Wide-area transepithelial sampling with 3D (WATS-3D) analysis increased detection of dysplasia when used as an adjunct to the Seattle forceps biopsy protocol in patients with Barrett’s esophagus, according to a recent meta-analysis. While the findings demonstrate potential for increased dysplasia detection, the analysis failed to identify the clinical significance of this detection.

©Nephron/Wikimedia Commons/CC BY-SA 3.0/No changes

Despite its ability to evaluate Barrett’s esophagus segments and examine targeted biopsies of mucosal abnormalities, the Seattle protocol is primarily limited by lack of adherence and increased risk of sampling error. “Moreover, the rates of ‘missed’ dysplasia and EAC [esophageal adenocarcinoma] remain high, with up to a quarter of all EAC being ‘missed,’ ” wrote study authors Don Codipilly, MD, of the Mayo Clinic, and colleagues. The report is in Gastrointestinal Endoscopy.

There are challenges associated with the Seattle protocol, specifically poor protocol adherence and missed identification of subtle abnormalities potentially harboring dysplasia. In contrast, the novel WATS-3D may overcome issues related to sampling error due to its ability to obtain higher proportions of Barrett’s esophagus mucosa through the use of a brush-only technique. According to the researchers, previous studies suggest WATS-3D may increase dysplasia yield by approximately 40% compared with conventional surveillance methods.

To gauge the incremental yield of WATS-3D for dysplasia detection compared with the Seattle forceps biopsy protocol, Dr. Codipilly and colleagues performed a systematic review and meta-analysis of seven studies using the two techniques from 2000 to 2020. The researchers defined “incremental yield” of detected dysplasia as a composite of indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia (HGD), and esophageal adenocarcinoma (EAC). They also compared the two surveillance techniques in terms of incremental yields of HGD/EAC, as well as the rate of reconfirmation of WATS-3D dysplasia on subsequent forceps biopsies.

The seven studies in the final analysis included a pooled cohort of 3,206 patients. According to the meta-analysis, forceps biopsies diagnosed dysplasia in 15.9% (95% confidence interval, 5.4-30.5) of all cases, while the incremental yield of WATS-3D was 7.2% (95% CI, 3.9-11.5). In the pooled analysis of six studies that reported the secondary outcomes, forceps biopsies diagnosed HGD/EAC in 2.3% (95% CI, 0.6-5.1) of patients, while the incremental yield with WATS-3D was 2.1% (95% CI, 0.4-5.3). The researchers point out that WATS-3D was negative in 62.5% of cases where forceps biopsies detected dysplasia. Reports from two of the studies reconfirmed WATS-3D dysplasia with forceps biopsies histology in 20 patients.

“Based on these findings, it cannot be recommended to replace the Seattle Protocol but instead to use both techniques in conjunction to detect dysplasia most effectively,” Omar Awais, DO, assistant professor of surgery in the Department of Cardiothoracic Surgery at the University of Pittsburgh School of Medicine, said in an email to this news organization.

Dr. Awais, who was not involved in the meta-analysis, suggests further prospective, randomized studies are needed to confirm the results. “Additionally, we will also need studies to show cost-effectiveness for using WATS-3D in addition to Seattle protocol, as these may help verify WATS-3D dysplasia by standard endoscopic protocol and show we are not missing dysplasia using the technique,” he said.

Felice H. Schnoll-Sussman, MD, professor of clinical medicine and director of the Jay Monahan Center for Gastrointestinal Health at New York–Presbyterian Hospital/Weill Medical College, added that the meta-analysis “adds to our understanding” of the place of WATS as an adjunct approach in dysplasia detection. “In spite of the rigid selection of studies, this analysis also leaves us with questions about the overall utility of WATS given the lack of follow-up cases where dysplasia was only identified on the WATS brush as well as the overall cost-effectiveness of this approach,” she said.

Dr. Schnoll-Sussman, who was not involved in the study conducted by Dr. Codipilly and colleagues, told this news organization that one of the issues with the WATS brush is obtaining adequate sampling, which may impede adherence. “Attention has to be paid to sampling all quadrants with the brush, which at times may be challenging, especially in esophagi that are tortuous, angulated, or dilated,” she explained. “Like with any endoscopic technique, care must be taken to obtain high-yield sampling.”

Dr. Schnoll-Sussman noted that the subtle, small areas of denuded mucosa left where the brush has made appropriate contact with the mucosa should be appreciated during sampling. “Taking one’s time to sample the esophageal lining – a major reason for missed lesions in the Seattle protocol – can also become an issue with WATS,” she added.

The study researchers reported conflicts of interest with several pharmaceutical companies. No funding was reported for the study. Dr. Awais and Dr. Schnoll-Sussman had no conflicts to disclose.

Help your patients better understand the risks, testing and treatment options for Barrett’s esophagus by sharing education from the AGA GI Patient Center: www.gastro.org/BE. 

Wide-area transepithelial sampling with 3D (WATS-3D) analysis increased detection of dysplasia when used as an adjunct to the Seattle forceps biopsy protocol in patients with Barrett’s esophagus, according to a recent meta-analysis. While the findings demonstrate potential for increased dysplasia detection, the analysis failed to identify the clinical significance of this detection.

©Nephron/Wikimedia Commons/CC BY-SA 3.0/No changes

Despite its ability to evaluate Barrett’s esophagus segments and examine targeted biopsies of mucosal abnormalities, the Seattle protocol is primarily limited by lack of adherence and increased risk of sampling error. “Moreover, the rates of ‘missed’ dysplasia and EAC [esophageal adenocarcinoma] remain high, with up to a quarter of all EAC being ‘missed,’ ” wrote study authors Don Codipilly, MD, of the Mayo Clinic, and colleagues. The report is in Gastrointestinal Endoscopy.

There are challenges associated with the Seattle protocol, specifically poor protocol adherence and missed identification of subtle abnormalities potentially harboring dysplasia. In contrast, the novel WATS-3D may overcome issues related to sampling error due to its ability to obtain higher proportions of Barrett’s esophagus mucosa through the use of a brush-only technique. According to the researchers, previous studies suggest WATS-3D may increase dysplasia yield by approximately 40% compared with conventional surveillance methods.

To gauge the incremental yield of WATS-3D for dysplasia detection compared with the Seattle forceps biopsy protocol, Dr. Codipilly and colleagues performed a systematic review and meta-analysis of seven studies using the two techniques from 2000 to 2020. The researchers defined “incremental yield” of detected dysplasia as a composite of indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia (HGD), and esophageal adenocarcinoma (EAC). They also compared the two surveillance techniques in terms of incremental yields of HGD/EAC, as well as the rate of reconfirmation of WATS-3D dysplasia on subsequent forceps biopsies.

The seven studies in the final analysis included a pooled cohort of 3,206 patients. According to the meta-analysis, forceps biopsies diagnosed dysplasia in 15.9% (95% confidence interval, 5.4-30.5) of all cases, while the incremental yield of WATS-3D was 7.2% (95% CI, 3.9-11.5). In the pooled analysis of six studies that reported the secondary outcomes, forceps biopsies diagnosed HGD/EAC in 2.3% (95% CI, 0.6-5.1) of patients, while the incremental yield with WATS-3D was 2.1% (95% CI, 0.4-5.3). The researchers point out that WATS-3D was negative in 62.5% of cases where forceps biopsies detected dysplasia. Reports from two of the studies reconfirmed WATS-3D dysplasia with forceps biopsies histology in 20 patients.

“Based on these findings, it cannot be recommended to replace the Seattle Protocol but instead to use both techniques in conjunction to detect dysplasia most effectively,” Omar Awais, DO, assistant professor of surgery in the Department of Cardiothoracic Surgery at the University of Pittsburgh School of Medicine, said in an email to this news organization.

Dr. Awais, who was not involved in the meta-analysis, suggests further prospective, randomized studies are needed to confirm the results. “Additionally, we will also need studies to show cost-effectiveness for using WATS-3D in addition to Seattle protocol, as these may help verify WATS-3D dysplasia by standard endoscopic protocol and show we are not missing dysplasia using the technique,” he said.

Felice H. Schnoll-Sussman, MD, professor of clinical medicine and director of the Jay Monahan Center for Gastrointestinal Health at New York–Presbyterian Hospital/Weill Medical College, added that the meta-analysis “adds to our understanding” of the place of WATS as an adjunct approach in dysplasia detection. “In spite of the rigid selection of studies, this analysis also leaves us with questions about the overall utility of WATS given the lack of follow-up cases where dysplasia was only identified on the WATS brush as well as the overall cost-effectiveness of this approach,” she said.

Dr. Schnoll-Sussman, who was not involved in the study conducted by Dr. Codipilly and colleagues, told this news organization that one of the issues with the WATS brush is obtaining adequate sampling, which may impede adherence. “Attention has to be paid to sampling all quadrants with the brush, which at times may be challenging, especially in esophagi that are tortuous, angulated, or dilated,” she explained. “Like with any endoscopic technique, care must be taken to obtain high-yield sampling.”

Dr. Schnoll-Sussman noted that the subtle, small areas of denuded mucosa left where the brush has made appropriate contact with the mucosa should be appreciated during sampling. “Taking one’s time to sample the esophageal lining – a major reason for missed lesions in the Seattle protocol – can also become an issue with WATS,” she added.

The study researchers reported conflicts of interest with several pharmaceutical companies. No funding was reported for the study. Dr. Awais and Dr. Schnoll-Sussman had no conflicts to disclose.

Help your patients better understand the risks, testing and treatment options for Barrett’s esophagus by sharing education from the AGA GI Patient Center: www.gastro.org/BE. 

Wide-area transepithelial sampling with 3D (WATS-3D) analysis increased detection of dysplasia when used as an adjunct to the Seattle forceps biopsy protocol in patients with Barrett’s esophagus, according to a recent meta-analysis. While the findings demonstrate potential for increased dysplasia detection, the analysis failed to identify the clinical significance of this detection.

©Nephron/Wikimedia Commons/CC BY-SA 3.0/No changes

Despite its ability to evaluate Barrett’s esophagus segments and examine targeted biopsies of mucosal abnormalities, the Seattle protocol is primarily limited by lack of adherence and increased risk of sampling error. “Moreover, the rates of ‘missed’ dysplasia and EAC [esophageal adenocarcinoma] remain high, with up to a quarter of all EAC being ‘missed,’ ” wrote study authors Don Codipilly, MD, of the Mayo Clinic, and colleagues. The report is in Gastrointestinal Endoscopy.

There are challenges associated with the Seattle protocol, specifically poor protocol adherence and missed identification of subtle abnormalities potentially harboring dysplasia. In contrast, the novel WATS-3D may overcome issues related to sampling error due to its ability to obtain higher proportions of Barrett’s esophagus mucosa through the use of a brush-only technique. According to the researchers, previous studies suggest WATS-3D may increase dysplasia yield by approximately 40% compared with conventional surveillance methods.

To gauge the incremental yield of WATS-3D for dysplasia detection compared with the Seattle forceps biopsy protocol, Dr. Codipilly and colleagues performed a systematic review and meta-analysis of seven studies using the two techniques from 2000 to 2020. The researchers defined “incremental yield” of detected dysplasia as a composite of indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia (HGD), and esophageal adenocarcinoma (EAC). They also compared the two surveillance techniques in terms of incremental yields of HGD/EAC, as well as the rate of reconfirmation of WATS-3D dysplasia on subsequent forceps biopsies.

The seven studies in the final analysis included a pooled cohort of 3,206 patients. According to the meta-analysis, forceps biopsies diagnosed dysplasia in 15.9% (95% confidence interval, 5.4-30.5) of all cases, while the incremental yield of WATS-3D was 7.2% (95% CI, 3.9-11.5). In the pooled analysis of six studies that reported the secondary outcomes, forceps biopsies diagnosed HGD/EAC in 2.3% (95% CI, 0.6-5.1) of patients, while the incremental yield with WATS-3D was 2.1% (95% CI, 0.4-5.3). The researchers point out that WATS-3D was negative in 62.5% of cases where forceps biopsies detected dysplasia. Reports from two of the studies reconfirmed WATS-3D dysplasia with forceps biopsies histology in 20 patients.

“Based on these findings, it cannot be recommended to replace the Seattle Protocol but instead to use both techniques in conjunction to detect dysplasia most effectively,” Omar Awais, DO, assistant professor of surgery in the Department of Cardiothoracic Surgery at the University of Pittsburgh School of Medicine, said in an email to this news organization.

Dr. Awais, who was not involved in the meta-analysis, suggests further prospective, randomized studies are needed to confirm the results. “Additionally, we will also need studies to show cost-effectiveness for using WATS-3D in addition to Seattle protocol, as these may help verify WATS-3D dysplasia by standard endoscopic protocol and show we are not missing dysplasia using the technique,” he said.

Felice H. Schnoll-Sussman, MD, professor of clinical medicine and director of the Jay Monahan Center for Gastrointestinal Health at New York–Presbyterian Hospital/Weill Medical College, added that the meta-analysis “adds to our understanding” of the place of WATS as an adjunct approach in dysplasia detection. “In spite of the rigid selection of studies, this analysis also leaves us with questions about the overall utility of WATS given the lack of follow-up cases where dysplasia was only identified on the WATS brush as well as the overall cost-effectiveness of this approach,” she said.

Dr. Schnoll-Sussman, who was not involved in the study conducted by Dr. Codipilly and colleagues, told this news organization that one of the issues with the WATS brush is obtaining adequate sampling, which may impede adherence. “Attention has to be paid to sampling all quadrants with the brush, which at times may be challenging, especially in esophagi that are tortuous, angulated, or dilated,” she explained. “Like with any endoscopic technique, care must be taken to obtain high-yield sampling.”

Dr. Schnoll-Sussman noted that the subtle, small areas of denuded mucosa left where the brush has made appropriate contact with the mucosa should be appreciated during sampling. “Taking one’s time to sample the esophageal lining – a major reason for missed lesions in the Seattle protocol – can also become an issue with WATS,” she added.

The study researchers reported conflicts of interest with several pharmaceutical companies. No funding was reported for the study. Dr. Awais and Dr. Schnoll-Sussman had no conflicts to disclose.

Help your patients better understand the risks, testing and treatment options for Barrett’s esophagus by sharing education from the AGA GI Patient Center: www.gastro.org/BE. 

The Barcelona baseline risk score predicted progression of multiple sclerosis (MS) in patients by assigning them to low-, medium-, and high-risk groups. The high-risk group had the shortest time to progression to an Expanded Disability Status Score (EDSS) of 3.0, and were also more likely to progress by MRI and quality of life measures.

The ranking is based on sex, age at the first clinically isolated syndrome, CIS topography, the number of T2 lesions, and the presence of infratentorial and spinal cord lesions, contrast-enhancing lesions, and oligoclonal bands.

“What we wanted to do is merge all of the different prognostic variables for one single patient into one single score,” said Mar Tintoré, MD, PhD, in an interview. Dr. Tintoré is a professor of neurology at Vall d’Hebron University Hospital in Barcelona and a senior consultant at the Multiple Sclerosis Centre of Catalonia (Cemcat). Dr. Tintoré presented the results of the study at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

The three groups had different outcomes in MRI, clinical factors, and MRI scans, and quality of life outcomes over the course of their disease. “So this is a confirmation that this classification at baseline is really meaningful,” Dr. Tintoré said in an interview.

She attributed the success of the model to its reliance on multiple factors, but it is also designed to be simple to use. “We have been trying to use it with simple factors, [information] that you always have, like age, sex, gender, number of lesions, and topography of the region. Everybody has this information at their desk.”
 

Proof of concept

The study validates the approach that neurologists already utilize, according to Patricia Coyle, MD, who moderated the session. “I think the prospective study is a really unique and powerful concept,” said Dr. Coyle, who is a professor of neurology, vice chair of neurology, and director of the Stony Brook (N.Y.) Comprehensive Care Center.

The new study “kind of confirmed their concept of the initial rating, judging long-term disability progression measures in subsets. They also looked at brain atrophy, they looked at gray-matter atrophy, and that also traveled with these three different groups of severity. So it kind of gives value to looking at prognostic indicators at a first attack,” said Dr. Coyle.

The results also validate the Barcelona group’s heavy emphasis on MRI, which Dr. Coyle pointed out is common practice. “If the brain MRI looks very bad, if there are a lot of spinal cord lesions, then that’s somebody we’re much more worried about.”

Once the model is confirmed in other cohorts, the researchers plan to release the model as a generally available algorithm that clinicians could use to help manage patients. Dr. Tintoré pointed out the debate over when to begin a patient on high-efficacy disease-modifying therapies. That choice depends on a lot of factors, including patient choice, safety, and comorbidities. “But knowing that your patient is at risk of having a bad prognosis is something that is helpful” in that decision-making process, she said.
 

Predicting time to EDSS 3.0

The researchers used the Barcelona CIS cohort to build a Weibull survival regression in order to estimate the median time to EDSS 3.0. The model produced three categories with widely divergent predicted times from CIS to EDSS 3.0: low risk, medium risk, and high risk.

In the current report, the researchers compared the model to a “360 degree” measure of measures in 1,308 patients, including clinical milestones (McDonald 2017 MS, confirmed secondary progressive MS, progression independent of relapse activity [PIRA], EDSS disability, number of T2 MRI lesions and brain atrophy, and Patient Reported Outcomes for MS [walking speed, manual dexterity, processing speed, and contrast sensitivity]).

At 30 years after CIS, the risk of reaching EDSS 3.0 was higher in the medium risk (hazard ratio, 3.0 versus low risk) and in the high risk group (HR, 8.3 versus low risk). At 10 years, the low risk group had a 40% risk of fulfilling McDonald 2017 criteria, versus 89% in the intermediate group, and 98% in the high risk group. A similar relationship was seen for SPMS (1%, 8%, 16%) and PIRA (17%, 26%, 35%).

At 10 years, the estimated accumulated T2 lesions was 7 in the low-risk group (95% CI, 5-9), 15 in the medium-risk group (95% CI, 12-17), and 21 in the high-risk group (95% CI, 15-27).

Compared with the low- and medium-risk groups, the high-risk group had lower brain parenchymal fraction and gray-matter fraction at 5 years. They also experienced higher stigma, had worse perception of upper and lower limb function as measured by Neuro QoL, and had worse cognitive performance.

Dr. Tintoré has received compensation for consulting services and speaking honoraria from Aimirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Janssen, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Teva Pharmaceuticals, and Viela Bio. Dr. Coyle has no relevant disclosures.

The Barcelona baseline risk score predicted progression of multiple sclerosis (MS) in patients by assigning them to low-, medium-, and high-risk groups. The high-risk group had the shortest time to progression to an Expanded Disability Status Score (EDSS) of 3.0, and were also more likely to progress by MRI and quality of life measures.

The ranking is based on sex, age at the first clinically isolated syndrome, CIS topography, the number of T2 lesions, and the presence of infratentorial and spinal cord lesions, contrast-enhancing lesions, and oligoclonal bands.

“What we wanted to do is merge all of the different prognostic variables for one single patient into one single score,” said Mar Tintoré, MD, PhD, in an interview. Dr. Tintoré is a professor of neurology at Vall d’Hebron University Hospital in Barcelona and a senior consultant at the Multiple Sclerosis Centre of Catalonia (Cemcat). Dr. Tintoré presented the results of the study at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

The three groups had different outcomes in MRI, clinical factors, and MRI scans, and quality of life outcomes over the course of their disease. “So this is a confirmation that this classification at baseline is really meaningful,” Dr. Tintoré said in an interview.

She attributed the success of the model to its reliance on multiple factors, but it is also designed to be simple to use. “We have been trying to use it with simple factors, [information] that you always have, like age, sex, gender, number of lesions, and topography of the region. Everybody has this information at their desk.”
 

Proof of concept

The study validates the approach that neurologists already utilize, according to Patricia Coyle, MD, who moderated the session. “I think the prospective study is a really unique and powerful concept,” said Dr. Coyle, who is a professor of neurology, vice chair of neurology, and director of the Stony Brook (N.Y.) Comprehensive Care Center.

The new study “kind of confirmed their concept of the initial rating, judging long-term disability progression measures in subsets. They also looked at brain atrophy, they looked at gray-matter atrophy, and that also traveled with these three different groups of severity. So it kind of gives value to looking at prognostic indicators at a first attack,” said Dr. Coyle.

The results also validate the Barcelona group’s heavy emphasis on MRI, which Dr. Coyle pointed out is common practice. “If the brain MRI looks very bad, if there are a lot of spinal cord lesions, then that’s somebody we’re much more worried about.”

Once the model is confirmed in other cohorts, the researchers plan to release the model as a generally available algorithm that clinicians could use to help manage patients. Dr. Tintoré pointed out the debate over when to begin a patient on high-efficacy disease-modifying therapies. That choice depends on a lot of factors, including patient choice, safety, and comorbidities. “But knowing that your patient is at risk of having a bad prognosis is something that is helpful” in that decision-making process, she said.
 

Predicting time to EDSS 3.0

The researchers used the Barcelona CIS cohort to build a Weibull survival regression in order to estimate the median time to EDSS 3.0. The model produced three categories with widely divergent predicted times from CIS to EDSS 3.0: low risk, medium risk, and high risk.

In the current report, the researchers compared the model to a “360 degree” measure of measures in 1,308 patients, including clinical milestones (McDonald 2017 MS, confirmed secondary progressive MS, progression independent of relapse activity [PIRA], EDSS disability, number of T2 MRI lesions and brain atrophy, and Patient Reported Outcomes for MS [walking speed, manual dexterity, processing speed, and contrast sensitivity]).

At 30 years after CIS, the risk of reaching EDSS 3.0 was higher in the medium risk (hazard ratio, 3.0 versus low risk) and in the high risk group (HR, 8.3 versus low risk). At 10 years, the low risk group had a 40% risk of fulfilling McDonald 2017 criteria, versus 89% in the intermediate group, and 98% in the high risk group. A similar relationship was seen for SPMS (1%, 8%, 16%) and PIRA (17%, 26%, 35%).

At 10 years, the estimated accumulated T2 lesions was 7 in the low-risk group (95% CI, 5-9), 15 in the medium-risk group (95% CI, 12-17), and 21 in the high-risk group (95% CI, 15-27).

Compared with the low- and medium-risk groups, the high-risk group had lower brain parenchymal fraction and gray-matter fraction at 5 years. They also experienced higher stigma, had worse perception of upper and lower limb function as measured by Neuro QoL, and had worse cognitive performance.

Dr. Tintoré has received compensation for consulting services and speaking honoraria from Aimirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Janssen, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Teva Pharmaceuticals, and Viela Bio. Dr. Coyle has no relevant disclosures.

The Barcelona baseline risk score predicted progression of multiple sclerosis (MS) in patients by assigning them to low-, medium-, and high-risk groups. The high-risk group had the shortest time to progression to an Expanded Disability Status Score (EDSS) of 3.0, and were also more likely to progress by MRI and quality of life measures.

The ranking is based on sex, age at the first clinically isolated syndrome, CIS topography, the number of T2 lesions, and the presence of infratentorial and spinal cord lesions, contrast-enhancing lesions, and oligoclonal bands.

“What we wanted to do is merge all of the different prognostic variables for one single patient into one single score,” said Mar Tintoré, MD, PhD, in an interview. Dr. Tintoré is a professor of neurology at Vall d’Hebron University Hospital in Barcelona and a senior consultant at the Multiple Sclerosis Centre of Catalonia (Cemcat). Dr. Tintoré presented the results of the study at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

The three groups had different outcomes in MRI, clinical factors, and MRI scans, and quality of life outcomes over the course of their disease. “So this is a confirmation that this classification at baseline is really meaningful,” Dr. Tintoré said in an interview.

She attributed the success of the model to its reliance on multiple factors, but it is also designed to be simple to use. “We have been trying to use it with simple factors, [information] that you always have, like age, sex, gender, number of lesions, and topography of the region. Everybody has this information at their desk.”
 

Proof of concept

The study validates the approach that neurologists already utilize, according to Patricia Coyle, MD, who moderated the session. “I think the prospective study is a really unique and powerful concept,” said Dr. Coyle, who is a professor of neurology, vice chair of neurology, and director of the Stony Brook (N.Y.) Comprehensive Care Center.

The new study “kind of confirmed their concept of the initial rating, judging long-term disability progression measures in subsets. They also looked at brain atrophy, they looked at gray-matter atrophy, and that also traveled with these three different groups of severity. So it kind of gives value to looking at prognostic indicators at a first attack,” said Dr. Coyle.

The results also validate the Barcelona group’s heavy emphasis on MRI, which Dr. Coyle pointed out is common practice. “If the brain MRI looks very bad, if there are a lot of spinal cord lesions, then that’s somebody we’re much more worried about.”

Once the model is confirmed in other cohorts, the researchers plan to release the model as a generally available algorithm that clinicians could use to help manage patients. Dr. Tintoré pointed out the debate over when to begin a patient on high-efficacy disease-modifying therapies. That choice depends on a lot of factors, including patient choice, safety, and comorbidities. “But knowing that your patient is at risk of having a bad prognosis is something that is helpful” in that decision-making process, she said.
 

Predicting time to EDSS 3.0

The researchers used the Barcelona CIS cohort to build a Weibull survival regression in order to estimate the median time to EDSS 3.0. The model produced three categories with widely divergent predicted times from CIS to EDSS 3.0: low risk, medium risk, and high risk.

In the current report, the researchers compared the model to a “360 degree” measure of measures in 1,308 patients, including clinical milestones (McDonald 2017 MS, confirmed secondary progressive MS, progression independent of relapse activity [PIRA], EDSS disability, number of T2 MRI lesions and brain atrophy, and Patient Reported Outcomes for MS [walking speed, manual dexterity, processing speed, and contrast sensitivity]).

At 30 years after CIS, the risk of reaching EDSS 3.0 was higher in the medium risk (hazard ratio, 3.0 versus low risk) and in the high risk group (HR, 8.3 versus low risk). At 10 years, the low risk group had a 40% risk of fulfilling McDonald 2017 criteria, versus 89% in the intermediate group, and 98% in the high risk group. A similar relationship was seen for SPMS (1%, 8%, 16%) and PIRA (17%, 26%, 35%).

At 10 years, the estimated accumulated T2 lesions was 7 in the low-risk group (95% CI, 5-9), 15 in the medium-risk group (95% CI, 12-17), and 21 in the high-risk group (95% CI, 15-27).

Compared with the low- and medium-risk groups, the high-risk group had lower brain parenchymal fraction and gray-matter fraction at 5 years. They also experienced higher stigma, had worse perception of upper and lower limb function as measured by Neuro QoL, and had worse cognitive performance.

Dr. Tintoré has received compensation for consulting services and speaking honoraria from Aimirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Janssen, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Teva Pharmaceuticals, and Viela Bio. Dr. Coyle has no relevant disclosures.

Add-on treatment with dupilumab may improve lung function in children aged 6-11 years with uncontrolled moderate to severe type 2 inflammatory asthma, results from a randomized, placebo-controlled, phase 3 study show.

Improvements in lung function parameters were observed as early as 2 weeks and persisted over the 52-week treatment period among children in the LIBERTY ASTHMA VOYAGE study, according to investigator Leonard B. Bacharier, MD, of Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center, Nashville, Tenn.

“Dupilumab led to clinically meaningful rapid and sustained improvements in lung function parameters,” Dr. Bacharier said in an online poster presentation at the annual meeting of the American College of Chest Physicians, held virtually this year.

The improvements in forced expiratory volume in 1 second (FEV₁) and other measures reported for children with moderate to severe asthma who have the type 2 phenotype, which is the most common driver of pediatric asthma, according to Dr. Bacharier.

“Many children with moderate to severe asthma have abnormal lung function, and this can be a risk factor for future lung disease in adulthood,” Dr. Bacharier said in his presentation.
 

The VOYAGE continues

The findings presented at the meeting build on another report earlier this year from the LIBERTY ASTHMA VOYAGE study demonstrating that add-on dupilumab treatment led to a significant improvement versus placebo in FEV₁ up to 12 weeks.

“We now have a long term data on this drug as well, showing its efficacy over a period of time,” said Muhammad Adrish, MD, MBA, FCCP, associate professor of pulmonary, critical care and sleep medicine at Baylor College of Medicine, Houston.

“I think that’s pretty exciting, and that’s another step towards precision medicine in treatment of asthma,” Dr. Adrish, who is Vice-Chair of CHEST’s Airways Disorders NetWork Steering Committee and was not involved in the study.

Dupilumab received Food and Drug Administration approval in 2018 as add-on maintenance therapy for the treatment of patients aged 12 years or older with moderate to severe asthma that has an eosinophilic phenotype or that is dependent on oral corticosteroid treatment.

In March 2021, Sanofi and Regeneron announced that the FDA had accepted for review a supplemental Biologics License Application for dupilumab as an add-on treatment in children aged 6-11 years with uncontrolled moderate to severe asthma.

That sBLA is supported by data from the LIBERTY ASTHMA VOYAGE study, Sanofi and Regeneron said.

In results of the phase 3 study that Dr. Bacharier presented in May at the American Thoracic Society International Conference, add-on dupilumab dosed every 2 weeks significant improved percent predicted prebronchodilator FEV₁ by an additional 5.21 percentage points versus placebo at week 12.
 

Dupilumab and the type 2 phenotype

The new data reported at the CHEST meeting come from a prespecified analysis evaluating the impact of dupilumab on lung function over a 52-week treatment period in patients with a T2 inflammatory asthma phenotype.

“Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and -13, key and central drivers of T2 inflammation in multiple diseases,” Dr. Bacharier and coinvestigators reported in their study abstract.

Of 408 patients in the study, 350 met the T2 phenotype criteria, including 236 in the dupilumab arm and 114 in the placebo arm.

Patients met T2 phenotype criteria if they had blood eosinophils of at least 150 cells/mcL or fractional exhaled nitric oxide FeNO of at least 20 parts per billion at baseline, investigators said.

Dr. Bacharier and coinvestigators reported on several different endpoints, including absolute and percent predicted prebronchodilator FEV₁, percent predicted postbronchodilator FEV₁, prebronchodilator forced expiratory flow at 25%-75% of pulmonary volume (FEF_25%-75%), and forced vital capacity (FVC).

Dupilumab, when compared with placebo, significantly improved prebronchodilator FEV₁ in pediatric patients with uncontrolled moderate to severe type 2 asthma, according to Dr. Bacharier.

“Patients receiving dupilumab experienced rapid improvements by week 2, and this was sustained for up to 52 weeks,” he said.

The prebronchodilator FEV₁ improved from baseline for dupilumab versus placebo, with a least squares mean difference of 0.06 L at week 2, which reached 0.17 L by week 52, according to their data. Similarly, postbronchodilator FEV₁ improved from baseline for dupilumab, with a least square mean difference versus placebo of 0.09 L at week 52.

Dupilumab compared to placebo also significantly improved percent predicted FEF_25%-75%, and percent predicted FVC over the 52-week treatment period, according to Dr. Bacharier.

“Dupilumab led to significant, rapid, and sustained improvements in multiple aspects of lung function in children aged 6-11 years,” Dr. Bacharier added in a CHEST press release that described the findings.

The LIBERTY ASTHMA VOYAGE study was sponsored by Sanofi and Regeneron Pharmaceuticals. Dr. Bacharier provided disclosures related to AstraZeneca, GlaxoSmithKline, Regeneron Pharmaceuticals, Sanofi, CF Foundation, DBV Technologies, NIH, and Vectura.

Add-on treatment with dupilumab may improve lung function in children aged 6-11 years with uncontrolled moderate to severe type 2 inflammatory asthma, results from a randomized, placebo-controlled, phase 3 study show.

Improvements in lung function parameters were observed as early as 2 weeks and persisted over the 52-week treatment period among children in the LIBERTY ASTHMA VOYAGE study, according to investigator Leonard B. Bacharier, MD, of Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center, Nashville, Tenn.

“Dupilumab led to clinically meaningful rapid and sustained improvements in lung function parameters,” Dr. Bacharier said in an online poster presentation at the annual meeting of the American College of Chest Physicians, held virtually this year.

The improvements in forced expiratory volume in 1 second (FEV₁) and other measures reported for children with moderate to severe asthma who have the type 2 phenotype, which is the most common driver of pediatric asthma, according to Dr. Bacharier.

“Many children with moderate to severe asthma have abnormal lung function, and this can be a risk factor for future lung disease in adulthood,” Dr. Bacharier said in his presentation.
 

The VOYAGE continues

The findings presented at the meeting build on another report earlier this year from the LIBERTY ASTHMA VOYAGE study demonstrating that add-on dupilumab treatment led to a significant improvement versus placebo in FEV₁ up to 12 weeks.

“We now have a long term data on this drug as well, showing its efficacy over a period of time,” said Muhammad Adrish, MD, MBA, FCCP, associate professor of pulmonary, critical care and sleep medicine at Baylor College of Medicine, Houston.

“I think that’s pretty exciting, and that’s another step towards precision medicine in treatment of asthma,” Dr. Adrish, who is Vice-Chair of CHEST’s Airways Disorders NetWork Steering Committee and was not involved in the study.

Dupilumab received Food and Drug Administration approval in 2018 as add-on maintenance therapy for the treatment of patients aged 12 years or older with moderate to severe asthma that has an eosinophilic phenotype or that is dependent on oral corticosteroid treatment.

In March 2021, Sanofi and Regeneron announced that the FDA had accepted for review a supplemental Biologics License Application for dupilumab as an add-on treatment in children aged 6-11 years with uncontrolled moderate to severe asthma.

That sBLA is supported by data from the LIBERTY ASTHMA VOYAGE study, Sanofi and Regeneron said.

In results of the phase 3 study that Dr. Bacharier presented in May at the American Thoracic Society International Conference, add-on dupilumab dosed every 2 weeks significant improved percent predicted prebronchodilator FEV₁ by an additional 5.21 percentage points versus placebo at week 12.
 

Dupilumab and the type 2 phenotype

The new data reported at the CHEST meeting come from a prespecified analysis evaluating the impact of dupilumab on lung function over a 52-week treatment period in patients with a T2 inflammatory asthma phenotype.

“Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and -13, key and central drivers of T2 inflammation in multiple diseases,” Dr. Bacharier and coinvestigators reported in their study abstract.

Of 408 patients in the study, 350 met the T2 phenotype criteria, including 236 in the dupilumab arm and 114 in the placebo arm.

Patients met T2 phenotype criteria if they had blood eosinophils of at least 150 cells/mcL or fractional exhaled nitric oxide FeNO of at least 20 parts per billion at baseline, investigators said.

Dr. Bacharier and coinvestigators reported on several different endpoints, including absolute and percent predicted prebronchodilator FEV₁, percent predicted postbronchodilator FEV₁, prebronchodilator forced expiratory flow at 25%-75% of pulmonary volume (FEF_25%-75%), and forced vital capacity (FVC).

Dupilumab, when compared with placebo, significantly improved prebronchodilator FEV₁ in pediatric patients with uncontrolled moderate to severe type 2 asthma, according to Dr. Bacharier.

“Patients receiving dupilumab experienced rapid improvements by week 2, and this was sustained for up to 52 weeks,” he said.

The prebronchodilator FEV₁ improved from baseline for dupilumab versus placebo, with a least squares mean difference of 0.06 L at week 2, which reached 0.17 L by week 52, according to their data. Similarly, postbronchodilator FEV₁ improved from baseline for dupilumab, with a least square mean difference versus placebo of 0.09 L at week 52.

Dupilumab compared to placebo also significantly improved percent predicted FEF_25%-75%, and percent predicted FVC over the 52-week treatment period, according to Dr. Bacharier.

“Dupilumab led to significant, rapid, and sustained improvements in multiple aspects of lung function in children aged 6-11 years,” Dr. Bacharier added in a CHEST press release that described the findings.

The LIBERTY ASTHMA VOYAGE study was sponsored by Sanofi and Regeneron Pharmaceuticals. Dr. Bacharier provided disclosures related to AstraZeneca, GlaxoSmithKline, Regeneron Pharmaceuticals, Sanofi, CF Foundation, DBV Technologies, NIH, and Vectura.

Add-on treatment with dupilumab may improve lung function in children aged 6-11 years with uncontrolled moderate to severe type 2 inflammatory asthma, results from a randomized, placebo-controlled, phase 3 study show.

Improvements in lung function parameters were observed as early as 2 weeks and persisted over the 52-week treatment period among children in the LIBERTY ASTHMA VOYAGE study, according to investigator Leonard B. Bacharier, MD, of Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center, Nashville, Tenn.

“Dupilumab led to clinically meaningful rapid and sustained improvements in lung function parameters,” Dr. Bacharier said in an online poster presentation at the annual meeting of the American College of Chest Physicians, held virtually this year.

The improvements in forced expiratory volume in 1 second (FEV₁) and other measures reported for children with moderate to severe asthma who have the type 2 phenotype, which is the most common driver of pediatric asthma, according to Dr. Bacharier.

“Many children with moderate to severe asthma have abnormal lung function, and this can be a risk factor for future lung disease in adulthood,” Dr. Bacharier said in his presentation.
 

The VOYAGE continues

The findings presented at the meeting build on another report earlier this year from the LIBERTY ASTHMA VOYAGE study demonstrating that add-on dupilumab treatment led to a significant improvement versus placebo in FEV₁ up to 12 weeks.

“We now have a long term data on this drug as well, showing its efficacy over a period of time,” said Muhammad Adrish, MD, MBA, FCCP, associate professor of pulmonary, critical care and sleep medicine at Baylor College of Medicine, Houston.

“I think that’s pretty exciting, and that’s another step towards precision medicine in treatment of asthma,” Dr. Adrish, who is Vice-Chair of CHEST’s Airways Disorders NetWork Steering Committee and was not involved in the study.

Dupilumab received Food and Drug Administration approval in 2018 as add-on maintenance therapy for the treatment of patients aged 12 years or older with moderate to severe asthma that has an eosinophilic phenotype or that is dependent on oral corticosteroid treatment.

In March 2021, Sanofi and Regeneron announced that the FDA had accepted for review a supplemental Biologics License Application for dupilumab as an add-on treatment in children aged 6-11 years with uncontrolled moderate to severe asthma.

That sBLA is supported by data from the LIBERTY ASTHMA VOYAGE study, Sanofi and Regeneron said.

In results of the phase 3 study that Dr. Bacharier presented in May at the American Thoracic Society International Conference, add-on dupilumab dosed every 2 weeks significant improved percent predicted prebronchodilator FEV₁ by an additional 5.21 percentage points versus placebo at week 12.
 

Dupilumab and the type 2 phenotype

The new data reported at the CHEST meeting come from a prespecified analysis evaluating the impact of dupilumab on lung function over a 52-week treatment period in patients with a T2 inflammatory asthma phenotype.

“Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and -13, key and central drivers of T2 inflammation in multiple diseases,” Dr. Bacharier and coinvestigators reported in their study abstract.

Of 408 patients in the study, 350 met the T2 phenotype criteria, including 236 in the dupilumab arm and 114 in the placebo arm.

Patients met T2 phenotype criteria if they had blood eosinophils of at least 150 cells/mcL or fractional exhaled nitric oxide FeNO of at least 20 parts per billion at baseline, investigators said.

Dr. Bacharier and coinvestigators reported on several different endpoints, including absolute and percent predicted prebronchodilator FEV₁, percent predicted postbronchodilator FEV₁, prebronchodilator forced expiratory flow at 25%-75% of pulmonary volume (FEF_25%-75%), and forced vital capacity (FVC).

Dupilumab, when compared with placebo, significantly improved prebronchodilator FEV₁ in pediatric patients with uncontrolled moderate to severe type 2 asthma, according to Dr. Bacharier.

“Patients receiving dupilumab experienced rapid improvements by week 2, and this was sustained for up to 52 weeks,” he said.

The prebronchodilator FEV₁ improved from baseline for dupilumab versus placebo, with a least squares mean difference of 0.06 L at week 2, which reached 0.17 L by week 52, according to their data. Similarly, postbronchodilator FEV₁ improved from baseline for dupilumab, with a least square mean difference versus placebo of 0.09 L at week 52.

Dupilumab compared to placebo also significantly improved percent predicted FEF_25%-75%, and percent predicted FVC over the 52-week treatment period, according to Dr. Bacharier.

“Dupilumab led to significant, rapid, and sustained improvements in multiple aspects of lung function in children aged 6-11 years,” Dr. Bacharier added in a CHEST press release that described the findings.

The LIBERTY ASTHMA VOYAGE study was sponsored by Sanofi and Regeneron Pharmaceuticals. Dr. Bacharier provided disclosures related to AstraZeneca, GlaxoSmithKline, Regeneron Pharmaceuticals, Sanofi, CF Foundation, DBV Technologies, NIH, and Vectura.

Adverse event rates were similarly low overall for women delivering at home or at community birth centers, based on data from a retrospective study of more than 10,000 births.

Increasing numbers of women in the United States are choosing to give birth at home or in freestanding out-of-hospital birth centers, prompted by high patient satisfaction and low intervention, wrote Elizabeth Nethery, MSc, MSM, of the University of British Columbia, Vancouver, and colleagues. Although data from other countries with well-integrated midwifery show no significant difference in outcomes between home or community births and hospital births, data in the United States are limited, and some studies have shown an increase in perinatal mortality for home births, the researchers said.

“ACOG identified elements for safe planned home birth: high degree of integration of midwives, education meeting International Confederation of Midwives standards, ready access to consultation and transfer, and ‘appropriate selection of candidates,’ all of which are present in Washington State,” the researchers wrote.

In a study published in Obstetrics & Gynecology, the researchers reviewed outcomes for 10,609 births attended by members of a professional midwifery association in Washington State between Jan. 1, 2015, and June 30, 2020. Of these, 40.9% (4,344) were planned to take place at home and 59.1% (6,265) were planned to take place at birth centers. The births were attended by a total of 139 midwives. A majority (84%) of the women planning a home or community center birth were White non-Hispanic, and 64% were multiparous.

Overall, 86% of the women gave birth in the location of their choice. Intrapartum transfers to hospitals were significantly more likely for nulliparous women, compared with multiparous women (30.5% vs. 4.2%). However, the cesarean birth rates were not significantly different based on birth location (11% for nulliparous women vs. 1% for multiparous women overall), and maternal and neonatal outcomes were similar for home births and birth center births.

Approximately two-thirds (66%) of the women who transferred to a hospital had a vaginal birth, including 37% of nulliparous women and 20% of multiparous women.

Overall perinatal mortality after the onset of labor and within 7 days was 0.57 per 1,000 births, which was similar to rates seen in other high-income countries with established systems for community birth and midwifery, the researchers noted.

“This large study population of planned home and planned birth center births in a single state with well-integrated midwifery enabled our study to overcome previous limitations to studying planned community births in the United States,” they said.

The study findings were limited by several other factors, notably the inclusion only of members of the Midwives’ Association of Washington State, the researchers said. Although demographics of the women in the study were similar to those in other states, the results may not be generalizable to other states with different programs for training midwives or to a more diverse population; however, better integration of community midwives in the United States overall could lead to comparable outcomes in other states, the researchers concluded.

Birth location should be an informed decision

The current study takes on the controversial topic of safety differences between planned birth locations, wrote Julia C. Phillippi, PhD, CNM, of Vanderbilt University, Nashville, Tenn., in an accompanying editorial.

“Rates of community birth in the United States have increased by 85% since 2004, to more than 62,000 births in 2017, and thousands more individuals planned community births but needed transfer to hospital care,” she said. The interest in and use of home or community births may have increased in the wake of the COVID-19 pandemic as families considered the perceived risks of being in a hospital, she noted.

“There is broad consensus among U.S. perinatal and neonatal health care leadership that informed choice should be a cornerstone of maternity care,” Dr. Phillippi emphasized. Although outcomes were favorable for most patients using community or home birth options in the current study, the selection criteria encouraged only low-risk women to plan home or community births, and they were not compared directly to outcomes for low-risk patients in planned hospital birth settings, she noted.

“Evidence-based information about systems-level and individual characteristics associated with safe, physiologic birth can be helpful in assisting individuals planning location of birth – in terms of selecting hospital birth or opting for community birth if key safety provisions are met,” said Dr. Phillippi. However, “For community birth to have favorable outcomes, systems need open channels for transfer when laboring individuals are no longer low risk or require interventions,” she added.

Larger, prospective studies and ongoing risk assessment is needed to support informed decision-making, said Dr. Phillippi. Publicizing safety considerations and developing transfer pathways can not only improve patient satisfaction, but also reduce preventable perinatal morbidity and mortality, she concluded.
 

Patient selection is key to successful community birth

The current study is important at this time because of the relatively limited evidence on outcomes with planned community births in the United States, said Iris Krishna, MD, of Emory University, Atlanta, in an interview.

“Most information available is based on observational studies, as is the case with this study, and it is important to continue to add to growing literature,” she said.

Overall, Dr. Krishna said she was not surprised by the study findings. “In the well-selected, low-risk patient with a certified or licensed nurse-midwife, a low rate of adverse outcomes is to be expected,” she said.

“Strict criteria are necessary to guide selection of appropriate candidates for planned community birth to reduce the risk of adverse maternal and/or fetal outcomes,” Dr. Krishna added. “In the appropriately selected low-risk patient with a certified or licensed nurse-midwife, a favorable outcome is achievable. It is also important to have ready access to safe and timely transport to nearby hospitals,” she noted.

“Physicians should counsel patients contemplating a planned community birth that available data may not be generalizable to all birth settings in the United States or to all patients,” Dr. Krishna emphasized. “For example, this cohort is predominantly non-Hispanic White patients, which typically have lower rates of adverse perinatal events in comparison to other ethnicities,” she explained.

“More research is needed, and in particular research comparing planned community births with planned hospital births in the appropriately selected low-risk patient,” Dr. Krishna said.

The study received no outside funding. Lead author Ms. Nethery disclosed support from a Canadian Vanier Graduate Scholarship. The researchers had no financial conflicts to disclose. Dr. Phillippi had no financial conflicts to disclose. Dr. Krishna had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Ob.Gyn News.

Adverse event rates were similarly low overall for women delivering at home or at community birth centers, based on data from a retrospective study of more than 10,000 births.

Increasing numbers of women in the United States are choosing to give birth at home or in freestanding out-of-hospital birth centers, prompted by high patient satisfaction and low intervention, wrote Elizabeth Nethery, MSc, MSM, of the University of British Columbia, Vancouver, and colleagues. Although data from other countries with well-integrated midwifery show no significant difference in outcomes between home or community births and hospital births, data in the United States are limited, and some studies have shown an increase in perinatal mortality for home births, the researchers said.

“ACOG identified elements for safe planned home birth: high degree of integration of midwives, education meeting International Confederation of Midwives standards, ready access to consultation and transfer, and ‘appropriate selection of candidates,’ all of which are present in Washington State,” the researchers wrote.

In a study published in Obstetrics & Gynecology, the researchers reviewed outcomes for 10,609 births attended by members of a professional midwifery association in Washington State between Jan. 1, 2015, and June 30, 2020. Of these, 40.9% (4,344) were planned to take place at home and 59.1% (6,265) were planned to take place at birth centers. The births were attended by a total of 139 midwives. A majority (84%) of the women planning a home or community center birth were White non-Hispanic, and 64% were multiparous.

Overall, 86% of the women gave birth in the location of their choice. Intrapartum transfers to hospitals were significantly more likely for nulliparous women, compared with multiparous women (30.5% vs. 4.2%). However, the cesarean birth rates were not significantly different based on birth location (11% for nulliparous women vs. 1% for multiparous women overall), and maternal and neonatal outcomes were similar for home births and birth center births.

Approximately two-thirds (66%) of the women who transferred to a hospital had a vaginal birth, including 37% of nulliparous women and 20% of multiparous women.

Overall perinatal mortality after the onset of labor and within 7 days was 0.57 per 1,000 births, which was similar to rates seen in other high-income countries with established systems for community birth and midwifery, the researchers noted.

“This large study population of planned home and planned birth center births in a single state with well-integrated midwifery enabled our study to overcome previous limitations to studying planned community births in the United States,” they said.

The study findings were limited by several other factors, notably the inclusion only of members of the Midwives’ Association of Washington State, the researchers said. Although demographics of the women in the study were similar to those in other states, the results may not be generalizable to other states with different programs for training midwives or to a more diverse population; however, better integration of community midwives in the United States overall could lead to comparable outcomes in other states, the researchers concluded.

Birth location should be an informed decision

The current study takes on the controversial topic of safety differences between planned birth locations, wrote Julia C. Phillippi, PhD, CNM, of Vanderbilt University, Nashville, Tenn., in an accompanying editorial.

“Rates of community birth in the United States have increased by 85% since 2004, to more than 62,000 births in 2017, and thousands more individuals planned community births but needed transfer to hospital care,” she said. The interest in and use of home or community births may have increased in the wake of the COVID-19 pandemic as families considered the perceived risks of being in a hospital, she noted.

“There is broad consensus among U.S. perinatal and neonatal health care leadership that informed choice should be a cornerstone of maternity care,” Dr. Phillippi emphasized. Although outcomes were favorable for most patients using community or home birth options in the current study, the selection criteria encouraged only low-risk women to plan home or community births, and they were not compared directly to outcomes for low-risk patients in planned hospital birth settings, she noted.

“Evidence-based information about systems-level and individual characteristics associated with safe, physiologic birth can be helpful in assisting individuals planning location of birth – in terms of selecting hospital birth or opting for community birth if key safety provisions are met,” said Dr. Phillippi. However, “For community birth to have favorable outcomes, systems need open channels for transfer when laboring individuals are no longer low risk or require interventions,” she added.

Larger, prospective studies and ongoing risk assessment is needed to support informed decision-making, said Dr. Phillippi. Publicizing safety considerations and developing transfer pathways can not only improve patient satisfaction, but also reduce preventable perinatal morbidity and mortality, she concluded.
 

Patient selection is key to successful community birth

The current study is important at this time because of the relatively limited evidence on outcomes with planned community births in the United States, said Iris Krishna, MD, of Emory University, Atlanta, in an interview.

“Most information available is based on observational studies, as is the case with this study, and it is important to continue to add to growing literature,” she said.

Overall, Dr. Krishna said she was not surprised by the study findings. “In the well-selected, low-risk patient with a certified or licensed nurse-midwife, a low rate of adverse outcomes is to be expected,” she said.

“Strict criteria are necessary to guide selection of appropriate candidates for planned community birth to reduce the risk of adverse maternal and/or fetal outcomes,” Dr. Krishna added. “In the appropriately selected low-risk patient with a certified or licensed nurse-midwife, a favorable outcome is achievable. It is also important to have ready access to safe and timely transport to nearby hospitals,” she noted.

“Physicians should counsel patients contemplating a planned community birth that available data may not be generalizable to all birth settings in the United States or to all patients,” Dr. Krishna emphasized. “For example, this cohort is predominantly non-Hispanic White patients, which typically have lower rates of adverse perinatal events in comparison to other ethnicities,” she explained.

“More research is needed, and in particular research comparing planned community births with planned hospital births in the appropriately selected low-risk patient,” Dr. Krishna said.

The study received no outside funding. Lead author Ms. Nethery disclosed support from a Canadian Vanier Graduate Scholarship. The researchers had no financial conflicts to disclose. Dr. Phillippi had no financial conflicts to disclose. Dr. Krishna had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Ob.Gyn News.

Adverse event rates were similarly low overall for women delivering at home or at community birth centers, based on data from a retrospective study of more than 10,000 births.

Increasing numbers of women in the United States are choosing to give birth at home or in freestanding out-of-hospital birth centers, prompted by high patient satisfaction and low intervention, wrote Elizabeth Nethery, MSc, MSM, of the University of British Columbia, Vancouver, and colleagues. Although data from other countries with well-integrated midwifery show no significant difference in outcomes between home or community births and hospital births, data in the United States are limited, and some studies have shown an increase in perinatal mortality for home births, the researchers said.

“ACOG identified elements for safe planned home birth: high degree of integration of midwives, education meeting International Confederation of Midwives standards, ready access to consultation and transfer, and ‘appropriate selection of candidates,’ all of which are present in Washington State,” the researchers wrote.

In a study published in Obstetrics & Gynecology, the researchers reviewed outcomes for 10,609 births attended by members of a professional midwifery association in Washington State between Jan. 1, 2015, and June 30, 2020. Of these, 40.9% (4,344) were planned to take place at home and 59.1% (6,265) were planned to take place at birth centers. The births were attended by a total of 139 midwives. A majority (84%) of the women planning a home or community center birth were White non-Hispanic, and 64% were multiparous.

Overall, 86% of the women gave birth in the location of their choice. Intrapartum transfers to hospitals were significantly more likely for nulliparous women, compared with multiparous women (30.5% vs. 4.2%). However, the cesarean birth rates were not significantly different based on birth location (11% for nulliparous women vs. 1% for multiparous women overall), and maternal and neonatal outcomes were similar for home births and birth center births.

Approximately two-thirds (66%) of the women who transferred to a hospital had a vaginal birth, including 37% of nulliparous women and 20% of multiparous women.

Overall perinatal mortality after the onset of labor and within 7 days was 0.57 per 1,000 births, which was similar to rates seen in other high-income countries with established systems for community birth and midwifery, the researchers noted.

“This large study population of planned home and planned birth center births in a single state with well-integrated midwifery enabled our study to overcome previous limitations to studying planned community births in the United States,” they said.

The study findings were limited by several other factors, notably the inclusion only of members of the Midwives’ Association of Washington State, the researchers said. Although demographics of the women in the study were similar to those in other states, the results may not be generalizable to other states with different programs for training midwives or to a more diverse population; however, better integration of community midwives in the United States overall could lead to comparable outcomes in other states, the researchers concluded.

Birth location should be an informed decision

The current study takes on the controversial topic of safety differences between planned birth locations, wrote Julia C. Phillippi, PhD, CNM, of Vanderbilt University, Nashville, Tenn., in an accompanying editorial.

“Rates of community birth in the United States have increased by 85% since 2004, to more than 62,000 births in 2017, and thousands more individuals planned community births but needed transfer to hospital care,” she said. The interest in and use of home or community births may have increased in the wake of the COVID-19 pandemic as families considered the perceived risks of being in a hospital, she noted.

“There is broad consensus among U.S. perinatal and neonatal health care leadership that informed choice should be a cornerstone of maternity care,” Dr. Phillippi emphasized. Although outcomes were favorable for most patients using community or home birth options in the current study, the selection criteria encouraged only low-risk women to plan home or community births, and they were not compared directly to outcomes for low-risk patients in planned hospital birth settings, she noted.

“Evidence-based information about systems-level and individual characteristics associated with safe, physiologic birth can be helpful in assisting individuals planning location of birth – in terms of selecting hospital birth or opting for community birth if key safety provisions are met,” said Dr. Phillippi. However, “For community birth to have favorable outcomes, systems need open channels for transfer when laboring individuals are no longer low risk or require interventions,” she added.

Larger, prospective studies and ongoing risk assessment is needed to support informed decision-making, said Dr. Phillippi. Publicizing safety considerations and developing transfer pathways can not only improve patient satisfaction, but also reduce preventable perinatal morbidity and mortality, she concluded.
 

Patient selection is key to successful community birth

The current study is important at this time because of the relatively limited evidence on outcomes with planned community births in the United States, said Iris Krishna, MD, of Emory University, Atlanta, in an interview.

“Most information available is based on observational studies, as is the case with this study, and it is important to continue to add to growing literature,” she said.

Overall, Dr. Krishna said she was not surprised by the study findings. “In the well-selected, low-risk patient with a certified or licensed nurse-midwife, a low rate of adverse outcomes is to be expected,” she said.

“Strict criteria are necessary to guide selection of appropriate candidates for planned community birth to reduce the risk of adverse maternal and/or fetal outcomes,” Dr. Krishna added. “In the appropriately selected low-risk patient with a certified or licensed nurse-midwife, a favorable outcome is achievable. It is also important to have ready access to safe and timely transport to nearby hospitals,” she noted.

“Physicians should counsel patients contemplating a planned community birth that available data may not be generalizable to all birth settings in the United States or to all patients,” Dr. Krishna emphasized. “For example, this cohort is predominantly non-Hispanic White patients, which typically have lower rates of adverse perinatal events in comparison to other ethnicities,” she explained.

“More research is needed, and in particular research comparing planned community births with planned hospital births in the appropriately selected low-risk patient,” Dr. Krishna said.

The study received no outside funding. Lead author Ms. Nethery disclosed support from a Canadian Vanier Graduate Scholarship. The researchers had no financial conflicts to disclose. Dr. Phillippi had no financial conflicts to disclose. Dr. Krishna had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Ob.Gyn News.

Physician employment contracts include some new dangers. This includes physicians taking a new job, but it also includes already-employed doctors who are being asked to resign a new contract that contains new conditions. A number of these new clauses have arisen because of COVID-19. When the pandemic dramatically reduced patient flow, many employers didn’t have enough money to pay doctors and didn’t always have physicians in the right location or practice setting.

Vowing this would never happen again, some employers have rewritten their physician contracts to make it easier to reassign and terminate physicians.

Here are 12 potential land mines in a physician employment contract, some of which were added as a result of the pandemic.
 

You could be immediately terminated without notice

One outcome of the pandemic is the growing use of “force majeure” clauses, which give the employer the right to reduce your compensation or even terminate you due to a natural disaster, which could include COVID.

“COVID made employers aware of the potential impact of disasters on their operations,” said Dan Shay, a health law attorney at Alice Gosfield & Associates in Philadelphia. “Therefore, even as the threat of COVID abates in many places, employers are continuing to put this provision in the contract.”

What can you do? “One way to get some protection is to rule out a termination without cause in the first year,” said Michael A. Cassidy, a physician contract attorney at Tucker Arensberg in Pittsburgh.

The force majeure clause is less likely to affect salary, but could impact bonus and incentive tied to performance. It’s wise to try to specifically limit how much the force majeure could reduce pay tied to performance, and to be prepared to negotiate that aspect of your contract.
 

No protections if you’re let go through no fault of your own

You could lose your job if your employer could not generate enough business and has to let some doctors go. This happened quite often in the early days of the COVID pandemic.

In these situations, the doctor has not done anything wrong to prompt the termination, but the restrictive covenant may still apply, meaning that the doctor would have to leave the area to find work.

What can you do? You’re in a good position to get this changed, said Christopher L. Nuland, a solo physician contract attorney in Jacksonville, Fla. “Many employers recognize that it would be draconian to require a restrictive covenant in this case, and they will agree to modify this provision.”

Similarly, the employer may not cover your tail insurance even if you were let go from your work through no fault of your own. Most malpractice policies for employer physicians require buying an extra policy, called a tail, if you leave. In some cases, the employer won’t provide a tail and will make the departing doctor buy it.

In these cases, “try for a compromise, such as stipulating that the party that caused the termination should pay for the tail,” Mr. Nuland said. “The employer may not agree to anything more than that because they want to set up a disincentive against you leaving.”
 

Employer could unilaterally alter your compensation

Many recent contracts give the employer the option to unilaterally modify compensation, such as changing the base salary or raising the target required for meeting the productivity bonus, said Ericka L. Adler, a physician contract attorney at Roetzel & Andress in Chicago.

Ms. Adler thought this change could have been prompted by employers’ financial problems during the pandemic. In the early months of COVID, many physicians were not making much money for the employer but still had to be paid. So employers added a clause saying they could reduce compensation at any time, she said.

What can you do? Harsh provisions like this often come up in contracts with private equity firms, Mr. Cassidy said. “The contract might say the employer can adjust compensation or even terminate physicians based on productivity or their profitability. And it may say that if they reassign you to a new location and you refuse, they can terminate you.”

“If you can’t get these clauses removed, try to reduce the impact of a termination by providing longer notice periods or by inserting a severance agreement,” Mr. Cassidy said.
 

Accelerating notice for without-cause terminations

Physicians who are convicted of a felony or other moral issue can usually be terminated immediately. But if you are terminated for other reasons – that is, “without cause” – you are given notice at a certain number of days before you have to leave (typically 60-90 days), so that you have time to find a new job.

Some recent contracts, however, allow for very little notice in without-cause terminations, which allows the employer to fire you in as little as 0 days after providing notice, Ms. Adler said.

“This means that, even if 90 days’ notice is provided in the contract, the employer can decide that your last day will be an earlier date,” she said.

Why is this happening? Ms. Adler said employers want to begin reallocating resources and patients as soon as possible. The problem came to employers’ attention during the COVID pandemic, when they were contractually forced to pay doctors for doing little or nothing during the notice period.

What can you do? Possibly not much, other than attempt to negotiate. “Large employers typically don’t want to drop this provision, but at the least, the doctor needs to understand the risk it creates for them,” she said.
 

You could be assigned to far-off locations

As patient care needs changed dramatically during the pandemic, employers needed to reassign doctors to new locations.

Some new contracts allow employers to simply inform the doctor that they are changing the work location. However, “you don’t want to be assigned to a new work location that is 50 miles away,” Mr. Nuland said.

What can you do? Mr. Nuland recommended adding new language saying that, if the new assignment is more than 20 miles away, both parties would have to approve it.

You could end up working too many off-hours

“Most employers won’t issue a specific work schedule,” Mr. Nuland said. “They want the flexibility to assign evening or weekend work, and it would be difficult for a young doctor to change this.”

What can you do? Mr. Nuland recommended trying to set some limits. “You can try to limit off-hours work to two times a month or something like that,” she said. And if you need to have a special schedule, such as not working on Fridays, Adler advises that this should be put into the contract.

If you can’t get anything changed in the contract, Mr. Nuland said the next-best thing is to ask employers to tell you specifically what they plan to do with you. “Most employers will give you an informal idea of what’s expected – maybe not an exact schedule, but it’s quite likely they will honor it.”
 

You wouldn’t be able to work nearby if you left the job

Most contracts have a noncompete clause, also known as a “restrictive covenant,” which prevents employed physicians from working in the area if they left the job.

“Almost every doctor I represent has told me that they’re not concerned about the noncompete clause because, they believe, it is not enforceable anyway,” Ms. Adler said. “This is incorrect.”

Mr. Nuland said the faster pace of job-changing during the pandemic makes it all the more likely that doctors have to deal with a restrictive covenant. At the same time, some employers have been expanding the restriction – either by enlarging the radius where the restriction applies or by making the restriction apply to each of their sites, so that each one has a restricted radius around it.

For example, one contract Mr. Nuland is currently reviewing has a 20-mile radius that in effect becomes a 120-mile radius because the employer is counting four offices.

What can you do? Mr. Nuland advised trying to reduce the impact of the noncompete – for instance, making it apply only to the offices where you worked, or trading more time for less distance. “If you have a 2-year, 20-mile restriction, ask for a 3-year, 10-mile restriction, where the radius could be easier to deal with,” he said.
 

You might end up with too much call

Contracts rarely detail your call schedule because employers want flexibility to expand call as patient care needs change, but you can try adding some specificity, said Sanja Ord, a physician contract attorney at Greensfelder, Hemker & Gale in St. Louis.

Contracts often use wide-open language to describe call, such as simply making it “subject to the house call policies,” Mr. Cassidy said. Language that is more beneficial to the physician would say that call must be “equal” among “similarly situated” physicians.

But Ms. Ord said even provisions for equal call can turn out to be onerous if there are too few doctors in the call roster, so it’s a good idea to find out just how many doctors will be participating in call.

Still, Adler said even that strategy can’t remove all risk. What happens, she asked, if several physicians participating in call decide to leave? Then you might end up with call every other night.

What can you do? Mr. Cassidy recommends specifying a maximum amount of call – for example, no more frequent than one in four nights.
 

Physician must pay for reimbursement claw-backs by payers

When auditors for Medicare or other payers find overpayments after the fact, called a ‘claw-back,’ the provider must pay them back. But which provider has to do that – you or your employer?

In many cases, your employer’s billing office may have introduced the error, but there may be a clause in the contract stating that the physician is solely responsible for all claw-backs. That could be costly.

What can you do? Mr. Shay said the clause should state that you have to pay only when it is the result of your own error or omission, and also not when it was made at the direction of the employer.
 

Some work may be outside of your subspecialty

In some cases, the employer may assign subspecialized doctors to work outside their subspecialty, Mr. Nuland said.

For example, he said he represented an endocrinologist who expected to see only diabetes patients but was assigned to some general internal medicine work as well, and an otolaryngologist client of his who completed a fellowship on facial plastic surgery was expected to do liposuction in a cosmetic surgery group.

What can you do? To prevent this from happening, Mr. Nuland recommends a clause stating that your work will be restricted to your subspecialty.

What the employer promised isn’t in the contract

“Beware of promises that are not in the contract,” Mr. Shay said. “You might feel you can really trust your new boss and what he tells you, but what if that person resigns, or the organization gets a new owner who doesn’t honor unwritten agreements?”

Many contracts have an integration clause, which specifies that the contract constitutes the complete agreement between the two parties, and it nullifies any other oral or written promises made to the physician.

For example, the employer might have promised a relocation bonus and a sign-on bonus, but for some reason it didn’t get into the contract, Ms. Ord said. In those cases, the employer is under no obligation to honor the promise.

What can you do? Mr. Cassidy said it is possible to hold the employer to a commitment made outside the contract. The alternative document, such as an offer letter, has to specifically state that the commitment is protected from the integration clause in the contract, he said, adding: “It is still better to have the commitment put into the contract.”
 

Contract is simply accepted as is

“Generally, the bigger the employer, the less likely they will alter an agreement just to make you happy,” Mr. Shay said.

But even in these contracts, he said there is still opportunity to fix errors and ambiguities that could harm you later – or even alter a provision if you can’t remove it outright.

The back-and-forth is important, Ms. Adler said. “Negotiation means trying to have some control over your job and your life.”

Mr. Cassidy said a big part of contract review is facing up to the possibility that you may have to resign or be let go.

“Many physicians don’t like to think about leaving when they’re just starting a job, but they need to,” he said. “You need to begin with the end in mind. Think about what would happen if this job didn’t work out.”

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

Physician employment contracts include some new dangers. This includes physicians taking a new job, but it also includes already-employed doctors who are being asked to resign a new contract that contains new conditions. A number of these new clauses have arisen because of COVID-19. When the pandemic dramatically reduced patient flow, many employers didn’t have enough money to pay doctors and didn’t always have physicians in the right location or practice setting.

Vowing this would never happen again, some employers have rewritten their physician contracts to make it easier to reassign and terminate physicians.

Here are 12 potential land mines in a physician employment contract, some of which were added as a result of the pandemic.
 

You could be immediately terminated without notice

One outcome of the pandemic is the growing use of “force majeure” clauses, which give the employer the right to reduce your compensation or even terminate you due to a natural disaster, which could include COVID.

“COVID made employers aware of the potential impact of disasters on their operations,” said Dan Shay, a health law attorney at Alice Gosfield & Associates in Philadelphia. “Therefore, even as the threat of COVID abates in many places, employers are continuing to put this provision in the contract.”

What can you do? “One way to get some protection is to rule out a termination without cause in the first year,” said Michael A. Cassidy, a physician contract attorney at Tucker Arensberg in Pittsburgh.

The force majeure clause is less likely to affect salary, but could impact bonus and incentive tied to performance. It’s wise to try to specifically limit how much the force majeure could reduce pay tied to performance, and to be prepared to negotiate that aspect of your contract.
 

No protections if you’re let go through no fault of your own

You could lose your job if your employer could not generate enough business and has to let some doctors go. This happened quite often in the early days of the COVID pandemic.

In these situations, the doctor has not done anything wrong to prompt the termination, but the restrictive covenant may still apply, meaning that the doctor would have to leave the area to find work.

What can you do? You’re in a good position to get this changed, said Christopher L. Nuland, a solo physician contract attorney in Jacksonville, Fla. “Many employers recognize that it would be draconian to require a restrictive covenant in this case, and they will agree to modify this provision.”

Similarly, the employer may not cover your tail insurance even if you were let go from your work through no fault of your own. Most malpractice policies for employer physicians require buying an extra policy, called a tail, if you leave. In some cases, the employer won’t provide a tail and will make the departing doctor buy it.

In these cases, “try for a compromise, such as stipulating that the party that caused the termination should pay for the tail,” Mr. Nuland said. “The employer may not agree to anything more than that because they want to set up a disincentive against you leaving.”
 

Employer could unilaterally alter your compensation

Many recent contracts give the employer the option to unilaterally modify compensation, such as changing the base salary or raising the target required for meeting the productivity bonus, said Ericka L. Adler, a physician contract attorney at Roetzel & Andress in Chicago.

Ms. Adler thought this change could have been prompted by employers’ financial problems during the pandemic. In the early months of COVID, many physicians were not making much money for the employer but still had to be paid. So employers added a clause saying they could reduce compensation at any time, she said.

What can you do? Harsh provisions like this often come up in contracts with private equity firms, Mr. Cassidy said. “The contract might say the employer can adjust compensation or even terminate physicians based on productivity or their profitability. And it may say that if they reassign you to a new location and you refuse, they can terminate you.”

“If you can’t get these clauses removed, try to reduce the impact of a termination by providing longer notice periods or by inserting a severance agreement,” Mr. Cassidy said.
 

Accelerating notice for without-cause terminations

Physicians who are convicted of a felony or other moral issue can usually be terminated immediately. But if you are terminated for other reasons – that is, “without cause” – you are given notice at a certain number of days before you have to leave (typically 60-90 days), so that you have time to find a new job.

Some recent contracts, however, allow for very little notice in without-cause terminations, which allows the employer to fire you in as little as 0 days after providing notice, Ms. Adler said.

“This means that, even if 90 days’ notice is provided in the contract, the employer can decide that your last day will be an earlier date,” she said.

Why is this happening? Ms. Adler said employers want to begin reallocating resources and patients as soon as possible. The problem came to employers’ attention during the COVID pandemic, when they were contractually forced to pay doctors for doing little or nothing during the notice period.

What can you do? Possibly not much, other than attempt to negotiate. “Large employers typically don’t want to drop this provision, but at the least, the doctor needs to understand the risk it creates for them,” she said.
 

You could be assigned to far-off locations

As patient care needs changed dramatically during the pandemic, employers needed to reassign doctors to new locations.

Some new contracts allow employers to simply inform the doctor that they are changing the work location. However, “you don’t want to be assigned to a new work location that is 50 miles away,” Mr. Nuland said.

What can you do? Mr. Nuland recommended adding new language saying that, if the new assignment is more than 20 miles away, both parties would have to approve it.

You could end up working too many off-hours

“Most employers won’t issue a specific work schedule,” Mr. Nuland said. “They want the flexibility to assign evening or weekend work, and it would be difficult for a young doctor to change this.”

What can you do? Mr. Nuland recommended trying to set some limits. “You can try to limit off-hours work to two times a month or something like that,” she said. And if you need to have a special schedule, such as not working on Fridays, Adler advises that this should be put into the contract.

If you can’t get anything changed in the contract, Mr. Nuland said the next-best thing is to ask employers to tell you specifically what they plan to do with you. “Most employers will give you an informal idea of what’s expected – maybe not an exact schedule, but it’s quite likely they will honor it.”
 

You wouldn’t be able to work nearby if you left the job

Most contracts have a noncompete clause, also known as a “restrictive covenant,” which prevents employed physicians from working in the area if they left the job.

“Almost every doctor I represent has told me that they’re not concerned about the noncompete clause because, they believe, it is not enforceable anyway,” Ms. Adler said. “This is incorrect.”

Mr. Nuland said the faster pace of job-changing during the pandemic makes it all the more likely that doctors have to deal with a restrictive covenant. At the same time, some employers have been expanding the restriction – either by enlarging the radius where the restriction applies or by making the restriction apply to each of their sites, so that each one has a restricted radius around it.

For example, one contract Mr. Nuland is currently reviewing has a 20-mile radius that in effect becomes a 120-mile radius because the employer is counting four offices.

What can you do? Mr. Nuland advised trying to reduce the impact of the noncompete – for instance, making it apply only to the offices where you worked, or trading more time for less distance. “If you have a 2-year, 20-mile restriction, ask for a 3-year, 10-mile restriction, where the radius could be easier to deal with,” he said.
 

You might end up with too much call

Contracts rarely detail your call schedule because employers want flexibility to expand call as patient care needs change, but you can try adding some specificity, said Sanja Ord, a physician contract attorney at Greensfelder, Hemker & Gale in St. Louis.

Contracts often use wide-open language to describe call, such as simply making it “subject to the house call policies,” Mr. Cassidy said. Language that is more beneficial to the physician would say that call must be “equal” among “similarly situated” physicians.

But Ms. Ord said even provisions for equal call can turn out to be onerous if there are too few doctors in the call roster, so it’s a good idea to find out just how many doctors will be participating in call.

Still, Adler said even that strategy can’t remove all risk. What happens, she asked, if several physicians participating in call decide to leave? Then you might end up with call every other night.

What can you do? Mr. Cassidy recommends specifying a maximum amount of call – for example, no more frequent than one in four nights.
 

Physician must pay for reimbursement claw-backs by payers

When auditors for Medicare or other payers find overpayments after the fact, called a ‘claw-back,’ the provider must pay them back. But which provider has to do that – you or your employer?

In many cases, your employer’s billing office may have introduced the error, but there may be a clause in the contract stating that the physician is solely responsible for all claw-backs. That could be costly.

What can you do? Mr. Shay said the clause should state that you have to pay only when it is the result of your own error or omission, and also not when it was made at the direction of the employer.
 

Some work may be outside of your subspecialty

In some cases, the employer may assign subspecialized doctors to work outside their subspecialty, Mr. Nuland said.

For example, he said he represented an endocrinologist who expected to see only diabetes patients but was assigned to some general internal medicine work as well, and an otolaryngologist client of his who completed a fellowship on facial plastic surgery was expected to do liposuction in a cosmetic surgery group.

What can you do? To prevent this from happening, Mr. Nuland recommends a clause stating that your work will be restricted to your subspecialty.

What the employer promised isn’t in the contract

“Beware of promises that are not in the contract,” Mr. Shay said. “You might feel you can really trust your new boss and what he tells you, but what if that person resigns, or the organization gets a new owner who doesn’t honor unwritten agreements?”

Many contracts have an integration clause, which specifies that the contract constitutes the complete agreement between the two parties, and it nullifies any other oral or written promises made to the physician.

For example, the employer might have promised a relocation bonus and a sign-on bonus, but for some reason it didn’t get into the contract, Ms. Ord said. In those cases, the employer is under no obligation to honor the promise.

What can you do? Mr. Cassidy said it is possible to hold the employer to a commitment made outside the contract. The alternative document, such as an offer letter, has to specifically state that the commitment is protected from the integration clause in the contract, he said, adding: “It is still better to have the commitment put into the contract.”
 

Contract is simply accepted as is

“Generally, the bigger the employer, the less likely they will alter an agreement just to make you happy,” Mr. Shay said.

But even in these contracts, he said there is still opportunity to fix errors and ambiguities that could harm you later – or even alter a provision if you can’t remove it outright.

The back-and-forth is important, Ms. Adler said. “Negotiation means trying to have some control over your job and your life.”

Mr. Cassidy said a big part of contract review is facing up to the possibility that you may have to resign or be let go.

“Many physicians don’t like to think about leaving when they’re just starting a job, but they need to,” he said. “You need to begin with the end in mind. Think about what would happen if this job didn’t work out.”

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

Physician employment contracts include some new dangers. This includes physicians taking a new job, but it also includes already-employed doctors who are being asked to resign a new contract that contains new conditions. A number of these new clauses have arisen because of COVID-19. When the pandemic dramatically reduced patient flow, many employers didn’t have enough money to pay doctors and didn’t always have physicians in the right location or practice setting.

Vowing this would never happen again, some employers have rewritten their physician contracts to make it easier to reassign and terminate physicians.

Here are 12 potential land mines in a physician employment contract, some of which were added as a result of the pandemic.
 

You could be immediately terminated without notice

One outcome of the pandemic is the growing use of “force majeure” clauses, which give the employer the right to reduce your compensation or even terminate you due to a natural disaster, which could include COVID.

“COVID made employers aware of the potential impact of disasters on their operations,” said Dan Shay, a health law attorney at Alice Gosfield & Associates in Philadelphia. “Therefore, even as the threat of COVID abates in many places, employers are continuing to put this provision in the contract.”

What can you do? “One way to get some protection is to rule out a termination without cause in the first year,” said Michael A. Cassidy, a physician contract attorney at Tucker Arensberg in Pittsburgh.

The force majeure clause is less likely to affect salary, but could impact bonus and incentive tied to performance. It’s wise to try to specifically limit how much the force majeure could reduce pay tied to performance, and to be prepared to negotiate that aspect of your contract.
 

No protections if you’re let go through no fault of your own

You could lose your job if your employer could not generate enough business and has to let some doctors go. This happened quite often in the early days of the COVID pandemic.

In these situations, the doctor has not done anything wrong to prompt the termination, but the restrictive covenant may still apply, meaning that the doctor would have to leave the area to find work.

What can you do? You’re in a good position to get this changed, said Christopher L. Nuland, a solo physician contract attorney in Jacksonville, Fla. “Many employers recognize that it would be draconian to require a restrictive covenant in this case, and they will agree to modify this provision.”

Similarly, the employer may not cover your tail insurance even if you were let go from your work through no fault of your own. Most malpractice policies for employer physicians require buying an extra policy, called a tail, if you leave. In some cases, the employer won’t provide a tail and will make the departing doctor buy it.

In these cases, “try for a compromise, such as stipulating that the party that caused the termination should pay for the tail,” Mr. Nuland said. “The employer may not agree to anything more than that because they want to set up a disincentive against you leaving.”
 

Employer could unilaterally alter your compensation

Many recent contracts give the employer the option to unilaterally modify compensation, such as changing the base salary or raising the target required for meeting the productivity bonus, said Ericka L. Adler, a physician contract attorney at Roetzel & Andress in Chicago.

Ms. Adler thought this change could have been prompted by employers’ financial problems during the pandemic. In the early months of COVID, many physicians were not making much money for the employer but still had to be paid. So employers added a clause saying they could reduce compensation at any time, she said.

What can you do? Harsh provisions like this often come up in contracts with private equity firms, Mr. Cassidy said. “The contract might say the employer can adjust compensation or even terminate physicians based on productivity or their profitability. And it may say that if they reassign you to a new location and you refuse, they can terminate you.”

“If you can’t get these clauses removed, try to reduce the impact of a termination by providing longer notice periods or by inserting a severance agreement,” Mr. Cassidy said.
 

Accelerating notice for without-cause terminations

Physicians who are convicted of a felony or other moral issue can usually be terminated immediately. But if you are terminated for other reasons – that is, “without cause” – you are given notice at a certain number of days before you have to leave (typically 60-90 days), so that you have time to find a new job.

Some recent contracts, however, allow for very little notice in without-cause terminations, which allows the employer to fire you in as little as 0 days after providing notice, Ms. Adler said.

“This means that, even if 90 days’ notice is provided in the contract, the employer can decide that your last day will be an earlier date,” she said.

Why is this happening? Ms. Adler said employers want to begin reallocating resources and patients as soon as possible. The problem came to employers’ attention during the COVID pandemic, when they were contractually forced to pay doctors for doing little or nothing during the notice period.

What can you do? Possibly not much, other than attempt to negotiate. “Large employers typically don’t want to drop this provision, but at the least, the doctor needs to understand the risk it creates for them,” she said.
 

You could be assigned to far-off locations

As patient care needs changed dramatically during the pandemic, employers needed to reassign doctors to new locations.

Some new contracts allow employers to simply inform the doctor that they are changing the work location. However, “you don’t want to be assigned to a new work location that is 50 miles away,” Mr. Nuland said.

What can you do? Mr. Nuland recommended adding new language saying that, if the new assignment is more than 20 miles away, both parties would have to approve it.

You could end up working too many off-hours

“Most employers won’t issue a specific work schedule,” Mr. Nuland said. “They want the flexibility to assign evening or weekend work, and it would be difficult for a young doctor to change this.”

What can you do? Mr. Nuland recommended trying to set some limits. “You can try to limit off-hours work to two times a month or something like that,” she said. And if you need to have a special schedule, such as not working on Fridays, Adler advises that this should be put into the contract.

If you can’t get anything changed in the contract, Mr. Nuland said the next-best thing is to ask employers to tell you specifically what they plan to do with you. “Most employers will give you an informal idea of what’s expected – maybe not an exact schedule, but it’s quite likely they will honor it.”
 

You wouldn’t be able to work nearby if you left the job

Most contracts have a noncompete clause, also known as a “restrictive covenant,” which prevents employed physicians from working in the area if they left the job.

“Almost every doctor I represent has told me that they’re not concerned about the noncompete clause because, they believe, it is not enforceable anyway,” Ms. Adler said. “This is incorrect.”

Mr. Nuland said the faster pace of job-changing during the pandemic makes it all the more likely that doctors have to deal with a restrictive covenant. At the same time, some employers have been expanding the restriction – either by enlarging the radius where the restriction applies or by making the restriction apply to each of their sites, so that each one has a restricted radius around it.

For example, one contract Mr. Nuland is currently reviewing has a 20-mile radius that in effect becomes a 120-mile radius because the employer is counting four offices.

What can you do? Mr. Nuland advised trying to reduce the impact of the noncompete – for instance, making it apply only to the offices where you worked, or trading more time for less distance. “If you have a 2-year, 20-mile restriction, ask for a 3-year, 10-mile restriction, where the radius could be easier to deal with,” he said.
 

You might end up with too much call

Contracts rarely detail your call schedule because employers want flexibility to expand call as patient care needs change, but you can try adding some specificity, said Sanja Ord, a physician contract attorney at Greensfelder, Hemker & Gale in St. Louis.

Contracts often use wide-open language to describe call, such as simply making it “subject to the house call policies,” Mr. Cassidy said. Language that is more beneficial to the physician would say that call must be “equal” among “similarly situated” physicians.

But Ms. Ord said even provisions for equal call can turn out to be onerous if there are too few doctors in the call roster, so it’s a good idea to find out just how many doctors will be participating in call.

Still, Adler said even that strategy can’t remove all risk. What happens, she asked, if several physicians participating in call decide to leave? Then you might end up with call every other night.

What can you do? Mr. Cassidy recommends specifying a maximum amount of call – for example, no more frequent than one in four nights.
 

Physician must pay for reimbursement claw-backs by payers

When auditors for Medicare or other payers find overpayments after the fact, called a ‘claw-back,’ the provider must pay them back. But which provider has to do that – you or your employer?

In many cases, your employer’s billing office may have introduced the error, but there may be a clause in the contract stating that the physician is solely responsible for all claw-backs. That could be costly.

What can you do? Mr. Shay said the clause should state that you have to pay only when it is the result of your own error or omission, and also not when it was made at the direction of the employer.
 

Some work may be outside of your subspecialty

In some cases, the employer may assign subspecialized doctors to work outside their subspecialty, Mr. Nuland said.

For example, he said he represented an endocrinologist who expected to see only diabetes patients but was assigned to some general internal medicine work as well, and an otolaryngologist client of his who completed a fellowship on facial plastic surgery was expected to do liposuction in a cosmetic surgery group.

What can you do? To prevent this from happening, Mr. Nuland recommends a clause stating that your work will be restricted to your subspecialty.

What the employer promised isn’t in the contract

“Beware of promises that are not in the contract,” Mr. Shay said. “You might feel you can really trust your new boss and what he tells you, but what if that person resigns, or the organization gets a new owner who doesn’t honor unwritten agreements?”

Many contracts have an integration clause, which specifies that the contract constitutes the complete agreement between the two parties, and it nullifies any other oral or written promises made to the physician.

For example, the employer might have promised a relocation bonus and a sign-on bonus, but for some reason it didn’t get into the contract, Ms. Ord said. In those cases, the employer is under no obligation to honor the promise.

What can you do? Mr. Cassidy said it is possible to hold the employer to a commitment made outside the contract. The alternative document, such as an offer letter, has to specifically state that the commitment is protected from the integration clause in the contract, he said, adding: “It is still better to have the commitment put into the contract.”
 

Contract is simply accepted as is

“Generally, the bigger the employer, the less likely they will alter an agreement just to make you happy,” Mr. Shay said.

But even in these contracts, he said there is still opportunity to fix errors and ambiguities that could harm you later – or even alter a provision if you can’t remove it outright.

The back-and-forth is important, Ms. Adler said. “Negotiation means trying to have some control over your job and your life.”

Mr. Cassidy said a big part of contract review is facing up to the possibility that you may have to resign or be let go.

“Many physicians don’t like to think about leaving when they’re just starting a job, but they need to,” he said. “You need to begin with the end in mind. Think about what would happen if this job didn’t work out.”

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

New classes of antimigraine drugs demonstrate efficacy and improved tolerability for patients with chronic migraine, a new systematic review and meta-analysis finds.

“[T]he lack of cardiovascular risks of these new classes of migraine-specific treatments may provide alternative treatment options for individuals for whom currently available acute treatments have failed or for those with cardiovascular contraindications,” write lead author Chun-Pai Yang, MD, PhD, of Taichung (Taiwan) Veterans General Hospital and colleagues, in the paper, published online in JAMA Network Open.
 

Methods

The new study compared the outcomes for acute migraine management using the ditan, lasmiditan (a 5-hydroxytryptamine [5HT]1F–receptor agonist), and the two gepants, rimegepant, and ubrogepant (calcitonin gene–related peptide [CGRP] antagonists), with standard triptan (selective 5-HT1B/1D–receptor agonist) therapy.

The researchers evaluated 64 double-blind randomized clinical trials which included 46,442 patients, the majority of whom (74%-87%) were women with an age range of 36-43 years.

The primary outcome evaluated was the odds ratio for freedom from pain at 2 hours after a single dose and secondary outcomes were the OR for pain relief at 2 hours following a dose, as well as any adverse events.
 

Results

Dr. Yang and colleagues found that virtually all medications with widespread clinical use, regardless of class, were associated with higher ORs for pain freedom when compared with placebo.

Compared to ditan and gepant agents, however, triptans were associated with significantly higher ORs for pain freedom. The odds ratio ranges were 1.72-3.40 for lasmiditan, 1.58-3.13 for rimegepant, and 1.54-3.05 for ubrogepant.

With respect to pain relief at 2 hours, while all medications were more effective than placebo, triptans were associated with higher ORs when compared with the other drug classes: lasmiditan (range: OR, 1.46; 95% confidence interval, 1.09-1.96 to OR, 3.31; 95% CI, 2.41-4.55), rimegepant (range: OR, 1.33; 95% CI, 1.01-1.76 to OR, 3.01; 95% CI, 2.33-3.88), and ubrogepant (range: OR, 1.38; 95% CI, 1.02-1.88 to OR, 3.13; 95% CI, 2.35-4.15)

When assessing tolerability, the researchers found that overall, triptans were associated with the higher ORs for any adverse events (AE) with a trend of dose-response relationship. Lasmiditan (in the ditan class) was associated with the highest risk for AEs among all treatments. Most of the AEs were mild to moderate and included chest pain, tightness, heaviness, and pressure.

Dr. Yang and colleagues note that, “although these two new classes of antimigraine drugs may not be as efficacious as triptans, these novel abortive agents without cardiovascular risks might offer an alternative to current specific migraine treatments for patients at risk of cardiovascular disease.”
 

Balancing efficacy and tolerability

“When choosing an acute medication for a patient there is always a balance between efficacy and tolerability,” headache specialist and associate director of North Shore Headache and Spine Lauren Natbony, MD, said in an interview.

“A medication can only be effective if a patient is able to tolerate it and will actually use it,” Dr. Natbony said.

With respect to the current review, Dr. Natbony pointed out, “response to acute therapy can differ between migraine attacks and may be based on variables not controlled for, such as how early in an attack the medication was taken, associated symptoms such as nausea that may make oral medications less efficacious, etc.”

The authors acknowledge that the focus on short-term responses and AEs after a single dose is a limitation of the study. They also pointed out what they considered to be a strength of the study, which was its network meta-analysis design. According to the authors, this design allowed for “multiple direct and indirect comparisons, ranking the efficacy and safety of individual pharmacologic interventions and providing more precise estimates than those of RCTs and traditional meta-analysis.”

Funding for this study was provided through grants from the Ministry of Science and Technology, Taiwan; the Brain Research Center; and National Yang Ming Chiao Tung University.

Dr. Yang has received personal fees and grants from various pharmaceutical companies. He has also received grants from the Taiwan Ministry of Technology and Science, the Brain Research Center, National Yang Ming Chiao Tung University, and Taipei Veterans General Hospital outside the submitted work. The other authors and Dr. Natbony disclosed no relevant financial relationships.

New classes of antimigraine drugs demonstrate efficacy and improved tolerability for patients with chronic migraine, a new systematic review and meta-analysis finds.

“[T]he lack of cardiovascular risks of these new classes of migraine-specific treatments may provide alternative treatment options for individuals for whom currently available acute treatments have failed or for those with cardiovascular contraindications,” write lead author Chun-Pai Yang, MD, PhD, of Taichung (Taiwan) Veterans General Hospital and colleagues, in the paper, published online in JAMA Network Open.
 

Methods

The new study compared the outcomes for acute migraine management using the ditan, lasmiditan (a 5-hydroxytryptamine [5HT]1F–receptor agonist), and the two gepants, rimegepant, and ubrogepant (calcitonin gene–related peptide [CGRP] antagonists), with standard triptan (selective 5-HT1B/1D–receptor agonist) therapy.

The researchers evaluated 64 double-blind randomized clinical trials which included 46,442 patients, the majority of whom (74%-87%) were women with an age range of 36-43 years.

The primary outcome evaluated was the odds ratio for freedom from pain at 2 hours after a single dose and secondary outcomes were the OR for pain relief at 2 hours following a dose, as well as any adverse events.
 

Results

Dr. Yang and colleagues found that virtually all medications with widespread clinical use, regardless of class, were associated with higher ORs for pain freedom when compared with placebo.

Compared to ditan and gepant agents, however, triptans were associated with significantly higher ORs for pain freedom. The odds ratio ranges were 1.72-3.40 for lasmiditan, 1.58-3.13 for rimegepant, and 1.54-3.05 for ubrogepant.

With respect to pain relief at 2 hours, while all medications were more effective than placebo, triptans were associated with higher ORs when compared with the other drug classes: lasmiditan (range: OR, 1.46; 95% confidence interval, 1.09-1.96 to OR, 3.31; 95% CI, 2.41-4.55), rimegepant (range: OR, 1.33; 95% CI, 1.01-1.76 to OR, 3.01; 95% CI, 2.33-3.88), and ubrogepant (range: OR, 1.38; 95% CI, 1.02-1.88 to OR, 3.13; 95% CI, 2.35-4.15)

When assessing tolerability, the researchers found that overall, triptans were associated with the higher ORs for any adverse events (AE) with a trend of dose-response relationship. Lasmiditan (in the ditan class) was associated with the highest risk for AEs among all treatments. Most of the AEs were mild to moderate and included chest pain, tightness, heaviness, and pressure.

Dr. Yang and colleagues note that, “although these two new classes of antimigraine drugs may not be as efficacious as triptans, these novel abortive agents without cardiovascular risks might offer an alternative to current specific migraine treatments for patients at risk of cardiovascular disease.”
 

Balancing efficacy and tolerability

“When choosing an acute medication for a patient there is always a balance between efficacy and tolerability,” headache specialist and associate director of North Shore Headache and Spine Lauren Natbony, MD, said in an interview.

“A medication can only be effective if a patient is able to tolerate it and will actually use it,” Dr. Natbony said.

With respect to the current review, Dr. Natbony pointed out, “response to acute therapy can differ between migraine attacks and may be based on variables not controlled for, such as how early in an attack the medication was taken, associated symptoms such as nausea that may make oral medications less efficacious, etc.”

The authors acknowledge that the focus on short-term responses and AEs after a single dose is a limitation of the study. They also pointed out what they considered to be a strength of the study, which was its network meta-analysis design. According to the authors, this design allowed for “multiple direct and indirect comparisons, ranking the efficacy and safety of individual pharmacologic interventions and providing more precise estimates than those of RCTs and traditional meta-analysis.”

Funding for this study was provided through grants from the Ministry of Science and Technology, Taiwan; the Brain Research Center; and National Yang Ming Chiao Tung University.

Dr. Yang has received personal fees and grants from various pharmaceutical companies. He has also received grants from the Taiwan Ministry of Technology and Science, the Brain Research Center, National Yang Ming Chiao Tung University, and Taipei Veterans General Hospital outside the submitted work. The other authors and Dr. Natbony disclosed no relevant financial relationships.

New classes of antimigraine drugs demonstrate efficacy and improved tolerability for patients with chronic migraine, a new systematic review and meta-analysis finds.

“[T]he lack of cardiovascular risks of these new classes of migraine-specific treatments may provide alternative treatment options for individuals for whom currently available acute treatments have failed or for those with cardiovascular contraindications,” write lead author Chun-Pai Yang, MD, PhD, of Taichung (Taiwan) Veterans General Hospital and colleagues, in the paper, published online in JAMA Network Open.
 

Methods

The new study compared the outcomes for acute migraine management using the ditan, lasmiditan (a 5-hydroxytryptamine [5HT]1F–receptor agonist), and the two gepants, rimegepant, and ubrogepant (calcitonin gene–related peptide [CGRP] antagonists), with standard triptan (selective 5-HT1B/1D–receptor agonist) therapy.

The researchers evaluated 64 double-blind randomized clinical trials which included 46,442 patients, the majority of whom (74%-87%) were women with an age range of 36-43 years.

The primary outcome evaluated was the odds ratio for freedom from pain at 2 hours after a single dose and secondary outcomes were the OR for pain relief at 2 hours following a dose, as well as any adverse events.
 

Results

Dr. Yang and colleagues found that virtually all medications with widespread clinical use, regardless of class, were associated with higher ORs for pain freedom when compared with placebo.

Compared to ditan and gepant agents, however, triptans were associated with significantly higher ORs for pain freedom. The odds ratio ranges were 1.72-3.40 for lasmiditan, 1.58-3.13 for rimegepant, and 1.54-3.05 for ubrogepant.

With respect to pain relief at 2 hours, while all medications were more effective than placebo, triptans were associated with higher ORs when compared with the other drug classes: lasmiditan (range: OR, 1.46; 95% confidence interval, 1.09-1.96 to OR, 3.31; 95% CI, 2.41-4.55), rimegepant (range: OR, 1.33; 95% CI, 1.01-1.76 to OR, 3.01; 95% CI, 2.33-3.88), and ubrogepant (range: OR, 1.38; 95% CI, 1.02-1.88 to OR, 3.13; 95% CI, 2.35-4.15)

When assessing tolerability, the researchers found that overall, triptans were associated with the higher ORs for any adverse events (AE) with a trend of dose-response relationship. Lasmiditan (in the ditan class) was associated with the highest risk for AEs among all treatments. Most of the AEs were mild to moderate and included chest pain, tightness, heaviness, and pressure.

Dr. Yang and colleagues note that, “although these two new classes of antimigraine drugs may not be as efficacious as triptans, these novel abortive agents without cardiovascular risks might offer an alternative to current specific migraine treatments for patients at risk of cardiovascular disease.”
 

Balancing efficacy and tolerability

“When choosing an acute medication for a patient there is always a balance between efficacy and tolerability,” headache specialist and associate director of North Shore Headache and Spine Lauren Natbony, MD, said in an interview.

“A medication can only be effective if a patient is able to tolerate it and will actually use it,” Dr. Natbony said.

With respect to the current review, Dr. Natbony pointed out, “response to acute therapy can differ between migraine attacks and may be based on variables not controlled for, such as how early in an attack the medication was taken, associated symptoms such as nausea that may make oral medications less efficacious, etc.”

The authors acknowledge that the focus on short-term responses and AEs after a single dose is a limitation of the study. They also pointed out what they considered to be a strength of the study, which was its network meta-analysis design. According to the authors, this design allowed for “multiple direct and indirect comparisons, ranking the efficacy and safety of individual pharmacologic interventions and providing more precise estimates than those of RCTs and traditional meta-analysis.”

Funding for this study was provided through grants from the Ministry of Science and Technology, Taiwan; the Brain Research Center; and National Yang Ming Chiao Tung University.

Dr. Yang has received personal fees and grants from various pharmaceutical companies. He has also received grants from the Taiwan Ministry of Technology and Science, the Brain Research Center, National Yang Ming Chiao Tung University, and Taipei Veterans General Hospital outside the submitted work. The other authors and Dr. Natbony disclosed no relevant financial relationships.

Two biomarkers could potentially indicate which children with SARS-CoV-2 infection will develop severe disease, according to research presented at the American Academy of Pediatrics 2021 National Conference.

“Most children with COVID-19 present with common symptoms, such as fever, vomiting, and abdominal pain, which are very similar to other common viruses,” said senior researcher Usha Sethuraman, MD, professor of pediatric emergency medicine at Central Michigan University in Detroit.

“It is impossible, in many instances, to predict which child, even after identification of SARS-CoV-2 infection, is going to develop severe consequences, such as multisystem inflammatory syndrome [MIS-C] or severe pneumonia,” she said in an interview.

“In fact, many of these kids have been sent home the first time around as they appeared clinically well, only to return a couple of days later in cardiogenic shock and requiring invasive interventions,” she added. “It would be invaluable to have the ability to know which child is likely to develop severe infection so appropriate disposition can be made and treatment initiated.”

In their prospective observational cohort study, Dr. Sethuraman and her colleagues collected saliva samples from children and adolescents when they were diagnosed with SARS-CoV-2 infection. They assessed the saliva for micro (mi)RNAs, which are small noncoding RNAs that help regulate gene expression and are “thought to play a role in the regulation of inflammation following an infection,” the researchers write in their poster.

Of the 129 young people assessed, 32 (25%) developed severe infection and 97 (75%) did not. The researchers defined severe infection as an MIS-C diagnosis, death in the 30 days after diagnosis, or the need for at least 2 L of oxygen, inotropes, mechanical ventilation, or extracorporeal membrane oxygenation.

The expression of 63 miRNAs was significantly different between young people who developed severe infection and those who did not (P < .05). In cases of severe disease, expression was downregulated for 38 of the 63 miRNAs (60%).

“A model of six miRNAs was able to discriminate between severe and nonsevere infections with high sensitivity and accuracy in a preliminary analysis,” Dr. Sethuraman reported. “While salivary miRNA has been shown in other studies to help differentiate persistent concussion in children, we did not expect them to be downregulated in children with severe COVID-19.”

The significant differences in miRNA expression in those with and without severe disease is “striking,” despite this being an interim analysis in a fairly small sample size, said Sindhu Mohandas, MD, a pediatric infectious disease specialist at Children’s Hospital Los Angeles.

“It will be interesting to see if these findings persist when larger numbers are analyzed,” she told this news organization. “Biomarkers that can predict potential severity can be very useful in making risk and management determinations. A child who has the biomarkers that indicate increased severity can be monitored more closely and complications can be preempted and prevented.”

The largest difference between severe and nonsevere cases was in the expression of miRNA 4495. In addition, miRNA 6125 appears to have prognostic potential, the researchers conclude. And three cytokines from saliva samples were elevated in cases of severe infection, but cytokine levels could not distinguish between severe and nonsevere infections, Dr. Sethuraman said.

If further research confirms these findings and determines that these miRNAs truly can provide insight into the likely course of an infection, it “would be a game changer, clinically,” she added, particularly because saliva samples are less invasive and less painful than blood draws.

The potential applications of these biomarkers could extend beyond children admitted to the hospital, Dr. Mohandas noted.

“For example, it would be a noninvasive and easy method to predict potential severity in a child seen in the emergency room and could help with deciding between observation, admission to the general floor, or admission to the ICU,” she told this news organization. “However, this test is not easily or routinely available at present, and cost and accessibility will be the main factors that will have to be overcome before it can be used for this purpose.”

These findings are preliminary, from a small sample, and require confirmation and validation, Dr. Sethuraman cautioned. And the team only analyzed saliva collected at diagnosis, so they have no data on potential changes in cytokines or miRNAs that occur as the disease progresses.

The next step is to “better characterize what happens with time to these profiles,” she explained. “The role of age, race, and gender differences in saliva biomarker profiles needs additional investigation as well.”

It would also be interesting to see whether varied expression of miRNAs “can help differentiate the various complications after COVID-19, like acute respiratory failure, MIS-C, and long COVID,” said Dr. Mohandas. “That would mean it could be used not only to potentially predict severity, but also to predict longer-term outcomes.”

This study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the National Institutes of Health’s Rapid Acceleration of Diagnostics (RADx) program. Coauthor Steven D. Hicks, MD, PhD, reports being a paid consultant for Quadrant Biosciences.

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

Two biomarkers could potentially indicate which children with SARS-CoV-2 infection will develop severe disease, according to research presented at the American Academy of Pediatrics 2021 National Conference.

“Most children with COVID-19 present with common symptoms, such as fever, vomiting, and abdominal pain, which are very similar to other common viruses,” said senior researcher Usha Sethuraman, MD, professor of pediatric emergency medicine at Central Michigan University in Detroit.

“It is impossible, in many instances, to predict which child, even after identification of SARS-CoV-2 infection, is going to develop severe consequences, such as multisystem inflammatory syndrome [MIS-C] or severe pneumonia,” she said in an interview.

“In fact, many of these kids have been sent home the first time around as they appeared clinically well, only to return a couple of days later in cardiogenic shock and requiring invasive interventions,” she added. “It would be invaluable to have the ability to know which child is likely to develop severe infection so appropriate disposition can be made and treatment initiated.”

In their prospective observational cohort study, Dr. Sethuraman and her colleagues collected saliva samples from children and adolescents when they were diagnosed with SARS-CoV-2 infection. They assessed the saliva for micro (mi)RNAs, which are small noncoding RNAs that help regulate gene expression and are “thought to play a role in the regulation of inflammation following an infection,” the researchers write in their poster.

Of the 129 young people assessed, 32 (25%) developed severe infection and 97 (75%) did not. The researchers defined severe infection as an MIS-C diagnosis, death in the 30 days after diagnosis, or the need for at least 2 L of oxygen, inotropes, mechanical ventilation, or extracorporeal membrane oxygenation.

The expression of 63 miRNAs was significantly different between young people who developed severe infection and those who did not (P < .05). In cases of severe disease, expression was downregulated for 38 of the 63 miRNAs (60%).

“A model of six miRNAs was able to discriminate between severe and nonsevere infections with high sensitivity and accuracy in a preliminary analysis,” Dr. Sethuraman reported. “While salivary miRNA has been shown in other studies to help differentiate persistent concussion in children, we did not expect them to be downregulated in children with severe COVID-19.”

The significant differences in miRNA expression in those with and without severe disease is “striking,” despite this being an interim analysis in a fairly small sample size, said Sindhu Mohandas, MD, a pediatric infectious disease specialist at Children’s Hospital Los Angeles.

“It will be interesting to see if these findings persist when larger numbers are analyzed,” she told this news organization. “Biomarkers that can predict potential severity can be very useful in making risk and management determinations. A child who has the biomarkers that indicate increased severity can be monitored more closely and complications can be preempted and prevented.”

The largest difference between severe and nonsevere cases was in the expression of miRNA 4495. In addition, miRNA 6125 appears to have prognostic potential, the researchers conclude. And three cytokines from saliva samples were elevated in cases of severe infection, but cytokine levels could not distinguish between severe and nonsevere infections, Dr. Sethuraman said.

If further research confirms these findings and determines that these miRNAs truly can provide insight into the likely course of an infection, it “would be a game changer, clinically,” she added, particularly because saliva samples are less invasive and less painful than blood draws.

The potential applications of these biomarkers could extend beyond children admitted to the hospital, Dr. Mohandas noted.

“For example, it would be a noninvasive and easy method to predict potential severity in a child seen in the emergency room and could help with deciding between observation, admission to the general floor, or admission to the ICU,” she told this news organization. “However, this test is not easily or routinely available at present, and cost and accessibility will be the main factors that will have to be overcome before it can be used for this purpose.”

These findings are preliminary, from a small sample, and require confirmation and validation, Dr. Sethuraman cautioned. And the team only analyzed saliva collected at diagnosis, so they have no data on potential changes in cytokines or miRNAs that occur as the disease progresses.

The next step is to “better characterize what happens with time to these profiles,” she explained. “The role of age, race, and gender differences in saliva biomarker profiles needs additional investigation as well.”

It would also be interesting to see whether varied expression of miRNAs “can help differentiate the various complications after COVID-19, like acute respiratory failure, MIS-C, and long COVID,” said Dr. Mohandas. “That would mean it could be used not only to potentially predict severity, but also to predict longer-term outcomes.”

This study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the National Institutes of Health’s Rapid Acceleration of Diagnostics (RADx) program. Coauthor Steven D. Hicks, MD, PhD, reports being a paid consultant for Quadrant Biosciences.

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

Two biomarkers could potentially indicate which children with SARS-CoV-2 infection will develop severe disease, according to research presented at the American Academy of Pediatrics 2021 National Conference.

“Most children with COVID-19 present with common symptoms, such as fever, vomiting, and abdominal pain, which are very similar to other common viruses,” said senior researcher Usha Sethuraman, MD, professor of pediatric emergency medicine at Central Michigan University in Detroit.

“It is impossible, in many instances, to predict which child, even after identification of SARS-CoV-2 infection, is going to develop severe consequences, such as multisystem inflammatory syndrome [MIS-C] or severe pneumonia,” she said in an interview.

“In fact, many of these kids have been sent home the first time around as they appeared clinically well, only to return a couple of days later in cardiogenic shock and requiring invasive interventions,” she added. “It would be invaluable to have the ability to know which child is likely to develop severe infection so appropriate disposition can be made and treatment initiated.”

In their prospective observational cohort study, Dr. Sethuraman and her colleagues collected saliva samples from children and adolescents when they were diagnosed with SARS-CoV-2 infection. They assessed the saliva for micro (mi)RNAs, which are small noncoding RNAs that help regulate gene expression and are “thought to play a role in the regulation of inflammation following an infection,” the researchers write in their poster.

Of the 129 young people assessed, 32 (25%) developed severe infection and 97 (75%) did not. The researchers defined severe infection as an MIS-C diagnosis, death in the 30 days after diagnosis, or the need for at least 2 L of oxygen, inotropes, mechanical ventilation, or extracorporeal membrane oxygenation.

The expression of 63 miRNAs was significantly different between young people who developed severe infection and those who did not (P < .05). In cases of severe disease, expression was downregulated for 38 of the 63 miRNAs (60%).

“A model of six miRNAs was able to discriminate between severe and nonsevere infections with high sensitivity and accuracy in a preliminary analysis,” Dr. Sethuraman reported. “While salivary miRNA has been shown in other studies to help differentiate persistent concussion in children, we did not expect them to be downregulated in children with severe COVID-19.”

The significant differences in miRNA expression in those with and without severe disease is “striking,” despite this being an interim analysis in a fairly small sample size, said Sindhu Mohandas, MD, a pediatric infectious disease specialist at Children’s Hospital Los Angeles.

“It will be interesting to see if these findings persist when larger numbers are analyzed,” she told this news organization. “Biomarkers that can predict potential severity can be very useful in making risk and management determinations. A child who has the biomarkers that indicate increased severity can be monitored more closely and complications can be preempted and prevented.”

The largest difference between severe and nonsevere cases was in the expression of miRNA 4495. In addition, miRNA 6125 appears to have prognostic potential, the researchers conclude. And three cytokines from saliva samples were elevated in cases of severe infection, but cytokine levels could not distinguish between severe and nonsevere infections, Dr. Sethuraman said.

If further research confirms these findings and determines that these miRNAs truly can provide insight into the likely course of an infection, it “would be a game changer, clinically,” she added, particularly because saliva samples are less invasive and less painful than blood draws.

The potential applications of these biomarkers could extend beyond children admitted to the hospital, Dr. Mohandas noted.

“For example, it would be a noninvasive and easy method to predict potential severity in a child seen in the emergency room and could help with deciding between observation, admission to the general floor, or admission to the ICU,” she told this news organization. “However, this test is not easily or routinely available at present, and cost and accessibility will be the main factors that will have to be overcome before it can be used for this purpose.”

These findings are preliminary, from a small sample, and require confirmation and validation, Dr. Sethuraman cautioned. And the team only analyzed saliva collected at diagnosis, so they have no data on potential changes in cytokines or miRNAs that occur as the disease progresses.

The next step is to “better characterize what happens with time to these profiles,” she explained. “The role of age, race, and gender differences in saliva biomarker profiles needs additional investigation as well.”

It would also be interesting to see whether varied expression of miRNAs “can help differentiate the various complications after COVID-19, like acute respiratory failure, MIS-C, and long COVID,” said Dr. Mohandas. “That would mean it could be used not only to potentially predict severity, but also to predict longer-term outcomes.”

This study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the National Institutes of Health’s Rapid Acceleration of Diagnostics (RADx) program. Coauthor Steven D. Hicks, MD, PhD, reports being a paid consultant for Quadrant Biosciences.

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

A U.S. Food and Drug Administration (FDA) advisory committee on Oct. 15 voted 19-0 to authorize second doses of the Johnson & Johnson COVID-19 vaccine in an effort to boost immunity. It was the second vote in as many days to back a change to a COVID vaccine timeline.
 

Johnson &amp; Johnson

In its vote, the committee said that boosters could be offered to people as young as age 18. However, it is not clear that everyone who got a Johnson & Johnson vaccine needs to get a second dose. The same panel voted Oct. 14 to recommend booster shots for the Moderna vaccine, but for a narrower group of people.

It will be up to a Centers for Disease Control and Prevention (CDC) panel to make more specific recommendations for who might need another shot. The CDC’s Advisory Committee on Immunization Practices is scheduled to meet next Oct. 21 to discuss issues related to COVID-19 vaccines.

Studies of the effectiveness of the Johnson & Johnson vaccine in the real world show that its protection — while good — has not been as strong as that of the mRNA vaccines made by Pfizer and Moderna, which are given as part of a two-dose series.

In the end, the members of the FDA’s Vaccines and Related Biological Products Advisory Committee said they felt that the company hadn’t made a case for calling their second shot a booster, but had shown enough data to suggest that everyone over the age of 18 should consider getting two shots of the Johnson & Johnson vaccine as a matter of course.

This is an especially important issue for adults over the age of 50. A recent study in the New England Journal of Medicine found that older adults who got the Johnson & Johnson vaccine were less protected against infection and hospitalization than those who got mRNA vaccines.
 

Limited data

The company presented data from six studies to the FDA panel in support of a second dose that were limited. The only study looking at second doses after 6 months included just 17 people.

These studies did show that a second dose substantially increased levels of neutralizing antibodies, which are the body’s first line of protection against COVID-19 infection.

But the company turned this data over to the FDA so recently that agency scientists repeatedly stressed during the meeting that they did not have ample time to follow their normal process of independently verifying the data and following up with their own analysis of the study results.

Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said it would have taken months to complete that rigorous level of review.

Instead, in the interest of urgency, the FDA said it had tried to bring some clarity to the tangle of study results presented that included three dosing schedules and different measures of effectiveness.

“Here’s how this strikes me,” said committee member Paul Offit, MD, a professor of pediatrics and infectious disease at Children’s Hospital of Philadelphia. “I think this vaccine was always a two-dose vaccine. I think it’s better as a two-dose vaccine. I think it would be hard to recommend this as a single-dose vaccine at this point.”

“As far as I’m concerned, it was always going to be necessary for J&J recipients to get a second shot,” said James Hildreth, MD, PhD, president and CEO of Meharry Medical College in Nashville.

Archana Chatterjee, MD, PhD, dean of the Chicago Medical School at Rosalind Franklin University of Medicine and Science, said she had changed her vote during the course of the meeting.

She said that, based on the very limited safety and effectiveness data presented to the committee, she was prepared to vote against the idea of offering second doses of Johnson & Johnson shots.

But after considering the 15 million people who have been vaccinated with a single dose and studies that have suggested that close to 5 million older adults may still be at risk for hospitalization because they’ve just had one shot, “This is still a public health imperative,” she said.

“I’m in agreement with most of my colleagues that this second dose, booster, whatever you want to call it, is necessary in these individuals to boost up their immunity back into the 90-plus percentile range,” Dr. Chatterjee said.

Who needs a second dose?

On Oct. 14, the committee heard an update on data from Israel, which saw a wave of severe breakthrough infections during the Delta wave.

COVID-19 cases are falling rapidly there after the country widely deployed booster doses of the Pfizer vaccine.

The FDA’s Dr. Marks said Oct. 15 that the agency was leaning toward creating greater flexibility in the emergency use authorizations (EUAs) for the Johnson & Johnson and Moderna vaccines so that boosters could be more widely deployed in the United States too.

The FDA panel on Oct. 14 voted to authorize a 50-milligram dose of Moderna’s vaccine — half the dose used in the primary series of shots — to boost immunity at least 6 months after the second dose.

Those who might need a Moderna booster are the same groups who’ve gotten a green light for third Pfizer doses, including people over 65, adults at higher risk for severe COVID-19, and those who are at higher risk because of where they live or work.

The FDA asked the committee on Oct. 15 to discuss whether boosters should be offered to younger adults, even those without underlying health conditions.

“We’re concerned that what was seen in Israel could be seen here,” Dr. Marks said. “We don’t want to have a wave of severe COVID-19 before we deploy boosters.”
 

Trying to avoid confusion

Some members of the committee cautioned Dr. Marks to be careful when expanding the EUAs, because it could confuse people.

“When we say immunity is waning, what are the implications of that?” said Michael Kurilla, MD, PhD, director of the division of clinical innovation at the National Institutes of Health.

Overall, data show that all the vaccines currently being used in the United States — including Johnson & Johnson — remain highly effective for preventing severe outcomes from COVID-19, like hospitalization and death.

Booster doses could prevent more people from even getting mild or moderate symptoms from “breakthrough” COVID-19 cases, which began to rise during the recent Delta surge. The additional doses are also expected to prevent severe outcomes like hospitalization in older adults and those with underlying health conditions.

“I think we need to be clear when we say waning immunity and we need to do something about that, I think we need to be clear what we’re really targeting [with boosters] in terms of clinical impact we expect to have,” Dr. Kurilla said.

Others pointed out that preventing even mild-to-moderate infections was a worthy goal, especially considering the implications of long-haul COVID-19.

“COVID does have tremendous downstream effects, even in those who are not hospitalized. Whenever we can prevent significant morbidity in a population, there are advantages to that,” said Steven Pergam, MD, MPH, medical director of infection prevention at the Seattle Cancer Care Alliance.

“I’d really be in the camp that would be moving towards a younger age range for allowing boosters,” he said.
 

This article was updated on 10/18/21. A version of this article first appeared on Medscape.com.

A U.S. Food and Drug Administration (FDA) advisory committee on Oct. 15 voted 19-0 to authorize second doses of the Johnson & Johnson COVID-19 vaccine in an effort to boost immunity. It was the second vote in as many days to back a change to a COVID vaccine timeline.
 

Johnson &amp; Johnson

In its vote, the committee said that boosters could be offered to people as young as age 18. However, it is not clear that everyone who got a Johnson & Johnson vaccine needs to get a second dose. The same panel voted Oct. 14 to recommend booster shots for the Moderna vaccine, but for a narrower group of people.

It will be up to a Centers for Disease Control and Prevention (CDC) panel to make more specific recommendations for who might need another shot. The CDC’s Advisory Committee on Immunization Practices is scheduled to meet next Oct. 21 to discuss issues related to COVID-19 vaccines.

Studies of the effectiveness of the Johnson & Johnson vaccine in the real world show that its protection — while good — has not been as strong as that of the mRNA vaccines made by Pfizer and Moderna, which are given as part of a two-dose series.

In the end, the members of the FDA’s Vaccines and Related Biological Products Advisory Committee said they felt that the company hadn’t made a case for calling their second shot a booster, but had shown enough data to suggest that everyone over the age of 18 should consider getting two shots of the Johnson & Johnson vaccine as a matter of course.

This is an especially important issue for adults over the age of 50. A recent study in the New England Journal of Medicine found that older adults who got the Johnson & Johnson vaccine were less protected against infection and hospitalization than those who got mRNA vaccines.
 

Limited data

The company presented data from six studies to the FDA panel in support of a second dose that were limited. The only study looking at second doses after 6 months included just 17 people.

These studies did show that a second dose substantially increased levels of neutralizing antibodies, which are the body’s first line of protection against COVID-19 infection.

But the company turned this data over to the FDA so recently that agency scientists repeatedly stressed during the meeting that they did not have ample time to follow their normal process of independently verifying the data and following up with their own analysis of the study results.

Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said it would have taken months to complete that rigorous level of review.

Instead, in the interest of urgency, the FDA said it had tried to bring some clarity to the tangle of study results presented that included three dosing schedules and different measures of effectiveness.

“Here’s how this strikes me,” said committee member Paul Offit, MD, a professor of pediatrics and infectious disease at Children’s Hospital of Philadelphia. “I think this vaccine was always a two-dose vaccine. I think it’s better as a two-dose vaccine. I think it would be hard to recommend this as a single-dose vaccine at this point.”

“As far as I’m concerned, it was always going to be necessary for J&J recipients to get a second shot,” said James Hildreth, MD, PhD, president and CEO of Meharry Medical College in Nashville.

Archana Chatterjee, MD, PhD, dean of the Chicago Medical School at Rosalind Franklin University of Medicine and Science, said she had changed her vote during the course of the meeting.

She said that, based on the very limited safety and effectiveness data presented to the committee, she was prepared to vote against the idea of offering second doses of Johnson & Johnson shots.

But after considering the 15 million people who have been vaccinated with a single dose and studies that have suggested that close to 5 million older adults may still be at risk for hospitalization because they’ve just had one shot, “This is still a public health imperative,” she said.

“I’m in agreement with most of my colleagues that this second dose, booster, whatever you want to call it, is necessary in these individuals to boost up their immunity back into the 90-plus percentile range,” Dr. Chatterjee said.

Who needs a second dose?

On Oct. 14, the committee heard an update on data from Israel, which saw a wave of severe breakthrough infections during the Delta wave.

COVID-19 cases are falling rapidly there after the country widely deployed booster doses of the Pfizer vaccine.

The FDA’s Dr. Marks said Oct. 15 that the agency was leaning toward creating greater flexibility in the emergency use authorizations (EUAs) for the Johnson & Johnson and Moderna vaccines so that boosters could be more widely deployed in the United States too.

The FDA panel on Oct. 14 voted to authorize a 50-milligram dose of Moderna’s vaccine — half the dose used in the primary series of shots — to boost immunity at least 6 months after the second dose.

Those who might need a Moderna booster are the same groups who’ve gotten a green light for third Pfizer doses, including people over 65, adults at higher risk for severe COVID-19, and those who are at higher risk because of where they live or work.

The FDA asked the committee on Oct. 15 to discuss whether boosters should be offered to younger adults, even those without underlying health conditions.

“We’re concerned that what was seen in Israel could be seen here,” Dr. Marks said. “We don’t want to have a wave of severe COVID-19 before we deploy boosters.”
 

Trying to avoid confusion

Some members of the committee cautioned Dr. Marks to be careful when expanding the EUAs, because it could confuse people.

“When we say immunity is waning, what are the implications of that?” said Michael Kurilla, MD, PhD, director of the division of clinical innovation at the National Institutes of Health.

Overall, data show that all the vaccines currently being used in the United States — including Johnson & Johnson — remain highly effective for preventing severe outcomes from COVID-19, like hospitalization and death.

Booster doses could prevent more people from even getting mild or moderate symptoms from “breakthrough” COVID-19 cases, which began to rise during the recent Delta surge. The additional doses are also expected to prevent severe outcomes like hospitalization in older adults and those with underlying health conditions.

“I think we need to be clear when we say waning immunity and we need to do something about that, I think we need to be clear what we’re really targeting [with boosters] in terms of clinical impact we expect to have,” Dr. Kurilla said.

Others pointed out that preventing even mild-to-moderate infections was a worthy goal, especially considering the implications of long-haul COVID-19.

“COVID does have tremendous downstream effects, even in those who are not hospitalized. Whenever we can prevent significant morbidity in a population, there are advantages to that,” said Steven Pergam, MD, MPH, medical director of infection prevention at the Seattle Cancer Care Alliance.

“I’d really be in the camp that would be moving towards a younger age range for allowing boosters,” he said.
 

This article was updated on 10/18/21. A version of this article first appeared on Medscape.com.

A U.S. Food and Drug Administration (FDA) advisory committee on Oct. 15 voted 19-0 to authorize second doses of the Johnson & Johnson COVID-19 vaccine in an effort to boost immunity. It was the second vote in as many days to back a change to a COVID vaccine timeline.
 

Johnson &amp; Johnson

In its vote, the committee said that boosters could be offered to people as young as age 18. However, it is not clear that everyone who got a Johnson & Johnson vaccine needs to get a second dose. The same panel voted Oct. 14 to recommend booster shots for the Moderna vaccine, but for a narrower group of people.

It will be up to a Centers for Disease Control and Prevention (CDC) panel to make more specific recommendations for who might need another shot. The CDC’s Advisory Committee on Immunization Practices is scheduled to meet next Oct. 21 to discuss issues related to COVID-19 vaccines.

Studies of the effectiveness of the Johnson & Johnson vaccine in the real world show that its protection — while good — has not been as strong as that of the mRNA vaccines made by Pfizer and Moderna, which are given as part of a two-dose series.

In the end, the members of the FDA’s Vaccines and Related Biological Products Advisory Committee said they felt that the company hadn’t made a case for calling their second shot a booster, but had shown enough data to suggest that everyone over the age of 18 should consider getting two shots of the Johnson & Johnson vaccine as a matter of course.

This is an especially important issue for adults over the age of 50. A recent study in the New England Journal of Medicine found that older adults who got the Johnson & Johnson vaccine were less protected against infection and hospitalization than those who got mRNA vaccines.
 

Limited data

The company presented data from six studies to the FDA panel in support of a second dose that were limited. The only study looking at second doses after 6 months included just 17 people.

These studies did show that a second dose substantially increased levels of neutralizing antibodies, which are the body’s first line of protection against COVID-19 infection.

But the company turned this data over to the FDA so recently that agency scientists repeatedly stressed during the meeting that they did not have ample time to follow their normal process of independently verifying the data and following up with their own analysis of the study results.

Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said it would have taken months to complete that rigorous level of review.

Instead, in the interest of urgency, the FDA said it had tried to bring some clarity to the tangle of study results presented that included three dosing schedules and different measures of effectiveness.

“Here’s how this strikes me,” said committee member Paul Offit, MD, a professor of pediatrics and infectious disease at Children’s Hospital of Philadelphia. “I think this vaccine was always a two-dose vaccine. I think it’s better as a two-dose vaccine. I think it would be hard to recommend this as a single-dose vaccine at this point.”

“As far as I’m concerned, it was always going to be necessary for J&J recipients to get a second shot,” said James Hildreth, MD, PhD, president and CEO of Meharry Medical College in Nashville.

Archana Chatterjee, MD, PhD, dean of the Chicago Medical School at Rosalind Franklin University of Medicine and Science, said she had changed her vote during the course of the meeting.

She said that, based on the very limited safety and effectiveness data presented to the committee, she was prepared to vote against the idea of offering second doses of Johnson & Johnson shots.

But after considering the 15 million people who have been vaccinated with a single dose and studies that have suggested that close to 5 million older adults may still be at risk for hospitalization because they’ve just had one shot, “This is still a public health imperative,” she said.

“I’m in agreement with most of my colleagues that this second dose, booster, whatever you want to call it, is necessary in these individuals to boost up their immunity back into the 90-plus percentile range,” Dr. Chatterjee said.

Who needs a second dose?

On Oct. 14, the committee heard an update on data from Israel, which saw a wave of severe breakthrough infections during the Delta wave.

COVID-19 cases are falling rapidly there after the country widely deployed booster doses of the Pfizer vaccine.

The FDA’s Dr. Marks said Oct. 15 that the agency was leaning toward creating greater flexibility in the emergency use authorizations (EUAs) for the Johnson & Johnson and Moderna vaccines so that boosters could be more widely deployed in the United States too.

The FDA panel on Oct. 14 voted to authorize a 50-milligram dose of Moderna’s vaccine — half the dose used in the primary series of shots — to boost immunity at least 6 months after the second dose.

Those who might need a Moderna booster are the same groups who’ve gotten a green light for third Pfizer doses, including people over 65, adults at higher risk for severe COVID-19, and those who are at higher risk because of where they live or work.

The FDA asked the committee on Oct. 15 to discuss whether boosters should be offered to younger adults, even those without underlying health conditions.

“We’re concerned that what was seen in Israel could be seen here,” Dr. Marks said. “We don’t want to have a wave of severe COVID-19 before we deploy boosters.”
 

Trying to avoid confusion

Some members of the committee cautioned Dr. Marks to be careful when expanding the EUAs, because it could confuse people.

“When we say immunity is waning, what are the implications of that?” said Michael Kurilla, MD, PhD, director of the division of clinical innovation at the National Institutes of Health.

Overall, data show that all the vaccines currently being used in the United States — including Johnson & Johnson — remain highly effective for preventing severe outcomes from COVID-19, like hospitalization and death.

Booster doses could prevent more people from even getting mild or moderate symptoms from “breakthrough” COVID-19 cases, which began to rise during the recent Delta surge. The additional doses are also expected to prevent severe outcomes like hospitalization in older adults and those with underlying health conditions.

“I think we need to be clear when we say waning immunity and we need to do something about that, I think we need to be clear what we’re really targeting [with boosters] in terms of clinical impact we expect to have,” Dr. Kurilla said.

Others pointed out that preventing even mild-to-moderate infections was a worthy goal, especially considering the implications of long-haul COVID-19.

“COVID does have tremendous downstream effects, even in those who are not hospitalized. Whenever we can prevent significant morbidity in a population, there are advantages to that,” said Steven Pergam, MD, MPH, medical director of infection prevention at the Seattle Cancer Care Alliance.

“I’d really be in the camp that would be moving towards a younger age range for allowing boosters,” he said.
 

This article was updated on 10/18/21. A version of this article first appeared on Medscape.com.

Individuals with substance use disorders (SUDs) have a twofold increased risk for COVID-related hospitalization and death even after vaccination, new research shows.

Investigators analyzed data on over 10,000 vaccinated individuals with various SUDs and almost 600,000 vaccinated individuals without an SUD. They found about twice as many individuals with an SUD had a breakthrough COVID-19 infection as their counterparts without an SUD, at 7% versus 3.6%, respectively.

Worrisome phase

SUDs are “often associated with multiple comorbid conditions that are known risk factors for severe outcome of COVID-19 infection,” the investigators note.

Research published early in the pandemic showed patients with SUDs, including alcohol, cannabis, cocaine, opioid, and tobacco use disorders, were “at increased risk for COVID-19 infection and associated severe outcomes, especially among African Americans,” they add.

To date, no research has focused on the potential risk for COVID in individuals with SUDs following vaccination. In addition, although vaccines are “very effective,” breakthrough infections have been recorded, “highlighting the need to identify populations that might be most vulnerable, as we have entered a worrisome new phase of the pandemic,” the authors write.

For the study, researchers used a data analytics platform that included de-identified information from 63 health care organizations across the U.S. to estimate the risk for breakthrough COVID-19 among vaccinated patients with SUD (n = 30,183; mean age 59.3, 51.4% male, 63.2% White, 26.2% African American), compared with vaccinated individuals without SUDs (n = 549,189; mean age 54.7, 43.2% male, 63.4% White, 14.3% African American) between December 2020 and August 2021.

They also conducted statistical analyses to examine how the rate of breakthrough cases changed over that timeframe.

The cohorts were matched by demographics, adverse socioeconomic determinants of health, lifetime medical and psychiatric comorbidities, and vaccine type.

Among vaccinated SUD patients, three-quarters received the Pfizer-BioNTech vaccine, one-fifth received the Moderna vaccine, and 3.3% received the Johnson & Johnson vaccine.

In contrast, among the vaccinated non-SUD population, almost all (88.2%) received the Pfizer-BioNTech vaccine, 10% received Moderna, and only 1.2% received the Johnson & Johnson vaccine.
 

Underlying drivers

The prevalence of adverse socioeconomic determinants of health was higher in vaccinated individuals with SUDs compared to those without (7.9% vs. 1.2%, respectively). Moreover, vaccinated patients with SUD had a higher lifetime prevalence of all comorbidities as well as transplants (all Ps < .001).

The risk for breakthrough infection was significantly higher in vaccinated individuals with SUDs compared to those without (all Ps < .001).

After controlling for adverse socioeconomic determinants of health and comorbid medical conditions, the risk for breakthrough infection “no longer differed in SUD compared to non-SUD cohorts, except for patients with cannabis use disorder, who remained at significantly increased risk,” the authors report.

In both populations, the rate of breakthrough infections “steadily increased” between January and August 2021.

The risk for hospitalization and death was higher among those with breakthrough infections, compared with those in the matched cohort without breakthrough infections, but the risk for hospitalization and death were higher in the SUD compared with the non-SUD population.

In the SUD patients, after matching an array of demographic, socioeconomic, and medical factors as well as vaccine type, only cannabis use disorder was associated with a higher risk in African Americans, compared with matched Caucasians (HR = 1.63; 95% confidence interval, 1.06-2.51).

“When we adjusted the data to account for comorbidities and for socioeconomic background, we no longer saw a difference between those with substance use disorders and those without – the only exception to this was for people with cannabis use disorder,” said Dr. Volkow.

“This suggests that these factors, which are often associated with substance use disorders, are likely the underlying drivers for the increased risk,” she continued.

She added that it is important for other studies to investigate why individuals with cannabis use disorder had a higher risk for breakthrough infections.
 

Good news, bad news

Commenting for this news organization, Anna Lembke, MD, professor of psychiatry and behavioral sciences, Stanford (Calif.) University, said the study is important and contains good news and bad news.

The good news, she said, “is that, after controlling for comorbidities and socioeconomic variables, patients with SUDs are no more likely than patients without SUDs to get COVID after getting vaccinated, and the bad news is that if vaccinated patients with SUDs do get COVID, they’re more likely to end up hospitalized or die from it,” said Dr. Lembke, who was not involved with the study.

“The take-home message for clinicians is that if your vaccinated patient with an SUD gets COVID, be on the alert for a more complicated medical outcome and a higher risk of death,” warned Dr. Lembke.

This study was supported by the U.S. National Institute on Drug Abuse, the U.S. National Institute of Aging, and the Clinical and Translational Science Collaborative (CTSC) of Cleveland. No disclosures were listed on the original study. Dr. Lembke has disclosed no relevant financial relationships.

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

Individuals with substance use disorders (SUDs) have a twofold increased risk for COVID-related hospitalization and death even after vaccination, new research shows.

Investigators analyzed data on over 10,000 vaccinated individuals with various SUDs and almost 600,000 vaccinated individuals without an SUD. They found about twice as many individuals with an SUD had a breakthrough COVID-19 infection as their counterparts without an SUD, at 7% versus 3.6%, respectively.

Worrisome phase

SUDs are “often associated with multiple comorbid conditions that are known risk factors for severe outcome of COVID-19 infection,” the investigators note.

Research published early in the pandemic showed patients with SUDs, including alcohol, cannabis, cocaine, opioid, and tobacco use disorders, were “at increased risk for COVID-19 infection and associated severe outcomes, especially among African Americans,” they add.

To date, no research has focused on the potential risk for COVID in individuals with SUDs following vaccination. In addition, although vaccines are “very effective,” breakthrough infections have been recorded, “highlighting the need to identify populations that might be most vulnerable, as we have entered a worrisome new phase of the pandemic,” the authors write.

For the study, researchers used a data analytics platform that included de-identified information from 63 health care organizations across the U.S. to estimate the risk for breakthrough COVID-19 among vaccinated patients with SUD (n = 30,183; mean age 59.3, 51.4% male, 63.2% White, 26.2% African American), compared with vaccinated individuals without SUDs (n = 549,189; mean age 54.7, 43.2% male, 63.4% White, 14.3% African American) between December 2020 and August 2021.

They also conducted statistical analyses to examine how the rate of breakthrough cases changed over that timeframe.

The cohorts were matched by demographics, adverse socioeconomic determinants of health, lifetime medical and psychiatric comorbidities, and vaccine type.

Among vaccinated SUD patients, three-quarters received the Pfizer-BioNTech vaccine, one-fifth received the Moderna vaccine, and 3.3% received the Johnson & Johnson vaccine.

In contrast, among the vaccinated non-SUD population, almost all (88.2%) received the Pfizer-BioNTech vaccine, 10% received Moderna, and only 1.2% received the Johnson & Johnson vaccine.
 

Underlying drivers

The prevalence of adverse socioeconomic determinants of health was higher in vaccinated individuals with SUDs compared to those without (7.9% vs. 1.2%, respectively). Moreover, vaccinated patients with SUD had a higher lifetime prevalence of all comorbidities as well as transplants (all Ps < .001).

The risk for breakthrough infection was significantly higher in vaccinated individuals with SUDs compared to those without (all Ps < .001).

After controlling for adverse socioeconomic determinants of health and comorbid medical conditions, the risk for breakthrough infection “no longer differed in SUD compared to non-SUD cohorts, except for patients with cannabis use disorder, who remained at significantly increased risk,” the authors report.

In both populations, the rate of breakthrough infections “steadily increased” between January and August 2021.

The risk for hospitalization and death was higher among those with breakthrough infections, compared with those in the matched cohort without breakthrough infections, but the risk for hospitalization and death were higher in the SUD compared with the non-SUD population.

In the SUD patients, after matching an array of demographic, socioeconomic, and medical factors as well as vaccine type, only cannabis use disorder was associated with a higher risk in African Americans, compared with matched Caucasians (HR = 1.63; 95% confidence interval, 1.06-2.51).

“When we adjusted the data to account for comorbidities and for socioeconomic background, we no longer saw a difference between those with substance use disorders and those without – the only exception to this was for people with cannabis use disorder,” said Dr. Volkow.

“This suggests that these factors, which are often associated with substance use disorders, are likely the underlying drivers for the increased risk,” she continued.

She added that it is important for other studies to investigate why individuals with cannabis use disorder had a higher risk for breakthrough infections.
 

Good news, bad news

Commenting for this news organization, Anna Lembke, MD, professor of psychiatry and behavioral sciences, Stanford (Calif.) University, said the study is important and contains good news and bad news.

The good news, she said, “is that, after controlling for comorbidities and socioeconomic variables, patients with SUDs are no more likely than patients without SUDs to get COVID after getting vaccinated, and the bad news is that if vaccinated patients with SUDs do get COVID, they’re more likely to end up hospitalized or die from it,” said Dr. Lembke, who was not involved with the study.

“The take-home message for clinicians is that if your vaccinated patient with an SUD gets COVID, be on the alert for a more complicated medical outcome and a higher risk of death,” warned Dr. Lembke.

This study was supported by the U.S. National Institute on Drug Abuse, the U.S. National Institute of Aging, and the Clinical and Translational Science Collaborative (CTSC) of Cleveland. No disclosures were listed on the original study. Dr. Lembke has disclosed no relevant financial relationships.

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

Individuals with substance use disorders (SUDs) have a twofold increased risk for COVID-related hospitalization and death even after vaccination, new research shows.

Investigators analyzed data on over 10,000 vaccinated individuals with various SUDs and almost 600,000 vaccinated individuals without an SUD. They found about twice as many individuals with an SUD had a breakthrough COVID-19 infection as their counterparts without an SUD, at 7% versus 3.6%, respectively.

Worrisome phase

SUDs are “often associated with multiple comorbid conditions that are known risk factors for severe outcome of COVID-19 infection,” the investigators note.

Research published early in the pandemic showed patients with SUDs, including alcohol, cannabis, cocaine, opioid, and tobacco use disorders, were “at increased risk for COVID-19 infection and associated severe outcomes, especially among African Americans,” they add.

To date, no research has focused on the potential risk for COVID in individuals with SUDs following vaccination. In addition, although vaccines are “very effective,” breakthrough infections have been recorded, “highlighting the need to identify populations that might be most vulnerable, as we have entered a worrisome new phase of the pandemic,” the authors write.

For the study, researchers used a data analytics platform that included de-identified information from 63 health care organizations across the U.S. to estimate the risk for breakthrough COVID-19 among vaccinated patients with SUD (n = 30,183; mean age 59.3, 51.4% male, 63.2% White, 26.2% African American), compared with vaccinated individuals without SUDs (n = 549,189; mean age 54.7, 43.2% male, 63.4% White, 14.3% African American) between December 2020 and August 2021.

They also conducted statistical analyses to examine how the rate of breakthrough cases changed over that timeframe.

The cohorts were matched by demographics, adverse socioeconomic determinants of health, lifetime medical and psychiatric comorbidities, and vaccine type.

Among vaccinated SUD patients, three-quarters received the Pfizer-BioNTech vaccine, one-fifth received the Moderna vaccine, and 3.3% received the Johnson & Johnson vaccine.

In contrast, among the vaccinated non-SUD population, almost all (88.2%) received the Pfizer-BioNTech vaccine, 10% received Moderna, and only 1.2% received the Johnson & Johnson vaccine.
 

Underlying drivers

The prevalence of adverse socioeconomic determinants of health was higher in vaccinated individuals with SUDs compared to those without (7.9% vs. 1.2%, respectively). Moreover, vaccinated patients with SUD had a higher lifetime prevalence of all comorbidities as well as transplants (all Ps < .001).

The risk for breakthrough infection was significantly higher in vaccinated individuals with SUDs compared to those without (all Ps < .001).

After controlling for adverse socioeconomic determinants of health and comorbid medical conditions, the risk for breakthrough infection “no longer differed in SUD compared to non-SUD cohorts, except for patients with cannabis use disorder, who remained at significantly increased risk,” the authors report.

In both populations, the rate of breakthrough infections “steadily increased” between January and August 2021.

The risk for hospitalization and death was higher among those with breakthrough infections, compared with those in the matched cohort without breakthrough infections, but the risk for hospitalization and death were higher in the SUD compared with the non-SUD population.

In the SUD patients, after matching an array of demographic, socioeconomic, and medical factors as well as vaccine type, only cannabis use disorder was associated with a higher risk in African Americans, compared with matched Caucasians (HR = 1.63; 95% confidence interval, 1.06-2.51).

“When we adjusted the data to account for comorbidities and for socioeconomic background, we no longer saw a difference between those with substance use disorders and those without – the only exception to this was for people with cannabis use disorder,” said Dr. Volkow.

“This suggests that these factors, which are often associated with substance use disorders, are likely the underlying drivers for the increased risk,” she continued.

She added that it is important for other studies to investigate why individuals with cannabis use disorder had a higher risk for breakthrough infections.
 

Good news, bad news

Commenting for this news organization, Anna Lembke, MD, professor of psychiatry and behavioral sciences, Stanford (Calif.) University, said the study is important and contains good news and bad news.

The good news, she said, “is that, after controlling for comorbidities and socioeconomic variables, patients with SUDs are no more likely than patients without SUDs to get COVID after getting vaccinated, and the bad news is that if vaccinated patients with SUDs do get COVID, they’re more likely to end up hospitalized or die from it,” said Dr. Lembke, who was not involved with the study.

“The take-home message for clinicians is that if your vaccinated patient with an SUD gets COVID, be on the alert for a more complicated medical outcome and a higher risk of death,” warned Dr. Lembke.

This study was supported by the U.S. National Institute on Drug Abuse, the U.S. National Institute of Aging, and the Clinical and Translational Science Collaborative (CTSC) of Cleveland. No disclosures were listed on the original study. Dr. Lembke has disclosed no relevant financial relationships.

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

Ready access to maternity services in rural areas is not a given, yet access to obstetric hospitals is associated with decreased rates of preterm birth and neonatal/perinatal mortality.

Little is known, however, about the availability of obstetric centers with respect to birth volume, geographic distribution among states, proximity of obstetric hospitals, and urban adjacency.

“This knowledge is fundamental to inform clinical and policy efforts to optimize perinatal regionalization, care delivery, and outcomes,” wrote Sara C. Handley, MD, MSCE, of the Roberts Center for Pediatric Research at the Children’s Hospital of Philadelphia, and colleagues, who undertook to fill that information gap in a study. It was published online Oct. 8 in JAMA Network Open.

Her group found birth volumes varied among obstetric hospitals, with many low-volume facilities located in rural, even isolated, areas, which suggests a need to ensure better access to perinatal care for women in these locations.

Using American Hospital Association data, the researchers examined the birth volumes and geographic distributions of 3,207 maternity hospitals from 2010 to 2018. In a cohort of 34,054,951 births, 56.8% occurred in high-volume obstetric facilities, and 37.4% in low-volume hospitals. Among the latter, 18.9% were isolated in location and not within 30 miles of any other obstetric hospital.

Most infants (19,327,487) were born in hospitals with more than 2,000 births per year, the study found, but a substantial 2,528,259, or 7.4%, were born in low-volume centers reporting 10 to 500 births annually.

“We were surprised by the number of low-volume hospitals and the number of births in low-volume hospitals,” Dr. Handley said in an interview. Many low-volume hospitals are in rural areas, which may require patients to drive long distances. These hospitals are at high risk of closure and such closures may further increase travel time.

Among low-volume hospitals, 23.9% were within the study proximity threshold of 30 miles of a hospital with more than 2,000 deliveries per year. “And when you’re in labor, even 30 miles is a long drive,” Dr. Handley said.

According to the authors, these findings highlight the need to balance care availability and sufficient patient volume by ensuring access and referral to high-quality perinatal care. They suggest perinatal care regionalization policies need review to improve maternal and infant outcomes.

But although the need is pressing, meeting it will not happen quickly, Dr. Handley said. “Change will require buy-in from multiple stakeholders and investment at many levels.”

The American College of Obstetrics and Gynecology has previously raised the alarm about general health disparities among women in underserved rural communities.

Anne L. Banfield, MD, director of women’s health services at Davis Medical Center in the mountain town of Elkins, W.V., is one obstetrician/gynecologist who is all too familiar with the problem of shrinking perinatal facilities. “Closures have impacted services,” she said in an interview, noting that one hospital in her region closed its birthing unit because of financial considerations. “The next closest facility to ours is 20 miles to the west and more than 60 miles in any other direction,” she said. “And geography can create challenges. Because we’re located in the mountains, it can take 2 hours to get to our facility.”

The hope is that these findings will inform discussions on regionalization policy for perinatal care to improve maternal and infant outcomes and address concerns about isolated obstetric hospitals, the authors said.

Dr. Banfield emphasized that obstetric facilities should be made a priority even if they’re less profitable than other services and not a major contributor to the bottom line. But that will require rethinking reimbursement models to align with community needs. “Everyone has a mother – no one springs from a pod – but the fact is, we’re not paying enough for maternal health care,” she said.

A top priority, she noted, is attracting sufficient staff; not only doctors, but also nurses and midwives with the skill sets required for perinatal care, which differ from those of general surgery and outpatient services. “We have to make financial changes to make this care feasible,” Dr. Banfield said.

In similar recent research, a study published online in the October issue of Health Affairs, showed that with rural hospitals facing increased financial distress, they may merge with other hospitals/systems, potentially reducing service lines that are less profitable or that duplicate services offered by the acquiring institution. Among those often on the chopping block is perinatal care.

“Our analysis of rural hospital discharge data found that merged hospitals were more likely than independent hospitals to eliminate maternal, neonatal, and also surgical care,” lead author Lan Liang, PhD, senior economist at the Agency for Healthcare Research and Quality (AHRQ) in Rockville, Md., said in an interview. This finding was consistent with previous AHRQ research using hospital self-reports, she added.

The study sample comprised 172 rural hospitals that merged during the period 2009-2016 in 32 states and 549 nonmerged comparison hospitals. In the premerger period, 74.5% of hospitals that merged provided maternal/neonatal care. This percentage decreased to 61.1% in the postmerger period. In contrast, the percentage of comparison hospitals providing these services remained stable during both periods (64.3% and 65.1%, respectively).

After weighting and adjusting for variables, the researchers found that from the premerger period to 1 year post merger, the percentage of hospitals providing these services decreased by 6.7 percentage points more for merged than for comparison hospitals (P = .06).

In the second year post merger, the percentage of hospitals providing maternal/neonatal services decreased by 7.2 percentage points more for merged than for comparison hospitals (P = .09).

“We did not, however, see a reduction in the volume of maternity services in rural communities, which suggests that women are just traveling farther to give birth,” Dr. Liang said.

Although mergers might salvage hospitals’ sustainability, the authors wrote, they do not necessarily mean that service lines are retained or that hospitals are as responsive to community needs as they were before the merger.

The analysis concluded that continuing access to maternal/neonatal care in rural areas is not a given. “Stakeholders, including payers, policy makers, and community-based organizations, need to monitor the availability of maternity services to ensure women have options in childbirth providers,” Dr. Liang said.

She and her associates called for payer-supported, multi-stakeholder initiatives to transform rural health care to be both financially sustainable and responsive to population needs.

The study by Dr. Handley and colleagues was supported by the National Institutes of Health (NIH) and the Eunice Shriver National Institute of Child Health and Human Development (NICHD). Dr. Handley reported grants from the NIH outside of the submitted work. Several coauthors reported grants from, variously, the NIH, the NICHD, and the Agency for Healthcare Research and Quality (AHRQ). The study by Dr. Liang and associates was supported by the AHRQ’s Center for Financing, Access, and Cost Trends, and the Healthcare Cost and Utilization Project. The authors disclosed no competing interests.

Ready access to maternity services in rural areas is not a given, yet access to obstetric hospitals is associated with decreased rates of preterm birth and neonatal/perinatal mortality.

Little is known, however, about the availability of obstetric centers with respect to birth volume, geographic distribution among states, proximity of obstetric hospitals, and urban adjacency.

“This knowledge is fundamental to inform clinical and policy efforts to optimize perinatal regionalization, care delivery, and outcomes,” wrote Sara C. Handley, MD, MSCE, of the Roberts Center for Pediatric Research at the Children’s Hospital of Philadelphia, and colleagues, who undertook to fill that information gap in a study. It was published online Oct. 8 in JAMA Network Open.

Her group found birth volumes varied among obstetric hospitals, with many low-volume facilities located in rural, even isolated, areas, which suggests a need to ensure better access to perinatal care for women in these locations.

Using American Hospital Association data, the researchers examined the birth volumes and geographic distributions of 3,207 maternity hospitals from 2010 to 2018. In a cohort of 34,054,951 births, 56.8% occurred in high-volume obstetric facilities, and 37.4% in low-volume hospitals. Among the latter, 18.9% were isolated in location and not within 30 miles of any other obstetric hospital.

Most infants (19,327,487) were born in hospitals with more than 2,000 births per year, the study found, but a substantial 2,528,259, or 7.4%, were born in low-volume centers reporting 10 to 500 births annually.

“We were surprised by the number of low-volume hospitals and the number of births in low-volume hospitals,” Dr. Handley said in an interview. Many low-volume hospitals are in rural areas, which may require patients to drive long distances. These hospitals are at high risk of closure and such closures may further increase travel time.

Among low-volume hospitals, 23.9% were within the study proximity threshold of 30 miles of a hospital with more than 2,000 deliveries per year. “And when you’re in labor, even 30 miles is a long drive,” Dr. Handley said.

According to the authors, these findings highlight the need to balance care availability and sufficient patient volume by ensuring access and referral to high-quality perinatal care. They suggest perinatal care regionalization policies need review to improve maternal and infant outcomes.

But although the need is pressing, meeting it will not happen quickly, Dr. Handley said. “Change will require buy-in from multiple stakeholders and investment at many levels.”

The American College of Obstetrics and Gynecology has previously raised the alarm about general health disparities among women in underserved rural communities.

Anne L. Banfield, MD, director of women’s health services at Davis Medical Center in the mountain town of Elkins, W.V., is one obstetrician/gynecologist who is all too familiar with the problem of shrinking perinatal facilities. “Closures have impacted services,” she said in an interview, noting that one hospital in her region closed its birthing unit because of financial considerations. “The next closest facility to ours is 20 miles to the west and more than 60 miles in any other direction,” she said. “And geography can create challenges. Because we’re located in the mountains, it can take 2 hours to get to our facility.”

The hope is that these findings will inform discussions on regionalization policy for perinatal care to improve maternal and infant outcomes and address concerns about isolated obstetric hospitals, the authors said.

Dr. Banfield emphasized that obstetric facilities should be made a priority even if they’re less profitable than other services and not a major contributor to the bottom line. But that will require rethinking reimbursement models to align with community needs. “Everyone has a mother – no one springs from a pod – but the fact is, we’re not paying enough for maternal health care,” she said.

A top priority, she noted, is attracting sufficient staff; not only doctors, but also nurses and midwives with the skill sets required for perinatal care, which differ from those of general surgery and outpatient services. “We have to make financial changes to make this care feasible,” Dr. Banfield said.

In similar recent research, a study published online in the October issue of Health Affairs, showed that with rural hospitals facing increased financial distress, they may merge with other hospitals/systems, potentially reducing service lines that are less profitable or that duplicate services offered by the acquiring institution. Among those often on the chopping block is perinatal care.

“Our analysis of rural hospital discharge data found that merged hospitals were more likely than independent hospitals to eliminate maternal, neonatal, and also surgical care,” lead author Lan Liang, PhD, senior economist at the Agency for Healthcare Research and Quality (AHRQ) in Rockville, Md., said in an interview. This finding was consistent with previous AHRQ research using hospital self-reports, she added.

The study sample comprised 172 rural hospitals that merged during the period 2009-2016 in 32 states and 549 nonmerged comparison hospitals. In the premerger period, 74.5% of hospitals that merged provided maternal/neonatal care. This percentage decreased to 61.1% in the postmerger period. In contrast, the percentage of comparison hospitals providing these services remained stable during both periods (64.3% and 65.1%, respectively).

After weighting and adjusting for variables, the researchers found that from the premerger period to 1 year post merger, the percentage of hospitals providing these services decreased by 6.7 percentage points more for merged than for comparison hospitals (P = .06).

In the second year post merger, the percentage of hospitals providing maternal/neonatal services decreased by 7.2 percentage points more for merged than for comparison hospitals (P = .09).

“We did not, however, see a reduction in the volume of maternity services in rural communities, which suggests that women are just traveling farther to give birth,” Dr. Liang said.

Although mergers might salvage hospitals’ sustainability, the authors wrote, they do not necessarily mean that service lines are retained or that hospitals are as responsive to community needs as they were before the merger.

The analysis concluded that continuing access to maternal/neonatal care in rural areas is not a given. “Stakeholders, including payers, policy makers, and community-based organizations, need to monitor the availability of maternity services to ensure women have options in childbirth providers,” Dr. Liang said.

She and her associates called for payer-supported, multi-stakeholder initiatives to transform rural health care to be both financially sustainable and responsive to population needs.

The study by Dr. Handley and colleagues was supported by the National Institutes of Health (NIH) and the Eunice Shriver National Institute of Child Health and Human Development (NICHD). Dr. Handley reported grants from the NIH outside of the submitted work. Several coauthors reported grants from, variously, the NIH, the NICHD, and the Agency for Healthcare Research and Quality (AHRQ). The study by Dr. Liang and associates was supported by the AHRQ’s Center for Financing, Access, and Cost Trends, and the Healthcare Cost and Utilization Project. The authors disclosed no competing interests.

Ready access to maternity services in rural areas is not a given, yet access to obstetric hospitals is associated with decreased rates of preterm birth and neonatal/perinatal mortality.

Little is known, however, about the availability of obstetric centers with respect to birth volume, geographic distribution among states, proximity of obstetric hospitals, and urban adjacency.

“This knowledge is fundamental to inform clinical and policy efforts to optimize perinatal regionalization, care delivery, and outcomes,” wrote Sara C. Handley, MD, MSCE, of the Roberts Center for Pediatric Research at the Children’s Hospital of Philadelphia, and colleagues, who undertook to fill that information gap in a study. It was published online Oct. 8 in JAMA Network Open.

Her group found birth volumes varied among obstetric hospitals, with many low-volume facilities located in rural, even isolated, areas, which suggests a need to ensure better access to perinatal care for women in these locations.

Using American Hospital Association data, the researchers examined the birth volumes and geographic distributions of 3,207 maternity hospitals from 2010 to 2018. In a cohort of 34,054,951 births, 56.8% occurred in high-volume obstetric facilities, and 37.4% in low-volume hospitals. Among the latter, 18.9% were isolated in location and not within 30 miles of any other obstetric hospital.

Most infants (19,327,487) were born in hospitals with more than 2,000 births per year, the study found, but a substantial 2,528,259, or 7.4%, were born in low-volume centers reporting 10 to 500 births annually.

“We were surprised by the number of low-volume hospitals and the number of births in low-volume hospitals,” Dr. Handley said in an interview. Many low-volume hospitals are in rural areas, which may require patients to drive long distances. These hospitals are at high risk of closure and such closures may further increase travel time.

Among low-volume hospitals, 23.9% were within the study proximity threshold of 30 miles of a hospital with more than 2,000 deliveries per year. “And when you’re in labor, even 30 miles is a long drive,” Dr. Handley said.

According to the authors, these findings highlight the need to balance care availability and sufficient patient volume by ensuring access and referral to high-quality perinatal care. They suggest perinatal care regionalization policies need review to improve maternal and infant outcomes.

But although the need is pressing, meeting it will not happen quickly, Dr. Handley said. “Change will require buy-in from multiple stakeholders and investment at many levels.”

The American College of Obstetrics and Gynecology has previously raised the alarm about general health disparities among women in underserved rural communities.

Anne L. Banfield, MD, director of women’s health services at Davis Medical Center in the mountain town of Elkins, W.V., is one obstetrician/gynecologist who is all too familiar with the problem of shrinking perinatal facilities. “Closures have impacted services,” she said in an interview, noting that one hospital in her region closed its birthing unit because of financial considerations. “The next closest facility to ours is 20 miles to the west and more than 60 miles in any other direction,” she said. “And geography can create challenges. Because we’re located in the mountains, it can take 2 hours to get to our facility.”

The hope is that these findings will inform discussions on regionalization policy for perinatal care to improve maternal and infant outcomes and address concerns about isolated obstetric hospitals, the authors said.

Dr. Banfield emphasized that obstetric facilities should be made a priority even if they’re less profitable than other services and not a major contributor to the bottom line. But that will require rethinking reimbursement models to align with community needs. “Everyone has a mother – no one springs from a pod – but the fact is, we’re not paying enough for maternal health care,” she said.

A top priority, she noted, is attracting sufficient staff; not only doctors, but also nurses and midwives with the skill sets required for perinatal care, which differ from those of general surgery and outpatient services. “We have to make financial changes to make this care feasible,” Dr. Banfield said.

In similar recent research, a study published online in the October issue of Health Affairs, showed that with rural hospitals facing increased financial distress, they may merge with other hospitals/systems, potentially reducing service lines that are less profitable or that duplicate services offered by the acquiring institution. Among those often on the chopping block is perinatal care.

“Our analysis of rural hospital discharge data found that merged hospitals were more likely than independent hospitals to eliminate maternal, neonatal, and also surgical care,” lead author Lan Liang, PhD, senior economist at the Agency for Healthcare Research and Quality (AHRQ) in Rockville, Md., said in an interview. This finding was consistent with previous AHRQ research using hospital self-reports, she added.

The study sample comprised 172 rural hospitals that merged during the period 2009-2016 in 32 states and 549 nonmerged comparison hospitals. In the premerger period, 74.5% of hospitals that merged provided maternal/neonatal care. This percentage decreased to 61.1% in the postmerger period. In contrast, the percentage of comparison hospitals providing these services remained stable during both periods (64.3% and 65.1%, respectively).

After weighting and adjusting for variables, the researchers found that from the premerger period to 1 year post merger, the percentage of hospitals providing these services decreased by 6.7 percentage points more for merged than for comparison hospitals (P = .06).

In the second year post merger, the percentage of hospitals providing maternal/neonatal services decreased by 7.2 percentage points more for merged than for comparison hospitals (P = .09).

“We did not, however, see a reduction in the volume of maternity services in rural communities, which suggests that women are just traveling farther to give birth,” Dr. Liang said.

Although mergers might salvage hospitals’ sustainability, the authors wrote, they do not necessarily mean that service lines are retained or that hospitals are as responsive to community needs as they were before the merger.

The analysis concluded that continuing access to maternal/neonatal care in rural areas is not a given. “Stakeholders, including payers, policy makers, and community-based organizations, need to monitor the availability of maternity services to ensure women have options in childbirth providers,” Dr. Liang said.

She and her associates called for payer-supported, multi-stakeholder initiatives to transform rural health care to be both financially sustainable and responsive to population needs.

The study by Dr. Handley and colleagues was supported by the National Institutes of Health (NIH) and the Eunice Shriver National Institute of Child Health and Human Development (NICHD). Dr. Handley reported grants from the NIH outside of the submitted work. Several coauthors reported grants from, variously, the NIH, the NICHD, and the Agency for Healthcare Research and Quality (AHRQ). The study by Dr. Liang and associates was supported by the AHRQ’s Center for Financing, Access, and Cost Trends, and the Healthcare Cost and Utilization Project. The authors disclosed no competing interests.