therapy regimen, according to the drug label, which also has a boxed warning describing the increased risk of infections and malignancies, including lymphoma.

The approval of voclosporin was based on data from two studies, the AURORA phase 3 study and the AURA-LV phase 2 study. The studies included 533 adults with lupus nephritis who were randomized to 23.7 mg or placebo of voclosporin twice daily in the form of oral capsules, or placebo capsules, in addition to standard of care (mycophenolate mofetil plus low-dose glucocorticoids).

In the AURORA phase 3 study of 357 patients, close to twice as many patients in the treatment group showed a complete renal response, compared with the placebo group after 1 year (40.8% vs. 22.5%). In addition, patients treated with voclosporin more quickly achieved a significant reduction in urine protein to creatinine ratio, compared with the placebo patients (169 days vs. 372 days).

Severe adverse events were similar between the groups, including the most common complication of infection (10.1% and 11.2% for voclosporin and control groups, respectively). Other adverse reactions reported in at least 3% of the study participants included a decrease in glomerular filtration rate, hypertension, diarrhea, headache, anemia, cough, urinary tract infection, upper abdominal pain, dyspepsia, alopecia, renal impairment, abdominal pain, mouth ulceration, fatigue, tremor, acute kidney injury, and decreased appetite, according to the company press release.

Full clinical trial information for the AURORA study is available here.

The Food and Drug Administration has approved voclosporin (Lupkynis) for the treatment of lupus nephritis, according to a Jan. 22 press release from manufacturer Aurinia Pharmaceuticals.

Lupkynis is a calcineurin-inhibitor immunosuppressant, and is the first oral medication to show effectiveness in lupus nephritis, according to the company. The drug is indicated for the treatment of adult patients with active lupus nephritis in combination with a background immunosuppressive therapy regimen, according to the drug label, which also has a boxed warning describing the increased risk of infections and malignancies, including lymphoma.

The approval of voclosporin was based on data from two studies, the AURORA phase 3 study and the AURA-LV phase 2 study. The studies included 533 adults with lupus nephritis who were randomized to 23.7 mg or placebo of voclosporin twice daily in the form of oral capsules, or placebo capsules, in addition to standard of care (mycophenolate mofetil plus low-dose glucocorticoids).

In the AURORA phase 3 study of 357 patients, close to twice as many patients in the treatment group showed a complete renal response, compared with the placebo group after 1 year (40.8% vs. 22.5%). In addition, patients treated with voclosporin more quickly achieved a significant reduction in urine protein to creatinine ratio, compared with the placebo patients (169 days vs. 372 days).

Severe adverse events were similar between the groups, including the most common complication of infection (10.1% and 11.2% for voclosporin and control groups, respectively). Other adverse reactions reported in at least 3% of the study participants included a decrease in glomerular filtration rate, hypertension, diarrhea, headache, anemia, cough, urinary tract infection, upper abdominal pain, dyspepsia, alopecia, renal impairment, abdominal pain, mouth ulceration, fatigue, tremor, acute kidney injury, and decreased appetite, according to the company press release.

Full clinical trial information for the AURORA study is available here.

Severe renal arteriosclerosis was associated with a ninefold increased risk of atherosclerotic cardiovascular disease in patients with lupus nephritis, based on data from an observational study of 189 individuals.

Mohammed Haneefa Nizamudeen/Getty Images

Atherosclerotic cardiovascular disease (ASCVD) has traditionally been thought to be a late complication of systemic lupus erythematosus (SLE), but this has been challenged in recent population-based studies of patients with SLE and lupus nephritis (LN) that indicated an early and increased risk of ASCVD at the time of diagnosis. However, it is unclear which early risk factors may predispose patients to ASCVD, Shivani Garg, MD, of the University of Wisconsin, Madison, and colleagues wrote in a study published in Arthritis Care & Research.

In patients with IgA nephropathy and renal transplantation, previous studies have shown that severe renal arteriosclerosis (r-ASCL) based on kidney biopsies at the time of diagnosis predicts ASCVD, but “a few studies including LN biopsies failed to report a similar association between the presence of severe r-ASCL and ASCVD occurrence,” possibly because of underreporting of r-ASCL. Dr. Garg and colleagues also noted the problem of underreporting of r-ASCL in their own previous study of its prevalence in LN patients at the time of diagnosis.

To get a more detailed view of how r-ASCL may be linked to early occurrence of ASCVD in LN patients, Dr. Garg and coauthors identified 189 consecutive patients with incident LN who underwent diagnostic biopsies between 1994 and 2017. The median age of the patients was 25 years, 78% were women, and 73% were white. The researchers developed a composite score for r-ASCL severity based on reported and overread biopsies.

Overall, 31% of the patients had any reported r-ASCL, and 7% had moderate-severe r-ASCL. After incorporating systematically reexamined r-ASCL grades, the prevalence of any and moderate-severe r-ASCL increased to 39% and 12%, respectively.

Based on their composite of reported and overread r-ASCL grade, severe r-ASCL in diagnostic LN biopsies was associated with a ninefold increased risk of ASCVD.

The researchers identified 22 incident ASCVD events over an 11-year follow-up for an overall 12% incidence of ASCVD in LN. ASCVD was defined as ischemic heart disease (including myocardial infarction, coronary artery revascularization, abnormal stress test, abnormal angiogram, and events documented by a cardiologist); stroke and transient ischemic attack (TIA); and peripheral vascular disease. Incident ASCVD was defined as the first ASCVD event between 1 and 10 years after LN diagnosis.

The most common ASCVD events were stroke or TIA (12 patients), events related to ischemic heart disease (7 patients), and events related to peripheral vascular disease (3 patients).

Lack of statin use

The researchers also hypothesized that the presence of gaps in statin use among eligible LN patients would be present in their study population. “Among the 20 patients with incident ASCVD events after LN diagnosis in our cohort, none was on statin therapy at the time of LN diagnosis,” the researchers said, noting that current guidelines from the American College of Rheumatology and the European League Against Rheumatism (now known as the European Alliance of Associations for Rheumatology) recommend initiating statin therapy at the time of LN diagnosis in all patients who have hyperlipidemia and chronic kidney disease (CKD) stage ≥3. “Further, 11 patients (55%) met high-risk criteria (hyperlipidemia and CKD stage ≥3) to implement statin therapy at the time of LN diagnosis, yet only one patient (9%) was initiated on statin therapy.” In addition, patients with stage 3 or higher CKD were more likely to develop ASCVD than patients without stage 3 or higher CKD, they said.

The study findings were limited by several factors including the majority white study population, the ability to overread only 25% of the biopsies, and the lack of data on the potential role of chronic lesions in ASCVD, the researchers noted. However, the results were strengthened by the use of a validated LN cohort, and the data provide “the basis to establish severe composite r-ASCL as a predictor of ASCVD events using a larger sample size in different cohorts,” they said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Severe renal arteriosclerosis was associated with a ninefold increased risk of atherosclerotic cardiovascular disease in patients with lupus nephritis, based on data from an observational study of 189 individuals.

Mohammed Haneefa Nizamudeen/Getty Images

Atherosclerotic cardiovascular disease (ASCVD) has traditionally been thought to be a late complication of systemic lupus erythematosus (SLE), but this has been challenged in recent population-based studies of patients with SLE and lupus nephritis (LN) that indicated an early and increased risk of ASCVD at the time of diagnosis. However, it is unclear which early risk factors may predispose patients to ASCVD, Shivani Garg, MD, of the University of Wisconsin, Madison, and colleagues wrote in a study published in Arthritis Care & Research.

In patients with IgA nephropathy and renal transplantation, previous studies have shown that severe renal arteriosclerosis (r-ASCL) based on kidney biopsies at the time of diagnosis predicts ASCVD, but “a few studies including LN biopsies failed to report a similar association between the presence of severe r-ASCL and ASCVD occurrence,” possibly because of underreporting of r-ASCL. Dr. Garg and colleagues also noted the problem of underreporting of r-ASCL in their own previous study of its prevalence in LN patients at the time of diagnosis.

To get a more detailed view of how r-ASCL may be linked to early occurrence of ASCVD in LN patients, Dr. Garg and coauthors identified 189 consecutive patients with incident LN who underwent diagnostic biopsies between 1994 and 2017. The median age of the patients was 25 years, 78% were women, and 73% were white. The researchers developed a composite score for r-ASCL severity based on reported and overread biopsies.

Overall, 31% of the patients had any reported r-ASCL, and 7% had moderate-severe r-ASCL. After incorporating systematically reexamined r-ASCL grades, the prevalence of any and moderate-severe r-ASCL increased to 39% and 12%, respectively.

Based on their composite of reported and overread r-ASCL grade, severe r-ASCL in diagnostic LN biopsies was associated with a ninefold increased risk of ASCVD.

The researchers identified 22 incident ASCVD events over an 11-year follow-up for an overall 12% incidence of ASCVD in LN. ASCVD was defined as ischemic heart disease (including myocardial infarction, coronary artery revascularization, abnormal stress test, abnormal angiogram, and events documented by a cardiologist); stroke and transient ischemic attack (TIA); and peripheral vascular disease. Incident ASCVD was defined as the first ASCVD event between 1 and 10 years after LN diagnosis.

The most common ASCVD events were stroke or TIA (12 patients), events related to ischemic heart disease (7 patients), and events related to peripheral vascular disease (3 patients).

Lack of statin use

The researchers also hypothesized that the presence of gaps in statin use among eligible LN patients would be present in their study population. “Among the 20 patients with incident ASCVD events after LN diagnosis in our cohort, none was on statin therapy at the time of LN diagnosis,” the researchers said, noting that current guidelines from the American College of Rheumatology and the European League Against Rheumatism (now known as the European Alliance of Associations for Rheumatology) recommend initiating statin therapy at the time of LN diagnosis in all patients who have hyperlipidemia and chronic kidney disease (CKD) stage ≥3. “Further, 11 patients (55%) met high-risk criteria (hyperlipidemia and CKD stage ≥3) to implement statin therapy at the time of LN diagnosis, yet only one patient (9%) was initiated on statin therapy.” In addition, patients with stage 3 or higher CKD were more likely to develop ASCVD than patients without stage 3 or higher CKD, they said.

The study findings were limited by several factors including the majority white study population, the ability to overread only 25% of the biopsies, and the lack of data on the potential role of chronic lesions in ASCVD, the researchers noted. However, the results were strengthened by the use of a validated LN cohort, and the data provide “the basis to establish severe composite r-ASCL as a predictor of ASCVD events using a larger sample size in different cohorts,” they said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Severe renal arteriosclerosis was associated with a ninefold increased risk of atherosclerotic cardiovascular disease in patients with lupus nephritis, based on data from an observational study of 189 individuals.

Mohammed Haneefa Nizamudeen/Getty Images

Atherosclerotic cardiovascular disease (ASCVD) has traditionally been thought to be a late complication of systemic lupus erythematosus (SLE), but this has been challenged in recent population-based studies of patients with SLE and lupus nephritis (LN) that indicated an early and increased risk of ASCVD at the time of diagnosis. However, it is unclear which early risk factors may predispose patients to ASCVD, Shivani Garg, MD, of the University of Wisconsin, Madison, and colleagues wrote in a study published in Arthritis Care & Research.

In patients with IgA nephropathy and renal transplantation, previous studies have shown that severe renal arteriosclerosis (r-ASCL) based on kidney biopsies at the time of diagnosis predicts ASCVD, but “a few studies including LN biopsies failed to report a similar association between the presence of severe r-ASCL and ASCVD occurrence,” possibly because of underreporting of r-ASCL. Dr. Garg and colleagues also noted the problem of underreporting of r-ASCL in their own previous study of its prevalence in LN patients at the time of diagnosis.

To get a more detailed view of how r-ASCL may be linked to early occurrence of ASCVD in LN patients, Dr. Garg and coauthors identified 189 consecutive patients with incident LN who underwent diagnostic biopsies between 1994 and 2017. The median age of the patients was 25 years, 78% were women, and 73% were white. The researchers developed a composite score for r-ASCL severity based on reported and overread biopsies.

Overall, 31% of the patients had any reported r-ASCL, and 7% had moderate-severe r-ASCL. After incorporating systematically reexamined r-ASCL grades, the prevalence of any and moderate-severe r-ASCL increased to 39% and 12%, respectively.

Based on their composite of reported and overread r-ASCL grade, severe r-ASCL in diagnostic LN biopsies was associated with a ninefold increased risk of ASCVD.

The researchers identified 22 incident ASCVD events over an 11-year follow-up for an overall 12% incidence of ASCVD in LN. ASCVD was defined as ischemic heart disease (including myocardial infarction, coronary artery revascularization, abnormal stress test, abnormal angiogram, and events documented by a cardiologist); stroke and transient ischemic attack (TIA); and peripheral vascular disease. Incident ASCVD was defined as the first ASCVD event between 1 and 10 years after LN diagnosis.

The most common ASCVD events were stroke or TIA (12 patients), events related to ischemic heart disease (7 patients), and events related to peripheral vascular disease (3 patients).

Lack of statin use

The researchers also hypothesized that the presence of gaps in statin use among eligible LN patients would be present in their study population. “Among the 20 patients with incident ASCVD events after LN diagnosis in our cohort, none was on statin therapy at the time of LN diagnosis,” the researchers said, noting that current guidelines from the American College of Rheumatology and the European League Against Rheumatism (now known as the European Alliance of Associations for Rheumatology) recommend initiating statin therapy at the time of LN diagnosis in all patients who have hyperlipidemia and chronic kidney disease (CKD) stage ≥3. “Further, 11 patients (55%) met high-risk criteria (hyperlipidemia and CKD stage ≥3) to implement statin therapy at the time of LN diagnosis, yet only one patient (9%) was initiated on statin therapy.” In addition, patients with stage 3 or higher CKD were more likely to develop ASCVD than patients without stage 3 or higher CKD, they said.

The study findings were limited by several factors including the majority white study population, the ability to overread only 25% of the biopsies, and the lack of data on the potential role of chronic lesions in ASCVD, the researchers noted. However, the results were strengthened by the use of a validated LN cohort, and the data provide “the basis to establish severe composite r-ASCL as a predictor of ASCVD events using a larger sample size in different cohorts,” they said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Childhood treatment with recombinant human growth hormone was associated with a significantly increased risk of cardiovascular events, based on data from more than 3,000 individuals.

“Both excess levels of growth hormone and [growth hormone deficiency] have been associated with increased cardiovascular morbidity and mortality,” but data on long-term cardiovascular morbidity in individuals treated with growth hormone in childhood are lacking, wrote Anders Tinblad, MD, of Karolinska Institutet, Stockholm, and colleagues.

In a population-based cohort study published in JAMA Pediatrics, the researchers identified 3,408 Swedish patients treated as children with recombinant human growth hormone (rhGH) between Jan. 1, 1985, and Dec. 31, 2010, and compared each with 15 matched controls (a total of 50,036 controls). The patients were treated for one of three conditions: isolated growth hormone deficiency (GHD), small for gestational age (SGA), and idiopathic short stature (ISS).

Data on cardiovascular outcomes were collected from health care and population-based registers and analyzed between Jan. 1, 1985, and Dec. 31, 2014. The average age of the participants at the study’s end was 25.1 years.

In all, 1,809 cardiovascular disease events were recorded over a median follow-up period of 14.9 years, for an incidence rate of 25.6 events per 10,000 person-years in patients and 22.6 events per 10,000 person-years in controls.

When separated by sex, the incidence was higher in female patients compared with controls (31.2 vs. 23.4 events per 10,000 person-years, respectively, but similar in male patients vs. controls (23.3 vs. 22.3 events per 10,000 person-years). “Differences in estrogen levels or responsiveness to rhGH treatment have previously been hypothesized as possible explanations, but the underlying mechanism for this sex difference still remains unclear and merits further investigation,” the researchers wrote.

Overall, the highest adjusted hazard ratios occurred in subgroups of patients with the longest treatment duration (HR 2.08) and highest cumulative dose of growth hormone (HR 2.05), but no association was noted between highest daily hormone dose and cardiovascular event risk. Hazard ratios were higher across all three treatment subgroups of SGA, GHD, and ISS compared with controls (HR 1.97, 1.66, and 1.55, respectively).

“The association between childhood rhGH treatment and CVD events was also seen when assessing only severe CVD outcomes, but with even lower absolute risks,” the researchers noted.

The study findings were limited by several factors including the potential for confounding by treatment indication and the lack of long-term follow-up data given the relatively young age of the study population, the researchers said. The results were strengthened by the large sample size and showed that the absolute risk for overall and severe cardiovascular disease in children treated with growth hormones was low, “which could be reassuring to individual patients,” they added. However, “At the group level, and perhaps especially for female patients and those treated for SGA indication, further close monitoring and future studies of CVD safety are warranted,” they concluded.
 

Safety and ethical concerns persist

Although the study authors cite limited conclusions on causality and low absolute risk, several issues persist that prompt ongoing analysis of pediatric growth hormone use, namely “worrisome indirect evidence, challenges and limitations in the direct evidence, and the changing world of growth hormone treatment,” Adda Grimberg, MD, of the University of Pennsylvania, Philadelphia, wrote in an accompanying editorial.

“Although evidence asserts that neither growth hormone nor insulinlike growth factor I is carcinogenic, the basic science and oncology literatures are rife with reports showing that they can make aberrant cells more aggressive,” and such indirect evidence supports the need for more direct evidence of possible harm from growth hormone treatment, Dr. Grimberg wrote. Most current safety data on growth hormone come from postmarketing surveillance studies, but these studies do not include controls or data on outcomes after discontinuation of treatment, she noted.

The current study, while able to follow patients across the lifespan, cannot indicate “whether the small but increased risk of cardiovascular disease found in this study was caused by the pediatric growth hormone treatment that identified the participants, by the conditions being treated, by other potential confounder(s) not captured by the study’s methods, or by a combination of the above,” said Dr. Grimberg.

In addition, “the move from replacement of GHD to pharmacologic height augmentation in children who already make sufficient growth hormone had the potential to change the safety profile of treatment,” she said.

“Parents of patients in pediatric primary care practices and of patients seeking growth-related care in a subspecialty endocrine clinic rated treatment characteristics (i.e., proven efficacy and safety) as the factor most having a big or extreme effect on their growth-related medical decision-making,” Dr. Grimberg said. “The centrality of treatment safety to patient-family decision-making underscores the importance of continued scrutiny of growth hormone safety as the treatment and its recipients continue to evolve,” she concluded.

The study was supported by the Swedish Research Council, the Stockholm City Council, the Karolinska Institute, the Society for Child Care, Sahlgrenska University Hospital, and the Stockholm County Council’s combined clinical residency and PhD training program. Lead author Dr. Tidblad disclosed funding from the Society for Child Care and Stockholm County Council during the conduct of the study and personal fees from Pfizer. Dr. Grimberg disclosed serving as a member of the steering committee for the Pfizer International Growth Study Database, and as a consultant for the Pediatric Endocrine Society GH Deficiency Knowledge Center, sponsored by Sandoz AG.

Childhood treatment with recombinant human growth hormone was associated with a significantly increased risk of cardiovascular events, based on data from more than 3,000 individuals.

“Both excess levels of growth hormone and [growth hormone deficiency] have been associated with increased cardiovascular morbidity and mortality,” but data on long-term cardiovascular morbidity in individuals treated with growth hormone in childhood are lacking, wrote Anders Tinblad, MD, of Karolinska Institutet, Stockholm, and colleagues.

In a population-based cohort study published in JAMA Pediatrics, the researchers identified 3,408 Swedish patients treated as children with recombinant human growth hormone (rhGH) between Jan. 1, 1985, and Dec. 31, 2010, and compared each with 15 matched controls (a total of 50,036 controls). The patients were treated for one of three conditions: isolated growth hormone deficiency (GHD), small for gestational age (SGA), and idiopathic short stature (ISS).

Data on cardiovascular outcomes were collected from health care and population-based registers and analyzed between Jan. 1, 1985, and Dec. 31, 2014. The average age of the participants at the study’s end was 25.1 years.

In all, 1,809 cardiovascular disease events were recorded over a median follow-up period of 14.9 years, for an incidence rate of 25.6 events per 10,000 person-years in patients and 22.6 events per 10,000 person-years in controls.

When separated by sex, the incidence was higher in female patients compared with controls (31.2 vs. 23.4 events per 10,000 person-years, respectively, but similar in male patients vs. controls (23.3 vs. 22.3 events per 10,000 person-years). “Differences in estrogen levels or responsiveness to rhGH treatment have previously been hypothesized as possible explanations, but the underlying mechanism for this sex difference still remains unclear and merits further investigation,” the researchers wrote.

Overall, the highest adjusted hazard ratios occurred in subgroups of patients with the longest treatment duration (HR 2.08) and highest cumulative dose of growth hormone (HR 2.05), but no association was noted between highest daily hormone dose and cardiovascular event risk. Hazard ratios were higher across all three treatment subgroups of SGA, GHD, and ISS compared with controls (HR 1.97, 1.66, and 1.55, respectively).

“The association between childhood rhGH treatment and CVD events was also seen when assessing only severe CVD outcomes, but with even lower absolute risks,” the researchers noted.

The study findings were limited by several factors including the potential for confounding by treatment indication and the lack of long-term follow-up data given the relatively young age of the study population, the researchers said. The results were strengthened by the large sample size and showed that the absolute risk for overall and severe cardiovascular disease in children treated with growth hormones was low, “which could be reassuring to individual patients,” they added. However, “At the group level, and perhaps especially for female patients and those treated for SGA indication, further close monitoring and future studies of CVD safety are warranted,” they concluded.
 

Safety and ethical concerns persist

Although the study authors cite limited conclusions on causality and low absolute risk, several issues persist that prompt ongoing analysis of pediatric growth hormone use, namely “worrisome indirect evidence, challenges and limitations in the direct evidence, and the changing world of growth hormone treatment,” Adda Grimberg, MD, of the University of Pennsylvania, Philadelphia, wrote in an accompanying editorial.

“Although evidence asserts that neither growth hormone nor insulinlike growth factor I is carcinogenic, the basic science and oncology literatures are rife with reports showing that they can make aberrant cells more aggressive,” and such indirect evidence supports the need for more direct evidence of possible harm from growth hormone treatment, Dr. Grimberg wrote. Most current safety data on growth hormone come from postmarketing surveillance studies, but these studies do not include controls or data on outcomes after discontinuation of treatment, she noted.

The current study, while able to follow patients across the lifespan, cannot indicate “whether the small but increased risk of cardiovascular disease found in this study was caused by the pediatric growth hormone treatment that identified the participants, by the conditions being treated, by other potential confounder(s) not captured by the study’s methods, or by a combination of the above,” said Dr. Grimberg.

In addition, “the move from replacement of GHD to pharmacologic height augmentation in children who already make sufficient growth hormone had the potential to change the safety profile of treatment,” she said.

“Parents of patients in pediatric primary care practices and of patients seeking growth-related care in a subspecialty endocrine clinic rated treatment characteristics (i.e., proven efficacy and safety) as the factor most having a big or extreme effect on their growth-related medical decision-making,” Dr. Grimberg said. “The centrality of treatment safety to patient-family decision-making underscores the importance of continued scrutiny of growth hormone safety as the treatment and its recipients continue to evolve,” she concluded.

The study was supported by the Swedish Research Council, the Stockholm City Council, the Karolinska Institute, the Society for Child Care, Sahlgrenska University Hospital, and the Stockholm County Council’s combined clinical residency and PhD training program. Lead author Dr. Tidblad disclosed funding from the Society for Child Care and Stockholm County Council during the conduct of the study and personal fees from Pfizer. Dr. Grimberg disclosed serving as a member of the steering committee for the Pfizer International Growth Study Database, and as a consultant for the Pediatric Endocrine Society GH Deficiency Knowledge Center, sponsored by Sandoz AG.

Childhood treatment with recombinant human growth hormone was associated with a significantly increased risk of cardiovascular events, based on data from more than 3,000 individuals.

“Both excess levels of growth hormone and [growth hormone deficiency] have been associated with increased cardiovascular morbidity and mortality,” but data on long-term cardiovascular morbidity in individuals treated with growth hormone in childhood are lacking, wrote Anders Tinblad, MD, of Karolinska Institutet, Stockholm, and colleagues.

In a population-based cohort study published in JAMA Pediatrics, the researchers identified 3,408 Swedish patients treated as children with recombinant human growth hormone (rhGH) between Jan. 1, 1985, and Dec. 31, 2010, and compared each with 15 matched controls (a total of 50,036 controls). The patients were treated for one of three conditions: isolated growth hormone deficiency (GHD), small for gestational age (SGA), and idiopathic short stature (ISS).

Data on cardiovascular outcomes were collected from health care and population-based registers and analyzed between Jan. 1, 1985, and Dec. 31, 2014. The average age of the participants at the study’s end was 25.1 years.

In all, 1,809 cardiovascular disease events were recorded over a median follow-up period of 14.9 years, for an incidence rate of 25.6 events per 10,000 person-years in patients and 22.6 events per 10,000 person-years in controls.

When separated by sex, the incidence was higher in female patients compared with controls (31.2 vs. 23.4 events per 10,000 person-years, respectively, but similar in male patients vs. controls (23.3 vs. 22.3 events per 10,000 person-years). “Differences in estrogen levels or responsiveness to rhGH treatment have previously been hypothesized as possible explanations, but the underlying mechanism for this sex difference still remains unclear and merits further investigation,” the researchers wrote.

Overall, the highest adjusted hazard ratios occurred in subgroups of patients with the longest treatment duration (HR 2.08) and highest cumulative dose of growth hormone (HR 2.05), but no association was noted between highest daily hormone dose and cardiovascular event risk. Hazard ratios were higher across all three treatment subgroups of SGA, GHD, and ISS compared with controls (HR 1.97, 1.66, and 1.55, respectively).

“The association between childhood rhGH treatment and CVD events was also seen when assessing only severe CVD outcomes, but with even lower absolute risks,” the researchers noted.

The study findings were limited by several factors including the potential for confounding by treatment indication and the lack of long-term follow-up data given the relatively young age of the study population, the researchers said. The results were strengthened by the large sample size and showed that the absolute risk for overall and severe cardiovascular disease in children treated with growth hormones was low, “which could be reassuring to individual patients,” they added. However, “At the group level, and perhaps especially for female patients and those treated for SGA indication, further close monitoring and future studies of CVD safety are warranted,” they concluded.
 

Safety and ethical concerns persist

Although the study authors cite limited conclusions on causality and low absolute risk, several issues persist that prompt ongoing analysis of pediatric growth hormone use, namely “worrisome indirect evidence, challenges and limitations in the direct evidence, and the changing world of growth hormone treatment,” Adda Grimberg, MD, of the University of Pennsylvania, Philadelphia, wrote in an accompanying editorial.

“Although evidence asserts that neither growth hormone nor insulinlike growth factor I is carcinogenic, the basic science and oncology literatures are rife with reports showing that they can make aberrant cells more aggressive,” and such indirect evidence supports the need for more direct evidence of possible harm from growth hormone treatment, Dr. Grimberg wrote. Most current safety data on growth hormone come from postmarketing surveillance studies, but these studies do not include controls or data on outcomes after discontinuation of treatment, she noted.

The current study, while able to follow patients across the lifespan, cannot indicate “whether the small but increased risk of cardiovascular disease found in this study was caused by the pediatric growth hormone treatment that identified the participants, by the conditions being treated, by other potential confounder(s) not captured by the study’s methods, or by a combination of the above,” said Dr. Grimberg.

In addition, “the move from replacement of GHD to pharmacologic height augmentation in children who already make sufficient growth hormone had the potential to change the safety profile of treatment,” she said.

“Parents of patients in pediatric primary care practices and of patients seeking growth-related care in a subspecialty endocrine clinic rated treatment characteristics (i.e., proven efficacy and safety) as the factor most having a big or extreme effect on their growth-related medical decision-making,” Dr. Grimberg said. “The centrality of treatment safety to patient-family decision-making underscores the importance of continued scrutiny of growth hormone safety as the treatment and its recipients continue to evolve,” she concluded.

The study was supported by the Swedish Research Council, the Stockholm City Council, the Karolinska Institute, the Society for Child Care, Sahlgrenska University Hospital, and the Stockholm County Council’s combined clinical residency and PhD training program. Lead author Dr. Tidblad disclosed funding from the Society for Child Care and Stockholm County Council during the conduct of the study and personal fees from Pfizer. Dr. Grimberg disclosed serving as a member of the steering committee for the Pfizer International Growth Study Database, and as a consultant for the Pediatric Endocrine Society GH Deficiency Knowledge Center, sponsored by Sandoz AG.

Birth rates for women who underwent assisted reproduction using fresh donor oocytes were significantly higher than for women who used cryopreserved-thawed embryos, based on data from more than 33,000 women.

Cryopreserved-thawed embryo transfers in donor oocyte cycles have gained in popularity in recent years for reasons including “convenience, elimination of the need for synchronization between donor and recipient cycles, and/or increasing utilization of preimplantation genetic testing for aneuploidy,” wrote Iris G. Insogna, MD, of Brigham and Women’s Hospital, Boston, and colleagues.“ However, to date, no comparison of pregnancy outcomes has been made between transfers of fresh embryos and cryopreserved-thawed embryos derived exclusively from fresh donor oocytes,” they said.

In a retrospective cohort study published in JAMA, the researchers identified 33,863 women who underwent IVF cycles using freshly retrieved oocytes with a total of 51,942 embryo transfer cycles; 15,308 fresh embryo transfer cycles, and 36,634 cryopreserved-thawed embryo transfer cycles.

Overall, the live birth rate was 56.6% for cycles involving fresh donor oocytes compared to 44.0% for cycles with cryopreserved-thawed embryos, with an adjusted relative risk of 1.42 after the researchers controlled for donor age, day of embryo transfer, use of gestational carrier, and assisted hatching. Demographics were similar between women who received fresh vs. cryopreserved-thawed embryos including median age (42 years for both), gravidity (1 for both), parity (0 vs. 1), and body mass index (24.5 vs. 24.4 kg/m²).

Clinical pregnancy rates for women with fresh vs. cryopreserved-thawed embryo transfers were 66.7% and 54.2%, respectively, and miscarriage rates were approximately 9% for both groups.

The average number of embryos transferred was similar between the groups, and blastocysts were transferred in 92.4% and 96.5% of fresh embryo and cryopreserved-thawed embryo transfer cycles, respectively.

The finding that, in cycles using fresh donor oocytes, fresh embryo transfer yielded higher birth rates than transfer of cryopreserved-thawed embryo transfer “was in contrast to previous investigations of cycles using autologous oocytes that demonstrated higher live birth rates following cryopreserved-thawed embryo transfers,” the researchers noted.

Live birth rates remained higher in cases of fresh embryo transfer when preimplantation genetic testing for aneuploidy (PGT-A) was performed, they added.

The study findings were limited by several factors, including the retrospective design and lack of data on potential confounding factors in the donor population, such as age, ethnicity, BMI, and smoking status, the researchers said. However, the results have implications for clinical practice by providing informed counseling information, given the significantly greater complexity of preparing a fresh transfer of an embryo from a fresh donor oocyte, the researchers noted. In addition, “given the considerable financial investment, these data may influence patient decision-making regarding transferring a fresh embryo derived from a fresh donor oocyte vs. cryopreserving all embryos a priori for convenience,” they said. More data on the cost-effectiveness of fresh vs. cryopreserved-thawed embryo transfer in the study population also would help guide clinical practice, they said.
 

Prospective studies needed to confirm potential

“For women who use autologous oocytes, there is increasing evidence for improved pregnancy rates by frozen embryo transfer (FET) rather than fresh, particularly in women with good ovarian response to gonadotropins,” Mark P. Trolice, MD, of the University of Central Florida, Orlando, said in an interview. The current study was important because it examined “whether the same concept applies with the use of embryos from donor oocytes,” he said.

Dr. Trolice, director of Fertility CARE: The IVF Center, in Orlando, said he was surprised by the study findings. The study “contradicts the experience in cycles using autologous oocytes,” he said. “Fresh embryo superiority remained after a subgroup analysis of first embryo transfers for fresh and frozen cycles as well as for embryos that underwent PGT-A (preimplantation genetic testing for aneuploidy, typically resulting in FET cycles, although a small percentage of cycles underwent fresh embryo transfer), yielding no difference to non-PGT-A fresh cycles. This reinforces the prior evidence for lack of improvement following PGT-A in women less than age 35 years,” he noted.

“Coincidentally, the same findings were discovered using the same SART [Society for Assisted Reproductive Technology] database (from 2013 to 2015), namely fresh embryo transfer from donor oocytes was more likely to result in a live birth – 55.7% versus 39.5%,” said Dr. Trolice. “An abstract presented at the 2017 ASRM annual meeting also used the SART data base (from 2003 to 2014) and demonstrated live birth rates from fresh transfer of embryos using donor oocytes were 15%-20% higher than those from frozen embryo transfers,” he noted.

“In summary, the use of fresh embryos from donor oocytes consistently appears to have superior pregnancy outcomes compared with frozen embryos; a nearly 13% absolute difference in this recent study,” said Dr. Trolice. The strengths of the study included the primary outcome of live births and the heterogeneity, with cycles taken from all participating U.S. SART clinics, Dr. Trolice noted. Limitations included the “retrospective design with the inherent risk of selection bias and the lack of information on the embryo freezing method, i.e., the older ‘slow-freeze’ or the more advanced and popular method of vitrification,” he added. “Randomized, prospective studies are needed to more accurately address this important issue,” he emphasized.

The study received no outside funding. Lead author Dr. Insogna disclosed part-time work as an assistant physician for Teladoc Health. Dr. Trolice had no relevant financial conflicts to disclose.

Birth rates for women who underwent assisted reproduction using fresh donor oocytes were significantly higher than for women who used cryopreserved-thawed embryos, based on data from more than 33,000 women.

Cryopreserved-thawed embryo transfers in donor oocyte cycles have gained in popularity in recent years for reasons including “convenience, elimination of the need for synchronization between donor and recipient cycles, and/or increasing utilization of preimplantation genetic testing for aneuploidy,” wrote Iris G. Insogna, MD, of Brigham and Women’s Hospital, Boston, and colleagues.“ However, to date, no comparison of pregnancy outcomes has been made between transfers of fresh embryos and cryopreserved-thawed embryos derived exclusively from fresh donor oocytes,” they said.

In a retrospective cohort study published in JAMA, the researchers identified 33,863 women who underwent IVF cycles using freshly retrieved oocytes with a total of 51,942 embryo transfer cycles; 15,308 fresh embryo transfer cycles, and 36,634 cryopreserved-thawed embryo transfer cycles.

Overall, the live birth rate was 56.6% for cycles involving fresh donor oocytes compared to 44.0% for cycles with cryopreserved-thawed embryos, with an adjusted relative risk of 1.42 after the researchers controlled for donor age, day of embryo transfer, use of gestational carrier, and assisted hatching. Demographics were similar between women who received fresh vs. cryopreserved-thawed embryos including median age (42 years for both), gravidity (1 for both), parity (0 vs. 1), and body mass index (24.5 vs. 24.4 kg/m²).

Clinical pregnancy rates for women with fresh vs. cryopreserved-thawed embryo transfers were 66.7% and 54.2%, respectively, and miscarriage rates were approximately 9% for both groups.

The average number of embryos transferred was similar between the groups, and blastocysts were transferred in 92.4% and 96.5% of fresh embryo and cryopreserved-thawed embryo transfer cycles, respectively.

The finding that, in cycles using fresh donor oocytes, fresh embryo transfer yielded higher birth rates than transfer of cryopreserved-thawed embryo transfer “was in contrast to previous investigations of cycles using autologous oocytes that demonstrated higher live birth rates following cryopreserved-thawed embryo transfers,” the researchers noted.

Live birth rates remained higher in cases of fresh embryo transfer when preimplantation genetic testing for aneuploidy (PGT-A) was performed, they added.

The study findings were limited by several factors, including the retrospective design and lack of data on potential confounding factors in the donor population, such as age, ethnicity, BMI, and smoking status, the researchers said. However, the results have implications for clinical practice by providing informed counseling information, given the significantly greater complexity of preparing a fresh transfer of an embryo from a fresh donor oocyte, the researchers noted. In addition, “given the considerable financial investment, these data may influence patient decision-making regarding transferring a fresh embryo derived from a fresh donor oocyte vs. cryopreserving all embryos a priori for convenience,” they said. More data on the cost-effectiveness of fresh vs. cryopreserved-thawed embryo transfer in the study population also would help guide clinical practice, they said.
 

Prospective studies needed to confirm potential

“For women who use autologous oocytes, there is increasing evidence for improved pregnancy rates by frozen embryo transfer (FET) rather than fresh, particularly in women with good ovarian response to gonadotropins,” Mark P. Trolice, MD, of the University of Central Florida, Orlando, said in an interview. The current study was important because it examined “whether the same concept applies with the use of embryos from donor oocytes,” he said.

Dr. Trolice, director of Fertility CARE: The IVF Center, in Orlando, said he was surprised by the study findings. The study “contradicts the experience in cycles using autologous oocytes,” he said. “Fresh embryo superiority remained after a subgroup analysis of first embryo transfers for fresh and frozen cycles as well as for embryos that underwent PGT-A (preimplantation genetic testing for aneuploidy, typically resulting in FET cycles, although a small percentage of cycles underwent fresh embryo transfer), yielding no difference to non-PGT-A fresh cycles. This reinforces the prior evidence for lack of improvement following PGT-A in women less than age 35 years,” he noted.

“Coincidentally, the same findings were discovered using the same SART [Society for Assisted Reproductive Technology] database (from 2013 to 2015), namely fresh embryo transfer from donor oocytes was more likely to result in a live birth – 55.7% versus 39.5%,” said Dr. Trolice. “An abstract presented at the 2017 ASRM annual meeting also used the SART data base (from 2003 to 2014) and demonstrated live birth rates from fresh transfer of embryos using donor oocytes were 15%-20% higher than those from frozen embryo transfers,” he noted.

“In summary, the use of fresh embryos from donor oocytes consistently appears to have superior pregnancy outcomes compared with frozen embryos; a nearly 13% absolute difference in this recent study,” said Dr. Trolice. The strengths of the study included the primary outcome of live births and the heterogeneity, with cycles taken from all participating U.S. SART clinics, Dr. Trolice noted. Limitations included the “retrospective design with the inherent risk of selection bias and the lack of information on the embryo freezing method, i.e., the older ‘slow-freeze’ or the more advanced and popular method of vitrification,” he added. “Randomized, prospective studies are needed to more accurately address this important issue,” he emphasized.

The study received no outside funding. Lead author Dr. Insogna disclosed part-time work as an assistant physician for Teladoc Health. Dr. Trolice had no relevant financial conflicts to disclose.

Birth rates for women who underwent assisted reproduction using fresh donor oocytes were significantly higher than for women who used cryopreserved-thawed embryos, based on data from more than 33,000 women.

Cryopreserved-thawed embryo transfers in donor oocyte cycles have gained in popularity in recent years for reasons including “convenience, elimination of the need for synchronization between donor and recipient cycles, and/or increasing utilization of preimplantation genetic testing for aneuploidy,” wrote Iris G. Insogna, MD, of Brigham and Women’s Hospital, Boston, and colleagues.“ However, to date, no comparison of pregnancy outcomes has been made between transfers of fresh embryos and cryopreserved-thawed embryos derived exclusively from fresh donor oocytes,” they said.

In a retrospective cohort study published in JAMA, the researchers identified 33,863 women who underwent IVF cycles using freshly retrieved oocytes with a total of 51,942 embryo transfer cycles; 15,308 fresh embryo transfer cycles, and 36,634 cryopreserved-thawed embryo transfer cycles.

Overall, the live birth rate was 56.6% for cycles involving fresh donor oocytes compared to 44.0% for cycles with cryopreserved-thawed embryos, with an adjusted relative risk of 1.42 after the researchers controlled for donor age, day of embryo transfer, use of gestational carrier, and assisted hatching. Demographics were similar between women who received fresh vs. cryopreserved-thawed embryos including median age (42 years for both), gravidity (1 for both), parity (0 vs. 1), and body mass index (24.5 vs. 24.4 kg/m²).

Clinical pregnancy rates for women with fresh vs. cryopreserved-thawed embryo transfers were 66.7% and 54.2%, respectively, and miscarriage rates were approximately 9% for both groups.

The average number of embryos transferred was similar between the groups, and blastocysts were transferred in 92.4% and 96.5% of fresh embryo and cryopreserved-thawed embryo transfer cycles, respectively.

The finding that, in cycles using fresh donor oocytes, fresh embryo transfer yielded higher birth rates than transfer of cryopreserved-thawed embryo transfer “was in contrast to previous investigations of cycles using autologous oocytes that demonstrated higher live birth rates following cryopreserved-thawed embryo transfers,” the researchers noted.

Live birth rates remained higher in cases of fresh embryo transfer when preimplantation genetic testing for aneuploidy (PGT-A) was performed, they added.

The study findings were limited by several factors, including the retrospective design and lack of data on potential confounding factors in the donor population, such as age, ethnicity, BMI, and smoking status, the researchers said. However, the results have implications for clinical practice by providing informed counseling information, given the significantly greater complexity of preparing a fresh transfer of an embryo from a fresh donor oocyte, the researchers noted. In addition, “given the considerable financial investment, these data may influence patient decision-making regarding transferring a fresh embryo derived from a fresh donor oocyte vs. cryopreserving all embryos a priori for convenience,” they said. More data on the cost-effectiveness of fresh vs. cryopreserved-thawed embryo transfer in the study population also would help guide clinical practice, they said.
 

Prospective studies needed to confirm potential

“For women who use autologous oocytes, there is increasing evidence for improved pregnancy rates by frozen embryo transfer (FET) rather than fresh, particularly in women with good ovarian response to gonadotropins,” Mark P. Trolice, MD, of the University of Central Florida, Orlando, said in an interview. The current study was important because it examined “whether the same concept applies with the use of embryos from donor oocytes,” he said.

Dr. Trolice, director of Fertility CARE: The IVF Center, in Orlando, said he was surprised by the study findings. The study “contradicts the experience in cycles using autologous oocytes,” he said. “Fresh embryo superiority remained after a subgroup analysis of first embryo transfers for fresh and frozen cycles as well as for embryos that underwent PGT-A (preimplantation genetic testing for aneuploidy, typically resulting in FET cycles, although a small percentage of cycles underwent fresh embryo transfer), yielding no difference to non-PGT-A fresh cycles. This reinforces the prior evidence for lack of improvement following PGT-A in women less than age 35 years,” he noted.

“Coincidentally, the same findings were discovered using the same SART [Society for Assisted Reproductive Technology] database (from 2013 to 2015), namely fresh embryo transfer from donor oocytes was more likely to result in a live birth – 55.7% versus 39.5%,” said Dr. Trolice. “An abstract presented at the 2017 ASRM annual meeting also used the SART data base (from 2003 to 2014) and demonstrated live birth rates from fresh transfer of embryos using donor oocytes were 15%-20% higher than those from frozen embryo transfers,” he noted.

“In summary, the use of fresh embryos from donor oocytes consistently appears to have superior pregnancy outcomes compared with frozen embryos; a nearly 13% absolute difference in this recent study,” said Dr. Trolice. The strengths of the study included the primary outcome of live births and the heterogeneity, with cycles taken from all participating U.S. SART clinics, Dr. Trolice noted. Limitations included the “retrospective design with the inherent risk of selection bias and the lack of information on the embryo freezing method, i.e., the older ‘slow-freeze’ or the more advanced and popular method of vitrification,” he added. “Randomized, prospective studies are needed to more accurately address this important issue,” he emphasized.

The study received no outside funding. Lead author Dr. Insogna disclosed part-time work as an assistant physician for Teladoc Health. Dr. Trolice had no relevant financial conflicts to disclose.