Spectra Optia Apheresis System

Image courtesy of Terumo BCT

The National Institute for Health and Care Excellence (NICE) has issued a guidance recommending a new device for managing sickle cell disease (SCD).

The device is the Spectra Optia Apheresis System for automated red blood cell (RBC) exchange in patients with SCD who need regular blood transfusions.

The Spectra Optia Apheresis System automatically replaces sickled RBCs with healthy RBCs.

The system is made up of 3 components: an apheresis machine, embedded software, and a single-use, disposable blood tubing set.

NICE said the Spectra Optia system is faster than manual RBC exchange, and patients need RBC exchange less often with this device. In addition, the system could provide considerable savings to the National Health Service (NHS) in England.

“The device could save the NHS in England an estimated £13 million each year—around £18,000 per patient—with the size of the saving depending on the patient’s condition and the equipment already owned by the NHS,” said Carole Longson, director of the NICE Centre for Health Technology Evaluation.

“We also recommend that specialists collaborate to collect and publish data on some outcomes of treatment with Spectra Optia to provide further clinical evidence. It would be particularly helpful to have long-term data on how automated and manual exchange affects the amount of iron in the body and the need to treat this complication.”

Treatment with the Spectra Optia system is intended to be iron-neutral, meaning that patients who are already iron-overloaded can have their condition managed effectively.

The Spectra Optia Apheresis System is manufactured by Terumo BCT.

Costs and savings

The list prices (excluding tax) for the components of the Spectra Optia Apheresis System are as follows:

• Spectra Optia device: £45,350
• RBC exchange software: £6700
• Spectra Optia exchange set: £1007 per 6
• Astotube with injection port: £218 per 50
• ACD-A anticoagulant (750 ml): £57 per 12
• Service charge: £4572 per year.

Bulk order discounts are available.

Based on current evidence and expert advice on the anticipated benefits of the technology when used in patients with iron overload, cost modelling shows that, in most cases, using Spectra Optia is cost-saving compared with manual RBC exchange or top-up transfusion.

The savings depend on the iron overload status of the patient and are more likely to be achieved if devices already owned by the NHS can be used to treat SCD.

The estimated cost saving for adopting Spectra Optia is £18,100 per patient per year, which has the potential to save the NHS £12.9 million each year.

Spectra Optia Apheresis System

Image courtesy of Terumo BCT

The National Institute for Health and Care Excellence (NICE) has issued a guidance recommending a new device for managing sickle cell disease (SCD).

The device is the Spectra Optia Apheresis System for automated red blood cell (RBC) exchange in patients with SCD who need regular blood transfusions.

The Spectra Optia Apheresis System automatically replaces sickled RBCs with healthy RBCs.

The system is made up of 3 components: an apheresis machine, embedded software, and a single-use, disposable blood tubing set.

NICE said the Spectra Optia system is faster than manual RBC exchange, and patients need RBC exchange less often with this device. In addition, the system could provide considerable savings to the National Health Service (NHS) in England.

“The device could save the NHS in England an estimated £13 million each year—around £18,000 per patient—with the size of the saving depending on the patient’s condition and the equipment already owned by the NHS,” said Carole Longson, director of the NICE Centre for Health Technology Evaluation.

“We also recommend that specialists collaborate to collect and publish data on some outcomes of treatment with Spectra Optia to provide further clinical evidence. It would be particularly helpful to have long-term data on how automated and manual exchange affects the amount of iron in the body and the need to treat this complication.”

Treatment with the Spectra Optia system is intended to be iron-neutral, meaning that patients who are already iron-overloaded can have their condition managed effectively.

The Spectra Optia Apheresis System is manufactured by Terumo BCT.

Costs and savings

The list prices (excluding tax) for the components of the Spectra Optia Apheresis System are as follows:

• Spectra Optia device: £45,350
• RBC exchange software: £6700
• Spectra Optia exchange set: £1007 per 6
• Astotube with injection port: £218 per 50
• ACD-A anticoagulant (750 ml): £57 per 12
• Service charge: £4572 per year.

Bulk order discounts are available.

Based on current evidence and expert advice on the anticipated benefits of the technology when used in patients with iron overload, cost modelling shows that, in most cases, using Spectra Optia is cost-saving compared with manual RBC exchange or top-up transfusion.

The savings depend on the iron overload status of the patient and are more likely to be achieved if devices already owned by the NHS can be used to treat SCD.

The estimated cost saving for adopting Spectra Optia is £18,100 per patient per year, which has the potential to save the NHS £12.9 million each year.

Spectra Optia Apheresis System

Image courtesy of Terumo BCT

The National Institute for Health and Care Excellence (NICE) has issued a guidance recommending a new device for managing sickle cell disease (SCD).

The device is the Spectra Optia Apheresis System for automated red blood cell (RBC) exchange in patients with SCD who need regular blood transfusions.

The Spectra Optia Apheresis System automatically replaces sickled RBCs with healthy RBCs.

The system is made up of 3 components: an apheresis machine, embedded software, and a single-use, disposable blood tubing set.

NICE said the Spectra Optia system is faster than manual RBC exchange, and patients need RBC exchange less often with this device. In addition, the system could provide considerable savings to the National Health Service (NHS) in England.

“The device could save the NHS in England an estimated £13 million each year—around £18,000 per patient—with the size of the saving depending on the patient’s condition and the equipment already owned by the NHS,” said Carole Longson, director of the NICE Centre for Health Technology Evaluation.

“We also recommend that specialists collaborate to collect and publish data on some outcomes of treatment with Spectra Optia to provide further clinical evidence. It would be particularly helpful to have long-term data on how automated and manual exchange affects the amount of iron in the body and the need to treat this complication.”

Treatment with the Spectra Optia system is intended to be iron-neutral, meaning that patients who are already iron-overloaded can have their condition managed effectively.

The Spectra Optia Apheresis System is manufactured by Terumo BCT.

Costs and savings

The list prices (excluding tax) for the components of the Spectra Optia Apheresis System are as follows:

• Spectra Optia device: £45,350
• RBC exchange software: £6700
• Spectra Optia exchange set: £1007 per 6
• Astotube with injection port: £218 per 50
• ACD-A anticoagulant (750 ml): £57 per 12
• Service charge: £4572 per year.

Bulk order discounts are available.

Based on current evidence and expert advice on the anticipated benefits of the technology when used in patients with iron overload, cost modelling shows that, in most cases, using Spectra Optia is cost-saving compared with manual RBC exchange or top-up transfusion.

The savings depend on the iron overload status of the patient and are more likely to be achieved if devices already owned by the NHS can be used to treat SCD.

The estimated cost saving for adopting Spectra Optia is £18,100 per patient per year, which has the potential to save the NHS £12.9 million each year.

LOS ANGELES – Atrial fibrillation is three times more likely to be detected within 6 months of an ischemic stroke if, instead of the usual 24 or so hours of Holter ECG monitoring, patients are monitored for 10 days poststroke, and then again for 10 days at 3 and 6 months, according to German investigators.

“Enhanced and prolonged monitoring should be considered for all stroke patients to improve the detection of atrial fibrillation,” said investigator Dr. Rolf Wachter, a cardiologist at the University of Göttingen (Germany).

Patients in the trial had no history of atrial fibrillation (AF) and were at least 60 years old; 200 were randomized to the extended-monitoring protocol, and 198 to standard of care, which included a median of 24 hours of Holter monitoring. The median time from symptom onset to randomization was 3 days. All patients were enrolled by day 5.

The study wasn’t limited to cryptogenic strokes; although the first stroke may not have been related to atrial fibrillation, a recurrent stroke could be, so “our approach was to look for AF in all stroke patients irrespective of etiology,” Dr. Wachter said at the International Stroke Conference.

By 6 months, AF was detected in 27 patients (13.5 %) in the extended-monitoring group versus 9 (4.5 %) in the control group (absolute difference, 9%; 95% confidence interval, 3.5%-14.6%; P = .002). The findings were largely the same when results were broken down by age, sex, National Institutes of Health Stroke Scale scores, and other metrics. AF was detected in the majority of both groups within a month.

Dr. Wachter did not elaborate on the frequency and duration of AF, but inclusion criteria required at least one episode lasting 30 seconds or longer.

The work touches on key issues facing neurologists and cardiologists today: How aggressive should post-stroke AF monitoring be, and when should treatment start?

Every AF patient in the study was orally anticoagulated, and almost all remained on their anticoagulant at 1 year. Their oral anticoagulant wasn’t reported, and the study wasn’t powered to detect differences in clinical outcomes. Even so, “we saw very positive trends in the right direction” for prolonged monitoring, he said.

Five patients in the intervention arm (2.5%) had a recurrent stroke and three (1.5%) had transient ischemic events at 1 year, versus nine (4.5%) recurrent strokes and five (2.5%) TIAs in the control arm. Six intervention patients (3%) and nine (4.5%) in the control group, had died.

A total of 60% of the subjects were men, and the mean age in the study was 73 years. The mean NIH Stroke Scale score was 3 in the intervention group and 2 in the control group. The mean CHADS2 (heart failure, hypertension, age, diabetes, stroke) score – a marker of thromboembolic risk – was 3.5 in both. Patients in the extended-monitoring group wore their Holter monitors for a median of 9.5 days at all three time points, but the initial compliance of 100% dropped to about 75% by the third session.

The work was funded by Boehringer Ingelheim, maker of the oral anticoagulant dabigatran (Pradaxa). Dr. Wachter is a speaker and consultant for the company.

[email protected]

LOS ANGELES – Atrial fibrillation is three times more likely to be detected within 6 months of an ischemic stroke if, instead of the usual 24 or so hours of Holter ECG monitoring, patients are monitored for 10 days poststroke, and then again for 10 days at 3 and 6 months, according to German investigators.

“Enhanced and prolonged monitoring should be considered for all stroke patients to improve the detection of atrial fibrillation,” said investigator Dr. Rolf Wachter, a cardiologist at the University of Göttingen (Germany).

Patients in the trial had no history of atrial fibrillation (AF) and were at least 60 years old; 200 were randomized to the extended-monitoring protocol, and 198 to standard of care, which included a median of 24 hours of Holter monitoring. The median time from symptom onset to randomization was 3 days. All patients were enrolled by day 5.

The study wasn’t limited to cryptogenic strokes; although the first stroke may not have been related to atrial fibrillation, a recurrent stroke could be, so “our approach was to look for AF in all stroke patients irrespective of etiology,” Dr. Wachter said at the International Stroke Conference.

By 6 months, AF was detected in 27 patients (13.5 %) in the extended-monitoring group versus 9 (4.5 %) in the control group (absolute difference, 9%; 95% confidence interval, 3.5%-14.6%; P = .002). The findings were largely the same when results were broken down by age, sex, National Institutes of Health Stroke Scale scores, and other metrics. AF was detected in the majority of both groups within a month.

Dr. Wachter did not elaborate on the frequency and duration of AF, but inclusion criteria required at least one episode lasting 30 seconds or longer.

The work touches on key issues facing neurologists and cardiologists today: How aggressive should post-stroke AF monitoring be, and when should treatment start?

Every AF patient in the study was orally anticoagulated, and almost all remained on their anticoagulant at 1 year. Their oral anticoagulant wasn’t reported, and the study wasn’t powered to detect differences in clinical outcomes. Even so, “we saw very positive trends in the right direction” for prolonged monitoring, he said.

Five patients in the intervention arm (2.5%) had a recurrent stroke and three (1.5%) had transient ischemic events at 1 year, versus nine (4.5%) recurrent strokes and five (2.5%) TIAs in the control arm. Six intervention patients (3%) and nine (4.5%) in the control group, had died.

A total of 60% of the subjects were men, and the mean age in the study was 73 years. The mean NIH Stroke Scale score was 3 in the intervention group and 2 in the control group. The mean CHADS2 (heart failure, hypertension, age, diabetes, stroke) score – a marker of thromboembolic risk – was 3.5 in both. Patients in the extended-monitoring group wore their Holter monitors for a median of 9.5 days at all three time points, but the initial compliance of 100% dropped to about 75% by the third session.

The work was funded by Boehringer Ingelheim, maker of the oral anticoagulant dabigatran (Pradaxa). Dr. Wachter is a speaker and consultant for the company.

[email protected]

LOS ANGELES – Atrial fibrillation is three times more likely to be detected within 6 months of an ischemic stroke if, instead of the usual 24 or so hours of Holter ECG monitoring, patients are monitored for 10 days poststroke, and then again for 10 days at 3 and 6 months, according to German investigators.

“Enhanced and prolonged monitoring should be considered for all stroke patients to improve the detection of atrial fibrillation,” said investigator Dr. Rolf Wachter, a cardiologist at the University of Göttingen (Germany).

Patients in the trial had no history of atrial fibrillation (AF) and were at least 60 years old; 200 were randomized to the extended-monitoring protocol, and 198 to standard of care, which included a median of 24 hours of Holter monitoring. The median time from symptom onset to randomization was 3 days. All patients were enrolled by day 5.

The study wasn’t limited to cryptogenic strokes; although the first stroke may not have been related to atrial fibrillation, a recurrent stroke could be, so “our approach was to look for AF in all stroke patients irrespective of etiology,” Dr. Wachter said at the International Stroke Conference.

By 6 months, AF was detected in 27 patients (13.5 %) in the extended-monitoring group versus 9 (4.5 %) in the control group (absolute difference, 9%; 95% confidence interval, 3.5%-14.6%; P = .002). The findings were largely the same when results were broken down by age, sex, National Institutes of Health Stroke Scale scores, and other metrics. AF was detected in the majority of both groups within a month.

Dr. Wachter did not elaborate on the frequency and duration of AF, but inclusion criteria required at least one episode lasting 30 seconds or longer.

The work touches on key issues facing neurologists and cardiologists today: How aggressive should post-stroke AF monitoring be, and when should treatment start?

Every AF patient in the study was orally anticoagulated, and almost all remained on their anticoagulant at 1 year. Their oral anticoagulant wasn’t reported, and the study wasn’t powered to detect differences in clinical outcomes. Even so, “we saw very positive trends in the right direction” for prolonged monitoring, he said.

Five patients in the intervention arm (2.5%) had a recurrent stroke and three (1.5%) had transient ischemic events at 1 year, versus nine (4.5%) recurrent strokes and five (2.5%) TIAs in the control arm. Six intervention patients (3%) and nine (4.5%) in the control group, had died.

A total of 60% of the subjects were men, and the mean age in the study was 73 years. The mean NIH Stroke Scale score was 3 in the intervention group and 2 in the control group. The mean CHADS2 (heart failure, hypertension, age, diabetes, stroke) score – a marker of thromboembolic risk – was 3.5 in both. Patients in the extended-monitoring group wore their Holter monitors for a median of 9.5 days at all three time points, but the initial compliance of 100% dropped to about 75% by the third session.

The work was funded by Boehringer Ingelheim, maker of the oral anticoagulant dabigatran (Pradaxa). Dr. Wachter is a speaker and consultant for the company.

[email protected]

NEW ORLEANS – The long-term safety of interferon beta-1b for the treatment of multiple sclerosis is well established, and 11-year outcomes from the randomized, placebo-controlled BENEFIT trial (BENEFIT 11) provide further support for the existing data.

Eleven years after patients with clinically isolated syndrome were randomized to receive 250 mcg every other day or placebo (with an option at 2 years to switch to active treatment), no new safety signals were found, and the safety profile remained favorable, Dr. Mark S. Freedman of the University of Ottawa and his colleagues reported in a poster at the meeting sponsored by the Americas Committee for Treatment and Research in Multiple Sclerosis.

©Eraxion/thinkstockphotos.com

In the 278 of the 468 patients originally enrolled in BENEFIT who were evaluated at 11 years, 107 (38.5%) reported one or more safety events (total, 278). Interferon beta-1b was used continuously during the 2 years prior to the 11-year evaluation in 82 patients (29.5%), and 28 (34.1%) of those reported an adverse event or medical history event (total, 72 events). Of 196 patients not treated continuously with interferon beta-1b in the 2 years prior to BENEFIT 11, 79 (40.3%) reported an adverse event or medical history event (total, 206 events), the investigators said.

The events reported in BENEFIT 11 were consistent with those seen previously in interferon beta-1b–treated patients; back pain was the most commonly reported musculoskeletal/connective tissue adverse event (reported by 2.4% of patients in the continuous treatment group and 2.6% in the remaining patients, and headache was the most common neurologic adverse event (reported by 1.2% and 2.0% of patients in the groups, respectively).

Neoplasms occurred in 3.7% and 3.6%; most were benign.

“Overall, the safety results from BENEFIT 11 supported the already well-established long-term safety profile of interferon beta-1b,” the investigators wrote.

The higher rates of some events in patients without continuous interferon beta-1b treatment may be due to escalation to second-line therapy in some patients who required agents that may be associated with greater frequency of safety events, they explained.

This study was supported by Bayer. Dr. Freedman has received compensation from Actelion, Bayer, Biogen Idec, Chugai, EMD Canada, Genzyme, Merck Serono, Novartis, Roche Canada, Sanofi-Aventis, and Teva Canada Innovation for consulting services. He also participates in a Genzyme-sponsored speakers bureau.

[email protected]

NEW ORLEANS – The long-term safety of interferon beta-1b for the treatment of multiple sclerosis is well established, and 11-year outcomes from the randomized, placebo-controlled BENEFIT trial (BENEFIT 11) provide further support for the existing data.

Eleven years after patients with clinically isolated syndrome were randomized to receive 250 mcg every other day or placebo (with an option at 2 years to switch to active treatment), no new safety signals were found, and the safety profile remained favorable, Dr. Mark S. Freedman of the University of Ottawa and his colleagues reported in a poster at the meeting sponsored by the Americas Committee for Treatment and Research in Multiple Sclerosis.

©Eraxion/thinkstockphotos.com

In the 278 of the 468 patients originally enrolled in BENEFIT who were evaluated at 11 years, 107 (38.5%) reported one or more safety events (total, 278). Interferon beta-1b was used continuously during the 2 years prior to the 11-year evaluation in 82 patients (29.5%), and 28 (34.1%) of those reported an adverse event or medical history event (total, 72 events). Of 196 patients not treated continuously with interferon beta-1b in the 2 years prior to BENEFIT 11, 79 (40.3%) reported an adverse event or medical history event (total, 206 events), the investigators said.

The events reported in BENEFIT 11 were consistent with those seen previously in interferon beta-1b–treated patients; back pain was the most commonly reported musculoskeletal/connective tissue adverse event (reported by 2.4% of patients in the continuous treatment group and 2.6% in the remaining patients, and headache was the most common neurologic adverse event (reported by 1.2% and 2.0% of patients in the groups, respectively).

Neoplasms occurred in 3.7% and 3.6%; most were benign.

“Overall, the safety results from BENEFIT 11 supported the already well-established long-term safety profile of interferon beta-1b,” the investigators wrote.

The higher rates of some events in patients without continuous interferon beta-1b treatment may be due to escalation to second-line therapy in some patients who required agents that may be associated with greater frequency of safety events, they explained.

This study was supported by Bayer. Dr. Freedman has received compensation from Actelion, Bayer, Biogen Idec, Chugai, EMD Canada, Genzyme, Merck Serono, Novartis, Roche Canada, Sanofi-Aventis, and Teva Canada Innovation for consulting services. He also participates in a Genzyme-sponsored speakers bureau.

[email protected]

NEW ORLEANS – The long-term safety of interferon beta-1b for the treatment of multiple sclerosis is well established, and 11-year outcomes from the randomized, placebo-controlled BENEFIT trial (BENEFIT 11) provide further support for the existing data.

Eleven years after patients with clinically isolated syndrome were randomized to receive 250 mcg every other day or placebo (with an option at 2 years to switch to active treatment), no new safety signals were found, and the safety profile remained favorable, Dr. Mark S. Freedman of the University of Ottawa and his colleagues reported in a poster at the meeting sponsored by the Americas Committee for Treatment and Research in Multiple Sclerosis.

©Eraxion/thinkstockphotos.com

In the 278 of the 468 patients originally enrolled in BENEFIT who were evaluated at 11 years, 107 (38.5%) reported one or more safety events (total, 278). Interferon beta-1b was used continuously during the 2 years prior to the 11-year evaluation in 82 patients (29.5%), and 28 (34.1%) of those reported an adverse event or medical history event (total, 72 events). Of 196 patients not treated continuously with interferon beta-1b in the 2 years prior to BENEFIT 11, 79 (40.3%) reported an adverse event or medical history event (total, 206 events), the investigators said.

The events reported in BENEFIT 11 were consistent with those seen previously in interferon beta-1b–treated patients; back pain was the most commonly reported musculoskeletal/connective tissue adverse event (reported by 2.4% of patients in the continuous treatment group and 2.6% in the remaining patients, and headache was the most common neurologic adverse event (reported by 1.2% and 2.0% of patients in the groups, respectively).

Neoplasms occurred in 3.7% and 3.6%; most were benign.

“Overall, the safety results from BENEFIT 11 supported the already well-established long-term safety profile of interferon beta-1b,” the investigators wrote.

The higher rates of some events in patients without continuous interferon beta-1b treatment may be due to escalation to second-line therapy in some patients who required agents that may be associated with greater frequency of safety events, they explained.

This study was supported by Bayer. Dr. Freedman has received compensation from Actelion, Bayer, Biogen Idec, Chugai, EMD Canada, Genzyme, Merck Serono, Novartis, Roche Canada, Sanofi-Aventis, and Teva Canada Innovation for consulting services. He also participates in a Genzyme-sponsored speakers bureau.

[email protected]

The rate of unintended pregnancies in the United States declined 18% between 2008 and 2011 after a long interval of minimal change, and it is now at the lowest level in 30 years, according to a report published online March 2 in the New England Journal of Medicine.

This “substantial” reduction occurred across all ages, ethnicities, income levels, education levels, and religious affiliations. However, large disparities among demographic groups were still present in 2011, the most recent year for which national data are available for analysis.

©Thinkstock Images

“In particular, poor, black, and Hispanic women and girls continued to have much higher rates of unintended pregnancy than did whites and those with higher incomes. Much more progress can be made in eliminating these disparities,” wrote Lawrence B. Finer, Ph.D., and Mia R. Zolna of the Guttmacher Institute, New York.

National rates of unintended pregnancies haven’t been examined since 2008. To update these figures, the investigators analyzed information from the National Center for Health Statistics, the National Survey of Family Growth, and others.

They calculated that there were 6.1 million pregnancies in the United States in 2011, of which 45% (2.8 million) were unintended. The rate was 45 unintended pregnancies for every 1,000 women of childbearing age in 2011, compared with 54/1,000 in 2008, which corresponds to an 18% decline (N Engl J Med.2016;374:843-52. doi: 10.1056/NEJMsa1506575).

“This was the first substantial decline since at least 1981,” the investigators wrote.

Abortion rates remained steady during the study period. In 2011, the percentage of unintended pregnancies that ended in abortion was 42%, compared with 40% in 2008.

Although the study was not designed to determine the reasons for the decline, several possible factors deserve consideration, according to the investigators. Changes in sexual behavior are unlikely to have driven this reduction, since the incidence of sexual activity tends to remain static over time; changes in the composition of the population also aren’t likely causes, since the demographic subgroups who have higher rates of unintended pregnancy actually increased during this period, the investigators said.

Changes in the desire for pregnancy may have contributed a small amount to the decline, as surveys showed that many women said they would reduce or delay their childbearing during the recent economic recession.

The most likely explanation for the decline, the investigators wrote, is a change in the frequency and type of contraceptive use. Several studies have reported that women at high risk of unintended pregnancy increased both their use of any contraception and their use of highly effective long-acting methods, particularly IUDs.

This study was supported chiefly by the Susan Thompson Buffet Foundation, with additional support from the Guttmacher Center through a grant from the National Institutes of Health. The investigators reported having no other relevant financial disclosures.

The rate of unintended pregnancies in the United States declined 18% between 2008 and 2011 after a long interval of minimal change, and it is now at the lowest level in 30 years, according to a report published online March 2 in the New England Journal of Medicine.

This “substantial” reduction occurred across all ages, ethnicities, income levels, education levels, and religious affiliations. However, large disparities among demographic groups were still present in 2011, the most recent year for which national data are available for analysis.

©Thinkstock Images

“In particular, poor, black, and Hispanic women and girls continued to have much higher rates of unintended pregnancy than did whites and those with higher incomes. Much more progress can be made in eliminating these disparities,” wrote Lawrence B. Finer, Ph.D., and Mia R. Zolna of the Guttmacher Institute, New York.

National rates of unintended pregnancies haven’t been examined since 2008. To update these figures, the investigators analyzed information from the National Center for Health Statistics, the National Survey of Family Growth, and others.

They calculated that there were 6.1 million pregnancies in the United States in 2011, of which 45% (2.8 million) were unintended. The rate was 45 unintended pregnancies for every 1,000 women of childbearing age in 2011, compared with 54/1,000 in 2008, which corresponds to an 18% decline (N Engl J Med.2016;374:843-52. doi: 10.1056/NEJMsa1506575).

“This was the first substantial decline since at least 1981,” the investigators wrote.

Abortion rates remained steady during the study period. In 2011, the percentage of unintended pregnancies that ended in abortion was 42%, compared with 40% in 2008.

Although the study was not designed to determine the reasons for the decline, several possible factors deserve consideration, according to the investigators. Changes in sexual behavior are unlikely to have driven this reduction, since the incidence of sexual activity tends to remain static over time; changes in the composition of the population also aren’t likely causes, since the demographic subgroups who have higher rates of unintended pregnancy actually increased during this period, the investigators said.

Changes in the desire for pregnancy may have contributed a small amount to the decline, as surveys showed that many women said they would reduce or delay their childbearing during the recent economic recession.

The most likely explanation for the decline, the investigators wrote, is a change in the frequency and type of contraceptive use. Several studies have reported that women at high risk of unintended pregnancy increased both their use of any contraception and their use of highly effective long-acting methods, particularly IUDs.

This study was supported chiefly by the Susan Thompson Buffet Foundation, with additional support from the Guttmacher Center through a grant from the National Institutes of Health. The investigators reported having no other relevant financial disclosures.

The rate of unintended pregnancies in the United States declined 18% between 2008 and 2011 after a long interval of minimal change, and it is now at the lowest level in 30 years, according to a report published online March 2 in the New England Journal of Medicine.

This “substantial” reduction occurred across all ages, ethnicities, income levels, education levels, and religious affiliations. However, large disparities among demographic groups were still present in 2011, the most recent year for which national data are available for analysis.

©Thinkstock Images

“In particular, poor, black, and Hispanic women and girls continued to have much higher rates of unintended pregnancy than did whites and those with higher incomes. Much more progress can be made in eliminating these disparities,” wrote Lawrence B. Finer, Ph.D., and Mia R. Zolna of the Guttmacher Institute, New York.

National rates of unintended pregnancies haven’t been examined since 2008. To update these figures, the investigators analyzed information from the National Center for Health Statistics, the National Survey of Family Growth, and others.

They calculated that there were 6.1 million pregnancies in the United States in 2011, of which 45% (2.8 million) were unintended. The rate was 45 unintended pregnancies for every 1,000 women of childbearing age in 2011, compared with 54/1,000 in 2008, which corresponds to an 18% decline (N Engl J Med.2016;374:843-52. doi: 10.1056/NEJMsa1506575).

“This was the first substantial decline since at least 1981,” the investigators wrote.

Abortion rates remained steady during the study period. In 2011, the percentage of unintended pregnancies that ended in abortion was 42%, compared with 40% in 2008.

Although the study was not designed to determine the reasons for the decline, several possible factors deserve consideration, according to the investigators. Changes in sexual behavior are unlikely to have driven this reduction, since the incidence of sexual activity tends to remain static over time; changes in the composition of the population also aren’t likely causes, since the demographic subgroups who have higher rates of unintended pregnancy actually increased during this period, the investigators said.

Changes in the desire for pregnancy may have contributed a small amount to the decline, as surveys showed that many women said they would reduce or delay their childbearing during the recent economic recession.

The most likely explanation for the decline, the investigators wrote, is a change in the frequency and type of contraceptive use. Several studies have reported that women at high risk of unintended pregnancy increased both their use of any contraception and their use of highly effective long-acting methods, particularly IUDs.

This study was supported chiefly by the Susan Thompson Buffet Foundation, with additional support from the Guttmacher Center through a grant from the National Institutes of Health. The investigators reported having no other relevant financial disclosures.

Progression-free survival was significantly better when patients with relapsed or refractory mantle-cell lymphoma were treated with oral ibrutinib than with intravenous temsirolimus, based on results from 280 patients in an international, randomized, open-label phase III trial.

Study subjects had undergone one or more previous rituximab-containing chemotherapy regimens to receive intravenous temsirolimus or oral ibrutinib at a daily dose of 560 mg.

Compared with temsirolimus, ibrutinib resulted in a 57% reduction in the risk of disease progression or death at a median follow-up of 20 months. Median progression-free survival – the trial’s primary endpoint – was 14.6 months for the ibrutinib group and 6.2 months for the temsirolimus group.

Ibrutinib was also better tolerated, with 68% of patients having grade 3 or higher treatment-emergent adverse events as compared to 87% of patients in the temsirolimus group, despite a median 4-fold longer treatment duration for the ibrutinib group than the temsirolimus group. Additionally, 6% of patients discontinued ibrutinib because of adverse events versus 26% in the temsirolimus group, reported Dr. Martin Dreyling of Klinikum der Universität in Munich, Germany, and his associates.

Courtesy Wikimedia Commons/Nephron/Creative Commons

Based on results of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) questionnaire, ibrutinib was associated with greater and more rapid improvements, and also with less worsening in lymphoma symptoms, as measured by the lymphoma subscale of the FACT-Lym (Lancet. 2016;387:770-78).

Ibrutinib, a first-in-class oral inhibitor of Bruton’s tyrosine kinase, is approved in the United States and the European Union at a dose of 560 mg per day for patients with mantle cell lymphoma who have received at least one previous line of therapy.

The mammalian target of rapamycin (mTOR) inhibitor temsirolimus is approved in the European Union for relapsed or refractory mantle-cell lymphoma, but does not have FDA approval for this indication.

The study, funded by Janssen, is ongoing. Future research, the investigators say, should examine ibrutinib-based combination approaches for patients with relapsed or refractory mantle-cell lymphoma and in front-line therapy.

Dr. Dreyling reported grants and personal fees from Janssen and Pfizer outside of the study. Several other authors reported grants from Janssen during the study and financial ties to the company.

Progression-free survival was significantly better when patients with relapsed or refractory mantle-cell lymphoma were treated with oral ibrutinib than with intravenous temsirolimus, based on results from 280 patients in an international, randomized, open-label phase III trial.

Study subjects had undergone one or more previous rituximab-containing chemotherapy regimens to receive intravenous temsirolimus or oral ibrutinib at a daily dose of 560 mg.

Compared with temsirolimus, ibrutinib resulted in a 57% reduction in the risk of disease progression or death at a median follow-up of 20 months. Median progression-free survival – the trial’s primary endpoint – was 14.6 months for the ibrutinib group and 6.2 months for the temsirolimus group.

Ibrutinib was also better tolerated, with 68% of patients having grade 3 or higher treatment-emergent adverse events as compared to 87% of patients in the temsirolimus group, despite a median 4-fold longer treatment duration for the ibrutinib group than the temsirolimus group. Additionally, 6% of patients discontinued ibrutinib because of adverse events versus 26% in the temsirolimus group, reported Dr. Martin Dreyling of Klinikum der Universität in Munich, Germany, and his associates.

Courtesy Wikimedia Commons/Nephron/Creative Commons

Based on results of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) questionnaire, ibrutinib was associated with greater and more rapid improvements, and also with less worsening in lymphoma symptoms, as measured by the lymphoma subscale of the FACT-Lym (Lancet. 2016;387:770-78).

Ibrutinib, a first-in-class oral inhibitor of Bruton’s tyrosine kinase, is approved in the United States and the European Union at a dose of 560 mg per day for patients with mantle cell lymphoma who have received at least one previous line of therapy.

The mammalian target of rapamycin (mTOR) inhibitor temsirolimus is approved in the European Union for relapsed or refractory mantle-cell lymphoma, but does not have FDA approval for this indication.

The study, funded by Janssen, is ongoing. Future research, the investigators say, should examine ibrutinib-based combination approaches for patients with relapsed or refractory mantle-cell lymphoma and in front-line therapy.

Dr. Dreyling reported grants and personal fees from Janssen and Pfizer outside of the study. Several other authors reported grants from Janssen during the study and financial ties to the company.

Progression-free survival was significantly better when patients with relapsed or refractory mantle-cell lymphoma were treated with oral ibrutinib than with intravenous temsirolimus, based on results from 280 patients in an international, randomized, open-label phase III trial.

Study subjects had undergone one or more previous rituximab-containing chemotherapy regimens to receive intravenous temsirolimus or oral ibrutinib at a daily dose of 560 mg.

Compared with temsirolimus, ibrutinib resulted in a 57% reduction in the risk of disease progression or death at a median follow-up of 20 months. Median progression-free survival – the trial’s primary endpoint – was 14.6 months for the ibrutinib group and 6.2 months for the temsirolimus group.

Ibrutinib was also better tolerated, with 68% of patients having grade 3 or higher treatment-emergent adverse events as compared to 87% of patients in the temsirolimus group, despite a median 4-fold longer treatment duration for the ibrutinib group than the temsirolimus group. Additionally, 6% of patients discontinued ibrutinib because of adverse events versus 26% in the temsirolimus group, reported Dr. Martin Dreyling of Klinikum der Universität in Munich, Germany, and his associates.

Courtesy Wikimedia Commons/Nephron/Creative Commons

Based on results of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) questionnaire, ibrutinib was associated with greater and more rapid improvements, and also with less worsening in lymphoma symptoms, as measured by the lymphoma subscale of the FACT-Lym (Lancet. 2016;387:770-78).

Ibrutinib, a first-in-class oral inhibitor of Bruton’s tyrosine kinase, is approved in the United States and the European Union at a dose of 560 mg per day for patients with mantle cell lymphoma who have received at least one previous line of therapy.

The mammalian target of rapamycin (mTOR) inhibitor temsirolimus is approved in the European Union for relapsed or refractory mantle-cell lymphoma, but does not have FDA approval for this indication.

The study, funded by Janssen, is ongoing. Future research, the investigators say, should examine ibrutinib-based combination approaches for patients with relapsed or refractory mantle-cell lymphoma and in front-line therapy.

Dr. Dreyling reported grants and personal fees from Janssen and Pfizer outside of the study. Several other authors reported grants from Janssen during the study and financial ties to the company.

Emotionally abused children are 52% more likely to develop migraine in young adulthood than are those who were never abused, based on longitudinal survey data from nearly 15,000 individuals.

“Childhood maltreatment, and especially emotional abuse, is a common, likely under-recognized occurrence, which has enduring consequences for health throughout life. The association of emotional abuse with migraine has not heretofore been well studied, being the subject of only population-based study,” lead author Dr. Gretchen E. Tietjen of the University of Toledo (Ohio) said in an interview in advance of the presentation of the study at the annual meeting of the American Academy of Neurology in Vancouver in April.

Dr. Tietjen and her colleagues assessed data from 14,484 adults aged 24-32 years who took part in wave four of the National Longitudinal Study of Adolescent to Adult Health. Of these, 2,061 (14%) reported a migraine diagnosis, and 1,246 (60%) of those diagnosed with migraines reported some type of childhood abuse. A total of 6,088 (49%) individuals without migraine reported some type of childhood abuse.

Overall, the odds of migraine in adulthood was 55% higher in children who reported emotional abuse, physical abuse, or sexual abuse, compared with those who reported no childhood abuse, after controlling for age, race, sex, and income (odds ratio, 1.55; 95% confidence interval, 1.35-1.77). However, only emotional abuse remained significantly associated with increased odds for migraine after controlling for other types of abuse (OR, 1.52; 95% CI, 1.34-1.73).

Emotional abuse was assessed by asking, “How often did a parent or other adult caregiver say things that really hurt your feelings or made you feel like you were not wanted or loved?” Physical abuse was defined as being hit with a fist, kicked, or thrown down on the floor, into a wall, or down stairs. Sexual abuse included forced sexual touching or sexual relations.

Controlling for depression and anxiety weakened the associations between childhood abuse overall and likelihood of migraine in young adulthood, as well as for emotional abuse in particular, but the relationships remained statistically significant (OR, 1.32 and 1.33, respectively).

Dr. Tietjen said she was surprised by the absence of an association between migraine and physical and sexual abuse after controlling for other types of abuse.

“Sexual and physical abuse may be less frequent, occur over a briefer duration, and if limited, lead in some cases to resilience,” Dr. Tietjen noted. “Emotional abuse is likely more insidious, being ingrained in the fabric of the family dynamic. It may occur over years without recognition or intervention,” she said. “This type of abuse may cause more cumulative stress, with subsequent dysregulation of the HPA axis, immune, autonomic, and metabolic systems,” she added. 

The study does not show cause and effect, the researchers noted, and more research is needed. But the findings suggest that clinicians might consider childhood abuse when counseling adult migraine patients.

“In migraineurs, childhood abuse, particularly emotional abuse, is common and possibly causally related,” Dr. Tietjen said. “Knowledge of adverse childhood experiences allows physicians to identify migraineurs at higher risk for psychiatric disease, pain comorbidities, and conditions associated with inflammation. These patients would likely benefit from exposure to cognitive behavioral therapy strategies, in order to decrease neurophysiological responses to stress,” she noted.

“There are currently therapies which reverse stress-induced epigenetic changes, which might be particularly useful in the subset of migraineurs who have been abused,” said Dr. Tietjen. Her next steps for research involve studying the effect of early life stress on factors such as pain sensitivity, anxiety, and depression.

The University of Toledo and the Clair Martig Endowment funded the study.

Emotionally abused children are 52% more likely to develop migraine in young adulthood than are those who were never abused, based on longitudinal survey data from nearly 15,000 individuals.

“Childhood maltreatment, and especially emotional abuse, is a common, likely under-recognized occurrence, which has enduring consequences for health throughout life. The association of emotional abuse with migraine has not heretofore been well studied, being the subject of only population-based study,” lead author Dr. Gretchen E. Tietjen of the University of Toledo (Ohio) said in an interview in advance of the presentation of the study at the annual meeting of the American Academy of Neurology in Vancouver in April.

Dr. Tietjen and her colleagues assessed data from 14,484 adults aged 24-32 years who took part in wave four of the National Longitudinal Study of Adolescent to Adult Health. Of these, 2,061 (14%) reported a migraine diagnosis, and 1,246 (60%) of those diagnosed with migraines reported some type of childhood abuse. A total of 6,088 (49%) individuals without migraine reported some type of childhood abuse.

Overall, the odds of migraine in adulthood was 55% higher in children who reported emotional abuse, physical abuse, or sexual abuse, compared with those who reported no childhood abuse, after controlling for age, race, sex, and income (odds ratio, 1.55; 95% confidence interval, 1.35-1.77). However, only emotional abuse remained significantly associated with increased odds for migraine after controlling for other types of abuse (OR, 1.52; 95% CI, 1.34-1.73).

Emotional abuse was assessed by asking, “How often did a parent or other adult caregiver say things that really hurt your feelings or made you feel like you were not wanted or loved?” Physical abuse was defined as being hit with a fist, kicked, or thrown down on the floor, into a wall, or down stairs. Sexual abuse included forced sexual touching or sexual relations.

Controlling for depression and anxiety weakened the associations between childhood abuse overall and likelihood of migraine in young adulthood, as well as for emotional abuse in particular, but the relationships remained statistically significant (OR, 1.32 and 1.33, respectively).

Dr. Tietjen said she was surprised by the absence of an association between migraine and physical and sexual abuse after controlling for other types of abuse.

“Sexual and physical abuse may be less frequent, occur over a briefer duration, and if limited, lead in some cases to resilience,” Dr. Tietjen noted. “Emotional abuse is likely more insidious, being ingrained in the fabric of the family dynamic. It may occur over years without recognition or intervention,” she said. “This type of abuse may cause more cumulative stress, with subsequent dysregulation of the HPA axis, immune, autonomic, and metabolic systems,” she added. 

The study does not show cause and effect, the researchers noted, and more research is needed. But the findings suggest that clinicians might consider childhood abuse when counseling adult migraine patients.

“In migraineurs, childhood abuse, particularly emotional abuse, is common and possibly causally related,” Dr. Tietjen said. “Knowledge of adverse childhood experiences allows physicians to identify migraineurs at higher risk for psychiatric disease, pain comorbidities, and conditions associated with inflammation. These patients would likely benefit from exposure to cognitive behavioral therapy strategies, in order to decrease neurophysiological responses to stress,” she noted.

“There are currently therapies which reverse stress-induced epigenetic changes, which might be particularly useful in the subset of migraineurs who have been abused,” said Dr. Tietjen. Her next steps for research involve studying the effect of early life stress on factors such as pain sensitivity, anxiety, and depression.

The University of Toledo and the Clair Martig Endowment funded the study.

Emotionally abused children are 52% more likely to develop migraine in young adulthood than are those who were never abused, based on longitudinal survey data from nearly 15,000 individuals.

“Childhood maltreatment, and especially emotional abuse, is a common, likely under-recognized occurrence, which has enduring consequences for health throughout life. The association of emotional abuse with migraine has not heretofore been well studied, being the subject of only population-based study,” lead author Dr. Gretchen E. Tietjen of the University of Toledo (Ohio) said in an interview in advance of the presentation of the study at the annual meeting of the American Academy of Neurology in Vancouver in April.

Dr. Tietjen and her colleagues assessed data from 14,484 adults aged 24-32 years who took part in wave four of the National Longitudinal Study of Adolescent to Adult Health. Of these, 2,061 (14%) reported a migraine diagnosis, and 1,246 (60%) of those diagnosed with migraines reported some type of childhood abuse. A total of 6,088 (49%) individuals without migraine reported some type of childhood abuse.

Overall, the odds of migraine in adulthood was 55% higher in children who reported emotional abuse, physical abuse, or sexual abuse, compared with those who reported no childhood abuse, after controlling for age, race, sex, and income (odds ratio, 1.55; 95% confidence interval, 1.35-1.77). However, only emotional abuse remained significantly associated with increased odds for migraine after controlling for other types of abuse (OR, 1.52; 95% CI, 1.34-1.73).

Emotional abuse was assessed by asking, “How often did a parent or other adult caregiver say things that really hurt your feelings or made you feel like you were not wanted or loved?” Physical abuse was defined as being hit with a fist, kicked, or thrown down on the floor, into a wall, or down stairs. Sexual abuse included forced sexual touching or sexual relations.

Controlling for depression and anxiety weakened the associations between childhood abuse overall and likelihood of migraine in young adulthood, as well as for emotional abuse in particular, but the relationships remained statistically significant (OR, 1.32 and 1.33, respectively).

Dr. Tietjen said she was surprised by the absence of an association between migraine and physical and sexual abuse after controlling for other types of abuse.

“Sexual and physical abuse may be less frequent, occur over a briefer duration, and if limited, lead in some cases to resilience,” Dr. Tietjen noted. “Emotional abuse is likely more insidious, being ingrained in the fabric of the family dynamic. It may occur over years without recognition or intervention,” she said. “This type of abuse may cause more cumulative stress, with subsequent dysregulation of the HPA axis, immune, autonomic, and metabolic systems,” she added. 

The study does not show cause and effect, the researchers noted, and more research is needed. But the findings suggest that clinicians might consider childhood abuse when counseling adult migraine patients.

“In migraineurs, childhood abuse, particularly emotional abuse, is common and possibly causally related,” Dr. Tietjen said. “Knowledge of adverse childhood experiences allows physicians to identify migraineurs at higher risk for psychiatric disease, pain comorbidities, and conditions associated with inflammation. These patients would likely benefit from exposure to cognitive behavioral therapy strategies, in order to decrease neurophysiological responses to stress,” she noted.

“There are currently therapies which reverse stress-induced epigenetic changes, which might be particularly useful in the subset of migraineurs who have been abused,” said Dr. Tietjen. Her next steps for research involve studying the effect of early life stress on factors such as pain sensitivity, anxiety, and depression.

The University of Toledo and the Clair Martig Endowment funded the study.

The results of the highly anticipated Antenatal Late Preterm Study recently have become available.¹ Data from this randomized controlled trial, conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network, demonstrated that administration of betamethasone to women at risk for preterm delivery between 34 weeks 0 days and 36 weeks 6 days of gestation significantly reduces the rate of neonatal respiratory complications. It may represent the largest study of antenatal corticosteroids (ACS) to date, with 2,827 infants studied, and its results inevitably lead to the logical practical question: Should ACS use be extended beyond the 34 weeks’ gestation limit previously recommended by professional guidelines in the United States²?

There are some issues that bear discussion before such a significant change in standard of care should be promoted.²

Antenatal Late Preterm Study outcomesThe primary outcome in the study was a composite end point describing the need for respiratory support within 72 hours after birth. Based on a pilot study, the investigators had anticipated a 33% decrease in the rate of the primary outcome; however, the reduction was only 20% (relative risk [RR], 0.80; 95% confidence interval [CI], 0.66−0.97). Although the effect size was statistically significant, one could question the clinical relevance of such a small difference.

A 33% reduction effect, more consistent with the preliminary expectations, was noted in the prespecified secondary composite outcome of severe respiratory complications (RR, 0.67; 95% CI, 0.53−0.84). Occurrences included in the secondary composite outcome that also showed significant rate reductions were:

The reported reduction in bronchopulmonary dysplasia (RR, 0.22; 95% CI, 0.02−0.92) cannot plausibly be attributed to ACS. Randomized data aggregated by the Cochrane Database of Systematic Reviews³ do not show improvement in chronic lung disease with ACS use. Moreover, the authors recognize that the assessment for bronchopulmonary dysplasia at only 28 days of life is only partially informative and that longer childhood follow-up is required to confirm the finding.

We recommend caution before changing current practiceWe propose prudence with ACS use after 34 weeks’ gestation for the following reasons: the increased risk for neonatal hypoglycemia associated with ACS, the increased risk for ACS-related harm in term-born babies, and safety concerns with ACS in the late preterm period.

Evidence shows an increased risk for neonatal hypoglycemiaThe most profound effect modification observed in the study was an adverse effect—namely, a 60% increase in neonatal hypoglycemia with ACS administration (RR, 1.6; 95% CI, 1.37−1.87). The rate of neonatal hypoglycemia was 24% in the ACS group, compared with 15% in the placebo group.

Results of prior studies have demonstrated either no increased risk of hypoglycemia with ACS use⁴⁻⁷ or a much smaller increase (from 4.2% to 5.7%).⁸ The higher rate of neonatal hypoglycemia seen in this study suggests the possibility that the late preterm population may be more vulnerable to the negative impact of ACS on neonatal glucose/insulin homeostasis. Presumed mechanisms of action are either maternal hyperglycemia or fetal adrenal suppression or both, with potential for fetal adrenal suppression resulting from betamethasone exposure to affect long-term metabolic outcomes.⁹

Of note, women with pregestational diabetes were excluded from the study and, in routine practice, inclusion of such patients may further increase the risk of neonatal hypoglycemia.

There are few data on the prognostic significance of neonatal hypoglycemia in preterm infants, with the exception of a single study, the results of which show that it is associated with adverse neurodevelopment at 18 months of age.¹⁰

Data reveal increased risk for harm in term-born babiesIn spite of strict protocol specifications to increase the probability of delivery before 37 weeks’ gestation, 16% of women in the trial delivered at term. Investigators of prior randomized studies of ACS, aimed at reducing the risks of prematurity, have reported a rate of term delivery of about one-third,^4,11 and in routine practice, administration of ACS after 34 weeks may be associated with even higher rates of term delivery.

This is important because recent evidence shows an unfavorable impact of ACS exposure in term-born children.¹² The 5-year follow-up of the largest randomized trial in which multiple ACS courses were used noted that babies born at term had a 4-fold increased odds ratio for neurosensory disability.¹¹ There was no dose−response interaction, with the same adverse odds ratio after 1 or 4 additional ACS courses. This observation was consistent with a previously reported Swedish national cohort, pointing to an unfavorable impact of even a single course of ACS in term-born children, with a greater likelihood of harm than benefit.¹³

In a UK follow-up of children aged 8 to 15 years who were enrolled in an RCT of ACS before cesarean delivery at term, low academic achievement was significantly more common in the group whose mothers had received ACS.¹⁴ In another study of 304 children born at term after exposure to a single course of ACS, investigators noted significantly increased cortisol reactivity to acute psychological stress at ages 6 to 11 years in the ACS-exposed patients, compared with 212 babies of women with threatened preterm labor who did not receive ACS and 372 babies from uncomplicated term pregnancies.¹⁵

The relevance of such study findings extends beyond childhood given the fact that elevated hypothalamic-pituitary-adrenal (HPA) axis reactivity has been linked to the pathogenesis of metabolic syndrome and depression in adult life.¹⁶ As recently as 2015, investigators of a randomized trial of ACS in 6 low- and middle-income countries highlighted their concern regarding “potentially harmful use of antenatal corticosteroids for infants not delivered preterm.”¹⁷

There are safety concerns with ACS in the late preterm periodThe effects of ACS are more pleiotropic than those reflected in a lower incidence of respiratory difficulties. Knowledge of the overall consequences of ACS exposure in infants born late-preterm or at term is still limited. The close-to-term fetus exposed to exogenous corticosteroids is also exposed to the physiologic endogenous surge of cortisol known to occur in the maternal circulation in late pregnancy, which reaches levels 3 times higher than those seen in nonpregnant women.¹⁸ Although placental 11 beta-hydroxysteroid dehydrogenase type 2 plays a protective role by allowing no more than 10% to 20% of maternal corticosteroids to cross the placenta, fetal overexposure from concomitant exogenous maternal corticosteroid administration remains a theoretical concern close to term. This is especially worrisome if there is a gestational age−related increase in the sensitivity to corticosteroid-induced in utero fetal programming. It has been reported that fetal overexposure to corticosteroids in late pregnancy can permanently increase the activity of the HPA-axis, with likely consequences in adult life.¹⁹

Another concern relates to oligodendrocytes development. Although the neuronal division process in humans usually is completed by 24 weeks’ gestation, the most rapid growth for oligodendrocytes occurs between 34 and 36 weeks’ gestation; these are the cells responsible for the synthesis of myelin. Overexposure to corticosteroids at this vulnerable time in the late preterm fetus potentially may have unanticipated negative neurologic consequences.²⁰

Where should future studies focus?There is clear neonatal benefit from a single course of ACS given to women who will deliver before 34 weeks’ gestation. It is widely accepted, based on the evidence provided by the 30-year follow-up of the cohort of 534 participants from the Auckland trial (the longest follow-up for any pregnancy trial), that administration of ACS at less than 34 weeks’ gestation is not associated with any obvious major developmental risk.²¹⁻²³

However, the reassurances provided by the Auckland cohort should be neither directly extrapolated to the administration of ACS in the late preterm period nor applied to term-born babies exposed to ACS, for the simple reason that these subgroups never have been analyzed separately. The risk:benefit ratio of ACS use in the late-preterm period is as yet unknown, and in term-born babies the ratio may be unfavorable.

Follow-up studies are neededWe consider that there is a vital need for long-term follow-up studies. The focus of research on the effects of ACS no longer is on the immediate neonatal outcomes and now is on safety and the long-term outcomes of this exposure.

Bottom lineWe regard the large, high-quality study conducted by the NICHD MFMU Network¹ as an opportunity to answer current concerns. It is hoped that the resources necessaryfor in-depth follow-up of the children involved in this study will be provided to the investigators and to the NICHD. It is only with such follow-up that mid- and long-term adverse effects can be assessed. We believe that, at a minimum, mid-term follow-up data should be available before it is wise to make any definitive recommendations for a sweeping change in clinical practice.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The results of the highly anticipated Antenatal Late Preterm Study recently have become available.¹ Data from this randomized controlled trial, conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network, demonstrated that administration of betamethasone to women at risk for preterm delivery between 34 weeks 0 days and 36 weeks 6 days of gestation significantly reduces the rate of neonatal respiratory complications. It may represent the largest study of antenatal corticosteroids (ACS) to date, with 2,827 infants studied, and its results inevitably lead to the logical practical question: Should ACS use be extended beyond the 34 weeks’ gestation limit previously recommended by professional guidelines in the United States²?

There are some issues that bear discussion before such a significant change in standard of care should be promoted.²

Antenatal Late Preterm Study outcomesThe primary outcome in the study was a composite end point describing the need for respiratory support within 72 hours after birth. Based on a pilot study, the investigators had anticipated a 33% decrease in the rate of the primary outcome; however, the reduction was only 20% (relative risk [RR], 0.80; 95% confidence interval [CI], 0.66−0.97). Although the effect size was statistically significant, one could question the clinical relevance of such a small difference.

A 33% reduction effect, more consistent with the preliminary expectations, was noted in the prespecified secondary composite outcome of severe respiratory complications (RR, 0.67; 95% CI, 0.53−0.84). Occurrences included in the secondary composite outcome that also showed significant rate reductions were:

The reported reduction in bronchopulmonary dysplasia (RR, 0.22; 95% CI, 0.02−0.92) cannot plausibly be attributed to ACS. Randomized data aggregated by the Cochrane Database of Systematic Reviews³ do not show improvement in chronic lung disease with ACS use. Moreover, the authors recognize that the assessment for bronchopulmonary dysplasia at only 28 days of life is only partially informative and that longer childhood follow-up is required to confirm the finding.

We recommend caution before changing current practiceWe propose prudence with ACS use after 34 weeks’ gestation for the following reasons: the increased risk for neonatal hypoglycemia associated with ACS, the increased risk for ACS-related harm in term-born babies, and safety concerns with ACS in the late preterm period.

Evidence shows an increased risk for neonatal hypoglycemiaThe most profound effect modification observed in the study was an adverse effect—namely, a 60% increase in neonatal hypoglycemia with ACS administration (RR, 1.6; 95% CI, 1.37−1.87). The rate of neonatal hypoglycemia was 24% in the ACS group, compared with 15% in the placebo group.

Results of prior studies have demonstrated either no increased risk of hypoglycemia with ACS use⁴⁻⁷ or a much smaller increase (from 4.2% to 5.7%).⁸ The higher rate of neonatal hypoglycemia seen in this study suggests the possibility that the late preterm population may be more vulnerable to the negative impact of ACS on neonatal glucose/insulin homeostasis. Presumed mechanisms of action are either maternal hyperglycemia or fetal adrenal suppression or both, with potential for fetal adrenal suppression resulting from betamethasone exposure to affect long-term metabolic outcomes.⁹

Of note, women with pregestational diabetes were excluded from the study and, in routine practice, inclusion of such patients may further increase the risk of neonatal hypoglycemia.

There are few data on the prognostic significance of neonatal hypoglycemia in preterm infants, with the exception of a single study, the results of which show that it is associated with adverse neurodevelopment at 18 months of age.¹⁰

Data reveal increased risk for harm in term-born babiesIn spite of strict protocol specifications to increase the probability of delivery before 37 weeks’ gestation, 16% of women in the trial delivered at term. Investigators of prior randomized studies of ACS, aimed at reducing the risks of prematurity, have reported a rate of term delivery of about one-third,^4,11 and in routine practice, administration of ACS after 34 weeks may be associated with even higher rates of term delivery.

This is important because recent evidence shows an unfavorable impact of ACS exposure in term-born children.¹² The 5-year follow-up of the largest randomized trial in which multiple ACS courses were used noted that babies born at term had a 4-fold increased odds ratio for neurosensory disability.¹¹ There was no dose−response interaction, with the same adverse odds ratio after 1 or 4 additional ACS courses. This observation was consistent with a previously reported Swedish national cohort, pointing to an unfavorable impact of even a single course of ACS in term-born children, with a greater likelihood of harm than benefit.¹³

In a UK follow-up of children aged 8 to 15 years who were enrolled in an RCT of ACS before cesarean delivery at term, low academic achievement was significantly more common in the group whose mothers had received ACS.¹⁴ In another study of 304 children born at term after exposure to a single course of ACS, investigators noted significantly increased cortisol reactivity to acute psychological stress at ages 6 to 11 years in the ACS-exposed patients, compared with 212 babies of women with threatened preterm labor who did not receive ACS and 372 babies from uncomplicated term pregnancies.¹⁵

The relevance of such study findings extends beyond childhood given the fact that elevated hypothalamic-pituitary-adrenal (HPA) axis reactivity has been linked to the pathogenesis of metabolic syndrome and depression in adult life.¹⁶ As recently as 2015, investigators of a randomized trial of ACS in 6 low- and middle-income countries highlighted their concern regarding “potentially harmful use of antenatal corticosteroids for infants not delivered preterm.”¹⁷

There are safety concerns with ACS in the late preterm periodThe effects of ACS are more pleiotropic than those reflected in a lower incidence of respiratory difficulties. Knowledge of the overall consequences of ACS exposure in infants born late-preterm or at term is still limited. The close-to-term fetus exposed to exogenous corticosteroids is also exposed to the physiologic endogenous surge of cortisol known to occur in the maternal circulation in late pregnancy, which reaches levels 3 times higher than those seen in nonpregnant women.¹⁸ Although placental 11 beta-hydroxysteroid dehydrogenase type 2 plays a protective role by allowing no more than 10% to 20% of maternal corticosteroids to cross the placenta, fetal overexposure from concomitant exogenous maternal corticosteroid administration remains a theoretical concern close to term. This is especially worrisome if there is a gestational age−related increase in the sensitivity to corticosteroid-induced in utero fetal programming. It has been reported that fetal overexposure to corticosteroids in late pregnancy can permanently increase the activity of the HPA-axis, with likely consequences in adult life.¹⁹

Another concern relates to oligodendrocytes development. Although the neuronal division process in humans usually is completed by 24 weeks’ gestation, the most rapid growth for oligodendrocytes occurs between 34 and 36 weeks’ gestation; these are the cells responsible for the synthesis of myelin. Overexposure to corticosteroids at this vulnerable time in the late preterm fetus potentially may have unanticipated negative neurologic consequences.²⁰

Where should future studies focus?There is clear neonatal benefit from a single course of ACS given to women who will deliver before 34 weeks’ gestation. It is widely accepted, based on the evidence provided by the 30-year follow-up of the cohort of 534 participants from the Auckland trial (the longest follow-up for any pregnancy trial), that administration of ACS at less than 34 weeks’ gestation is not associated with any obvious major developmental risk.²¹⁻²³

However, the reassurances provided by the Auckland cohort should be neither directly extrapolated to the administration of ACS in the late preterm period nor applied to term-born babies exposed to ACS, for the simple reason that these subgroups never have been analyzed separately. The risk:benefit ratio of ACS use in the late-preterm period is as yet unknown, and in term-born babies the ratio may be unfavorable.

Follow-up studies are neededWe consider that there is a vital need for long-term follow-up studies. The focus of research on the effects of ACS no longer is on the immediate neonatal outcomes and now is on safety and the long-term outcomes of this exposure.

Bottom lineWe regard the large, high-quality study conducted by the NICHD MFMU Network¹ as an opportunity to answer current concerns. It is hoped that the resources necessaryfor in-depth follow-up of the children involved in this study will be provided to the investigators and to the NICHD. It is only with such follow-up that mid- and long-term adverse effects can be assessed. We believe that, at a minimum, mid-term follow-up data should be available before it is wise to make any definitive recommendations for a sweeping change in clinical practice.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The results of the highly anticipated Antenatal Late Preterm Study recently have become available.¹ Data from this randomized controlled trial, conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network, demonstrated that administration of betamethasone to women at risk for preterm delivery between 34 weeks 0 days and 36 weeks 6 days of gestation significantly reduces the rate of neonatal respiratory complications. It may represent the largest study of antenatal corticosteroids (ACS) to date, with 2,827 infants studied, and its results inevitably lead to the logical practical question: Should ACS use be extended beyond the 34 weeks’ gestation limit previously recommended by professional guidelines in the United States²?

There are some issues that bear discussion before such a significant change in standard of care should be promoted.²

Antenatal Late Preterm Study outcomesThe primary outcome in the study was a composite end point describing the need for respiratory support within 72 hours after birth. Based on a pilot study, the investigators had anticipated a 33% decrease in the rate of the primary outcome; however, the reduction was only 20% (relative risk [RR], 0.80; 95% confidence interval [CI], 0.66−0.97). Although the effect size was statistically significant, one could question the clinical relevance of such a small difference.

A 33% reduction effect, more consistent with the preliminary expectations, was noted in the prespecified secondary composite outcome of severe respiratory complications (RR, 0.67; 95% CI, 0.53−0.84). Occurrences included in the secondary composite outcome that also showed significant rate reductions were:

The reported reduction in bronchopulmonary dysplasia (RR, 0.22; 95% CI, 0.02−0.92) cannot plausibly be attributed to ACS. Randomized data aggregated by the Cochrane Database of Systematic Reviews³ do not show improvement in chronic lung disease with ACS use. Moreover, the authors recognize that the assessment for bronchopulmonary dysplasia at only 28 days of life is only partially informative and that longer childhood follow-up is required to confirm the finding.

We recommend caution before changing current practiceWe propose prudence with ACS use after 34 weeks’ gestation for the following reasons: the increased risk for neonatal hypoglycemia associated with ACS, the increased risk for ACS-related harm in term-born babies, and safety concerns with ACS in the late preterm period.

Evidence shows an increased risk for neonatal hypoglycemiaThe most profound effect modification observed in the study was an adverse effect—namely, a 60% increase in neonatal hypoglycemia with ACS administration (RR, 1.6; 95% CI, 1.37−1.87). The rate of neonatal hypoglycemia was 24% in the ACS group, compared with 15% in the placebo group.

Results of prior studies have demonstrated either no increased risk of hypoglycemia with ACS use⁴⁻⁷ or a much smaller increase (from 4.2% to 5.7%).⁸ The higher rate of neonatal hypoglycemia seen in this study suggests the possibility that the late preterm population may be more vulnerable to the negative impact of ACS on neonatal glucose/insulin homeostasis. Presumed mechanisms of action are either maternal hyperglycemia or fetal adrenal suppression or both, with potential for fetal adrenal suppression resulting from betamethasone exposure to affect long-term metabolic outcomes.⁹

Of note, women with pregestational diabetes were excluded from the study and, in routine practice, inclusion of such patients may further increase the risk of neonatal hypoglycemia.

There are few data on the prognostic significance of neonatal hypoglycemia in preterm infants, with the exception of a single study, the results of which show that it is associated with adverse neurodevelopment at 18 months of age.¹⁰

Data reveal increased risk for harm in term-born babiesIn spite of strict protocol specifications to increase the probability of delivery before 37 weeks’ gestation, 16% of women in the trial delivered at term. Investigators of prior randomized studies of ACS, aimed at reducing the risks of prematurity, have reported a rate of term delivery of about one-third,^4,11 and in routine practice, administration of ACS after 34 weeks may be associated with even higher rates of term delivery.

This is important because recent evidence shows an unfavorable impact of ACS exposure in term-born children.¹² The 5-year follow-up of the largest randomized trial in which multiple ACS courses were used noted that babies born at term had a 4-fold increased odds ratio for neurosensory disability.¹¹ There was no dose−response interaction, with the same adverse odds ratio after 1 or 4 additional ACS courses. This observation was consistent with a previously reported Swedish national cohort, pointing to an unfavorable impact of even a single course of ACS in term-born children, with a greater likelihood of harm than benefit.¹³

In a UK follow-up of children aged 8 to 15 years who were enrolled in an RCT of ACS before cesarean delivery at term, low academic achievement was significantly more common in the group whose mothers had received ACS.¹⁴ In another study of 304 children born at term after exposure to a single course of ACS, investigators noted significantly increased cortisol reactivity to acute psychological stress at ages 6 to 11 years in the ACS-exposed patients, compared with 212 babies of women with threatened preterm labor who did not receive ACS and 372 babies from uncomplicated term pregnancies.¹⁵

The relevance of such study findings extends beyond childhood given the fact that elevated hypothalamic-pituitary-adrenal (HPA) axis reactivity has been linked to the pathogenesis of metabolic syndrome and depression in adult life.¹⁶ As recently as 2015, investigators of a randomized trial of ACS in 6 low- and middle-income countries highlighted their concern regarding “potentially harmful use of antenatal corticosteroids for infants not delivered preterm.”¹⁷

There are safety concerns with ACS in the late preterm periodThe effects of ACS are more pleiotropic than those reflected in a lower incidence of respiratory difficulties. Knowledge of the overall consequences of ACS exposure in infants born late-preterm or at term is still limited. The close-to-term fetus exposed to exogenous corticosteroids is also exposed to the physiologic endogenous surge of cortisol known to occur in the maternal circulation in late pregnancy, which reaches levels 3 times higher than those seen in nonpregnant women.¹⁸ Although placental 11 beta-hydroxysteroid dehydrogenase type 2 plays a protective role by allowing no more than 10% to 20% of maternal corticosteroids to cross the placenta, fetal overexposure from concomitant exogenous maternal corticosteroid administration remains a theoretical concern close to term. This is especially worrisome if there is a gestational age−related increase in the sensitivity to corticosteroid-induced in utero fetal programming. It has been reported that fetal overexposure to corticosteroids in late pregnancy can permanently increase the activity of the HPA-axis, with likely consequences in adult life.¹⁹

Another concern relates to oligodendrocytes development. Although the neuronal division process in humans usually is completed by 24 weeks’ gestation, the most rapid growth for oligodendrocytes occurs between 34 and 36 weeks’ gestation; these are the cells responsible for the synthesis of myelin. Overexposure to corticosteroids at this vulnerable time in the late preterm fetus potentially may have unanticipated negative neurologic consequences.²⁰

Where should future studies focus?There is clear neonatal benefit from a single course of ACS given to women who will deliver before 34 weeks’ gestation. It is widely accepted, based on the evidence provided by the 30-year follow-up of the cohort of 534 participants from the Auckland trial (the longest follow-up for any pregnancy trial), that administration of ACS at less than 34 weeks’ gestation is not associated with any obvious major developmental risk.²¹⁻²³

However, the reassurances provided by the Auckland cohort should be neither directly extrapolated to the administration of ACS in the late preterm period nor applied to term-born babies exposed to ACS, for the simple reason that these subgroups never have been analyzed separately. The risk:benefit ratio of ACS use in the late-preterm period is as yet unknown, and in term-born babies the ratio may be unfavorable.

Follow-up studies are neededWe consider that there is a vital need for long-term follow-up studies. The focus of research on the effects of ACS no longer is on the immediate neonatal outcomes and now is on safety and the long-term outcomes of this exposure.

Bottom lineWe regard the large, high-quality study conducted by the NICHD MFMU Network¹ as an opportunity to answer current concerns. It is hoped that the resources necessaryfor in-depth follow-up of the children involved in this study will be provided to the investigators and to the NICHD. It is only with such follow-up that mid- and long-term adverse effects can be assessed. We believe that, at a minimum, mid-term follow-up data should be available before it is wise to make any definitive recommendations for a sweeping change in clinical practice.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

NEW ORLEANS – Fatigue: Take Control (FTC), a 6-week group education and behavioral program widely used to address fatigue in patients with multiple sclerosis, was comparable to a general MS education program for decreasing fatigue and improving self-efficacy in a randomized, controlled study.

In 218 subjects randomized to participate in either FTC or a general MS education program (MS: Take Control, or MSTC), Modified Fatigue Impact Scale scores improved significantly, compared with baseline and regardless of group assignment; there was no difference between the groups at visit 6 (mean change, –4.5 and –3.6 in the FTC and MSTC groups, respectively), Cinda L. Hugos of the VA Portland (Ore.) Health Care System and her colleagues reported at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

©RusN/Thinkstock.com

Multiple Sclerosis Self-Efficacy scale scores did, however, improve significantly in the FTC group vs. the MSTC group (mean increase of 45.5 vs. a decrease of 15.8), but the improvement was not maintained at 6 months, the investigators reported in a poster at the meeting.

The two groups had comparable baseline characteristics, with a mean age of nearly 54 years, as well as similar mean time since diagnosis (12.5 years), self-administered Expanded Disability Status Scale scores (5.2), and demographics.

Fatigue is common in MS patients, occurring in up to 95% of patients, and many report that it is the most disabling symptom. FTC, which addresses medical management of fatigue, exercise, environment, and changes and choices with respect to energy and fatigue control, is often used by chapters of the National MS Society, but its effectiveness for decreasing fatigue or improving self-efficacy has not been proven, the investigators noted.

To determine if FTC decreases fatigue and increases self-efficacy, compared with a general MS education program that addresses issues such as nutrition, emotional health, cognitive problems, and fitness, the investigators randomized subjects at four sites in groups of between 3 and 10 participants to either an FTC or MSTC group. All subjects had moderate to severe fatigue. Those with pregnancy, severe depression, uncontrolled problems that would limit participation, relapse in the prior month, or initiation of a new disease-modifying treatment within the prior 3 months were excluded.

“Both FTC and MSTC structured small group programs were associated with improved self-reported fatigue at program completion and at 3- and 6-month follow-up, but there were no significant differences in fatigue scores between FTC and MSTC participants at any time point,” the investigators wrote.

Self-efficacy was significantly better among FTC participants at program completion, but was not sustained, they noted, concluding that the findings suggest that “participating in structured small group programs is associated with prolonged reductions in fatigue in people with MS and that supporting goal setting provides short-term improvements in self-efficacy.”

Further research is needed to determine whether booster sessions would be beneficial for sustaining improvements in self-efficacy, they added.

This study was supported by the Rehabilitation, Research, & Development Service of the Veterans Affairs Office of Research & Development. The authors reported having no disclosures.

[email protected]

NEW ORLEANS – Fatigue: Take Control (FTC), a 6-week group education and behavioral program widely used to address fatigue in patients with multiple sclerosis, was comparable to a general MS education program for decreasing fatigue and improving self-efficacy in a randomized, controlled study.

In 218 subjects randomized to participate in either FTC or a general MS education program (MS: Take Control, or MSTC), Modified Fatigue Impact Scale scores improved significantly, compared with baseline and regardless of group assignment; there was no difference between the groups at visit 6 (mean change, –4.5 and –3.6 in the FTC and MSTC groups, respectively), Cinda L. Hugos of the VA Portland (Ore.) Health Care System and her colleagues reported at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

©RusN/Thinkstock.com

Multiple Sclerosis Self-Efficacy scale scores did, however, improve significantly in the FTC group vs. the MSTC group (mean increase of 45.5 vs. a decrease of 15.8), but the improvement was not maintained at 6 months, the investigators reported in a poster at the meeting.

The two groups had comparable baseline characteristics, with a mean age of nearly 54 years, as well as similar mean time since diagnosis (12.5 years), self-administered Expanded Disability Status Scale scores (5.2), and demographics.

Fatigue is common in MS patients, occurring in up to 95% of patients, and many report that it is the most disabling symptom. FTC, which addresses medical management of fatigue, exercise, environment, and changes and choices with respect to energy and fatigue control, is often used by chapters of the National MS Society, but its effectiveness for decreasing fatigue or improving self-efficacy has not been proven, the investigators noted.

To determine if FTC decreases fatigue and increases self-efficacy, compared with a general MS education program that addresses issues such as nutrition, emotional health, cognitive problems, and fitness, the investigators randomized subjects at four sites in groups of between 3 and 10 participants to either an FTC or MSTC group. All subjects had moderate to severe fatigue. Those with pregnancy, severe depression, uncontrolled problems that would limit participation, relapse in the prior month, or initiation of a new disease-modifying treatment within the prior 3 months were excluded.

“Both FTC and MSTC structured small group programs were associated with improved self-reported fatigue at program completion and at 3- and 6-month follow-up, but there were no significant differences in fatigue scores between FTC and MSTC participants at any time point,” the investigators wrote.

Self-efficacy was significantly better among FTC participants at program completion, but was not sustained, they noted, concluding that the findings suggest that “participating in structured small group programs is associated with prolonged reductions in fatigue in people with MS and that supporting goal setting provides short-term improvements in self-efficacy.”

Further research is needed to determine whether booster sessions would be beneficial for sustaining improvements in self-efficacy, they added.

This study was supported by the Rehabilitation, Research, & Development Service of the Veterans Affairs Office of Research & Development. The authors reported having no disclosures.

[email protected]

NEW ORLEANS – Fatigue: Take Control (FTC), a 6-week group education and behavioral program widely used to address fatigue in patients with multiple sclerosis, was comparable to a general MS education program for decreasing fatigue and improving self-efficacy in a randomized, controlled study.

In 218 subjects randomized to participate in either FTC or a general MS education program (MS: Take Control, or MSTC), Modified Fatigue Impact Scale scores improved significantly, compared with baseline and regardless of group assignment; there was no difference between the groups at visit 6 (mean change, –4.5 and –3.6 in the FTC and MSTC groups, respectively), Cinda L. Hugos of the VA Portland (Ore.) Health Care System and her colleagues reported at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

©RusN/Thinkstock.com

Multiple Sclerosis Self-Efficacy scale scores did, however, improve significantly in the FTC group vs. the MSTC group (mean increase of 45.5 vs. a decrease of 15.8), but the improvement was not maintained at 6 months, the investigators reported in a poster at the meeting.

The two groups had comparable baseline characteristics, with a mean age of nearly 54 years, as well as similar mean time since diagnosis (12.5 years), self-administered Expanded Disability Status Scale scores (5.2), and demographics.

Fatigue is common in MS patients, occurring in up to 95% of patients, and many report that it is the most disabling symptom. FTC, which addresses medical management of fatigue, exercise, environment, and changes and choices with respect to energy and fatigue control, is often used by chapters of the National MS Society, but its effectiveness for decreasing fatigue or improving self-efficacy has not been proven, the investigators noted.

To determine if FTC decreases fatigue and increases self-efficacy, compared with a general MS education program that addresses issues such as nutrition, emotional health, cognitive problems, and fitness, the investigators randomized subjects at four sites in groups of between 3 and 10 participants to either an FTC or MSTC group. All subjects had moderate to severe fatigue. Those with pregnancy, severe depression, uncontrolled problems that would limit participation, relapse in the prior month, or initiation of a new disease-modifying treatment within the prior 3 months were excluded.

“Both FTC and MSTC structured small group programs were associated with improved self-reported fatigue at program completion and at 3- and 6-month follow-up, but there were no significant differences in fatigue scores between FTC and MSTC participants at any time point,” the investigators wrote.

Self-efficacy was significantly better among FTC participants at program completion, but was not sustained, they noted, concluding that the findings suggest that “participating in structured small group programs is associated with prolonged reductions in fatigue in people with MS and that supporting goal setting provides short-term improvements in self-efficacy.”

Further research is needed to determine whether booster sessions would be beneficial for sustaining improvements in self-efficacy, they added.

This study was supported by the Rehabilitation, Research, & Development Service of the Veterans Affairs Office of Research & Development. The authors reported having no disclosures.

[email protected]

Because the prevalence of BRCA1 and BRCA2 mutations is elevated among young women diagnosed with breast cancer, guidelines recommend carrier testing for women diagnosed with this disease at age 50 years or younger.¹ Are women being tested, however, and what are their treatment decisions surrounding those test results? The Young Women’s Breast Cancer Study (YWBCS) seeks to answer such questions.

Details of the study
Study investigators recruited women diagnosed with breast cancer at age 40 or younger from 11 academic and community hospitals in the United States and Canada beginning in 2006. There were 897 evaluable participants who were recruited between 2006 and 2014. Their mean age at diagnosis was 35.5 years and 86.1% of them were white non-Hispanic. A respective 84.5% and 99.8% of women had at least a college education and were insured.

Overall, BRCA testing was performed within 1 year of breast cancer diagnosis in 87% of participants, with rates rising from 77% in 2006 to 95% in 2013. Among participants tested, 7.6% had a BRCA1 mutation, 4.5% had a BRCA2 mutation, 4.6% had an indeterminate result of unknown clinical significance, and 81.3% had a negative test result.

A total of 86.4% of women found to be mutation carriers proceeded with risk-reducing bilateral mastectomy; 51.2% found not to be mutation carriers had this same prophylactic surgery.  

What this evidence means for practice
Although it is encouraging to see that the proportion of young women with breast cancer who are receiving counseling and genetic testing is rising, the findings from this study of highly educated, largely white and affluent women is not generalizable to all US women diagnosed with breast cancer at a young age.
     That more than half of BRCA-negative women in this study chose bilateral prophylactic mastectomy, a procedure not recommended in this population, is concerning, and reflects nationwide trends.² The increasing use of next-generation sequencing (which yields information on moderate- and low-penetrance genes in addition to BRCA status) means that women and their providers increasingly are being confronted with genetic testing results that call for formal genetics expertise. Unfortunately, genetics counselors remain in short supply and many clinicians without specific genetics training are offering these tests. As editorialists appropriately point out, these trends may further increase the number of relatively low-risk women proceeding with unwarranted bilateral mastectomy.³ In my practice, I continue to refer women whose family or personal histories indicate high-risk status to a cancer genetics counselor for formal counseling and possible testing.
—Andrew M. Kaunitz, MD

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Because the prevalence of BRCA1 and BRCA2 mutations is elevated among young women diagnosed with breast cancer, guidelines recommend carrier testing for women diagnosed with this disease at age 50 years or younger.¹ Are women being tested, however, and what are their treatment decisions surrounding those test results? The Young Women’s Breast Cancer Study (YWBCS) seeks to answer such questions.

Details of the study
Study investigators recruited women diagnosed with breast cancer at age 40 or younger from 11 academic and community hospitals in the United States and Canada beginning in 2006. There were 897 evaluable participants who were recruited between 2006 and 2014. Their mean age at diagnosis was 35.5 years and 86.1% of them were white non-Hispanic. A respective 84.5% and 99.8% of women had at least a college education and were insured.

Overall, BRCA testing was performed within 1 year of breast cancer diagnosis in 87% of participants, with rates rising from 77% in 2006 to 95% in 2013. Among participants tested, 7.6% had a BRCA1 mutation, 4.5% had a BRCA2 mutation, 4.6% had an indeterminate result of unknown clinical significance, and 81.3% had a negative test result.

A total of 86.4% of women found to be mutation carriers proceeded with risk-reducing bilateral mastectomy; 51.2% found not to be mutation carriers had this same prophylactic surgery.  

What this evidence means for practice
Although it is encouraging to see that the proportion of young women with breast cancer who are receiving counseling and genetic testing is rising, the findings from this study of highly educated, largely white and affluent women is not generalizable to all US women diagnosed with breast cancer at a young age.
     That more than half of BRCA-negative women in this study chose bilateral prophylactic mastectomy, a procedure not recommended in this population, is concerning, and reflects nationwide trends.² The increasing use of next-generation sequencing (which yields information on moderate- and low-penetrance genes in addition to BRCA status) means that women and their providers increasingly are being confronted with genetic testing results that call for formal genetics expertise. Unfortunately, genetics counselors remain in short supply and many clinicians without specific genetics training are offering these tests. As editorialists appropriately point out, these trends may further increase the number of relatively low-risk women proceeding with unwarranted bilateral mastectomy.³ In my practice, I continue to refer women whose family or personal histories indicate high-risk status to a cancer genetics counselor for formal counseling and possible testing.
—Andrew M. Kaunitz, MD

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Because the prevalence of BRCA1 and BRCA2 mutations is elevated among young women diagnosed with breast cancer, guidelines recommend carrier testing for women diagnosed with this disease at age 50 years or younger.¹ Are women being tested, however, and what are their treatment decisions surrounding those test results? The Young Women’s Breast Cancer Study (YWBCS) seeks to answer such questions.

Details of the study
Study investigators recruited women diagnosed with breast cancer at age 40 or younger from 11 academic and community hospitals in the United States and Canada beginning in 2006. There were 897 evaluable participants who were recruited between 2006 and 2014. Their mean age at diagnosis was 35.5 years and 86.1% of them were white non-Hispanic. A respective 84.5% and 99.8% of women had at least a college education and were insured.

Overall, BRCA testing was performed within 1 year of breast cancer diagnosis in 87% of participants, with rates rising from 77% in 2006 to 95% in 2013. Among participants tested, 7.6% had a BRCA1 mutation, 4.5% had a BRCA2 mutation, 4.6% had an indeterminate result of unknown clinical significance, and 81.3% had a negative test result.

A total of 86.4% of women found to be mutation carriers proceeded with risk-reducing bilateral mastectomy; 51.2% found not to be mutation carriers had this same prophylactic surgery.  

What this evidence means for practice
Although it is encouraging to see that the proportion of young women with breast cancer who are receiving counseling and genetic testing is rising, the findings from this study of highly educated, largely white and affluent women is not generalizable to all US women diagnosed with breast cancer at a young age.
     That more than half of BRCA-negative women in this study chose bilateral prophylactic mastectomy, a procedure not recommended in this population, is concerning, and reflects nationwide trends.² The increasing use of next-generation sequencing (which yields information on moderate- and low-penetrance genes in addition to BRCA status) means that women and their providers increasingly are being confronted with genetic testing results that call for formal genetics expertise. Unfortunately, genetics counselors remain in short supply and many clinicians without specific genetics training are offering these tests. As editorialists appropriately point out, these trends may further increase the number of relatively low-risk women proceeding with unwarranted bilateral mastectomy.³ In my practice, I continue to refer women whose family or personal histories indicate high-risk status to a cancer genetics counselor for formal counseling and possible testing.
—Andrew M. Kaunitz, MD

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Sacroiliitis observed in patients with axial spondyloarthritis more often regressed rather than progressed on radiography over nearly 5 years of follow-up of the Assessment of SpondyloArthritis international Society (ASAS) cohort, which lead author Dr. Alexandre Sepriano and his colleagues called “strange” and “sobering.”

The findings call into question the reliability of plain pelvic radiographs for detecting subtle change in sacroiliitis and should prompt the evaluation of alternative imaging modalities such as MRI and low-dose CT, according to Dr. Sepriano of Leiden (the Netherlands) University Medical Center and his associates.

©Rocky89/Thinkstock.com

Determining the presence of radiographic sacroiliitis is prognostically relevant and can pave the way for treatment with biologics, but ambiguity in making this decision and in tracking progression has been revealed in the large inter-and intrareader variability found in previous studies. Furthermore, previous studies tracking progression of nonradiographic axial spondyloarthritis (axSpA) to radiographic axSpA have addressed only disease progression and ignored regression. While regression is likely to be rare, it cannot be ignored from a methodologic standpoint, the investigators wrote.

The researchers therefore set out in the current study to assess positive and negative changes in sacroiliitis on plain pelvic radiographs over time in 975 patients from the ASAS cohort who had chronic back pain of unknown origin or undiagnosed peripheral symptoms (Ann Rheum Dis. 2016 Feb 22. doi: 10.1136/annrheumdis-2015-208964).

Of the 357 of the patients who had paired plain pelvic radiographs available at baseline and follow-up, 17.4% (62/357) fulfilled the criteria for radiographic axSpA at baseline, as defined by modified New York criteria (mNY). At a mean follow-up of 4.4 years, this figure had risen to 22.4% (80/357), suggesting a net progression of 5%.

However, when the authors cross-tabulated their figures, more than half (36/62) of the patients considered mNY positive at baseline were assessed as mNY negative at follow-up. This would mean that radiographic sacroiliitis would have regressed in 58% of the cases; conversely, only 54 of 295 patients (18.3%) became mNY positive at follow-up.

“If only positive change (progression) is valued and negative change is ignored, one would disregard measurement error and spuriously attribute part of the observed positive change to real progression,” the research team explained. “The most likely explanation of our strange and extreme observation is that subtle radiographic progression (the signal) – if truly present – cannot be reliably distinguished from measurement error (the noise). These sobering data clearly illustrate that more research is needed in visualising progression in axSpA.”

ASAS funded the study. The authors had no competing interests to declare.

Sacroiliitis observed in patients with axial spondyloarthritis more often regressed rather than progressed on radiography over nearly 5 years of follow-up of the Assessment of SpondyloArthritis international Society (ASAS) cohort, which lead author Dr. Alexandre Sepriano and his colleagues called “strange” and “sobering.”

The findings call into question the reliability of plain pelvic radiographs for detecting subtle change in sacroiliitis and should prompt the evaluation of alternative imaging modalities such as MRI and low-dose CT, according to Dr. Sepriano of Leiden (the Netherlands) University Medical Center and his associates.

©Rocky89/Thinkstock.com

Determining the presence of radiographic sacroiliitis is prognostically relevant and can pave the way for treatment with biologics, but ambiguity in making this decision and in tracking progression has been revealed in the large inter-and intrareader variability found in previous studies. Furthermore, previous studies tracking progression of nonradiographic axial spondyloarthritis (axSpA) to radiographic axSpA have addressed only disease progression and ignored regression. While regression is likely to be rare, it cannot be ignored from a methodologic standpoint, the investigators wrote.

The researchers therefore set out in the current study to assess positive and negative changes in sacroiliitis on plain pelvic radiographs over time in 975 patients from the ASAS cohort who had chronic back pain of unknown origin or undiagnosed peripheral symptoms (Ann Rheum Dis. 2016 Feb 22. doi: 10.1136/annrheumdis-2015-208964).

Of the 357 of the patients who had paired plain pelvic radiographs available at baseline and follow-up, 17.4% (62/357) fulfilled the criteria for radiographic axSpA at baseline, as defined by modified New York criteria (mNY). At a mean follow-up of 4.4 years, this figure had risen to 22.4% (80/357), suggesting a net progression of 5%.

However, when the authors cross-tabulated their figures, more than half (36/62) of the patients considered mNY positive at baseline were assessed as mNY negative at follow-up. This would mean that radiographic sacroiliitis would have regressed in 58% of the cases; conversely, only 54 of 295 patients (18.3%) became mNY positive at follow-up.

“If only positive change (progression) is valued and negative change is ignored, one would disregard measurement error and spuriously attribute part of the observed positive change to real progression,” the research team explained. “The most likely explanation of our strange and extreme observation is that subtle radiographic progression (the signal) – if truly present – cannot be reliably distinguished from measurement error (the noise). These sobering data clearly illustrate that more research is needed in visualising progression in axSpA.”

ASAS funded the study. The authors had no competing interests to declare.

Sacroiliitis observed in patients with axial spondyloarthritis more often regressed rather than progressed on radiography over nearly 5 years of follow-up of the Assessment of SpondyloArthritis international Society (ASAS) cohort, which lead author Dr. Alexandre Sepriano and his colleagues called “strange” and “sobering.”

The findings call into question the reliability of plain pelvic radiographs for detecting subtle change in sacroiliitis and should prompt the evaluation of alternative imaging modalities such as MRI and low-dose CT, according to Dr. Sepriano of Leiden (the Netherlands) University Medical Center and his associates.

©Rocky89/Thinkstock.com

Determining the presence of radiographic sacroiliitis is prognostically relevant and can pave the way for treatment with biologics, but ambiguity in making this decision and in tracking progression has been revealed in the large inter-and intrareader variability found in previous studies. Furthermore, previous studies tracking progression of nonradiographic axial spondyloarthritis (axSpA) to radiographic axSpA have addressed only disease progression and ignored regression. While regression is likely to be rare, it cannot be ignored from a methodologic standpoint, the investigators wrote.

The researchers therefore set out in the current study to assess positive and negative changes in sacroiliitis on plain pelvic radiographs over time in 975 patients from the ASAS cohort who had chronic back pain of unknown origin or undiagnosed peripheral symptoms (Ann Rheum Dis. 2016 Feb 22. doi: 10.1136/annrheumdis-2015-208964).

Of the 357 of the patients who had paired plain pelvic radiographs available at baseline and follow-up, 17.4% (62/357) fulfilled the criteria for radiographic axSpA at baseline, as defined by modified New York criteria (mNY). At a mean follow-up of 4.4 years, this figure had risen to 22.4% (80/357), suggesting a net progression of 5%.

However, when the authors cross-tabulated their figures, more than half (36/62) of the patients considered mNY positive at baseline were assessed as mNY negative at follow-up. This would mean that radiographic sacroiliitis would have regressed in 58% of the cases; conversely, only 54 of 295 patients (18.3%) became mNY positive at follow-up.

“If only positive change (progression) is valued and negative change is ignored, one would disregard measurement error and spuriously attribute part of the observed positive change to real progression,” the research team explained. “The most likely explanation of our strange and extreme observation is that subtle radiographic progression (the signal) – if truly present – cannot be reliably distinguished from measurement error (the noise). These sobering data clearly illustrate that more research is needed in visualising progression in axSpA.”

ASAS funded the study. The authors had no competing interests to declare.