Clinician Reviews

Adolescents who undergo sleeve gastrectomy have lower bone density and higher bone marrow fat at 1 year following surgery, new research shows.

“It’s almost paradoxical,” Miriam Bredella, MD, of Massachusetts General Hospital in Boston, told Medscape Medical News. “Despite marked loss of body fat, these children have more fat in their bones and decreased bone density.”

She explained that the dissected part of the stomach is filled with anabolic cells that are important for building bone mass. “When those cells are cut out, the body cannot produce the hormones for building up bone.” It’s a malabsorption problem, she added. “Cutting out parts of the stomach or gut leads to less absorption.”

It is well known that bariatric surgery in adults has long-term effects on bone, she said, but this is the first time it has been studied in children.

“Nobody thinks about bone loss in children, but it’s extremely important,” Bredella reports. “The adolescent years up to age 25 are when we accrue bone density, so if something happens during this critical time, it can lead to weak bones later in life.” In the case of these adolescents, peak bone mass is never reached.

To investigate the effects of sleeve gastrectomy on bone density and marrow adipose tissue in extremely obese teenagers, researchers at Massachusetts General Hospital and Harvard Medical School recruited 52 adolescents with a mean body mass index (BMI) of 45. They measured volumetric bone mineral density using quantitative computer tomography (QCT) of the lumbar spine.

“We used QCT instead of DEXA [dual energy x-ray absorptiometry] scan because it isn’t affected by changes in soft tissue; it’s less susceptible to extreme changes in body weight,” Bredella said. “With DEXA scan there are too many artifacts.”

Half of the group (n = 26) underwent surgery. At 1 year, those who underwent surgery lost an average of 34 kg (75 lb). Adolescents in the control group lost an average of 0.2 kg (0.5 lb) (P < .0001).

Both groups repeated the QCT scan at the 1-year follow-up. Researchers found a decrease in bone density in those who underwent sleeve gastrectomy vs. controls (P = .046).

In her presentation, Bredella showed the QCT of the L2 spine in a 17-year old female before surgery and 12 months later. Her volumetric bone mineral density decreased from 183 mg/cm³ to 146 mg/cm³.

“Sleeve gastrectomy in children is bad for bones,” Bradella said. “You have to take care of your bones. This is something people are not thinking about and it probably won’t be a problem when they’re young but will likely affect these patients with osteoporosis when they are older.”

Patients need to be aware of this, she warns, and take steps to combat the bone loss. “Drinking milk, taking vitamin D, and doing weight-bearing exercise may help increase the bone density,” she said.

The increased fat in the bone is also concerning, she said. “Increased fat in the bone is a phenomenon that we see in anorexic patients,” Bredella explained.

The body appears to store the fat in bone in case of need later on, she explained. “We know that in severe states of malnutrition the body has the ability to metabolize the fat in the bones.”

The obesity epidemic in America has given way to a 100-fold increase in sleeve gastrectomy procedures in teenagers between 2005 and 2014. “These patients need this surgery so they don›t die of cardiac arrest or diabetes,” she said. “But we need to make sure they get their bone mineral density checked frequently.”

“The results of this study are important,” Marc Michalsky, MD, Nationwide Children’s Hospital, Columbus, Ohio, told Medscape Medical News. “But they need to be put into context.”

“There is an impetus and argument to support bariatric surgery as it offers a significant reduction in BMI and an associated reversal and complete amelioration of obesity related diseases.”

What this study doesn’t address, he said, is whether this population will experience an increase in bone density-related fractures down the road.

“These results are a snapshot in time — a picture of one postoperative time point,” Michalsky pointed out. “Are we seeing a process that represents continued change in bone mineralization? It’s not unreasonable to assume that the radiological findings here may lead to real clinical impact, but we don’t know.”

Bredella and Michalsky have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Adolescents who undergo sleeve gastrectomy have lower bone density and higher bone marrow fat at 1 year following surgery, new research shows.

“It’s almost paradoxical,” Miriam Bredella, MD, of Massachusetts General Hospital in Boston, told Medscape Medical News. “Despite marked loss of body fat, these children have more fat in their bones and decreased bone density.”

She explained that the dissected part of the stomach is filled with anabolic cells that are important for building bone mass. “When those cells are cut out, the body cannot produce the hormones for building up bone.” It’s a malabsorption problem, she added. “Cutting out parts of the stomach or gut leads to less absorption.”

It is well known that bariatric surgery in adults has long-term effects on bone, she said, but this is the first time it has been studied in children.

“Nobody thinks about bone loss in children, but it’s extremely important,” Bredella reports. “The adolescent years up to age 25 are when we accrue bone density, so if something happens during this critical time, it can lead to weak bones later in life.” In the case of these adolescents, peak bone mass is never reached.

To investigate the effects of sleeve gastrectomy on bone density and marrow adipose tissue in extremely obese teenagers, researchers at Massachusetts General Hospital and Harvard Medical School recruited 52 adolescents with a mean body mass index (BMI) of 45. They measured volumetric bone mineral density using quantitative computer tomography (QCT) of the lumbar spine.

“We used QCT instead of DEXA [dual energy x-ray absorptiometry] scan because it isn’t affected by changes in soft tissue; it’s less susceptible to extreme changes in body weight,” Bredella said. “With DEXA scan there are too many artifacts.”

Half of the group (n = 26) underwent surgery. At 1 year, those who underwent surgery lost an average of 34 kg (75 lb). Adolescents in the control group lost an average of 0.2 kg (0.5 lb) (P < .0001).

Both groups repeated the QCT scan at the 1-year follow-up. Researchers found a decrease in bone density in those who underwent sleeve gastrectomy vs. controls (P = .046).

In her presentation, Bredella showed the QCT of the L2 spine in a 17-year old female before surgery and 12 months later. Her volumetric bone mineral density decreased from 183 mg/cm³ to 146 mg/cm³.

“Sleeve gastrectomy in children is bad for bones,” Bradella said. “You have to take care of your bones. This is something people are not thinking about and it probably won’t be a problem when they’re young but will likely affect these patients with osteoporosis when they are older.”

Patients need to be aware of this, she warns, and take steps to combat the bone loss. “Drinking milk, taking vitamin D, and doing weight-bearing exercise may help increase the bone density,” she said.

The increased fat in the bone is also concerning, she said. “Increased fat in the bone is a phenomenon that we see in anorexic patients,” Bredella explained.

The body appears to store the fat in bone in case of need later on, she explained. “We know that in severe states of malnutrition the body has the ability to metabolize the fat in the bones.”

The obesity epidemic in America has given way to a 100-fold increase in sleeve gastrectomy procedures in teenagers between 2005 and 2014. “These patients need this surgery so they don›t die of cardiac arrest or diabetes,” she said. “But we need to make sure they get their bone mineral density checked frequently.”

“The results of this study are important,” Marc Michalsky, MD, Nationwide Children’s Hospital, Columbus, Ohio, told Medscape Medical News. “But they need to be put into context.”

“There is an impetus and argument to support bariatric surgery as it offers a significant reduction in BMI and an associated reversal and complete amelioration of obesity related diseases.”

What this study doesn’t address, he said, is whether this population will experience an increase in bone density-related fractures down the road.

“These results are a snapshot in time — a picture of one postoperative time point,” Michalsky pointed out. “Are we seeing a process that represents continued change in bone mineralization? It’s not unreasonable to assume that the radiological findings here may lead to real clinical impact, but we don’t know.”

Bredella and Michalsky have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Adolescents who undergo sleeve gastrectomy have lower bone density and higher bone marrow fat at 1 year following surgery, new research shows.

“It’s almost paradoxical,” Miriam Bredella, MD, of Massachusetts General Hospital in Boston, told Medscape Medical News. “Despite marked loss of body fat, these children have more fat in their bones and decreased bone density.”

She explained that the dissected part of the stomach is filled with anabolic cells that are important for building bone mass. “When those cells are cut out, the body cannot produce the hormones for building up bone.” It’s a malabsorption problem, she added. “Cutting out parts of the stomach or gut leads to less absorption.”

It is well known that bariatric surgery in adults has long-term effects on bone, she said, but this is the first time it has been studied in children.

“Nobody thinks about bone loss in children, but it’s extremely important,” Bredella reports. “The adolescent years up to age 25 are when we accrue bone density, so if something happens during this critical time, it can lead to weak bones later in life.” In the case of these adolescents, peak bone mass is never reached.

To investigate the effects of sleeve gastrectomy on bone density and marrow adipose tissue in extremely obese teenagers, researchers at Massachusetts General Hospital and Harvard Medical School recruited 52 adolescents with a mean body mass index (BMI) of 45. They measured volumetric bone mineral density using quantitative computer tomography (QCT) of the lumbar spine.

“We used QCT instead of DEXA [dual energy x-ray absorptiometry] scan because it isn’t affected by changes in soft tissue; it’s less susceptible to extreme changes in body weight,” Bredella said. “With DEXA scan there are too many artifacts.”

Half of the group (n = 26) underwent surgery. At 1 year, those who underwent surgery lost an average of 34 kg (75 lb). Adolescents in the control group lost an average of 0.2 kg (0.5 lb) (P < .0001).

Both groups repeated the QCT scan at the 1-year follow-up. Researchers found a decrease in bone density in those who underwent sleeve gastrectomy vs. controls (P = .046).

In her presentation, Bredella showed the QCT of the L2 spine in a 17-year old female before surgery and 12 months later. Her volumetric bone mineral density decreased from 183 mg/cm³ to 146 mg/cm³.

“Sleeve gastrectomy in children is bad for bones,” Bradella said. “You have to take care of your bones. This is something people are not thinking about and it probably won’t be a problem when they’re young but will likely affect these patients with osteoporosis when they are older.”

Patients need to be aware of this, she warns, and take steps to combat the bone loss. “Drinking milk, taking vitamin D, and doing weight-bearing exercise may help increase the bone density,” she said.

The increased fat in the bone is also concerning, she said. “Increased fat in the bone is a phenomenon that we see in anorexic patients,” Bredella explained.

The body appears to store the fat in bone in case of need later on, she explained. “We know that in severe states of malnutrition the body has the ability to metabolize the fat in the bones.”

The obesity epidemic in America has given way to a 100-fold increase in sleeve gastrectomy procedures in teenagers between 2005 and 2014. “These patients need this surgery so they don›t die of cardiac arrest or diabetes,” she said. “But we need to make sure they get their bone mineral density checked frequently.”

“The results of this study are important,” Marc Michalsky, MD, Nationwide Children’s Hospital, Columbus, Ohio, told Medscape Medical News. “But they need to be put into context.”

“There is an impetus and argument to support bariatric surgery as it offers a significant reduction in BMI and an associated reversal and complete amelioration of obesity related diseases.”

What this study doesn’t address, he said, is whether this population will experience an increase in bone density-related fractures down the road.

“These results are a snapshot in time — a picture of one postoperative time point,” Michalsky pointed out. “Are we seeing a process that represents continued change in bone mineralization? It’s not unreasonable to assume that the radiological findings here may lead to real clinical impact, but we don’t know.”

Bredella and Michalsky have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Vaccine-preventable infections (VPIs) in pediatric hematopoietic cell transplantation (HCT) recipients cause significant morbidity, health care burden, and mortality.

Dana Danino, MD, and colleagues presented their evaluation of the prevalence and epidemiology of pediatric VPI-associated hospitalizations occurring within 5 years post HCT at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.

“Pediatric HCT recipients are at increased risk of VPIs, and HCT recipients have poor outcomes from VPIs, compared with the general population,” explained Dr. Danino, of the department of pediatrics, and divisions of infectious diseases and host defense at the Ohio State University, Columbus. “However, the contemporary prevalence, risk factors, morbidity and mortality resulting from VPIs in children post HCT are not well known.”

Their epidemiological study, using the Pediatric Health Information System (PHIS) database, identified all children under 18 years that underwent allogeneic or autologous HCT in an 8-year period. A total of 9,591 unique HCT recipients were identified.

The researchers demonstrated that 7.1% of this cohort were hospitalized for a VPI in the first 5 years post HCT. Dr. Danino explained that 67% of VPI hospitalizations occurred during the first year, at a median of 222 days, and 22% of VPIs occurred during the initial HCT admission.

As to the type of infection, Dr. Danino and colleagues found that, the prevalence of VPI hospitalizations were highest for influenza, followed by varicella and invasive pneumococcal infections. They identified no hospitalizations due to measles or rubella during the study period.

The study findings revealed that the influenza infections occurred a median 231 days post HCT; varicella infections occurred a median 190 days; and invasive pneumococcal infections occurred a median 311 days post HCT.

“When we did a multivariate analysis by time post HCT, we found that age at transplantation, primary immune deficiency as an indication for transplantation, and graft versus host disease were independent predictors of VPIs during the initial HCT admission,” said Dr. Danino.

Children with a VPI who spent longer in hospital were more likely to be admitted to an ICU and have higher mortality, compared with children without a VPI diagnosis.

“VPIs led to longer duration of hospitalization, higher rates of ICU admission, and higher mortality, compared to HCT recipients without VPIs,” Dr. Danino explained. It was not possible in this retrospective study to determine whether increased mortality was VPI related.

These results underline the seriousness of infections in vulnerable children after HCT. Dr. Danino concluded by saying that “efforts to optimize vaccination strategies early post HCT are warranted to decrease VPIs.”

Dr. Danino had nothing to disclose.

Vaccine-preventable infections (VPIs) in pediatric hematopoietic cell transplantation (HCT) recipients cause significant morbidity, health care burden, and mortality.

Dana Danino, MD, and colleagues presented their evaluation of the prevalence and epidemiology of pediatric VPI-associated hospitalizations occurring within 5 years post HCT at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.

“Pediatric HCT recipients are at increased risk of VPIs, and HCT recipients have poor outcomes from VPIs, compared with the general population,” explained Dr. Danino, of the department of pediatrics, and divisions of infectious diseases and host defense at the Ohio State University, Columbus. “However, the contemporary prevalence, risk factors, morbidity and mortality resulting from VPIs in children post HCT are not well known.”

Their epidemiological study, using the Pediatric Health Information System (PHIS) database, identified all children under 18 years that underwent allogeneic or autologous HCT in an 8-year period. A total of 9,591 unique HCT recipients were identified.

The researchers demonstrated that 7.1% of this cohort were hospitalized for a VPI in the first 5 years post HCT. Dr. Danino explained that 67% of VPI hospitalizations occurred during the first year, at a median of 222 days, and 22% of VPIs occurred during the initial HCT admission.

As to the type of infection, Dr. Danino and colleagues found that, the prevalence of VPI hospitalizations were highest for influenza, followed by varicella and invasive pneumococcal infections. They identified no hospitalizations due to measles or rubella during the study period.

The study findings revealed that the influenza infections occurred a median 231 days post HCT; varicella infections occurred a median 190 days; and invasive pneumococcal infections occurred a median 311 days post HCT.

“When we did a multivariate analysis by time post HCT, we found that age at transplantation, primary immune deficiency as an indication for transplantation, and graft versus host disease were independent predictors of VPIs during the initial HCT admission,” said Dr. Danino.

Children with a VPI who spent longer in hospital were more likely to be admitted to an ICU and have higher mortality, compared with children without a VPI diagnosis.

“VPIs led to longer duration of hospitalization, higher rates of ICU admission, and higher mortality, compared to HCT recipients without VPIs,” Dr. Danino explained. It was not possible in this retrospective study to determine whether increased mortality was VPI related.

These results underline the seriousness of infections in vulnerable children after HCT. Dr. Danino concluded by saying that “efforts to optimize vaccination strategies early post HCT are warranted to decrease VPIs.”

Dr. Danino had nothing to disclose.

Vaccine-preventable infections (VPIs) in pediatric hematopoietic cell transplantation (HCT) recipients cause significant morbidity, health care burden, and mortality.

Dana Danino, MD, and colleagues presented their evaluation of the prevalence and epidemiology of pediatric VPI-associated hospitalizations occurring within 5 years post HCT at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.

“Pediatric HCT recipients are at increased risk of VPIs, and HCT recipients have poor outcomes from VPIs, compared with the general population,” explained Dr. Danino, of the department of pediatrics, and divisions of infectious diseases and host defense at the Ohio State University, Columbus. “However, the contemporary prevalence, risk factors, morbidity and mortality resulting from VPIs in children post HCT are not well known.”

Their epidemiological study, using the Pediatric Health Information System (PHIS) database, identified all children under 18 years that underwent allogeneic or autologous HCT in an 8-year period. A total of 9,591 unique HCT recipients were identified.

The researchers demonstrated that 7.1% of this cohort were hospitalized for a VPI in the first 5 years post HCT. Dr. Danino explained that 67% of VPI hospitalizations occurred during the first year, at a median of 222 days, and 22% of VPIs occurred during the initial HCT admission.

As to the type of infection, Dr. Danino and colleagues found that, the prevalence of VPI hospitalizations were highest for influenza, followed by varicella and invasive pneumococcal infections. They identified no hospitalizations due to measles or rubella during the study period.

The study findings revealed that the influenza infections occurred a median 231 days post HCT; varicella infections occurred a median 190 days; and invasive pneumococcal infections occurred a median 311 days post HCT.

“When we did a multivariate analysis by time post HCT, we found that age at transplantation, primary immune deficiency as an indication for transplantation, and graft versus host disease were independent predictors of VPIs during the initial HCT admission,” said Dr. Danino.

Children with a VPI who spent longer in hospital were more likely to be admitted to an ICU and have higher mortality, compared with children without a VPI diagnosis.

“VPIs led to longer duration of hospitalization, higher rates of ICU admission, and higher mortality, compared to HCT recipients without VPIs,” Dr. Danino explained. It was not possible in this retrospective study to determine whether increased mortality was VPI related.

These results underline the seriousness of infections in vulnerable children after HCT. Dr. Danino concluded by saying that “efforts to optimize vaccination strategies early post HCT are warranted to decrease VPIs.”

Dr. Danino had nothing to disclose.

Rheumatoid arthritis patients who are on both oral glucocorticoids (CGs) and proton pump inhibitors (PPIs) have an increased risk of osteoporotic fractures, according to a retrospective study of RA patients in the United Kingdom.

“Considering the increasing life expectancies and high consumption of PPIs among elderly patients, fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs,” wrote Shahab Abtahi, MD, of Maastricht (Netherlands) University Medical Centre and colleagues. The study was published in Annals of the Rheumatic Diseases.

To determine if concomitant use of the two medications – both already associated with osteoporotic fractures – would lead to a notable increase in fracture risk, the researchers conducted a population-based cohort study of RA patients aged 50 years or older who were diagnosed during 1997-2017. Patient data was gathered via the Clinical Practice Research Datalink, a primary care database of millions of U.K. medical records.

Patients with a recent history of GC/PPI use or those with a previous osteoporotic fracture were excluded from the study. Osteoporotic fractures were defined as fractures of the hip, vertebrae, humerus, forearm, pelvis, or rib. The study population included 12,351 patients, roughly two-thirds of whom were women, with a mean age of 68 years. Of the population, 4,254 patients were concomitant users of oral GCs and PPIs, compared with 3,138 patients who were not on either medication.

Among all patients, 1,411 osteoporotic fractures occurred, 264 of which occurred in the concomitant users group. After adjustments for age and sex, patients on both medications had a higher risk of fracture (adjusted hazard ratio, 1.93; 95% confidence interval, 1.65-2.27), compared to patients on oral GCs alone (aHR, 1.34; 95% CI, 1.12-1.59) or PPIs alone (aHR, 1.32; 95% CI, 1.14-1.54). After full adjustment, concomitant users again had a higher risk of fracture (aHR, 1.60; 95% CI, 1.35-1.89).

Regarding specific types of breaks, the concomitant users had a notably higher risk of hip (aHR, 1.45; 95% CI, 1.11-1.91), vertebrae (aHR, 2.84; 95% CI, 1.87-4.32), pelvis (aHR, 2.47; 95% CI, 1.41-4.34), and rib fractures (aHR, 4.03; 95% CI, 2.13-7.63). No increased risk was found for either humerus or forearm fractures. The risk of fracture did not rise for concomitant users who had either increasing daily doses of PPI or a longer duration of use.

The authors noted their study’s potential limitations, including having access to data on prescriptions only, not the actual use of medication, and a lack of information in the medical records regarding biologic therapies or certain indicators of RA disease activity. In addition, there was a likelihood that some patients who were improving might have stopped taking the drugs and lessened their risk of fracture, though the researchers attempted to account for this by “adjusting our analyses for six indicators of RA severity, including analgesics and csDMARDs.”

Two of the authors reported receiving research grants and speakers’ fees from various pharmaceutical companies. The others reported no conflicts of interest.

SOURCE: Abtahi S et al. Ann Rheum Dis. 2020 Dec 11. doi: 10.1136/annrheumdis-2020-218758.

Rheumatoid arthritis patients who are on both oral glucocorticoids (CGs) and proton pump inhibitors (PPIs) have an increased risk of osteoporotic fractures, according to a retrospective study of RA patients in the United Kingdom.

“Considering the increasing life expectancies and high consumption of PPIs among elderly patients, fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs,” wrote Shahab Abtahi, MD, of Maastricht (Netherlands) University Medical Centre and colleagues. The study was published in Annals of the Rheumatic Diseases.

To determine if concomitant use of the two medications – both already associated with osteoporotic fractures – would lead to a notable increase in fracture risk, the researchers conducted a population-based cohort study of RA patients aged 50 years or older who were diagnosed during 1997-2017. Patient data was gathered via the Clinical Practice Research Datalink, a primary care database of millions of U.K. medical records.

Patients with a recent history of GC/PPI use or those with a previous osteoporotic fracture were excluded from the study. Osteoporotic fractures were defined as fractures of the hip, vertebrae, humerus, forearm, pelvis, or rib. The study population included 12,351 patients, roughly two-thirds of whom were women, with a mean age of 68 years. Of the population, 4,254 patients were concomitant users of oral GCs and PPIs, compared with 3,138 patients who were not on either medication.

Among all patients, 1,411 osteoporotic fractures occurred, 264 of which occurred in the concomitant users group. After adjustments for age and sex, patients on both medications had a higher risk of fracture (adjusted hazard ratio, 1.93; 95% confidence interval, 1.65-2.27), compared to patients on oral GCs alone (aHR, 1.34; 95% CI, 1.12-1.59) or PPIs alone (aHR, 1.32; 95% CI, 1.14-1.54). After full adjustment, concomitant users again had a higher risk of fracture (aHR, 1.60; 95% CI, 1.35-1.89).

Regarding specific types of breaks, the concomitant users had a notably higher risk of hip (aHR, 1.45; 95% CI, 1.11-1.91), vertebrae (aHR, 2.84; 95% CI, 1.87-4.32), pelvis (aHR, 2.47; 95% CI, 1.41-4.34), and rib fractures (aHR, 4.03; 95% CI, 2.13-7.63). No increased risk was found for either humerus or forearm fractures. The risk of fracture did not rise for concomitant users who had either increasing daily doses of PPI or a longer duration of use.

The authors noted their study’s potential limitations, including having access to data on prescriptions only, not the actual use of medication, and a lack of information in the medical records regarding biologic therapies or certain indicators of RA disease activity. In addition, there was a likelihood that some patients who were improving might have stopped taking the drugs and lessened their risk of fracture, though the researchers attempted to account for this by “adjusting our analyses for six indicators of RA severity, including analgesics and csDMARDs.”

Two of the authors reported receiving research grants and speakers’ fees from various pharmaceutical companies. The others reported no conflicts of interest.

SOURCE: Abtahi S et al. Ann Rheum Dis. 2020 Dec 11. doi: 10.1136/annrheumdis-2020-218758.

Rheumatoid arthritis patients who are on both oral glucocorticoids (CGs) and proton pump inhibitors (PPIs) have an increased risk of osteoporotic fractures, according to a retrospective study of RA patients in the United Kingdom.

“Considering the increasing life expectancies and high consumption of PPIs among elderly patients, fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs,” wrote Shahab Abtahi, MD, of Maastricht (Netherlands) University Medical Centre and colleagues. The study was published in Annals of the Rheumatic Diseases.

To determine if concomitant use of the two medications – both already associated with osteoporotic fractures – would lead to a notable increase in fracture risk, the researchers conducted a population-based cohort study of RA patients aged 50 years or older who were diagnosed during 1997-2017. Patient data was gathered via the Clinical Practice Research Datalink, a primary care database of millions of U.K. medical records.

Patients with a recent history of GC/PPI use or those with a previous osteoporotic fracture were excluded from the study. Osteoporotic fractures were defined as fractures of the hip, vertebrae, humerus, forearm, pelvis, or rib. The study population included 12,351 patients, roughly two-thirds of whom were women, with a mean age of 68 years. Of the population, 4,254 patients were concomitant users of oral GCs and PPIs, compared with 3,138 patients who were not on either medication.

Among all patients, 1,411 osteoporotic fractures occurred, 264 of which occurred in the concomitant users group. After adjustments for age and sex, patients on both medications had a higher risk of fracture (adjusted hazard ratio, 1.93; 95% confidence interval, 1.65-2.27), compared to patients on oral GCs alone (aHR, 1.34; 95% CI, 1.12-1.59) or PPIs alone (aHR, 1.32; 95% CI, 1.14-1.54). After full adjustment, concomitant users again had a higher risk of fracture (aHR, 1.60; 95% CI, 1.35-1.89).

Regarding specific types of breaks, the concomitant users had a notably higher risk of hip (aHR, 1.45; 95% CI, 1.11-1.91), vertebrae (aHR, 2.84; 95% CI, 1.87-4.32), pelvis (aHR, 2.47; 95% CI, 1.41-4.34), and rib fractures (aHR, 4.03; 95% CI, 2.13-7.63). No increased risk was found for either humerus or forearm fractures. The risk of fracture did not rise for concomitant users who had either increasing daily doses of PPI or a longer duration of use.

The authors noted their study’s potential limitations, including having access to data on prescriptions only, not the actual use of medication, and a lack of information in the medical records regarding biologic therapies or certain indicators of RA disease activity. In addition, there was a likelihood that some patients who were improving might have stopped taking the drugs and lessened their risk of fracture, though the researchers attempted to account for this by “adjusting our analyses for six indicators of RA severity, including analgesics and csDMARDs.”

Two of the authors reported receiving research grants and speakers’ fees from various pharmaceutical companies. The others reported no conflicts of interest.

SOURCE: Abtahi S et al. Ann Rheum Dis. 2020 Dec 11. doi: 10.1136/annrheumdis-2020-218758.

Although guidelines generally recommend ambulatory over home blood pressure monitoring for diagnosing hypertension, new research questions home BP monitoring’s role as second fiddle.

One week of home BP monitoring (HBPM) was more reliable than one 24-hour ambulatory BP or nine mercury readings across three office visits among younger, untreated participants in the Improving the Detection of Hypertension study.

The reliability coefficients were 0.938, 0.846, and 0.894 for systolic BP and 0.918, 0.843, and 0.847 for diastolic BP, respectively.

Further, HBPM had the strongest association with left ventricular mass index (LVMI), a predictor of adverse cardiovascular events, according to researchers led by Joseph E. Schwartz, PhD, Stony Brook (N.Y.) University and Columbia University Irving Medical Center, New York.

The association with LVMI also remained after multivariate adjustment and after correcting for regression dilution bias, indicating the results were not a result of differences in the number of readings, they write in the study, published online in the Journal of the American College of Cardiology.

Whenever patients have an elevated blood pressure for the first time or even borderline elevated BP, guidelines recommend clinicians request a 24-hour ambulatory recording or home monitoring, Dr. Schwartz said in an interview. “I think this has the potential, for that purpose, to put ambulatory blood pressure monitoring out of business, even though that’s what I’ve done for 30 years.”

Previous studies have shown that home and ambulatory BP monitoring (ABPM) correlate more strongly with target-organ damage and cardiovascular outcomes than office BP, but head-to-head outcomes trials of the two techniques are lacking. A recent systematic review also found scant evidence supporting one approach over the other for predicting cardiovascular events or mortality.

An accompanying editorial notes that ABPM is largely unavailable to primary care physicians in the United States and poorly reimbursed. “Thus the demonstration that HBPM is more reliable and associates more closely with LVMI than ABPM, if confirmed, would carry the potential to change clinical practice,” wrote Robert M. Carey, MD, University of Virginia Health System in Charlottesville, and Thomas H. Marwick, MBBS, PhD, MPH, Baker Heart and Diabetes Institute, Melbourne.

In a comment, ABPM proponent Raymond R. Townsend, MD, said, “Honestly, it may be that we’ll need to act on this. I’m not quite ready to do that and change my practice patterns but, on the other hand, I can’t sweep this under the rug.”

He noted that it’s ironic the study is coauthored by the late Thomas Pickering, MD, a maven of ABPM who coined the term “white-coat hypertension” and pointed out masked hypertension.

That said, “it raised the bar on ambulatory blood pressure monitoring: Is it really worth our public health dollars? So I think it’s a very good call to arms,” said Dr. Townsend, who directs the hypertension program at the University of Pennsylvania, Philadelphia.

Ambulatory BP monitoring has long been considered the preferred method but, from a cost standpoint, HBPM is more attractive because the devices can be used more than once and track more than one person in a household, he said. The Center for Medicare Management also has a code in the 2020 bundle to reimburse physicians $15 for training patients and has a monthly charge for communicating with those filing regularly. “You’re not going to get rich doing monitoring of home BP, but at least the government is recognizing we are moving more and more to the home base in terms of our managing common conditions like blood pressure.”

One of the attractions of ABPM is the ability to do every half hour to every hour nocturnal pressures, but at least one home monitor, manufactured by Microlife, has added a nocturnal feature, Dr. Townsend noted. “So that’s just one more incoming against the ABPM defenses about why ABPMs are still better.”

The study enrolled a community-based sample of 408 participants who had office BP assessed at three visits (three readings per visit) using a mercury sphygmomanometer, a BpTRU (VSM MedTech) automated oscillometric device, and a home-validated Omron Healthcare oscillometric device.

After 5 minutes of in-office training and receipt of a reference sheet, participants also completed 3 weeks of HBPM with the Omron device as well as two 24-hour ambulatory measurements (Spacelabs Healthcare, Model 90207). Cardiovascular evaluations, including two-dimensional echocardiograms, were performed during the fifth office visit.

The 400 participants who completed all five visits had a mean age of 41 years, mean LVMI of 79.3 g/m², and mean office systolic BP ranging from 116.0 to 117.2 mm Hg and diastolic BP from 75.6 to 76.5 mm Hg.

Both before and after correction for regression dilution bias, home systolic and diastolic BP were more highly correlated with LVMI than 24-hour ambulatory or office mercury readings. The corrected correlations for systolic BP were 0.501, 0.430, and 0.389, respectively.

After multivariable adjustment including office and 24-hour ambulatory BP, 10 mm Hg higher systolic and diastolic home BP were associated with 5.07 g/m² (P = .001) and 3.92 g/m² (P = .07) higher LVMI, respectively. After adjustment for home BP, however, neither systolic or diastolic office BP nor ambulatory BP was associated with LVMI.

Dr. Townsend and editorialists Dr. Carey and Dr. Marwick pointed out the study included a younger population in whom just 30% to 50% would have been classified as having hypertension by the 2017 American College of Cardiology/American Heart Association guidelines, which Dr. Carey helped to pen.

“These people are young and older people have a different kind of blood pressure driven more by the stiffness in their circulation and less by the resistance to blood flow that you find more characteristic in younger people,” Dr. Townsend observed.

“I don’t know that you can extrapolate the findings from this study in healthy, younger untreated people to older, perhaps sicker, and more diabetic people where the real action is and where the endpoints like heart attack, death, and stroke actually occur,” he said.

The results suggest measurement of resting daytime BP may be relatively more important than dynamic daytime and/or nocturnal parameters in predicting subclinical cardiac target organ damage, but this requires further study, Dr. Carey and Dr. Marwick noted.

Commenting further, they wrote that the results suggest “HBPM could be especially important for detecting elevated BP and hypertension early in life, when adults are relatively healthy, but those with hypertension have a high lifetime risk of CVD.”

Dr. Schwartz acknowledged the study didn’t include the typical hypertensive patient but said it goes to the central question of whether the risk associated with blood pressure is because of the heart’s cumulative exposure over its lifetime and, thus, best measured with multiple readings taken under a variety of circumstances or with readings taken only at rest. 

“I’ve been posing that question at a conceptual level for 15 years, never in print, and this paper is the first hint, at least with respect to the left ventricular mass index … that getting a better measure of resting blood pressure is more important for controlling risk than the heart’s cumulative exposure to blood pressure, as measured by ambulatory,” he said.

The Improving the Detection of Hypertension study was supported by a grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health. The authors disclosed no relevant financial relationships. Dr. Townsend reported receiving royalties as a writer for UpToDate and serving as an unpaid reviewer for ValidateBP.org. Dr. Carey is principal investigator and project director of a NIH R01 and P01 grant, respectively; vice chair of the 2017 ACC/AHA hypertension guideline writing committee; and chair of the AHA Resistant Hypertension Scientific Statement writing committee. Dr. Marwick disclosed no relevant financial relationships.

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

Although guidelines generally recommend ambulatory over home blood pressure monitoring for diagnosing hypertension, new research questions home BP monitoring’s role as second fiddle.

One week of home BP monitoring (HBPM) was more reliable than one 24-hour ambulatory BP or nine mercury readings across three office visits among younger, untreated participants in the Improving the Detection of Hypertension study.

The reliability coefficients were 0.938, 0.846, and 0.894 for systolic BP and 0.918, 0.843, and 0.847 for diastolic BP, respectively.

Further, HBPM had the strongest association with left ventricular mass index (LVMI), a predictor of adverse cardiovascular events, according to researchers led by Joseph E. Schwartz, PhD, Stony Brook (N.Y.) University and Columbia University Irving Medical Center, New York.

The association with LVMI also remained after multivariate adjustment and after correcting for regression dilution bias, indicating the results were not a result of differences in the number of readings, they write in the study, published online in the Journal of the American College of Cardiology.

Whenever patients have an elevated blood pressure for the first time or even borderline elevated BP, guidelines recommend clinicians request a 24-hour ambulatory recording or home monitoring, Dr. Schwartz said in an interview. “I think this has the potential, for that purpose, to put ambulatory blood pressure monitoring out of business, even though that’s what I’ve done for 30 years.”

Previous studies have shown that home and ambulatory BP monitoring (ABPM) correlate more strongly with target-organ damage and cardiovascular outcomes than office BP, but head-to-head outcomes trials of the two techniques are lacking. A recent systematic review also found scant evidence supporting one approach over the other for predicting cardiovascular events or mortality.

An accompanying editorial notes that ABPM is largely unavailable to primary care physicians in the United States and poorly reimbursed. “Thus the demonstration that HBPM is more reliable and associates more closely with LVMI than ABPM, if confirmed, would carry the potential to change clinical practice,” wrote Robert M. Carey, MD, University of Virginia Health System in Charlottesville, and Thomas H. Marwick, MBBS, PhD, MPH, Baker Heart and Diabetes Institute, Melbourne.

In a comment, ABPM proponent Raymond R. Townsend, MD, said, “Honestly, it may be that we’ll need to act on this. I’m not quite ready to do that and change my practice patterns but, on the other hand, I can’t sweep this under the rug.”

He noted that it’s ironic the study is coauthored by the late Thomas Pickering, MD, a maven of ABPM who coined the term “white-coat hypertension” and pointed out masked hypertension.

That said, “it raised the bar on ambulatory blood pressure monitoring: Is it really worth our public health dollars? So I think it’s a very good call to arms,” said Dr. Townsend, who directs the hypertension program at the University of Pennsylvania, Philadelphia.

Ambulatory BP monitoring has long been considered the preferred method but, from a cost standpoint, HBPM is more attractive because the devices can be used more than once and track more than one person in a household, he said. The Center for Medicare Management also has a code in the 2020 bundle to reimburse physicians $15 for training patients and has a monthly charge for communicating with those filing regularly. “You’re not going to get rich doing monitoring of home BP, but at least the government is recognizing we are moving more and more to the home base in terms of our managing common conditions like blood pressure.”

One of the attractions of ABPM is the ability to do every half hour to every hour nocturnal pressures, but at least one home monitor, manufactured by Microlife, has added a nocturnal feature, Dr. Townsend noted. “So that’s just one more incoming against the ABPM defenses about why ABPMs are still better.”

The study enrolled a community-based sample of 408 participants who had office BP assessed at three visits (three readings per visit) using a mercury sphygmomanometer, a BpTRU (VSM MedTech) automated oscillometric device, and a home-validated Omron Healthcare oscillometric device.

After 5 minutes of in-office training and receipt of a reference sheet, participants also completed 3 weeks of HBPM with the Omron device as well as two 24-hour ambulatory measurements (Spacelabs Healthcare, Model 90207). Cardiovascular evaluations, including two-dimensional echocardiograms, were performed during the fifth office visit.

The 400 participants who completed all five visits had a mean age of 41 years, mean LVMI of 79.3 g/m², and mean office systolic BP ranging from 116.0 to 117.2 mm Hg and diastolic BP from 75.6 to 76.5 mm Hg.

Both before and after correction for regression dilution bias, home systolic and diastolic BP were more highly correlated with LVMI than 24-hour ambulatory or office mercury readings. The corrected correlations for systolic BP were 0.501, 0.430, and 0.389, respectively.

After multivariable adjustment including office and 24-hour ambulatory BP, 10 mm Hg higher systolic and diastolic home BP were associated with 5.07 g/m² (P = .001) and 3.92 g/m² (P = .07) higher LVMI, respectively. After adjustment for home BP, however, neither systolic or diastolic office BP nor ambulatory BP was associated with LVMI.

Dr. Townsend and editorialists Dr. Carey and Dr. Marwick pointed out the study included a younger population in whom just 30% to 50% would have been classified as having hypertension by the 2017 American College of Cardiology/American Heart Association guidelines, which Dr. Carey helped to pen.

“These people are young and older people have a different kind of blood pressure driven more by the stiffness in their circulation and less by the resistance to blood flow that you find more characteristic in younger people,” Dr. Townsend observed.

“I don’t know that you can extrapolate the findings from this study in healthy, younger untreated people to older, perhaps sicker, and more diabetic people where the real action is and where the endpoints like heart attack, death, and stroke actually occur,” he said.

The results suggest measurement of resting daytime BP may be relatively more important than dynamic daytime and/or nocturnal parameters in predicting subclinical cardiac target organ damage, but this requires further study, Dr. Carey and Dr. Marwick noted.

Commenting further, they wrote that the results suggest “HBPM could be especially important for detecting elevated BP and hypertension early in life, when adults are relatively healthy, but those with hypertension have a high lifetime risk of CVD.”

Dr. Schwartz acknowledged the study didn’t include the typical hypertensive patient but said it goes to the central question of whether the risk associated with blood pressure is because of the heart’s cumulative exposure over its lifetime and, thus, best measured with multiple readings taken under a variety of circumstances or with readings taken only at rest. 

“I’ve been posing that question at a conceptual level for 15 years, never in print, and this paper is the first hint, at least with respect to the left ventricular mass index … that getting a better measure of resting blood pressure is more important for controlling risk than the heart’s cumulative exposure to blood pressure, as measured by ambulatory,” he said.

The Improving the Detection of Hypertension study was supported by a grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health. The authors disclosed no relevant financial relationships. Dr. Townsend reported receiving royalties as a writer for UpToDate and serving as an unpaid reviewer for ValidateBP.org. Dr. Carey is principal investigator and project director of a NIH R01 and P01 grant, respectively; vice chair of the 2017 ACC/AHA hypertension guideline writing committee; and chair of the AHA Resistant Hypertension Scientific Statement writing committee. Dr. Marwick disclosed no relevant financial relationships.

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

Although guidelines generally recommend ambulatory over home blood pressure monitoring for diagnosing hypertension, new research questions home BP monitoring’s role as second fiddle.

One week of home BP monitoring (HBPM) was more reliable than one 24-hour ambulatory BP or nine mercury readings across three office visits among younger, untreated participants in the Improving the Detection of Hypertension study.

The reliability coefficients were 0.938, 0.846, and 0.894 for systolic BP and 0.918, 0.843, and 0.847 for diastolic BP, respectively.

Further, HBPM had the strongest association with left ventricular mass index (LVMI), a predictor of adverse cardiovascular events, according to researchers led by Joseph E. Schwartz, PhD, Stony Brook (N.Y.) University and Columbia University Irving Medical Center, New York.

The association with LVMI also remained after multivariate adjustment and after correcting for regression dilution bias, indicating the results were not a result of differences in the number of readings, they write in the study, published online in the Journal of the American College of Cardiology.

Whenever patients have an elevated blood pressure for the first time or even borderline elevated BP, guidelines recommend clinicians request a 24-hour ambulatory recording or home monitoring, Dr. Schwartz said in an interview. “I think this has the potential, for that purpose, to put ambulatory blood pressure monitoring out of business, even though that’s what I’ve done for 30 years.”

Previous studies have shown that home and ambulatory BP monitoring (ABPM) correlate more strongly with target-organ damage and cardiovascular outcomes than office BP, but head-to-head outcomes trials of the two techniques are lacking. A recent systematic review also found scant evidence supporting one approach over the other for predicting cardiovascular events or mortality.

An accompanying editorial notes that ABPM is largely unavailable to primary care physicians in the United States and poorly reimbursed. “Thus the demonstration that HBPM is more reliable and associates more closely with LVMI than ABPM, if confirmed, would carry the potential to change clinical practice,” wrote Robert M. Carey, MD, University of Virginia Health System in Charlottesville, and Thomas H. Marwick, MBBS, PhD, MPH, Baker Heart and Diabetes Institute, Melbourne.

In a comment, ABPM proponent Raymond R. Townsend, MD, said, “Honestly, it may be that we’ll need to act on this. I’m not quite ready to do that and change my practice patterns but, on the other hand, I can’t sweep this under the rug.”

He noted that it’s ironic the study is coauthored by the late Thomas Pickering, MD, a maven of ABPM who coined the term “white-coat hypertension” and pointed out masked hypertension.

That said, “it raised the bar on ambulatory blood pressure monitoring: Is it really worth our public health dollars? So I think it’s a very good call to arms,” said Dr. Townsend, who directs the hypertension program at the University of Pennsylvania, Philadelphia.

Ambulatory BP monitoring has long been considered the preferred method but, from a cost standpoint, HBPM is more attractive because the devices can be used more than once and track more than one person in a household, he said. The Center for Medicare Management also has a code in the 2020 bundle to reimburse physicians $15 for training patients and has a monthly charge for communicating with those filing regularly. “You’re not going to get rich doing monitoring of home BP, but at least the government is recognizing we are moving more and more to the home base in terms of our managing common conditions like blood pressure.”

One of the attractions of ABPM is the ability to do every half hour to every hour nocturnal pressures, but at least one home monitor, manufactured by Microlife, has added a nocturnal feature, Dr. Townsend noted. “So that’s just one more incoming against the ABPM defenses about why ABPMs are still better.”

The study enrolled a community-based sample of 408 participants who had office BP assessed at three visits (three readings per visit) using a mercury sphygmomanometer, a BpTRU (VSM MedTech) automated oscillometric device, and a home-validated Omron Healthcare oscillometric device.

After 5 minutes of in-office training and receipt of a reference sheet, participants also completed 3 weeks of HBPM with the Omron device as well as two 24-hour ambulatory measurements (Spacelabs Healthcare, Model 90207). Cardiovascular evaluations, including two-dimensional echocardiograms, were performed during the fifth office visit.

The 400 participants who completed all five visits had a mean age of 41 years, mean LVMI of 79.3 g/m², and mean office systolic BP ranging from 116.0 to 117.2 mm Hg and diastolic BP from 75.6 to 76.5 mm Hg.

Both before and after correction for regression dilution bias, home systolic and diastolic BP were more highly correlated with LVMI than 24-hour ambulatory or office mercury readings. The corrected correlations for systolic BP were 0.501, 0.430, and 0.389, respectively.

After multivariable adjustment including office and 24-hour ambulatory BP, 10 mm Hg higher systolic and diastolic home BP were associated with 5.07 g/m² (P = .001) and 3.92 g/m² (P = .07) higher LVMI, respectively. After adjustment for home BP, however, neither systolic or diastolic office BP nor ambulatory BP was associated with LVMI.

Dr. Townsend and editorialists Dr. Carey and Dr. Marwick pointed out the study included a younger population in whom just 30% to 50% would have been classified as having hypertension by the 2017 American College of Cardiology/American Heart Association guidelines, which Dr. Carey helped to pen.

“These people are young and older people have a different kind of blood pressure driven more by the stiffness in their circulation and less by the resistance to blood flow that you find more characteristic in younger people,” Dr. Townsend observed.

“I don’t know that you can extrapolate the findings from this study in healthy, younger untreated people to older, perhaps sicker, and more diabetic people where the real action is and where the endpoints like heart attack, death, and stroke actually occur,” he said.

The results suggest measurement of resting daytime BP may be relatively more important than dynamic daytime and/or nocturnal parameters in predicting subclinical cardiac target organ damage, but this requires further study, Dr. Carey and Dr. Marwick noted.

Commenting further, they wrote that the results suggest “HBPM could be especially important for detecting elevated BP and hypertension early in life, when adults are relatively healthy, but those with hypertension have a high lifetime risk of CVD.”

Dr. Schwartz acknowledged the study didn’t include the typical hypertensive patient but said it goes to the central question of whether the risk associated with blood pressure is because of the heart’s cumulative exposure over its lifetime and, thus, best measured with multiple readings taken under a variety of circumstances or with readings taken only at rest. 

“I’ve been posing that question at a conceptual level for 15 years, never in print, and this paper is the first hint, at least with respect to the left ventricular mass index … that getting a better measure of resting blood pressure is more important for controlling risk than the heart’s cumulative exposure to blood pressure, as measured by ambulatory,” he said.

The Improving the Detection of Hypertension study was supported by a grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health. The authors disclosed no relevant financial relationships. Dr. Townsend reported receiving royalties as a writer for UpToDate and serving as an unpaid reviewer for ValidateBP.org. Dr. Carey is principal investigator and project director of a NIH R01 and P01 grant, respectively; vice chair of the 2017 ACC/AHA hypertension guideline writing committee; and chair of the AHA Resistant Hypertension Scientific Statement writing committee. Dr. Marwick disclosed no relevant financial relationships.

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

Treat acne from near birth to adulthood with a growing level of aggressiveness as a child ages, a dermatologist urged colleagues.

No treatment may be necessary for acne in the first few months of life, but the condition can leave scars in children as young as ages 3-6 months, said Andrea L. Zaenglein, MD, professor of dermatology and pediatric dermatology, Penn State University, Hershey, Penn., said in a presentation at MedscapeLive’s virtual Women’s & Pediatric Dermatology Seminar.

Neonatal acne occurs in more than 20% of newborns aged 2 weeks to 3 months. “Typically we don’t need to treat it. But if you do, you could use a topical antifungal like clotrimazole cream twice a day,” but in most babies, “this will just improve over time and resolve without any scarring or sequelae,” she said.

Infantile acne begins about 3-6 months of age typically, or a little bit older, and lasts up to 2 years of age, Dr. Zaenglein said. “You will see comedones in infantile acne, so this is actually a true form of acne. It’s due to increased adrenal production of androgens.”

She added: “The scarring can be permanent. It’s important that you recognize infantile acne and treat it, even though it seems pretty mild.”

For infantile acne, she recommends performing a full-skin exam to rule out hyperandrogenic disorders such as Cushing syndrome, congenital adrenal hyperplasia, premature adrenarche, a gonadal/adrenal tumor and precocious puberty.

Treatments are similar to those in teenagers, she said, “but make sure you use baby-friendly formulations,” with lower concentrations of active ingredients – and avoid tetracyclines and benzoyl peroxide (BPO) washes. BPO can be used in leave-on formulations/creams at lower strengths (2.5%-5%).

One possible combination option is tretinoin 0.025% cream or adapalene 0.1% gel plus BPO 2.5% cream or clindamycin/BPO gel. Another combination is adapalene/BPO 2.5% gel.

Erythromycin can be appropriate at 30-50 mg/kg per day divided in two or three doses a day, but beware of possible gastrointestinal upset. Azithromycin at 5 mg/kg per day is another option.

“Rarely do we have to go to isotretinoin,” Dr. Zaenglein said. “I think in all my years, I’ve only treated one baby with isotretinoin for infantile acne. But severe forms can occur.”

Midchildhood and preadolescent acne conditions occur in children starting at ages 1 up to 10 years, Dr. Zaenglein said. In this population, she also recommends ruling out hyperandrogenism by looking for secondary sexual characteristics with full-body skin exams. “The workup can be broad and includes looking at adrenal androgens and total and free testosterone, as well as looking at growth charts and bone age. Typically, you’ll refer these kids to pediatric endocrinology.”

Keep in mind, she said, that early adrenarche starts at ages 6-7 years in girls and 7-8 years in boys. “That’s when we expect to start seeing that very early acne. You can see it even earlier in patients with elevated BMI, and it’s more common in Hispanic and Black children as well.”

She added that it’s important to remember that early adrenarche is a risk factor for polycystic ovarian syndrome (PCOS). “So ask patients about their family history and look for other signs of PCOS as they move further into adolescence.”

Milder cases of acne in this age group can be treated with “salicylic acid wipes and things that are kind of a rite of passage. But if they have any more severe acne, you’re going to want to treat it more or less like you do adolescent acne.”

MedscapeLive and this news organization are owned by the same parent company. Dr. Zaenglein disclosed receiving consulting fees from Cassiopea, Dermata, and Regeneron and fees for contracted research support from Incyte.

Treat acne from near birth to adulthood with a growing level of aggressiveness as a child ages, a dermatologist urged colleagues.

No treatment may be necessary for acne in the first few months of life, but the condition can leave scars in children as young as ages 3-6 months, said Andrea L. Zaenglein, MD, professor of dermatology and pediatric dermatology, Penn State University, Hershey, Penn., said in a presentation at MedscapeLive’s virtual Women’s & Pediatric Dermatology Seminar.

Neonatal acne occurs in more than 20% of newborns aged 2 weeks to 3 months. “Typically we don’t need to treat it. But if you do, you could use a topical antifungal like clotrimazole cream twice a day,” but in most babies, “this will just improve over time and resolve without any scarring or sequelae,” she said.

Infantile acne begins about 3-6 months of age typically, or a little bit older, and lasts up to 2 years of age, Dr. Zaenglein said. “You will see comedones in infantile acne, so this is actually a true form of acne. It’s due to increased adrenal production of androgens.”

She added: “The scarring can be permanent. It’s important that you recognize infantile acne and treat it, even though it seems pretty mild.”

For infantile acne, she recommends performing a full-skin exam to rule out hyperandrogenic disorders such as Cushing syndrome, congenital adrenal hyperplasia, premature adrenarche, a gonadal/adrenal tumor and precocious puberty.

Treatments are similar to those in teenagers, she said, “but make sure you use baby-friendly formulations,” with lower concentrations of active ingredients – and avoid tetracyclines and benzoyl peroxide (BPO) washes. BPO can be used in leave-on formulations/creams at lower strengths (2.5%-5%).

One possible combination option is tretinoin 0.025% cream or adapalene 0.1% gel plus BPO 2.5% cream or clindamycin/BPO gel. Another combination is adapalene/BPO 2.5% gel.

Erythromycin can be appropriate at 30-50 mg/kg per day divided in two or three doses a day, but beware of possible gastrointestinal upset. Azithromycin at 5 mg/kg per day is another option.

“Rarely do we have to go to isotretinoin,” Dr. Zaenglein said. “I think in all my years, I’ve only treated one baby with isotretinoin for infantile acne. But severe forms can occur.”

Midchildhood and preadolescent acne conditions occur in children starting at ages 1 up to 10 years, Dr. Zaenglein said. In this population, she also recommends ruling out hyperandrogenism by looking for secondary sexual characteristics with full-body skin exams. “The workup can be broad and includes looking at adrenal androgens and total and free testosterone, as well as looking at growth charts and bone age. Typically, you’ll refer these kids to pediatric endocrinology.”

Keep in mind, she said, that early adrenarche starts at ages 6-7 years in girls and 7-8 years in boys. “That’s when we expect to start seeing that very early acne. You can see it even earlier in patients with elevated BMI, and it’s more common in Hispanic and Black children as well.”

She added that it’s important to remember that early adrenarche is a risk factor for polycystic ovarian syndrome (PCOS). “So ask patients about their family history and look for other signs of PCOS as they move further into adolescence.”

Milder cases of acne in this age group can be treated with “salicylic acid wipes and things that are kind of a rite of passage. But if they have any more severe acne, you’re going to want to treat it more or less like you do adolescent acne.”

MedscapeLive and this news organization are owned by the same parent company. Dr. Zaenglein disclosed receiving consulting fees from Cassiopea, Dermata, and Regeneron and fees for contracted research support from Incyte.

Treat acne from near birth to adulthood with a growing level of aggressiveness as a child ages, a dermatologist urged colleagues.

No treatment may be necessary for acne in the first few months of life, but the condition can leave scars in children as young as ages 3-6 months, said Andrea L. Zaenglein, MD, professor of dermatology and pediatric dermatology, Penn State University, Hershey, Penn., said in a presentation at MedscapeLive’s virtual Women’s & Pediatric Dermatology Seminar.

Neonatal acne occurs in more than 20% of newborns aged 2 weeks to 3 months. “Typically we don’t need to treat it. But if you do, you could use a topical antifungal like clotrimazole cream twice a day,” but in most babies, “this will just improve over time and resolve without any scarring or sequelae,” she said.

Infantile acne begins about 3-6 months of age typically, or a little bit older, and lasts up to 2 years of age, Dr. Zaenglein said. “You will see comedones in infantile acne, so this is actually a true form of acne. It’s due to increased adrenal production of androgens.”

She added: “The scarring can be permanent. It’s important that you recognize infantile acne and treat it, even though it seems pretty mild.”

For infantile acne, she recommends performing a full-skin exam to rule out hyperandrogenic disorders such as Cushing syndrome, congenital adrenal hyperplasia, premature adrenarche, a gonadal/adrenal tumor and precocious puberty.

Treatments are similar to those in teenagers, she said, “but make sure you use baby-friendly formulations,” with lower concentrations of active ingredients – and avoid tetracyclines and benzoyl peroxide (BPO) washes. BPO can be used in leave-on formulations/creams at lower strengths (2.5%-5%).

One possible combination option is tretinoin 0.025% cream or adapalene 0.1% gel plus BPO 2.5% cream or clindamycin/BPO gel. Another combination is adapalene/BPO 2.5% gel.

Erythromycin can be appropriate at 30-50 mg/kg per day divided in two or three doses a day, but beware of possible gastrointestinal upset. Azithromycin at 5 mg/kg per day is another option.

“Rarely do we have to go to isotretinoin,” Dr. Zaenglein said. “I think in all my years, I’ve only treated one baby with isotretinoin for infantile acne. But severe forms can occur.”

Midchildhood and preadolescent acne conditions occur in children starting at ages 1 up to 10 years, Dr. Zaenglein said. In this population, she also recommends ruling out hyperandrogenism by looking for secondary sexual characteristics with full-body skin exams. “The workup can be broad and includes looking at adrenal androgens and total and free testosterone, as well as looking at growth charts and bone age. Typically, you’ll refer these kids to pediatric endocrinology.”

Keep in mind, she said, that early adrenarche starts at ages 6-7 years in girls and 7-8 years in boys. “That’s when we expect to start seeing that very early acne. You can see it even earlier in patients with elevated BMI, and it’s more common in Hispanic and Black children as well.”

She added that it’s important to remember that early adrenarche is a risk factor for polycystic ovarian syndrome (PCOS). “So ask patients about their family history and look for other signs of PCOS as they move further into adolescence.”

Milder cases of acne in this age group can be treated with “salicylic acid wipes and things that are kind of a rite of passage. But if they have any more severe acne, you’re going to want to treat it more or less like you do adolescent acne.”

MedscapeLive and this news organization are owned by the same parent company. Dr. Zaenglein disclosed receiving consulting fees from Cassiopea, Dermata, and Regeneron and fees for contracted research support from Incyte.

Eczema herpeticum and staphylococcal scalded skin syndrome can be emergencies in children and require immediate care, warned dermatologist George Hightower, MD, PhD, in a presentation at MedscapeLive’s virtual Women’s & Pediatric Dermatology Seminar.

Eczema herpeticum is a condition in which a herpes simplex virus (HSV-1 or HSV-2) is superimposed over preexisting eczema. “The infection may be primary and sustained from a close contact or result in some of our older patients from reactivation and spread through autoinoculation,” said Dr. Hightower, of Rady Children’s Hospital and the University of California, both in San Diego.

Signs, he said, include acute worsening of atopic dermatitis with new-onset vesicles, pustules, and “punched-out” hemorrhagic crusted erosions. “Presentation ranges from mild to transient to life threatening.”

Potential complications include meningitis, encephalitis, hepatitis, and chronic conjunctivitis. “That’s why immediate ophthalmological evaluation is needed when there’s involvement on the face near the eye,” he said.

As for management and care, “where I have concern for HSV patients, I get HSV [polymerase chain reaction] as well as a bacterial culture,” he said. But even before the results are available, empiric treatment with acyclovir can be appropriate. “It’s got to be systemic for these kids with severe involvement,” he said, and they should also be started on medication for staphylococci and streptococci.

During his presentation, Dr. Hightower also highlighted staphylococcal scalded skin syndrome. Patients with the disease commonly have concurrent skin pain (which can appear to be fussiness), fever, irritability, malaise, and poor feeding. Examination may reveal widespread erythema with accentuation at folds/peeling at hands and large sheets of superficial peeling scale with diffuse erythema.

Widespread skin involvement “results not from the presence of staph throughout the skin, but the exotoxin that it produces that becomes systemic,” he said. “Clinical diagnosis is supported by presence of S. aureus on bacterial culture, but the presence of staph is not necessary to make the diagnosis. When in doubt, histopathology is helpful. But again, it’s not necessary to make the diagnosis.”

Cases can be managed with a first- or second-generation cephalosporin, he said. Alternative therapies include antistaphylococcus penicillinase-resistant penicillins (oxacillin or nafcillin) or vancomycin.

While Dr. Hightower doesn’t use clindamycin in these patients, he said it’s an option that some dermatologists consider because of its antistaphylococcus activity. “Historically, people thought it may decrease exotoxin production. The big concern if you are going to use clindamycin is that there are high rates of community resistance,” he said. “So you want to be careful that you know your resistance patterns wherever you are. Follow up on culture to make sure that you have adequate coverage for the bug that the kiddo in front of you has.”

Dr. Hightower reported no relevant disclosures. MedscapeLive and this news organization are owned by the same parent company.

Eczema herpeticum and staphylococcal scalded skin syndrome can be emergencies in children and require immediate care, warned dermatologist George Hightower, MD, PhD, in a presentation at MedscapeLive’s virtual Women’s & Pediatric Dermatology Seminar.

Eczema herpeticum is a condition in which a herpes simplex virus (HSV-1 or HSV-2) is superimposed over preexisting eczema. “The infection may be primary and sustained from a close contact or result in some of our older patients from reactivation and spread through autoinoculation,” said Dr. Hightower, of Rady Children’s Hospital and the University of California, both in San Diego.

Signs, he said, include acute worsening of atopic dermatitis with new-onset vesicles, pustules, and “punched-out” hemorrhagic crusted erosions. “Presentation ranges from mild to transient to life threatening.”

Potential complications include meningitis, encephalitis, hepatitis, and chronic conjunctivitis. “That’s why immediate ophthalmological evaluation is needed when there’s involvement on the face near the eye,” he said.

As for management and care, “where I have concern for HSV patients, I get HSV [polymerase chain reaction] as well as a bacterial culture,” he said. But even before the results are available, empiric treatment with acyclovir can be appropriate. “It’s got to be systemic for these kids with severe involvement,” he said, and they should also be started on medication for staphylococci and streptococci.

During his presentation, Dr. Hightower also highlighted staphylococcal scalded skin syndrome. Patients with the disease commonly have concurrent skin pain (which can appear to be fussiness), fever, irritability, malaise, and poor feeding. Examination may reveal widespread erythema with accentuation at folds/peeling at hands and large sheets of superficial peeling scale with diffuse erythema.

Widespread skin involvement “results not from the presence of staph throughout the skin, but the exotoxin that it produces that becomes systemic,” he said. “Clinical diagnosis is supported by presence of S. aureus on bacterial culture, but the presence of staph is not necessary to make the diagnosis. When in doubt, histopathology is helpful. But again, it’s not necessary to make the diagnosis.”

Cases can be managed with a first- or second-generation cephalosporin, he said. Alternative therapies include antistaphylococcus penicillinase-resistant penicillins (oxacillin or nafcillin) or vancomycin.

While Dr. Hightower doesn’t use clindamycin in these patients, he said it’s an option that some dermatologists consider because of its antistaphylococcus activity. “Historically, people thought it may decrease exotoxin production. The big concern if you are going to use clindamycin is that there are high rates of community resistance,” he said. “So you want to be careful that you know your resistance patterns wherever you are. Follow up on culture to make sure that you have adequate coverage for the bug that the kiddo in front of you has.”

Dr. Hightower reported no relevant disclosures. MedscapeLive and this news organization are owned by the same parent company.

Eczema herpeticum and staphylococcal scalded skin syndrome can be emergencies in children and require immediate care, warned dermatologist George Hightower, MD, PhD, in a presentation at MedscapeLive’s virtual Women’s & Pediatric Dermatology Seminar.

Eczema herpeticum is a condition in which a herpes simplex virus (HSV-1 or HSV-2) is superimposed over preexisting eczema. “The infection may be primary and sustained from a close contact or result in some of our older patients from reactivation and spread through autoinoculation,” said Dr. Hightower, of Rady Children’s Hospital and the University of California, both in San Diego.

Signs, he said, include acute worsening of atopic dermatitis with new-onset vesicles, pustules, and “punched-out” hemorrhagic crusted erosions. “Presentation ranges from mild to transient to life threatening.”

Potential complications include meningitis, encephalitis, hepatitis, and chronic conjunctivitis. “That’s why immediate ophthalmological evaluation is needed when there’s involvement on the face near the eye,” he said.

As for management and care, “where I have concern for HSV patients, I get HSV [polymerase chain reaction] as well as a bacterial culture,” he said. But even before the results are available, empiric treatment with acyclovir can be appropriate. “It’s got to be systemic for these kids with severe involvement,” he said, and they should also be started on medication for staphylococci and streptococci.

During his presentation, Dr. Hightower also highlighted staphylococcal scalded skin syndrome. Patients with the disease commonly have concurrent skin pain (which can appear to be fussiness), fever, irritability, malaise, and poor feeding. Examination may reveal widespread erythema with accentuation at folds/peeling at hands and large sheets of superficial peeling scale with diffuse erythema.

Widespread skin involvement “results not from the presence of staph throughout the skin, but the exotoxin that it produces that becomes systemic,” he said. “Clinical diagnosis is supported by presence of S. aureus on bacterial culture, but the presence of staph is not necessary to make the diagnosis. When in doubt, histopathology is helpful. But again, it’s not necessary to make the diagnosis.”

Cases can be managed with a first- or second-generation cephalosporin, he said. Alternative therapies include antistaphylococcus penicillinase-resistant penicillins (oxacillin or nafcillin) or vancomycin.

While Dr. Hightower doesn’t use clindamycin in these patients, he said it’s an option that some dermatologists consider because of its antistaphylococcus activity. “Historically, people thought it may decrease exotoxin production. The big concern if you are going to use clindamycin is that there are high rates of community resistance,” he said. “So you want to be careful that you know your resistance patterns wherever you are. Follow up on culture to make sure that you have adequate coverage for the bug that the kiddo in front of you has.”

Dr. Hightower reported no relevant disclosures. MedscapeLive and this news organization are owned by the same parent company.

UPDATED DECEMBER 17

A panel of federal advisers on Tuesday effectively backed a bid to expand approval of sacubitril/valsartan for use in a form of heart failure for which there is not yet an approved medication.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The U.S. Food and Drug Administration asked its Cardiovascular and Renal Drugs Advisory Committee to broadly consider whether new analyses of data from the PARAGON-HF trial, combined with other information, could support use of sacubitril/valsartan (Entresto, Novartis) in heart failure with preserved ejection fraction (HFpEF).

The advisory committee voted 12-1 on this question, which can be seen as a marker for an expanded approval: “Does PARAGON-HF, perhaps supported by previous studies, provide sufficient evidence to support any indication?”

The dissenting vote was cast by the panel’s chairperson, Julia B. Lewis, MD, a professor of medicine from Vanderbilt University. In explaining her vote, Dr. Lewis cited concerns about expanding use of the drug, which has a potential for hypotension. But she noted that the rest of the panelists were “impressed by the totality of the evidence” presented, including a willingness to take a new look at the PARAGON-HF trial. This study was perceived at first pass as having failed to prove a benefit for people with HFpEF.

The 2019 initial unveiling of the PARAGON-HF results had dampened hopes for an evidence-based drug therapy for HFpEF. Patients treated with the first-of-its-kind renin-angiotensin system (RAS) inhibitor, compared with those who received standard valsartan, had 13% fewer heart failure hospitalizations or cardiovascular (CV) deaths over an average of about 3 years, but the difference missed significance at a P value of .059.

“Everybody agreed that the P value of .05 was not written in stone,” Dr. Lewis said in summarizing the panelists’ views on the voting question.

At the FDA’s request, the panel also addressed several other questions without voting on them. The agency asked the panel to describe the patient population for whom an expanded approval would be appropriate. The FDA initially approved sacubitril/valsartan in 2015 to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.

Novartis in April submitted an application to the FDA, seeking to expand the use of sacubitril/valsartan from the currently approved indication for the treatment of chronic heart failure (CHF) patients with reduced ejection fraction (HFrEF) to include what the company terms “the adjacent population of patients with preserved ejection fraction (HFpEF) who have a left ventricular ejection fraction (LVEF) below normal.” The American Society of Echocardiography and European Association of Cardiovascular Imaging define normal LVEF and normal range (±2 standard deviations) as 62% (range, 52%-72%) in men and 64% (range, 54%-74%) in women, Novartis said in its briefing materials for the meeting.

FDA panelist Christopher M. O’Connor, MD, for example, suggested that an expanded approval could allow for use of sacubitril/valsartan for the reduction of heart failure or hospitalization in patients with mildly reduced ejection fraction as defined by greater than 45% through 55%. FDA panelist C. Noel Bairey Merz, MD, director of the Barbra Streisand Women’s Heart Center at Cedars-Sinai Medical Center in Los Angeles, suggested extending this to 57% to acknowledge the higher threshold for women.

Another FDA panelist, Steven E. Nissen, MD, of the Cleveland Clinic, argued against use of imprecise terms in defining an expanded patient population for sacubitril/valsartan. If used in the right patient population, the drug could provide a benefit for people who have active heart failure with symptoms, including preventing hospitalizations and renal disease, he said.

“If you are symptomatic with a syndrome that’s consistent with heart failure and you have an ejection fraction below the lower limits of normal, I believe it’s in the public interest for you to get sacubitril/valsartan,” Dr. Nissen said.

The FDA usually follows the advice of its panels, but is not obligated to. But in this case, the agency staff were clearly seeking a path for an expanded approval of sacubitril/valsartan.


 

Challenging a standard

The FDA had encouraged Novartis to submit the supplementary application for the HFpEF indication and even suggested some of the post-hoc analyses, the agency staff said in a briefing document for the meeting.

PARAGON-HF illustrated some of the agency’s concerns about missed opportunities in general in large research trials. Some events of interest in studies may be miscounted due to a lack of information such as a requirement for the presence of physical examination findings that are not documented in the patient’s dossier, the FDA staff said.

“We would like to consider giving ‘partial credit’ to events based on the level of evidence provided, e.g., use of an ordinal variable rather than a dichotomous ‘yes’ or ‘no,’ ” the staff said in the briefing document.

At the panel meeting, Norman Stockbridge, MD, PhD, director of the Division of Cardiology and Nephrology in the FDA’s Center for Drug Evaluation and Research, told the panelists there is no basis in law for setting a P value of .05 as the benchmark on whether to declare a trial a success or failure.

“I wanted to take a few minutes and make sure that you on the committee understands what flexibility you have in addressing the case study in question,” Dr. Stockbridge said at the start of the meeting.

He then reviewed cases where the FDA had approved claims for cardiac medicines that had not shown desired results in key tests. These include approval of enalapril for use in asymptomatic left ventricular dysfunction on the basis of the SOLVD-Prevention trial, approval of digoxin for heart failure on the basis of the DIG study, and approval of carvedilol for reduced ejection fraction following myocardial infarction on

the basis of the CAPRICORN study, Dr. Stockbridge said.

In reviewing the data for sacubitril/valsartan, FDA staff noted a similarity between investigator-reported and adjudicated results, Stockbridge said.

“This suggested that there were events that did not need all evidentiary criteria as qualified events, but likely were nonetheless,” he said. “This is an example of dichotomization of events being wasteful of information.”

Post-hoc exploratory analyses in PARAGON-HF were able to meet the commonly used standard, according to the FDA briefing document. Among the key findings of these analyses were:

• An analysis of investigator-reported events for the primary composite endpoint of total hospitalizations for heart failure (HHF) and cardiovascular (CV) death demonstrated a rate ratio (RR) of 0.84 (95% confidence interval 0.74- 0.97; P = .01).
• Investigator-reported events added 226 and 290 HHF events but decreased CV death by 56 and 58 events in the sacubitril/valsartan and valsartan arms, respectively. Hence, a net 170 and 232 events were added to the clinical endpoint committee–reported primary composite endpoint leading to a P value of .01, without a significant change in RR.
• Analysis of investigator-reported expanded primary composite endpoint events including total HHF, urgent HF visits, and CV death demonstrated a RR of 0.83 (95% CI, 0.73-0.95; P = .006. There were 136 and 173 investigator-reported urgent HF events in sacubitril/valsartan and valsartan arms, respectively.

Opening a floodgate?

Cynthia L. Chauhan, MSW, of Wichita, Kansas, who served as the consumer representative on the panel, questioned whether a decision to revisit the data on PARAGON-HF might lead drugmakers to seek to repurpose other failed trials.

“Are we opening any kind of floodgate for other researchers to go back and see this is an invitation to try to, for want of a better term, back-door their way into some approvals?” Ms. Chauhan asked.

Dr. Nissen assured her that this concern was valid and would be considered. The goal would be to allow some flexibility in cases that merit further consideration, while preventing companies from data mining until they find some evidence to support an FDA application, he said.

Re-analyzing trials “should be done carefully, conservatively, and only when it really is compelling that the public interest supports it,” Dr. Nissen stressed.

Panelists reported no conflicts of interest related to the topic of the meeting.
 

UPDATED DECEMBER 17

A panel of federal advisers on Tuesday effectively backed a bid to expand approval of sacubitril/valsartan for use in a form of heart failure for which there is not yet an approved medication.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The U.S. Food and Drug Administration asked its Cardiovascular and Renal Drugs Advisory Committee to broadly consider whether new analyses of data from the PARAGON-HF trial, combined with other information, could support use of sacubitril/valsartan (Entresto, Novartis) in heart failure with preserved ejection fraction (HFpEF).

The advisory committee voted 12-1 on this question, which can be seen as a marker for an expanded approval: “Does PARAGON-HF, perhaps supported by previous studies, provide sufficient evidence to support any indication?”

The dissenting vote was cast by the panel’s chairperson, Julia B. Lewis, MD, a professor of medicine from Vanderbilt University. In explaining her vote, Dr. Lewis cited concerns about expanding use of the drug, which has a potential for hypotension. But she noted that the rest of the panelists were “impressed by the totality of the evidence” presented, including a willingness to take a new look at the PARAGON-HF trial. This study was perceived at first pass as having failed to prove a benefit for people with HFpEF.

The 2019 initial unveiling of the PARAGON-HF results had dampened hopes for an evidence-based drug therapy for HFpEF. Patients treated with the first-of-its-kind renin-angiotensin system (RAS) inhibitor, compared with those who received standard valsartan, had 13% fewer heart failure hospitalizations or cardiovascular (CV) deaths over an average of about 3 years, but the difference missed significance at a P value of .059.

“Everybody agreed that the P value of .05 was not written in stone,” Dr. Lewis said in summarizing the panelists’ views on the voting question.

At the FDA’s request, the panel also addressed several other questions without voting on them. The agency asked the panel to describe the patient population for whom an expanded approval would be appropriate. The FDA initially approved sacubitril/valsartan in 2015 to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.

Novartis in April submitted an application to the FDA, seeking to expand the use of sacubitril/valsartan from the currently approved indication for the treatment of chronic heart failure (CHF) patients with reduced ejection fraction (HFrEF) to include what the company terms “the adjacent population of patients with preserved ejection fraction (HFpEF) who have a left ventricular ejection fraction (LVEF) below normal.” The American Society of Echocardiography and European Association of Cardiovascular Imaging define normal LVEF and normal range (±2 standard deviations) as 62% (range, 52%-72%) in men and 64% (range, 54%-74%) in women, Novartis said in its briefing materials for the meeting.

FDA panelist Christopher M. O’Connor, MD, for example, suggested that an expanded approval could allow for use of sacubitril/valsartan for the reduction of heart failure or hospitalization in patients with mildly reduced ejection fraction as defined by greater than 45% through 55%. FDA panelist C. Noel Bairey Merz, MD, director of the Barbra Streisand Women’s Heart Center at Cedars-Sinai Medical Center in Los Angeles, suggested extending this to 57% to acknowledge the higher threshold for women.

Another FDA panelist, Steven E. Nissen, MD, of the Cleveland Clinic, argued against use of imprecise terms in defining an expanded patient population for sacubitril/valsartan. If used in the right patient population, the drug could provide a benefit for people who have active heart failure with symptoms, including preventing hospitalizations and renal disease, he said.

“If you are symptomatic with a syndrome that’s consistent with heart failure and you have an ejection fraction below the lower limits of normal, I believe it’s in the public interest for you to get sacubitril/valsartan,” Dr. Nissen said.

The FDA usually follows the advice of its panels, but is not obligated to. But in this case, the agency staff were clearly seeking a path for an expanded approval of sacubitril/valsartan.


 

Challenging a standard

The FDA had encouraged Novartis to submit the supplementary application for the HFpEF indication and even suggested some of the post-hoc analyses, the agency staff said in a briefing document for the meeting.

PARAGON-HF illustrated some of the agency’s concerns about missed opportunities in general in large research trials. Some events of interest in studies may be miscounted due to a lack of information such as a requirement for the presence of physical examination findings that are not documented in the patient’s dossier, the FDA staff said.

“We would like to consider giving ‘partial credit’ to events based on the level of evidence provided, e.g., use of an ordinal variable rather than a dichotomous ‘yes’ or ‘no,’ ” the staff said in the briefing document.

At the panel meeting, Norman Stockbridge, MD, PhD, director of the Division of Cardiology and Nephrology in the FDA’s Center for Drug Evaluation and Research, told the panelists there is no basis in law for setting a P value of .05 as the benchmark on whether to declare a trial a success or failure.

“I wanted to take a few minutes and make sure that you on the committee understands what flexibility you have in addressing the case study in question,” Dr. Stockbridge said at the start of the meeting.

He then reviewed cases where the FDA had approved claims for cardiac medicines that had not shown desired results in key tests. These include approval of enalapril for use in asymptomatic left ventricular dysfunction on the basis of the SOLVD-Prevention trial, approval of digoxin for heart failure on the basis of the DIG study, and approval of carvedilol for reduced ejection fraction following myocardial infarction on

the basis of the CAPRICORN study, Dr. Stockbridge said.

In reviewing the data for sacubitril/valsartan, FDA staff noted a similarity between investigator-reported and adjudicated results, Stockbridge said.

“This suggested that there were events that did not need all evidentiary criteria as qualified events, but likely were nonetheless,” he said. “This is an example of dichotomization of events being wasteful of information.”

Post-hoc exploratory analyses in PARAGON-HF were able to meet the commonly used standard, according to the FDA briefing document. Among the key findings of these analyses were:

• An analysis of investigator-reported events for the primary composite endpoint of total hospitalizations for heart failure (HHF) and cardiovascular (CV) death demonstrated a rate ratio (RR) of 0.84 (95% confidence interval 0.74- 0.97; P = .01).
• Investigator-reported events added 226 and 290 HHF events but decreased CV death by 56 and 58 events in the sacubitril/valsartan and valsartan arms, respectively. Hence, a net 170 and 232 events were added to the clinical endpoint committee–reported primary composite endpoint leading to a P value of .01, without a significant change in RR.
• Analysis of investigator-reported expanded primary composite endpoint events including total HHF, urgent HF visits, and CV death demonstrated a RR of 0.83 (95% CI, 0.73-0.95; P = .006. There were 136 and 173 investigator-reported urgent HF events in sacubitril/valsartan and valsartan arms, respectively.

Opening a floodgate?

Cynthia L. Chauhan, MSW, of Wichita, Kansas, who served as the consumer representative on the panel, questioned whether a decision to revisit the data on PARAGON-HF might lead drugmakers to seek to repurpose other failed trials.

“Are we opening any kind of floodgate for other researchers to go back and see this is an invitation to try to, for want of a better term, back-door their way into some approvals?” Ms. Chauhan asked.

Dr. Nissen assured her that this concern was valid and would be considered. The goal would be to allow some flexibility in cases that merit further consideration, while preventing companies from data mining until they find some evidence to support an FDA application, he said.

Re-analyzing trials “should be done carefully, conservatively, and only when it really is compelling that the public interest supports it,” Dr. Nissen stressed.

Panelists reported no conflicts of interest related to the topic of the meeting.
 

UPDATED DECEMBER 17

A panel of federal advisers on Tuesday effectively backed a bid to expand approval of sacubitril/valsartan for use in a form of heart failure for which there is not yet an approved medication.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The U.S. Food and Drug Administration asked its Cardiovascular and Renal Drugs Advisory Committee to broadly consider whether new analyses of data from the PARAGON-HF trial, combined with other information, could support use of sacubitril/valsartan (Entresto, Novartis) in heart failure with preserved ejection fraction (HFpEF).

The advisory committee voted 12-1 on this question, which can be seen as a marker for an expanded approval: “Does PARAGON-HF, perhaps supported by previous studies, provide sufficient evidence to support any indication?”

The dissenting vote was cast by the panel’s chairperson, Julia B. Lewis, MD, a professor of medicine from Vanderbilt University. In explaining her vote, Dr. Lewis cited concerns about expanding use of the drug, which has a potential for hypotension. But she noted that the rest of the panelists were “impressed by the totality of the evidence” presented, including a willingness to take a new look at the PARAGON-HF trial. This study was perceived at first pass as having failed to prove a benefit for people with HFpEF.

The 2019 initial unveiling of the PARAGON-HF results had dampened hopes for an evidence-based drug therapy for HFpEF. Patients treated with the first-of-its-kind renin-angiotensin system (RAS) inhibitor, compared with those who received standard valsartan, had 13% fewer heart failure hospitalizations or cardiovascular (CV) deaths over an average of about 3 years, but the difference missed significance at a P value of .059.

“Everybody agreed that the P value of .05 was not written in stone,” Dr. Lewis said in summarizing the panelists’ views on the voting question.

At the FDA’s request, the panel also addressed several other questions without voting on them. The agency asked the panel to describe the patient population for whom an expanded approval would be appropriate. The FDA initially approved sacubitril/valsartan in 2015 to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.

Novartis in April submitted an application to the FDA, seeking to expand the use of sacubitril/valsartan from the currently approved indication for the treatment of chronic heart failure (CHF) patients with reduced ejection fraction (HFrEF) to include what the company terms “the adjacent population of patients with preserved ejection fraction (HFpEF) who have a left ventricular ejection fraction (LVEF) below normal.” The American Society of Echocardiography and European Association of Cardiovascular Imaging define normal LVEF and normal range (±2 standard deviations) as 62% (range, 52%-72%) in men and 64% (range, 54%-74%) in women, Novartis said in its briefing materials for the meeting.

FDA panelist Christopher M. O’Connor, MD, for example, suggested that an expanded approval could allow for use of sacubitril/valsartan for the reduction of heart failure or hospitalization in patients with mildly reduced ejection fraction as defined by greater than 45% through 55%. FDA panelist C. Noel Bairey Merz, MD, director of the Barbra Streisand Women’s Heart Center at Cedars-Sinai Medical Center in Los Angeles, suggested extending this to 57% to acknowledge the higher threshold for women.

Another FDA panelist, Steven E. Nissen, MD, of the Cleveland Clinic, argued against use of imprecise terms in defining an expanded patient population for sacubitril/valsartan. If used in the right patient population, the drug could provide a benefit for people who have active heart failure with symptoms, including preventing hospitalizations and renal disease, he said.

“If you are symptomatic with a syndrome that’s consistent with heart failure and you have an ejection fraction below the lower limits of normal, I believe it’s in the public interest for you to get sacubitril/valsartan,” Dr. Nissen said.

The FDA usually follows the advice of its panels, but is not obligated to. But in this case, the agency staff were clearly seeking a path for an expanded approval of sacubitril/valsartan.


 

Challenging a standard

The FDA had encouraged Novartis to submit the supplementary application for the HFpEF indication and even suggested some of the post-hoc analyses, the agency staff said in a briefing document for the meeting.

PARAGON-HF illustrated some of the agency’s concerns about missed opportunities in general in large research trials. Some events of interest in studies may be miscounted due to a lack of information such as a requirement for the presence of physical examination findings that are not documented in the patient’s dossier, the FDA staff said.

“We would like to consider giving ‘partial credit’ to events based on the level of evidence provided, e.g., use of an ordinal variable rather than a dichotomous ‘yes’ or ‘no,’ ” the staff said in the briefing document.

At the panel meeting, Norman Stockbridge, MD, PhD, director of the Division of Cardiology and Nephrology in the FDA’s Center for Drug Evaluation and Research, told the panelists there is no basis in law for setting a P value of .05 as the benchmark on whether to declare a trial a success or failure.

“I wanted to take a few minutes and make sure that you on the committee understands what flexibility you have in addressing the case study in question,” Dr. Stockbridge said at the start of the meeting.

He then reviewed cases where the FDA had approved claims for cardiac medicines that had not shown desired results in key tests. These include approval of enalapril for use in asymptomatic left ventricular dysfunction on the basis of the SOLVD-Prevention trial, approval of digoxin for heart failure on the basis of the DIG study, and approval of carvedilol for reduced ejection fraction following myocardial infarction on

the basis of the CAPRICORN study, Dr. Stockbridge said.

In reviewing the data for sacubitril/valsartan, FDA staff noted a similarity between investigator-reported and adjudicated results, Stockbridge said.

“This suggested that there were events that did not need all evidentiary criteria as qualified events, but likely were nonetheless,” he said. “This is an example of dichotomization of events being wasteful of information.”

Post-hoc exploratory analyses in PARAGON-HF were able to meet the commonly used standard, according to the FDA briefing document. Among the key findings of these analyses were:

• An analysis of investigator-reported events for the primary composite endpoint of total hospitalizations for heart failure (HHF) and cardiovascular (CV) death demonstrated a rate ratio (RR) of 0.84 (95% confidence interval 0.74- 0.97; P = .01).
• Investigator-reported events added 226 and 290 HHF events but decreased CV death by 56 and 58 events in the sacubitril/valsartan and valsartan arms, respectively. Hence, a net 170 and 232 events were added to the clinical endpoint committee–reported primary composite endpoint leading to a P value of .01, without a significant change in RR.
• Analysis of investigator-reported expanded primary composite endpoint events including total HHF, urgent HF visits, and CV death demonstrated a RR of 0.83 (95% CI, 0.73-0.95; P = .006. There were 136 and 173 investigator-reported urgent HF events in sacubitril/valsartan and valsartan arms, respectively.

Opening a floodgate?

Cynthia L. Chauhan, MSW, of Wichita, Kansas, who served as the consumer representative on the panel, questioned whether a decision to revisit the data on PARAGON-HF might lead drugmakers to seek to repurpose other failed trials.

“Are we opening any kind of floodgate for other researchers to go back and see this is an invitation to try to, for want of a better term, back-door their way into some approvals?” Ms. Chauhan asked.

Dr. Nissen assured her that this concern was valid and would be considered. The goal would be to allow some flexibility in cases that merit further consideration, while preventing companies from data mining until they find some evidence to support an FDA application, he said.

Re-analyzing trials “should be done carefully, conservatively, and only when it really is compelling that the public interest supports it,” Dr. Nissen stressed.

Panelists reported no conflicts of interest related to the topic of the meeting.
 

Working with a registered dietitian (RD) can help ensure that changing the way patients with inflammatory bowel disease (IBD) eat won’t deprive them of the nutrients they need.

Depending on the location and resources of a medical practice, calling in a dietitian may seem like a luxury. But making those connections can be more accessible during the COVID-19 pandemic as more dietitians are working virtually.

Kelly Issokson, MS, RD, clinical nutrition coordinator for IBD at Cedars Sinai Medical Center in Los Angeles, suggested two websites that allow users to search for RDs by ZIP code or by those working virtually: the International Foundation for Gastrointestinal Disorders and eatright.org, the website for the professional body for the dietetics community, which also has a searchable database.

Ashwin N. Ananthakrishnan, MD, MPH, director of the Crohn’s and colitis center at Massachusetts General Hospital in Boston, said it’s key for gastroenterologists to communicate what exactly they want the dietitian to address and not merely refer the patient.

The provider should know what therapies exist and then have the dietitian walk the patient through the plan, he said.

Mark Mattar, MD, with MedStar Georgetown University Hospital in Washington, said that, in addition to connecting patients with dietitians, “I always refer my patient to the Crohn’s and Colitis Foundation for the most recently updated patient education materials on nutrition.”

Panelists at the Advances in Inflammatory Bowel Diseases 2020 annual meeting on Wednesday weighed in on dietary considerations for two patient scenarios posed by Maria Abreu, MD, director of the Crohn’s & Colitis Center at the University of Miami.

The first scenario involved a 54-year-old man with long-standing fibrostenotic Crohn’s disease, recently hospitalized for obstruction and discharged with a prescription for prednisone 40 mg daily. The patient had been on infliximab (Remicade), and now is taking now adalimumab (Humira) weekly. He will undergo surgery to remove an ileal stricture. Dr. Abreu asked what dietary changes the panelists would make to ensure adequate nutrition prior to surgery and prevent another obstruction.

Dr. Ananthakrishnan said he would check vitamin B_₁₂, vitamin D, iron, and albumin levels to see if any micronutrients need to be replaced.

He said that, although he thinks low-fiber diets are used too often as the default for Crohn’s and ulcerative colitis, in this case he would recommend low fiber and urge the patient to avoid raw fruits, vegetables, nuts, and seeds.

The patient can remove the skins and still have shakes and smoothies to get the benefits of fiber-containing foods without the fiber component, he said.

Discussing a pediatric version of that scenario, Andrew Grossman, MD, a pediatric gastroenterologist at the Children’s Hospital of Philadelphia, said he would turn to enteral nutrition therapy.

“We would strongly encourage using a formula to try to improve nutritional status, which we know can improve surgical outcomes,” he said.

The second case was a 15-year-old girl with growth stunting. She was diagnosed at age 10 with Crohn’s disease, currently has moderate disease, and continues to have five to seven liquid bowel movements daily, along with abdominal pain after meals. She is starting adalimumab induction.

Dr. Grossman said, “first, I would not be managing this alone. I would be managing this with a dietitian and working together to improve outcomes. We need to consider aggressive therapy, and to me that would include consideration of biological therapy but also possible dietary therapy – the Crohn’s Disease Exclusion Diet or enteral nutrition therapy as possibilities.”

He pointed out that in pediatrics there must be consideration both for what the parent wants the child to do and what the child is willing to do.

“My primary focus would be on improving caloric intake, working with the dietitian to avoid foods that bother the most,” he said.

Dr. Issokson said she would recommend either exclusive enteral nutrition or a specific carbohydrate diet (SCD) for the teen.

“We see [SCD] doesn’t impair growth in our patients as long as they are being followed by a dietitian, and we’re making sure they are getting adequate nutrient intake,” she said.

Dr. Abreu said in an interview that “diet is important in patients with IBD; it is a complement to the therapies that we use and a potential opportunity to solidify a long-lived remission.”

“Although studies of diet are only now being done,” she said, “we already have some good foundational ideas about diet and its role in reducing inflammation and reducing symptoms.” And she added that treating gastroenterologists should certainly avoid telling patients that “diet does not matter.”

Dr. Abreu has relationships with Boehringer Ingelheim, Cosmo Biopharma, Eli Lilly, Gilead, Janssen, Landos Biopharma, Prometheus Bioscience, Takeda, UCB Biopharma, Pfizer, and Prometheus Laboratories. Dr. Ananthakrishnan, Dr. Grossman, and Dr. Issokson have disclosed no relevant financial relationships.
 

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

Working with a registered dietitian (RD) can help ensure that changing the way patients with inflammatory bowel disease (IBD) eat won’t deprive them of the nutrients they need.

Depending on the location and resources of a medical practice, calling in a dietitian may seem like a luxury. But making those connections can be more accessible during the COVID-19 pandemic as more dietitians are working virtually.

Kelly Issokson, MS, RD, clinical nutrition coordinator for IBD at Cedars Sinai Medical Center in Los Angeles, suggested two websites that allow users to search for RDs by ZIP code or by those working virtually: the International Foundation for Gastrointestinal Disorders and eatright.org, the website for the professional body for the dietetics community, which also has a searchable database.

Ashwin N. Ananthakrishnan, MD, MPH, director of the Crohn’s and colitis center at Massachusetts General Hospital in Boston, said it’s key for gastroenterologists to communicate what exactly they want the dietitian to address and not merely refer the patient.

The provider should know what therapies exist and then have the dietitian walk the patient through the plan, he said.

Mark Mattar, MD, with MedStar Georgetown University Hospital in Washington, said that, in addition to connecting patients with dietitians, “I always refer my patient to the Crohn’s and Colitis Foundation for the most recently updated patient education materials on nutrition.”

Panelists at the Advances in Inflammatory Bowel Diseases 2020 annual meeting on Wednesday weighed in on dietary considerations for two patient scenarios posed by Maria Abreu, MD, director of the Crohn’s & Colitis Center at the University of Miami.

The first scenario involved a 54-year-old man with long-standing fibrostenotic Crohn’s disease, recently hospitalized for obstruction and discharged with a prescription for prednisone 40 mg daily. The patient had been on infliximab (Remicade), and now is taking now adalimumab (Humira) weekly. He will undergo surgery to remove an ileal stricture. Dr. Abreu asked what dietary changes the panelists would make to ensure adequate nutrition prior to surgery and prevent another obstruction.

Dr. Ananthakrishnan said he would check vitamin B_₁₂, vitamin D, iron, and albumin levels to see if any micronutrients need to be replaced.

He said that, although he thinks low-fiber diets are used too often as the default for Crohn’s and ulcerative colitis, in this case he would recommend low fiber and urge the patient to avoid raw fruits, vegetables, nuts, and seeds.

The patient can remove the skins and still have shakes and smoothies to get the benefits of fiber-containing foods without the fiber component, he said.

Discussing a pediatric version of that scenario, Andrew Grossman, MD, a pediatric gastroenterologist at the Children’s Hospital of Philadelphia, said he would turn to enteral nutrition therapy.

“We would strongly encourage using a formula to try to improve nutritional status, which we know can improve surgical outcomes,” he said.

The second case was a 15-year-old girl with growth stunting. She was diagnosed at age 10 with Crohn’s disease, currently has moderate disease, and continues to have five to seven liquid bowel movements daily, along with abdominal pain after meals. She is starting adalimumab induction.

Dr. Grossman said, “first, I would not be managing this alone. I would be managing this with a dietitian and working together to improve outcomes. We need to consider aggressive therapy, and to me that would include consideration of biological therapy but also possible dietary therapy – the Crohn’s Disease Exclusion Diet or enteral nutrition therapy as possibilities.”

He pointed out that in pediatrics there must be consideration both for what the parent wants the child to do and what the child is willing to do.

“My primary focus would be on improving caloric intake, working with the dietitian to avoid foods that bother the most,” he said.

Dr. Issokson said she would recommend either exclusive enteral nutrition or a specific carbohydrate diet (SCD) for the teen.

“We see [SCD] doesn’t impair growth in our patients as long as they are being followed by a dietitian, and we’re making sure they are getting adequate nutrient intake,” she said.

Dr. Abreu said in an interview that “diet is important in patients with IBD; it is a complement to the therapies that we use and a potential opportunity to solidify a long-lived remission.”

“Although studies of diet are only now being done,” she said, “we already have some good foundational ideas about diet and its role in reducing inflammation and reducing symptoms.” And she added that treating gastroenterologists should certainly avoid telling patients that “diet does not matter.”

Dr. Abreu has relationships with Boehringer Ingelheim, Cosmo Biopharma, Eli Lilly, Gilead, Janssen, Landos Biopharma, Prometheus Bioscience, Takeda, UCB Biopharma, Pfizer, and Prometheus Laboratories. Dr. Ananthakrishnan, Dr. Grossman, and Dr. Issokson have disclosed no relevant financial relationships.
 

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

Working with a registered dietitian (RD) can help ensure that changing the way patients with inflammatory bowel disease (IBD) eat won’t deprive them of the nutrients they need.

Depending on the location and resources of a medical practice, calling in a dietitian may seem like a luxury. But making those connections can be more accessible during the COVID-19 pandemic as more dietitians are working virtually.

Kelly Issokson, MS, RD, clinical nutrition coordinator for IBD at Cedars Sinai Medical Center in Los Angeles, suggested two websites that allow users to search for RDs by ZIP code or by those working virtually: the International Foundation for Gastrointestinal Disorders and eatright.org, the website for the professional body for the dietetics community, which also has a searchable database.

Ashwin N. Ananthakrishnan, MD, MPH, director of the Crohn’s and colitis center at Massachusetts General Hospital in Boston, said it’s key for gastroenterologists to communicate what exactly they want the dietitian to address and not merely refer the patient.

The provider should know what therapies exist and then have the dietitian walk the patient through the plan, he said.

Mark Mattar, MD, with MedStar Georgetown University Hospital in Washington, said that, in addition to connecting patients with dietitians, “I always refer my patient to the Crohn’s and Colitis Foundation for the most recently updated patient education materials on nutrition.”

Panelists at the Advances in Inflammatory Bowel Diseases 2020 annual meeting on Wednesday weighed in on dietary considerations for two patient scenarios posed by Maria Abreu, MD, director of the Crohn’s & Colitis Center at the University of Miami.

The first scenario involved a 54-year-old man with long-standing fibrostenotic Crohn’s disease, recently hospitalized for obstruction and discharged with a prescription for prednisone 40 mg daily. The patient had been on infliximab (Remicade), and now is taking now adalimumab (Humira) weekly. He will undergo surgery to remove an ileal stricture. Dr. Abreu asked what dietary changes the panelists would make to ensure adequate nutrition prior to surgery and prevent another obstruction.

Dr. Ananthakrishnan said he would check vitamin B_₁₂, vitamin D, iron, and albumin levels to see if any micronutrients need to be replaced.

He said that, although he thinks low-fiber diets are used too often as the default for Crohn’s and ulcerative colitis, in this case he would recommend low fiber and urge the patient to avoid raw fruits, vegetables, nuts, and seeds.

The patient can remove the skins and still have shakes and smoothies to get the benefits of fiber-containing foods without the fiber component, he said.

Discussing a pediatric version of that scenario, Andrew Grossman, MD, a pediatric gastroenterologist at the Children’s Hospital of Philadelphia, said he would turn to enteral nutrition therapy.

“We would strongly encourage using a formula to try to improve nutritional status, which we know can improve surgical outcomes,” he said.

The second case was a 15-year-old girl with growth stunting. She was diagnosed at age 10 with Crohn’s disease, currently has moderate disease, and continues to have five to seven liquid bowel movements daily, along with abdominal pain after meals. She is starting adalimumab induction.

Dr. Grossman said, “first, I would not be managing this alone. I would be managing this with a dietitian and working together to improve outcomes. We need to consider aggressive therapy, and to me that would include consideration of biological therapy but also possible dietary therapy – the Crohn’s Disease Exclusion Diet or enteral nutrition therapy as possibilities.”

He pointed out that in pediatrics there must be consideration both for what the parent wants the child to do and what the child is willing to do.

“My primary focus would be on improving caloric intake, working with the dietitian to avoid foods that bother the most,” he said.

Dr. Issokson said she would recommend either exclusive enteral nutrition or a specific carbohydrate diet (SCD) for the teen.

“We see [SCD] doesn’t impair growth in our patients as long as they are being followed by a dietitian, and we’re making sure they are getting adequate nutrient intake,” she said.

Dr. Abreu said in an interview that “diet is important in patients with IBD; it is a complement to the therapies that we use and a potential opportunity to solidify a long-lived remission.”

“Although studies of diet are only now being done,” she said, “we already have some good foundational ideas about diet and its role in reducing inflammation and reducing symptoms.” And she added that treating gastroenterologists should certainly avoid telling patients that “diet does not matter.”

Dr. Abreu has relationships with Boehringer Ingelheim, Cosmo Biopharma, Eli Lilly, Gilead, Janssen, Landos Biopharma, Prometheus Bioscience, Takeda, UCB Biopharma, Pfizer, and Prometheus Laboratories. Dr. Ananthakrishnan, Dr. Grossman, and Dr. Issokson have disclosed no relevant financial relationships.
 

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

Editor’s note: This article has been provided by The Doctors Company, the exclusively endorsed medical malpractice carrier for the Society of Hospital Medicine.

As the pandemic hits its third nationwide surge, families are gathering for the holidays, and medical practices are preparing for a potential increase in cases. Medical offices in states that were not strongly affected by the first and second waves of the virus may now be facing an influx of COVID-19 patients. Therefore, medical offices must remain very attentive to the widespread outbreak of COVID-19, continuing to proactively take steps to safely manage patients while protecting clinical staff.

Here are tips and resources for this season of the pandemic:

• Documentation: Maintain administrative records of how you have adapted to the evolving crisis, including the challenges you faced. For details, see Keep a COVID-19 Diary: Document Now in Case of Future Lawsuits.
• Legislation and Guidance: Reference the CDC; your state medical board; professional societies; and federal, state, and local authorities daily for public health guidance and new legislation, as this continues to be a fluid situation.
• Screening Criteria: Follow the CDC’s patient assessment protocol for early disease detection for patients presenting to your practice. Patients should be screened using these guidelines: Overview of Testing for SARS-CoV-2 (COVID-19). Essential visitors to your facility should also be assessed for symptoms of coronavirus and contact exposure and redirected to remain outside if suspect.
• Accepting Patients: Do not turn patients away simply because a patient calls with acute respiratory symptoms. Refusing assessment/care may lead to concerns of patient abandonment.
• Designated Triage Location: Check with your local public health authorities for locations designated to triage suspected patients, so exposure is limited in general medical offices.
• Telehealth Triage: Licensed staff should be trained in triage protocol to determine which patients can be managed safely at home. See Healthcare Facilities: Managing Operations During the COVID-19 Pandemic. The Doctors Company offers resources on telemedicine in our COVID-19 Telehealth Resource Center.
• Patient Testing: When there is a reasonable presumption that a patient may have been exposed to COVID-19, contact the local or state health department to coordinate testing using available community resources. See the CDC’s Testing for COVID-19 , the COVID-19 Testing Overview, and the Clinician Call Center.
• Elective Services: Check with regional governmental and health authorities on the provision of nonessential and elective health care visits and group-related activities. Many states continue or have reinstated restrictions on the provision of nonurgent, elective surgeries and procedures.
• Patient Precautions: Educational resources, including posters for use in the medical office, are available from the WHO and for health care workers from the CDC (Contact Precautions, Droplet Precautions, and Airborne Precautions). Reference the CDC’s and Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19) for patient management guidance.
• Provider/Staff Precautions: Follow Standard Precautions and Transmission-Based Precautions, including gloves, gowns, protective eyewear, and NIOSH-certified N95 respirators that have been properly fit-tested. If there is a shortage of N95 respirators in your facility, access current CDC respirator recommendations and review Optimizing Personal Protective Equipment (PPE) Supplies.
• Limit Exposure: Limit staff exposure to suspected patients, with the exam room door kept closed. Ideally, the designated exam room should be at the back of the office, far away from other staff and patients.
• Surface Disinfection: Once the patient exits the room, conduct surface disinfection while staff continues to wear PPE.
• Patient Education: Provide up-to-date, factual information on the virus to suspected COVID-19–positive patients and their close contacts.
• Provider/Staff Exposure: Screen health care personnel daily for symptoms/contacts relevant to COVID-19. Any unprotected occupational exposure by staff members should be assessed and monitored. See Interim U.S. Guidance for Risk Assessment and Work Restrictions for Healthcare Personnel with Potential Exposure to COVID-19. Should providers and/or staff test positive within your facility, conduct and document a risk assessment identifying contacts, type of interaction, and PPE in use, then contact local health authorities for additional instruction. The CDC provides guidance here under the section “Infection Control.” The health department may assist with patient notification if determined to be necessary. For return-to-work guidance, review the Criteria for Return to Work for Healthcare Personnel with SARS-CoV-2 Infection (Interim Guidance).
• Staff Training: Provide and document additional staff training as protocols change. Maintain training records in administrative files.

Ms. Hill is senior patient safety risk manager at The Doctors Company. The guidelines suggested here are not rules, do not constitute legal advice, and do not ensure a successful outcome. The ultimate decision regarding the appropriateness of any treatment must be made by each health care provider considering the circumstances of the individual situation and in accordance with the laws of the jurisdiction in which the care is rendered.

Editor’s note: This article has been provided by The Doctors Company, the exclusively endorsed medical malpractice carrier for the Society of Hospital Medicine.

As the pandemic hits its third nationwide surge, families are gathering for the holidays, and medical practices are preparing for a potential increase in cases. Medical offices in states that were not strongly affected by the first and second waves of the virus may now be facing an influx of COVID-19 patients. Therefore, medical offices must remain very attentive to the widespread outbreak of COVID-19, continuing to proactively take steps to safely manage patients while protecting clinical staff.

Here are tips and resources for this season of the pandemic:

• Documentation: Maintain administrative records of how you have adapted to the evolving crisis, including the challenges you faced. For details, see Keep a COVID-19 Diary: Document Now in Case of Future Lawsuits.
• Legislation and Guidance: Reference the CDC; your state medical board; professional societies; and federal, state, and local authorities daily for public health guidance and new legislation, as this continues to be a fluid situation.
• Screening Criteria: Follow the CDC’s patient assessment protocol for early disease detection for patients presenting to your practice. Patients should be screened using these guidelines: Overview of Testing for SARS-CoV-2 (COVID-19). Essential visitors to your facility should also be assessed for symptoms of coronavirus and contact exposure and redirected to remain outside if suspect.
• Accepting Patients: Do not turn patients away simply because a patient calls with acute respiratory symptoms. Refusing assessment/care may lead to concerns of patient abandonment.
• Designated Triage Location: Check with your local public health authorities for locations designated to triage suspected patients, so exposure is limited in general medical offices.
• Telehealth Triage: Licensed staff should be trained in triage protocol to determine which patients can be managed safely at home. See Healthcare Facilities: Managing Operations During the COVID-19 Pandemic. The Doctors Company offers resources on telemedicine in our COVID-19 Telehealth Resource Center.
• Patient Testing: When there is a reasonable presumption that a patient may have been exposed to COVID-19, contact the local or state health department to coordinate testing using available community resources. See the CDC’s Testing for COVID-19 , the COVID-19 Testing Overview, and the Clinician Call Center.
• Elective Services: Check with regional governmental and health authorities on the provision of nonessential and elective health care visits and group-related activities. Many states continue or have reinstated restrictions on the provision of nonurgent, elective surgeries and procedures.
• Patient Precautions: Educational resources, including posters for use in the medical office, are available from the WHO and for health care workers from the CDC (Contact Precautions, Droplet Precautions, and Airborne Precautions). Reference the CDC’s and Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19) for patient management guidance.
• Provider/Staff Precautions: Follow Standard Precautions and Transmission-Based Precautions, including gloves, gowns, protective eyewear, and NIOSH-certified N95 respirators that have been properly fit-tested. If there is a shortage of N95 respirators in your facility, access current CDC respirator recommendations and review Optimizing Personal Protective Equipment (PPE) Supplies.
• Limit Exposure: Limit staff exposure to suspected patients, with the exam room door kept closed. Ideally, the designated exam room should be at the back of the office, far away from other staff and patients.
• Surface Disinfection: Once the patient exits the room, conduct surface disinfection while staff continues to wear PPE.
• Patient Education: Provide up-to-date, factual information on the virus to suspected COVID-19–positive patients and their close contacts.
• Provider/Staff Exposure: Screen health care personnel daily for symptoms/contacts relevant to COVID-19. Any unprotected occupational exposure by staff members should be assessed and monitored. See Interim U.S. Guidance for Risk Assessment and Work Restrictions for Healthcare Personnel with Potential Exposure to COVID-19. Should providers and/or staff test positive within your facility, conduct and document a risk assessment identifying contacts, type of interaction, and PPE in use, then contact local health authorities for additional instruction. The CDC provides guidance here under the section “Infection Control.” The health department may assist with patient notification if determined to be necessary. For return-to-work guidance, review the Criteria for Return to Work for Healthcare Personnel with SARS-CoV-2 Infection (Interim Guidance).
• Staff Training: Provide and document additional staff training as protocols change. Maintain training records in administrative files.

Ms. Hill is senior patient safety risk manager at The Doctors Company. The guidelines suggested here are not rules, do not constitute legal advice, and do not ensure a successful outcome. The ultimate decision regarding the appropriateness of any treatment must be made by each health care provider considering the circumstances of the individual situation and in accordance with the laws of the jurisdiction in which the care is rendered.

Editor’s note: This article has been provided by The Doctors Company, the exclusively endorsed medical malpractice carrier for the Society of Hospital Medicine.

As the pandemic hits its third nationwide surge, families are gathering for the holidays, and medical practices are preparing for a potential increase in cases. Medical offices in states that were not strongly affected by the first and second waves of the virus may now be facing an influx of COVID-19 patients. Therefore, medical offices must remain very attentive to the widespread outbreak of COVID-19, continuing to proactively take steps to safely manage patients while protecting clinical staff.

Here are tips and resources for this season of the pandemic:

• Documentation: Maintain administrative records of how you have adapted to the evolving crisis, including the challenges you faced. For details, see Keep a COVID-19 Diary: Document Now in Case of Future Lawsuits.
• Legislation and Guidance: Reference the CDC; your state medical board; professional societies; and federal, state, and local authorities daily for public health guidance and new legislation, as this continues to be a fluid situation.
• Screening Criteria: Follow the CDC’s patient assessment protocol for early disease detection for patients presenting to your practice. Patients should be screened using these guidelines: Overview of Testing for SARS-CoV-2 (COVID-19). Essential visitors to your facility should also be assessed for symptoms of coronavirus and contact exposure and redirected to remain outside if suspect.
• Accepting Patients: Do not turn patients away simply because a patient calls with acute respiratory symptoms. Refusing assessment/care may lead to concerns of patient abandonment.
• Designated Triage Location: Check with your local public health authorities for locations designated to triage suspected patients, so exposure is limited in general medical offices.
• Telehealth Triage: Licensed staff should be trained in triage protocol to determine which patients can be managed safely at home. See Healthcare Facilities: Managing Operations During the COVID-19 Pandemic. The Doctors Company offers resources on telemedicine in our COVID-19 Telehealth Resource Center.
• Patient Testing: When there is a reasonable presumption that a patient may have been exposed to COVID-19, contact the local or state health department to coordinate testing using available community resources. See the CDC’s Testing for COVID-19 , the COVID-19 Testing Overview, and the Clinician Call Center.
• Elective Services: Check with regional governmental and health authorities on the provision of nonessential and elective health care visits and group-related activities. Many states continue or have reinstated restrictions on the provision of nonurgent, elective surgeries and procedures.
• Patient Precautions: Educational resources, including posters for use in the medical office, are available from the WHO and for health care workers from the CDC (Contact Precautions, Droplet Precautions, and Airborne Precautions). Reference the CDC’s and Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19) for patient management guidance.
• Provider/Staff Precautions: Follow Standard Precautions and Transmission-Based Precautions, including gloves, gowns, protective eyewear, and NIOSH-certified N95 respirators that have been properly fit-tested. If there is a shortage of N95 respirators in your facility, access current CDC respirator recommendations and review Optimizing Personal Protective Equipment (PPE) Supplies.
• Limit Exposure: Limit staff exposure to suspected patients, with the exam room door kept closed. Ideally, the designated exam room should be at the back of the office, far away from other staff and patients.
• Surface Disinfection: Once the patient exits the room, conduct surface disinfection while staff continues to wear PPE.
• Patient Education: Provide up-to-date, factual information on the virus to suspected COVID-19–positive patients and their close contacts.
• Provider/Staff Exposure: Screen health care personnel daily for symptoms/contacts relevant to COVID-19. Any unprotected occupational exposure by staff members should be assessed and monitored. See Interim U.S. Guidance for Risk Assessment and Work Restrictions for Healthcare Personnel with Potential Exposure to COVID-19. Should providers and/or staff test positive within your facility, conduct and document a risk assessment identifying contacts, type of interaction, and PPE in use, then contact local health authorities for additional instruction. The CDC provides guidance here under the section “Infection Control.” The health department may assist with patient notification if determined to be necessary. For return-to-work guidance, review the Criteria for Return to Work for Healthcare Personnel with SARS-CoV-2 Infection (Interim Guidance).
• Staff Training: Provide and document additional staff training as protocols change. Maintain training records in administrative files.

Ms. Hill is senior patient safety risk manager at The Doctors Company. The guidelines suggested here are not rules, do not constitute legal advice, and do not ensure a successful outcome. The ultimate decision regarding the appropriateness of any treatment must be made by each health care provider considering the circumstances of the individual situation and in accordance with the laws of the jurisdiction in which the care is rendered.

A long-awaited update to asthma management guidelines, developed by an expert panel at the National Heart, Lung, and Blood Institute, has been released.

Courtesy University of Wisconsin Health System

The updated guidelines address six priority topics, including refined recommendations for the use of fractional exhaled nitric oxide (FeNO) testing, intermittent inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA), and bronchial thermoplasty, but notably exclude any recommendations for the use of fast-emerging biological therapy.

“Biological therapy is the major step forward,” said William W. Busse, MD, professor of allergy and immunology at the University of Wisconsin–Madison, and lead author of the previous guidelines (Bethesda, Md.: NHLBI, 2007). “It wasn’t within the scope of work, so it’s not a criticism, but it is an important shortcoming,” he said. The omission identifies the need for the next update. “This is an area that has to be dealt with,” Dr. Busse stated in an interview.

Including biologic agents would have delayed the release of the recommendations for another year or 2, wrote the expert panel working group of the NHLBI, “and this was felt to be unacceptable.” The working group, overseen by the National Asthma Education and Prevention Program Coordinating Committee, also acknowledged the update is “not a complete revision” of the 2007 guidelines.

The update provides an evidenced-based review of six key topics in asthma care, as Mary Cataletto, MD, FCCP, professor of pediatrics at New York University Long Island, Mineola, pointed out: use of FeNO, indoor allergen mitigation, use of intermittent ICS and LAMA for asthma, role of subcutaneous and sublingual immunotherapy in the treatment of allergic asthma, and the use of bronchial thermoplasty.

“It has been 13 years since the last update and substantial progress has been made since then in understanding how to best treat children and adults with asthma,” said working group member Michael Schatz, MD, MS, FCCP, an allergy specialist at Kaiser Permanente Medical Center in San Diego.

According to Dr. Schatz, the most important updated recommendations are:

• Conditional recommendation for the use of ICS in children aged infant to 4 years with recurrent wheezing with respiratory infections.
• Use of combination ICS-formoterol for maintenance and to relieve flares in patients with moderate to severe asthma.
• Addition of the LAMA inhaled bronchodilator as add-on therapy for severe asthma not controlled by long-acting beta-agonist (LABA)/ICS combination medications.

Another important update, Dr. Cataletto said, is “shared decision-making among members of asthma teams in order to improve asthma care across all age groups.”

In all, the update includes 19 recommendations in the six subject areas. Each recommendation is notated with two values: its strength, either strong or conditional, and the certainty of evidence behind it, either low, moderate, or high. For example, the recommendation for ICS in young children that Dr. Schatz referred to has a conditional strength of recommendation with moderate certainty of evidence.

Using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology to determine strength of recommendation is a notable innovation of the latest guidelines, Dr. Busse noted.

Recommendations (strength of recommendation/certainty of evidence) include:

• Use of FeNO in children and adults when the asthma diagnosis is uncertain (conditional/moderate) or in those with allergic asthma and an uncertain course of management (conditional/low).
• Avoid standalone FeNO to evaluate asthma control or the likelihood or severity of future exacerbations, or for in infants to 4-year-olds with recurrent wheezing (strong/low for both).
• Avoid allergen mitigation in routine asthma management for patients who don’t have sensitivity to specific indoor allergens (conditional/low).
• Multicomponent allergen-specific mitigation when specific allergen sensitivity has been identified and pest management alone for symptoms related to specific pest exposure (conditional/low for both).
• Impermeable bedding covers should be part of a multicomponent mitigation strategy, not as a standalone tool, for patients with asthma and dust mite sensitivity (conditional/moderate).
• Daily ICS at onset of a respiratory tract infection along with as-needed short-acting beta-agonists in children aged 4 years and younger with recurrent wheezing but no wheezing between infections rather than as-needed standalone SABA (conditional/high).
• For adults and children aged 12 years and older with mild persistent asthma, either daily low-dose ICS with as-needed SABA or as-needed ICS and SABA concomitantly (conditional/moderate).
• Avoid short-course increased ICS dosing for patients aged 4 years and older with good adherence to daily ICS therapy (conditional/low).
• For patients aged 4 years and older with moderate to severe persistent asthma, a preference for combined ICS-formoterol inhaler over higher dose ICS daily and intermittent SABA or daily ICS-LABA with intermittent SABA (strong/high [aged 12 years and older]; moderate [aged 4-11 years]).
• A preference for combined ICS-formoterol for both daily and relief therapy for patients 12 years and older with severe persistent asthma over higher-dose ICS-LABA daily and intermittent SABA (conditional/high).
• A preference for adding LABA rather than LAMA to ICS in patients aged 12 years and older with uncontrolled persistent asthma (conditional/moderate).
• If LABA isn’t used, add LAMA to ICS in patients aged 12 years and older with uncontrolled persistent asthma rather than continuing the same dose of ICS alone (conditional/moderate).
• In those same patients already on combined ICS-LABA therapy, add LAMA rather than continuing the same dose of ICS-LABA (conditional/moderate).
• Use subcutaneous immunotherapy as a potential adjunct to standard drug therapy in patients aged 5 years and older with mild to moderate allergic asthma when their asthma is controlled on immunotherapy (conditional/moderate).
• Avoid sublingual immunotherapy in patients with persistent allergic asthma (conditional/moderate).
• Avoid bronchial thermoplasty in those 18 years and older with persistent asthma, but consider it in patients who can accept the short-term worsening symptoms or unknown long-term side effects in exchange for the potential benefits (conditional/moderate).

One of the key elements of the guidelines is the use of the SMART (single maintenance and reliever therapy) approach to evaluate the comparative effectiveness of intermittent ICS with formoterol, Dr. Busse noted. “I think that’s a very significant advance. The literature is replete with evidence to support this. Secondly, it really makes life convenient for patients; you have one inhaler.”

The recommendation on SABA use is also significant, Dr. Busse said. “Data have emerged to suggest that if you’re having a need for one of these rescue medications, it’s due to an increase in inflammation in the lower airway, and you want to give an ICS which will act on the inflammation along with the bronchodilator. That’s a new concept, and it’s a very significant step forward.”

Dr. Schatz disclosed financial relationships with Merck, Teva, and ALK-Abello, but was recused from the writing, discussion, and voting related to the immunotherapy recommendation. Dr. Cataletto and Dr. Busse have no relevant relationships to disclose.

SOURCE: Schatz M et al. J Allergy Clin Immunol. 2020;146:1217-70.

A long-awaited update to asthma management guidelines, developed by an expert panel at the National Heart, Lung, and Blood Institute, has been released.

Courtesy University of Wisconsin Health System

The updated guidelines address six priority topics, including refined recommendations for the use of fractional exhaled nitric oxide (FeNO) testing, intermittent inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA), and bronchial thermoplasty, but notably exclude any recommendations for the use of fast-emerging biological therapy.

“Biological therapy is the major step forward,” said William W. Busse, MD, professor of allergy and immunology at the University of Wisconsin–Madison, and lead author of the previous guidelines (Bethesda, Md.: NHLBI, 2007). “It wasn’t within the scope of work, so it’s not a criticism, but it is an important shortcoming,” he said. The omission identifies the need for the next update. “This is an area that has to be dealt with,” Dr. Busse stated in an interview.

Including biologic agents would have delayed the release of the recommendations for another year or 2, wrote the expert panel working group of the NHLBI, “and this was felt to be unacceptable.” The working group, overseen by the National Asthma Education and Prevention Program Coordinating Committee, also acknowledged the update is “not a complete revision” of the 2007 guidelines.

The update provides an evidenced-based review of six key topics in asthma care, as Mary Cataletto, MD, FCCP, professor of pediatrics at New York University Long Island, Mineola, pointed out: use of FeNO, indoor allergen mitigation, use of intermittent ICS and LAMA for asthma, role of subcutaneous and sublingual immunotherapy in the treatment of allergic asthma, and the use of bronchial thermoplasty.

“It has been 13 years since the last update and substantial progress has been made since then in understanding how to best treat children and adults with asthma,” said working group member Michael Schatz, MD, MS, FCCP, an allergy specialist at Kaiser Permanente Medical Center in San Diego.

According to Dr. Schatz, the most important updated recommendations are:

• Conditional recommendation for the use of ICS in children aged infant to 4 years with recurrent wheezing with respiratory infections.
• Use of combination ICS-formoterol for maintenance and to relieve flares in patients with moderate to severe asthma.
• Addition of the LAMA inhaled bronchodilator as add-on therapy for severe asthma not controlled by long-acting beta-agonist (LABA)/ICS combination medications.

Another important update, Dr. Cataletto said, is “shared decision-making among members of asthma teams in order to improve asthma care across all age groups.”

In all, the update includes 19 recommendations in the six subject areas. Each recommendation is notated with two values: its strength, either strong or conditional, and the certainty of evidence behind it, either low, moderate, or high. For example, the recommendation for ICS in young children that Dr. Schatz referred to has a conditional strength of recommendation with moderate certainty of evidence.

Using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology to determine strength of recommendation is a notable innovation of the latest guidelines, Dr. Busse noted.

Recommendations (strength of recommendation/certainty of evidence) include:

• Use of FeNO in children and adults when the asthma diagnosis is uncertain (conditional/moderate) or in those with allergic asthma and an uncertain course of management (conditional/low).
• Avoid standalone FeNO to evaluate asthma control or the likelihood or severity of future exacerbations, or for in infants to 4-year-olds with recurrent wheezing (strong/low for both).
• Avoid allergen mitigation in routine asthma management for patients who don’t have sensitivity to specific indoor allergens (conditional/low).
• Multicomponent allergen-specific mitigation when specific allergen sensitivity has been identified and pest management alone for symptoms related to specific pest exposure (conditional/low for both).
• Impermeable bedding covers should be part of a multicomponent mitigation strategy, not as a standalone tool, for patients with asthma and dust mite sensitivity (conditional/moderate).
• Daily ICS at onset of a respiratory tract infection along with as-needed short-acting beta-agonists in children aged 4 years and younger with recurrent wheezing but no wheezing between infections rather than as-needed standalone SABA (conditional/high).
• For adults and children aged 12 years and older with mild persistent asthma, either daily low-dose ICS with as-needed SABA or as-needed ICS and SABA concomitantly (conditional/moderate).
• Avoid short-course increased ICS dosing for patients aged 4 years and older with good adherence to daily ICS therapy (conditional/low).
• For patients aged 4 years and older with moderate to severe persistent asthma, a preference for combined ICS-formoterol inhaler over higher dose ICS daily and intermittent SABA or daily ICS-LABA with intermittent SABA (strong/high [aged 12 years and older]; moderate [aged 4-11 years]).
• A preference for combined ICS-formoterol for both daily and relief therapy for patients 12 years and older with severe persistent asthma over higher-dose ICS-LABA daily and intermittent SABA (conditional/high).
• A preference for adding LABA rather than LAMA to ICS in patients aged 12 years and older with uncontrolled persistent asthma (conditional/moderate).
• If LABA isn’t used, add LAMA to ICS in patients aged 12 years and older with uncontrolled persistent asthma rather than continuing the same dose of ICS alone (conditional/moderate).
• In those same patients already on combined ICS-LABA therapy, add LAMA rather than continuing the same dose of ICS-LABA (conditional/moderate).
• Use subcutaneous immunotherapy as a potential adjunct to standard drug therapy in patients aged 5 years and older with mild to moderate allergic asthma when their asthma is controlled on immunotherapy (conditional/moderate).
• Avoid sublingual immunotherapy in patients with persistent allergic asthma (conditional/moderate).
• Avoid bronchial thermoplasty in those 18 years and older with persistent asthma, but consider it in patients who can accept the short-term worsening symptoms or unknown long-term side effects in exchange for the potential benefits (conditional/moderate).

One of the key elements of the guidelines is the use of the SMART (single maintenance and reliever therapy) approach to evaluate the comparative effectiveness of intermittent ICS with formoterol, Dr. Busse noted. “I think that’s a very significant advance. The literature is replete with evidence to support this. Secondly, it really makes life convenient for patients; you have one inhaler.”

The recommendation on SABA use is also significant, Dr. Busse said. “Data have emerged to suggest that if you’re having a need for one of these rescue medications, it’s due to an increase in inflammation in the lower airway, and you want to give an ICS which will act on the inflammation along with the bronchodilator. That’s a new concept, and it’s a very significant step forward.”

Dr. Schatz disclosed financial relationships with Merck, Teva, and ALK-Abello, but was recused from the writing, discussion, and voting related to the immunotherapy recommendation. Dr. Cataletto and Dr. Busse have no relevant relationships to disclose.

SOURCE: Schatz M et al. J Allergy Clin Immunol. 2020;146:1217-70.

A long-awaited update to asthma management guidelines, developed by an expert panel at the National Heart, Lung, and Blood Institute, has been released.

Courtesy University of Wisconsin Health System

The updated guidelines address six priority topics, including refined recommendations for the use of fractional exhaled nitric oxide (FeNO) testing, intermittent inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA), and bronchial thermoplasty, but notably exclude any recommendations for the use of fast-emerging biological therapy.

“Biological therapy is the major step forward,” said William W. Busse, MD, professor of allergy and immunology at the University of Wisconsin–Madison, and lead author of the previous guidelines (Bethesda, Md.: NHLBI, 2007). “It wasn’t within the scope of work, so it’s not a criticism, but it is an important shortcoming,” he said. The omission identifies the need for the next update. “This is an area that has to be dealt with,” Dr. Busse stated in an interview.

Including biologic agents would have delayed the release of the recommendations for another year or 2, wrote the expert panel working group of the NHLBI, “and this was felt to be unacceptable.” The working group, overseen by the National Asthma Education and Prevention Program Coordinating Committee, also acknowledged the update is “not a complete revision” of the 2007 guidelines.

The update provides an evidenced-based review of six key topics in asthma care, as Mary Cataletto, MD, FCCP, professor of pediatrics at New York University Long Island, Mineola, pointed out: use of FeNO, indoor allergen mitigation, use of intermittent ICS and LAMA for asthma, role of subcutaneous and sublingual immunotherapy in the treatment of allergic asthma, and the use of bronchial thermoplasty.

“It has been 13 years since the last update and substantial progress has been made since then in understanding how to best treat children and adults with asthma,” said working group member Michael Schatz, MD, MS, FCCP, an allergy specialist at Kaiser Permanente Medical Center in San Diego.

According to Dr. Schatz, the most important updated recommendations are:

• Conditional recommendation for the use of ICS in children aged infant to 4 years with recurrent wheezing with respiratory infections.
• Use of combination ICS-formoterol for maintenance and to relieve flares in patients with moderate to severe asthma.
• Addition of the LAMA inhaled bronchodilator as add-on therapy for severe asthma not controlled by long-acting beta-agonist (LABA)/ICS combination medications.

Another important update, Dr. Cataletto said, is “shared decision-making among members of asthma teams in order to improve asthma care across all age groups.”

In all, the update includes 19 recommendations in the six subject areas. Each recommendation is notated with two values: its strength, either strong or conditional, and the certainty of evidence behind it, either low, moderate, or high. For example, the recommendation for ICS in young children that Dr. Schatz referred to has a conditional strength of recommendation with moderate certainty of evidence.

Using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology to determine strength of recommendation is a notable innovation of the latest guidelines, Dr. Busse noted.

Recommendations (strength of recommendation/certainty of evidence) include:

• Use of FeNO in children and adults when the asthma diagnosis is uncertain (conditional/moderate) or in those with allergic asthma and an uncertain course of management (conditional/low).
• Avoid standalone FeNO to evaluate asthma control or the likelihood or severity of future exacerbations, or for in infants to 4-year-olds with recurrent wheezing (strong/low for both).
• Avoid allergen mitigation in routine asthma management for patients who don’t have sensitivity to specific indoor allergens (conditional/low).
• Multicomponent allergen-specific mitigation when specific allergen sensitivity has been identified and pest management alone for symptoms related to specific pest exposure (conditional/low for both).
• Impermeable bedding covers should be part of a multicomponent mitigation strategy, not as a standalone tool, for patients with asthma and dust mite sensitivity (conditional/moderate).
• Daily ICS at onset of a respiratory tract infection along with as-needed short-acting beta-agonists in children aged 4 years and younger with recurrent wheezing but no wheezing between infections rather than as-needed standalone SABA (conditional/high).
• For adults and children aged 12 years and older with mild persistent asthma, either daily low-dose ICS with as-needed SABA or as-needed ICS and SABA concomitantly (conditional/moderate).
• Avoid short-course increased ICS dosing for patients aged 4 years and older with good adherence to daily ICS therapy (conditional/low).
• For patients aged 4 years and older with moderate to severe persistent asthma, a preference for combined ICS-formoterol inhaler over higher dose ICS daily and intermittent SABA or daily ICS-LABA with intermittent SABA (strong/high [aged 12 years and older]; moderate [aged 4-11 years]).
• A preference for combined ICS-formoterol for both daily and relief therapy for patients 12 years and older with severe persistent asthma over higher-dose ICS-LABA daily and intermittent SABA (conditional/high).
• A preference for adding LABA rather than LAMA to ICS in patients aged 12 years and older with uncontrolled persistent asthma (conditional/moderate).
• If LABA isn’t used, add LAMA to ICS in patients aged 12 years and older with uncontrolled persistent asthma rather than continuing the same dose of ICS alone (conditional/moderate).
• In those same patients already on combined ICS-LABA therapy, add LAMA rather than continuing the same dose of ICS-LABA (conditional/moderate).
• Use subcutaneous immunotherapy as a potential adjunct to standard drug therapy in patients aged 5 years and older with mild to moderate allergic asthma when their asthma is controlled on immunotherapy (conditional/moderate).
• Avoid sublingual immunotherapy in patients with persistent allergic asthma (conditional/moderate).
• Avoid bronchial thermoplasty in those 18 years and older with persistent asthma, but consider it in patients who can accept the short-term worsening symptoms or unknown long-term side effects in exchange for the potential benefits (conditional/moderate).

One of the key elements of the guidelines is the use of the SMART (single maintenance and reliever therapy) approach to evaluate the comparative effectiveness of intermittent ICS with formoterol, Dr. Busse noted. “I think that’s a very significant advance. The literature is replete with evidence to support this. Secondly, it really makes life convenient for patients; you have one inhaler.”

The recommendation on SABA use is also significant, Dr. Busse said. “Data have emerged to suggest that if you’re having a need for one of these rescue medications, it’s due to an increase in inflammation in the lower airway, and you want to give an ICS which will act on the inflammation along with the bronchodilator. That’s a new concept, and it’s a very significant step forward.”

Dr. Schatz disclosed financial relationships with Merck, Teva, and ALK-Abello, but was recused from the writing, discussion, and voting related to the immunotherapy recommendation. Dr. Cataletto and Dr. Busse have no relevant relationships to disclose.

SOURCE: Schatz M et al. J Allergy Clin Immunol. 2020;146:1217-70.