Women's Health

Cervical cancer screening is a routine procedure, but in rare instances, there can be medical complications. A new study finds that, compared with women who have normal results, women who are diagnosed with an invasive malignancy have an increased risk for iatrogenic injuries.

Researchers in Sweden analyzed data on more than 3 million women who had undergone cervical cancer screening. The team found that 42 iatrogenic injuries that required at least 2 days of hospitalization occurred during the diagnostic work-up of women who had an abnormal screening test.

“Although cervical cancer screening is one of the most successful cancer prevention programs ... our research indicates that women with invasive cervical cancer experienced medical complications and psychological stress during their diagnostic work-up, although at a very low level,” commented corresponding author Qing Shen, PhD, from the department of medical epidemiology and biostatistics at the Karolinska Institute in Stockholm, Sweden.

The study was published in Cancer Epidemiology, Biomarkers & Prevention.

“Injuries can occur with diagnostic evaluation for cervical cancer,” commented Kecia Gaither, MD, MPH, FACOG, director of perinatal services at Lincoln Medical and Mental Health Center, New York City Health and Hospitals System, who was not involved in the study.

“Given the fact that neovascularization occurs with cancers, a large biopsy in such a circumstance could lead to a hematoma or excessive blood loss. It rarely occurs but most certainly is possible,” said Dr. Gaither.

Also weighing in with comments, Cathy Popadiuk, MD, FRCS, an associate professor of medicine in the department of obstetrics and gynecology at Memorial University of Newfoundland, St. John’s, said the findings are reflective of the real-world and North American experience.

“There are indeed rare bad things that can happen during diagnostic work-up of abnormal pap smears, and usually this is with associated other disease, such as actual cancer or fibroids that can also bleed and may be in the cervix, etc.,” she told this news organization. “And definitely, when there is undetected cancer, this can bleed, requiring transfusion and hospital admission.”

Dr. Popadiuk pointed out that Sweden may be more liberal in admitting patients to hospital, whereas in North America, “we are trying to move away from inpatient care.” She added, “When you are getting these relatively minor procedures, you don’t expect something bad to happen in the clinic.”

Women may become anxious, and admission is the easiest way to arrange for care such as transfusions or observation for more bleeding, she noted. In addition, vaginal packing may be needed to control hemorrhage, and “with vaginal packing, women are unable to void and need a Foley catheter, and that, again, cannot be managed at home easily,” she explained. “After bleeding settles, the vaginal pack is removed, often the next day.” This may be why some women are admitted to hospital.
 

Increased risk of injury

In a previous study, Dr. Shen and colleagues found there was an increased risk for injuries during the period before and after a diagnosis of any cancer (BMJ. 2016;354:i4218). Those findings suggested the interval between first suspicion of cancer and diagnosis or initiation of treatment might be a high-risk time for injuries in cancer care.

In this latest study, they assessed whether there was a similar increase in injury risk among patients screened for cervical cancer. Using the Swedish Total Population Register, they identified 3,016,307 women who had undergone cervical screening during the period 2001-2012.

The final analysis included 1,853,510 women whose pap smear results were normal; 22,435 women who were diagnosed with cervical intraepithelial neoplasia (CIN); 20,692 women with CIN2; 36,542 women with CIN3 or adenocarcinoma in situ (AIS); and 5,189 women with invasive cervical cancer.

The team found that, among women who had an abnormal screening test, 42 iatrogenic injuries occurred that required at least 2 days of hospital admission. The highest risk was among women diagnosed with invasive cancer. The risk was also increased among women diagnosed with CIN3/AIS, but not among women with lower grades of CIN.

The most common types of iatrogenic injuries were hemorrhage or hematoma and infections. Among all groups of women, the incidence rate of injuries that were caused by medical procedures and care was greater than that of injuries caused by drugs or biological substances.

A total of 91 noniatrogenic injuries that required at least 1 day of hospitalization were identified. The risk was increased among women with invasive cervical cancer but not for women with other cervical abnormalities. The most common type of noniatrogenic injury was unintentional injuries.

The study was sponsored by the Swedish Cancer Society and the Swedish Research Council for Health, Working Life and Welfare. One author received a Karolinska Institute Senior Researcher Award and a Strategic Research Area in Epidemiology Award, and one author received a grant from the China Scholarship Council. Dr. Shen has disclosed no relevant financial relationships. Dr. Popadiuk has received personal fees and nonfinancial support as a member of the OncoSim Initiative from the Canadian Partnership Against Cancer.
 

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

Cervical cancer screening is a routine procedure, but in rare instances, there can be medical complications. A new study finds that, compared with women who have normal results, women who are diagnosed with an invasive malignancy have an increased risk for iatrogenic injuries.

Researchers in Sweden analyzed data on more than 3 million women who had undergone cervical cancer screening. The team found that 42 iatrogenic injuries that required at least 2 days of hospitalization occurred during the diagnostic work-up of women who had an abnormal screening test.

“Although cervical cancer screening is one of the most successful cancer prevention programs ... our research indicates that women with invasive cervical cancer experienced medical complications and psychological stress during their diagnostic work-up, although at a very low level,” commented corresponding author Qing Shen, PhD, from the department of medical epidemiology and biostatistics at the Karolinska Institute in Stockholm, Sweden.

The study was published in Cancer Epidemiology, Biomarkers & Prevention.

“Injuries can occur with diagnostic evaluation for cervical cancer,” commented Kecia Gaither, MD, MPH, FACOG, director of perinatal services at Lincoln Medical and Mental Health Center, New York City Health and Hospitals System, who was not involved in the study.

“Given the fact that neovascularization occurs with cancers, a large biopsy in such a circumstance could lead to a hematoma or excessive blood loss. It rarely occurs but most certainly is possible,” said Dr. Gaither.

Also weighing in with comments, Cathy Popadiuk, MD, FRCS, an associate professor of medicine in the department of obstetrics and gynecology at Memorial University of Newfoundland, St. John’s, said the findings are reflective of the real-world and North American experience.

“There are indeed rare bad things that can happen during diagnostic work-up of abnormal pap smears, and usually this is with associated other disease, such as actual cancer or fibroids that can also bleed and may be in the cervix, etc.,” she told this news organization. “And definitely, when there is undetected cancer, this can bleed, requiring transfusion and hospital admission.”

Dr. Popadiuk pointed out that Sweden may be more liberal in admitting patients to hospital, whereas in North America, “we are trying to move away from inpatient care.” She added, “When you are getting these relatively minor procedures, you don’t expect something bad to happen in the clinic.”

Women may become anxious, and admission is the easiest way to arrange for care such as transfusions or observation for more bleeding, she noted. In addition, vaginal packing may be needed to control hemorrhage, and “with vaginal packing, women are unable to void and need a Foley catheter, and that, again, cannot be managed at home easily,” she explained. “After bleeding settles, the vaginal pack is removed, often the next day.” This may be why some women are admitted to hospital.
 

Increased risk of injury

In a previous study, Dr. Shen and colleagues found there was an increased risk for injuries during the period before and after a diagnosis of any cancer (BMJ. 2016;354:i4218). Those findings suggested the interval between first suspicion of cancer and diagnosis or initiation of treatment might be a high-risk time for injuries in cancer care.

In this latest study, they assessed whether there was a similar increase in injury risk among patients screened for cervical cancer. Using the Swedish Total Population Register, they identified 3,016,307 women who had undergone cervical screening during the period 2001-2012.

The final analysis included 1,853,510 women whose pap smear results were normal; 22,435 women who were diagnosed with cervical intraepithelial neoplasia (CIN); 20,692 women with CIN2; 36,542 women with CIN3 or adenocarcinoma in situ (AIS); and 5,189 women with invasive cervical cancer.

The team found that, among women who had an abnormal screening test, 42 iatrogenic injuries occurred that required at least 2 days of hospital admission. The highest risk was among women diagnosed with invasive cancer. The risk was also increased among women diagnosed with CIN3/AIS, but not among women with lower grades of CIN.

The most common types of iatrogenic injuries were hemorrhage or hematoma and infections. Among all groups of women, the incidence rate of injuries that were caused by medical procedures and care was greater than that of injuries caused by drugs or biological substances.

A total of 91 noniatrogenic injuries that required at least 1 day of hospitalization were identified. The risk was increased among women with invasive cervical cancer but not for women with other cervical abnormalities. The most common type of noniatrogenic injury was unintentional injuries.

The study was sponsored by the Swedish Cancer Society and the Swedish Research Council for Health, Working Life and Welfare. One author received a Karolinska Institute Senior Researcher Award and a Strategic Research Area in Epidemiology Award, and one author received a grant from the China Scholarship Council. Dr. Shen has disclosed no relevant financial relationships. Dr. Popadiuk has received personal fees and nonfinancial support as a member of the OncoSim Initiative from the Canadian Partnership Against Cancer.
 

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

Cervical cancer screening is a routine procedure, but in rare instances, there can be medical complications. A new study finds that, compared with women who have normal results, women who are diagnosed with an invasive malignancy have an increased risk for iatrogenic injuries.

Researchers in Sweden analyzed data on more than 3 million women who had undergone cervical cancer screening. The team found that 42 iatrogenic injuries that required at least 2 days of hospitalization occurred during the diagnostic work-up of women who had an abnormal screening test.

“Although cervical cancer screening is one of the most successful cancer prevention programs ... our research indicates that women with invasive cervical cancer experienced medical complications and psychological stress during their diagnostic work-up, although at a very low level,” commented corresponding author Qing Shen, PhD, from the department of medical epidemiology and biostatistics at the Karolinska Institute in Stockholm, Sweden.

The study was published in Cancer Epidemiology, Biomarkers & Prevention.

“Injuries can occur with diagnostic evaluation for cervical cancer,” commented Kecia Gaither, MD, MPH, FACOG, director of perinatal services at Lincoln Medical and Mental Health Center, New York City Health and Hospitals System, who was not involved in the study.

“Given the fact that neovascularization occurs with cancers, a large biopsy in such a circumstance could lead to a hematoma or excessive blood loss. It rarely occurs but most certainly is possible,” said Dr. Gaither.

Also weighing in with comments, Cathy Popadiuk, MD, FRCS, an associate professor of medicine in the department of obstetrics and gynecology at Memorial University of Newfoundland, St. John’s, said the findings are reflective of the real-world and North American experience.

“There are indeed rare bad things that can happen during diagnostic work-up of abnormal pap smears, and usually this is with associated other disease, such as actual cancer or fibroids that can also bleed and may be in the cervix, etc.,” she told this news organization. “And definitely, when there is undetected cancer, this can bleed, requiring transfusion and hospital admission.”

Dr. Popadiuk pointed out that Sweden may be more liberal in admitting patients to hospital, whereas in North America, “we are trying to move away from inpatient care.” She added, “When you are getting these relatively minor procedures, you don’t expect something bad to happen in the clinic.”

Women may become anxious, and admission is the easiest way to arrange for care such as transfusions or observation for more bleeding, she noted. In addition, vaginal packing may be needed to control hemorrhage, and “with vaginal packing, women are unable to void and need a Foley catheter, and that, again, cannot be managed at home easily,” she explained. “After bleeding settles, the vaginal pack is removed, often the next day.” This may be why some women are admitted to hospital.
 

Increased risk of injury

In a previous study, Dr. Shen and colleagues found there was an increased risk for injuries during the period before and after a diagnosis of any cancer (BMJ. 2016;354:i4218). Those findings suggested the interval between first suspicion of cancer and diagnosis or initiation of treatment might be a high-risk time for injuries in cancer care.

In this latest study, they assessed whether there was a similar increase in injury risk among patients screened for cervical cancer. Using the Swedish Total Population Register, they identified 3,016,307 women who had undergone cervical screening during the period 2001-2012.

The final analysis included 1,853,510 women whose pap smear results were normal; 22,435 women who were diagnosed with cervical intraepithelial neoplasia (CIN); 20,692 women with CIN2; 36,542 women with CIN3 or adenocarcinoma in situ (AIS); and 5,189 women with invasive cervical cancer.

The team found that, among women who had an abnormal screening test, 42 iatrogenic injuries occurred that required at least 2 days of hospital admission. The highest risk was among women diagnosed with invasive cancer. The risk was also increased among women diagnosed with CIN3/AIS, but not among women with lower grades of CIN.

The most common types of iatrogenic injuries were hemorrhage or hematoma and infections. Among all groups of women, the incidence rate of injuries that were caused by medical procedures and care was greater than that of injuries caused by drugs or biological substances.

A total of 91 noniatrogenic injuries that required at least 1 day of hospitalization were identified. The risk was increased among women with invasive cervical cancer but not for women with other cervical abnormalities. The most common type of noniatrogenic injury was unintentional injuries.

The study was sponsored by the Swedish Cancer Society and the Swedish Research Council for Health, Working Life and Welfare. One author received a Karolinska Institute Senior Researcher Award and a Strategic Research Area in Epidemiology Award, and one author received a grant from the China Scholarship Council. Dr. Shen has disclosed no relevant financial relationships. Dr. Popadiuk has received personal fees and nonfinancial support as a member of the OncoSim Initiative from the Canadian Partnership Against Cancer.
 

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

Denosumab boosted bone mineral density (BMD) over 12 months to a greater extent than did alendronate in a randomized, 12-month study. The investigator-initiated research compared BMD at the lumbar spine and elsewhere among people with systemic lupus erythematosus (SLE) and other autoimmune conditions. Long-term glucocorticoid therapy places some people in this group at higher risk for adverse effects of bone density loss.

“Glucocorticoids remain the mainstay of treatment of rheumatic diseases, but [they are] a major risk factor for osteoporosis and fracture,” study author Chi Chiu Mok, MD, said in an interview.

Compared with baseline, adults randomly assigned to denosumab had a 3.5% increase in lumbar spine BMD at 12 months, compared with 2.5% among those taking alendronate, a significant difference. Dr. Mok, a consultant and honorary associate professor in the department of medicine and nuclear medicine at Tuen Mun Hospital in Hong Kong, presented the study results at the virtual annual meeting of the American College of Rheumatology.

“Given the knowledge that denosumab is more effective than alendronate in raising spinal BMD in chronic users of GCs without increasing adverse events, this drug may be considered as an alternative first-line therapy in higher-risk patients and in those who are contraindicated for the oral bisphosphonates,” he said.
 

Cost considerations

Denosumab is a human monoclonal antibody administered as a subcutaneous injection, available under the brand names Prolia and Xgeva. Alendronate is an oral agent available as both generic and brand name formulations.

“Yes, denosumab is more expensive, more costly than oral alendronate, but our study shows efficacy is better for steroid users,” Dr. Mok said in answer to a question about cost disparity between the two agents during his presentation at the meeting. “For patients who are contraindicated or have low compliance for bisphosphonate, or are high-risk patients, I recommend first-line use of denosumab.”

Researchers previously studied these agents, including a smaller study by Dr. Mok and colleagues that showed a BMD benefit after switching people on an oral bisphosphonate to denosumab. However, he said, “There is a paucity of data regarding comparative efficacy of denosumab and the bisphosphonates in long-term steroid users.”

To explore any differences in a larger patient population, the investigators randomly assigned adults with SLE and other autoimmune conditions to the two treatments: denosumab 60 mg subcutaneoulsy every 6 months or oral alendronate 70 mg/week. All patients also received 3,000 mg calcium and 1,000 IU vitamin D₃ (cholecalciferol) each day.

After three discontinuations in denosumab cohort and four in the alendronate group, the researchers evaluated 69 people taking denosumab and 70 others taking alendronate. The discontinuations were caused by noncompliance, Dr. Mok said, not by adverse events.

Adverse events were reported, but the rate did not differ significantly between groups. Dr. Mok highlighted some notable differences, including more minor infections and arthralgias reported in the denosumab cohort. Chest discomfort was reported in one denosumab recipient versus no patients in the alendronate group. Dyspepsia/upper GI symptoms and dizziness/vertigo occurred more often in the alendronate group.

Women were 96% of the study population, and mean age was 50 years. A majority, 81%, had underlying SLE. Other diagnoses included rheumatoid arthritis, myositis, antineutrophil cytoplasmic antibody–associated vasculitis, and polymyalgia rheumatica. The mean dose of prednisolone at study entry was 5.1 mg/day.
 

Key BMD and biomarker findings

BMD increased significantly in the spine, hip, and femoral neck in both treatment groups by 12 months. However, after adjustment for baseline BMD and covariates including age, menopause, and history of fracture, the gains in the denosumab group were significantly higher.

The increase in lumbar spine BMD at 12 months of 3.5% in the denosumab group versus 2.5% in the alendronate group was statistically significant (P = .045). Less significant was a 0.9% increase at the hip in the denosumab patients versus 1.6% in the alendronate group (P = .10), as well as femoral neck BMD gains of 1% in the denosumab group versus 1.5% in the alendronate group (P = .86).

Furthermore, “denosumab was more potent in suppressing the bone markers at 12 months,” Dr. Mok said.

Specifically, the percentage decrease in serum PINP (procollagen type I N-terminal propeptide) levels in the denosumab group was significantly greater than in the alendronate group (P = .001). Likewise, the decrease in CTX (C-terminal telopeptide of type I collagen) was significantly greater in the denosumab cohort versus the alendronate cohort (P < .001).

“Dr. Mok’s study was a well-controlled investigation. The superiority of denosumab was impressive, especially given the small group sizes of 69 and 70,” session comoderator Gregg Silverman, MD, professor in the department of internal medicine and the department of pathology at New York University, said when asked for comment.

“However, bone density measurements may not tell the whole story. These results support a bigger and much larger-scale study to confirm that rates of fracture on denosumab are also reduced.”

No new symptomatic fractures occurred in either group during the study. The investigators are evaluating for any new radiologic fractures, with results pending.

Dr. Mok said “results of our study in Asian patients are largely confirmatory” of a previous 2018 comparison study and a 2019 comparison study, each sponsored by Amgen.

A small sample size, short duration of treatment, and the open-label design were limitations of the study.

The trial was an investigator-initiated study. Dr. Mok and colleagues had no relevant financial disclosures. Dr. Silverman had no relevant financial disclosures.

SOURCE: Mok CC et al. Arthritis Rheumatol. 2020;72(suppl 10). ACR 2020, Abstract 1442.

Denosumab boosted bone mineral density (BMD) over 12 months to a greater extent than did alendronate in a randomized, 12-month study. The investigator-initiated research compared BMD at the lumbar spine and elsewhere among people with systemic lupus erythematosus (SLE) and other autoimmune conditions. Long-term glucocorticoid therapy places some people in this group at higher risk for adverse effects of bone density loss.

“Glucocorticoids remain the mainstay of treatment of rheumatic diseases, but [they are] a major risk factor for osteoporosis and fracture,” study author Chi Chiu Mok, MD, said in an interview.

Compared with baseline, adults randomly assigned to denosumab had a 3.5% increase in lumbar spine BMD at 12 months, compared with 2.5% among those taking alendronate, a significant difference. Dr. Mok, a consultant and honorary associate professor in the department of medicine and nuclear medicine at Tuen Mun Hospital in Hong Kong, presented the study results at the virtual annual meeting of the American College of Rheumatology.

“Given the knowledge that denosumab is more effective than alendronate in raising spinal BMD in chronic users of GCs without increasing adverse events, this drug may be considered as an alternative first-line therapy in higher-risk patients and in those who are contraindicated for the oral bisphosphonates,” he said.
 

Cost considerations

Denosumab is a human monoclonal antibody administered as a subcutaneous injection, available under the brand names Prolia and Xgeva. Alendronate is an oral agent available as both generic and brand name formulations.

“Yes, denosumab is more expensive, more costly than oral alendronate, but our study shows efficacy is better for steroid users,” Dr. Mok said in answer to a question about cost disparity between the two agents during his presentation at the meeting. “For patients who are contraindicated or have low compliance for bisphosphonate, or are high-risk patients, I recommend first-line use of denosumab.”

Researchers previously studied these agents, including a smaller study by Dr. Mok and colleagues that showed a BMD benefit after switching people on an oral bisphosphonate to denosumab. However, he said, “There is a paucity of data regarding comparative efficacy of denosumab and the bisphosphonates in long-term steroid users.”

To explore any differences in a larger patient population, the investigators randomly assigned adults with SLE and other autoimmune conditions to the two treatments: denosumab 60 mg subcutaneoulsy every 6 months or oral alendronate 70 mg/week. All patients also received 3,000 mg calcium and 1,000 IU vitamin D₃ (cholecalciferol) each day.

After three discontinuations in denosumab cohort and four in the alendronate group, the researchers evaluated 69 people taking denosumab and 70 others taking alendronate. The discontinuations were caused by noncompliance, Dr. Mok said, not by adverse events.

Adverse events were reported, but the rate did not differ significantly between groups. Dr. Mok highlighted some notable differences, including more minor infections and arthralgias reported in the denosumab cohort. Chest discomfort was reported in one denosumab recipient versus no patients in the alendronate group. Dyspepsia/upper GI symptoms and dizziness/vertigo occurred more often in the alendronate group.

Women were 96% of the study population, and mean age was 50 years. A majority, 81%, had underlying SLE. Other diagnoses included rheumatoid arthritis, myositis, antineutrophil cytoplasmic antibody–associated vasculitis, and polymyalgia rheumatica. The mean dose of prednisolone at study entry was 5.1 mg/day.
 

Key BMD and biomarker findings

BMD increased significantly in the spine, hip, and femoral neck in both treatment groups by 12 months. However, after adjustment for baseline BMD and covariates including age, menopause, and history of fracture, the gains in the denosumab group were significantly higher.

The increase in lumbar spine BMD at 12 months of 3.5% in the denosumab group versus 2.5% in the alendronate group was statistically significant (P = .045). Less significant was a 0.9% increase at the hip in the denosumab patients versus 1.6% in the alendronate group (P = .10), as well as femoral neck BMD gains of 1% in the denosumab group versus 1.5% in the alendronate group (P = .86).

Furthermore, “denosumab was more potent in suppressing the bone markers at 12 months,” Dr. Mok said.

Specifically, the percentage decrease in serum PINP (procollagen type I N-terminal propeptide) levels in the denosumab group was significantly greater than in the alendronate group (P = .001). Likewise, the decrease in CTX (C-terminal telopeptide of type I collagen) was significantly greater in the denosumab cohort versus the alendronate cohort (P < .001).

“Dr. Mok’s study was a well-controlled investigation. The superiority of denosumab was impressive, especially given the small group sizes of 69 and 70,” session comoderator Gregg Silverman, MD, professor in the department of internal medicine and the department of pathology at New York University, said when asked for comment.

“However, bone density measurements may not tell the whole story. These results support a bigger and much larger-scale study to confirm that rates of fracture on denosumab are also reduced.”

No new symptomatic fractures occurred in either group during the study. The investigators are evaluating for any new radiologic fractures, with results pending.

Dr. Mok said “results of our study in Asian patients are largely confirmatory” of a previous 2018 comparison study and a 2019 comparison study, each sponsored by Amgen.

A small sample size, short duration of treatment, and the open-label design were limitations of the study.

The trial was an investigator-initiated study. Dr. Mok and colleagues had no relevant financial disclosures. Dr. Silverman had no relevant financial disclosures.

SOURCE: Mok CC et al. Arthritis Rheumatol. 2020;72(suppl 10). ACR 2020, Abstract 1442.

Denosumab boosted bone mineral density (BMD) over 12 months to a greater extent than did alendronate in a randomized, 12-month study. The investigator-initiated research compared BMD at the lumbar spine and elsewhere among people with systemic lupus erythematosus (SLE) and other autoimmune conditions. Long-term glucocorticoid therapy places some people in this group at higher risk for adverse effects of bone density loss.

“Glucocorticoids remain the mainstay of treatment of rheumatic diseases, but [they are] a major risk factor for osteoporosis and fracture,” study author Chi Chiu Mok, MD, said in an interview.

Compared with baseline, adults randomly assigned to denosumab had a 3.5% increase in lumbar spine BMD at 12 months, compared with 2.5% among those taking alendronate, a significant difference. Dr. Mok, a consultant and honorary associate professor in the department of medicine and nuclear medicine at Tuen Mun Hospital in Hong Kong, presented the study results at the virtual annual meeting of the American College of Rheumatology.

“Given the knowledge that denosumab is more effective than alendronate in raising spinal BMD in chronic users of GCs without increasing adverse events, this drug may be considered as an alternative first-line therapy in higher-risk patients and in those who are contraindicated for the oral bisphosphonates,” he said.
 

Cost considerations

Denosumab is a human monoclonal antibody administered as a subcutaneous injection, available under the brand names Prolia and Xgeva. Alendronate is an oral agent available as both generic and brand name formulations.

“Yes, denosumab is more expensive, more costly than oral alendronate, but our study shows efficacy is better for steroid users,” Dr. Mok said in answer to a question about cost disparity between the two agents during his presentation at the meeting. “For patients who are contraindicated or have low compliance for bisphosphonate, or are high-risk patients, I recommend first-line use of denosumab.”

Researchers previously studied these agents, including a smaller study by Dr. Mok and colleagues that showed a BMD benefit after switching people on an oral bisphosphonate to denosumab. However, he said, “There is a paucity of data regarding comparative efficacy of denosumab and the bisphosphonates in long-term steroid users.”

To explore any differences in a larger patient population, the investigators randomly assigned adults with SLE and other autoimmune conditions to the two treatments: denosumab 60 mg subcutaneoulsy every 6 months or oral alendronate 70 mg/week. All patients also received 3,000 mg calcium and 1,000 IU vitamin D₃ (cholecalciferol) each day.

After three discontinuations in denosumab cohort and four in the alendronate group, the researchers evaluated 69 people taking denosumab and 70 others taking alendronate. The discontinuations were caused by noncompliance, Dr. Mok said, not by adverse events.

Adverse events were reported, but the rate did not differ significantly between groups. Dr. Mok highlighted some notable differences, including more minor infections and arthralgias reported in the denosumab cohort. Chest discomfort was reported in one denosumab recipient versus no patients in the alendronate group. Dyspepsia/upper GI symptoms and dizziness/vertigo occurred more often in the alendronate group.

Women were 96% of the study population, and mean age was 50 years. A majority, 81%, had underlying SLE. Other diagnoses included rheumatoid arthritis, myositis, antineutrophil cytoplasmic antibody–associated vasculitis, and polymyalgia rheumatica. The mean dose of prednisolone at study entry was 5.1 mg/day.
 

Key BMD and biomarker findings

BMD increased significantly in the spine, hip, and femoral neck in both treatment groups by 12 months. However, after adjustment for baseline BMD and covariates including age, menopause, and history of fracture, the gains in the denosumab group were significantly higher.

The increase in lumbar spine BMD at 12 months of 3.5% in the denosumab group versus 2.5% in the alendronate group was statistically significant (P = .045). Less significant was a 0.9% increase at the hip in the denosumab patients versus 1.6% in the alendronate group (P = .10), as well as femoral neck BMD gains of 1% in the denosumab group versus 1.5% in the alendronate group (P = .86).

Furthermore, “denosumab was more potent in suppressing the bone markers at 12 months,” Dr. Mok said.

Specifically, the percentage decrease in serum PINP (procollagen type I N-terminal propeptide) levels in the denosumab group was significantly greater than in the alendronate group (P = .001). Likewise, the decrease in CTX (C-terminal telopeptide of type I collagen) was significantly greater in the denosumab cohort versus the alendronate cohort (P < .001).

“Dr. Mok’s study was a well-controlled investigation. The superiority of denosumab was impressive, especially given the small group sizes of 69 and 70,” session comoderator Gregg Silverman, MD, professor in the department of internal medicine and the department of pathology at New York University, said when asked for comment.

“However, bone density measurements may not tell the whole story. These results support a bigger and much larger-scale study to confirm that rates of fracture on denosumab are also reduced.”

No new symptomatic fractures occurred in either group during the study. The investigators are evaluating for any new radiologic fractures, with results pending.

Dr. Mok said “results of our study in Asian patients are largely confirmatory” of a previous 2018 comparison study and a 2019 comparison study, each sponsored by Amgen.

A small sample size, short duration of treatment, and the open-label design were limitations of the study.

The trial was an investigator-initiated study. Dr. Mok and colleagues had no relevant financial disclosures. Dr. Silverman had no relevant financial disclosures.

SOURCE: Mok CC et al. Arthritis Rheumatol. 2020;72(suppl 10). ACR 2020, Abstract 1442.

Timing is everything when it comes to the use of the anabolic agent romosozumab (Evenity) for the treatment of advanced osteoporosis, a review of clinical trials suggests.

In four studies with treatment sequences in which romosozumab was administered either before or following the use of an antiresorptive agent, initial treatment with 1 year of romosozumab produced substantial bone mineral density (BMD) gains in the total hip and lumbar spine.

Transition from romosozumab to a potent resorptive agent, either alendronate or denosumab (Prolia) augmented the initial gains, reported Felicia Cosman, MD, professor of clinical medicine at Columbia University, New York.

Romosozumab was the third approved agent in its class, following teriparatide in 2002, and abaloparatide (Tymlos) in 2017, both of which have been shown to produce rapid reductions in fracture risk and large improvements in BMD when they were administered up front, followed by an antiresorptive agent.

“But since romosozumab has a very different mechanism of action compared to both teriparatide and abaloparatide, we didn’t know if treatment sequence would be as important for this agent as it was for teriparatide,” she said during a press briefing prior to her presentation of the data in an oral abstract session at the virtual annual meeting of the American College of Rheumatology.

Two-for-one

Romosozumab is unique in that it both increases bone formation and decreases bone resorption, and has been shown in treatment-naive postmenopausal women with osteoporosis to significantly improve BMD and reduce fracture risk, compared with either placebo or alendronate. Romosozumab has also been studied as sequential therapy in patients treated initially with either alendronate or denosumab.

To see whether treatment sequence could have differential effects on clinical outcomes for patients with osteoporosis, Dr. Cosman and colleagues looked at results from four clinical trials, using levels of bone turnover markers (procollagen type I N-terminal propeptide [PINP] and beta-isomer of the C-terminal telopeptide of type I collagen [beta-CTX]) and BMD gains in the total hip and spine as outcomes.

The two trials of romosozumab in treatment-naive women were the ARCH trial comparing romosozumab with alendronate in a double-blind phase for 1 year, followed by 1 year of open-label alendronate, and the FRAME trial, in which romosozumab was compared with placebo in a 1-year double-blind phase, followed by 1-year of open-label denosumab.

The two trials of romosozumab in women treated initially with antiresorptive agents were the STRUCTURE trial in which patients on oral bisphosphonates for at least 3 years or alendronate 70 mg weekly for 1 year were randomized to receive either romosozumab or teriparatide, and a phase 2 trial (NCT00896532) that included a 24-month romosozumab or placebo treatment phase followed by rerandomization to a 12-month extension phase with denosumab or placebo, followed by a 12-month retreatment phase with romosozumab, followed by a 24-month follow-on phase with zoledronic acid or no intervention.

Total hip BMD gains

In the ARCH trial, total hip BMD increased 6.2% with 1 year of romosozumab, and a cumulative total of 7.1% with the 2-year romosozumab/alendronate sequence. In the FRAME trial, patients gained 6.8% in total hip BMD after 1 year of romosozumab and a total of 8.8% after 2 years of romosozumab followed by denosumab.

In contrast, in the STRUCTURE trial, patients treated for 1 year or longer with alendronate and then with 1 year of romosozumab had a 2.9% BMD gain in the total hip. In the phase 2 trial, 1 year of romosozumab following 1 year of denosumab yielded a 0.9% BMD gain, for a total gain of 3.8% with the denosumab sequence.
 

Lumbar spine BMD gains

In ARCH, lumbar spine BMD increased 13.7% with 1 year of romosozumab, and a total of 15.2% with the 2-year sequence of romosozumab followed by alendronate. Similarly, in FRAME, patients gained 13.3% in BMD after a year of romosozumab, and total of 17.6% by the end of the 2-year romosozumab/denosumab sequence.

In contrast, in STRUCTURE, patients who had previously been on alendronate for at least 1 year had a gain of 9.8% after 1 year of romosozumab, and in the phase 2 study, patients who had been on denosumab for 1 year had an increase in lumbar spine BMD of 5.3% after 1 year on romosozumab, and a total gain of 11.5% at the end of the 2-year sequence.
 

Serum PINP and beta-CTX

Looking at the markers of bone turnover, the investigators saw that, in both ARCH and FRAME, PINP peaked at over 80% of baseline at 1 month, and then continued to steadily decline past 1 year. The beta-CTX nadir was 40%-50% below baseline at 1 year.

At the end of year 2, the PINP nadir was –67% with follow-on alendronate, and –69% with denosumab, and the beta-CTX nadir was –72% and –92%, respectively.

In the two trials where romosozumab was the follow-on therapy, however, the trends were distinctly different. In STRUCTURE, for example, PINP peaked at 141% of baseline at 1 month, and then returned toward baseline, whereas beta-CTX remained largely unchanged.

In the phase 2 trial, PINP peaked at 28% above baseline at 9 months, and then only slightly declined, and beta-CTX peaked at 211% at the end of 1 year of romosozumab.

Best used up front

“This study is important, because it suggests that for the three bone-building drugs that the best effects will really be attained on bone strength if the agents are used as initial therapy in very-high-risk patients. Those are people who have sustained fractures within the preceding 2 years, who had multiple fractures at any point in their adulthood, and who present with very low BMD, particularly if they have any associated clinical risk factors such as family history or other underlying diseases or medications that have detrimental effects on bone,” Dr. Cosman said at the briefing.

Marcy Bolster, MD, from the division of rheumatology, allergy, and immunology at Massachusetts General Hospital, Boston, and associate professor of medicine at Harvard Medical School in Boston, who was not involved in the study, commented that the study provides important information for clinicians who treat patients with osteoporosis.

“We have an increasing number of medications available for use in the treatment of patients with osteoporosis, and as we consider the importance of reducing fracture risk, the duration of therapy, the timing of a bisphosphonate holiday, it is essential that we consider any advantages to the order or sequence of our medications,” she said when asked for comment.

“This study provides evidence supporting the concept of the ‘anabolic window’ in which there is a demonstrated advantage in treating patients with an anabolic agent prior to treatment with an antiresorptive agent, and while gains in bone mineral density were achieved with either order of medication use, the gains were more dramatic with treatment with romosozumab as the first agent,” she added.

Dr. Bolster also noted it will be important to demonstrate reduction in fracture risk as well as gain in BMD.

The study was sponsored by Amgen, Astellas, and UCB. Dr. Cosman disclosed grants/research support from Amgen, and consulting fees and speaker activities for Amgen and Radius Health. Dr. Bolster disclosed relationships with AbbVie, Corbus, Cumberland, Gilead, Johnson & Johnson, and Pfizer.

SOURCE: Cosman F et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1973.

Timing is everything when it comes to the use of the anabolic agent romosozumab (Evenity) for the treatment of advanced osteoporosis, a review of clinical trials suggests.

In four studies with treatment sequences in which romosozumab was administered either before or following the use of an antiresorptive agent, initial treatment with 1 year of romosozumab produced substantial bone mineral density (BMD) gains in the total hip and lumbar spine.

Transition from romosozumab to a potent resorptive agent, either alendronate or denosumab (Prolia) augmented the initial gains, reported Felicia Cosman, MD, professor of clinical medicine at Columbia University, New York.

Romosozumab was the third approved agent in its class, following teriparatide in 2002, and abaloparatide (Tymlos) in 2017, both of which have been shown to produce rapid reductions in fracture risk and large improvements in BMD when they were administered up front, followed by an antiresorptive agent.

“But since romosozumab has a very different mechanism of action compared to both teriparatide and abaloparatide, we didn’t know if treatment sequence would be as important for this agent as it was for teriparatide,” she said during a press briefing prior to her presentation of the data in an oral abstract session at the virtual annual meeting of the American College of Rheumatology.

Two-for-one

Romosozumab is unique in that it both increases bone formation and decreases bone resorption, and has been shown in treatment-naive postmenopausal women with osteoporosis to significantly improve BMD and reduce fracture risk, compared with either placebo or alendronate. Romosozumab has also been studied as sequential therapy in patients treated initially with either alendronate or denosumab.

To see whether treatment sequence could have differential effects on clinical outcomes for patients with osteoporosis, Dr. Cosman and colleagues looked at results from four clinical trials, using levels of bone turnover markers (procollagen type I N-terminal propeptide [PINP] and beta-isomer of the C-terminal telopeptide of type I collagen [beta-CTX]) and BMD gains in the total hip and spine as outcomes.

The two trials of romosozumab in treatment-naive women were the ARCH trial comparing romosozumab with alendronate in a double-blind phase for 1 year, followed by 1 year of open-label alendronate, and the FRAME trial, in which romosozumab was compared with placebo in a 1-year double-blind phase, followed by 1-year of open-label denosumab.

The two trials of romosozumab in women treated initially with antiresorptive agents were the STRUCTURE trial in which patients on oral bisphosphonates for at least 3 years or alendronate 70 mg weekly for 1 year were randomized to receive either romosozumab or teriparatide, and a phase 2 trial (NCT00896532) that included a 24-month romosozumab or placebo treatment phase followed by rerandomization to a 12-month extension phase with denosumab or placebo, followed by a 12-month retreatment phase with romosozumab, followed by a 24-month follow-on phase with zoledronic acid or no intervention.

Total hip BMD gains

In the ARCH trial, total hip BMD increased 6.2% with 1 year of romosozumab, and a cumulative total of 7.1% with the 2-year romosozumab/alendronate sequence. In the FRAME trial, patients gained 6.8% in total hip BMD after 1 year of romosozumab and a total of 8.8% after 2 years of romosozumab followed by denosumab.

In contrast, in the STRUCTURE trial, patients treated for 1 year or longer with alendronate and then with 1 year of romosozumab had a 2.9% BMD gain in the total hip. In the phase 2 trial, 1 year of romosozumab following 1 year of denosumab yielded a 0.9% BMD gain, for a total gain of 3.8% with the denosumab sequence.
 

Lumbar spine BMD gains

In ARCH, lumbar spine BMD increased 13.7% with 1 year of romosozumab, and a total of 15.2% with the 2-year sequence of romosozumab followed by alendronate. Similarly, in FRAME, patients gained 13.3% in BMD after a year of romosozumab, and total of 17.6% by the end of the 2-year romosozumab/denosumab sequence.

In contrast, in STRUCTURE, patients who had previously been on alendronate for at least 1 year had a gain of 9.8% after 1 year of romosozumab, and in the phase 2 study, patients who had been on denosumab for 1 year had an increase in lumbar spine BMD of 5.3% after 1 year on romosozumab, and a total gain of 11.5% at the end of the 2-year sequence.
 

Serum PINP and beta-CTX

Looking at the markers of bone turnover, the investigators saw that, in both ARCH and FRAME, PINP peaked at over 80% of baseline at 1 month, and then continued to steadily decline past 1 year. The beta-CTX nadir was 40%-50% below baseline at 1 year.

At the end of year 2, the PINP nadir was –67% with follow-on alendronate, and –69% with denosumab, and the beta-CTX nadir was –72% and –92%, respectively.

In the two trials where romosozumab was the follow-on therapy, however, the trends were distinctly different. In STRUCTURE, for example, PINP peaked at 141% of baseline at 1 month, and then returned toward baseline, whereas beta-CTX remained largely unchanged.

In the phase 2 trial, PINP peaked at 28% above baseline at 9 months, and then only slightly declined, and beta-CTX peaked at 211% at the end of 1 year of romosozumab.

Best used up front

“This study is important, because it suggests that for the three bone-building drugs that the best effects will really be attained on bone strength if the agents are used as initial therapy in very-high-risk patients. Those are people who have sustained fractures within the preceding 2 years, who had multiple fractures at any point in their adulthood, and who present with very low BMD, particularly if they have any associated clinical risk factors such as family history or other underlying diseases or medications that have detrimental effects on bone,” Dr. Cosman said at the briefing.

Marcy Bolster, MD, from the division of rheumatology, allergy, and immunology at Massachusetts General Hospital, Boston, and associate professor of medicine at Harvard Medical School in Boston, who was not involved in the study, commented that the study provides important information for clinicians who treat patients with osteoporosis.

“We have an increasing number of medications available for use in the treatment of patients with osteoporosis, and as we consider the importance of reducing fracture risk, the duration of therapy, the timing of a bisphosphonate holiday, it is essential that we consider any advantages to the order or sequence of our medications,” she said when asked for comment.

“This study provides evidence supporting the concept of the ‘anabolic window’ in which there is a demonstrated advantage in treating patients with an anabolic agent prior to treatment with an antiresorptive agent, and while gains in bone mineral density were achieved with either order of medication use, the gains were more dramatic with treatment with romosozumab as the first agent,” she added.

Dr. Bolster also noted it will be important to demonstrate reduction in fracture risk as well as gain in BMD.

The study was sponsored by Amgen, Astellas, and UCB. Dr. Cosman disclosed grants/research support from Amgen, and consulting fees and speaker activities for Amgen and Radius Health. Dr. Bolster disclosed relationships with AbbVie, Corbus, Cumberland, Gilead, Johnson & Johnson, and Pfizer.

SOURCE: Cosman F et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1973.

Timing is everything when it comes to the use of the anabolic agent romosozumab (Evenity) for the treatment of advanced osteoporosis, a review of clinical trials suggests.

In four studies with treatment sequences in which romosozumab was administered either before or following the use of an antiresorptive agent, initial treatment with 1 year of romosozumab produced substantial bone mineral density (BMD) gains in the total hip and lumbar spine.

Transition from romosozumab to a potent resorptive agent, either alendronate or denosumab (Prolia) augmented the initial gains, reported Felicia Cosman, MD, professor of clinical medicine at Columbia University, New York.

Romosozumab was the third approved agent in its class, following teriparatide in 2002, and abaloparatide (Tymlos) in 2017, both of which have been shown to produce rapid reductions in fracture risk and large improvements in BMD when they were administered up front, followed by an antiresorptive agent.

“But since romosozumab has a very different mechanism of action compared to both teriparatide and abaloparatide, we didn’t know if treatment sequence would be as important for this agent as it was for teriparatide,” she said during a press briefing prior to her presentation of the data in an oral abstract session at the virtual annual meeting of the American College of Rheumatology.

Two-for-one

Romosozumab is unique in that it both increases bone formation and decreases bone resorption, and has been shown in treatment-naive postmenopausal women with osteoporosis to significantly improve BMD and reduce fracture risk, compared with either placebo or alendronate. Romosozumab has also been studied as sequential therapy in patients treated initially with either alendronate or denosumab.

To see whether treatment sequence could have differential effects on clinical outcomes for patients with osteoporosis, Dr. Cosman and colleagues looked at results from four clinical trials, using levels of bone turnover markers (procollagen type I N-terminal propeptide [PINP] and beta-isomer of the C-terminal telopeptide of type I collagen [beta-CTX]) and BMD gains in the total hip and spine as outcomes.

The two trials of romosozumab in treatment-naive women were the ARCH trial comparing romosozumab with alendronate in a double-blind phase for 1 year, followed by 1 year of open-label alendronate, and the FRAME trial, in which romosozumab was compared with placebo in a 1-year double-blind phase, followed by 1-year of open-label denosumab.

The two trials of romosozumab in women treated initially with antiresorptive agents were the STRUCTURE trial in which patients on oral bisphosphonates for at least 3 years or alendronate 70 mg weekly for 1 year were randomized to receive either romosozumab or teriparatide, and a phase 2 trial (NCT00896532) that included a 24-month romosozumab or placebo treatment phase followed by rerandomization to a 12-month extension phase with denosumab or placebo, followed by a 12-month retreatment phase with romosozumab, followed by a 24-month follow-on phase with zoledronic acid or no intervention.

Total hip BMD gains

In the ARCH trial, total hip BMD increased 6.2% with 1 year of romosozumab, and a cumulative total of 7.1% with the 2-year romosozumab/alendronate sequence. In the FRAME trial, patients gained 6.8% in total hip BMD after 1 year of romosozumab and a total of 8.8% after 2 years of romosozumab followed by denosumab.

In contrast, in the STRUCTURE trial, patients treated for 1 year or longer with alendronate and then with 1 year of romosozumab had a 2.9% BMD gain in the total hip. In the phase 2 trial, 1 year of romosozumab following 1 year of denosumab yielded a 0.9% BMD gain, for a total gain of 3.8% with the denosumab sequence.
 

Lumbar spine BMD gains

In ARCH, lumbar spine BMD increased 13.7% with 1 year of romosozumab, and a total of 15.2% with the 2-year sequence of romosozumab followed by alendronate. Similarly, in FRAME, patients gained 13.3% in BMD after a year of romosozumab, and total of 17.6% by the end of the 2-year romosozumab/denosumab sequence.

In contrast, in STRUCTURE, patients who had previously been on alendronate for at least 1 year had a gain of 9.8% after 1 year of romosozumab, and in the phase 2 study, patients who had been on denosumab for 1 year had an increase in lumbar spine BMD of 5.3% after 1 year on romosozumab, and a total gain of 11.5% at the end of the 2-year sequence.
 

Serum PINP and beta-CTX

Looking at the markers of bone turnover, the investigators saw that, in both ARCH and FRAME, PINP peaked at over 80% of baseline at 1 month, and then continued to steadily decline past 1 year. The beta-CTX nadir was 40%-50% below baseline at 1 year.

At the end of year 2, the PINP nadir was –67% with follow-on alendronate, and –69% with denosumab, and the beta-CTX nadir was –72% and –92%, respectively.

In the two trials where romosozumab was the follow-on therapy, however, the trends were distinctly different. In STRUCTURE, for example, PINP peaked at 141% of baseline at 1 month, and then returned toward baseline, whereas beta-CTX remained largely unchanged.

In the phase 2 trial, PINP peaked at 28% above baseline at 9 months, and then only slightly declined, and beta-CTX peaked at 211% at the end of 1 year of romosozumab.

Best used up front

“This study is important, because it suggests that for the three bone-building drugs that the best effects will really be attained on bone strength if the agents are used as initial therapy in very-high-risk patients. Those are people who have sustained fractures within the preceding 2 years, who had multiple fractures at any point in their adulthood, and who present with very low BMD, particularly if they have any associated clinical risk factors such as family history or other underlying diseases or medications that have detrimental effects on bone,” Dr. Cosman said at the briefing.

Marcy Bolster, MD, from the division of rheumatology, allergy, and immunology at Massachusetts General Hospital, Boston, and associate professor of medicine at Harvard Medical School in Boston, who was not involved in the study, commented that the study provides important information for clinicians who treat patients with osteoporosis.

“We have an increasing number of medications available for use in the treatment of patients with osteoporosis, and as we consider the importance of reducing fracture risk, the duration of therapy, the timing of a bisphosphonate holiday, it is essential that we consider any advantages to the order or sequence of our medications,” she said when asked for comment.

“This study provides evidence supporting the concept of the ‘anabolic window’ in which there is a demonstrated advantage in treating patients with an anabolic agent prior to treatment with an antiresorptive agent, and while gains in bone mineral density were achieved with either order of medication use, the gains were more dramatic with treatment with romosozumab as the first agent,” she added.

Dr. Bolster also noted it will be important to demonstrate reduction in fracture risk as well as gain in BMD.

The study was sponsored by Amgen, Astellas, and UCB. Dr. Cosman disclosed grants/research support from Amgen, and consulting fees and speaker activities for Amgen and Radius Health. Dr. Bolster disclosed relationships with AbbVie, Corbus, Cumberland, Gilead, Johnson & Johnson, and Pfizer.

SOURCE: Cosman F et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1973.

Pregnant women with interstitial lung disease (ILD) related to autoimmune disease may not need to terminate their pregnancies if they have close monitoring before, during, and after pregnancy with a multidisciplinary team of physicians, new research suggests.

Senior author Megan Clowse, MD, MPH, associate professor of medicine in the division of rheumatology at Duke University, Durham, N.C., explained during a press conference at the virtual annual meeting of the American College of Rheumatology that women with ILD are often advised by obstetricians or rheumatologists to avoid conception or terminate their pregnancies, though evidence for that has been based on small studies of 9-15 patients that have had mixed results.

“Many of these pregnancies were delivered 20-30 years ago, definitely with different rheumatic and obstetric care than we can provide now,” she said. “It’s really time to rethink our approach to interstitial lung disease and pregnancy.”

This study showed that while adverse pregnancy outcomes are common in these women, overall maternal morbidity and mortality are low.

ILD may be a secondary disease in people who have scleroderma, lupus, and sarcoidosis.

Largest study to date

This Pfizer-sponsored retrospective study of 67 pregnant women is the largest to date, and it analyzed 94 pregnancies (including five sets of twins).

Sarah Rae Easter, MD, maternal-fetal medicine doctor in the department of obstetrics and gynecology at Brigham and Women’s Hospital, Boston, called the work “exciting” as the researchers were able to look back at a large number of cases for a rare condition for more than 20 years.

“Their data provides much-needed evidence to provide some reassurance for women affected by this type of pulmonary disease regarding the relative safety of pregnancy,” she said in an interview.
 

Study spanned 23 years

The researchers reviewed pregnancy records in patients diagnosed with ILD secondary to autoimmune disease at Duke University Health System from January 1996 to July 2019.

They classified the severity of ILD based on two standard breathing tests – forced vital capacity and diffusion capacity for carbon monoxide.

Overall, 69% of the women were diagnosed with sarcoidosis and the remaining 31% had a connective tissue disease associated with ILD (CTD-ILD). Of those measured for ILD severity, 11% were severe, 25% were moderate, 50% were mild, and 14% were normal. Their average maternal age was 32.1 and 83% were Black.

While 70% of the pregnancies resulted in live births, 9% were terminated. The remainder resulted in miscarriage or stillbirth.

Researchers reported a 15% rate of preeclampsia, a 34% rate of the composite measure PROMISSE-Adverse Pregnancy Outcome (APO), and a 15% rate of PROMISSE-APO SEVERE. Patients with severe disease had the highest rates of PROMISSE-APO (P = .03 across groups).

(PROMISSE stands for the Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus study.)

None of the women died

Dr. Clowse said it was a pleasant surprise to find that none of the women died, though patients with severe ILD had more adverse outcomes. Only 2.1% were treated in an intensive care unit during or soon after delivery. In 4.2%, ILD patients had significant shortness of breath due to fluid volume overload around the time of delivery.

For the women who had normal-to-moderate lung disease, Dr. Clowse said, “they really had remarkably good outcomes, really pretty comparable to the general population. About 15% delivered preterm and about 20% suffered a pregnancy loss.”

Dr. Easter, who was not involved with the study, noted the large number of Black women in the cohort.

“Focusing in on improving outcomes for Black and Brown women related to pregnancy in our country is a much-needed undertaking,” Dr. Easter said.

Being able to quote percentages from this research, based on a good-sized study “at least gives people a benchmark about what kind of risk they are willing to assume for themselves,” she said.

For providers, being able to place this rare disease within the spectrum of other diseases where there is more data is also very helpful, she said.

Dr. Clowse said in an interview that the preponderance of Black women in the study was a surprise but may be explained by two factors: Sarcoidosis is seen more frequently in Black women and in the study area in North Carolina there is a large population of Black women.

“Also, our patients with more severe lupus, the ones who are more likely to have interstitial lung disease, are often Black and that’s likely contributing as well,” she said.
 

Multidisciplinary teams advised

Dr. Clowse emphasized that women with ILD need multidisciplinary teams in pregnancy and should be managed at tertiary care centers where there is a full complement of obstetric and internal medicine experts.

“We do recommend evaluating the severity of their lungs and their heart disease around the time of pregnancy and during pregnancy if they have shortness of breath,” she said.

“We currently recommend that these patients with moderate or severe disease stay in the hospital for up to a week, just for monitoring,” she said.

Dr. Easter said having that kind of access to a large academic healthcare center should be an important part of the decision-making.

Patients need to think about whether they would have access to care similar to what the researchers are describing when they are making the decision to pursue or continue pregnancy, she said.

The study was sponsored by Pfizer Inc. Dr. Clowse reported relationships with UCB, GlaxoSmithKline, AstraZeneca, and Pfizer. Dr. Easter has disclosed no relevant financial relationships.

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

Pregnant women with interstitial lung disease (ILD) related to autoimmune disease may not need to terminate their pregnancies if they have close monitoring before, during, and after pregnancy with a multidisciplinary team of physicians, new research suggests.

Senior author Megan Clowse, MD, MPH, associate professor of medicine in the division of rheumatology at Duke University, Durham, N.C., explained during a press conference at the virtual annual meeting of the American College of Rheumatology that women with ILD are often advised by obstetricians or rheumatologists to avoid conception or terminate their pregnancies, though evidence for that has been based on small studies of 9-15 patients that have had mixed results.

“Many of these pregnancies were delivered 20-30 years ago, definitely with different rheumatic and obstetric care than we can provide now,” she said. “It’s really time to rethink our approach to interstitial lung disease and pregnancy.”

This study showed that while adverse pregnancy outcomes are common in these women, overall maternal morbidity and mortality are low.

ILD may be a secondary disease in people who have scleroderma, lupus, and sarcoidosis.

Largest study to date

This Pfizer-sponsored retrospective study of 67 pregnant women is the largest to date, and it analyzed 94 pregnancies (including five sets of twins).

Sarah Rae Easter, MD, maternal-fetal medicine doctor in the department of obstetrics and gynecology at Brigham and Women’s Hospital, Boston, called the work “exciting” as the researchers were able to look back at a large number of cases for a rare condition for more than 20 years.

“Their data provides much-needed evidence to provide some reassurance for women affected by this type of pulmonary disease regarding the relative safety of pregnancy,” she said in an interview.
 

Study spanned 23 years

The researchers reviewed pregnancy records in patients diagnosed with ILD secondary to autoimmune disease at Duke University Health System from January 1996 to July 2019.

They classified the severity of ILD based on two standard breathing tests – forced vital capacity and diffusion capacity for carbon monoxide.

Overall, 69% of the women were diagnosed with sarcoidosis and the remaining 31% had a connective tissue disease associated with ILD (CTD-ILD). Of those measured for ILD severity, 11% were severe, 25% were moderate, 50% were mild, and 14% were normal. Their average maternal age was 32.1 and 83% were Black.

While 70% of the pregnancies resulted in live births, 9% were terminated. The remainder resulted in miscarriage or stillbirth.

Researchers reported a 15% rate of preeclampsia, a 34% rate of the composite measure PROMISSE-Adverse Pregnancy Outcome (APO), and a 15% rate of PROMISSE-APO SEVERE. Patients with severe disease had the highest rates of PROMISSE-APO (P = .03 across groups).

(PROMISSE stands for the Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus study.)

None of the women died

Dr. Clowse said it was a pleasant surprise to find that none of the women died, though patients with severe ILD had more adverse outcomes. Only 2.1% were treated in an intensive care unit during or soon after delivery. In 4.2%, ILD patients had significant shortness of breath due to fluid volume overload around the time of delivery.

For the women who had normal-to-moderate lung disease, Dr. Clowse said, “they really had remarkably good outcomes, really pretty comparable to the general population. About 15% delivered preterm and about 20% suffered a pregnancy loss.”

Dr. Easter, who was not involved with the study, noted the large number of Black women in the cohort.

“Focusing in on improving outcomes for Black and Brown women related to pregnancy in our country is a much-needed undertaking,” Dr. Easter said.

Being able to quote percentages from this research, based on a good-sized study “at least gives people a benchmark about what kind of risk they are willing to assume for themselves,” she said.

For providers, being able to place this rare disease within the spectrum of other diseases where there is more data is also very helpful, she said.

Dr. Clowse said in an interview that the preponderance of Black women in the study was a surprise but may be explained by two factors: Sarcoidosis is seen more frequently in Black women and in the study area in North Carolina there is a large population of Black women.

“Also, our patients with more severe lupus, the ones who are more likely to have interstitial lung disease, are often Black and that’s likely contributing as well,” she said.
 

Multidisciplinary teams advised

Dr. Clowse emphasized that women with ILD need multidisciplinary teams in pregnancy and should be managed at tertiary care centers where there is a full complement of obstetric and internal medicine experts.

“We do recommend evaluating the severity of their lungs and their heart disease around the time of pregnancy and during pregnancy if they have shortness of breath,” she said.

“We currently recommend that these patients with moderate or severe disease stay in the hospital for up to a week, just for monitoring,” she said.

Dr. Easter said having that kind of access to a large academic healthcare center should be an important part of the decision-making.

Patients need to think about whether they would have access to care similar to what the researchers are describing when they are making the decision to pursue or continue pregnancy, she said.

The study was sponsored by Pfizer Inc. Dr. Clowse reported relationships with UCB, GlaxoSmithKline, AstraZeneca, and Pfizer. Dr. Easter has disclosed no relevant financial relationships.

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

Pregnant women with interstitial lung disease (ILD) related to autoimmune disease may not need to terminate their pregnancies if they have close monitoring before, during, and after pregnancy with a multidisciplinary team of physicians, new research suggests.

Senior author Megan Clowse, MD, MPH, associate professor of medicine in the division of rheumatology at Duke University, Durham, N.C., explained during a press conference at the virtual annual meeting of the American College of Rheumatology that women with ILD are often advised by obstetricians or rheumatologists to avoid conception or terminate their pregnancies, though evidence for that has been based on small studies of 9-15 patients that have had mixed results.

“Many of these pregnancies were delivered 20-30 years ago, definitely with different rheumatic and obstetric care than we can provide now,” she said. “It’s really time to rethink our approach to interstitial lung disease and pregnancy.”

This study showed that while adverse pregnancy outcomes are common in these women, overall maternal morbidity and mortality are low.

ILD may be a secondary disease in people who have scleroderma, lupus, and sarcoidosis.

Largest study to date

This Pfizer-sponsored retrospective study of 67 pregnant women is the largest to date, and it analyzed 94 pregnancies (including five sets of twins).

Sarah Rae Easter, MD, maternal-fetal medicine doctor in the department of obstetrics and gynecology at Brigham and Women’s Hospital, Boston, called the work “exciting” as the researchers were able to look back at a large number of cases for a rare condition for more than 20 years.

“Their data provides much-needed evidence to provide some reassurance for women affected by this type of pulmonary disease regarding the relative safety of pregnancy,” she said in an interview.
 

Study spanned 23 years

The researchers reviewed pregnancy records in patients diagnosed with ILD secondary to autoimmune disease at Duke University Health System from January 1996 to July 2019.

They classified the severity of ILD based on two standard breathing tests – forced vital capacity and diffusion capacity for carbon monoxide.

Overall, 69% of the women were diagnosed with sarcoidosis and the remaining 31% had a connective tissue disease associated with ILD (CTD-ILD). Of those measured for ILD severity, 11% were severe, 25% were moderate, 50% were mild, and 14% were normal. Their average maternal age was 32.1 and 83% were Black.

While 70% of the pregnancies resulted in live births, 9% were terminated. The remainder resulted in miscarriage or stillbirth.

Researchers reported a 15% rate of preeclampsia, a 34% rate of the composite measure PROMISSE-Adverse Pregnancy Outcome (APO), and a 15% rate of PROMISSE-APO SEVERE. Patients with severe disease had the highest rates of PROMISSE-APO (P = .03 across groups).

(PROMISSE stands for the Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus study.)

None of the women died

Dr. Clowse said it was a pleasant surprise to find that none of the women died, though patients with severe ILD had more adverse outcomes. Only 2.1% were treated in an intensive care unit during or soon after delivery. In 4.2%, ILD patients had significant shortness of breath due to fluid volume overload around the time of delivery.

For the women who had normal-to-moderate lung disease, Dr. Clowse said, “they really had remarkably good outcomes, really pretty comparable to the general population. About 15% delivered preterm and about 20% suffered a pregnancy loss.”

Dr. Easter, who was not involved with the study, noted the large number of Black women in the cohort.

“Focusing in on improving outcomes for Black and Brown women related to pregnancy in our country is a much-needed undertaking,” Dr. Easter said.

Being able to quote percentages from this research, based on a good-sized study “at least gives people a benchmark about what kind of risk they are willing to assume for themselves,” she said.

For providers, being able to place this rare disease within the spectrum of other diseases where there is more data is also very helpful, she said.

Dr. Clowse said in an interview that the preponderance of Black women in the study was a surprise but may be explained by two factors: Sarcoidosis is seen more frequently in Black women and in the study area in North Carolina there is a large population of Black women.

“Also, our patients with more severe lupus, the ones who are more likely to have interstitial lung disease, are often Black and that’s likely contributing as well,” she said.
 

Multidisciplinary teams advised

Dr. Clowse emphasized that women with ILD need multidisciplinary teams in pregnancy and should be managed at tertiary care centers where there is a full complement of obstetric and internal medicine experts.

“We do recommend evaluating the severity of their lungs and their heart disease around the time of pregnancy and during pregnancy if they have shortness of breath,” she said.

“We currently recommend that these patients with moderate or severe disease stay in the hospital for up to a week, just for monitoring,” she said.

Dr. Easter said having that kind of access to a large academic healthcare center should be an important part of the decision-making.

Patients need to think about whether they would have access to care similar to what the researchers are describing when they are making the decision to pursue or continue pregnancy, she said.

The study was sponsored by Pfizer Inc. Dr. Clowse reported relationships with UCB, GlaxoSmithKline, AstraZeneca, and Pfizer. Dr. Easter has disclosed no relevant financial relationships.

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

Medication adherence remains a truly challenging issue. For most chronic diseases, up to 20%-30% of the pills that are prescribed are not taken. In the case of inhalers for asthma and COPD, patients miss over half of the prescribed doses.

There are many things that contribute to the problem of poor adherence, but people often just simply forget. Thankfully, there are tools designed to help remind patients of what they need to take and when. A survey of apps developed to help patients remember to take their medicines found more than 700 available in Apple and Android app stores.¹ Most apps focus on medication alerts, reminders, and medication logs.² A recent review showed that apps have some – yet limited – effectiveness in increasing adherence, with patient self-reported improvements of 7%-40%.³

Another perhaps more promising area of improving adherence involves high-tech advances in the way medications can be taken. Inhalers are a primary target as they are complicated devices. A patient has to breathe in at the correct time after the inhaler is actuated, and the inhaler works optimally only if the rate of inhalation is sufficient to carry the medication into the lungs.

A number of companies have developed attachments for inhalers (and even inhalers themselves) that can record when the medication is taken through a Bluetooth connection to a patient’s smartphone. These can also assess inspiratory flow. Reminders to take the medication are built into the app, and those reminders disappear if the medication is taken. Patients can receive feedback about the quality of their timing and inspiratory rate to maximize medication delivery to the lungs.⁴

We learned long ago that it is difficult to take medications three to four times a day, so extended-release tablets were developed to reduce the frequency to once or twice a day. A great deal of work is now being done behind the scenes to develop medications that decrease the need for patients to remember to take their medications. The best examples of this are the long-acting reversible contraception (LARC) devices, specifically IUDs and Nexplanon. Compared with traditional oral contraceptives that need to be taken daily, LARCs reduce the rate of pregnancy by five- to tenfold.

We also now have medications for osteoporosis that can be taken monthly, or even annually. When bisphosphonates were first developed for osteoporosis prevention, they needed to be taken daily. Then a weekly bisphosphonate was developed. Now there is a once-monthly oral bisphosphonate, Ibandronate, and even a once yearly IV bisphosphonate.

Exciting developments have also occurred in the management of diabetes. We may be tempted to take for granted how once-daily long-acting insulin, which releases insulin slowly over the course of a day, has revolutionized the diabetic treatment since its Food and Drug Administration approval in 2000. Yet progress did not end there. The first GLP-1 receptor agonist for diabetes was approved in 2005 and was a twice-a-day medicine. Shortly afterward, a daily GLP-1 was approved, and now there are three once-weekly GLP-1 receptor agonists.

Several pharmaceutical manufacturers are now working on a once-weekly insulin,⁵ as well as an implantable GLP-1 receptor agonist that will need to be replaced every 6-12 months.⁶ Imagine your patient coming in once a year to replace his or her potent glucose lowering medication – one that offers a low incidence of hypoglycemia, maintains glucose control all year long, and requires no adherence to a complicated medication regimen.

Similar technology is being used to develop a once-yearly anti-HIV prophylactic medication delivery system.⁷ This could help prevent the spread of HIV in areas of the world where it may be difficult for people to take daily medications.⁷

The many technological advances we have described may help us reduce our likelihood of missing a dose of a medication. We are hopeful that progress in this area will continue, and that one day medication adherence will require even less effort from patients than it does today.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

References

1. Tabi K et al. Mobile apps for medication management: Review and analysis. JMIR Mhealth Uhealth. 2019 Sep 7(9):13608.

2. Park JYE et al. Mobile phone apps targeting medication adherence: Quality assessment and content analysis of user reviews. JMIR Mhealth Uhealth. 2019 Jan 31;7(1):e11919.

3. Pérez-Jover V et al. Mobile apps for increasing treatment adherence: Systematic review. J Med Internet Res. 2019;21(6):e12505. doi: 10.2196/12505.

4. 4 Smart inhalers that could be lifesaving for people living with asthma & COPD. MyTherapy, July 11, 2019.

5. Rosenstock J et al. Once-weekly insulin for type 2 diabetes without previous insulin treatment. N Engl J Med. 2020 Sep 22. doi: 10.1056/NEJMoa2022474.

6. GLP-1 agonists: From 2 daily injections to 1 per week and beyond. DiaTribe, Jan. 10, 2018.

7. Long-acting HIV prevention tools. Hiv.gov, July 20, 2019.

Medication adherence remains a truly challenging issue. For most chronic diseases, up to 20%-30% of the pills that are prescribed are not taken. In the case of inhalers for asthma and COPD, patients miss over half of the prescribed doses.

There are many things that contribute to the problem of poor adherence, but people often just simply forget. Thankfully, there are tools designed to help remind patients of what they need to take and when. A survey of apps developed to help patients remember to take their medicines found more than 700 available in Apple and Android app stores.¹ Most apps focus on medication alerts, reminders, and medication logs.² A recent review showed that apps have some – yet limited – effectiveness in increasing adherence, with patient self-reported improvements of 7%-40%.³

Another perhaps more promising area of improving adherence involves high-tech advances in the way medications can be taken. Inhalers are a primary target as they are complicated devices. A patient has to breathe in at the correct time after the inhaler is actuated, and the inhaler works optimally only if the rate of inhalation is sufficient to carry the medication into the lungs.

A number of companies have developed attachments for inhalers (and even inhalers themselves) that can record when the medication is taken through a Bluetooth connection to a patient’s smartphone. These can also assess inspiratory flow. Reminders to take the medication are built into the app, and those reminders disappear if the medication is taken. Patients can receive feedback about the quality of their timing and inspiratory rate to maximize medication delivery to the lungs.⁴

We learned long ago that it is difficult to take medications three to four times a day, so extended-release tablets were developed to reduce the frequency to once or twice a day. A great deal of work is now being done behind the scenes to develop medications that decrease the need for patients to remember to take their medications. The best examples of this are the long-acting reversible contraception (LARC) devices, specifically IUDs and Nexplanon. Compared with traditional oral contraceptives that need to be taken daily, LARCs reduce the rate of pregnancy by five- to tenfold.

We also now have medications for osteoporosis that can be taken monthly, or even annually. When bisphosphonates were first developed for osteoporosis prevention, they needed to be taken daily. Then a weekly bisphosphonate was developed. Now there is a once-monthly oral bisphosphonate, Ibandronate, and even a once yearly IV bisphosphonate.

Exciting developments have also occurred in the management of diabetes. We may be tempted to take for granted how once-daily long-acting insulin, which releases insulin slowly over the course of a day, has revolutionized the diabetic treatment since its Food and Drug Administration approval in 2000. Yet progress did not end there. The first GLP-1 receptor agonist for diabetes was approved in 2005 and was a twice-a-day medicine. Shortly afterward, a daily GLP-1 was approved, and now there are three once-weekly GLP-1 receptor agonists.

Several pharmaceutical manufacturers are now working on a once-weekly insulin,⁵ as well as an implantable GLP-1 receptor agonist that will need to be replaced every 6-12 months.⁶ Imagine your patient coming in once a year to replace his or her potent glucose lowering medication – one that offers a low incidence of hypoglycemia, maintains glucose control all year long, and requires no adherence to a complicated medication regimen.

Similar technology is being used to develop a once-yearly anti-HIV prophylactic medication delivery system.⁷ This could help prevent the spread of HIV in areas of the world where it may be difficult for people to take daily medications.⁷

The many technological advances we have described may help us reduce our likelihood of missing a dose of a medication. We are hopeful that progress in this area will continue, and that one day medication adherence will require even less effort from patients than it does today.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

References

1. Tabi K et al. Mobile apps for medication management: Review and analysis. JMIR Mhealth Uhealth. 2019 Sep 7(9):13608.

2. Park JYE et al. Mobile phone apps targeting medication adherence: Quality assessment and content analysis of user reviews. JMIR Mhealth Uhealth. 2019 Jan 31;7(1):e11919.

3. Pérez-Jover V et al. Mobile apps for increasing treatment adherence: Systematic review. J Med Internet Res. 2019;21(6):e12505. doi: 10.2196/12505.

4. 4 Smart inhalers that could be lifesaving for people living with asthma & COPD. MyTherapy, July 11, 2019.

5. Rosenstock J et al. Once-weekly insulin for type 2 diabetes without previous insulin treatment. N Engl J Med. 2020 Sep 22. doi: 10.1056/NEJMoa2022474.

6. GLP-1 agonists: From 2 daily injections to 1 per week and beyond. DiaTribe, Jan. 10, 2018.

7. Long-acting HIV prevention tools. Hiv.gov, July 20, 2019.

Medication adherence remains a truly challenging issue. For most chronic diseases, up to 20%-30% of the pills that are prescribed are not taken. In the case of inhalers for asthma and COPD, patients miss over half of the prescribed doses.

There are many things that contribute to the problem of poor adherence, but people often just simply forget. Thankfully, there are tools designed to help remind patients of what they need to take and when. A survey of apps developed to help patients remember to take their medicines found more than 700 available in Apple and Android app stores.¹ Most apps focus on medication alerts, reminders, and medication logs.² A recent review showed that apps have some – yet limited – effectiveness in increasing adherence, with patient self-reported improvements of 7%-40%.³

Another perhaps more promising area of improving adherence involves high-tech advances in the way medications can be taken. Inhalers are a primary target as they are complicated devices. A patient has to breathe in at the correct time after the inhaler is actuated, and the inhaler works optimally only if the rate of inhalation is sufficient to carry the medication into the lungs.

A number of companies have developed attachments for inhalers (and even inhalers themselves) that can record when the medication is taken through a Bluetooth connection to a patient’s smartphone. These can also assess inspiratory flow. Reminders to take the medication are built into the app, and those reminders disappear if the medication is taken. Patients can receive feedback about the quality of their timing and inspiratory rate to maximize medication delivery to the lungs.⁴

We learned long ago that it is difficult to take medications three to four times a day, so extended-release tablets were developed to reduce the frequency to once or twice a day. A great deal of work is now being done behind the scenes to develop medications that decrease the need for patients to remember to take their medications. The best examples of this are the long-acting reversible contraception (LARC) devices, specifically IUDs and Nexplanon. Compared with traditional oral contraceptives that need to be taken daily, LARCs reduce the rate of pregnancy by five- to tenfold.

We also now have medications for osteoporosis that can be taken monthly, or even annually. When bisphosphonates were first developed for osteoporosis prevention, they needed to be taken daily. Then a weekly bisphosphonate was developed. Now there is a once-monthly oral bisphosphonate, Ibandronate, and even a once yearly IV bisphosphonate.

Exciting developments have also occurred in the management of diabetes. We may be tempted to take for granted how once-daily long-acting insulin, which releases insulin slowly over the course of a day, has revolutionized the diabetic treatment since its Food and Drug Administration approval in 2000. Yet progress did not end there. The first GLP-1 receptor agonist for diabetes was approved in 2005 and was a twice-a-day medicine. Shortly afterward, a daily GLP-1 was approved, and now there are three once-weekly GLP-1 receptor agonists.

Several pharmaceutical manufacturers are now working on a once-weekly insulin,⁵ as well as an implantable GLP-1 receptor agonist that will need to be replaced every 6-12 months.⁶ Imagine your patient coming in once a year to replace his or her potent glucose lowering medication – one that offers a low incidence of hypoglycemia, maintains glucose control all year long, and requires no adherence to a complicated medication regimen.

Similar technology is being used to develop a once-yearly anti-HIV prophylactic medication delivery system.⁷ This could help prevent the spread of HIV in areas of the world where it may be difficult for people to take daily medications.⁷

The many technological advances we have described may help us reduce our likelihood of missing a dose of a medication. We are hopeful that progress in this area will continue, and that one day medication adherence will require even less effort from patients than it does today.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

References

1. Tabi K et al. Mobile apps for medication management: Review and analysis. JMIR Mhealth Uhealth. 2019 Sep 7(9):13608.

2. Park JYE et al. Mobile phone apps targeting medication adherence: Quality assessment and content analysis of user reviews. JMIR Mhealth Uhealth. 2019 Jan 31;7(1):e11919.

3. Pérez-Jover V et al. Mobile apps for increasing treatment adherence: Systematic review. J Med Internet Res. 2019;21(6):e12505. doi: 10.2196/12505.

4. 4 Smart inhalers that could be lifesaving for people living with asthma & COPD. MyTherapy, July 11, 2019.

5. Rosenstock J et al. Once-weekly insulin for type 2 diabetes without previous insulin treatment. N Engl J Med. 2020 Sep 22. doi: 10.1056/NEJMoa2022474.

6. GLP-1 agonists: From 2 daily injections to 1 per week and beyond. DiaTribe, Jan. 10, 2018.

7. Long-acting HIV prevention tools. Hiv.gov, July 20, 2019.

SARS-CoV-2 infection posed increased risk for pregnant women in terms of severe disease and poor pregnancy outcomes including preterm birth, based on data from two studies published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

In a study of birth and infant outcomes, rates of preterm birth (less than 37 weeks’ gestational age) were higher among women with confirmed SARS-CoV-2 infections compared with the national average (12.9% vs. 10.2%) wrote Kate R. Woodworth, MD, and colleagues of the CDC COVID-19 Response Pregnancy and Linked Outcomes Team.

The researchers collected information on pregnancy and infant outcomes from 16 jurisdictions through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). The study included 5,252 women with laboratory-confirmed SARS-CoV-2 infection reported during March 29–Oct. 14, 2020.

Overall, 12.9% of the 3,912 live births with known gestational age were preterm. A total of 610 infants were tested for SARS-CoV-2, and 2.6% were positive. Most of these perinatal infections (85%) occurred among infants born to women with SARS-CoV-2 infection within 1 week of delivery.

Half of the infants with positive test results were preterm, possibly reflecting higher screening rates in the ICU, the researchers said. “These findings also support the growing evidence that although severe COVID-19 does occur in neonates the majority of term neonates experience asymptomatic infection or mild disease; however, information on long term outcomes among exposed infants is unknown.”

Address disparities that amplify risk

The study findings were limited by several factors including inconsistent symptom reporting, overrepresentation of Hispanic women, and incomplete information on pregnancy loss, Dr. Woodworth and associates noted. However, the results add to the knowledge about the impact of COVID-19 disease on pregnancy by providing a large, population-based cohort with completed pregnancy outcomes as well as infant testing.

“SET-NET will continue to follow pregnancies affected by SARS-CoV-2 through completion of pregnancy and infants until age 6 months to guide clinical and public health practice,” the researchers noted. “Longer-term investigation into solutions to alleviate underlying inequities in social determinants of health associated with disparities in maternal morbidity, mortality, and adverse pregnancy outcomes, and effectively addressing these inequities, could reduce the prevalence of conditions and experiences that might amplify risks from COVID-19,” they added.

Severe disease and death increased in pregnant women

In a second study published in the MMWR, Laura D. Zambrano, PhD, and colleagues, also of the CDC COVID-19 Response Pregnancy and Linked Outcomes Team, compared data on 23,434 reportedly pregnant and 386,028 nonpregnant women of reproductive age (15-44 years) with confirmed and symptomatic SARS-CoV-2 infections reported to the CDC between Jan. 22, 2020, and Oct. 3, 2020.

After adjustment for age, race, and underlying medical conditions, pregnant women with COVID-19 disease were significantly more likely than were nonpregnant women to be admitted to intensive care (10.5 per 1,000 cases vs. 3.9 per 1,000 cases), to receive invasive ventilation (2.9 vs. 1.1), receive extracorporeal membrane oxygenation (0.7 vs. 0.3) and to die (1.5 vs. 1.2).

“Irrespective of pregnancy status, ICU admissions, receipt of invasive ventilation, and death occurred more often among women aged 35-44 years than among those aged 15-24 years,” Dr. Zambrano and associates noted. In addition, non-Hispanic Black and Black women comprised 14.1% of the study population but accounted for 36.6% of deaths overall (9 in pregnant women and 167 in nonpregnant women).

The findings in the study of characteristics were limited by several factors including the voluntary reporting of COVID-19 cases, potential reporting bias, and inadequate time to assess severe cases, the researchers noted. However, “data from previous influenza pandemics, including 2009 H1N1, have shown that pregnant women are at increased risk for severe outcomes including death and the absolute risks for severe outcomes were higher than in this study of COVID-19 during pregnancy.”

“Pregnant women should be informed of their risk for severe COVID-19–associated illness and the warning signs of severe COVID-19,” Dr. Zambrano and associates said. “Providers who care for pregnant women should be familiar with guidelines for medical management of COVID-19, including considerations for management of COVID-19 in pregnancy.”

More data needed for informed counseling

“It is important to conduct research trials involving pregnant women so that we have reliable data regarding outcomes with which to counsel women,” Angela Bianco, MD, a maternal fetal medicine specialist at Mount Sinai Hospital in New York, said in an interview.

“Often pregnant women are excluded from research trials, but the impact of the current public health crisis affects all persons regardless of pregnancy status,” she said.

Dr. Bianco said that she was not surprised by the findings of either study. “In fact, our own research produced similar results.”

“These recent publications found that age-matched pregnant versus nonpregnant women had more severe manifestations of COVID-19, and specifically that pregnant women had a higher risk of requiring ventilation and intensive care admission, as well as higher risk of death,” she said. “Previous studies examining the effect of other SARS viruses have demonstrated that pregnancy is associated with worse outcomes; these findings are likely attributable to the relative state of immunosuppression in pregnancy.” Also, “one of these trials found a greater risk of premature birth in women with COVID-19; this may largely be attributable to iatrogenic delivery due to maternal illness as opposed to spontaneous preterm birth,” Dr. Bianco explained.

“Data are emerging regarding the impact of SARS-CoV-2 on pregnancy outcomes, however information remains limited,” Dr. Bianco noted. “Clinicians need to make patients aware that SARS-CoV-2 infection during pregnancy is associated with a greater risk of severe illness requiring intensive care and/or ventilatory support and even death; however, the precise rates remain unknown. “COVID-19 during pregnancy may result in a preterm birth, but at this time the rate of fetal infection remains unknown,” she said. “Clinicians need to reinforce the importance of physical distancing, mask use, and proper hand hygiene, particularly in this vulnerable population.”

Dr. Bianco emphasized: “Longitudinal studies assessing the impact of SARS-CoV-2 infection at various gestational age periods are needed, as at this time most of the available data includes women with SARS-CoV-2 infection around the time of delivery. Long-term infant outcomes are needed, as well as studies assessing the risk of fetal infection.”

The studies were supported by the Centers for Disease Control and Prevention. The researchers had no financial conflicts to disclose. Dr. Bianco had no relevant financial disclosures.

SOURCE: Woodworth KR et al. MMWR. 2020 Nov 2. doi: 10.15585/mmwr.mm6944e2; Zambrano LD et al. MMWR. 2020 Nov 2. doi: 10.15585/mmwr.mm6944e3.

SARS-CoV-2 infection posed increased risk for pregnant women in terms of severe disease and poor pregnancy outcomes including preterm birth, based on data from two studies published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

In a study of birth and infant outcomes, rates of preterm birth (less than 37 weeks’ gestational age) were higher among women with confirmed SARS-CoV-2 infections compared with the national average (12.9% vs. 10.2%) wrote Kate R. Woodworth, MD, and colleagues of the CDC COVID-19 Response Pregnancy and Linked Outcomes Team.

The researchers collected information on pregnancy and infant outcomes from 16 jurisdictions through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). The study included 5,252 women with laboratory-confirmed SARS-CoV-2 infection reported during March 29–Oct. 14, 2020.

Overall, 12.9% of the 3,912 live births with known gestational age were preterm. A total of 610 infants were tested for SARS-CoV-2, and 2.6% were positive. Most of these perinatal infections (85%) occurred among infants born to women with SARS-CoV-2 infection within 1 week of delivery.

Half of the infants with positive test results were preterm, possibly reflecting higher screening rates in the ICU, the researchers said. “These findings also support the growing evidence that although severe COVID-19 does occur in neonates the majority of term neonates experience asymptomatic infection or mild disease; however, information on long term outcomes among exposed infants is unknown.”

Address disparities that amplify risk

The study findings were limited by several factors including inconsistent symptom reporting, overrepresentation of Hispanic women, and incomplete information on pregnancy loss, Dr. Woodworth and associates noted. However, the results add to the knowledge about the impact of COVID-19 disease on pregnancy by providing a large, population-based cohort with completed pregnancy outcomes as well as infant testing.

“SET-NET will continue to follow pregnancies affected by SARS-CoV-2 through completion of pregnancy and infants until age 6 months to guide clinical and public health practice,” the researchers noted. “Longer-term investigation into solutions to alleviate underlying inequities in social determinants of health associated with disparities in maternal morbidity, mortality, and adverse pregnancy outcomes, and effectively addressing these inequities, could reduce the prevalence of conditions and experiences that might amplify risks from COVID-19,” they added.

Severe disease and death increased in pregnant women

In a second study published in the MMWR, Laura D. Zambrano, PhD, and colleagues, also of the CDC COVID-19 Response Pregnancy and Linked Outcomes Team, compared data on 23,434 reportedly pregnant and 386,028 nonpregnant women of reproductive age (15-44 years) with confirmed and symptomatic SARS-CoV-2 infections reported to the CDC between Jan. 22, 2020, and Oct. 3, 2020.

After adjustment for age, race, and underlying medical conditions, pregnant women with COVID-19 disease were significantly more likely than were nonpregnant women to be admitted to intensive care (10.5 per 1,000 cases vs. 3.9 per 1,000 cases), to receive invasive ventilation (2.9 vs. 1.1), receive extracorporeal membrane oxygenation (0.7 vs. 0.3) and to die (1.5 vs. 1.2).

“Irrespective of pregnancy status, ICU admissions, receipt of invasive ventilation, and death occurred more often among women aged 35-44 years than among those aged 15-24 years,” Dr. Zambrano and associates noted. In addition, non-Hispanic Black and Black women comprised 14.1% of the study population but accounted for 36.6% of deaths overall (9 in pregnant women and 167 in nonpregnant women).

The findings in the study of characteristics were limited by several factors including the voluntary reporting of COVID-19 cases, potential reporting bias, and inadequate time to assess severe cases, the researchers noted. However, “data from previous influenza pandemics, including 2009 H1N1, have shown that pregnant women are at increased risk for severe outcomes including death and the absolute risks for severe outcomes were higher than in this study of COVID-19 during pregnancy.”

“Pregnant women should be informed of their risk for severe COVID-19–associated illness and the warning signs of severe COVID-19,” Dr. Zambrano and associates said. “Providers who care for pregnant women should be familiar with guidelines for medical management of COVID-19, including considerations for management of COVID-19 in pregnancy.”

More data needed for informed counseling

“It is important to conduct research trials involving pregnant women so that we have reliable data regarding outcomes with which to counsel women,” Angela Bianco, MD, a maternal fetal medicine specialist at Mount Sinai Hospital in New York, said in an interview.

“Often pregnant women are excluded from research trials, but the impact of the current public health crisis affects all persons regardless of pregnancy status,” she said.

Dr. Bianco said that she was not surprised by the findings of either study. “In fact, our own research produced similar results.”

“These recent publications found that age-matched pregnant versus nonpregnant women had more severe manifestations of COVID-19, and specifically that pregnant women had a higher risk of requiring ventilation and intensive care admission, as well as higher risk of death,” she said. “Previous studies examining the effect of other SARS viruses have demonstrated that pregnancy is associated with worse outcomes; these findings are likely attributable to the relative state of immunosuppression in pregnancy.” Also, “one of these trials found a greater risk of premature birth in women with COVID-19; this may largely be attributable to iatrogenic delivery due to maternal illness as opposed to spontaneous preterm birth,” Dr. Bianco explained.

“Data are emerging regarding the impact of SARS-CoV-2 on pregnancy outcomes, however information remains limited,” Dr. Bianco noted. “Clinicians need to make patients aware that SARS-CoV-2 infection during pregnancy is associated with a greater risk of severe illness requiring intensive care and/or ventilatory support and even death; however, the precise rates remain unknown. “COVID-19 during pregnancy may result in a preterm birth, but at this time the rate of fetal infection remains unknown,” she said. “Clinicians need to reinforce the importance of physical distancing, mask use, and proper hand hygiene, particularly in this vulnerable population.”

Dr. Bianco emphasized: “Longitudinal studies assessing the impact of SARS-CoV-2 infection at various gestational age periods are needed, as at this time most of the available data includes women with SARS-CoV-2 infection around the time of delivery. Long-term infant outcomes are needed, as well as studies assessing the risk of fetal infection.”

The studies were supported by the Centers for Disease Control and Prevention. The researchers had no financial conflicts to disclose. Dr. Bianco had no relevant financial disclosures.

SOURCE: Woodworth KR et al. MMWR. 2020 Nov 2. doi: 10.15585/mmwr.mm6944e2; Zambrano LD et al. MMWR. 2020 Nov 2. doi: 10.15585/mmwr.mm6944e3.

SARS-CoV-2 infection posed increased risk for pregnant women in terms of severe disease and poor pregnancy outcomes including preterm birth, based on data from two studies published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

In a study of birth and infant outcomes, rates of preterm birth (less than 37 weeks’ gestational age) were higher among women with confirmed SARS-CoV-2 infections compared with the national average (12.9% vs. 10.2%) wrote Kate R. Woodworth, MD, and colleagues of the CDC COVID-19 Response Pregnancy and Linked Outcomes Team.

The researchers collected information on pregnancy and infant outcomes from 16 jurisdictions through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). The study included 5,252 women with laboratory-confirmed SARS-CoV-2 infection reported during March 29–Oct. 14, 2020.

Overall, 12.9% of the 3,912 live births with known gestational age were preterm. A total of 610 infants were tested for SARS-CoV-2, and 2.6% were positive. Most of these perinatal infections (85%) occurred among infants born to women with SARS-CoV-2 infection within 1 week of delivery.

Half of the infants with positive test results were preterm, possibly reflecting higher screening rates in the ICU, the researchers said. “These findings also support the growing evidence that although severe COVID-19 does occur in neonates the majority of term neonates experience asymptomatic infection or mild disease; however, information on long term outcomes among exposed infants is unknown.”

Address disparities that amplify risk

The study findings were limited by several factors including inconsistent symptom reporting, overrepresentation of Hispanic women, and incomplete information on pregnancy loss, Dr. Woodworth and associates noted. However, the results add to the knowledge about the impact of COVID-19 disease on pregnancy by providing a large, population-based cohort with completed pregnancy outcomes as well as infant testing.

“SET-NET will continue to follow pregnancies affected by SARS-CoV-2 through completion of pregnancy and infants until age 6 months to guide clinical and public health practice,” the researchers noted. “Longer-term investigation into solutions to alleviate underlying inequities in social determinants of health associated with disparities in maternal morbidity, mortality, and adverse pregnancy outcomes, and effectively addressing these inequities, could reduce the prevalence of conditions and experiences that might amplify risks from COVID-19,” they added.

Severe disease and death increased in pregnant women

In a second study published in the MMWR, Laura D. Zambrano, PhD, and colleagues, also of the CDC COVID-19 Response Pregnancy and Linked Outcomes Team, compared data on 23,434 reportedly pregnant and 386,028 nonpregnant women of reproductive age (15-44 years) with confirmed and symptomatic SARS-CoV-2 infections reported to the CDC between Jan. 22, 2020, and Oct. 3, 2020.

After adjustment for age, race, and underlying medical conditions, pregnant women with COVID-19 disease were significantly more likely than were nonpregnant women to be admitted to intensive care (10.5 per 1,000 cases vs. 3.9 per 1,000 cases), to receive invasive ventilation (2.9 vs. 1.1), receive extracorporeal membrane oxygenation (0.7 vs. 0.3) and to die (1.5 vs. 1.2).

“Irrespective of pregnancy status, ICU admissions, receipt of invasive ventilation, and death occurred more often among women aged 35-44 years than among those aged 15-24 years,” Dr. Zambrano and associates noted. In addition, non-Hispanic Black and Black women comprised 14.1% of the study population but accounted for 36.6% of deaths overall (9 in pregnant women and 167 in nonpregnant women).

The findings in the study of characteristics were limited by several factors including the voluntary reporting of COVID-19 cases, potential reporting bias, and inadequate time to assess severe cases, the researchers noted. However, “data from previous influenza pandemics, including 2009 H1N1, have shown that pregnant women are at increased risk for severe outcomes including death and the absolute risks for severe outcomes were higher than in this study of COVID-19 during pregnancy.”

“Pregnant women should be informed of their risk for severe COVID-19–associated illness and the warning signs of severe COVID-19,” Dr. Zambrano and associates said. “Providers who care for pregnant women should be familiar with guidelines for medical management of COVID-19, including considerations for management of COVID-19 in pregnancy.”

More data needed for informed counseling

“It is important to conduct research trials involving pregnant women so that we have reliable data regarding outcomes with which to counsel women,” Angela Bianco, MD, a maternal fetal medicine specialist at Mount Sinai Hospital in New York, said in an interview.

“Often pregnant women are excluded from research trials, but the impact of the current public health crisis affects all persons regardless of pregnancy status,” she said.

Dr. Bianco said that she was not surprised by the findings of either study. “In fact, our own research produced similar results.”

“These recent publications found that age-matched pregnant versus nonpregnant women had more severe manifestations of COVID-19, and specifically that pregnant women had a higher risk of requiring ventilation and intensive care admission, as well as higher risk of death,” she said. “Previous studies examining the effect of other SARS viruses have demonstrated that pregnancy is associated with worse outcomes; these findings are likely attributable to the relative state of immunosuppression in pregnancy.” Also, “one of these trials found a greater risk of premature birth in women with COVID-19; this may largely be attributable to iatrogenic delivery due to maternal illness as opposed to spontaneous preterm birth,” Dr. Bianco explained.

“Data are emerging regarding the impact of SARS-CoV-2 on pregnancy outcomes, however information remains limited,” Dr. Bianco noted. “Clinicians need to make patients aware that SARS-CoV-2 infection during pregnancy is associated with a greater risk of severe illness requiring intensive care and/or ventilatory support and even death; however, the precise rates remain unknown. “COVID-19 during pregnancy may result in a preterm birth, but at this time the rate of fetal infection remains unknown,” she said. “Clinicians need to reinforce the importance of physical distancing, mask use, and proper hand hygiene, particularly in this vulnerable population.”

Dr. Bianco emphasized: “Longitudinal studies assessing the impact of SARS-CoV-2 infection at various gestational age periods are needed, as at this time most of the available data includes women with SARS-CoV-2 infection around the time of delivery. Long-term infant outcomes are needed, as well as studies assessing the risk of fetal infection.”

The studies were supported by the Centers for Disease Control and Prevention. The researchers had no financial conflicts to disclose. Dr. Bianco had no relevant financial disclosures.

SOURCE: Woodworth KR et al. MMWR. 2020 Nov 2. doi: 10.15585/mmwr.mm6944e2; Zambrano LD et al. MMWR. 2020 Nov 2. doi: 10.15585/mmwr.mm6944e3.

The number of primary care providers is increasing per capita in the United States, but they are still disproportionately concentrated in urban centers, researchers say.

The finding may provide some reassurance for those who have worried about a shortage of health care workers and whether they will be able to meet the nation’s growing burden of chronic diseases.

“Access to primary care doctors is critical to population health and to reduce health care disparities in this country,” said Donglan Zhang, PhD, an assistant professor of public health at the University of Georgia, Athens.

However, many counties remain underserved, Dr. Zhang said in an interview. The need for primary care in the United States is increasing not only with population growth but because the population is aging.

Dr. Zhang and colleagues published the finding in JAMA Network Open.

Many previous reports have warned of a shortage in primary care providers. To examine recent trends in the primary care workforce, Dr. Zhang and colleagues obtained data on all the primary care clinicians registered with the Centers for Medicare & Medicaid Services from 2009 to 2017.

For the study, the researchers included general practitioners, family physicians and internists without subspecialties, nurse practitioners, and physician assistants. They then compared the number of providers with the number of residents in each county as recorded by the US Census, using urban or rural classifications for each county from the Centers for Disease Control and Prevention.

Because the U.S. Health Resources and Services Administration defines a primary care “shortage” as fewer than 1 primary care practitioner per 3,500 people, the researchers focused on this ratio. They found that the number of nurse practitioners and physician assistants was increasing much faster than the number of primary care physicians. This was true especially in rural areas, but the percentage increase for both nurse practitioners and physician assistants was lower in rural areas versus urban.

The researchers also found that there were more primary care physicians per capita in counties with higher household incomes, a higher proportion of Asian residents, and a higher proportion of college graduates.

They didn’t find a significant association between the median household income and per capita number of nurse practitioners.

They found that counties with a higher proportion of Black and Asian residents had a higher number of nurse practitioners per capita. But they found an opposite association between the proportion of Black residents and the number of physician assistants per capita.

The authors hypothesized that health care reform, particularly the passage of the Affordable Care Act in 2010, may explain the recent increase in the primary care workforce. The legislation expanded the number of people with health insurance and provided incentives for primary and preventive care.

Another factor behind the increase in the primary care workforce could be state laws that have expanded the scope of practice for nurse practitioners and primary care providers, she said.
 

Numbers may overestimate available care

The gap between rural and urban areas could be even wider than this study suggests, Ada D. Stewart, MD, president of the American Academy of Family Physicians, said in an interview. Many nurse practitioners and physician assistants don’t actually practice primary care, but instead assist physicians in other specialties such as orthopedics or general surgery.

“They are part of a team and I don’t want to diminish that at all, but especially when we talk about infant and maternal mortality, family physicians need to be there themselves providing primary care,” she said. “We’re there in hospitals and emergency rooms, and not just taking care of diabetes and hypertension.”

In addition, the primary care workforce may have been reduced since the conclusion of the study period (Dec. 31, 2017) as a result of the COVID-19 pandemic forcing some primary care physicians into retirement, Dr. Stewart said.

Measures that could help reduce the disparity include a more robust system of teaching health centers in rural counties, higher reimbursement for primary care, a lower cost of medical education, and recruiting more people from rural areas to become physicians, Dr. Stewart said.

Telehealth can enhance health care in rural areas, but many people in rural areas lack internet or cellular service, or don’t have access to computers. “We don’t want to create another healthcare disparity,” she said.

And physicians can get to know their patients’ needs better in a face-to-face visit, she said. “Telehealth does have a place, but it does not replace that person-to-person visit.”

This study was funded by National Institute on Minority Health and Health Disparities. Dr. Zhang and Dr. Stewart disclosed no relevant financial relationships.

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

The number of primary care providers is increasing per capita in the United States, but they are still disproportionately concentrated in urban centers, researchers say.

The finding may provide some reassurance for those who have worried about a shortage of health care workers and whether they will be able to meet the nation’s growing burden of chronic diseases.

“Access to primary care doctors is critical to population health and to reduce health care disparities in this country,” said Donglan Zhang, PhD, an assistant professor of public health at the University of Georgia, Athens.

However, many counties remain underserved, Dr. Zhang said in an interview. The need for primary care in the United States is increasing not only with population growth but because the population is aging.

Dr. Zhang and colleagues published the finding in JAMA Network Open.

Many previous reports have warned of a shortage in primary care providers. To examine recent trends in the primary care workforce, Dr. Zhang and colleagues obtained data on all the primary care clinicians registered with the Centers for Medicare & Medicaid Services from 2009 to 2017.

For the study, the researchers included general practitioners, family physicians and internists without subspecialties, nurse practitioners, and physician assistants. They then compared the number of providers with the number of residents in each county as recorded by the US Census, using urban or rural classifications for each county from the Centers for Disease Control and Prevention.

Because the U.S. Health Resources and Services Administration defines a primary care “shortage” as fewer than 1 primary care practitioner per 3,500 people, the researchers focused on this ratio. They found that the number of nurse practitioners and physician assistants was increasing much faster than the number of primary care physicians. This was true especially in rural areas, but the percentage increase for both nurse practitioners and physician assistants was lower in rural areas versus urban.

The researchers also found that there were more primary care physicians per capita in counties with higher household incomes, a higher proportion of Asian residents, and a higher proportion of college graduates.

They didn’t find a significant association between the median household income and per capita number of nurse practitioners.

They found that counties with a higher proportion of Black and Asian residents had a higher number of nurse practitioners per capita. But they found an opposite association between the proportion of Black residents and the number of physician assistants per capita.

The authors hypothesized that health care reform, particularly the passage of the Affordable Care Act in 2010, may explain the recent increase in the primary care workforce. The legislation expanded the number of people with health insurance and provided incentives for primary and preventive care.

Another factor behind the increase in the primary care workforce could be state laws that have expanded the scope of practice for nurse practitioners and primary care providers, she said.
 

Numbers may overestimate available care

The gap between rural and urban areas could be even wider than this study suggests, Ada D. Stewart, MD, president of the American Academy of Family Physicians, said in an interview. Many nurse practitioners and physician assistants don’t actually practice primary care, but instead assist physicians in other specialties such as orthopedics or general surgery.

“They are part of a team and I don’t want to diminish that at all, but especially when we talk about infant and maternal mortality, family physicians need to be there themselves providing primary care,” she said. “We’re there in hospitals and emergency rooms, and not just taking care of diabetes and hypertension.”

In addition, the primary care workforce may have been reduced since the conclusion of the study period (Dec. 31, 2017) as a result of the COVID-19 pandemic forcing some primary care physicians into retirement, Dr. Stewart said.

Measures that could help reduce the disparity include a more robust system of teaching health centers in rural counties, higher reimbursement for primary care, a lower cost of medical education, and recruiting more people from rural areas to become physicians, Dr. Stewart said.

Telehealth can enhance health care in rural areas, but many people in rural areas lack internet or cellular service, or don’t have access to computers. “We don’t want to create another healthcare disparity,” she said.

And physicians can get to know their patients’ needs better in a face-to-face visit, she said. “Telehealth does have a place, but it does not replace that person-to-person visit.”

This study was funded by National Institute on Minority Health and Health Disparities. Dr. Zhang and Dr. Stewart disclosed no relevant financial relationships.

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

The number of primary care providers is increasing per capita in the United States, but they are still disproportionately concentrated in urban centers, researchers say.

The finding may provide some reassurance for those who have worried about a shortage of health care workers and whether they will be able to meet the nation’s growing burden of chronic diseases.

“Access to primary care doctors is critical to population health and to reduce health care disparities in this country,” said Donglan Zhang, PhD, an assistant professor of public health at the University of Georgia, Athens.

However, many counties remain underserved, Dr. Zhang said in an interview. The need for primary care in the United States is increasing not only with population growth but because the population is aging.

Dr. Zhang and colleagues published the finding in JAMA Network Open.

Many previous reports have warned of a shortage in primary care providers. To examine recent trends in the primary care workforce, Dr. Zhang and colleagues obtained data on all the primary care clinicians registered with the Centers for Medicare & Medicaid Services from 2009 to 2017.

For the study, the researchers included general practitioners, family physicians and internists without subspecialties, nurse practitioners, and physician assistants. They then compared the number of providers with the number of residents in each county as recorded by the US Census, using urban or rural classifications for each county from the Centers for Disease Control and Prevention.

Because the U.S. Health Resources and Services Administration defines a primary care “shortage” as fewer than 1 primary care practitioner per 3,500 people, the researchers focused on this ratio. They found that the number of nurse practitioners and physician assistants was increasing much faster than the number of primary care physicians. This was true especially in rural areas, but the percentage increase for both nurse practitioners and physician assistants was lower in rural areas versus urban.

The researchers also found that there were more primary care physicians per capita in counties with higher household incomes, a higher proportion of Asian residents, and a higher proportion of college graduates.

They didn’t find a significant association between the median household income and per capita number of nurse practitioners.

They found that counties with a higher proportion of Black and Asian residents had a higher number of nurse practitioners per capita. But they found an opposite association between the proportion of Black residents and the number of physician assistants per capita.

The authors hypothesized that health care reform, particularly the passage of the Affordable Care Act in 2010, may explain the recent increase in the primary care workforce. The legislation expanded the number of people with health insurance and provided incentives for primary and preventive care.

Another factor behind the increase in the primary care workforce could be state laws that have expanded the scope of practice for nurse practitioners and primary care providers, she said.
 

Numbers may overestimate available care

The gap between rural and urban areas could be even wider than this study suggests, Ada D. Stewart, MD, president of the American Academy of Family Physicians, said in an interview. Many nurse practitioners and physician assistants don’t actually practice primary care, but instead assist physicians in other specialties such as orthopedics or general surgery.

“They are part of a team and I don’t want to diminish that at all, but especially when we talk about infant and maternal mortality, family physicians need to be there themselves providing primary care,” she said. “We’re there in hospitals and emergency rooms, and not just taking care of diabetes and hypertension.”

In addition, the primary care workforce may have been reduced since the conclusion of the study period (Dec. 31, 2017) as a result of the COVID-19 pandemic forcing some primary care physicians into retirement, Dr. Stewart said.

Measures that could help reduce the disparity include a more robust system of teaching health centers in rural counties, higher reimbursement for primary care, a lower cost of medical education, and recruiting more people from rural areas to become physicians, Dr. Stewart said.

Telehealth can enhance health care in rural areas, but many people in rural areas lack internet or cellular service, or don’t have access to computers. “We don’t want to create another healthcare disparity,” she said.

And physicians can get to know their patients’ needs better in a face-to-face visit, she said. “Telehealth does have a place, but it does not replace that person-to-person visit.”

This study was funded by National Institute on Minority Health and Health Disparities. Dr. Zhang and Dr. Stewart disclosed no relevant financial relationships.

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

The Oct. 5, 2020 move by the Food and Drug Administration’s Center for Drug Evaluation and Research (CDER) suggesting the withdrawal of the approval of Makena incited some opposition.

herjua/Thinkstock

Amag Pharmaceuticals’ 17 alpha-hydroxyprogesterone caproate (17OHP) injection received accelerated approval in 2011 to reduce the risk of recurrent preterm birth in women with previous unexplained preterm birth. Makena is the only drug approved for preventing recurrent preterm birth.
 

The back story

The approval was based on findings from a randomized, placebo-controlled trial that demonstrated a 34% relative risk reduction in births before 37 weeks – from 55% in the placebo arm to 36% in the 17OHP-treated arm.

The trial was not designed to measure neonatal outcomes, with the surrogate outcome of recurrent preterm birth being determined as “reasonably likely” to predict benefit to the neonate.

Subsequently, results of the required postapproval confirmatory PROLONG trialproduced conflicting results, failing to show a benefit of 17OHP on either preterm birth or neonatal outcome, which prompted the proposed withdrawal of the drug’s approval.

The CDER advisory committee agreed unanimously that the PROLONG trial did not support the clinical benefit of 17OHP, but the committee was not unanimous in deciding what to do. Of the 16 members, 9 voted to withdraw the drug’s approval, while seven voted to retain it and require another confirmatory trial.

When CDER recommends withdrawal, the company can request a public hearing, which it has done. The FDA commissioner will recommend whether to grant this request.

In the meantime, the New England Journal of Medicine has published opposing views on withdrawal of FDA approval of 170HP: one from a group of three doctors who are against it and the other from the CDER.
 

Arguments from the opposing views

“We sympathize with women who are at risk for recurrent preterm birth that could result in death or significant lifelong health effects in neonates, but retaining on the market a drug not shown to be effective for this use does not protect or promote their health,” wrote Christina Chang, MD, MPH and associates from CDER.

On the other hand, “the widespread use of 17OHP after accelerated approval has not uncovered important safety signals,” countered Michael F. Greene, MD, from Massachusetts General Hospital, Boston; David Harrington, PhD, from the Harvard T. Chan School of Public Health, Boston; and Mark A. Klebanoff, MD, MPH, who was coauthor on the original preapproval study and is with Nationwide Children’s Hospital, the Ohio State University College of Medicine, and Ohio State University College of Public Health, all in Columbus. “Withdrawal of the approval for 17OHP, as imperfect as it may be, will leave a very vulnerable demographic group of U.S. women at high risk for this complication of pregnancy with absolutely no available therapeutic option.”

While both the preapproval study and postapproval PROLONG trial had the same enrollment criteria – namely women with a singleton pregnancy and previous singleton spontaneous preterm birth – all parties acknowledged that the studies ended up with very different cohorts. Approval of the drug in the United States made it difficult to recruit U.S. participants for the second trial “because of a lack of equipoise perceived by health care providers and patients,” noted Dr. Greene and associates, resulting in 75% of the PROLONG study’s cohort coming from Europe. This meant that 59% of those in the first study were non-Hispanic black compared with just 6.6% in the PROLONG study, a difference that is important because of the increased risk of preterm birth in Black women.

“Black women are generally underrepresented in U.S. clinical trials, and they are clearly underrepresented in the PROLONG study,” noted Dr. Greene and colleagues, adding that “the total number of qualifying composite neonatal outcome events among Blacks or African Americans in the entire PROLONG study population of 1,700 participants was 9 (6 of 69 in the 17OHP group and 3 of 40 in the placebo group). This is not a robust database from which to conclude that there is no effect in Black women.”

But, Dr. Chang and the CDER group argued, while the first study showed 17OHP “reduced the risk of recurrent preterm birth in both Black and non-Black participants, the lack of even a trend toward efficacy among either Black or non-Black women in [the PROLONG study] argues that the smaller proportion of Black women [in the PROLONG study] does not explain the lack of efficacy.”

In addition to race, there were other risk factors for preterm birth, such as tobacco, alcohol, and street drug use; marital status; and age that differed between the two study cohorts. Even after subcategorizing PROLONG trial participants into higher or lower risk for preterm birth based on these risk factors, Dr. Chang and associates still found no evidence of benefit to 17OHP treatment in any risk group.

Withdrawing approval of 17OHP for a recurrent preterm indication would still allow off-label prescribing, but would most likely end insurance coverage and eventually manufacturing of the drug, noted Dr. Greene and associates.

“When the majority of a population achieves little benefit from a drug, but a minority demographic group at greatest risk for a serious medical problem appears to obtain significant benefit, any decision that will ultimately make it impossible to obtain the drug should be undertaken cautiously,” they warned. “This issue is particularly pressing when that minority group may be the least able to find and financially afford work-arounds to obtain the needed medication in our complex medical system that has a history of failing to serve them well.”

Dr. Chang and associates reported they had no relevant financial disclosures. Dr. Greene and associates reported that they had no relevant conflicts of interest or financial disclosures. Dr. Greene reported he is employed by the New England Journal of Medicine as associate editor. Dr. Harrington reported being employed by the journal as statistical consultant. Dr. Klebanoff reported he was an author of the original article about 17OHP published in the journal and referenced in this article.
 

The Oct. 5, 2020 move by the Food and Drug Administration’s Center for Drug Evaluation and Research (CDER) suggesting the withdrawal of the approval of Makena incited some opposition.

herjua/Thinkstock

Amag Pharmaceuticals’ 17 alpha-hydroxyprogesterone caproate (17OHP) injection received accelerated approval in 2011 to reduce the risk of recurrent preterm birth in women with previous unexplained preterm birth. Makena is the only drug approved for preventing recurrent preterm birth.
 

The back story

The approval was based on findings from a randomized, placebo-controlled trial that demonstrated a 34% relative risk reduction in births before 37 weeks – from 55% in the placebo arm to 36% in the 17OHP-treated arm.

The trial was not designed to measure neonatal outcomes, with the surrogate outcome of recurrent preterm birth being determined as “reasonably likely” to predict benefit to the neonate.

Subsequently, results of the required postapproval confirmatory PROLONG trialproduced conflicting results, failing to show a benefit of 17OHP on either preterm birth or neonatal outcome, which prompted the proposed withdrawal of the drug’s approval.

The CDER advisory committee agreed unanimously that the PROLONG trial did not support the clinical benefit of 17OHP, but the committee was not unanimous in deciding what to do. Of the 16 members, 9 voted to withdraw the drug’s approval, while seven voted to retain it and require another confirmatory trial.

When CDER recommends withdrawal, the company can request a public hearing, which it has done. The FDA commissioner will recommend whether to grant this request.

In the meantime, the New England Journal of Medicine has published opposing views on withdrawal of FDA approval of 170HP: one from a group of three doctors who are against it and the other from the CDER.
 

Arguments from the opposing views

“We sympathize with women who are at risk for recurrent preterm birth that could result in death or significant lifelong health effects in neonates, but retaining on the market a drug not shown to be effective for this use does not protect or promote their health,” wrote Christina Chang, MD, MPH and associates from CDER.

On the other hand, “the widespread use of 17OHP after accelerated approval has not uncovered important safety signals,” countered Michael F. Greene, MD, from Massachusetts General Hospital, Boston; David Harrington, PhD, from the Harvard T. Chan School of Public Health, Boston; and Mark A. Klebanoff, MD, MPH, who was coauthor on the original preapproval study and is with Nationwide Children’s Hospital, the Ohio State University College of Medicine, and Ohio State University College of Public Health, all in Columbus. “Withdrawal of the approval for 17OHP, as imperfect as it may be, will leave a very vulnerable demographic group of U.S. women at high risk for this complication of pregnancy with absolutely no available therapeutic option.”

While both the preapproval study and postapproval PROLONG trial had the same enrollment criteria – namely women with a singleton pregnancy and previous singleton spontaneous preterm birth – all parties acknowledged that the studies ended up with very different cohorts. Approval of the drug in the United States made it difficult to recruit U.S. participants for the second trial “because of a lack of equipoise perceived by health care providers and patients,” noted Dr. Greene and associates, resulting in 75% of the PROLONG study’s cohort coming from Europe. This meant that 59% of those in the first study were non-Hispanic black compared with just 6.6% in the PROLONG study, a difference that is important because of the increased risk of preterm birth in Black women.

“Black women are generally underrepresented in U.S. clinical trials, and they are clearly underrepresented in the PROLONG study,” noted Dr. Greene and colleagues, adding that “the total number of qualifying composite neonatal outcome events among Blacks or African Americans in the entire PROLONG study population of 1,700 participants was 9 (6 of 69 in the 17OHP group and 3 of 40 in the placebo group). This is not a robust database from which to conclude that there is no effect in Black women.”

But, Dr. Chang and the CDER group argued, while the first study showed 17OHP “reduced the risk of recurrent preterm birth in both Black and non-Black participants, the lack of even a trend toward efficacy among either Black or non-Black women in [the PROLONG study] argues that the smaller proportion of Black women [in the PROLONG study] does not explain the lack of efficacy.”

In addition to race, there were other risk factors for preterm birth, such as tobacco, alcohol, and street drug use; marital status; and age that differed between the two study cohorts. Even after subcategorizing PROLONG trial participants into higher or lower risk for preterm birth based on these risk factors, Dr. Chang and associates still found no evidence of benefit to 17OHP treatment in any risk group.

Withdrawing approval of 17OHP for a recurrent preterm indication would still allow off-label prescribing, but would most likely end insurance coverage and eventually manufacturing of the drug, noted Dr. Greene and associates.

“When the majority of a population achieves little benefit from a drug, but a minority demographic group at greatest risk for a serious medical problem appears to obtain significant benefit, any decision that will ultimately make it impossible to obtain the drug should be undertaken cautiously,” they warned. “This issue is particularly pressing when that minority group may be the least able to find and financially afford work-arounds to obtain the needed medication in our complex medical system that has a history of failing to serve them well.”

Dr. Chang and associates reported they had no relevant financial disclosures. Dr. Greene and associates reported that they had no relevant conflicts of interest or financial disclosures. Dr. Greene reported he is employed by the New England Journal of Medicine as associate editor. Dr. Harrington reported being employed by the journal as statistical consultant. Dr. Klebanoff reported he was an author of the original article about 17OHP published in the journal and referenced in this article.
 

The Oct. 5, 2020 move by the Food and Drug Administration’s Center for Drug Evaluation and Research (CDER) suggesting the withdrawal of the approval of Makena incited some opposition.

herjua/Thinkstock

Amag Pharmaceuticals’ 17 alpha-hydroxyprogesterone caproate (17OHP) injection received accelerated approval in 2011 to reduce the risk of recurrent preterm birth in women with previous unexplained preterm birth. Makena is the only drug approved for preventing recurrent preterm birth.
 

The back story

The approval was based on findings from a randomized, placebo-controlled trial that demonstrated a 34% relative risk reduction in births before 37 weeks – from 55% in the placebo arm to 36% in the 17OHP-treated arm.

The trial was not designed to measure neonatal outcomes, with the surrogate outcome of recurrent preterm birth being determined as “reasonably likely” to predict benefit to the neonate.

Subsequently, results of the required postapproval confirmatory PROLONG trialproduced conflicting results, failing to show a benefit of 17OHP on either preterm birth or neonatal outcome, which prompted the proposed withdrawal of the drug’s approval.

The CDER advisory committee agreed unanimously that the PROLONG trial did not support the clinical benefit of 17OHP, but the committee was not unanimous in deciding what to do. Of the 16 members, 9 voted to withdraw the drug’s approval, while seven voted to retain it and require another confirmatory trial.

When CDER recommends withdrawal, the company can request a public hearing, which it has done. The FDA commissioner will recommend whether to grant this request.

In the meantime, the New England Journal of Medicine has published opposing views on withdrawal of FDA approval of 170HP: one from a group of three doctors who are against it and the other from the CDER.
 

Arguments from the opposing views

“We sympathize with women who are at risk for recurrent preterm birth that could result in death or significant lifelong health effects in neonates, but retaining on the market a drug not shown to be effective for this use does not protect or promote their health,” wrote Christina Chang, MD, MPH and associates from CDER.

On the other hand, “the widespread use of 17OHP after accelerated approval has not uncovered important safety signals,” countered Michael F. Greene, MD, from Massachusetts General Hospital, Boston; David Harrington, PhD, from the Harvard T. Chan School of Public Health, Boston; and Mark A. Klebanoff, MD, MPH, who was coauthor on the original preapproval study and is with Nationwide Children’s Hospital, the Ohio State University College of Medicine, and Ohio State University College of Public Health, all in Columbus. “Withdrawal of the approval for 17OHP, as imperfect as it may be, will leave a very vulnerable demographic group of U.S. women at high risk for this complication of pregnancy with absolutely no available therapeutic option.”

While both the preapproval study and postapproval PROLONG trial had the same enrollment criteria – namely women with a singleton pregnancy and previous singleton spontaneous preterm birth – all parties acknowledged that the studies ended up with very different cohorts. Approval of the drug in the United States made it difficult to recruit U.S. participants for the second trial “because of a lack of equipoise perceived by health care providers and patients,” noted Dr. Greene and associates, resulting in 75% of the PROLONG study’s cohort coming from Europe. This meant that 59% of those in the first study were non-Hispanic black compared with just 6.6% in the PROLONG study, a difference that is important because of the increased risk of preterm birth in Black women.

“Black women are generally underrepresented in U.S. clinical trials, and they are clearly underrepresented in the PROLONG study,” noted Dr. Greene and colleagues, adding that “the total number of qualifying composite neonatal outcome events among Blacks or African Americans in the entire PROLONG study population of 1,700 participants was 9 (6 of 69 in the 17OHP group and 3 of 40 in the placebo group). This is not a robust database from which to conclude that there is no effect in Black women.”

But, Dr. Chang and the CDER group argued, while the first study showed 17OHP “reduced the risk of recurrent preterm birth in both Black and non-Black participants, the lack of even a trend toward efficacy among either Black or non-Black women in [the PROLONG study] argues that the smaller proportion of Black women [in the PROLONG study] does not explain the lack of efficacy.”

In addition to race, there were other risk factors for preterm birth, such as tobacco, alcohol, and street drug use; marital status; and age that differed between the two study cohorts. Even after subcategorizing PROLONG trial participants into higher or lower risk for preterm birth based on these risk factors, Dr. Chang and associates still found no evidence of benefit to 17OHP treatment in any risk group.

Withdrawing approval of 17OHP for a recurrent preterm indication would still allow off-label prescribing, but would most likely end insurance coverage and eventually manufacturing of the drug, noted Dr. Greene and associates.

“When the majority of a population achieves little benefit from a drug, but a minority demographic group at greatest risk for a serious medical problem appears to obtain significant benefit, any decision that will ultimately make it impossible to obtain the drug should be undertaken cautiously,” they warned. “This issue is particularly pressing when that minority group may be the least able to find and financially afford work-arounds to obtain the needed medication in our complex medical system that has a history of failing to serve them well.”

Dr. Chang and associates reported they had no relevant financial disclosures. Dr. Greene and associates reported that they had no relevant conflicts of interest or financial disclosures. Dr. Greene reported he is employed by the New England Journal of Medicine as associate editor. Dr. Harrington reported being employed by the journal as statistical consultant. Dr. Klebanoff reported he was an author of the original article about 17OHP published in the journal and referenced in this article.
 

A new, large study has confirmed that different types of hormone replacement therapy (HRT) are associated with an increased risk for breast cancer and has provided additional information on factors associated with that increased risk.

The study was published online on October 28 in The BMJ.

“The study confirms increased risk of breast cancer in patients taking HRT but shows that the magnitude of risk depends on a number of factors,” first author Yana Vinogradova, PhD, said in an interview. Dr. Vinogradova is a medical statistician at the University of Nottingham (England).

The study also suggests the risk may be lower than was estimated in a large meta-analysis of 24 trials that was published in 2019 in The Lancet. In that study, researchers suggested the risk for breast cancer with HRT was higher and persisted longer than had been thought.

This conclusion from the meta-analysis was widely reported in the lay press and led to the UK Medicine and Healthcare Products Regulatory Agency issuing a safety alert for HRT regarding breast cancer. Experts in the field questioned the alert and said it caused undue anxiety. The European Medicines Agency also issued a safety alert because of the study.

This new study was begun before publication of the meta-analysis. Although the results are broadly similar in suggesting increased risk for breast cancer with HRT use, findings from the new study suggest the risk is lower than had been estimated in the meta-analysis and that the risk diminishes more rapidly after stopping HRT than was suggested by the meta-analysis.

“The publicity surrounding publication of the meta-analysis highlighted unexpectedly high risks and led to a heightened level of concern in some quarters,” Dr. Vinogradova commented. “Our study, based on general population data, has not confirmed any such findings. In general, it showed lower levels of risk and clarified the variability of magnitude within them.”

Dr. Vinogradova said the discrepancy could be related to the fact that the studies were designed differently. The meta-analysis relied on results from 24 studies that were conducted around the world at different periods and included women of different ages and backgrounds. The studies in the meta-analysis used different methods, including questionnaires that relied on women’s memories and therefore could have been biased, she said.

In contrast, the new study analyzed EMR data collected prospectively by general practices in the United Kingdom. The data came from the QResearch and from the Clinical Practice Research Datalink (CPRD) databases, the two largest primary care databases in the United Kingdom, which were linked to hospital, mortality, and cancer registries.

Because this study used a “consistent design” and “consistent data sources,” these new results “are likely to be more accurate and reliable for assessing risks among HRT users,” Dr. Vinogradova commented.

This study used an observational design, so it cannot prove that HRT causes breast cancer. These results may better represent women in the general U.K. population, compared with the earlier meta-analysis, she added.

Commenting on the new study, Michael Jones, PhD, senior staff scientist in genetics and epidemiology at the Institute of Cancer Research, London, also emphasized that it was large and its data came from general practitioner medical records, “so the strong statistical associations are unlikely to be due to chance.

“The results of this study generally confirm what has been seen before and is well established – that the use of combined estrogen plus progestogen HRT is associated with increased risk of breast cancer, and this risk increases with duration of use. But reassuringly, after stopping HRT, the raised risk of breast cancer mostly returns to that seen in nonusers of HRT,” he said.

“It’s important to note that no one study should be considered in isolation,” he added. “Even though some risks were found to be slightly smaller than those reported in another meta-analysis of the worldwide epidemiological evidence recently published in 2019, women considering use of HRT should still follow advice given to them by their [general practitioners].”
 

Study details

In the study, researchers evaluated all types of HRT commonly prescribed in the United Kingdom over the past 20 years, including topical estrogen, vaginal pessaries, and creams. They grouped HRT use by recent (within the past 5 years) and past (5 or more years ago) and HRT duration as short term (less than 5 years) and long term (5 years or longer). Results were adjusted for a range of factors that could affect breast cancer risk, including lifestyle, smoking, alcohol consumption, other medical conditions, family history, and use of other prescribed drugs.

The analysis included 98,611 women aged 50-79 years who were first diagnosed with breast cancer between 1998 and 2019. These women were matched by age and general practice to 457,498 women who were not diagnosed with breast cancer over these years. HRT use was reported in 34% (33,703) of women with breast cancer and in 31% (134,391) of women without breast cancer.

Overall, the risk for breast cancer was increased with use of most HRT drugs (adjusted odds ratio, 1.21; 95% confidence, 1.19-1.23), compared with not using HRT drugs. The highest risk was tied to combined estrogen/progestogen HRT (adjusted OR, 1.26; 95% CI, 1.24-1.29). The lowest risk was tied to estrogen-only HRT (adjusted OR, 1.06; 95% CI, 1.03-1.10). Estrogen cream and vaginal estrogen were not associated with increased breast cancer risk.

In general, breast cancer risk was higher among recent HRT users and those receiving long-term therapy. HRT-associated breast cancer risk increased with age and declined after discontinuing treatment. Therapy of less than 1 year was not associated with increased breast cancer risk.

Women who had recently been receiving long-term combined estrogen/progestogen HRT had a 79% increased risk for breast cancer (adjusted OR, 1.79; 95% CI, 1.73-1.85), compared with never-users. Among recent long-term users of combined HRT, breast cancer risk was highest for norethisterone (adjusted OR, 1.88; 95% CI, 1.79-1.99) and lowest for dydrogesterone (adjusted OR, 1.24; 95% CI, 1.03-1.48). Women who had recently been receiving long-term estrogen-only HRT had a 15% increased risk for breast cancer compared to never-users (adjusted OR, 1.15; 95% CI, 1.09-1.21).

Among women who discontinued HRT 5 or more years ago, risk for breast cancer was no longer increased for long-term estrogen-only therapy and short-term estrogen/progestogen therapy. However, breast cancer risk remained elevated 5 years after discontinuing long-term estrogen/progestogen (adjusted OR, 1.16; 95% CI, 1.11-1.21).

HRT-associated risk for breast cancer increased with age across all durations of therapy.

Compared with never-use, recent long-term estrogen-only therapy was associated with zero extra breast cancer cases per 10,000 women-years among women aged 50-59 years and eight extra cases per 10,000 women-years among women aged 70-79.

Recent long-term estrogen/progestogen use was associated with 15 extra breast cancer cases among women aged 50-59 and 36 extra cases among women aged 70-79 per 10,000 women-years.

Past long-term estrogen/progestogen use was associated with zero extra breast cancer cases among women aged 50-59 and eight extra cases among women aged 70-79 per 10,000 women-years.

Summarizing, Dr. Vinogradova said the increased risk for breast cancer with HRT appears to be “relatively small, particularly for younger women and for any women who use HRT only for a restricted period.”

Decisions about whether to use HRT and which type to use should depend on symptom severity, patient factors, and suitability of other treatment options, she commented.

“Particularly for those women who our study has shown to be most at risk, these decisions should be made through discussions between the patient and her doctor,” she concluded. “We hope that the new and more detailed information provided by our study will facilitate such prescribing decisions.”

The study was partially funded by the School for Primary Care Research of the National Institute for Health Research, by Cancer Research UK, and by the Cancer Research UK Oxford Center. Dr. Vinogradova has disclosed no relevant financial relationships. Senior author Julia Hippisley-Cox is an unpaid director of QResearch and was a paid director of ClinRisk until 2019. The other authors have disclosed no relevant financial relationships.
 

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

A new, large study has confirmed that different types of hormone replacement therapy (HRT) are associated with an increased risk for breast cancer and has provided additional information on factors associated with that increased risk.

The study was published online on October 28 in The BMJ.

“The study confirms increased risk of breast cancer in patients taking HRT but shows that the magnitude of risk depends on a number of factors,” first author Yana Vinogradova, PhD, said in an interview. Dr. Vinogradova is a medical statistician at the University of Nottingham (England).

The study also suggests the risk may be lower than was estimated in a large meta-analysis of 24 trials that was published in 2019 in The Lancet. In that study, researchers suggested the risk for breast cancer with HRT was higher and persisted longer than had been thought.

This conclusion from the meta-analysis was widely reported in the lay press and led to the UK Medicine and Healthcare Products Regulatory Agency issuing a safety alert for HRT regarding breast cancer. Experts in the field questioned the alert and said it caused undue anxiety. The European Medicines Agency also issued a safety alert because of the study.

This new study was begun before publication of the meta-analysis. Although the results are broadly similar in suggesting increased risk for breast cancer with HRT use, findings from the new study suggest the risk is lower than had been estimated in the meta-analysis and that the risk diminishes more rapidly after stopping HRT than was suggested by the meta-analysis.

“The publicity surrounding publication of the meta-analysis highlighted unexpectedly high risks and led to a heightened level of concern in some quarters,” Dr. Vinogradova commented. “Our study, based on general population data, has not confirmed any such findings. In general, it showed lower levels of risk and clarified the variability of magnitude within them.”

Dr. Vinogradova said the discrepancy could be related to the fact that the studies were designed differently. The meta-analysis relied on results from 24 studies that were conducted around the world at different periods and included women of different ages and backgrounds. The studies in the meta-analysis used different methods, including questionnaires that relied on women’s memories and therefore could have been biased, she said.

In contrast, the new study analyzed EMR data collected prospectively by general practices in the United Kingdom. The data came from the QResearch and from the Clinical Practice Research Datalink (CPRD) databases, the two largest primary care databases in the United Kingdom, which were linked to hospital, mortality, and cancer registries.

Because this study used a “consistent design” and “consistent data sources,” these new results “are likely to be more accurate and reliable for assessing risks among HRT users,” Dr. Vinogradova commented.

This study used an observational design, so it cannot prove that HRT causes breast cancer. These results may better represent women in the general U.K. population, compared with the earlier meta-analysis, she added.

Commenting on the new study, Michael Jones, PhD, senior staff scientist in genetics and epidemiology at the Institute of Cancer Research, London, also emphasized that it was large and its data came from general practitioner medical records, “so the strong statistical associations are unlikely to be due to chance.

“The results of this study generally confirm what has been seen before and is well established – that the use of combined estrogen plus progestogen HRT is associated with increased risk of breast cancer, and this risk increases with duration of use. But reassuringly, after stopping HRT, the raised risk of breast cancer mostly returns to that seen in nonusers of HRT,” he said.

“It’s important to note that no one study should be considered in isolation,” he added. “Even though some risks were found to be slightly smaller than those reported in another meta-analysis of the worldwide epidemiological evidence recently published in 2019, women considering use of HRT should still follow advice given to them by their [general practitioners].”
 

Study details

In the study, researchers evaluated all types of HRT commonly prescribed in the United Kingdom over the past 20 years, including topical estrogen, vaginal pessaries, and creams. They grouped HRT use by recent (within the past 5 years) and past (5 or more years ago) and HRT duration as short term (less than 5 years) and long term (5 years or longer). Results were adjusted for a range of factors that could affect breast cancer risk, including lifestyle, smoking, alcohol consumption, other medical conditions, family history, and use of other prescribed drugs.

The analysis included 98,611 women aged 50-79 years who were first diagnosed with breast cancer between 1998 and 2019. These women were matched by age and general practice to 457,498 women who were not diagnosed with breast cancer over these years. HRT use was reported in 34% (33,703) of women with breast cancer and in 31% (134,391) of women without breast cancer.

Overall, the risk for breast cancer was increased with use of most HRT drugs (adjusted odds ratio, 1.21; 95% confidence, 1.19-1.23), compared with not using HRT drugs. The highest risk was tied to combined estrogen/progestogen HRT (adjusted OR, 1.26; 95% CI, 1.24-1.29). The lowest risk was tied to estrogen-only HRT (adjusted OR, 1.06; 95% CI, 1.03-1.10). Estrogen cream and vaginal estrogen were not associated with increased breast cancer risk.

In general, breast cancer risk was higher among recent HRT users and those receiving long-term therapy. HRT-associated breast cancer risk increased with age and declined after discontinuing treatment. Therapy of less than 1 year was not associated with increased breast cancer risk.

Women who had recently been receiving long-term combined estrogen/progestogen HRT had a 79% increased risk for breast cancer (adjusted OR, 1.79; 95% CI, 1.73-1.85), compared with never-users. Among recent long-term users of combined HRT, breast cancer risk was highest for norethisterone (adjusted OR, 1.88; 95% CI, 1.79-1.99) and lowest for dydrogesterone (adjusted OR, 1.24; 95% CI, 1.03-1.48). Women who had recently been receiving long-term estrogen-only HRT had a 15% increased risk for breast cancer compared to never-users (adjusted OR, 1.15; 95% CI, 1.09-1.21).

Among women who discontinued HRT 5 or more years ago, risk for breast cancer was no longer increased for long-term estrogen-only therapy and short-term estrogen/progestogen therapy. However, breast cancer risk remained elevated 5 years after discontinuing long-term estrogen/progestogen (adjusted OR, 1.16; 95% CI, 1.11-1.21).

HRT-associated risk for breast cancer increased with age across all durations of therapy.

Compared with never-use, recent long-term estrogen-only therapy was associated with zero extra breast cancer cases per 10,000 women-years among women aged 50-59 years and eight extra cases per 10,000 women-years among women aged 70-79.

Recent long-term estrogen/progestogen use was associated with 15 extra breast cancer cases among women aged 50-59 and 36 extra cases among women aged 70-79 per 10,000 women-years.

Past long-term estrogen/progestogen use was associated with zero extra breast cancer cases among women aged 50-59 and eight extra cases among women aged 70-79 per 10,000 women-years.

Summarizing, Dr. Vinogradova said the increased risk for breast cancer with HRT appears to be “relatively small, particularly for younger women and for any women who use HRT only for a restricted period.”

Decisions about whether to use HRT and which type to use should depend on symptom severity, patient factors, and suitability of other treatment options, she commented.

“Particularly for those women who our study has shown to be most at risk, these decisions should be made through discussions between the patient and her doctor,” she concluded. “We hope that the new and more detailed information provided by our study will facilitate such prescribing decisions.”

The study was partially funded by the School for Primary Care Research of the National Institute for Health Research, by Cancer Research UK, and by the Cancer Research UK Oxford Center. Dr. Vinogradova has disclosed no relevant financial relationships. Senior author Julia Hippisley-Cox is an unpaid director of QResearch and was a paid director of ClinRisk until 2019. The other authors have disclosed no relevant financial relationships.
 

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

A new, large study has confirmed that different types of hormone replacement therapy (HRT) are associated with an increased risk for breast cancer and has provided additional information on factors associated with that increased risk.

The study was published online on October 28 in The BMJ.

“The study confirms increased risk of breast cancer in patients taking HRT but shows that the magnitude of risk depends on a number of factors,” first author Yana Vinogradova, PhD, said in an interview. Dr. Vinogradova is a medical statistician at the University of Nottingham (England).

The study also suggests the risk may be lower than was estimated in a large meta-analysis of 24 trials that was published in 2019 in The Lancet. In that study, researchers suggested the risk for breast cancer with HRT was higher and persisted longer than had been thought.

This conclusion from the meta-analysis was widely reported in the lay press and led to the UK Medicine and Healthcare Products Regulatory Agency issuing a safety alert for HRT regarding breast cancer. Experts in the field questioned the alert and said it caused undue anxiety. The European Medicines Agency also issued a safety alert because of the study.

This new study was begun before publication of the meta-analysis. Although the results are broadly similar in suggesting increased risk for breast cancer with HRT use, findings from the new study suggest the risk is lower than had been estimated in the meta-analysis and that the risk diminishes more rapidly after stopping HRT than was suggested by the meta-analysis.

“The publicity surrounding publication of the meta-analysis highlighted unexpectedly high risks and led to a heightened level of concern in some quarters,” Dr. Vinogradova commented. “Our study, based on general population data, has not confirmed any such findings. In general, it showed lower levels of risk and clarified the variability of magnitude within them.”

Dr. Vinogradova said the discrepancy could be related to the fact that the studies were designed differently. The meta-analysis relied on results from 24 studies that were conducted around the world at different periods and included women of different ages and backgrounds. The studies in the meta-analysis used different methods, including questionnaires that relied on women’s memories and therefore could have been biased, she said.

In contrast, the new study analyzed EMR data collected prospectively by general practices in the United Kingdom. The data came from the QResearch and from the Clinical Practice Research Datalink (CPRD) databases, the two largest primary care databases in the United Kingdom, which were linked to hospital, mortality, and cancer registries.

Because this study used a “consistent design” and “consistent data sources,” these new results “are likely to be more accurate and reliable for assessing risks among HRT users,” Dr. Vinogradova commented.

This study used an observational design, so it cannot prove that HRT causes breast cancer. These results may better represent women in the general U.K. population, compared with the earlier meta-analysis, she added.

Commenting on the new study, Michael Jones, PhD, senior staff scientist in genetics and epidemiology at the Institute of Cancer Research, London, also emphasized that it was large and its data came from general practitioner medical records, “so the strong statistical associations are unlikely to be due to chance.

“The results of this study generally confirm what has been seen before and is well established – that the use of combined estrogen plus progestogen HRT is associated with increased risk of breast cancer, and this risk increases with duration of use. But reassuringly, after stopping HRT, the raised risk of breast cancer mostly returns to that seen in nonusers of HRT,” he said.

“It’s important to note that no one study should be considered in isolation,” he added. “Even though some risks were found to be slightly smaller than those reported in another meta-analysis of the worldwide epidemiological evidence recently published in 2019, women considering use of HRT should still follow advice given to them by their [general practitioners].”
 

Study details

In the study, researchers evaluated all types of HRT commonly prescribed in the United Kingdom over the past 20 years, including topical estrogen, vaginal pessaries, and creams. They grouped HRT use by recent (within the past 5 years) and past (5 or more years ago) and HRT duration as short term (less than 5 years) and long term (5 years or longer). Results were adjusted for a range of factors that could affect breast cancer risk, including lifestyle, smoking, alcohol consumption, other medical conditions, family history, and use of other prescribed drugs.

The analysis included 98,611 women aged 50-79 years who were first diagnosed with breast cancer between 1998 and 2019. These women were matched by age and general practice to 457,498 women who were not diagnosed with breast cancer over these years. HRT use was reported in 34% (33,703) of women with breast cancer and in 31% (134,391) of women without breast cancer.

Overall, the risk for breast cancer was increased with use of most HRT drugs (adjusted odds ratio, 1.21; 95% confidence, 1.19-1.23), compared with not using HRT drugs. The highest risk was tied to combined estrogen/progestogen HRT (adjusted OR, 1.26; 95% CI, 1.24-1.29). The lowest risk was tied to estrogen-only HRT (adjusted OR, 1.06; 95% CI, 1.03-1.10). Estrogen cream and vaginal estrogen were not associated with increased breast cancer risk.

In general, breast cancer risk was higher among recent HRT users and those receiving long-term therapy. HRT-associated breast cancer risk increased with age and declined after discontinuing treatment. Therapy of less than 1 year was not associated with increased breast cancer risk.

Women who had recently been receiving long-term combined estrogen/progestogen HRT had a 79% increased risk for breast cancer (adjusted OR, 1.79; 95% CI, 1.73-1.85), compared with never-users. Among recent long-term users of combined HRT, breast cancer risk was highest for norethisterone (adjusted OR, 1.88; 95% CI, 1.79-1.99) and lowest for dydrogesterone (adjusted OR, 1.24; 95% CI, 1.03-1.48). Women who had recently been receiving long-term estrogen-only HRT had a 15% increased risk for breast cancer compared to never-users (adjusted OR, 1.15; 95% CI, 1.09-1.21).

Among women who discontinued HRT 5 or more years ago, risk for breast cancer was no longer increased for long-term estrogen-only therapy and short-term estrogen/progestogen therapy. However, breast cancer risk remained elevated 5 years after discontinuing long-term estrogen/progestogen (adjusted OR, 1.16; 95% CI, 1.11-1.21).

HRT-associated risk for breast cancer increased with age across all durations of therapy.

Compared with never-use, recent long-term estrogen-only therapy was associated with zero extra breast cancer cases per 10,000 women-years among women aged 50-59 years and eight extra cases per 10,000 women-years among women aged 70-79.

Recent long-term estrogen/progestogen use was associated with 15 extra breast cancer cases among women aged 50-59 and 36 extra cases among women aged 70-79 per 10,000 women-years.

Past long-term estrogen/progestogen use was associated with zero extra breast cancer cases among women aged 50-59 and eight extra cases among women aged 70-79 per 10,000 women-years.

Summarizing, Dr. Vinogradova said the increased risk for breast cancer with HRT appears to be “relatively small, particularly for younger women and for any women who use HRT only for a restricted period.”

Decisions about whether to use HRT and which type to use should depend on symptom severity, patient factors, and suitability of other treatment options, she commented.

“Particularly for those women who our study has shown to be most at risk, these decisions should be made through discussions between the patient and her doctor,” she concluded. “We hope that the new and more detailed information provided by our study will facilitate such prescribing decisions.”

The study was partially funded by the School for Primary Care Research of the National Institute for Health Research, by Cancer Research UK, and by the Cancer Research UK Oxford Center. Dr. Vinogradova has disclosed no relevant financial relationships. Senior author Julia Hippisley-Cox is an unpaid director of QResearch and was a paid director of ClinRisk until 2019. The other authors have disclosed no relevant financial relationships.
 

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

A multidisciplinary cardio-obstetrics team-based care model may help improve cardiovascular care for pregnant women with cardiovascular disease (CVD), according to a recent study.

©4774344sean/Thinkstock

“We sought to describe clinical characteristics, maternal and fetal outcomes, and cardiovascular readmissions in a cohort of pregnant women with underlying CVD followed by a cardio-obstetrics team,” wrote Ella Magun, MD, of Columbia University, New York, and coauthors. Their report is in the Journal of the American College of Cardiology.

The researchers reported the outcomes of a retrospective cohort analysis involving 306 pregnant women with CVD, who were treated at a quaternary care hospital in New York City.

They defined cardio-obstetrics as a team-based collaborative approach to maternal care that includes maternal fetal medicine, cardiology, anesthesiology, neonatology, nursing, social work, and pharmacy.

More than half of the women in the cohort (53%) were Hispanic and Latino, and 74% were receiving Medicaid, suggesting low socioeconomic status. Key outcomes of interest were cardiovascular readmissions at 30 days, 90 days, and 1 year. Secondary endpoints included maternal death, need for a left ventricular assist device or heart transplantation, and fetal demise.

The most frequently observed forms of CVD were arrhythmias (29%), cardiomyopathy (24%), congenital heart disease (24%), valvular disease (16%), and coronary artery disease (4%). The median Cardiac Disease in Pregnancy (CARPREG II) score was 3, and 43% of women had a CARPREG II score of 4 or higher.

After a median follow-up of 2.6 years, the 30-day and 90-day cardiovascular readmission rates were 1.9% and 4.6%, which was lower than the national 30-day postpartum rate of readmission (3.6%). One maternal death (0.3%) occurred within a year of delivery (woman with Eisenmenger syndrome).

“Despite high CARPREG II scores in this patient population, we found low rates of maternal and fetal complications with a low rate of 30- and 90-day readmissions following delivery,” the researchers wrote.
 

Experts weigh in

“We’re seeing widely increasing interest in the implementation of cardio-obstetrics models for multidisciplinary collaborative care and initial studies suggest these team-based models improve pregnancy and postpartum outcomes for women with cardiac disease,” said Lisa M. Hollier, MD, past president of the American College of Obstetricians and Gynecologists and professor at Baylor College of Medicine in Houston.

Dr. Magun and colleagues acknowledged that a key limitation of the present study was the retrospective, single-center design.

“With program expansions over the next 2-3 years, I expect to see an increasing number of prospective studies with larger sample sizes evaluating the impact of cardio-obstetrics teams on maternal morbidity and mortality,” Dr. Hollier said.

SOURCE: Magun E et al. JACC. 2020 Nov 3. doi: 10.1016/j.jacc.2020.08.071.

A multidisciplinary cardio-obstetrics team-based care model may help improve cardiovascular care for pregnant women with cardiovascular disease (CVD), according to a recent study.

©4774344sean/Thinkstock

“We sought to describe clinical characteristics, maternal and fetal outcomes, and cardiovascular readmissions in a cohort of pregnant women with underlying CVD followed by a cardio-obstetrics team,” wrote Ella Magun, MD, of Columbia University, New York, and coauthors. Their report is in the Journal of the American College of Cardiology.

The researchers reported the outcomes of a retrospective cohort analysis involving 306 pregnant women with CVD, who were treated at a quaternary care hospital in New York City.

They defined cardio-obstetrics as a team-based collaborative approach to maternal care that includes maternal fetal medicine, cardiology, anesthesiology, neonatology, nursing, social work, and pharmacy.

More than half of the women in the cohort (53%) were Hispanic and Latino, and 74% were receiving Medicaid, suggesting low socioeconomic status. Key outcomes of interest were cardiovascular readmissions at 30 days, 90 days, and 1 year. Secondary endpoints included maternal death, need for a left ventricular assist device or heart transplantation, and fetal demise.

The most frequently observed forms of CVD were arrhythmias (29%), cardiomyopathy (24%), congenital heart disease (24%), valvular disease (16%), and coronary artery disease (4%). The median Cardiac Disease in Pregnancy (CARPREG II) score was 3, and 43% of women had a CARPREG II score of 4 or higher.

After a median follow-up of 2.6 years, the 30-day and 90-day cardiovascular readmission rates were 1.9% and 4.6%, which was lower than the national 30-day postpartum rate of readmission (3.6%). One maternal death (0.3%) occurred within a year of delivery (woman with Eisenmenger syndrome).

“Despite high CARPREG II scores in this patient population, we found low rates of maternal and fetal complications with a low rate of 30- and 90-day readmissions following delivery,” the researchers wrote.
 

Experts weigh in

“We’re seeing widely increasing interest in the implementation of cardio-obstetrics models for multidisciplinary collaborative care and initial studies suggest these team-based models improve pregnancy and postpartum outcomes for women with cardiac disease,” said Lisa M. Hollier, MD, past president of the American College of Obstetricians and Gynecologists and professor at Baylor College of Medicine in Houston.

Dr. Magun and colleagues acknowledged that a key limitation of the present study was the retrospective, single-center design.

“With program expansions over the next 2-3 years, I expect to see an increasing number of prospective studies with larger sample sizes evaluating the impact of cardio-obstetrics teams on maternal morbidity and mortality,” Dr. Hollier said.

SOURCE: Magun E et al. JACC. 2020 Nov 3. doi: 10.1016/j.jacc.2020.08.071.

A multidisciplinary cardio-obstetrics team-based care model may help improve cardiovascular care for pregnant women with cardiovascular disease (CVD), according to a recent study.

©4774344sean/Thinkstock

“We sought to describe clinical characteristics, maternal and fetal outcomes, and cardiovascular readmissions in a cohort of pregnant women with underlying CVD followed by a cardio-obstetrics team,” wrote Ella Magun, MD, of Columbia University, New York, and coauthors. Their report is in the Journal of the American College of Cardiology.

The researchers reported the outcomes of a retrospective cohort analysis involving 306 pregnant women with CVD, who were treated at a quaternary care hospital in New York City.

They defined cardio-obstetrics as a team-based collaborative approach to maternal care that includes maternal fetal medicine, cardiology, anesthesiology, neonatology, nursing, social work, and pharmacy.

More than half of the women in the cohort (53%) were Hispanic and Latino, and 74% were receiving Medicaid, suggesting low socioeconomic status. Key outcomes of interest were cardiovascular readmissions at 30 days, 90 days, and 1 year. Secondary endpoints included maternal death, need for a left ventricular assist device or heart transplantation, and fetal demise.

The most frequently observed forms of CVD were arrhythmias (29%), cardiomyopathy (24%), congenital heart disease (24%), valvular disease (16%), and coronary artery disease (4%). The median Cardiac Disease in Pregnancy (CARPREG II) score was 3, and 43% of women had a CARPREG II score of 4 or higher.

After a median follow-up of 2.6 years, the 30-day and 90-day cardiovascular readmission rates were 1.9% and 4.6%, which was lower than the national 30-day postpartum rate of readmission (3.6%). One maternal death (0.3%) occurred within a year of delivery (woman with Eisenmenger syndrome).

“Despite high CARPREG II scores in this patient population, we found low rates of maternal and fetal complications with a low rate of 30- and 90-day readmissions following delivery,” the researchers wrote.
 

Experts weigh in

“We’re seeing widely increasing interest in the implementation of cardio-obstetrics models for multidisciplinary collaborative care and initial studies suggest these team-based models improve pregnancy and postpartum outcomes for women with cardiac disease,” said Lisa M. Hollier, MD, past president of the American College of Obstetricians and Gynecologists and professor at Baylor College of Medicine in Houston.

Dr. Magun and colleagues acknowledged that a key limitation of the present study was the retrospective, single-center design.

“With program expansions over the next 2-3 years, I expect to see an increasing number of prospective studies with larger sample sizes evaluating the impact of cardio-obstetrics teams on maternal morbidity and mortality,” Dr. Hollier said.

SOURCE: Magun E et al. JACC. 2020 Nov 3. doi: 10.1016/j.jacc.2020.08.071.