WASHINGTON – Acute respiratory distress syndrome (ARDS) appears to exist in at least two major forms, and one of these, the hyperinflammatory form, seemed responsive to simvastatin in a post-hoc analysis of trial data.

The other version of ARDs is a hypoinflammatory form, which occurred in 70% of ARDS patients in most of the analyses that have been done.

Researchers classified the 540 ARDS patients enrolled in a 2014 study of simvastatin as either hyperinflammatory or hypoinflammatory. Separating out the hyperinflammatory patients created a subclass that responded to simvastatin, with a 13% absolute reduction in mortality during follow-up, compared with no response among patients in the hypoinflammatory group, Carolyn S. Calfee, MD, said at an international conference of the American Thoracic Society.

“Hyperinflammatory patients treated with simvastatin may have improved outcomes, compared with hypoinflammatory* patients treated with placebo,” said Dr. Calfee, a pulmonologist at the University of California, San Francisco.

The finding raises the possibility that simvastatin, as well as other statins, may be an effective treatment for selected patients with ARDS, but proving this requires new prospective, randomized trials in hyperinflammatory patients, Dr. Calfee said in a video interview.

Currently, the tests Dr. Calfee uses to distinguish hyperinflammatory and hypoinflammatory ARDS patients take about 6-8 hours to complete. A “point of care test to stratify patients in real time,” is needed to further study the various forms of ARDs, Dr. Calfee noted. A critical next step would be the development of a “practical, rapid, bedside assay” to ease identification of hyperinflammatory ARDS patients. “The work we’ve done prior seems to indicate that we are going to definitely need to measure biomarkers in order to identity these subgroups,” she noted.

Hypoinflammatory patients also merit study, she added. Although hyperinflammatory patients have significant worse mortality rates, the hypoinflammatory subclass includes about 70% of ARDS patients, “so we need to better understand how to potentially treat this group.”

Dr. Calfee and her associates first reported finding the two ARDS subclasses, what they also call subphenotypes or endotypes, in two separate cohorts of ARDS patients in a 2014 report (Lancet Resp Med. 2014 Aug;2[8]:611-20). Then, they confirmed the finding in a third ARDS cohort in a 2017 report (Amer J Resp Crit Care Med. 2017 Feb 1;195[3]:331-8). These reports have documented other characteristics of the hyperinflammatory ARDS subclass: hypotension, metabolic acidosis, more frequent treatment with vasopressors, and a higher prevalence of sepsis and shock. Concurrent with the 2017 report, an editorial hailed the finding as “the dawn of personalized medicine for ARDS” (Amer J resp Crit Care Med. 2017 Feb 1;195[3]: 280-1).

To build on this, Dr. Calfee and her associates applied their method for identifying ARDS subclasses to a different cohort of 540 patients enrolled in the The HARP (Hydroxymethylglutaryl-CoA Reductase Inhibition with Simvastatin in Acute Lung Injury to Reduce Pulmonary Dysfunction)–2 study, a multicenter UK and Irish study designed to test the efficacy of daily simvastatin treatment in a heterogeneous group of ARDS patients. A 2014 report of the study’s primary results showed no significant effect from simvastatin for increasing the number of ventilator-free days nor did the drug improve any other measured efficacy endpoints (New Engl J Med. 2014 Oct 30;371[18]:1695-703).

Applying a statistical analysis called “latent class analysis,” which is designed to recognize subclass groupings that might not be readily apparent, Dr. Calfee and her team first confirmed that, in this fourth cohort, the ARDS patients again split into a hyperinflammatory subclass, in this case including 188 (35%) of the cohort, and a hypoinflammatory subclass with 352 (65%) patients. The next step was to see what impact simvastatin treatment had in each of the two patient subclasses. They focused the analysis on a secondary outcome in HARP-2, 28-day survival.

They found that simvastatin produced no significant difference in 28-day survival, compared with placebo among the hypoinflammatory patients, but, in the hyperinflammatory subclass, 28-day survival was 68% for patients on simvastatin and 55% for those on placebo, a statistically significant difference, Dr. Calfee reported (Am J Resp Crit Care Med. 2017;195:A6749).

“I’m excited that we are seeing, for the first time, a different response to pharmacotherapy” after dividing ARDS patients into these two subclasses, she said. But, the work remains in an early stage, she cautioned. “We need to test treatments [like statins] prospectively.” The new finding for simvastatin “is not the same as showing benefit in a prospective, randomized trial.”

In the meantime, Dr. Calfee plans to apply the same analytic approach to data collected in another failed statin trial in ARDS patients, the SAILS trial. That study failed to show benefit from rosuvastatin treatment in an unselected population of patients with sepsis-associated ARDS (New Engl J Med. 2014 June 5;370[23]:2191-200).

Dr. Calfee is a consultant to Bayer, Boehringer Ingelheim, and GlaxoSmithKline. She received research funding from GlaxoSmithKline.

[email protected]

On Twitter @mitchelzoler

*An earlier version of this article misquoted Dr. Calfee.

WASHINGTON – Acute respiratory distress syndrome (ARDS) appears to exist in at least two major forms, and one of these, the hyperinflammatory form, seemed responsive to simvastatin in a post-hoc analysis of trial data.

The other version of ARDs is a hypoinflammatory form, which occurred in 70% of ARDS patients in most of the analyses that have been done.

Researchers classified the 540 ARDS patients enrolled in a 2014 study of simvastatin as either hyperinflammatory or hypoinflammatory. Separating out the hyperinflammatory patients created a subclass that responded to simvastatin, with a 13% absolute reduction in mortality during follow-up, compared with no response among patients in the hypoinflammatory group, Carolyn S. Calfee, MD, said at an international conference of the American Thoracic Society.

“Hyperinflammatory patients treated with simvastatin may have improved outcomes, compared with hypoinflammatory* patients treated with placebo,” said Dr. Calfee, a pulmonologist at the University of California, San Francisco.

The finding raises the possibility that simvastatin, as well as other statins, may be an effective treatment for selected patients with ARDS, but proving this requires new prospective, randomized trials in hyperinflammatory patients, Dr. Calfee said in a video interview.

Currently, the tests Dr. Calfee uses to distinguish hyperinflammatory and hypoinflammatory ARDS patients take about 6-8 hours to complete. A “point of care test to stratify patients in real time,” is needed to further study the various forms of ARDs, Dr. Calfee noted. A critical next step would be the development of a “practical, rapid, bedside assay” to ease identification of hyperinflammatory ARDS patients. “The work we’ve done prior seems to indicate that we are going to definitely need to measure biomarkers in order to identity these subgroups,” she noted.

Hypoinflammatory patients also merit study, she added. Although hyperinflammatory patients have significant worse mortality rates, the hypoinflammatory subclass includes about 70% of ARDS patients, “so we need to better understand how to potentially treat this group.”

Dr. Calfee and her associates first reported finding the two ARDS subclasses, what they also call subphenotypes or endotypes, in two separate cohorts of ARDS patients in a 2014 report (Lancet Resp Med. 2014 Aug;2[8]:611-20). Then, they confirmed the finding in a third ARDS cohort in a 2017 report (Amer J Resp Crit Care Med. 2017 Feb 1;195[3]:331-8). These reports have documented other characteristics of the hyperinflammatory ARDS subclass: hypotension, metabolic acidosis, more frequent treatment with vasopressors, and a higher prevalence of sepsis and shock. Concurrent with the 2017 report, an editorial hailed the finding as “the dawn of personalized medicine for ARDS” (Amer J resp Crit Care Med. 2017 Feb 1;195[3]: 280-1).

To build on this, Dr. Calfee and her associates applied their method for identifying ARDS subclasses to a different cohort of 540 patients enrolled in the The HARP (Hydroxymethylglutaryl-CoA Reductase Inhibition with Simvastatin in Acute Lung Injury to Reduce Pulmonary Dysfunction)–2 study, a multicenter UK and Irish study designed to test the efficacy of daily simvastatin treatment in a heterogeneous group of ARDS patients. A 2014 report of the study’s primary results showed no significant effect from simvastatin for increasing the number of ventilator-free days nor did the drug improve any other measured efficacy endpoints (New Engl J Med. 2014 Oct 30;371[18]:1695-703).

Applying a statistical analysis called “latent class analysis,” which is designed to recognize subclass groupings that might not be readily apparent, Dr. Calfee and her team first confirmed that, in this fourth cohort, the ARDS patients again split into a hyperinflammatory subclass, in this case including 188 (35%) of the cohort, and a hypoinflammatory subclass with 352 (65%) patients. The next step was to see what impact simvastatin treatment had in each of the two patient subclasses. They focused the analysis on a secondary outcome in HARP-2, 28-day survival.

They found that simvastatin produced no significant difference in 28-day survival, compared with placebo among the hypoinflammatory patients, but, in the hyperinflammatory subclass, 28-day survival was 68% for patients on simvastatin and 55% for those on placebo, a statistically significant difference, Dr. Calfee reported (Am J Resp Crit Care Med. 2017;195:A6749).

“I’m excited that we are seeing, for the first time, a different response to pharmacotherapy” after dividing ARDS patients into these two subclasses, she said. But, the work remains in an early stage, she cautioned. “We need to test treatments [like statins] prospectively.” The new finding for simvastatin “is not the same as showing benefit in a prospective, randomized trial.”

In the meantime, Dr. Calfee plans to apply the same analytic approach to data collected in another failed statin trial in ARDS patients, the SAILS trial. That study failed to show benefit from rosuvastatin treatment in an unselected population of patients with sepsis-associated ARDS (New Engl J Med. 2014 June 5;370[23]:2191-200).

Dr. Calfee is a consultant to Bayer, Boehringer Ingelheim, and GlaxoSmithKline. She received research funding from GlaxoSmithKline.

[email protected]

On Twitter @mitchelzoler

*An earlier version of this article misquoted Dr. Calfee.

WASHINGTON – Acute respiratory distress syndrome (ARDS) appears to exist in at least two major forms, and one of these, the hyperinflammatory form, seemed responsive to simvastatin in a post-hoc analysis of trial data.

The other version of ARDs is a hypoinflammatory form, which occurred in 70% of ARDS patients in most of the analyses that have been done.

Researchers classified the 540 ARDS patients enrolled in a 2014 study of simvastatin as either hyperinflammatory or hypoinflammatory. Separating out the hyperinflammatory patients created a subclass that responded to simvastatin, with a 13% absolute reduction in mortality during follow-up, compared with no response among patients in the hypoinflammatory group, Carolyn S. Calfee, MD, said at an international conference of the American Thoracic Society.

“Hyperinflammatory patients treated with simvastatin may have improved outcomes, compared with hypoinflammatory* patients treated with placebo,” said Dr. Calfee, a pulmonologist at the University of California, San Francisco.

The finding raises the possibility that simvastatin, as well as other statins, may be an effective treatment for selected patients with ARDS, but proving this requires new prospective, randomized trials in hyperinflammatory patients, Dr. Calfee said in a video interview.

Currently, the tests Dr. Calfee uses to distinguish hyperinflammatory and hypoinflammatory ARDS patients take about 6-8 hours to complete. A “point of care test to stratify patients in real time,” is needed to further study the various forms of ARDs, Dr. Calfee noted. A critical next step would be the development of a “practical, rapid, bedside assay” to ease identification of hyperinflammatory ARDS patients. “The work we’ve done prior seems to indicate that we are going to definitely need to measure biomarkers in order to identity these subgroups,” she noted.

Hypoinflammatory patients also merit study, she added. Although hyperinflammatory patients have significant worse mortality rates, the hypoinflammatory subclass includes about 70% of ARDS patients, “so we need to better understand how to potentially treat this group.”

Dr. Calfee and her associates first reported finding the two ARDS subclasses, what they also call subphenotypes or endotypes, in two separate cohorts of ARDS patients in a 2014 report (Lancet Resp Med. 2014 Aug;2[8]:611-20). Then, they confirmed the finding in a third ARDS cohort in a 2017 report (Amer J Resp Crit Care Med. 2017 Feb 1;195[3]:331-8). These reports have documented other characteristics of the hyperinflammatory ARDS subclass: hypotension, metabolic acidosis, more frequent treatment with vasopressors, and a higher prevalence of sepsis and shock. Concurrent with the 2017 report, an editorial hailed the finding as “the dawn of personalized medicine for ARDS” (Amer J resp Crit Care Med. 2017 Feb 1;195[3]: 280-1).

To build on this, Dr. Calfee and her associates applied their method for identifying ARDS subclasses to a different cohort of 540 patients enrolled in the The HARP (Hydroxymethylglutaryl-CoA Reductase Inhibition with Simvastatin in Acute Lung Injury to Reduce Pulmonary Dysfunction)–2 study, a multicenter UK and Irish study designed to test the efficacy of daily simvastatin treatment in a heterogeneous group of ARDS patients. A 2014 report of the study’s primary results showed no significant effect from simvastatin for increasing the number of ventilator-free days nor did the drug improve any other measured efficacy endpoints (New Engl J Med. 2014 Oct 30;371[18]:1695-703).

Applying a statistical analysis called “latent class analysis,” which is designed to recognize subclass groupings that might not be readily apparent, Dr. Calfee and her team first confirmed that, in this fourth cohort, the ARDS patients again split into a hyperinflammatory subclass, in this case including 188 (35%) of the cohort, and a hypoinflammatory subclass with 352 (65%) patients. The next step was to see what impact simvastatin treatment had in each of the two patient subclasses. They focused the analysis on a secondary outcome in HARP-2, 28-day survival.

They found that simvastatin produced no significant difference in 28-day survival, compared with placebo among the hypoinflammatory patients, but, in the hyperinflammatory subclass, 28-day survival was 68% for patients on simvastatin and 55% for those on placebo, a statistically significant difference, Dr. Calfee reported (Am J Resp Crit Care Med. 2017;195:A6749).

“I’m excited that we are seeing, for the first time, a different response to pharmacotherapy” after dividing ARDS patients into these two subclasses, she said. But, the work remains in an early stage, she cautioned. “We need to test treatments [like statins] prospectively.” The new finding for simvastatin “is not the same as showing benefit in a prospective, randomized trial.”

In the meantime, Dr. Calfee plans to apply the same analytic approach to data collected in another failed statin trial in ARDS patients, the SAILS trial. That study failed to show benefit from rosuvastatin treatment in an unselected population of patients with sepsis-associated ARDS (New Engl J Med. 2014 June 5;370[23]:2191-200).

Dr. Calfee is a consultant to Bayer, Boehringer Ingelheim, and GlaxoSmithKline. She received research funding from GlaxoSmithKline.

[email protected]

On Twitter @mitchelzoler

*An earlier version of this article misquoted Dr. Calfee.

NEW ORLEANS—Patients with multiple sclerosis (MS) had increased rates of in-hospital mortality and discharge to nursing facilities, compared with patients with MS plus a coexisting autoimmune disorder, according to research presented at the 31st Annual Meeting of the Consortium of MS Centers.

“The findings in this study suggest that a coexisting autoimmune disorder may in fact lessen the severity of the immune dysregulation of MS, which leads to improved health outcomes,” said Malik M. Adil, MD, a neurology resident at the Ochsner Clinic Foundation in New Orleans, and colleagues.

Studies have suggested an association between MS and autoimmune disorders, but research concerning clinical outcomes is limited. To determine whether coexisting autoimmune disorders affect outcomes in patients with MS, Dr. Adil and colleagues analyzed Nationwide Inpatient Survey data files from 2006 to 2010. The researchers classified patients with MS into two groups: an MS group (without coexisting autoimmune disorders) and an MS Plus group (with coexisting autoimmune disorders).

The investigators then compared the rate of clinical outcomes (ie, in-hospital mortality, discharge to home, discharge to nursing facilities, length of stay, and total charges) between the MS and MS Plus groups. Dr. Adil and colleagues used multivariate analysis to adjust for potential confounders when assessing in-hospital outcomes.

Of 115,120 patients with MS, 18,796 were in the MS Plus group. The adjusted odds of in-hospital mortality and of discharge to nursing facilities were significantly higher in the MS group, compared with the MS Plus group (odds ratios, 4.67 and 1.16, respectively). Length of stay and mean hospital charges were significantly higher in the MS Plus group, compared with the MS group.

A possible explanation for the findings is that coexisting autoimmune diseases involve different effector T cells that may regulate the effect of other effector T cells, said the authors. “Other possible explanations of better outcome in the MS Plus group might be the use of chronic immune suppressive agents in addition to MS immunotherapy, and multidisciplinary management,” they added.

NEW ORLEANS—Patients with multiple sclerosis (MS) had increased rates of in-hospital mortality and discharge to nursing facilities, compared with patients with MS plus a coexisting autoimmune disorder, according to research presented at the 31st Annual Meeting of the Consortium of MS Centers.

“The findings in this study suggest that a coexisting autoimmune disorder may in fact lessen the severity of the immune dysregulation of MS, which leads to improved health outcomes,” said Malik M. Adil, MD, a neurology resident at the Ochsner Clinic Foundation in New Orleans, and colleagues.

Studies have suggested an association between MS and autoimmune disorders, but research concerning clinical outcomes is limited. To determine whether coexisting autoimmune disorders affect outcomes in patients with MS, Dr. Adil and colleagues analyzed Nationwide Inpatient Survey data files from 2006 to 2010. The researchers classified patients with MS into two groups: an MS group (without coexisting autoimmune disorders) and an MS Plus group (with coexisting autoimmune disorders).

The investigators then compared the rate of clinical outcomes (ie, in-hospital mortality, discharge to home, discharge to nursing facilities, length of stay, and total charges) between the MS and MS Plus groups. Dr. Adil and colleagues used multivariate analysis to adjust for potential confounders when assessing in-hospital outcomes.

Of 115,120 patients with MS, 18,796 were in the MS Plus group. The adjusted odds of in-hospital mortality and of discharge to nursing facilities were significantly higher in the MS group, compared with the MS Plus group (odds ratios, 4.67 and 1.16, respectively). Length of stay and mean hospital charges were significantly higher in the MS Plus group, compared with the MS group.

A possible explanation for the findings is that coexisting autoimmune diseases involve different effector T cells that may regulate the effect of other effector T cells, said the authors. “Other possible explanations of better outcome in the MS Plus group might be the use of chronic immune suppressive agents in addition to MS immunotherapy, and multidisciplinary management,” they added.

NEW ORLEANS—Patients with multiple sclerosis (MS) had increased rates of in-hospital mortality and discharge to nursing facilities, compared with patients with MS plus a coexisting autoimmune disorder, according to research presented at the 31st Annual Meeting of the Consortium of MS Centers.

“The findings in this study suggest that a coexisting autoimmune disorder may in fact lessen the severity of the immune dysregulation of MS, which leads to improved health outcomes,” said Malik M. Adil, MD, a neurology resident at the Ochsner Clinic Foundation in New Orleans, and colleagues.

Studies have suggested an association between MS and autoimmune disorders, but research concerning clinical outcomes is limited. To determine whether coexisting autoimmune disorders affect outcomes in patients with MS, Dr. Adil and colleagues analyzed Nationwide Inpatient Survey data files from 2006 to 2010. The researchers classified patients with MS into two groups: an MS group (without coexisting autoimmune disorders) and an MS Plus group (with coexisting autoimmune disorders).

The investigators then compared the rate of clinical outcomes (ie, in-hospital mortality, discharge to home, discharge to nursing facilities, length of stay, and total charges) between the MS and MS Plus groups. Dr. Adil and colleagues used multivariate analysis to adjust for potential confounders when assessing in-hospital outcomes.

Of 115,120 patients with MS, 18,796 were in the MS Plus group. The adjusted odds of in-hospital mortality and of discharge to nursing facilities were significantly higher in the MS group, compared with the MS Plus group (odds ratios, 4.67 and 1.16, respectively). Length of stay and mean hospital charges were significantly higher in the MS Plus group, compared with the MS group.

A possible explanation for the findings is that coexisting autoimmune diseases involve different effector T cells that may regulate the effect of other effector T cells, said the authors. “Other possible explanations of better outcome in the MS Plus group might be the use of chronic immune suppressive agents in addition to MS immunotherapy, and multidisciplinary management,” they added.

SAN FRANCISCO – The 11-year follow-up results of the Caffeine for Apnea of Prematurity randomized, placebo-controlled trial has established the benefits of methylated xanthine therapy in the form of caffeine for very-low-birth-weight (VLBW) neonates in lessening the risk of motor impairment.

“The latest findings bolster the value of caffeine therapy to address apnea of prematurity in VLBW neonates. The CAP trial has provided compelling evidence for the use of caffeine even before this latest finding of improved motor function at age 11 years,” said presenter and the CAP trial’s principal investigator Barbara Schmidt, MD, of McMaster University, Hamilton, Ont.

Fuse/Thinkstock

The sponsor of study was McMaster University. The study was funded by the Canadian Institutes of Health Research and the National Health and Medical Research Council of Australia. Dr. Schmidt had no relevant financial disclosures to report.

SAN FRANCISCO – The 11-year follow-up results of the Caffeine for Apnea of Prematurity randomized, placebo-controlled trial has established the benefits of methylated xanthine therapy in the form of caffeine for very-low-birth-weight (VLBW) neonates in lessening the risk of motor impairment.

“The latest findings bolster the value of caffeine therapy to address apnea of prematurity in VLBW neonates. The CAP trial has provided compelling evidence for the use of caffeine even before this latest finding of improved motor function at age 11 years,” said presenter and the CAP trial’s principal investigator Barbara Schmidt, MD, of McMaster University, Hamilton, Ont.

Fuse/Thinkstock

The sponsor of study was McMaster University. The study was funded by the Canadian Institutes of Health Research and the National Health and Medical Research Council of Australia. Dr. Schmidt had no relevant financial disclosures to report.

SAN FRANCISCO – The 11-year follow-up results of the Caffeine for Apnea of Prematurity randomized, placebo-controlled trial has established the benefits of methylated xanthine therapy in the form of caffeine for very-low-birth-weight (VLBW) neonates in lessening the risk of motor impairment.

“The latest findings bolster the value of caffeine therapy to address apnea of prematurity in VLBW neonates. The CAP trial has provided compelling evidence for the use of caffeine even before this latest finding of improved motor function at age 11 years,” said presenter and the CAP trial’s principal investigator Barbara Schmidt, MD, of McMaster University, Hamilton, Ont.

Fuse/Thinkstock

The sponsor of study was McMaster University. The study was funded by the Canadian Institutes of Health Research and the National Health and Medical Research Council of Australia. Dr. Schmidt had no relevant financial disclosures to report.

The Food and Drug Administration has approved Rebinyn (nonacog beta pegol, N9-GP) for the treatment of hemophilia B, according to a statement from Novo Nordisk.

Caused by deficient blood clotting factor IX activity, hemophilia B affects about 5,000 people in the United States. The disease is chronic and inherited and causes prolonged and spontaneous bleeding, particularly into muscles, joints, or internal organs. Rebinyn is intended to control and treat bleeding episodes, as well as provide perioperative management of bleeding.

[email protected]

The Food and Drug Administration has approved Rebinyn (nonacog beta pegol, N9-GP) for the treatment of hemophilia B, according to a statement from Novo Nordisk.

Caused by deficient blood clotting factor IX activity, hemophilia B affects about 5,000 people in the United States. The disease is chronic and inherited and causes prolonged and spontaneous bleeding, particularly into muscles, joints, or internal organs. Rebinyn is intended to control and treat bleeding episodes, as well as provide perioperative management of bleeding.

[email protected]

The Food and Drug Administration has approved Rebinyn (nonacog beta pegol, N9-GP) for the treatment of hemophilia B, according to a statement from Novo Nordisk.

Caused by deficient blood clotting factor IX activity, hemophilia B affects about 5,000 people in the United States. The disease is chronic and inherited and causes prolonged and spontaneous bleeding, particularly into muscles, joints, or internal organs. Rebinyn is intended to control and treat bleeding episodes, as well as provide perioperative management of bleeding.

[email protected]

“WHY ARE THERE DELAYS IN THE DIAGNOSIS OF ENDOMETRIOSIS?”

ROBERT L. BARBIERI, MD (EDITORIAL; MARCH 2017)

Adenomyosis increasingly is a concern

Dr. Barbieri’s article on delay in diagnosis of endometriosis is timely and important. I agree that family history is very important, but often the mother had a hysterectomy at a relatively young age for heavy bleeding that was blamed on fibroids.

Adenomyosis seems to be increasing in prevalence and may be suggested by cystic changes in the endometrium on 3D ultrasonography. The patient often reports dark brown spotting before or after periods. The second day of the period is very heavy, and cramping may precede the period. Sometimes you can note punctate lesions on the cervix that cause a very friable cervix that is likely to bleed after the patient has coitus or a Pap smear. Adenomyosis may cause much of the troublesome bleeding seen after medroxyprogesterone acetate injection, insertion of a levonorgestrel-containing intrauterine device, etonogestrel implant placement, and even birth control pills, and it is often dismissed as dysfunctional uterine bleeding. The dark brown blood may represent blood exiting the crypts of the endometrium.

It is concerning that patients who are treated aggressively for adenomyosis in order to get pregnant seem to be at increased risk for retained placenta and decreased uterine tone in the third stage of labor. Certainly this makes intuitive sense if one surmises that the endometrium is abnormally deep into the myometrium, allowing for microscopic placental invasion and myometrial dysfunction.

Most troubling is the warning from the public health community regarding endocrine disruptors. Could BPA (bisphenol A) be contaminating our plastic water bottles and be causing an epidemic of younger-onset adenomyosis? It is certainly something worth studying.

John Lewis, MD
Waterbury, Connecticut

Endometriosis patients receive delayed diagnosis, ineffective treatments

Several points came to mind reading Dr. Barbieri’s article. First, with the surge in deep infiltrating endometriosis as reported in the literature, one has to ask about treating mild disease with hormones initially. Disease can and does progress with hormonal suppression, I assume because endometriosis makes its own estrogen. Yet when the surge is noticed, the recommendation, at least in Europe, is that we should look at pollution.

Second, I have to wonder why it is not reported that older women have endometriosis. I manage a 20,000-member education board for endometriosis patients and many of those seeking help are older and often already castrated. When I can find them access to advanced surgical skill, they are found to have active endometriosis.

The patients seeking more information (gaining 300 a week) have failed all that gynecology has to offer except expert surgical excision of their disease. In my view, gynecology in general has failed this patient population. I have worked with endometriosis patients for 32 years, and 75% of them have been dismissed as neurotic, with average time to diagnosis 9 years after symptoms appear.

It seems that the symptom profile found in endometriosis patients is not well known, and once the disease is diagnosed, the treatment options are ineffective.

Nancy Petersen, RN
Portland, Oregon

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.

“WHY ARE THERE DELAYS IN THE DIAGNOSIS OF ENDOMETRIOSIS?”

ROBERT L. BARBIERI, MD (EDITORIAL; MARCH 2017)

Adenomyosis increasingly is a concern

Dr. Barbieri’s article on delay in diagnosis of endometriosis is timely and important. I agree that family history is very important, but often the mother had a hysterectomy at a relatively young age for heavy bleeding that was blamed on fibroids.

Adenomyosis seems to be increasing in prevalence and may be suggested by cystic changes in the endometrium on 3D ultrasonography. The patient often reports dark brown spotting before or after periods. The second day of the period is very heavy, and cramping may precede the period. Sometimes you can note punctate lesions on the cervix that cause a very friable cervix that is likely to bleed after the patient has coitus or a Pap smear. Adenomyosis may cause much of the troublesome bleeding seen after medroxyprogesterone acetate injection, insertion of a levonorgestrel-containing intrauterine device, etonogestrel implant placement, and even birth control pills, and it is often dismissed as dysfunctional uterine bleeding. The dark brown blood may represent blood exiting the crypts of the endometrium.

It is concerning that patients who are treated aggressively for adenomyosis in order to get pregnant seem to be at increased risk for retained placenta and decreased uterine tone in the third stage of labor. Certainly this makes intuitive sense if one surmises that the endometrium is abnormally deep into the myometrium, allowing for microscopic placental invasion and myometrial dysfunction.

Most troubling is the warning from the public health community regarding endocrine disruptors. Could BPA (bisphenol A) be contaminating our plastic water bottles and be causing an epidemic of younger-onset adenomyosis? It is certainly something worth studying.

John Lewis, MD
Waterbury, Connecticut

Endometriosis patients receive delayed diagnosis, ineffective treatments

Several points came to mind reading Dr. Barbieri’s article. First, with the surge in deep infiltrating endometriosis as reported in the literature, one has to ask about treating mild disease with hormones initially. Disease can and does progress with hormonal suppression, I assume because endometriosis makes its own estrogen. Yet when the surge is noticed, the recommendation, at least in Europe, is that we should look at pollution.

Second, I have to wonder why it is not reported that older women have endometriosis. I manage a 20,000-member education board for endometriosis patients and many of those seeking help are older and often already castrated. When I can find them access to advanced surgical skill, they are found to have active endometriosis.

The patients seeking more information (gaining 300 a week) have failed all that gynecology has to offer except expert surgical excision of their disease. In my view, gynecology in general has failed this patient population. I have worked with endometriosis patients for 32 years, and 75% of them have been dismissed as neurotic, with average time to diagnosis 9 years after symptoms appear.

It seems that the symptom profile found in endometriosis patients is not well known, and once the disease is diagnosed, the treatment options are ineffective.

Nancy Petersen, RN
Portland, Oregon

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.

“WHY ARE THERE DELAYS IN THE DIAGNOSIS OF ENDOMETRIOSIS?”

ROBERT L. BARBIERI, MD (EDITORIAL; MARCH 2017)

Adenomyosis increasingly is a concern

Dr. Barbieri’s article on delay in diagnosis of endometriosis is timely and important. I agree that family history is very important, but often the mother had a hysterectomy at a relatively young age for heavy bleeding that was blamed on fibroids.

Adenomyosis seems to be increasing in prevalence and may be suggested by cystic changes in the endometrium on 3D ultrasonography. The patient often reports dark brown spotting before or after periods. The second day of the period is very heavy, and cramping may precede the period. Sometimes you can note punctate lesions on the cervix that cause a very friable cervix that is likely to bleed after the patient has coitus or a Pap smear. Adenomyosis may cause much of the troublesome bleeding seen after medroxyprogesterone acetate injection, insertion of a levonorgestrel-containing intrauterine device, etonogestrel implant placement, and even birth control pills, and it is often dismissed as dysfunctional uterine bleeding. The dark brown blood may represent blood exiting the crypts of the endometrium.

It is concerning that patients who are treated aggressively for adenomyosis in order to get pregnant seem to be at increased risk for retained placenta and decreased uterine tone in the third stage of labor. Certainly this makes intuitive sense if one surmises that the endometrium is abnormally deep into the myometrium, allowing for microscopic placental invasion and myometrial dysfunction.

Most troubling is the warning from the public health community regarding endocrine disruptors. Could BPA (bisphenol A) be contaminating our plastic water bottles and be causing an epidemic of younger-onset adenomyosis? It is certainly something worth studying.

John Lewis, MD
Waterbury, Connecticut

Endometriosis patients receive delayed diagnosis, ineffective treatments

Several points came to mind reading Dr. Barbieri’s article. First, with the surge in deep infiltrating endometriosis as reported in the literature, one has to ask about treating mild disease with hormones initially. Disease can and does progress with hormonal suppression, I assume because endometriosis makes its own estrogen. Yet when the surge is noticed, the recommendation, at least in Europe, is that we should look at pollution.

Second, I have to wonder why it is not reported that older women have endometriosis. I manage a 20,000-member education board for endometriosis patients and many of those seeking help are older and often already castrated. When I can find them access to advanced surgical skill, they are found to have active endometriosis.

The patients seeking more information (gaining 300 a week) have failed all that gynecology has to offer except expert surgical excision of their disease. In my view, gynecology in general has failed this patient population. I have worked with endometriosis patients for 32 years, and 75% of them have been dismissed as neurotic, with average time to diagnosis 9 years after symptoms appear.

It seems that the symptom profile found in endometriosis patients is not well known, and once the disease is diagnosed, the treatment options are ineffective.

Nancy Petersen, RN
Portland, Oregon

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SAN FRANCISCO – The 10-year follow-up of neonates treated for posthemorrhagic ventricular dilatation (PHVD) has demonstrated the long-term success of drainage, irrigation, and fibrinolytic therapy (DRIFT), with a cognitive advantage in the now school-age children evident, compared with those neonates who had not received the therapy.

“Children in the DRIFT group had a 23-point cognitive quotient advantage and were nine times more likely to be alive without severe cognitive disability at 10 years,” presenter and DRIFT investigator Karen Luyt, MBChB, PhD, of the University of Bristol and St. Michael’s Hospital, Bristol, England, said at the Pediatric Academic Societies meeting.

Herjua/Thinkstock

SAN FRANCISCO – The 10-year follow-up of neonates treated for posthemorrhagic ventricular dilatation (PHVD) has demonstrated the long-term success of drainage, irrigation, and fibrinolytic therapy (DRIFT), with a cognitive advantage in the now school-age children evident, compared with those neonates who had not received the therapy.

“Children in the DRIFT group had a 23-point cognitive quotient advantage and were nine times more likely to be alive without severe cognitive disability at 10 years,” presenter and DRIFT investigator Karen Luyt, MBChB, PhD, of the University of Bristol and St. Michael’s Hospital, Bristol, England, said at the Pediatric Academic Societies meeting.

Herjua/Thinkstock

SAN FRANCISCO – The 10-year follow-up of neonates treated for posthemorrhagic ventricular dilatation (PHVD) has demonstrated the long-term success of drainage, irrigation, and fibrinolytic therapy (DRIFT), with a cognitive advantage in the now school-age children evident, compared with those neonates who had not received the therapy.

“Children in the DRIFT group had a 23-point cognitive quotient advantage and were nine times more likely to be alive without severe cognitive disability at 10 years,” presenter and DRIFT investigator Karen Luyt, MBChB, PhD, of the University of Bristol and St. Michael’s Hospital, Bristol, England, said at the Pediatric Academic Societies meeting.

Herjua/Thinkstock

On December 13, 2016, the VA announced a change in its medical regulations to permit full practice authority for all VA advanced practice registered nurses (APRNs) when they are acting within the scope of their VA employment.This amendment removed the stipulation requiring physician supervision or collaboration for APRNs. Many states across the U.S. have similar statutes for APRNs.

Not surprisingly, the regulatorychange was met with resistance fromof the physician establishment. “TheAmerican Medical Association (AMA) is disappointed by the Department of Veterans Affairs’ unprecedented proposal to allow advanced practice nurses within the VA to practice independently of a physician’s clinical oversight, regardless of individual state law,” Stephen R. Permut, MD, JD, AMA immediate past-chair wrote in a statement.

The American Academy of Physician Assistants (AAPA) then announced that it was “actively working with senior officials at the VA to institute a similar rule for PAs (physician assistants).” The well-intentioned AAPA statement seems misguided. It implies that PAs should be granted full practice authority because APRNs were granted the authority.

No matter the rational for granting APRNs full practice authority, the VA should not pursue similar regulations for PAs only because APRNs were granted the privilege. If the VA should institute a new amendment granting full practice authority to PAs, this action should be done independent of actions taken by any other nonphysician profession. Full practice authority for PAs should be based on training, clinical experience, and competency. Rather than adjusting the previously established threshold to obtain full practice authority to meet current PA standards, PAs should pursue further training and certification to earn this privilege. Physician assistant didactic and clinical training is based on the same model as training for medical doctors.

Physician assistant programs generally have 1 year of didactic training and 1 year of clinical training before trainees are eligible to take the Physician Assistant National Certifying Exam. Many schools, such as my alma mater, George Washington University School of Medicine, have PA students in the same lecture hall training side by side with medical students.

Medical doctor training generally includes 2 years of didactic training, 2 years of clinical training in medical school, and 3 years of clinical training in residency (for internal medicine) before trainees are eligible to take the American Board of Internal Medicine (ABIM) exam. The didactic training in PA programs mirrors that of medical doctor programs. The real difference in education and preparation is the duration of clinical training; 1 year of clinical training for PAs vs 5 years of clinical training for MDs.

Therefore, my suggestion would be that leaders within the PA profession should work with the ABIM to create a pathway in which PAs who work in the VA could take the ABIM exam after 4 years of clinical experience. If a PA employed by the VA passes the ABIM exam, they would be granted full practice authority within their scope of practice at the VA. This requirement would validate that these PAs warrant this privilege and subsequently satisfy physician concerns by showing that they have passed the same exam required of physicians. Moreover, this additional level of preparation and testing would increase the competency of PAs and the quality of care they provide to the veterans they serve.

On December 13, 2016, the VA announced a change in its medical regulations to permit full practice authority for all VA advanced practice registered nurses (APRNs) when they are acting within the scope of their VA employment.This amendment removed the stipulation requiring physician supervision or collaboration for APRNs. Many states across the U.S. have similar statutes for APRNs.

Not surprisingly, the regulatorychange was met with resistance fromof the physician establishment. “TheAmerican Medical Association (AMA) is disappointed by the Department of Veterans Affairs’ unprecedented proposal to allow advanced practice nurses within the VA to practice independently of a physician’s clinical oversight, regardless of individual state law,” Stephen R. Permut, MD, JD, AMA immediate past-chair wrote in a statement.

The American Academy of Physician Assistants (AAPA) then announced that it was “actively working with senior officials at the VA to institute a similar rule for PAs (physician assistants).” The well-intentioned AAPA statement seems misguided. It implies that PAs should be granted full practice authority because APRNs were granted the authority.

No matter the rational for granting APRNs full practice authority, the VA should not pursue similar regulations for PAs only because APRNs were granted the privilege. If the VA should institute a new amendment granting full practice authority to PAs, this action should be done independent of actions taken by any other nonphysician profession. Full practice authority for PAs should be based on training, clinical experience, and competency. Rather than adjusting the previously established threshold to obtain full practice authority to meet current PA standards, PAs should pursue further training and certification to earn this privilege. Physician assistant didactic and clinical training is based on the same model as training for medical doctors.

Physician assistant programs generally have 1 year of didactic training and 1 year of clinical training before trainees are eligible to take the Physician Assistant National Certifying Exam. Many schools, such as my alma mater, George Washington University School of Medicine, have PA students in the same lecture hall training side by side with medical students.

Medical doctor training generally includes 2 years of didactic training, 2 years of clinical training in medical school, and 3 years of clinical training in residency (for internal medicine) before trainees are eligible to take the American Board of Internal Medicine (ABIM) exam. The didactic training in PA programs mirrors that of medical doctor programs. The real difference in education and preparation is the duration of clinical training; 1 year of clinical training for PAs vs 5 years of clinical training for MDs.

Therefore, my suggestion would be that leaders within the PA profession should work with the ABIM to create a pathway in which PAs who work in the VA could take the ABIM exam after 4 years of clinical experience. If a PA employed by the VA passes the ABIM exam, they would be granted full practice authority within their scope of practice at the VA. This requirement would validate that these PAs warrant this privilege and subsequently satisfy physician concerns by showing that they have passed the same exam required of physicians. Moreover, this additional level of preparation and testing would increase the competency of PAs and the quality of care they provide to the veterans they serve.

On December 13, 2016, the VA announced a change in its medical regulations to permit full practice authority for all VA advanced practice registered nurses (APRNs) when they are acting within the scope of their VA employment.This amendment removed the stipulation requiring physician supervision or collaboration for APRNs. Many states across the U.S. have similar statutes for APRNs.

Not surprisingly, the regulatorychange was met with resistance fromof the physician establishment. “TheAmerican Medical Association (AMA) is disappointed by the Department of Veterans Affairs’ unprecedented proposal to allow advanced practice nurses within the VA to practice independently of a physician’s clinical oversight, regardless of individual state law,” Stephen R. Permut, MD, JD, AMA immediate past-chair wrote in a statement.

The American Academy of Physician Assistants (AAPA) then announced that it was “actively working with senior officials at the VA to institute a similar rule for PAs (physician assistants).” The well-intentioned AAPA statement seems misguided. It implies that PAs should be granted full practice authority because APRNs were granted the authority.

No matter the rational for granting APRNs full practice authority, the VA should not pursue similar regulations for PAs only because APRNs were granted the privilege. If the VA should institute a new amendment granting full practice authority to PAs, this action should be done independent of actions taken by any other nonphysician profession. Full practice authority for PAs should be based on training, clinical experience, and competency. Rather than adjusting the previously established threshold to obtain full practice authority to meet current PA standards, PAs should pursue further training and certification to earn this privilege. Physician assistant didactic and clinical training is based on the same model as training for medical doctors.

Physician assistant programs generally have 1 year of didactic training and 1 year of clinical training before trainees are eligible to take the Physician Assistant National Certifying Exam. Many schools, such as my alma mater, George Washington University School of Medicine, have PA students in the same lecture hall training side by side with medical students.

Medical doctor training generally includes 2 years of didactic training, 2 years of clinical training in medical school, and 3 years of clinical training in residency (for internal medicine) before trainees are eligible to take the American Board of Internal Medicine (ABIM) exam. The didactic training in PA programs mirrors that of medical doctor programs. The real difference in education and preparation is the duration of clinical training; 1 year of clinical training for PAs vs 5 years of clinical training for MDs.

Therefore, my suggestion would be that leaders within the PA profession should work with the ABIM to create a pathway in which PAs who work in the VA could take the ABIM exam after 4 years of clinical experience. If a PA employed by the VA passes the ABIM exam, they would be granted full practice authority within their scope of practice at the VA. This requirement would validate that these PAs warrant this privilege and subsequently satisfy physician concerns by showing that they have passed the same exam required of physicians. Moreover, this additional level of preparation and testing would increase the competency of PAs and the quality of care they provide to the veterans they serve.

NEW ORLEANS—Ozanimod demonstrated durable efficacy with a favorable safety profile in patients continuing ozanimod for 120 weeks or switching from placebo to ozanimod for 96 weeks, according to results of a phase II study presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers. “These data support the ongoing RADIANCE and SUNBEAM phase III studies,” said Brett E. Skolnick, PhD, on behalf of his study collaborators. Dr. Skolnick is an employee of Receptos, a wholly owned subsidiary of Celgene, in San Diego.

Ozanimod, an oral, once-daily immunomodulator selectively targeting sphingosine 1-phosphate (S1P) receptor-1 and -5 , is in development for relapsing multiple sclerosis (MS). “The increased receptor selectivity of ozanimod and additional pharmaceutical properties may result in a more favorable safety profile versus other nonselective and selective S1P receptor modulators,” said Dr. Skolnick.

In the completed RADIANCE Part A phase II trial, patients with relapsing MS were randomized (1:1:1) to once-daily ozanimod 0.5 mg or 1.0 mg or to placebo for 24 weeks. At week 24, patients could enter a 96-week, blinded extension phase. Patients randomized to ozanimod continued their assigned dose; 85 patients received 0.5 mg, and 81 patients received 1.0 mg. Patients administered placebo were re-randomized (1:1) to ozanimod 0.5 mg (n = 41) or 1.0 mg (n = 42). Ozanimod was dose-escalated over seven days to attenuate first-dose effects.

A total of 89% of patients taking the 0.5 mg dose and 90% of patients taking the 1.0 mg dose completed the extension study. At week 120, 89% to 91% of patients were free of gadolinium-enhancing lesions. Unadjusted annualized relapse rates were 0.31 in the 0.5 mg group and 0.18 in the 1.0 mg group. One or more treatment-emergent adverse events were seen in 79% of patients taking the 0.5 mg dose and in 76% of those taking the 1.0 mg dose. The most common adverse events were increased alanine aminotransferases, nasopharyngitis, and upper respiratory tract infection. Serious treatment-emergent adverse events were seen in 12 patients in the 0.5 mg group and in nine patients in the 1.0 mg group. Mild blunting of the normal diurnal heart rate was observed. The largest mean decrease in heart rate relative to pre-dose was 3.5 bpm at hour 6 on day 1, with no associated symptoms. No type II or 2:1 atrioventricular block was reported.

At week 120, alanine aminotransferase (ALT) levels were three or more times upper limit of normal in 6% of the 0.5 mg group and in 7% of the 1.0 mg group. In the 0.5 mg group, 2% of patients discontinued ozanimod due to increased liver transaminases. Less than 1% of patients in the 1.0 mg group discontinued ozanimod for the same reason. Between baseline and week 120, three patients in the 1.0 mg group had absolute lymphocyte counts below 200 cells/μL; none was associated with severe or serious infection. There were no notable cases of pulmonary adverse events and no cases of macular edema, malignancy-related adverse events, or serious opportunistic infections.

This study was supported by Celgene.

Suggested Reading

Cohen JA, Arnold DL, Comi G, et al. Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016;15(4):373-381.

NEW ORLEANS—Ozanimod demonstrated durable efficacy with a favorable safety profile in patients continuing ozanimod for 120 weeks or switching from placebo to ozanimod for 96 weeks, according to results of a phase II study presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers. “These data support the ongoing RADIANCE and SUNBEAM phase III studies,” said Brett E. Skolnick, PhD, on behalf of his study collaborators. Dr. Skolnick is an employee of Receptos, a wholly owned subsidiary of Celgene, in San Diego.

Ozanimod, an oral, once-daily immunomodulator selectively targeting sphingosine 1-phosphate (S1P) receptor-1 and -5 , is in development for relapsing multiple sclerosis (MS). “The increased receptor selectivity of ozanimod and additional pharmaceutical properties may result in a more favorable safety profile versus other nonselective and selective S1P receptor modulators,” said Dr. Skolnick.

In the completed RADIANCE Part A phase II trial, patients with relapsing MS were randomized (1:1:1) to once-daily ozanimod 0.5 mg or 1.0 mg or to placebo for 24 weeks. At week 24, patients could enter a 96-week, blinded extension phase. Patients randomized to ozanimod continued their assigned dose; 85 patients received 0.5 mg, and 81 patients received 1.0 mg. Patients administered placebo were re-randomized (1:1) to ozanimod 0.5 mg (n = 41) or 1.0 mg (n = 42). Ozanimod was dose-escalated over seven days to attenuate first-dose effects.

A total of 89% of patients taking the 0.5 mg dose and 90% of patients taking the 1.0 mg dose completed the extension study. At week 120, 89% to 91% of patients were free of gadolinium-enhancing lesions. Unadjusted annualized relapse rates were 0.31 in the 0.5 mg group and 0.18 in the 1.0 mg group. One or more treatment-emergent adverse events were seen in 79% of patients taking the 0.5 mg dose and in 76% of those taking the 1.0 mg dose. The most common adverse events were increased alanine aminotransferases, nasopharyngitis, and upper respiratory tract infection. Serious treatment-emergent adverse events were seen in 12 patients in the 0.5 mg group and in nine patients in the 1.0 mg group. Mild blunting of the normal diurnal heart rate was observed. The largest mean decrease in heart rate relative to pre-dose was 3.5 bpm at hour 6 on day 1, with no associated symptoms. No type II or 2:1 atrioventricular block was reported.

At week 120, alanine aminotransferase (ALT) levels were three or more times upper limit of normal in 6% of the 0.5 mg group and in 7% of the 1.0 mg group. In the 0.5 mg group, 2% of patients discontinued ozanimod due to increased liver transaminases. Less than 1% of patients in the 1.0 mg group discontinued ozanimod for the same reason. Between baseline and week 120, three patients in the 1.0 mg group had absolute lymphocyte counts below 200 cells/μL; none was associated with severe or serious infection. There were no notable cases of pulmonary adverse events and no cases of macular edema, malignancy-related adverse events, or serious opportunistic infections.

This study was supported by Celgene.

Suggested Reading

Cohen JA, Arnold DL, Comi G, et al. Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016;15(4):373-381.

NEW ORLEANS—Ozanimod demonstrated durable efficacy with a favorable safety profile in patients continuing ozanimod for 120 weeks or switching from placebo to ozanimod for 96 weeks, according to results of a phase II study presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers. “These data support the ongoing RADIANCE and SUNBEAM phase III studies,” said Brett E. Skolnick, PhD, on behalf of his study collaborators. Dr. Skolnick is an employee of Receptos, a wholly owned subsidiary of Celgene, in San Diego.

Ozanimod, an oral, once-daily immunomodulator selectively targeting sphingosine 1-phosphate (S1P) receptor-1 and -5 , is in development for relapsing multiple sclerosis (MS). “The increased receptor selectivity of ozanimod and additional pharmaceutical properties may result in a more favorable safety profile versus other nonselective and selective S1P receptor modulators,” said Dr. Skolnick.

In the completed RADIANCE Part A phase II trial, patients with relapsing MS were randomized (1:1:1) to once-daily ozanimod 0.5 mg or 1.0 mg or to placebo for 24 weeks. At week 24, patients could enter a 96-week, blinded extension phase. Patients randomized to ozanimod continued their assigned dose; 85 patients received 0.5 mg, and 81 patients received 1.0 mg. Patients administered placebo were re-randomized (1:1) to ozanimod 0.5 mg (n = 41) or 1.0 mg (n = 42). Ozanimod was dose-escalated over seven days to attenuate first-dose effects.

A total of 89% of patients taking the 0.5 mg dose and 90% of patients taking the 1.0 mg dose completed the extension study. At week 120, 89% to 91% of patients were free of gadolinium-enhancing lesions. Unadjusted annualized relapse rates were 0.31 in the 0.5 mg group and 0.18 in the 1.0 mg group. One or more treatment-emergent adverse events were seen in 79% of patients taking the 0.5 mg dose and in 76% of those taking the 1.0 mg dose. The most common adverse events were increased alanine aminotransferases, nasopharyngitis, and upper respiratory tract infection. Serious treatment-emergent adverse events were seen in 12 patients in the 0.5 mg group and in nine patients in the 1.0 mg group. Mild blunting of the normal diurnal heart rate was observed. The largest mean decrease in heart rate relative to pre-dose was 3.5 bpm at hour 6 on day 1, with no associated symptoms. No type II or 2:1 atrioventricular block was reported.

At week 120, alanine aminotransferase (ALT) levels were three or more times upper limit of normal in 6% of the 0.5 mg group and in 7% of the 1.0 mg group. In the 0.5 mg group, 2% of patients discontinued ozanimod due to increased liver transaminases. Less than 1% of patients in the 1.0 mg group discontinued ozanimod for the same reason. Between baseline and week 120, three patients in the 1.0 mg group had absolute lymphocyte counts below 200 cells/μL; none was associated with severe or serious infection. There were no notable cases of pulmonary adverse events and no cases of macular edema, malignancy-related adverse events, or serious opportunistic infections.

This study was supported by Celgene.

Suggested Reading

Cohen JA, Arnold DL, Comi G, et al. Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016;15(4):373-381.

Less and less of the research presented at a prominent cancer conference is supported by the National Institutes of Health, a development that some of the country’s top scientists see as a worrisome trend.

The number of studies fully funded by the NIH at the annual meeting of the American Society of Clinical Oncology (ASCO) – the world’s largest gathering of cancer researchers – has fallen 75% in the past decade, from 575 papers in 2008 to 144 this year, according to the society, which meets June 2-6 in Chicago.

American researchers typically dominate the meeting’s press conferences – designed to feature the most important and newsworthy research. This year, there are 14 studies led by international scientists versus 12 led by U.S.-based research teams. That’s a big shift from just 5 years ago, when 15 studies in the “press program” were led by Americans versus 9 by international researchers.

Several of the studies on this weekend’s press program come from Europe and Canada, along with two from China.

President Donald Trump has proposed cutting the NIH budget for 2018 from $31.8 billion to $26 billion, a decline that many worry would jeopardize the fight against cancer and other diseases. Those cuts include $1 billion less for the National Cancer Institute.

On its website, the NCI notes that its purchasing power already has declined by 25% since 2003, because its budget – while growing – hasn’t kept up with inflation. Congress gave the NCI nearly $5.4 billion in fiscal year 2017, an increase of $174.6 million over last year. The NCI also received $300 million for the Beau Biden Cancer Moonshot through the 21st Century Cures Act in December 2016.

“America may be losing its edge in medical research,” said Otis Brawley, MD, chief medical officer at the American Cancer Society. The brightest young scientists are having trouble finding funding for their research, leading them to look for jobs not at universities but at drug companies “or even Wall Street,” he said. “I fear we are losing a generation of young, talented biomedical scientists.”

Some see America’s leading role in science as a point of national pride.

“Do we want the U.S. to remain at the center of biomedical innovation, or do we want to cede that to China or other countries?” said Dr. Stephan Grupp, director of the Cancer Immunotherapy Frontier Program at Children’s Hospital of Philadelphia. “If you don’t push to stay in front, you don’t stay in front.”

But more than pride is at stake.

Public funding is critical, because it allows researchers to answer questions that don’t interest drug companies, said Richard Schilsky, senior vice president and chief medical officer at ASCO.

While drug companies fund studies that help them get their medications approved, they tend not to pay for studies that focus on cancer prevention, screening, or quality of life, Mr. Schilsky said. The NIH also funds head-to-head comparisons of cancer drugs, which allow patients and doctors to select the most effective treatments.

“If the NIH-funded studies continue to decline, we simply won’t get the answers that patients are looking for,” he said.

While government research often addresses areas of greatest need, “industry research is geared toward marketable products,” Dr. Brawley said.

To help make up the deficit, the American Cancer Society will double its research budget to $240 million by 2021, he added.

But Dr. Grupp notes that charities and the drug industry are often reluctant to cover the indirect costs of research, such as labs. Without steady, predictable support from government grants, Dr. Grupp said he wouldn’t “have a building to do my research in or a way to keep the lights on.”


 

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

Less and less of the research presented at a prominent cancer conference is supported by the National Institutes of Health, a development that some of the country’s top scientists see as a worrisome trend.

The number of studies fully funded by the NIH at the annual meeting of the American Society of Clinical Oncology (ASCO) – the world’s largest gathering of cancer researchers – has fallen 75% in the past decade, from 575 papers in 2008 to 144 this year, according to the society, which meets June 2-6 in Chicago.

American researchers typically dominate the meeting’s press conferences – designed to feature the most important and newsworthy research. This year, there are 14 studies led by international scientists versus 12 led by U.S.-based research teams. That’s a big shift from just 5 years ago, when 15 studies in the “press program” were led by Americans versus 9 by international researchers.

Several of the studies on this weekend’s press program come from Europe and Canada, along with two from China.

President Donald Trump has proposed cutting the NIH budget for 2018 from $31.8 billion to $26 billion, a decline that many worry would jeopardize the fight against cancer and other diseases. Those cuts include $1 billion less for the National Cancer Institute.

On its website, the NCI notes that its purchasing power already has declined by 25% since 2003, because its budget – while growing – hasn’t kept up with inflation. Congress gave the NCI nearly $5.4 billion in fiscal year 2017, an increase of $174.6 million over last year. The NCI also received $300 million for the Beau Biden Cancer Moonshot through the 21st Century Cures Act in December 2016.

“America may be losing its edge in medical research,” said Otis Brawley, MD, chief medical officer at the American Cancer Society. The brightest young scientists are having trouble finding funding for their research, leading them to look for jobs not at universities but at drug companies “or even Wall Street,” he said. “I fear we are losing a generation of young, talented biomedical scientists.”

Some see America’s leading role in science as a point of national pride.

“Do we want the U.S. to remain at the center of biomedical innovation, or do we want to cede that to China or other countries?” said Dr. Stephan Grupp, director of the Cancer Immunotherapy Frontier Program at Children’s Hospital of Philadelphia. “If you don’t push to stay in front, you don’t stay in front.”

But more than pride is at stake.

Public funding is critical, because it allows researchers to answer questions that don’t interest drug companies, said Richard Schilsky, senior vice president and chief medical officer at ASCO.

While drug companies fund studies that help them get their medications approved, they tend not to pay for studies that focus on cancer prevention, screening, or quality of life, Mr. Schilsky said. The NIH also funds head-to-head comparisons of cancer drugs, which allow patients and doctors to select the most effective treatments.

“If the NIH-funded studies continue to decline, we simply won’t get the answers that patients are looking for,” he said.

While government research often addresses areas of greatest need, “industry research is geared toward marketable products,” Dr. Brawley said.

To help make up the deficit, the American Cancer Society will double its research budget to $240 million by 2021, he added.

But Dr. Grupp notes that charities and the drug industry are often reluctant to cover the indirect costs of research, such as labs. Without steady, predictable support from government grants, Dr. Grupp said he wouldn’t “have a building to do my research in or a way to keep the lights on.”


 

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

Less and less of the research presented at a prominent cancer conference is supported by the National Institutes of Health, a development that some of the country’s top scientists see as a worrisome trend.

The number of studies fully funded by the NIH at the annual meeting of the American Society of Clinical Oncology (ASCO) – the world’s largest gathering of cancer researchers – has fallen 75% in the past decade, from 575 papers in 2008 to 144 this year, according to the society, which meets June 2-6 in Chicago.

American researchers typically dominate the meeting’s press conferences – designed to feature the most important and newsworthy research. This year, there are 14 studies led by international scientists versus 12 led by U.S.-based research teams. That’s a big shift from just 5 years ago, when 15 studies in the “press program” were led by Americans versus 9 by international researchers.

Several of the studies on this weekend’s press program come from Europe and Canada, along with two from China.

President Donald Trump has proposed cutting the NIH budget for 2018 from $31.8 billion to $26 billion, a decline that many worry would jeopardize the fight against cancer and other diseases. Those cuts include $1 billion less for the National Cancer Institute.

On its website, the NCI notes that its purchasing power already has declined by 25% since 2003, because its budget – while growing – hasn’t kept up with inflation. Congress gave the NCI nearly $5.4 billion in fiscal year 2017, an increase of $174.6 million over last year. The NCI also received $300 million for the Beau Biden Cancer Moonshot through the 21st Century Cures Act in December 2016.

“America may be losing its edge in medical research,” said Otis Brawley, MD, chief medical officer at the American Cancer Society. The brightest young scientists are having trouble finding funding for their research, leading them to look for jobs not at universities but at drug companies “or even Wall Street,” he said. “I fear we are losing a generation of young, talented biomedical scientists.”

Some see America’s leading role in science as a point of national pride.

“Do we want the U.S. to remain at the center of biomedical innovation, or do we want to cede that to China or other countries?” said Dr. Stephan Grupp, director of the Cancer Immunotherapy Frontier Program at Children’s Hospital of Philadelphia. “If you don’t push to stay in front, you don’t stay in front.”

But more than pride is at stake.

Public funding is critical, because it allows researchers to answer questions that don’t interest drug companies, said Richard Schilsky, senior vice president and chief medical officer at ASCO.

While drug companies fund studies that help them get their medications approved, they tend not to pay for studies that focus on cancer prevention, screening, or quality of life, Mr. Schilsky said. The NIH also funds head-to-head comparisons of cancer drugs, which allow patients and doctors to select the most effective treatments.

“If the NIH-funded studies continue to decline, we simply won’t get the answers that patients are looking for,” he said.

While government research often addresses areas of greatest need, “industry research is geared toward marketable products,” Dr. Brawley said.

To help make up the deficit, the American Cancer Society will double its research budget to $240 million by 2021, he added.

But Dr. Grupp notes that charities and the drug industry are often reluctant to cover the indirect costs of research, such as labs. Without steady, predictable support from government grants, Dr. Grupp said he wouldn’t “have a building to do my research in or a way to keep the lights on.”


 

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

Zika virus infection has been occurring in pregnant women at a slow but steady clip over the last couple of months, but cases of liveborn infants with Zika-related birth defects have jumped in recent weeks, according to the Centers for Disease Control and Prevention.

Eight liveborn infants with Zika-related birth defects were reported to the U.S. Zika Pregnancy Registry during the 2 weeks ending May 23, more than any other 2-week period this year, and that was after six such infants were reported for the 2 weeks ending May 9. The total for the 50 states and the District of Columbia is now 72 for 2016-2017. No new pregnancy losses with birth defects were reported over the same 4-week span, so the 50 state/D.C. total remained at eight for 2016-2017, CDC data show.

[email protected]

Zika virus infection has been occurring in pregnant women at a slow but steady clip over the last couple of months, but cases of liveborn infants with Zika-related birth defects have jumped in recent weeks, according to the Centers for Disease Control and Prevention.

Eight liveborn infants with Zika-related birth defects were reported to the U.S. Zika Pregnancy Registry during the 2 weeks ending May 23, more than any other 2-week period this year, and that was after six such infants were reported for the 2 weeks ending May 9. The total for the 50 states and the District of Columbia is now 72 for 2016-2017. No new pregnancy losses with birth defects were reported over the same 4-week span, so the 50 state/D.C. total remained at eight for 2016-2017, CDC data show.

[email protected]

Zika virus infection has been occurring in pregnant women at a slow but steady clip over the last couple of months, but cases of liveborn infants with Zika-related birth defects have jumped in recent weeks, according to the Centers for Disease Control and Prevention.

Eight liveborn infants with Zika-related birth defects were reported to the U.S. Zika Pregnancy Registry during the 2 weeks ending May 23, more than any other 2-week period this year, and that was after six such infants were reported for the 2 weeks ending May 9. The total for the 50 states and the District of Columbia is now 72 for 2016-2017. No new pregnancy losses with birth defects were reported over the same 4-week span, so the 50 state/D.C. total remained at eight for 2016-2017, CDC data show.

[email protected]