Heidi Splete

The amount of prescription drugs given to children in the United States decreased by 27.1% between April and December 2020, compared with the same period in 2019, based on data from a national database.

Overall, dispensing of prescription drugs to all patients in the United States decreased in the wake of COVID-19 but has since rebounded, wrote Kao-Ping Chua, MD, of the University of Michigan, Ann Arbor, and colleagues. “However, whether these same trends occurred for children is unknown.”

In a study published in Pediatrics, the researchers used the IQVIA National Prescription Audit, a database that contains monthly dispensing details from 92% of retail pharmacies in the United States. They compared changes in the dispensing of prescriptions with children aged 0-19 years during 2018-2020.

In the April 2020–December 2020 time period, prescriptions for children aged 1-2 years, 3-9 years, and 10-19 years decreased by 48.7%, 40.6%, and 16.8%, respectively, compared with the same time period in 2019.

The overall dispensing total for children from April 2020 to December 2020 was 160,630,406, representing a 27.1% reduction, compared with the 220,284,613 total from April 2019 to December 2019.

By drug class, prescriptions for antibiotics, ADHD medications, and antidepressants decreased by 55.6%, 11.8%, and 0.1%, respectively, in comparing the two time periods. Prescriptions for drug classes used typically for acute infections decreased by 51.3%, and those used for chronic diseases decreased by 17.4%.

From January 2018 to February 2020, a median of 25,744,758 prescriptions were dispensed to children aged 0-19 years each month. The total prescriptions decreased from 25,684,219 in March 2020 to 16,742,568 in April 2020, increased to 19,657,289 in October 2020, and decreased again to 15,821,914 during December 2020.

In a subgroup analysis, the decline in prescriptions was greater in children aged 0-9 years, compared with those aged 10-19 years. “Because young children have a higher rate of antibiotic use than older children, declines in antibiotic dispensing might affect overall dispensing totals to a greater degree in young children,” the researchers said.

The study findings were limited by several factors including the lack of information on clinical outcomes, disease severity, and details of new versus ongoing prescriptions, as well as the possible heterogeneity in indications within drug classes, and lack of data from small pharmacies, the researchers noted. However, the results were strengthened by the use of a national all-payer database that including most prescriptions dispensed in the United States, and the use of objective measurements of prescribing practices rather than self-reports.

Despite concerns for the decreased dispensing of chronic disease drugs to children during the pandemic, “declines in dispensing of infection-related drugs, such as antitussives and antibiotics, may be welcome developments,” the researchers said. “These declines reveal that substantial reductions in prescribing of these drugs are possible,” and ongoing monitoring is needed to follow whether the reductions continue long term.
 

COVID precautions contributed to prescription declines

The mask-wearing and social distancing imposed by the COVID-19 pandemic has contributed to reduced rates of other illnesses, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

“On the surface, with masks and social isolation, we have seen a drastic reduction in infectious disease,” she said. Fewer infections mean a reduced need for prescriptions to treat them. However, Dr. Kinsella expects the situation to change as more venues and activities open. “I expect that, as things continue to open, we will continue to see more infectious disease,” which will likely lead to more prescription drug use.

Part of the study data were provided through the IQVIA Institute’s Human Data Science Research Collaborative. Lead author Dr. Chua was supported by a career development award from the National Institute on Drug Abuse, but had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves as a member of the Pediatric News editorial advisory board.

The amount of prescription drugs given to children in the United States decreased by 27.1% between April and December 2020, compared with the same period in 2019, based on data from a national database.

Overall, dispensing of prescription drugs to all patients in the United States decreased in the wake of COVID-19 but has since rebounded, wrote Kao-Ping Chua, MD, of the University of Michigan, Ann Arbor, and colleagues. “However, whether these same trends occurred for children is unknown.”

In a study published in Pediatrics, the researchers used the IQVIA National Prescription Audit, a database that contains monthly dispensing details from 92% of retail pharmacies in the United States. They compared changes in the dispensing of prescriptions with children aged 0-19 years during 2018-2020.

In the April 2020–December 2020 time period, prescriptions for children aged 1-2 years, 3-9 years, and 10-19 years decreased by 48.7%, 40.6%, and 16.8%, respectively, compared with the same time period in 2019.

The overall dispensing total for children from April 2020 to December 2020 was 160,630,406, representing a 27.1% reduction, compared with the 220,284,613 total from April 2019 to December 2019.

By drug class, prescriptions for antibiotics, ADHD medications, and antidepressants decreased by 55.6%, 11.8%, and 0.1%, respectively, in comparing the two time periods. Prescriptions for drug classes used typically for acute infections decreased by 51.3%, and those used for chronic diseases decreased by 17.4%.

From January 2018 to February 2020, a median of 25,744,758 prescriptions were dispensed to children aged 0-19 years each month. The total prescriptions decreased from 25,684,219 in March 2020 to 16,742,568 in April 2020, increased to 19,657,289 in October 2020, and decreased again to 15,821,914 during December 2020.

In a subgroup analysis, the decline in prescriptions was greater in children aged 0-9 years, compared with those aged 10-19 years. “Because young children have a higher rate of antibiotic use than older children, declines in antibiotic dispensing might affect overall dispensing totals to a greater degree in young children,” the researchers said.

The study findings were limited by several factors including the lack of information on clinical outcomes, disease severity, and details of new versus ongoing prescriptions, as well as the possible heterogeneity in indications within drug classes, and lack of data from small pharmacies, the researchers noted. However, the results were strengthened by the use of a national all-payer database that including most prescriptions dispensed in the United States, and the use of objective measurements of prescribing practices rather than self-reports.

Despite concerns for the decreased dispensing of chronic disease drugs to children during the pandemic, “declines in dispensing of infection-related drugs, such as antitussives and antibiotics, may be welcome developments,” the researchers said. “These declines reveal that substantial reductions in prescribing of these drugs are possible,” and ongoing monitoring is needed to follow whether the reductions continue long term.
 

COVID precautions contributed to prescription declines

The mask-wearing and social distancing imposed by the COVID-19 pandemic has contributed to reduced rates of other illnesses, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

“On the surface, with masks and social isolation, we have seen a drastic reduction in infectious disease,” she said. Fewer infections mean a reduced need for prescriptions to treat them. However, Dr. Kinsella expects the situation to change as more venues and activities open. “I expect that, as things continue to open, we will continue to see more infectious disease,” which will likely lead to more prescription drug use.

Part of the study data were provided through the IQVIA Institute’s Human Data Science Research Collaborative. Lead author Dr. Chua was supported by a career development award from the National Institute on Drug Abuse, but had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves as a member of the Pediatric News editorial advisory board.

The amount of prescription drugs given to children in the United States decreased by 27.1% between April and December 2020, compared with the same period in 2019, based on data from a national database.

Overall, dispensing of prescription drugs to all patients in the United States decreased in the wake of COVID-19 but has since rebounded, wrote Kao-Ping Chua, MD, of the University of Michigan, Ann Arbor, and colleagues. “However, whether these same trends occurred for children is unknown.”

In a study published in Pediatrics, the researchers used the IQVIA National Prescription Audit, a database that contains monthly dispensing details from 92% of retail pharmacies in the United States. They compared changes in the dispensing of prescriptions with children aged 0-19 years during 2018-2020.

In the April 2020–December 2020 time period, prescriptions for children aged 1-2 years, 3-9 years, and 10-19 years decreased by 48.7%, 40.6%, and 16.8%, respectively, compared with the same time period in 2019.

The overall dispensing total for children from April 2020 to December 2020 was 160,630,406, representing a 27.1% reduction, compared with the 220,284,613 total from April 2019 to December 2019.

By drug class, prescriptions for antibiotics, ADHD medications, and antidepressants decreased by 55.6%, 11.8%, and 0.1%, respectively, in comparing the two time periods. Prescriptions for drug classes used typically for acute infections decreased by 51.3%, and those used for chronic diseases decreased by 17.4%.

From January 2018 to February 2020, a median of 25,744,758 prescriptions were dispensed to children aged 0-19 years each month. The total prescriptions decreased from 25,684,219 in March 2020 to 16,742,568 in April 2020, increased to 19,657,289 in October 2020, and decreased again to 15,821,914 during December 2020.

In a subgroup analysis, the decline in prescriptions was greater in children aged 0-9 years, compared with those aged 10-19 years. “Because young children have a higher rate of antibiotic use than older children, declines in antibiotic dispensing might affect overall dispensing totals to a greater degree in young children,” the researchers said.

The study findings were limited by several factors including the lack of information on clinical outcomes, disease severity, and details of new versus ongoing prescriptions, as well as the possible heterogeneity in indications within drug classes, and lack of data from small pharmacies, the researchers noted. However, the results were strengthened by the use of a national all-payer database that including most prescriptions dispensed in the United States, and the use of objective measurements of prescribing practices rather than self-reports.

Despite concerns for the decreased dispensing of chronic disease drugs to children during the pandemic, “declines in dispensing of infection-related drugs, such as antitussives and antibiotics, may be welcome developments,” the researchers said. “These declines reveal that substantial reductions in prescribing of these drugs are possible,” and ongoing monitoring is needed to follow whether the reductions continue long term.
 

COVID precautions contributed to prescription declines

The mask-wearing and social distancing imposed by the COVID-19 pandemic has contributed to reduced rates of other illnesses, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

“On the surface, with masks and social isolation, we have seen a drastic reduction in infectious disease,” she said. Fewer infections mean a reduced need for prescriptions to treat them. However, Dr. Kinsella expects the situation to change as more venues and activities open. “I expect that, as things continue to open, we will continue to see more infectious disease,” which will likely lead to more prescription drug use.

Part of the study data were provided through the IQVIA Institute’s Human Data Science Research Collaborative. Lead author Dr. Chua was supported by a career development award from the National Institute on Drug Abuse, but had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves as a member of the Pediatric News editorial advisory board.

Black women undergoing hysterectomies were significantly more likely to be treated by low-volume surgeons than high-volume surgeons, and to experience perioperative complications as a result, based on data from more than 300,000 patients.

“Outcomes for hysterectomy, for both benign and malignant disease, are improved when the procedure is performed at high-volume hospitals and by high-volume surgeons,” Anne Knisely, MD, of Columbia University, New York, and colleagues wrote.

Historically, Black patients have been less likely to be referred to high-volume hospitals, the researchers noted. Recent efforts to regionalize surgical procedures to high-volume hospitals aim to reduce disparities and improve care for all patients, but the data on disparities in care within high-volume hospitals are limited, they said.

In a study published in Obstetrics & Gynecology, the researchers identified 300,586 women who underwent hysterectomy in New York state between 2000 and 2014. The researchers divided surgeons at these hospitals into volume groups based on average annual hysterectomy volume.

The women were treated by 5,505 surgeons at 59 hospitals. Overall, Black women comprised significantly more of the patients treated by low-volume surgeons compared with high-volume surgeons (19.4% vs. 14.3%; adjusted odds ratio, 1.26), and more women treated by low-volume surgeons had Medicare insurance compared with those treated by high-volume surgeons (20.6% vs. 14.5%; aOR, 1.22).

A majority of the patients (262,005 patients) were treated by a total of 1,377 high-volume surgeons, while 2,105 low-volume surgeons treated 2,900 patients. Abdominal hysterectomies accounted for 57.5% of the procedures, followed by laparoscopic (23.9%), vaginal (13.2%), and robotic assisted (5.3%). Approximately two-thirds (64.4%) of the patients were aged 40-59 years; 63.7% were White, 15.1% were Black, and 8.5% were Hispanic.

The overall complication rate was significantly higher in patients treated by low-volume surgeons, compared with high-volume surgeons (31.0% vs. 10.3%), including intraoperative complications, surgical-site complications, medical complications, and transfusions. The perioperative mortality rate also was significantly higher for patients of low-volume surgeons compared with high-volume surgeons (2.2% vs. 0.2%).

Low-volume surgeons were more likely to perform urgent or emergent procedures, compared with high-volume surgeons (26.1% vs 6.4%), and to perform abdominal hysterectomy versus minimally invasive hysterectomy compared with high-volume surgeons (77.8% vs. 54.7%), the researchers added.

The study findings were limited by several factors, including the observational design and possible undercoding of outcomes, inclusion only of New York state patients, lack of data on clinical characteristics such as surgical history and complexity, lack of data on surgeon characteristics, and changing practice patterns over time, the researchers noted.

However, “this study demonstrates increased perioperative morbidity and mortality for patients who underwent hysterectomy by low-volume surgeons, in comparison with high-volume surgeons, at high-volume hospitals,” and that Black patients were more likely to be treated by low-volume surgeons, they said. “Although centralization of complex surgical care to higher-volume hospitals may have benefit, there are additional surgeon-level factors that must be considered to address disparities in access to high-quality care for patients undergoing hysterectomy.”

Explore range of issues to improve access

“It is always beneficial to review morbidity and mortality statistics,” Constance Bohon, MD, a gynecologist in private practice in Washington, D.C., said in an interview. “With a heightened awareness of equity and equality, now is a good time to review the data with that focus in mind. Hospital committees review the data on a regular basis, but they may not have looked closely at demographics in the past.

“It was always my understanding that for many procedures, including surgery, volume impacts outcome, so the finding that low-volume surgeons had worse outcomes than high-volume surgeons was not particularly surprising,” said Dr. Bohon. However, the question of how hospitals might address disparities in access to high-volume surgeons “is a difficult question, because there are a variety of issues that may not be caused by disparities,” she added. “It may be that the high-volume surgeons do not take Medicare. It may be that some of the emergent/urgent surgeries come from patients seen in the ED and the high-volume surgeons may not take call or see new patients in the ED. There may be a difference in the preop testing done that may be more extensive with the high-volume surgeons as compared with the low-volume surgeons. It may be that it is easier to get an appointment with a low-volume rather than a high-volume surgeon.

“Additional research is needed to determine whether there is an algorithm that can be created to determine risk for morbidity or mortality based on factors such as the number of years in practice, the number of hysterectomies per year, and the age of the physician,” Dr. Bohon explained. “The patient data could include preexisting risk factors such as weight, preexisting medical conditions, prior surgeries, and current medications, along with demographics. It would be interesting to determine whether low-risk patients have similar outcomes with low- as compared with high-volume surgeons while high-risk patients do not. The demographics could then be evaluated to determine if disparities exist for both low- and high-risk patients.”

The study received no outside funding. One coauthor disclosed serving as a consultant for Clovis Oncology, receiving research funding from Merck, and receiving royalties from UpToDate. Lead author Dr. Knisely had no financial conflicts to disclose. Dr. Bohon had no financial conflicts to disclose, but serves on the Ob.Gyn. News editorial advisory board.

Black women undergoing hysterectomies were significantly more likely to be treated by low-volume surgeons than high-volume surgeons, and to experience perioperative complications as a result, based on data from more than 300,000 patients.

“Outcomes for hysterectomy, for both benign and malignant disease, are improved when the procedure is performed at high-volume hospitals and by high-volume surgeons,” Anne Knisely, MD, of Columbia University, New York, and colleagues wrote.

Historically, Black patients have been less likely to be referred to high-volume hospitals, the researchers noted. Recent efforts to regionalize surgical procedures to high-volume hospitals aim to reduce disparities and improve care for all patients, but the data on disparities in care within high-volume hospitals are limited, they said.

In a study published in Obstetrics & Gynecology, the researchers identified 300,586 women who underwent hysterectomy in New York state between 2000 and 2014. The researchers divided surgeons at these hospitals into volume groups based on average annual hysterectomy volume.

The women were treated by 5,505 surgeons at 59 hospitals. Overall, Black women comprised significantly more of the patients treated by low-volume surgeons compared with high-volume surgeons (19.4% vs. 14.3%; adjusted odds ratio, 1.26), and more women treated by low-volume surgeons had Medicare insurance compared with those treated by high-volume surgeons (20.6% vs. 14.5%; aOR, 1.22).

A majority of the patients (262,005 patients) were treated by a total of 1,377 high-volume surgeons, while 2,105 low-volume surgeons treated 2,900 patients. Abdominal hysterectomies accounted for 57.5% of the procedures, followed by laparoscopic (23.9%), vaginal (13.2%), and robotic assisted (5.3%). Approximately two-thirds (64.4%) of the patients were aged 40-59 years; 63.7% were White, 15.1% were Black, and 8.5% were Hispanic.

The overall complication rate was significantly higher in patients treated by low-volume surgeons, compared with high-volume surgeons (31.0% vs. 10.3%), including intraoperative complications, surgical-site complications, medical complications, and transfusions. The perioperative mortality rate also was significantly higher for patients of low-volume surgeons compared with high-volume surgeons (2.2% vs. 0.2%).

Low-volume surgeons were more likely to perform urgent or emergent procedures, compared with high-volume surgeons (26.1% vs 6.4%), and to perform abdominal hysterectomy versus minimally invasive hysterectomy compared with high-volume surgeons (77.8% vs. 54.7%), the researchers added.

The study findings were limited by several factors, including the observational design and possible undercoding of outcomes, inclusion only of New York state patients, lack of data on clinical characteristics such as surgical history and complexity, lack of data on surgeon characteristics, and changing practice patterns over time, the researchers noted.

However, “this study demonstrates increased perioperative morbidity and mortality for patients who underwent hysterectomy by low-volume surgeons, in comparison with high-volume surgeons, at high-volume hospitals,” and that Black patients were more likely to be treated by low-volume surgeons, they said. “Although centralization of complex surgical care to higher-volume hospitals may have benefit, there are additional surgeon-level factors that must be considered to address disparities in access to high-quality care for patients undergoing hysterectomy.”

Explore range of issues to improve access

“It is always beneficial to review morbidity and mortality statistics,” Constance Bohon, MD, a gynecologist in private practice in Washington, D.C., said in an interview. “With a heightened awareness of equity and equality, now is a good time to review the data with that focus in mind. Hospital committees review the data on a regular basis, but they may not have looked closely at demographics in the past.

“It was always my understanding that for many procedures, including surgery, volume impacts outcome, so the finding that low-volume surgeons had worse outcomes than high-volume surgeons was not particularly surprising,” said Dr. Bohon. However, the question of how hospitals might address disparities in access to high-volume surgeons “is a difficult question, because there are a variety of issues that may not be caused by disparities,” she added. “It may be that the high-volume surgeons do not take Medicare. It may be that some of the emergent/urgent surgeries come from patients seen in the ED and the high-volume surgeons may not take call or see new patients in the ED. There may be a difference in the preop testing done that may be more extensive with the high-volume surgeons as compared with the low-volume surgeons. It may be that it is easier to get an appointment with a low-volume rather than a high-volume surgeon.

“Additional research is needed to determine whether there is an algorithm that can be created to determine risk for morbidity or mortality based on factors such as the number of years in practice, the number of hysterectomies per year, and the age of the physician,” Dr. Bohon explained. “The patient data could include preexisting risk factors such as weight, preexisting medical conditions, prior surgeries, and current medications, along with demographics. It would be interesting to determine whether low-risk patients have similar outcomes with low- as compared with high-volume surgeons while high-risk patients do not. The demographics could then be evaluated to determine if disparities exist for both low- and high-risk patients.”

The study received no outside funding. One coauthor disclosed serving as a consultant for Clovis Oncology, receiving research funding from Merck, and receiving royalties from UpToDate. Lead author Dr. Knisely had no financial conflicts to disclose. Dr. Bohon had no financial conflicts to disclose, but serves on the Ob.Gyn. News editorial advisory board.

Black women undergoing hysterectomies were significantly more likely to be treated by low-volume surgeons than high-volume surgeons, and to experience perioperative complications as a result, based on data from more than 300,000 patients.

“Outcomes for hysterectomy, for both benign and malignant disease, are improved when the procedure is performed at high-volume hospitals and by high-volume surgeons,” Anne Knisely, MD, of Columbia University, New York, and colleagues wrote.

Historically, Black patients have been less likely to be referred to high-volume hospitals, the researchers noted. Recent efforts to regionalize surgical procedures to high-volume hospitals aim to reduce disparities and improve care for all patients, but the data on disparities in care within high-volume hospitals are limited, they said.

In a study published in Obstetrics & Gynecology, the researchers identified 300,586 women who underwent hysterectomy in New York state between 2000 and 2014. The researchers divided surgeons at these hospitals into volume groups based on average annual hysterectomy volume.

The women were treated by 5,505 surgeons at 59 hospitals. Overall, Black women comprised significantly more of the patients treated by low-volume surgeons compared with high-volume surgeons (19.4% vs. 14.3%; adjusted odds ratio, 1.26), and more women treated by low-volume surgeons had Medicare insurance compared with those treated by high-volume surgeons (20.6% vs. 14.5%; aOR, 1.22).

A majority of the patients (262,005 patients) were treated by a total of 1,377 high-volume surgeons, while 2,105 low-volume surgeons treated 2,900 patients. Abdominal hysterectomies accounted for 57.5% of the procedures, followed by laparoscopic (23.9%), vaginal (13.2%), and robotic assisted (5.3%). Approximately two-thirds (64.4%) of the patients were aged 40-59 years; 63.7% were White, 15.1% were Black, and 8.5% were Hispanic.

The overall complication rate was significantly higher in patients treated by low-volume surgeons, compared with high-volume surgeons (31.0% vs. 10.3%), including intraoperative complications, surgical-site complications, medical complications, and transfusions. The perioperative mortality rate also was significantly higher for patients of low-volume surgeons compared with high-volume surgeons (2.2% vs. 0.2%).

Low-volume surgeons were more likely to perform urgent or emergent procedures, compared with high-volume surgeons (26.1% vs 6.4%), and to perform abdominal hysterectomy versus minimally invasive hysterectomy compared with high-volume surgeons (77.8% vs. 54.7%), the researchers added.

The study findings were limited by several factors, including the observational design and possible undercoding of outcomes, inclusion only of New York state patients, lack of data on clinical characteristics such as surgical history and complexity, lack of data on surgeon characteristics, and changing practice patterns over time, the researchers noted.

However, “this study demonstrates increased perioperative morbidity and mortality for patients who underwent hysterectomy by low-volume surgeons, in comparison with high-volume surgeons, at high-volume hospitals,” and that Black patients were more likely to be treated by low-volume surgeons, they said. “Although centralization of complex surgical care to higher-volume hospitals may have benefit, there are additional surgeon-level factors that must be considered to address disparities in access to high-quality care for patients undergoing hysterectomy.”

Explore range of issues to improve access

“It is always beneficial to review morbidity and mortality statistics,” Constance Bohon, MD, a gynecologist in private practice in Washington, D.C., said in an interview. “With a heightened awareness of equity and equality, now is a good time to review the data with that focus in mind. Hospital committees review the data on a regular basis, but they may not have looked closely at demographics in the past.

“It was always my understanding that for many procedures, including surgery, volume impacts outcome, so the finding that low-volume surgeons had worse outcomes than high-volume surgeons was not particularly surprising,” said Dr. Bohon. However, the question of how hospitals might address disparities in access to high-volume surgeons “is a difficult question, because there are a variety of issues that may not be caused by disparities,” she added. “It may be that the high-volume surgeons do not take Medicare. It may be that some of the emergent/urgent surgeries come from patients seen in the ED and the high-volume surgeons may not take call or see new patients in the ED. There may be a difference in the preop testing done that may be more extensive with the high-volume surgeons as compared with the low-volume surgeons. It may be that it is easier to get an appointment with a low-volume rather than a high-volume surgeon.

“Additional research is needed to determine whether there is an algorithm that can be created to determine risk for morbidity or mortality based on factors such as the number of years in practice, the number of hysterectomies per year, and the age of the physician,” Dr. Bohon explained. “The patient data could include preexisting risk factors such as weight, preexisting medical conditions, prior surgeries, and current medications, along with demographics. It would be interesting to determine whether low-risk patients have similar outcomes with low- as compared with high-volume surgeons while high-risk patients do not. The demographics could then be evaluated to determine if disparities exist for both low- and high-risk patients.”

The study received no outside funding. One coauthor disclosed serving as a consultant for Clovis Oncology, receiving research funding from Merck, and receiving royalties from UpToDate. Lead author Dr. Knisely had no financial conflicts to disclose. Dr. Bohon had no financial conflicts to disclose, but serves on the Ob.Gyn. News editorial advisory board.

Only 1 child from a cohort of 45 children hospitalized with multisystem inflammatory syndrome following COVID-19 infection had persistent mild cardiac dysfunction after 9 months, according to data from patients younger than 21 years seen at a single center in 2020.

In a study published in Pediatrics, Kanwal M. Farooqi, MD, of Columbia University, New York, and colleagues provided the first report on longitudinal cardiac and immunologic outcomes in North American children hospitalized with multisystem inflammatory syndrome (MIS-C). In response to the COVID-19 pandemic, clinicians at New York–Presbyterian Hospital consolidated pediatric admissions and developed an interdisciplinary inpatient and outpatient MIS-C follow-up program to monitor cardiac and immunologic outcomes in their patients.

The study included all children younger than 21 years admitted to Columbia University Irving Medical Center/New York–Presbyterian Morgan Stanley Children’s Hospital for MIS-C in 2020. The median age of the patients was 9 years, and the median length of hospital stay was 5 days. Follow-up visits occurred at 1-4 weeks (average 2 weeks), 1-4 months (average 2 months), and 4-9 months (average 6 months) after hospital discharge. Follow-up visits included echocardiograms and measures of inflammatory markers.

Most of the children (84%) had no underlying medical conditions, but 24% presented with some level of respiratory distress or oxygen requirement, and 64% had vasodilatory shock. In addition, 80% had at least mild cardiac abnormalities and 66% had significant lymphopenia on admission.

Inflammatory profiles on admission showed elevation of C-reactive protein, ferritin, and D-dimer in 87%-98% of the patients. Consistent with cardiac involvement, 64% of the patients also had elevated troponin levels, and 91% had elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels.

“These parameters peaked at or shortly after admission and then gradually normalized,” the researchers said. “By the first follow-up, [C-reactive protein], troponin, and NT-proBNP had normalized in nearly all tested patients (97%-100%),” they noted.

By the first follow-up period at 1-4 weeks, all patients had normal coronary arteries, and 18% (seven patients) had mild echocardiographic findings. However, approximately one-third (32%) of the patients had persistent lymphocytosis at 1-4 weeks, and 23 of the 24 patients assessed had elevated double-negative T cells, which persisted in 96% of the patients at 1-4 months’ follow-up. However, during the last follow-up of 4-9 months, only one patient had persistent mild biventricular dysfunction and a second patient had mild mitral and tricuspid valve regurgitation.

All patients were treated with steroids and immunoglobulins (2 g/kg), as well as enoxaparin prophylaxis or low-dose aspirin and GI prophylaxis. Treatment with methylprednisolone varied based on disease severity; patients with mild presentation received 2 mg/kg per day; those with moderate presentation received a methylprednisolone pulse of 10 mg/kg per day, followed by 2 mg/kg per day; those with severe disease received methylprednisolone at 20-30 mg/kg per day for 1-3 days, followed by 2 mg/kg per day.

“Aggressive use of steroids may also explain the lower incidence of coronary artery abnormalities in our cohort,” the researchers noted.

The study findings were limited by the observational design and inability to make definitive conclusions about treatment and outcomes, as well as the evolving case definitions for MIS-C, the researchers said.

The persistence of double-negative T cells was surprising, and “likely represent a prolonged postinflammatory recovery cell population, but further study is ongoing to better define this observation,” they noted.

“Our study reveals generally encouraging medium-term outcomes, including rapid normalization of inflammatory markers and significant cardiac abnormalities in the majority of patients with MIS-C,” the researchers said. “The exact nature and potential for long-term cardiac fibrosis, exercise intolerance, or other changes remain unknown,” and long-term caution and follow-up are recommended, they concluded.
 

Cautious optimism, long-term monitoring

The study is important to provide guidance for clinicians on how to manage their patients who have been hospitalized with MIS-C, said Susan Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H.

“It was both surprising and reassuring to see that so many of the patients had positive outcomes in terms of cardiac function and that during the acute stage there were no deaths,” said Dr. Boulter. “Hospitalizations were brief, averaging just 5 days. The patients had many symptoms, but unlike adults, there was not a preponderance of underlying risk factors in this cohort of patients,” she said.

The results suggest optimism for MIS-C patients in that they generally recover, but the take-home message for clinicians is that these patients will require careful monitoring for long-term issues, Dr. Boulter said.

“These patients should be followed for years to assess long-term effects on morbidity and mortality,” Dr. Boulter emphasized.

The study was funded by Genentech. The researchers had no financial conflicts to disclose. Dr. Boulter had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

Only 1 child from a cohort of 45 children hospitalized with multisystem inflammatory syndrome following COVID-19 infection had persistent mild cardiac dysfunction after 9 months, according to data from patients younger than 21 years seen at a single center in 2020.

In a study published in Pediatrics, Kanwal M. Farooqi, MD, of Columbia University, New York, and colleagues provided the first report on longitudinal cardiac and immunologic outcomes in North American children hospitalized with multisystem inflammatory syndrome (MIS-C). In response to the COVID-19 pandemic, clinicians at New York–Presbyterian Hospital consolidated pediatric admissions and developed an interdisciplinary inpatient and outpatient MIS-C follow-up program to monitor cardiac and immunologic outcomes in their patients.

The study included all children younger than 21 years admitted to Columbia University Irving Medical Center/New York–Presbyterian Morgan Stanley Children’s Hospital for MIS-C in 2020. The median age of the patients was 9 years, and the median length of hospital stay was 5 days. Follow-up visits occurred at 1-4 weeks (average 2 weeks), 1-4 months (average 2 months), and 4-9 months (average 6 months) after hospital discharge. Follow-up visits included echocardiograms and measures of inflammatory markers.

Most of the children (84%) had no underlying medical conditions, but 24% presented with some level of respiratory distress or oxygen requirement, and 64% had vasodilatory shock. In addition, 80% had at least mild cardiac abnormalities and 66% had significant lymphopenia on admission.

Inflammatory profiles on admission showed elevation of C-reactive protein, ferritin, and D-dimer in 87%-98% of the patients. Consistent with cardiac involvement, 64% of the patients also had elevated troponin levels, and 91% had elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels.

“These parameters peaked at or shortly after admission and then gradually normalized,” the researchers said. “By the first follow-up, [C-reactive protein], troponin, and NT-proBNP had normalized in nearly all tested patients (97%-100%),” they noted.

By the first follow-up period at 1-4 weeks, all patients had normal coronary arteries, and 18% (seven patients) had mild echocardiographic findings. However, approximately one-third (32%) of the patients had persistent lymphocytosis at 1-4 weeks, and 23 of the 24 patients assessed had elevated double-negative T cells, which persisted in 96% of the patients at 1-4 months’ follow-up. However, during the last follow-up of 4-9 months, only one patient had persistent mild biventricular dysfunction and a second patient had mild mitral and tricuspid valve regurgitation.

All patients were treated with steroids and immunoglobulins (2 g/kg), as well as enoxaparin prophylaxis or low-dose aspirin and GI prophylaxis. Treatment with methylprednisolone varied based on disease severity; patients with mild presentation received 2 mg/kg per day; those with moderate presentation received a methylprednisolone pulse of 10 mg/kg per day, followed by 2 mg/kg per day; those with severe disease received methylprednisolone at 20-30 mg/kg per day for 1-3 days, followed by 2 mg/kg per day.

“Aggressive use of steroids may also explain the lower incidence of coronary artery abnormalities in our cohort,” the researchers noted.

The study findings were limited by the observational design and inability to make definitive conclusions about treatment and outcomes, as well as the evolving case definitions for MIS-C, the researchers said.

The persistence of double-negative T cells was surprising, and “likely represent a prolonged postinflammatory recovery cell population, but further study is ongoing to better define this observation,” they noted.

“Our study reveals generally encouraging medium-term outcomes, including rapid normalization of inflammatory markers and significant cardiac abnormalities in the majority of patients with MIS-C,” the researchers said. “The exact nature and potential for long-term cardiac fibrosis, exercise intolerance, or other changes remain unknown,” and long-term caution and follow-up are recommended, they concluded.
 

Cautious optimism, long-term monitoring

The study is important to provide guidance for clinicians on how to manage their patients who have been hospitalized with MIS-C, said Susan Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H.

“It was both surprising and reassuring to see that so many of the patients had positive outcomes in terms of cardiac function and that during the acute stage there were no deaths,” said Dr. Boulter. “Hospitalizations were brief, averaging just 5 days. The patients had many symptoms, but unlike adults, there was not a preponderance of underlying risk factors in this cohort of patients,” she said.

The results suggest optimism for MIS-C patients in that they generally recover, but the take-home message for clinicians is that these patients will require careful monitoring for long-term issues, Dr. Boulter said.

“These patients should be followed for years to assess long-term effects on morbidity and mortality,” Dr. Boulter emphasized.

The study was funded by Genentech. The researchers had no financial conflicts to disclose. Dr. Boulter had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

Only 1 child from a cohort of 45 children hospitalized with multisystem inflammatory syndrome following COVID-19 infection had persistent mild cardiac dysfunction after 9 months, according to data from patients younger than 21 years seen at a single center in 2020.

In a study published in Pediatrics, Kanwal M. Farooqi, MD, of Columbia University, New York, and colleagues provided the first report on longitudinal cardiac and immunologic outcomes in North American children hospitalized with multisystem inflammatory syndrome (MIS-C). In response to the COVID-19 pandemic, clinicians at New York–Presbyterian Hospital consolidated pediatric admissions and developed an interdisciplinary inpatient and outpatient MIS-C follow-up program to monitor cardiac and immunologic outcomes in their patients.

The study included all children younger than 21 years admitted to Columbia University Irving Medical Center/New York–Presbyterian Morgan Stanley Children’s Hospital for MIS-C in 2020. The median age of the patients was 9 years, and the median length of hospital stay was 5 days. Follow-up visits occurred at 1-4 weeks (average 2 weeks), 1-4 months (average 2 months), and 4-9 months (average 6 months) after hospital discharge. Follow-up visits included echocardiograms and measures of inflammatory markers.

Most of the children (84%) had no underlying medical conditions, but 24% presented with some level of respiratory distress or oxygen requirement, and 64% had vasodilatory shock. In addition, 80% had at least mild cardiac abnormalities and 66% had significant lymphopenia on admission.

Inflammatory profiles on admission showed elevation of C-reactive protein, ferritin, and D-dimer in 87%-98% of the patients. Consistent with cardiac involvement, 64% of the patients also had elevated troponin levels, and 91% had elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels.

“These parameters peaked at or shortly after admission and then gradually normalized,” the researchers said. “By the first follow-up, [C-reactive protein], troponin, and NT-proBNP had normalized in nearly all tested patients (97%-100%),” they noted.

By the first follow-up period at 1-4 weeks, all patients had normal coronary arteries, and 18% (seven patients) had mild echocardiographic findings. However, approximately one-third (32%) of the patients had persistent lymphocytosis at 1-4 weeks, and 23 of the 24 patients assessed had elevated double-negative T cells, which persisted in 96% of the patients at 1-4 months’ follow-up. However, during the last follow-up of 4-9 months, only one patient had persistent mild biventricular dysfunction and a second patient had mild mitral and tricuspid valve regurgitation.

All patients were treated with steroids and immunoglobulins (2 g/kg), as well as enoxaparin prophylaxis or low-dose aspirin and GI prophylaxis. Treatment with methylprednisolone varied based on disease severity; patients with mild presentation received 2 mg/kg per day; those with moderate presentation received a methylprednisolone pulse of 10 mg/kg per day, followed by 2 mg/kg per day; those with severe disease received methylprednisolone at 20-30 mg/kg per day for 1-3 days, followed by 2 mg/kg per day.

“Aggressive use of steroids may also explain the lower incidence of coronary artery abnormalities in our cohort,” the researchers noted.

The study findings were limited by the observational design and inability to make definitive conclusions about treatment and outcomes, as well as the evolving case definitions for MIS-C, the researchers said.

The persistence of double-negative T cells was surprising, and “likely represent a prolonged postinflammatory recovery cell population, but further study is ongoing to better define this observation,” they noted.

“Our study reveals generally encouraging medium-term outcomes, including rapid normalization of inflammatory markers and significant cardiac abnormalities in the majority of patients with MIS-C,” the researchers said. “The exact nature and potential for long-term cardiac fibrosis, exercise intolerance, or other changes remain unknown,” and long-term caution and follow-up are recommended, they concluded.
 

Cautious optimism, long-term monitoring

The study is important to provide guidance for clinicians on how to manage their patients who have been hospitalized with MIS-C, said Susan Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H.

“It was both surprising and reassuring to see that so many of the patients had positive outcomes in terms of cardiac function and that during the acute stage there were no deaths,” said Dr. Boulter. “Hospitalizations were brief, averaging just 5 days. The patients had many symptoms, but unlike adults, there was not a preponderance of underlying risk factors in this cohort of patients,” she said.

The results suggest optimism for MIS-C patients in that they generally recover, but the take-home message for clinicians is that these patients will require careful monitoring for long-term issues, Dr. Boulter said.

“These patients should be followed for years to assess long-term effects on morbidity and mortality,” Dr. Boulter emphasized.

The study was funded by Genentech. The researchers had no financial conflicts to disclose. Dr. Boulter had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

Practicing rheumatologists in the United States received more than $220 million from pharmaceutical companies during 2014-2019, with payments increasing each year, according to findings from a descriptive study of the Centers for Medicare & Medicaid Services Open Payments Database.

Rheumatologists have identified conflicts of interest as an ethical concern, but the details of industry payments to rheumatologists have not been investigated, wrote Michael Putman, MD, of the Medical College of Wisconsin, Milwaukee, and colleagues in Arthritis & Rheumatology. “Payments among rheumatologists may be of particular interest,” given their frequent prescription of expensive and primarily on-patent biologic and targeted disease-modifying antirheumatic drugs (DMARDs), the researchers said.

Over the 2014-2019 study period, 5,723 rheumatologists received a total of $221,254,966 from 1,610,668 payments. Of these, 3,416 (59%) received less than $5,000; 368 (6%) received more than $100,000, accounting for 78% of the total payments. The yearly value of the payments increased from $29,755,133 in 2014 to $46,308,926 in 2019, a 56% increase.

The payments to individual rheumatologists during the study period ranged from $8 to $5,612,254, with a median individual payment of $2,818. However, most (81%) of the payments were less than $25, and only 4% were more than $1,000.

Physicians who received more than $100,000 were significantly more likely to be paid speakers’ fees, consulting fees, and travel and lodging fees, but significantly less likely to receive payments for food and beverage than were those who received less than $100,000.

Overall, women made up 43% of the study population and received 34% of the total payments.

However, the median payment to male rheumatologists was significantly higher than the median payment to female rheumatologists ($3,732 vs. $2,084). Female rheumatologists were significantly more likely to receive payments for food and beverage and significantly less likely to receive speakers’ fees or travel and lodging coverage.

When the data were analyzed by state, California had the highest amount of total payments ($27,769,124), followed by New York and Texas, while Arizona had the highest spending per rheumatologist ($143,559). By region, based on U.S. Census divisions, the highest spending occurred in the Middle Atlantic Division ($46,327,351) and the highest per rheumatologist spending occurred in the East-South Central Division ($49,605).

“These data suggest industry payments in rheumatology have followed two distinct patterns, which have been observed in other medical subspecialties,” specifically, that many small payments are made to a large number of physicians, and large-value payments are made to a small number of physicians, the researchers noted.

The impact of small payments cannot be discounted, they said, “as even small gifts may affect behavior and are associated with prescribing patterns.” The impact of large payments on behavior and practice deserve further investigation, “but it is notable that a recent evaluation of rheumatology clinical practice guidelines identified substantial involvement from rheumatologists who had accepted large values of industry payments,” the researchers added.

Approximately half the total value of payments came from three companies: Bristol-Myers Squibb (20%), Abbvie (17%), and Pfizer (12%). Medications associated with the highest spending included Otezla, Humira, and Xeljanz.

Of note, the data showed that H.P. Acthar gel was among the top 10 agents for total payments, and “over 90% of rheumatologists who frequently prescribe H.P. Acthar gel have also received H.P. Acthar–related payments, raising the possibility that such payments have influenced prescribing behavior,” given the lack of high-quality evidence to support its use and the availability of less expensive alternatives, the researchers said.

The study findings were limited by several factors, including the focus only on general payments to rheumatologists, and the lack of external sources to verify payments, the researchers noted. “Most importantly, this was a descriptive study, and the degree to which payments have influenced physician behavior lies outside the scope of this work. Future studies should investigate the degree to which industry payments have influenced prescribing in the field of rheumatology.”

Focus on collaborations that add value

The study is important because previous data on the magnitude of payments or payment patterns from pharmaceutical companies to practicing rheumatologists were limited, lead author Dr. Putman said in an interview.

“I was most surprised by some of the medications that received high values of payments,” he said. “Many payments were linked to medications that we use commonly and that have high-quality data supporting their use. That was not surprising, and you could imagine dollars spent on [interleukin]-23 or IL-17 inhibitors being used in a way that is valuable to other physicians or to patients with rheumatic diseases. On the other hand, some medications – most notably H.P. Acthar gel – have no high-quality data supporting their use, are used by a very small cadre of physicians, and are extraordinarily expensive. At least in my opinion, there is no world where payments linked to H.P. Acthar gel provide any benefit for physicians or patients.”

Dr. Putman said he expected that the patterns and the increases observed in the study are likely to continue.

“Ultimately, I have a somewhat nuanced view of financial conflicts of interest,” he said. “Collaborations between the pharmaceutical industry and rheumatologists have provided extraordinary value to our field. I think rheumatologists should be much more involved in some areas. At the same time, I think we should be much less involved in marketing drugs that provide little value to patients and great cost to society. H.P. Acthar Gel is the classic example of this, but there are others as well. I think future research should focus on how these payments influence behavior and should seek to identify areas where they result in low-value care.” Going forward, valuable collaborations between rheumatologists and the pharmaceutical industry should be encouraged, but collaborations without value should be discouraged, he said.
 

Industry payments serve no useful purpose

The findings “highlight the overarching concern regarding the ability of industry payments to adversely affect care quality within the specific context of rheumatology practice,” Aaron P. Mitchell, MD, of Memorial Sloan Kettering Cancer Center, New York, wrote in an accompanying editorial.

Dr. Mitchell emphasized several points, starting with the temporal trend showing an increase in industry payments beyond the rate of inflation that has not been universal across specialties. He also emphasized the “highly skewed distribution of payments,” with a large majority going to a relatively small number of rheumatologists. “This suggests an industry strategy of targeting ‘key opinion leaders,’ or KOLs, with higher payments,” and which was not surprising, as similar patterns have been seen in other specialties. Dr. Mitchell noted that 10 drugs accounted for more than half of the payments, and that “the unifying feature of these drugs is their high cost.”

“The picture of industry strategy that emerges from Putman et al. and other similar reports is that of intense, sustained KOL-focused marketing soon after the release of a new high-margin drug,” he wrote.

Despite the descriptive nature of the study, the findings have clinical implications based on other studies of the consequences of industry payments with respect to care quality, Dr. Mitchell said. “Hypothetically, industry spending to promote drugs to physicians could increase dissemination of new, superior drugs, improving patient outcomes.” However, physicians tend to opt for game-changing drugs without added incentive; “it is the less-innovative drugs that industry has to push harder.”

The practice of industry payments for physicians becomes even more difficult to rationalize given the potential for increased out-of-pocket costs and potentially avoidable toxicities for patients, Dr. Mitchell said. “Moreover, industry payments serve no unmet need; through our professional societies and other nonprofit sources, we physicians are fully capable of staying up-to-date on new treatments without relying on industry meals and sponsored events.”
 

Disclosure of payments is important

The study is important because it is essential to understand how public disclosure of industry payments influences financial relationship between the biomedical industry and physicians, said Amarnath Annapureddy, MD, a clinical fellow in cardiology at Yale University, New Haven, Conn., who has studied and written about industry payments to physicians.

Dr. Annapureddy said in an interview that he was surprised by how the study findings were opposite to the assumption that public disclosure would dissuade continuation of financial ties between physicians and industry. “This study showed payments increased over time rather than decreasing due to public disclosure.”

However, Dr. Annapureddy said that he was not surprised at how few physicians received the bulk of industry payments. “These physicians are considered to be ‘key opinion leaders’ who could influence practicing patterns of other physicians. These findings are similar to payment patterns for other specialties, including cardiology.

“So far, no study has evaluated factors that drive changes in industry payment patterns,” Dr. Annapureddy said. “I anticipate the patterns noted in this study will continue at least in the short term. If health care systems mandate physicians to disclose potential conflicts of interest to the patients, it may reduce payments.”

However, “unless, there is a major health policy mandate by government, I anticipate public disclosure of payments through the open payments program will not impact industry-physician ties,” he said. “This study has not evaluated impact of payments on prescribing practices. There are overwhelming data from several studies that showed payments influence physicians practicing patterns, whether it is prescribing a medication or implanting a device.” However, as for additional research, Dr. Annapureddy said that it would interesting to see a randomized trial to show whether the way physicians disclose their financial ties with patients would impact their practicing patterns.

The study received no outside funding. Dr. Putman was supported by a Rheumatology Research grant, but he and the other researchers had no financial conflicts to disclose. Dr. Mitchell disclosed a merit award from the nonprofit Conquer Cancer Foundation, for which the Foundation received financial support from Merck. Dr. Annapureddy had no financial conflicts to disclose.

Practicing rheumatologists in the United States received more than $220 million from pharmaceutical companies during 2014-2019, with payments increasing each year, according to findings from a descriptive study of the Centers for Medicare & Medicaid Services Open Payments Database.

Rheumatologists have identified conflicts of interest as an ethical concern, but the details of industry payments to rheumatologists have not been investigated, wrote Michael Putman, MD, of the Medical College of Wisconsin, Milwaukee, and colleagues in Arthritis & Rheumatology. “Payments among rheumatologists may be of particular interest,” given their frequent prescription of expensive and primarily on-patent biologic and targeted disease-modifying antirheumatic drugs (DMARDs), the researchers said.

Over the 2014-2019 study period, 5,723 rheumatologists received a total of $221,254,966 from 1,610,668 payments. Of these, 3,416 (59%) received less than $5,000; 368 (6%) received more than $100,000, accounting for 78% of the total payments. The yearly value of the payments increased from $29,755,133 in 2014 to $46,308,926 in 2019, a 56% increase.

The payments to individual rheumatologists during the study period ranged from $8 to $5,612,254, with a median individual payment of $2,818. However, most (81%) of the payments were less than $25, and only 4% were more than $1,000.

Physicians who received more than $100,000 were significantly more likely to be paid speakers’ fees, consulting fees, and travel and lodging fees, but significantly less likely to receive payments for food and beverage than were those who received less than $100,000.

Overall, women made up 43% of the study population and received 34% of the total payments.

However, the median payment to male rheumatologists was significantly higher than the median payment to female rheumatologists ($3,732 vs. $2,084). Female rheumatologists were significantly more likely to receive payments for food and beverage and significantly less likely to receive speakers’ fees or travel and lodging coverage.

When the data were analyzed by state, California had the highest amount of total payments ($27,769,124), followed by New York and Texas, while Arizona had the highest spending per rheumatologist ($143,559). By region, based on U.S. Census divisions, the highest spending occurred in the Middle Atlantic Division ($46,327,351) and the highest per rheumatologist spending occurred in the East-South Central Division ($49,605).

“These data suggest industry payments in rheumatology have followed two distinct patterns, which have been observed in other medical subspecialties,” specifically, that many small payments are made to a large number of physicians, and large-value payments are made to a small number of physicians, the researchers noted.

The impact of small payments cannot be discounted, they said, “as even small gifts may affect behavior and are associated with prescribing patterns.” The impact of large payments on behavior and practice deserve further investigation, “but it is notable that a recent evaluation of rheumatology clinical practice guidelines identified substantial involvement from rheumatologists who had accepted large values of industry payments,” the researchers added.

Approximately half the total value of payments came from three companies: Bristol-Myers Squibb (20%), Abbvie (17%), and Pfizer (12%). Medications associated with the highest spending included Otezla, Humira, and Xeljanz.

Of note, the data showed that H.P. Acthar gel was among the top 10 agents for total payments, and “over 90% of rheumatologists who frequently prescribe H.P. Acthar gel have also received H.P. Acthar–related payments, raising the possibility that such payments have influenced prescribing behavior,” given the lack of high-quality evidence to support its use and the availability of less expensive alternatives, the researchers said.

The study findings were limited by several factors, including the focus only on general payments to rheumatologists, and the lack of external sources to verify payments, the researchers noted. “Most importantly, this was a descriptive study, and the degree to which payments have influenced physician behavior lies outside the scope of this work. Future studies should investigate the degree to which industry payments have influenced prescribing in the field of rheumatology.”

Focus on collaborations that add value

The study is important because previous data on the magnitude of payments or payment patterns from pharmaceutical companies to practicing rheumatologists were limited, lead author Dr. Putman said in an interview.

“I was most surprised by some of the medications that received high values of payments,” he said. “Many payments were linked to medications that we use commonly and that have high-quality data supporting their use. That was not surprising, and you could imagine dollars spent on [interleukin]-23 or IL-17 inhibitors being used in a way that is valuable to other physicians or to patients with rheumatic diseases. On the other hand, some medications – most notably H.P. Acthar gel – have no high-quality data supporting their use, are used by a very small cadre of physicians, and are extraordinarily expensive. At least in my opinion, there is no world where payments linked to H.P. Acthar gel provide any benefit for physicians or patients.”

Dr. Putman said he expected that the patterns and the increases observed in the study are likely to continue.

“Ultimately, I have a somewhat nuanced view of financial conflicts of interest,” he said. “Collaborations between the pharmaceutical industry and rheumatologists have provided extraordinary value to our field. I think rheumatologists should be much more involved in some areas. At the same time, I think we should be much less involved in marketing drugs that provide little value to patients and great cost to society. H.P. Acthar Gel is the classic example of this, but there are others as well. I think future research should focus on how these payments influence behavior and should seek to identify areas where they result in low-value care.” Going forward, valuable collaborations between rheumatologists and the pharmaceutical industry should be encouraged, but collaborations without value should be discouraged, he said.
 

Industry payments serve no useful purpose

The findings “highlight the overarching concern regarding the ability of industry payments to adversely affect care quality within the specific context of rheumatology practice,” Aaron P. Mitchell, MD, of Memorial Sloan Kettering Cancer Center, New York, wrote in an accompanying editorial.

Dr. Mitchell emphasized several points, starting with the temporal trend showing an increase in industry payments beyond the rate of inflation that has not been universal across specialties. He also emphasized the “highly skewed distribution of payments,” with a large majority going to a relatively small number of rheumatologists. “This suggests an industry strategy of targeting ‘key opinion leaders,’ or KOLs, with higher payments,” and which was not surprising, as similar patterns have been seen in other specialties. Dr. Mitchell noted that 10 drugs accounted for more than half of the payments, and that “the unifying feature of these drugs is their high cost.”

“The picture of industry strategy that emerges from Putman et al. and other similar reports is that of intense, sustained KOL-focused marketing soon after the release of a new high-margin drug,” he wrote.

Despite the descriptive nature of the study, the findings have clinical implications based on other studies of the consequences of industry payments with respect to care quality, Dr. Mitchell said. “Hypothetically, industry spending to promote drugs to physicians could increase dissemination of new, superior drugs, improving patient outcomes.” However, physicians tend to opt for game-changing drugs without added incentive; “it is the less-innovative drugs that industry has to push harder.”

The practice of industry payments for physicians becomes even more difficult to rationalize given the potential for increased out-of-pocket costs and potentially avoidable toxicities for patients, Dr. Mitchell said. “Moreover, industry payments serve no unmet need; through our professional societies and other nonprofit sources, we physicians are fully capable of staying up-to-date on new treatments without relying on industry meals and sponsored events.”
 

Disclosure of payments is important

The study is important because it is essential to understand how public disclosure of industry payments influences financial relationship between the biomedical industry and physicians, said Amarnath Annapureddy, MD, a clinical fellow in cardiology at Yale University, New Haven, Conn., who has studied and written about industry payments to physicians.

Dr. Annapureddy said in an interview that he was surprised by how the study findings were opposite to the assumption that public disclosure would dissuade continuation of financial ties between physicians and industry. “This study showed payments increased over time rather than decreasing due to public disclosure.”

However, Dr. Annapureddy said that he was not surprised at how few physicians received the bulk of industry payments. “These physicians are considered to be ‘key opinion leaders’ who could influence practicing patterns of other physicians. These findings are similar to payment patterns for other specialties, including cardiology.

“So far, no study has evaluated factors that drive changes in industry payment patterns,” Dr. Annapureddy said. “I anticipate the patterns noted in this study will continue at least in the short term. If health care systems mandate physicians to disclose potential conflicts of interest to the patients, it may reduce payments.”

However, “unless, there is a major health policy mandate by government, I anticipate public disclosure of payments through the open payments program will not impact industry-physician ties,” he said. “This study has not evaluated impact of payments on prescribing practices. There are overwhelming data from several studies that showed payments influence physicians practicing patterns, whether it is prescribing a medication or implanting a device.” However, as for additional research, Dr. Annapureddy said that it would interesting to see a randomized trial to show whether the way physicians disclose their financial ties with patients would impact their practicing patterns.

The study received no outside funding. Dr. Putman was supported by a Rheumatology Research grant, but he and the other researchers had no financial conflicts to disclose. Dr. Mitchell disclosed a merit award from the nonprofit Conquer Cancer Foundation, for which the Foundation received financial support from Merck. Dr. Annapureddy had no financial conflicts to disclose.

Practicing rheumatologists in the United States received more than $220 million from pharmaceutical companies during 2014-2019, with payments increasing each year, according to findings from a descriptive study of the Centers for Medicare & Medicaid Services Open Payments Database.

Rheumatologists have identified conflicts of interest as an ethical concern, but the details of industry payments to rheumatologists have not been investigated, wrote Michael Putman, MD, of the Medical College of Wisconsin, Milwaukee, and colleagues in Arthritis & Rheumatology. “Payments among rheumatologists may be of particular interest,” given their frequent prescription of expensive and primarily on-patent biologic and targeted disease-modifying antirheumatic drugs (DMARDs), the researchers said.

Over the 2014-2019 study period, 5,723 rheumatologists received a total of $221,254,966 from 1,610,668 payments. Of these, 3,416 (59%) received less than $5,000; 368 (6%) received more than $100,000, accounting for 78% of the total payments. The yearly value of the payments increased from $29,755,133 in 2014 to $46,308,926 in 2019, a 56% increase.

The payments to individual rheumatologists during the study period ranged from $8 to $5,612,254, with a median individual payment of $2,818. However, most (81%) of the payments were less than $25, and only 4% were more than $1,000.

Physicians who received more than $100,000 were significantly more likely to be paid speakers’ fees, consulting fees, and travel and lodging fees, but significantly less likely to receive payments for food and beverage than were those who received less than $100,000.

Overall, women made up 43% of the study population and received 34% of the total payments.

However, the median payment to male rheumatologists was significantly higher than the median payment to female rheumatologists ($3,732 vs. $2,084). Female rheumatologists were significantly more likely to receive payments for food and beverage and significantly less likely to receive speakers’ fees or travel and lodging coverage.

When the data were analyzed by state, California had the highest amount of total payments ($27,769,124), followed by New York and Texas, while Arizona had the highest spending per rheumatologist ($143,559). By region, based on U.S. Census divisions, the highest spending occurred in the Middle Atlantic Division ($46,327,351) and the highest per rheumatologist spending occurred in the East-South Central Division ($49,605).

“These data suggest industry payments in rheumatology have followed two distinct patterns, which have been observed in other medical subspecialties,” specifically, that many small payments are made to a large number of physicians, and large-value payments are made to a small number of physicians, the researchers noted.

The impact of small payments cannot be discounted, they said, “as even small gifts may affect behavior and are associated with prescribing patterns.” The impact of large payments on behavior and practice deserve further investigation, “but it is notable that a recent evaluation of rheumatology clinical practice guidelines identified substantial involvement from rheumatologists who had accepted large values of industry payments,” the researchers added.

Approximately half the total value of payments came from three companies: Bristol-Myers Squibb (20%), Abbvie (17%), and Pfizer (12%). Medications associated with the highest spending included Otezla, Humira, and Xeljanz.

Of note, the data showed that H.P. Acthar gel was among the top 10 agents for total payments, and “over 90% of rheumatologists who frequently prescribe H.P. Acthar gel have also received H.P. Acthar–related payments, raising the possibility that such payments have influenced prescribing behavior,” given the lack of high-quality evidence to support its use and the availability of less expensive alternatives, the researchers said.

The study findings were limited by several factors, including the focus only on general payments to rheumatologists, and the lack of external sources to verify payments, the researchers noted. “Most importantly, this was a descriptive study, and the degree to which payments have influenced physician behavior lies outside the scope of this work. Future studies should investigate the degree to which industry payments have influenced prescribing in the field of rheumatology.”

Focus on collaborations that add value

The study is important because previous data on the magnitude of payments or payment patterns from pharmaceutical companies to practicing rheumatologists were limited, lead author Dr. Putman said in an interview.

“I was most surprised by some of the medications that received high values of payments,” he said. “Many payments were linked to medications that we use commonly and that have high-quality data supporting their use. That was not surprising, and you could imagine dollars spent on [interleukin]-23 or IL-17 inhibitors being used in a way that is valuable to other physicians or to patients with rheumatic diseases. On the other hand, some medications – most notably H.P. Acthar gel – have no high-quality data supporting their use, are used by a very small cadre of physicians, and are extraordinarily expensive. At least in my opinion, there is no world where payments linked to H.P. Acthar gel provide any benefit for physicians or patients.”

Dr. Putman said he expected that the patterns and the increases observed in the study are likely to continue.

“Ultimately, I have a somewhat nuanced view of financial conflicts of interest,” he said. “Collaborations between the pharmaceutical industry and rheumatologists have provided extraordinary value to our field. I think rheumatologists should be much more involved in some areas. At the same time, I think we should be much less involved in marketing drugs that provide little value to patients and great cost to society. H.P. Acthar Gel is the classic example of this, but there are others as well. I think future research should focus on how these payments influence behavior and should seek to identify areas where they result in low-value care.” Going forward, valuable collaborations between rheumatologists and the pharmaceutical industry should be encouraged, but collaborations without value should be discouraged, he said.
 

Industry payments serve no useful purpose

The findings “highlight the overarching concern regarding the ability of industry payments to adversely affect care quality within the specific context of rheumatology practice,” Aaron P. Mitchell, MD, of Memorial Sloan Kettering Cancer Center, New York, wrote in an accompanying editorial.

Dr. Mitchell emphasized several points, starting with the temporal trend showing an increase in industry payments beyond the rate of inflation that has not been universal across specialties. He also emphasized the “highly skewed distribution of payments,” with a large majority going to a relatively small number of rheumatologists. “This suggests an industry strategy of targeting ‘key opinion leaders,’ or KOLs, with higher payments,” and which was not surprising, as similar patterns have been seen in other specialties. Dr. Mitchell noted that 10 drugs accounted for more than half of the payments, and that “the unifying feature of these drugs is their high cost.”

“The picture of industry strategy that emerges from Putman et al. and other similar reports is that of intense, sustained KOL-focused marketing soon after the release of a new high-margin drug,” he wrote.

Despite the descriptive nature of the study, the findings have clinical implications based on other studies of the consequences of industry payments with respect to care quality, Dr. Mitchell said. “Hypothetically, industry spending to promote drugs to physicians could increase dissemination of new, superior drugs, improving patient outcomes.” However, physicians tend to opt for game-changing drugs without added incentive; “it is the less-innovative drugs that industry has to push harder.”

The practice of industry payments for physicians becomes even more difficult to rationalize given the potential for increased out-of-pocket costs and potentially avoidable toxicities for patients, Dr. Mitchell said. “Moreover, industry payments serve no unmet need; through our professional societies and other nonprofit sources, we physicians are fully capable of staying up-to-date on new treatments without relying on industry meals and sponsored events.”
 

Disclosure of payments is important

The study is important because it is essential to understand how public disclosure of industry payments influences financial relationship between the biomedical industry and physicians, said Amarnath Annapureddy, MD, a clinical fellow in cardiology at Yale University, New Haven, Conn., who has studied and written about industry payments to physicians.

Dr. Annapureddy said in an interview that he was surprised by how the study findings were opposite to the assumption that public disclosure would dissuade continuation of financial ties between physicians and industry. “This study showed payments increased over time rather than decreasing due to public disclosure.”

However, Dr. Annapureddy said that he was not surprised at how few physicians received the bulk of industry payments. “These physicians are considered to be ‘key opinion leaders’ who could influence practicing patterns of other physicians. These findings are similar to payment patterns for other specialties, including cardiology.

“So far, no study has evaluated factors that drive changes in industry payment patterns,” Dr. Annapureddy said. “I anticipate the patterns noted in this study will continue at least in the short term. If health care systems mandate physicians to disclose potential conflicts of interest to the patients, it may reduce payments.”

However, “unless, there is a major health policy mandate by government, I anticipate public disclosure of payments through the open payments program will not impact industry-physician ties,” he said. “This study has not evaluated impact of payments on prescribing practices. There are overwhelming data from several studies that showed payments influence physicians practicing patterns, whether it is prescribing a medication or implanting a device.” However, as for additional research, Dr. Annapureddy said that it would interesting to see a randomized trial to show whether the way physicians disclose their financial ties with patients would impact their practicing patterns.

The study received no outside funding. Dr. Putman was supported by a Rheumatology Research grant, but he and the other researchers had no financial conflicts to disclose. Dr. Mitchell disclosed a merit award from the nonprofit Conquer Cancer Foundation, for which the Foundation received financial support from Merck. Dr. Annapureddy had no financial conflicts to disclose.

Use of metformin was associated with a significant reduction in the risk of developing basal cell carcinoma (BCC), based on data from a population case-control study in Iceland.

“In addition to general anticarcinogenic effects, metformin has also been shown to directly inhibit the sonic hedgehog pathway, a key pathway in basal cell carcinoma (BCC) pathogenesis,” Jonas A. Adalsteinsson, MD, of the University of Iceland, Reykjavik, and colleagues wrote. “The relationship between metformin and keratinocyte carcinoma has not been well-characterized but is of importance considering that metformin is a commonly prescribed medication.”

They added that the hedgehog pathway inhibitors vismodegib (Erivedge) and sonidegib (Odomzo), approved for treating BCC, “are highly effective for BCC prevention, but their broad use for BCC prophylaxis is limited due to numerous side effects.”

In the study, published in the Journal of the American Academy of Dermatology, the researchers identified 6,880 first-time cancer patients with BCC, squamous cell carcinoma in situ (SCCis), or invasive SCC, and 69,620 population controls using data from the Icelandic Cancer Registry and the Icelandic Prescription Medicine Register between 2003 and 2017. Metformin exposure was defined as having filled at least one prescription of metformin more than 2 years prior to cancer diagnosis. They used grams and daily dose units of metformin in their analysis; one DDU of metformin, “or its average daily maintenance dose when used for its primary indication, is 2 grams,” they noted.

Overall, metformin use was associated with a significantly lower risk of developing BCC, compared with nonuse (adjusted odds ratio, 0.71; 95% confidence interval, 0.61-0.83).

The reduced risk occurred similarly across age and gender subgroups, with the exception of individuals younger than 60 years, the researchers said. “This might signify that metformin has less of a protective effect in younger individuals, but we might also have lacked power in this category.” The association with reduced BCC risk remained significant at all three cumulative dose levels measured: 1-500 DDUs, 501-1,500 DDUs, and more than 1,500 DDUs.

Metformin use was not significantly associated with reduced risk of invasive SCC (aOR, 1.01) and in most cases of SCCis. However, the 501-1,500 DDU dose category was associated with a slight increase in risk of SCCis (aOR, 1.40; 95% CI, 1.00-1.96), “showing a possible increased risk of SCCis,” the authors wrote.

The decrease in BCC risk was seen across all metformin dosing levels, but the reason for this remains unclear, and might be related to a confounding factor that was not considered in this study, the researchers said. “It could also be that metformin’s BCC risk-lowering effect is immediate, with only a low dose being needed to see a clinical benefit.”

The study findings were limited by several factors, including the retrospective design and the inability to adjust for factors including ultraviolet exposure, Fitzpatrick skin type, and comorbidities. The frequent use of metformin by people with type 2 diabetes suggests diabetes itself or other diabetes medications could be possible confounding factors, the researchers wrote.

However, the results were strengthened by the large study population, and the data suggest an association between reduced risk of first-time BCC and metformin use, they added.

“Randomized, prospective trials are required to fully understand the effect metformin has on BCC and SCC risk,” the researchers concluded.

“There is a dire need to reduce incidence of skin cancers in general, and consequently a need for new non-surgical treatment options for keratinocytic nonmelanoma skin cancers,” Amor Khachemoune, MD, a dermatologist at the State University of New York, Brooklyn, and the department of dermatology of the Veteran Affairs NY Harbor Healthcare System, also in Brooklyn, said in an interview.

Dr. Khachemoune, who was not involved with the study, said that he was not surprised by the findings. “Like other well-studied sonic hedgehog inhibitors, vismodegib and sonidegib, metformin has a demonstrated effect on this pathway. The medical community outside of dermatology has extensive experience with the use of metformin for a host of other indications, including its role as anticarcinogenic, so it seemed natural that one would consider widening its use to quell the ever-expanding cases of basal cell carcinomas.”

However, complications from long-term use, though likely rare, could be a limitation in using metformin as a chemoprotective agent, Dr. Khachemoune said. Metformin-associated lactic acidosis is one example of a rare, but potentially life-threatening adverse event.

“Finding the right dosage and having an algorithm for follow up monitoring of side effects would certainly need to be put in place in a standardized way,” he emphasized. “As stated by the authors of this study, more inclusive research involving other groups with nonkeratinocytic malignancies in larger cohorts is needed.”

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

Use of metformin was associated with a significant reduction in the risk of developing basal cell carcinoma (BCC), based on data from a population case-control study in Iceland.

“In addition to general anticarcinogenic effects, metformin has also been shown to directly inhibit the sonic hedgehog pathway, a key pathway in basal cell carcinoma (BCC) pathogenesis,” Jonas A. Adalsteinsson, MD, of the University of Iceland, Reykjavik, and colleagues wrote. “The relationship between metformin and keratinocyte carcinoma has not been well-characterized but is of importance considering that metformin is a commonly prescribed medication.”

They added that the hedgehog pathway inhibitors vismodegib (Erivedge) and sonidegib (Odomzo), approved for treating BCC, “are highly effective for BCC prevention, but their broad use for BCC prophylaxis is limited due to numerous side effects.”

In the study, published in the Journal of the American Academy of Dermatology, the researchers identified 6,880 first-time cancer patients with BCC, squamous cell carcinoma in situ (SCCis), or invasive SCC, and 69,620 population controls using data from the Icelandic Cancer Registry and the Icelandic Prescription Medicine Register between 2003 and 2017. Metformin exposure was defined as having filled at least one prescription of metformin more than 2 years prior to cancer diagnosis. They used grams and daily dose units of metformin in their analysis; one DDU of metformin, “or its average daily maintenance dose when used for its primary indication, is 2 grams,” they noted.

Overall, metformin use was associated with a significantly lower risk of developing BCC, compared with nonuse (adjusted odds ratio, 0.71; 95% confidence interval, 0.61-0.83).

The reduced risk occurred similarly across age and gender subgroups, with the exception of individuals younger than 60 years, the researchers said. “This might signify that metformin has less of a protective effect in younger individuals, but we might also have lacked power in this category.” The association with reduced BCC risk remained significant at all three cumulative dose levels measured: 1-500 DDUs, 501-1,500 DDUs, and more than 1,500 DDUs.

Metformin use was not significantly associated with reduced risk of invasive SCC (aOR, 1.01) and in most cases of SCCis. However, the 501-1,500 DDU dose category was associated with a slight increase in risk of SCCis (aOR, 1.40; 95% CI, 1.00-1.96), “showing a possible increased risk of SCCis,” the authors wrote.

The decrease in BCC risk was seen across all metformin dosing levels, but the reason for this remains unclear, and might be related to a confounding factor that was not considered in this study, the researchers said. “It could also be that metformin’s BCC risk-lowering effect is immediate, with only a low dose being needed to see a clinical benefit.”

The study findings were limited by several factors, including the retrospective design and the inability to adjust for factors including ultraviolet exposure, Fitzpatrick skin type, and comorbidities. The frequent use of metformin by people with type 2 diabetes suggests diabetes itself or other diabetes medications could be possible confounding factors, the researchers wrote.

However, the results were strengthened by the large study population, and the data suggest an association between reduced risk of first-time BCC and metformin use, they added.

“Randomized, prospective trials are required to fully understand the effect metformin has on BCC and SCC risk,” the researchers concluded.

“There is a dire need to reduce incidence of skin cancers in general, and consequently a need for new non-surgical treatment options for keratinocytic nonmelanoma skin cancers,” Amor Khachemoune, MD, a dermatologist at the State University of New York, Brooklyn, and the department of dermatology of the Veteran Affairs NY Harbor Healthcare System, also in Brooklyn, said in an interview.

Dr. Khachemoune, who was not involved with the study, said that he was not surprised by the findings. “Like other well-studied sonic hedgehog inhibitors, vismodegib and sonidegib, metformin has a demonstrated effect on this pathway. The medical community outside of dermatology has extensive experience with the use of metformin for a host of other indications, including its role as anticarcinogenic, so it seemed natural that one would consider widening its use to quell the ever-expanding cases of basal cell carcinomas.”

However, complications from long-term use, though likely rare, could be a limitation in using metformin as a chemoprotective agent, Dr. Khachemoune said. Metformin-associated lactic acidosis is one example of a rare, but potentially life-threatening adverse event.

“Finding the right dosage and having an algorithm for follow up monitoring of side effects would certainly need to be put in place in a standardized way,” he emphasized. “As stated by the authors of this study, more inclusive research involving other groups with nonkeratinocytic malignancies in larger cohorts is needed.”

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

Use of metformin was associated with a significant reduction in the risk of developing basal cell carcinoma (BCC), based on data from a population case-control study in Iceland.

“In addition to general anticarcinogenic effects, metformin has also been shown to directly inhibit the sonic hedgehog pathway, a key pathway in basal cell carcinoma (BCC) pathogenesis,” Jonas A. Adalsteinsson, MD, of the University of Iceland, Reykjavik, and colleagues wrote. “The relationship between metformin and keratinocyte carcinoma has not been well-characterized but is of importance considering that metformin is a commonly prescribed medication.”

They added that the hedgehog pathway inhibitors vismodegib (Erivedge) and sonidegib (Odomzo), approved for treating BCC, “are highly effective for BCC prevention, but their broad use for BCC prophylaxis is limited due to numerous side effects.”

In the study, published in the Journal of the American Academy of Dermatology, the researchers identified 6,880 first-time cancer patients with BCC, squamous cell carcinoma in situ (SCCis), or invasive SCC, and 69,620 population controls using data from the Icelandic Cancer Registry and the Icelandic Prescription Medicine Register between 2003 and 2017. Metformin exposure was defined as having filled at least one prescription of metformin more than 2 years prior to cancer diagnosis. They used grams and daily dose units of metformin in their analysis; one DDU of metformin, “or its average daily maintenance dose when used for its primary indication, is 2 grams,” they noted.

Overall, metformin use was associated with a significantly lower risk of developing BCC, compared with nonuse (adjusted odds ratio, 0.71; 95% confidence interval, 0.61-0.83).

The reduced risk occurred similarly across age and gender subgroups, with the exception of individuals younger than 60 years, the researchers said. “This might signify that metformin has less of a protective effect in younger individuals, but we might also have lacked power in this category.” The association with reduced BCC risk remained significant at all three cumulative dose levels measured: 1-500 DDUs, 501-1,500 DDUs, and more than 1,500 DDUs.

Metformin use was not significantly associated with reduced risk of invasive SCC (aOR, 1.01) and in most cases of SCCis. However, the 501-1,500 DDU dose category was associated with a slight increase in risk of SCCis (aOR, 1.40; 95% CI, 1.00-1.96), “showing a possible increased risk of SCCis,” the authors wrote.

The decrease in BCC risk was seen across all metformin dosing levels, but the reason for this remains unclear, and might be related to a confounding factor that was not considered in this study, the researchers said. “It could also be that metformin’s BCC risk-lowering effect is immediate, with only a low dose being needed to see a clinical benefit.”

The study findings were limited by several factors, including the retrospective design and the inability to adjust for factors including ultraviolet exposure, Fitzpatrick skin type, and comorbidities. The frequent use of metformin by people with type 2 diabetes suggests diabetes itself or other diabetes medications could be possible confounding factors, the researchers wrote.

However, the results were strengthened by the large study population, and the data suggest an association between reduced risk of first-time BCC and metformin use, they added.

“Randomized, prospective trials are required to fully understand the effect metformin has on BCC and SCC risk,” the researchers concluded.

“There is a dire need to reduce incidence of skin cancers in general, and consequently a need for new non-surgical treatment options for keratinocytic nonmelanoma skin cancers,” Amor Khachemoune, MD, a dermatologist at the State University of New York, Brooklyn, and the department of dermatology of the Veteran Affairs NY Harbor Healthcare System, also in Brooklyn, said in an interview.

Dr. Khachemoune, who was not involved with the study, said that he was not surprised by the findings. “Like other well-studied sonic hedgehog inhibitors, vismodegib and sonidegib, metformin has a demonstrated effect on this pathway. The medical community outside of dermatology has extensive experience with the use of metformin for a host of other indications, including its role as anticarcinogenic, so it seemed natural that one would consider widening its use to quell the ever-expanding cases of basal cell carcinomas.”

However, complications from long-term use, though likely rare, could be a limitation in using metformin as a chemoprotective agent, Dr. Khachemoune said. Metformin-associated lactic acidosis is one example of a rare, but potentially life-threatening adverse event.

“Finding the right dosage and having an algorithm for follow up monitoring of side effects would certainly need to be put in place in a standardized way,” he emphasized. “As stated by the authors of this study, more inclusive research involving other groups with nonkeratinocytic malignancies in larger cohorts is needed.”

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

Patients with infected pancreatic necrosis (IPN) are more likely to experience organ failure and mortality, which makes identifying them as quickly as possible especially crucial. A new study aimed to make this task a bit easier by categorizing the main risk factors for IPN in a cohort of patients with severe acute pancreatitis, which included extensive spread of necrotic collections, preceding bacteremia, and preceding open abdomen treatment, as well as postinterventional pancreatitis.

In their study, published in the Journal of Gastrointestinal Surgery, Henrik L. Husu, MD, of the University of Helsinki, and colleagues noted the inherent challenges of rendering a preoperative diagnosis of IPN.

“Fever and increasing inflammation markers may indicate suspicion of IPN, but these are very common in patients with severe acute pancreatitis treated in the ICU,” and more knowledge of specific IPN risk factors is needed to improve clinical decision-making, they said.

Dr. Husu and colleagues identified 163 adults with acute pancreatitis admitted to the ICU at a single center between 2010 and 2018, approximately 68% of whom had alcoholic necrotizing pancreatitis. Pneumonia, bacteremia, and IPN occurred at an average of 4, 16, and 23 days, respectively, after ICU admission.

Forty-seven patients (28.8%) developed IPN within 90 days of ICU admission, all patients had a least one persistent organ failure, and 60% had multiple organ failure within 24 hours of ICU admission.

In a multivariate regression analysis, independent risk factors for IPN included postoperative or postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (odds ratio,13.5) and widespread necrotic collections (OR, 5.7 for unilateral paracolic or retromesenteric; OR, 21.8 for bilateral paracolic or unilateral paracolic and retromesenteric). Other risk factors were preceding bacteremia (OR, 4.8) and preceding open abdomen treatment for abdominal compartment syndrome (OR, 3.6).

After 90 days, 29 patients had died, including 7 with IPN and 22 without IPN. In addition, patients with IPN had longer overall hospital stays and ICU stays, higher rates of ICU readmission, and greater use of open necrosectomy, the researchers noted.

The study findings were limited by several factors, including the retrospective design, lack of controls, potential differences in treatment protocols, and the survival bias that prevented direct comparison of mortality in patients with and without IPN, the researchers noted. “This study cannot provide a reliable estimate of the difference in mortality attributable to IPN itself.”

However, the researchers noted that “the strength of the present study was to include only patients with persistent organ failure and admission to ICU in the early disease course,” and results indicate a significant morbid outcome associated with IPN. “In attempting to decrease the rate of IPN, efforts to identify and treat incipient organ failure with subsequent low threshold for admission to ICU becomes essential,” they emphasized. 
 

More data may prompt greater intervention

“IPN portends a poor prognosis, and can be challenging to both diagnose and treat,” Gyanprakash A. Ketwaroo, MD, of Baylor College of Medicine, Houston, said in an interview. “Identifying risk factors for development of IPN may facilitate earlier therapy that could modify the natural history of this disease.”

Dr. Ketwaroo said he was not surprised by the study findings. “This was a small single-center, retrospective study, where infection could only be ascertained among those who received interventions, and the findings should thus be interpreted within these limitations. Overall, however, I was not surprised. More extensive necrosis and opportunities for infectious seeding of necrosis such as interventions (ERCP) and bacteremia would be expected risk factors. I was surprised by the use of prophylactic antibiotics, as well as the high rate of open necrosectomy, though this should not affect the main findings of risk factors for infection.

“The studies highlight that a significant portion of patients with severe acute pancreatitis with necrosis will develop infection,” said Dr. Ketwaroo. “Being aware of the risk factors for infection, as identified in this study, can add to our clinical judgment in suspecting infection and opting for debridement. Especially with advancements in endoscopic necrosectomy, gastroenterologists may be more inclined to intervene when suspecting IPN. The next steps for research are to validate risk factors in larger, prospective studies.”

The study was supported by governmental competitive funds for medical research, a research grant from the Medical Society of Finland, and a research grant from Perkléns Foundation. The researchers had no financial conflicts to disclose. Dr. Ketwaroo had no financial conflicts to disclose but is a member of the GI & Hepatology News editorial advisory board.

Patients with infected pancreatic necrosis (IPN) are more likely to experience organ failure and mortality, which makes identifying them as quickly as possible especially crucial. A new study aimed to make this task a bit easier by categorizing the main risk factors for IPN in a cohort of patients with severe acute pancreatitis, which included extensive spread of necrotic collections, preceding bacteremia, and preceding open abdomen treatment, as well as postinterventional pancreatitis.

In their study, published in the Journal of Gastrointestinal Surgery, Henrik L. Husu, MD, of the University of Helsinki, and colleagues noted the inherent challenges of rendering a preoperative diagnosis of IPN.

“Fever and increasing inflammation markers may indicate suspicion of IPN, but these are very common in patients with severe acute pancreatitis treated in the ICU,” and more knowledge of specific IPN risk factors is needed to improve clinical decision-making, they said.

Dr. Husu and colleagues identified 163 adults with acute pancreatitis admitted to the ICU at a single center between 2010 and 2018, approximately 68% of whom had alcoholic necrotizing pancreatitis. Pneumonia, bacteremia, and IPN occurred at an average of 4, 16, and 23 days, respectively, after ICU admission.

Forty-seven patients (28.8%) developed IPN within 90 days of ICU admission, all patients had a least one persistent organ failure, and 60% had multiple organ failure within 24 hours of ICU admission.

In a multivariate regression analysis, independent risk factors for IPN included postoperative or postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (odds ratio,13.5) and widespread necrotic collections (OR, 5.7 for unilateral paracolic or retromesenteric; OR, 21.8 for bilateral paracolic or unilateral paracolic and retromesenteric). Other risk factors were preceding bacteremia (OR, 4.8) and preceding open abdomen treatment for abdominal compartment syndrome (OR, 3.6).

After 90 days, 29 patients had died, including 7 with IPN and 22 without IPN. In addition, patients with IPN had longer overall hospital stays and ICU stays, higher rates of ICU readmission, and greater use of open necrosectomy, the researchers noted.

The study findings were limited by several factors, including the retrospective design, lack of controls, potential differences in treatment protocols, and the survival bias that prevented direct comparison of mortality in patients with and without IPN, the researchers noted. “This study cannot provide a reliable estimate of the difference in mortality attributable to IPN itself.”

However, the researchers noted that “the strength of the present study was to include only patients with persistent organ failure and admission to ICU in the early disease course,” and results indicate a significant morbid outcome associated with IPN. “In attempting to decrease the rate of IPN, efforts to identify and treat incipient organ failure with subsequent low threshold for admission to ICU becomes essential,” they emphasized. 
 

More data may prompt greater intervention

“IPN portends a poor prognosis, and can be challenging to both diagnose and treat,” Gyanprakash A. Ketwaroo, MD, of Baylor College of Medicine, Houston, said in an interview. “Identifying risk factors for development of IPN may facilitate earlier therapy that could modify the natural history of this disease.”

Dr. Ketwaroo said he was not surprised by the study findings. “This was a small single-center, retrospective study, where infection could only be ascertained among those who received interventions, and the findings should thus be interpreted within these limitations. Overall, however, I was not surprised. More extensive necrosis and opportunities for infectious seeding of necrosis such as interventions (ERCP) and bacteremia would be expected risk factors. I was surprised by the use of prophylactic antibiotics, as well as the high rate of open necrosectomy, though this should not affect the main findings of risk factors for infection.

“The studies highlight that a significant portion of patients with severe acute pancreatitis with necrosis will develop infection,” said Dr. Ketwaroo. “Being aware of the risk factors for infection, as identified in this study, can add to our clinical judgment in suspecting infection and opting for debridement. Especially with advancements in endoscopic necrosectomy, gastroenterologists may be more inclined to intervene when suspecting IPN. The next steps for research are to validate risk factors in larger, prospective studies.”

The study was supported by governmental competitive funds for medical research, a research grant from the Medical Society of Finland, and a research grant from Perkléns Foundation. The researchers had no financial conflicts to disclose. Dr. Ketwaroo had no financial conflicts to disclose but is a member of the GI & Hepatology News editorial advisory board.

Patients with infected pancreatic necrosis (IPN) are more likely to experience organ failure and mortality, which makes identifying them as quickly as possible especially crucial. A new study aimed to make this task a bit easier by categorizing the main risk factors for IPN in a cohort of patients with severe acute pancreatitis, which included extensive spread of necrotic collections, preceding bacteremia, and preceding open abdomen treatment, as well as postinterventional pancreatitis.

In their study, published in the Journal of Gastrointestinal Surgery, Henrik L. Husu, MD, of the University of Helsinki, and colleagues noted the inherent challenges of rendering a preoperative diagnosis of IPN.

“Fever and increasing inflammation markers may indicate suspicion of IPN, but these are very common in patients with severe acute pancreatitis treated in the ICU,” and more knowledge of specific IPN risk factors is needed to improve clinical decision-making, they said.

Dr. Husu and colleagues identified 163 adults with acute pancreatitis admitted to the ICU at a single center between 2010 and 2018, approximately 68% of whom had alcoholic necrotizing pancreatitis. Pneumonia, bacteremia, and IPN occurred at an average of 4, 16, and 23 days, respectively, after ICU admission.

Forty-seven patients (28.8%) developed IPN within 90 days of ICU admission, all patients had a least one persistent organ failure, and 60% had multiple organ failure within 24 hours of ICU admission.

In a multivariate regression analysis, independent risk factors for IPN included postoperative or postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (odds ratio,13.5) and widespread necrotic collections (OR, 5.7 for unilateral paracolic or retromesenteric; OR, 21.8 for bilateral paracolic or unilateral paracolic and retromesenteric). Other risk factors were preceding bacteremia (OR, 4.8) and preceding open abdomen treatment for abdominal compartment syndrome (OR, 3.6).

After 90 days, 29 patients had died, including 7 with IPN and 22 without IPN. In addition, patients with IPN had longer overall hospital stays and ICU stays, higher rates of ICU readmission, and greater use of open necrosectomy, the researchers noted.

The study findings were limited by several factors, including the retrospective design, lack of controls, potential differences in treatment protocols, and the survival bias that prevented direct comparison of mortality in patients with and without IPN, the researchers noted. “This study cannot provide a reliable estimate of the difference in mortality attributable to IPN itself.”

However, the researchers noted that “the strength of the present study was to include only patients with persistent organ failure and admission to ICU in the early disease course,” and results indicate a significant morbid outcome associated with IPN. “In attempting to decrease the rate of IPN, efforts to identify and treat incipient organ failure with subsequent low threshold for admission to ICU becomes essential,” they emphasized. 
 

More data may prompt greater intervention

“IPN portends a poor prognosis, and can be challenging to both diagnose and treat,” Gyanprakash A. Ketwaroo, MD, of Baylor College of Medicine, Houston, said in an interview. “Identifying risk factors for development of IPN may facilitate earlier therapy that could modify the natural history of this disease.”

Dr. Ketwaroo said he was not surprised by the study findings. “This was a small single-center, retrospective study, where infection could only be ascertained among those who received interventions, and the findings should thus be interpreted within these limitations. Overall, however, I was not surprised. More extensive necrosis and opportunities for infectious seeding of necrosis such as interventions (ERCP) and bacteremia would be expected risk factors. I was surprised by the use of prophylactic antibiotics, as well as the high rate of open necrosectomy, though this should not affect the main findings of risk factors for infection.

“The studies highlight that a significant portion of patients with severe acute pancreatitis with necrosis will develop infection,” said Dr. Ketwaroo. “Being aware of the risk factors for infection, as identified in this study, can add to our clinical judgment in suspecting infection and opting for debridement. Especially with advancements in endoscopic necrosectomy, gastroenterologists may be more inclined to intervene when suspecting IPN. The next steps for research are to validate risk factors in larger, prospective studies.”

The study was supported by governmental competitive funds for medical research, a research grant from the Medical Society of Finland, and a research grant from Perkléns Foundation. The researchers had no financial conflicts to disclose. Dr. Ketwaroo had no financial conflicts to disclose but is a member of the GI & Hepatology News editorial advisory board.

Different kinds of neuropsychiatric (NP) events in patients with systemic lupus erythematosus (SLE) have substantial variability in their occurrence, resolution, and recurrence over time, as well as in their predictors, according to new research from a large, prospective, international, inception cohort study.

Because “multiple NP events due to different causes may present concurrently in individual patients, the findings emphasize the importance of recognizing attribution of NP events as a determinant of clinical outcome,” John G. Hanly, MD, of Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, N.S., and colleagues wrote in Arthritis & Rheumatology.

In a previous study of the same group of 1,827 patients with SLE, NP events occurred in about half and approximately one-third of these events were deemed disease related. They also “occurred most frequently around the diagnosis of SLE and had a significant negative impact on health-related quality of life,” the researchers wrote.

Researchers involved with the Systemic Lupus International Collaborating Clinics recruited the 1,827 adults with SLE over an 11-year period during 1999-2011 from a total of 31 sites in Europe, Asia, and North America. The average age of the patients at study enrollment was 35 years, 89% were women, and 49% were White. The mean disease duration was 5.6 months, and 70% of patients were taking corticosteroids at enrollment.

Over an average follow-up period of 7.6 years, 955 patients (52.3%) experienced a single neuropsychiatric event, and 493 (27.0%) experienced two or more events; the total number of unique NP events was 1,910. Most of these unique events (92%) involved the central nervous system, and 8.4% involved the peripheral nervous system.

The researchers used multistate models to attribute NP events to SLE based on factors that included the temporal onset of NP events in relation to SLE diagnosis, concurrent non-SLE factors, and NP events that are common in healthy controls. The four states in the multistate models were no NP events, no current NP event but a history of at least one event, new or ongoing NP events, and death. The results included a multivariate analysis of a model involving 492 observed transitions into new or ongoing NP events.

In the multivariate analysis, factors positively associated with SLE-attributed NP events included male sex (hazard ratio, 1.35; P = .028), concurrent non-SLE NP events excluding headache (HR, 1.83; P < .001), active SLE based on the Systemic Lupus Erythematosus Disease Activity Index 2000 (HR, 1.19; P = .012), and corticosteroid use (HR, 1.59; P = .008). The researchers also found that SLE-attributed NP events were negatively associated with Asian race/ethnicity, postsecondary education, and use of immunosuppressive drugs.

Another multivariate analysis found that non-SLE NP events were positively associated with only concurrent SLE-attributed NP events excluding headache (HR, 2.31; P < .001), but negative associations were seen with non-U.S. African race/ethnicity and Asian race/ethnicity.

The researchers found that SLE-attributed NP events had higher rates of resolution, compared with non-SLE NP events, with the exception of headache, which had similar resolution for both event groups.

“Resolution of SLE events was more likely in patients with Asian race/ethnicity and those with Central/Focal nervous system disease with no effect seen for age at diagnosis,” the researchers noted. “For non-SLE NP events, African race/ethnicity at non-U.S. sites and younger age at diagnosis was associated with a better outcome.”

The study findings were limited by several factors including the predominantly White patient population and the clustering of NP events into limited categories, which may have reduced the identification of more specific associations, the researchers noted. Also, the assessment of NP event outcomes did not include patient perceptions, and the relatively short follow-up period does not allow for assessment of later NP events such as cerebrovascular disease. However, “despite these limitations the current study provides valuable data on the presentation, outcome and predictors of NP disease in SLE patients enrolled in a long-term, international, disease inception cohort,” the researchers concluded.

The study received no outside funding. Dr. Hanly was supported by a grant from the Canadian Institutes of Health Research but had no financial conflicts to disclose. Several coauthors received grant support from various institutions, but not from industry, and had no financial conflicts to disclose.

Different kinds of neuropsychiatric (NP) events in patients with systemic lupus erythematosus (SLE) have substantial variability in their occurrence, resolution, and recurrence over time, as well as in their predictors, according to new research from a large, prospective, international, inception cohort study.

Because “multiple NP events due to different causes may present concurrently in individual patients, the findings emphasize the importance of recognizing attribution of NP events as a determinant of clinical outcome,” John G. Hanly, MD, of Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, N.S., and colleagues wrote in Arthritis & Rheumatology.

In a previous study of the same group of 1,827 patients with SLE, NP events occurred in about half and approximately one-third of these events were deemed disease related. They also “occurred most frequently around the diagnosis of SLE and had a significant negative impact on health-related quality of life,” the researchers wrote.

Researchers involved with the Systemic Lupus International Collaborating Clinics recruited the 1,827 adults with SLE over an 11-year period during 1999-2011 from a total of 31 sites in Europe, Asia, and North America. The average age of the patients at study enrollment was 35 years, 89% were women, and 49% were White. The mean disease duration was 5.6 months, and 70% of patients were taking corticosteroids at enrollment.

Over an average follow-up period of 7.6 years, 955 patients (52.3%) experienced a single neuropsychiatric event, and 493 (27.0%) experienced two or more events; the total number of unique NP events was 1,910. Most of these unique events (92%) involved the central nervous system, and 8.4% involved the peripheral nervous system.

The researchers used multistate models to attribute NP events to SLE based on factors that included the temporal onset of NP events in relation to SLE diagnosis, concurrent non-SLE factors, and NP events that are common in healthy controls. The four states in the multistate models were no NP events, no current NP event but a history of at least one event, new or ongoing NP events, and death. The results included a multivariate analysis of a model involving 492 observed transitions into new or ongoing NP events.

In the multivariate analysis, factors positively associated with SLE-attributed NP events included male sex (hazard ratio, 1.35; P = .028), concurrent non-SLE NP events excluding headache (HR, 1.83; P < .001), active SLE based on the Systemic Lupus Erythematosus Disease Activity Index 2000 (HR, 1.19; P = .012), and corticosteroid use (HR, 1.59; P = .008). The researchers also found that SLE-attributed NP events were negatively associated with Asian race/ethnicity, postsecondary education, and use of immunosuppressive drugs.

Another multivariate analysis found that non-SLE NP events were positively associated with only concurrent SLE-attributed NP events excluding headache (HR, 2.31; P < .001), but negative associations were seen with non-U.S. African race/ethnicity and Asian race/ethnicity.

The researchers found that SLE-attributed NP events had higher rates of resolution, compared with non-SLE NP events, with the exception of headache, which had similar resolution for both event groups.

“Resolution of SLE events was more likely in patients with Asian race/ethnicity and those with Central/Focal nervous system disease with no effect seen for age at diagnosis,” the researchers noted. “For non-SLE NP events, African race/ethnicity at non-U.S. sites and younger age at diagnosis was associated with a better outcome.”

The study findings were limited by several factors including the predominantly White patient population and the clustering of NP events into limited categories, which may have reduced the identification of more specific associations, the researchers noted. Also, the assessment of NP event outcomes did not include patient perceptions, and the relatively short follow-up period does not allow for assessment of later NP events such as cerebrovascular disease. However, “despite these limitations the current study provides valuable data on the presentation, outcome and predictors of NP disease in SLE patients enrolled in a long-term, international, disease inception cohort,” the researchers concluded.

The study received no outside funding. Dr. Hanly was supported by a grant from the Canadian Institutes of Health Research but had no financial conflicts to disclose. Several coauthors received grant support from various institutions, but not from industry, and had no financial conflicts to disclose.

Different kinds of neuropsychiatric (NP) events in patients with systemic lupus erythematosus (SLE) have substantial variability in their occurrence, resolution, and recurrence over time, as well as in their predictors, according to new research from a large, prospective, international, inception cohort study.

Because “multiple NP events due to different causes may present concurrently in individual patients, the findings emphasize the importance of recognizing attribution of NP events as a determinant of clinical outcome,” John G. Hanly, MD, of Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, N.S., and colleagues wrote in Arthritis & Rheumatology.

In a previous study of the same group of 1,827 patients with SLE, NP events occurred in about half and approximately one-third of these events were deemed disease related. They also “occurred most frequently around the diagnosis of SLE and had a significant negative impact on health-related quality of life,” the researchers wrote.

Researchers involved with the Systemic Lupus International Collaborating Clinics recruited the 1,827 adults with SLE over an 11-year period during 1999-2011 from a total of 31 sites in Europe, Asia, and North America. The average age of the patients at study enrollment was 35 years, 89% were women, and 49% were White. The mean disease duration was 5.6 months, and 70% of patients were taking corticosteroids at enrollment.

Over an average follow-up period of 7.6 years, 955 patients (52.3%) experienced a single neuropsychiatric event, and 493 (27.0%) experienced two or more events; the total number of unique NP events was 1,910. Most of these unique events (92%) involved the central nervous system, and 8.4% involved the peripheral nervous system.

The researchers used multistate models to attribute NP events to SLE based on factors that included the temporal onset of NP events in relation to SLE diagnosis, concurrent non-SLE factors, and NP events that are common in healthy controls. The four states in the multistate models were no NP events, no current NP event but a history of at least one event, new or ongoing NP events, and death. The results included a multivariate analysis of a model involving 492 observed transitions into new or ongoing NP events.

In the multivariate analysis, factors positively associated with SLE-attributed NP events included male sex (hazard ratio, 1.35; P = .028), concurrent non-SLE NP events excluding headache (HR, 1.83; P < .001), active SLE based on the Systemic Lupus Erythematosus Disease Activity Index 2000 (HR, 1.19; P = .012), and corticosteroid use (HR, 1.59; P = .008). The researchers also found that SLE-attributed NP events were negatively associated with Asian race/ethnicity, postsecondary education, and use of immunosuppressive drugs.

Another multivariate analysis found that non-SLE NP events were positively associated with only concurrent SLE-attributed NP events excluding headache (HR, 2.31; P < .001), but negative associations were seen with non-U.S. African race/ethnicity and Asian race/ethnicity.

The researchers found that SLE-attributed NP events had higher rates of resolution, compared with non-SLE NP events, with the exception of headache, which had similar resolution for both event groups.

“Resolution of SLE events was more likely in patients with Asian race/ethnicity and those with Central/Focal nervous system disease with no effect seen for age at diagnosis,” the researchers noted. “For non-SLE NP events, African race/ethnicity at non-U.S. sites and younger age at diagnosis was associated with a better outcome.”

The study findings were limited by several factors including the predominantly White patient population and the clustering of NP events into limited categories, which may have reduced the identification of more specific associations, the researchers noted. Also, the assessment of NP event outcomes did not include patient perceptions, and the relatively short follow-up period does not allow for assessment of later NP events such as cerebrovascular disease. However, “despite these limitations the current study provides valuable data on the presentation, outcome and predictors of NP disease in SLE patients enrolled in a long-term, international, disease inception cohort,” the researchers concluded.

The study received no outside funding. Dr. Hanly was supported by a grant from the Canadian Institutes of Health Research but had no financial conflicts to disclose. Several coauthors received grant support from various institutions, but not from industry, and had no financial conflicts to disclose.

Healthy first-degree relatives of individuals with HLA-B27–positive axial spondyloarthritis who also were HLA-B27 positive were at increased risk for developing the disease themselves within 1 year, based on data from an ongoing prospective cohort study that involved 202 first-degree relatives.

Axial spondyloarthritis (axSpA) generally arises between ages 18 and 40 years, but diagnosis can be delayed, in part because of the lack of biomarkers and nonspecific symptoms, wrote Henriëtte M.Y. de Jong, MD, PhD, of the University of Amsterdam, and colleagues.

Individuals who carry the HLA-B27 gene are predisposed to axSpA, and their first-degree relatives (FDRs) are at increased risk as well, the researchers said. Therefore, “studying [FDRs] could help to identify clinical signs, imaging abnormalities, and biomarkers that are predictive of development of axSpA,” they said.

In a study published in Arthritis Care & Research, the investigators reviewed data from patients in the Pre-SpA cohort, a 5-year prospective study of healthy-seeming FDRs of patients with HLA-B27–positive axSpA. The researchers previously reported that up to one-third of 51 FDRs had clinical features associated with SpA at baseline, despite the lack of a diagnosis.

The current study included an additional 151 FDRs who had answered yearly questions about back pain and undergone a yearly physical exam and plain radiographs and MRI imaging at baseline.

Overall, 65% reported back pain at baseline and 19% met criteria for inflammatory back pain, with a median visual analog score (VAS) for back pain of 22. No active arthritis was noted, but 5 FDRs reported a past arthritis diagnosis, 48 reported arthralgia, and 16 had at least one tender joint on physical exam. Eight FDRs had past diagnoses of enthesitis, and one had a history of dactylitis.

In assessing disease activity, the researchers found an elevated C-reactive protein (CRP) level in 24 FDRs and 11 had an elevated erythrocyte sedimentation rate (ESR).

On MRI of the sacroiliac joint at baseline, 10% of the FDRs had SPARCC (Spondyloarthritis Research Consortium of Canada) scores of 2 or higher, 4% had scores of 5 or higher, and 4% had deep lesions.

A total of 123 FDRs had complete data at a 1-year follow-up visit.

“All features were equally distributed between HLA-B27–positive and –negative FDRs,” the researchers noted. However, at the end of the 1-year follow-up period, seven (6%) of the FDRs were clinically diagnosed with axSpA, and six of them were HLA-B27 positive. Disease activity measures had increased at 1 year in all seven patients with newly diagnosed axSpA.

The study findings were limited by several factors, including the possible channeling of FDRs with current complaints of back pain into the study and the inability to confirm details of family and medical history, the researchers noted. However, the VAS back pain scores reported by the FDRs suggest that this pain was not a fixture in daily life, they wrote.

The results confirm the prevalent subclinical signs of SpA in healthy FDRs of patients with axSpA who were positive and negative for HLA-B27, but also confirm that clinical progression occurred primarily in the HLA-B27–positive patients in conjunction with inflammatory back pain, the researchers said.

“Further follow-up of the Pre-SpA cohort will give more robust insight into the characteristics of FDRs that progress towards clinical SpA, thereby hopefully enabling the characterization of high-risk FDRs,” they concluded.

The Pre-SpA cohort is supported by the Dutch Arthritis Society. Lead author Dr. de Jong had no financial conflicts to disclose. One coauthor is employed by UCB, and several others disclosed relationships with AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB.

Healthy first-degree relatives of individuals with HLA-B27–positive axial spondyloarthritis who also were HLA-B27 positive were at increased risk for developing the disease themselves within 1 year, based on data from an ongoing prospective cohort study that involved 202 first-degree relatives.

Axial spondyloarthritis (axSpA) generally arises between ages 18 and 40 years, but diagnosis can be delayed, in part because of the lack of biomarkers and nonspecific symptoms, wrote Henriëtte M.Y. de Jong, MD, PhD, of the University of Amsterdam, and colleagues.

Individuals who carry the HLA-B27 gene are predisposed to axSpA, and their first-degree relatives (FDRs) are at increased risk as well, the researchers said. Therefore, “studying [FDRs] could help to identify clinical signs, imaging abnormalities, and biomarkers that are predictive of development of axSpA,” they said.

In a study published in Arthritis Care & Research, the investigators reviewed data from patients in the Pre-SpA cohort, a 5-year prospective study of healthy-seeming FDRs of patients with HLA-B27–positive axSpA. The researchers previously reported that up to one-third of 51 FDRs had clinical features associated with SpA at baseline, despite the lack of a diagnosis.

The current study included an additional 151 FDRs who had answered yearly questions about back pain and undergone a yearly physical exam and plain radiographs and MRI imaging at baseline.

Overall, 65% reported back pain at baseline and 19% met criteria for inflammatory back pain, with a median visual analog score (VAS) for back pain of 22. No active arthritis was noted, but 5 FDRs reported a past arthritis diagnosis, 48 reported arthralgia, and 16 had at least one tender joint on physical exam. Eight FDRs had past diagnoses of enthesitis, and one had a history of dactylitis.

In assessing disease activity, the researchers found an elevated C-reactive protein (CRP) level in 24 FDRs and 11 had an elevated erythrocyte sedimentation rate (ESR).

On MRI of the sacroiliac joint at baseline, 10% of the FDRs had SPARCC (Spondyloarthritis Research Consortium of Canada) scores of 2 or higher, 4% had scores of 5 or higher, and 4% had deep lesions.

A total of 123 FDRs had complete data at a 1-year follow-up visit.

“All features were equally distributed between HLA-B27–positive and –negative FDRs,” the researchers noted. However, at the end of the 1-year follow-up period, seven (6%) of the FDRs were clinically diagnosed with axSpA, and six of them were HLA-B27 positive. Disease activity measures had increased at 1 year in all seven patients with newly diagnosed axSpA.

The study findings were limited by several factors, including the possible channeling of FDRs with current complaints of back pain into the study and the inability to confirm details of family and medical history, the researchers noted. However, the VAS back pain scores reported by the FDRs suggest that this pain was not a fixture in daily life, they wrote.

The results confirm the prevalent subclinical signs of SpA in healthy FDRs of patients with axSpA who were positive and negative for HLA-B27, but also confirm that clinical progression occurred primarily in the HLA-B27–positive patients in conjunction with inflammatory back pain, the researchers said.

“Further follow-up of the Pre-SpA cohort will give more robust insight into the characteristics of FDRs that progress towards clinical SpA, thereby hopefully enabling the characterization of high-risk FDRs,” they concluded.

The Pre-SpA cohort is supported by the Dutch Arthritis Society. Lead author Dr. de Jong had no financial conflicts to disclose. One coauthor is employed by UCB, and several others disclosed relationships with AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB.

Healthy first-degree relatives of individuals with HLA-B27–positive axial spondyloarthritis who also were HLA-B27 positive were at increased risk for developing the disease themselves within 1 year, based on data from an ongoing prospective cohort study that involved 202 first-degree relatives.

Axial spondyloarthritis (axSpA) generally arises between ages 18 and 40 years, but diagnosis can be delayed, in part because of the lack of biomarkers and nonspecific symptoms, wrote Henriëtte M.Y. de Jong, MD, PhD, of the University of Amsterdam, and colleagues.

Individuals who carry the HLA-B27 gene are predisposed to axSpA, and their first-degree relatives (FDRs) are at increased risk as well, the researchers said. Therefore, “studying [FDRs] could help to identify clinical signs, imaging abnormalities, and biomarkers that are predictive of development of axSpA,” they said.

In a study published in Arthritis Care & Research, the investigators reviewed data from patients in the Pre-SpA cohort, a 5-year prospective study of healthy-seeming FDRs of patients with HLA-B27–positive axSpA. The researchers previously reported that up to one-third of 51 FDRs had clinical features associated with SpA at baseline, despite the lack of a diagnosis.

The current study included an additional 151 FDRs who had answered yearly questions about back pain and undergone a yearly physical exam and plain radiographs and MRI imaging at baseline.

Overall, 65% reported back pain at baseline and 19% met criteria for inflammatory back pain, with a median visual analog score (VAS) for back pain of 22. No active arthritis was noted, but 5 FDRs reported a past arthritis diagnosis, 48 reported arthralgia, and 16 had at least one tender joint on physical exam. Eight FDRs had past diagnoses of enthesitis, and one had a history of dactylitis.

In assessing disease activity, the researchers found an elevated C-reactive protein (CRP) level in 24 FDRs and 11 had an elevated erythrocyte sedimentation rate (ESR).

On MRI of the sacroiliac joint at baseline, 10% of the FDRs had SPARCC (Spondyloarthritis Research Consortium of Canada) scores of 2 or higher, 4% had scores of 5 or higher, and 4% had deep lesions.

A total of 123 FDRs had complete data at a 1-year follow-up visit.

“All features were equally distributed between HLA-B27–positive and –negative FDRs,” the researchers noted. However, at the end of the 1-year follow-up period, seven (6%) of the FDRs were clinically diagnosed with axSpA, and six of them were HLA-B27 positive. Disease activity measures had increased at 1 year in all seven patients with newly diagnosed axSpA.

The study findings were limited by several factors, including the possible channeling of FDRs with current complaints of back pain into the study and the inability to confirm details of family and medical history, the researchers noted. However, the VAS back pain scores reported by the FDRs suggest that this pain was not a fixture in daily life, they wrote.

The results confirm the prevalent subclinical signs of SpA in healthy FDRs of patients with axSpA who were positive and negative for HLA-B27, but also confirm that clinical progression occurred primarily in the HLA-B27–positive patients in conjunction with inflammatory back pain, the researchers said.

“Further follow-up of the Pre-SpA cohort will give more robust insight into the characteristics of FDRs that progress towards clinical SpA, thereby hopefully enabling the characterization of high-risk FDRs,” they concluded.

The Pre-SpA cohort is supported by the Dutch Arthritis Society. Lead author Dr. de Jong had no financial conflicts to disclose. One coauthor is employed by UCB, and several others disclosed relationships with AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB.

The Food and Drug Administration has expanded the approval of secnidazole to include treatment of trichomoniasis in adults, according to a statement from manufacturer Lupin Pharmaceuticals.

Trichomoniasis vaginalis is a common, nonviral, curable sexually transmitted disease that affects approximately 3 million to 5 million adults in the United States each year; the infection can linger for months or years if left untreated, and may have a negative impact on reproductive health. The drug was approved for the treatment of bacterial vaginosis in 2017.

The availability of a single-dose oral treatment for both trichomoniasis and bacterial vaginosis may help improve adherence and reduce risk factors associated with these conditions, including pelvic inflammatory disease and other sexually transmitted infections, according to the statement.

The approval for the new indication was based primarily on data from a phase 3 clinical trial in which women with a confirmed trichomoniasis diagnosis were randomized to a single dose of 2 g oral secnidazole or a placebo. Secnidazole showed a 92.2% cure rate for patients with trichomoniasis, compared with placebo, based on cultures collected 6-12 days after dosing. Cure rates in subsets of patients with HIV and bacterial vaginosis were 100% and 95%, respectively.

The most common treatment-related adverse events were vulvovaginal candidiasis and nausea, each reported in 2.7% of study participants. The study findings were published in March 2021 in Clinical Infections Diseases.

Secnidazole also is approved for treatment of trichomoniasis in men, based on data from four open-label studies, one with men only and three including both men and women, according to the statement.

Full prescribing information for secnidazole is available here.

The Food and Drug Administration has expanded the approval of secnidazole to include treatment of trichomoniasis in adults, according to a statement from manufacturer Lupin Pharmaceuticals.

Trichomoniasis vaginalis is a common, nonviral, curable sexually transmitted disease that affects approximately 3 million to 5 million adults in the United States each year; the infection can linger for months or years if left untreated, and may have a negative impact on reproductive health. The drug was approved for the treatment of bacterial vaginosis in 2017.

The availability of a single-dose oral treatment for both trichomoniasis and bacterial vaginosis may help improve adherence and reduce risk factors associated with these conditions, including pelvic inflammatory disease and other sexually transmitted infections, according to the statement.

The approval for the new indication was based primarily on data from a phase 3 clinical trial in which women with a confirmed trichomoniasis diagnosis were randomized to a single dose of 2 g oral secnidazole or a placebo. Secnidazole showed a 92.2% cure rate for patients with trichomoniasis, compared with placebo, based on cultures collected 6-12 days after dosing. Cure rates in subsets of patients with HIV and bacterial vaginosis were 100% and 95%, respectively.

The most common treatment-related adverse events were vulvovaginal candidiasis and nausea, each reported in 2.7% of study participants. The study findings were published in March 2021 in Clinical Infections Diseases.

Secnidazole also is approved for treatment of trichomoniasis in men, based on data from four open-label studies, one with men only and three including both men and women, according to the statement.

Full prescribing information for secnidazole is available here.

The Food and Drug Administration has expanded the approval of secnidazole to include treatment of trichomoniasis in adults, according to a statement from manufacturer Lupin Pharmaceuticals.

Trichomoniasis vaginalis is a common, nonviral, curable sexually transmitted disease that affects approximately 3 million to 5 million adults in the United States each year; the infection can linger for months or years if left untreated, and may have a negative impact on reproductive health. The drug was approved for the treatment of bacterial vaginosis in 2017.

The availability of a single-dose oral treatment for both trichomoniasis and bacterial vaginosis may help improve adherence and reduce risk factors associated with these conditions, including pelvic inflammatory disease and other sexually transmitted infections, according to the statement.

The approval for the new indication was based primarily on data from a phase 3 clinical trial in which women with a confirmed trichomoniasis diagnosis were randomized to a single dose of 2 g oral secnidazole or a placebo. Secnidazole showed a 92.2% cure rate for patients with trichomoniasis, compared with placebo, based on cultures collected 6-12 days after dosing. Cure rates in subsets of patients with HIV and bacterial vaginosis were 100% and 95%, respectively.

The most common treatment-related adverse events were vulvovaginal candidiasis and nausea, each reported in 2.7% of study participants. The study findings were published in March 2021 in Clinical Infections Diseases.

Secnidazole also is approved for treatment of trichomoniasis in men, based on data from four open-label studies, one with men only and three including both men and women, according to the statement.

Full prescribing information for secnidazole is available here.

Frequency or timing of unprotected intercourse within 14 days before IUD placement had no impact on pregnancy if a preplacement pregnancy test was negative, based on data from 655 women who received IUDs.

Many women present for emergency contraception with a history of unprotected intercourse, often beyond the 5-day guidelines for emergency contraception recommended by the World Health Organization, wrote Abena BakenRa, MD, of the University of California, Berkeley, and colleagues. “As such, we lack data on situations in which multiple episodes of unprotected intercourse occurred in the same menstrual cycle of use, especially episodes occurring more than 5 days before emergency contraception use,” the researchers said.

To determine pregnancy risk during a longer period before IUD placement, the researchers reviewed secondary data from a randomized trial of 655 women who received the copper T380A IUD or levonorgestrel 52-mg intrauterine system for emergency contraception. The women were aged 18-35 years and were enrolled at one of six family planning clinics in Utah between August 2016 and December 2019.

In a study published in Obstetrics & Gynecology, the researchers assessed pregnancies at 1 month after IUD placement. All of the women had a confirmed negative urine pregnancy test result immediately before IUD placement.

Overall, 286 women (43.7%) reported multiple episodes of unprotected intercourse, with a median of three episodes. A total of 95 women (14.4%) reported at least one unprotected intercourse episode at 6 days or more prior to IUD placement. No pregnancies were reported among women in either of these categories (0.0% for both). Pregnancy risk was 0.2% among those who reported unprotected intercourse within 5 days of IUD placement.

No pregnancies occurred in those who reported additional episodes of unprotected intercourse at 6-7 days, 6-10 days, or 6-14 days before IUD placement (0% for all).

In both the copper IUD and levonorgestrel groups, 68% and 74%, respectively, of the women reported that all fertile-window unprotected intercourse events occurred in the 5 days prior to IUD placement.

The study findings were limited by several factors including the lack of power for analysis of certain categories of assessment, such as pregnancy rates by timing or frequency, the inclusion of patients only from the state of Utah, and the potential underreporting of unprotected intercourse, the researchers noted. However, the findings were strengthened by the relatively large sample size, and by data on unprotected intercourse before IUD placement in a randomized, controlled trial that included two types of IUDs, they said.

“For these situations with multiple unprotected intercourse episodes and extended time between unprotected intercourse and emergency contraception request, potential users should be informed of the evidence of IUD emergency contraception efficacy, compared with the current state of uncertain data for oral emergency contraception methods,” the researchers said.

“Given the multitude of barriers that may impede timely presentation to care (insurance and cost concerns, difficulty finding a capable health care professional, or sexual assault trauma), these data are critical to patient-centered family planning care,” they concluded.

Data support IUD placement in practice

“Understanding potential barriers to placement of long-acting reversible contraception such as IUDs is essential to expanding access to contraception,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

“This study is a secondary analysis of a randomized trial that compared copper versus levonorgestrel IUD placement for emergency contraception. Investigators were able to evaluate frequency and timing of unprotected intercourse up to 14 days prior to IUD placement and prospectively collect data assessing pregnancy risk 1 month after IUD placement,” she said.

The study findings suggest that the risk of pregnancy with unprotected intercourse within 14 days of IUD placement is low overall, and that this risk does not appear to increase with multiple episodes of unprotected intercourse during this time period, Dr. Krishna said. “In general, insertion of an IUD may occur at any time during the menstrual cycle as long as pregnancy may be reasonably excluded and clinicians are encouraged to initiate and place long-acting reversible contraceptives in a single visit, if possible,” she noted. However, “there is a paucity of data on risk of pregnancy when assessing efficacy of IUDs as emergency contraception with episodes of unprotected intercourse more than 5 days prior to IUD placement,” she added.

The study results also suggest that pregnancy risk is similar between women who reported unprotected intercourse within 5 days prior to IUD placement and those who reported unprotected intercourse up to 14 days prior to IUD placement, said Dr. Krishna. “These findings are clinically significant, as they add to our understanding of risk of pregnancy with unprotected intercourse up to 14 days prior to placement of an IUD,” she emphasized.

In practice, the study results “will help clinicians counsel patients on risk of pregnancy after IUD placement for emergency contraception,” said Dr. Krishna. “More studies evaluating risk of pregnancy after IUD placement for emergency contraception with episodes of unprotected intercourse more than 5 days prior to placement are needed to further assess the potential to expand the time frame for IUD use as emergency contraception,” she said. “Reducing barriers to IUD access, especially in setting of emergency contraception, is essential to lowering unintended pregnancy rates in the United States.”

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, as well as the University of Utah Population Health Research Foundation, the National Center for Research Resources, and the National Center for Advancing Translational Sciences at the National Institutes of Health. Several coauthors disclosed grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Office of Research on Women’s Health of the National Institutes of Health. The researchers, as well as Dr. Krishna, had no financial conflicts to disclose.

Frequency or timing of unprotected intercourse within 14 days before IUD placement had no impact on pregnancy if a preplacement pregnancy test was negative, based on data from 655 women who received IUDs.

Many women present for emergency contraception with a history of unprotected intercourse, often beyond the 5-day guidelines for emergency contraception recommended by the World Health Organization, wrote Abena BakenRa, MD, of the University of California, Berkeley, and colleagues. “As such, we lack data on situations in which multiple episodes of unprotected intercourse occurred in the same menstrual cycle of use, especially episodes occurring more than 5 days before emergency contraception use,” the researchers said.

To determine pregnancy risk during a longer period before IUD placement, the researchers reviewed secondary data from a randomized trial of 655 women who received the copper T380A IUD or levonorgestrel 52-mg intrauterine system for emergency contraception. The women were aged 18-35 years and were enrolled at one of six family planning clinics in Utah between August 2016 and December 2019.

In a study published in Obstetrics & Gynecology, the researchers assessed pregnancies at 1 month after IUD placement. All of the women had a confirmed negative urine pregnancy test result immediately before IUD placement.

Overall, 286 women (43.7%) reported multiple episodes of unprotected intercourse, with a median of three episodes. A total of 95 women (14.4%) reported at least one unprotected intercourse episode at 6 days or more prior to IUD placement. No pregnancies were reported among women in either of these categories (0.0% for both). Pregnancy risk was 0.2% among those who reported unprotected intercourse within 5 days of IUD placement.

No pregnancies occurred in those who reported additional episodes of unprotected intercourse at 6-7 days, 6-10 days, or 6-14 days before IUD placement (0% for all).

In both the copper IUD and levonorgestrel groups, 68% and 74%, respectively, of the women reported that all fertile-window unprotected intercourse events occurred in the 5 days prior to IUD placement.

The study findings were limited by several factors including the lack of power for analysis of certain categories of assessment, such as pregnancy rates by timing or frequency, the inclusion of patients only from the state of Utah, and the potential underreporting of unprotected intercourse, the researchers noted. However, the findings were strengthened by the relatively large sample size, and by data on unprotected intercourse before IUD placement in a randomized, controlled trial that included two types of IUDs, they said.

“For these situations with multiple unprotected intercourse episodes and extended time between unprotected intercourse and emergency contraception request, potential users should be informed of the evidence of IUD emergency contraception efficacy, compared with the current state of uncertain data for oral emergency contraception methods,” the researchers said.

“Given the multitude of barriers that may impede timely presentation to care (insurance and cost concerns, difficulty finding a capable health care professional, or sexual assault trauma), these data are critical to patient-centered family planning care,” they concluded.

Data support IUD placement in practice

“Understanding potential barriers to placement of long-acting reversible contraception such as IUDs is essential to expanding access to contraception,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

“This study is a secondary analysis of a randomized trial that compared copper versus levonorgestrel IUD placement for emergency contraception. Investigators were able to evaluate frequency and timing of unprotected intercourse up to 14 days prior to IUD placement and prospectively collect data assessing pregnancy risk 1 month after IUD placement,” she said.

The study findings suggest that the risk of pregnancy with unprotected intercourse within 14 days of IUD placement is low overall, and that this risk does not appear to increase with multiple episodes of unprotected intercourse during this time period, Dr. Krishna said. “In general, insertion of an IUD may occur at any time during the menstrual cycle as long as pregnancy may be reasonably excluded and clinicians are encouraged to initiate and place long-acting reversible contraceptives in a single visit, if possible,” she noted. However, “there is a paucity of data on risk of pregnancy when assessing efficacy of IUDs as emergency contraception with episodes of unprotected intercourse more than 5 days prior to IUD placement,” she added.

The study results also suggest that pregnancy risk is similar between women who reported unprotected intercourse within 5 days prior to IUD placement and those who reported unprotected intercourse up to 14 days prior to IUD placement, said Dr. Krishna. “These findings are clinically significant, as they add to our understanding of risk of pregnancy with unprotected intercourse up to 14 days prior to placement of an IUD,” she emphasized.

In practice, the study results “will help clinicians counsel patients on risk of pregnancy after IUD placement for emergency contraception,” said Dr. Krishna. “More studies evaluating risk of pregnancy after IUD placement for emergency contraception with episodes of unprotected intercourse more than 5 days prior to placement are needed to further assess the potential to expand the time frame for IUD use as emergency contraception,” she said. “Reducing barriers to IUD access, especially in setting of emergency contraception, is essential to lowering unintended pregnancy rates in the United States.”

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, as well as the University of Utah Population Health Research Foundation, the National Center for Research Resources, and the National Center for Advancing Translational Sciences at the National Institutes of Health. Several coauthors disclosed grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Office of Research on Women’s Health of the National Institutes of Health. The researchers, as well as Dr. Krishna, had no financial conflicts to disclose.

Frequency or timing of unprotected intercourse within 14 days before IUD placement had no impact on pregnancy if a preplacement pregnancy test was negative, based on data from 655 women who received IUDs.

Many women present for emergency contraception with a history of unprotected intercourse, often beyond the 5-day guidelines for emergency contraception recommended by the World Health Organization, wrote Abena BakenRa, MD, of the University of California, Berkeley, and colleagues. “As such, we lack data on situations in which multiple episodes of unprotected intercourse occurred in the same menstrual cycle of use, especially episodes occurring more than 5 days before emergency contraception use,” the researchers said.

To determine pregnancy risk during a longer period before IUD placement, the researchers reviewed secondary data from a randomized trial of 655 women who received the copper T380A IUD or levonorgestrel 52-mg intrauterine system for emergency contraception. The women were aged 18-35 years and were enrolled at one of six family planning clinics in Utah between August 2016 and December 2019.

In a study published in Obstetrics & Gynecology, the researchers assessed pregnancies at 1 month after IUD placement. All of the women had a confirmed negative urine pregnancy test result immediately before IUD placement.

Overall, 286 women (43.7%) reported multiple episodes of unprotected intercourse, with a median of three episodes. A total of 95 women (14.4%) reported at least one unprotected intercourse episode at 6 days or more prior to IUD placement. No pregnancies were reported among women in either of these categories (0.0% for both). Pregnancy risk was 0.2% among those who reported unprotected intercourse within 5 days of IUD placement.

No pregnancies occurred in those who reported additional episodes of unprotected intercourse at 6-7 days, 6-10 days, or 6-14 days before IUD placement (0% for all).

In both the copper IUD and levonorgestrel groups, 68% and 74%, respectively, of the women reported that all fertile-window unprotected intercourse events occurred in the 5 days prior to IUD placement.

The study findings were limited by several factors including the lack of power for analysis of certain categories of assessment, such as pregnancy rates by timing or frequency, the inclusion of patients only from the state of Utah, and the potential underreporting of unprotected intercourse, the researchers noted. However, the findings were strengthened by the relatively large sample size, and by data on unprotected intercourse before IUD placement in a randomized, controlled trial that included two types of IUDs, they said.

“For these situations with multiple unprotected intercourse episodes and extended time between unprotected intercourse and emergency contraception request, potential users should be informed of the evidence of IUD emergency contraception efficacy, compared with the current state of uncertain data for oral emergency contraception methods,” the researchers said.

“Given the multitude of barriers that may impede timely presentation to care (insurance and cost concerns, difficulty finding a capable health care professional, or sexual assault trauma), these data are critical to patient-centered family planning care,” they concluded.

Data support IUD placement in practice

“Understanding potential barriers to placement of long-acting reversible contraception such as IUDs is essential to expanding access to contraception,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

“This study is a secondary analysis of a randomized trial that compared copper versus levonorgestrel IUD placement for emergency contraception. Investigators were able to evaluate frequency and timing of unprotected intercourse up to 14 days prior to IUD placement and prospectively collect data assessing pregnancy risk 1 month after IUD placement,” she said.

The study findings suggest that the risk of pregnancy with unprotected intercourse within 14 days of IUD placement is low overall, and that this risk does not appear to increase with multiple episodes of unprotected intercourse during this time period, Dr. Krishna said. “In general, insertion of an IUD may occur at any time during the menstrual cycle as long as pregnancy may be reasonably excluded and clinicians are encouraged to initiate and place long-acting reversible contraceptives in a single visit, if possible,” she noted. However, “there is a paucity of data on risk of pregnancy when assessing efficacy of IUDs as emergency contraception with episodes of unprotected intercourse more than 5 days prior to IUD placement,” she added.

The study results also suggest that pregnancy risk is similar between women who reported unprotected intercourse within 5 days prior to IUD placement and those who reported unprotected intercourse up to 14 days prior to IUD placement, said Dr. Krishna. “These findings are clinically significant, as they add to our understanding of risk of pregnancy with unprotected intercourse up to 14 days prior to placement of an IUD,” she emphasized.

In practice, the study results “will help clinicians counsel patients on risk of pregnancy after IUD placement for emergency contraception,” said Dr. Krishna. “More studies evaluating risk of pregnancy after IUD placement for emergency contraception with episodes of unprotected intercourse more than 5 days prior to placement are needed to further assess the potential to expand the time frame for IUD use as emergency contraception,” she said. “Reducing barriers to IUD access, especially in setting of emergency contraception, is essential to lowering unintended pregnancy rates in the United States.”

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, as well as the University of Utah Population Health Research Foundation, the National Center for Research Resources, and the National Center for Advancing Translational Sciences at the National Institutes of Health. Several coauthors disclosed grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Office of Research on Women’s Health of the National Institutes of Health. The researchers, as well as Dr. Krishna, had no financial conflicts to disclose.