LJUBLJANA, SLOVENIA – Fever of unknown origin and pneumonia are two clinical features useful in distinguishing between influenza and respiratory syncytial virus infection as the cause of hospitalization in infants and young children, Cihan Papan, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

Dr. Papan, a pediatrician at University Children’s Hospital Mannheim (Germany) and Heidelberg (Germany) University, presented a retrospective single-center study of all 573 children aged under 2 years hospitalized over the course of several seasons for respiratory syncytial virus (RSV) or influenza as confirmed by rapid antigen testing. Even though these are two of the leading causes of hospitalization among young children, there is surprisingly sparse data comparing the two in terms of disease severity and hospital resource utilization, including antibiotic consumption. That information gap provided the basis for this study.

There were 476 children with confirmed RSV, 96 with influenza, and 1 RSV/influenza coinfection. Notably, even though the RSV group had lower temperatures and C-reactive protein levels, they were nevertheless more likely to be treated with antibiotics, by a margin of 29% to 23%.

“These findings open new possibilities for antimicrobial stewardship in these groups of virally infected children,” observed Dr. Papan.

Fever of unknown origin was present in 68.8% of the influenza-positive patients, compared with just 0.2% of the RSV-positive children. In contrast, 50.2% of the RSV group had pneumonia and 49.6% had bronchitis or bronchiolitis, versus just 22.9% and 6.3% of the influenza patients, respectively. A larger proportion of the young children with RSV infection presented in a severely ill–looking condition. Children with RSV infection also were significantly younger.

Dr. Papan reported having no financial conflicts regarding his study.

[email protected]

LJUBLJANA, SLOVENIA – Fever of unknown origin and pneumonia are two clinical features useful in distinguishing between influenza and respiratory syncytial virus infection as the cause of hospitalization in infants and young children, Cihan Papan, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

Dr. Papan, a pediatrician at University Children’s Hospital Mannheim (Germany) and Heidelberg (Germany) University, presented a retrospective single-center study of all 573 children aged under 2 years hospitalized over the course of several seasons for respiratory syncytial virus (RSV) or influenza as confirmed by rapid antigen testing. Even though these are two of the leading causes of hospitalization among young children, there is surprisingly sparse data comparing the two in terms of disease severity and hospital resource utilization, including antibiotic consumption. That information gap provided the basis for this study.

There were 476 children with confirmed RSV, 96 with influenza, and 1 RSV/influenza coinfection. Notably, even though the RSV group had lower temperatures and C-reactive protein levels, they were nevertheless more likely to be treated with antibiotics, by a margin of 29% to 23%.

“These findings open new possibilities for antimicrobial stewardship in these groups of virally infected children,” observed Dr. Papan.

Fever of unknown origin was present in 68.8% of the influenza-positive patients, compared with just 0.2% of the RSV-positive children. In contrast, 50.2% of the RSV group had pneumonia and 49.6% had bronchitis or bronchiolitis, versus just 22.9% and 6.3% of the influenza patients, respectively. A larger proportion of the young children with RSV infection presented in a severely ill–looking condition. Children with RSV infection also were significantly younger.

Dr. Papan reported having no financial conflicts regarding his study.

[email protected]

LJUBLJANA, SLOVENIA – Fever of unknown origin and pneumonia are two clinical features useful in distinguishing between influenza and respiratory syncytial virus infection as the cause of hospitalization in infants and young children, Cihan Papan, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

Dr. Papan, a pediatrician at University Children’s Hospital Mannheim (Germany) and Heidelberg (Germany) University, presented a retrospective single-center study of all 573 children aged under 2 years hospitalized over the course of several seasons for respiratory syncytial virus (RSV) or influenza as confirmed by rapid antigen testing. Even though these are two of the leading causes of hospitalization among young children, there is surprisingly sparse data comparing the two in terms of disease severity and hospital resource utilization, including antibiotic consumption. That information gap provided the basis for this study.

There were 476 children with confirmed RSV, 96 with influenza, and 1 RSV/influenza coinfection. Notably, even though the RSV group had lower temperatures and C-reactive protein levels, they were nevertheless more likely to be treated with antibiotics, by a margin of 29% to 23%.

“These findings open new possibilities for antimicrobial stewardship in these groups of virally infected children,” observed Dr. Papan.

Fever of unknown origin was present in 68.8% of the influenza-positive patients, compared with just 0.2% of the RSV-positive children. In contrast, 50.2% of the RSV group had pneumonia and 49.6% had bronchitis or bronchiolitis, versus just 22.9% and 6.3% of the influenza patients, respectively. A larger proportion of the young children with RSV infection presented in a severely ill–looking condition. Children with RSV infection also were significantly younger.

Dr. Papan reported having no financial conflicts regarding his study.

[email protected]

Clinical question

Does use of corticosteroids or infliximab in addition to intravenous immunoglobulin improve cardiac outcomes in children with Kawasaki disease and enlarged coronary arteries?

Background

Kawasaki disease is a medium-vessel vasculitis primarily of young children. While the underlying cause remains unknown, treatment with intravenous immunoglobulin (IVIG) substantially lowers the risk of coronary artery aneurysms (CAA), the most serious sequelae of Kawasaki disease. Recent studies have suggested that – in cases of high-risk or treatment-resistant Kawasaki disease – using an immunomodulator, such as a corticosteroid or a TNF-alpha blocker, may improve outcomes, though these studies involved relatively small and homogeneous patient populations. It is unknown if these medications could prevent progression of CAA.

Study design

Retrospective multicenter study.

Setting

Two freestanding children’s hospitals and one mother-child hospital.

Synopsis

The study identified 121 children diagnosed with Kawasaki disease with CAA (z score 2.5-10) from 2008 through 2017 treated at the three study hospitals. Children with giant CAA at the time of diagnosis (z score greater than 10) or significant preexisting congenital heart disease were excluded.

All study hospitals had protocols for treatment of Kawasaki disease: Center 1 used IVIG and corticosteroids, Center 2 used IVIG and infliximab, and Center 3 used IVIG alone. Patients at all centers also received aspirin. Center 1 used methylprednisolone IV initially, changing to oral prednisolone after clinical improvement. The researchers reviewed the charts of each patient and classified them as having complete or incomplete Kawasaki disease. They assigned z scores for CAA size based on both initial and follow-up echocardiograms. The primary outcome was change in z score of CAA over the first year.

The population of patients treated at each center was significantly different. Center 1 reported older patients (median age 2.6 vs. 2.0 and 1.1), as well as a higher rate of male patients (83% vs. 77% and 58%). However, there was no difference in baseline z scores between centers. Patients who initially received IVIG and corticosteroids were less likely to require additional therapy because of persistent fever versus those receiving IVIG only, or IVIG and infliximab (0% vs. 21% vs. 14%, P = .03).

Patients receiving IVIG and corticosteroids, or IVIG and infliximab, were less likely to have progression of CAA size, with 23% and 24% having an increase in z score of more than 1 versus 58% of those who received IVIG alone. No group had significant differences in maximum z score, the rate of giant aneurysms, or the rate of regression of CAA.

Bottom line

Using IVIG + corticosteroids or IVIG + infliximab versus IVIG alone for children with Kawasaki disease with coronary artery aneurysms decreases the rate of aneurysm enlargement.

Citation

Dionne A et al. Treatment intensification in patients with Kawasaki disease and coronary aneurysm at diagnosis. Pediatrics. May 2019:e20183341. doi: 10.1542/peds.2018-3341.

Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. duPont Hospital for Children in Wilmington, Del., and clinical assistant professor of pediatrics at Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia.

Clinical question

Does use of corticosteroids or infliximab in addition to intravenous immunoglobulin improve cardiac outcomes in children with Kawasaki disease and enlarged coronary arteries?

Background

Kawasaki disease is a medium-vessel vasculitis primarily of young children. While the underlying cause remains unknown, treatment with intravenous immunoglobulin (IVIG) substantially lowers the risk of coronary artery aneurysms (CAA), the most serious sequelae of Kawasaki disease. Recent studies have suggested that – in cases of high-risk or treatment-resistant Kawasaki disease – using an immunomodulator, such as a corticosteroid or a TNF-alpha blocker, may improve outcomes, though these studies involved relatively small and homogeneous patient populations. It is unknown if these medications could prevent progression of CAA.

Study design

Retrospective multicenter study.

Setting

Two freestanding children’s hospitals and one mother-child hospital.

Synopsis

The study identified 121 children diagnosed with Kawasaki disease with CAA (z score 2.5-10) from 2008 through 2017 treated at the three study hospitals. Children with giant CAA at the time of diagnosis (z score greater than 10) or significant preexisting congenital heart disease were excluded.

All study hospitals had protocols for treatment of Kawasaki disease: Center 1 used IVIG and corticosteroids, Center 2 used IVIG and infliximab, and Center 3 used IVIG alone. Patients at all centers also received aspirin. Center 1 used methylprednisolone IV initially, changing to oral prednisolone after clinical improvement. The researchers reviewed the charts of each patient and classified them as having complete or incomplete Kawasaki disease. They assigned z scores for CAA size based on both initial and follow-up echocardiograms. The primary outcome was change in z score of CAA over the first year.

The population of patients treated at each center was significantly different. Center 1 reported older patients (median age 2.6 vs. 2.0 and 1.1), as well as a higher rate of male patients (83% vs. 77% and 58%). However, there was no difference in baseline z scores between centers. Patients who initially received IVIG and corticosteroids were less likely to require additional therapy because of persistent fever versus those receiving IVIG only, or IVIG and infliximab (0% vs. 21% vs. 14%, P = .03).

Patients receiving IVIG and corticosteroids, or IVIG and infliximab, were less likely to have progression of CAA size, with 23% and 24% having an increase in z score of more than 1 versus 58% of those who received IVIG alone. No group had significant differences in maximum z score, the rate of giant aneurysms, or the rate of regression of CAA.

Bottom line

Using IVIG + corticosteroids or IVIG + infliximab versus IVIG alone for children with Kawasaki disease with coronary artery aneurysms decreases the rate of aneurysm enlargement.

Citation

Dionne A et al. Treatment intensification in patients with Kawasaki disease and coronary aneurysm at diagnosis. Pediatrics. May 2019:e20183341. doi: 10.1542/peds.2018-3341.

Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. duPont Hospital for Children in Wilmington, Del., and clinical assistant professor of pediatrics at Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia.

Clinical question

Does use of corticosteroids or infliximab in addition to intravenous immunoglobulin improve cardiac outcomes in children with Kawasaki disease and enlarged coronary arteries?

Background

Kawasaki disease is a medium-vessel vasculitis primarily of young children. While the underlying cause remains unknown, treatment with intravenous immunoglobulin (IVIG) substantially lowers the risk of coronary artery aneurysms (CAA), the most serious sequelae of Kawasaki disease. Recent studies have suggested that – in cases of high-risk or treatment-resistant Kawasaki disease – using an immunomodulator, such as a corticosteroid or a TNF-alpha blocker, may improve outcomes, though these studies involved relatively small and homogeneous patient populations. It is unknown if these medications could prevent progression of CAA.

Study design

Retrospective multicenter study.

Setting

Two freestanding children’s hospitals and one mother-child hospital.

Synopsis

The study identified 121 children diagnosed with Kawasaki disease with CAA (z score 2.5-10) from 2008 through 2017 treated at the three study hospitals. Children with giant CAA at the time of diagnosis (z score greater than 10) or significant preexisting congenital heart disease were excluded.

All study hospitals had protocols for treatment of Kawasaki disease: Center 1 used IVIG and corticosteroids, Center 2 used IVIG and infliximab, and Center 3 used IVIG alone. Patients at all centers also received aspirin. Center 1 used methylprednisolone IV initially, changing to oral prednisolone after clinical improvement. The researchers reviewed the charts of each patient and classified them as having complete or incomplete Kawasaki disease. They assigned z scores for CAA size based on both initial and follow-up echocardiograms. The primary outcome was change in z score of CAA over the first year.

The population of patients treated at each center was significantly different. Center 1 reported older patients (median age 2.6 vs. 2.0 and 1.1), as well as a higher rate of male patients (83% vs. 77% and 58%). However, there was no difference in baseline z scores between centers. Patients who initially received IVIG and corticosteroids were less likely to require additional therapy because of persistent fever versus those receiving IVIG only, or IVIG and infliximab (0% vs. 21% vs. 14%, P = .03).

Patients receiving IVIG and corticosteroids, or IVIG and infliximab, were less likely to have progression of CAA size, with 23% and 24% having an increase in z score of more than 1 versus 58% of those who received IVIG alone. No group had significant differences in maximum z score, the rate of giant aneurysms, or the rate of regression of CAA.

Bottom line

Using IVIG + corticosteroids or IVIG + infliximab versus IVIG alone for children with Kawasaki disease with coronary artery aneurysms decreases the rate of aneurysm enlargement.

Citation

Dionne A et al. Treatment intensification in patients with Kawasaki disease and coronary aneurysm at diagnosis. Pediatrics. May 2019:e20183341. doi: 10.1542/peds.2018-3341.

Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. duPont Hospital for Children in Wilmington, Del., and clinical assistant professor of pediatrics at Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia.

When it comes to treatment recommendations for high-risk breast cancer, oncologists agree with a leading artificial intelligence platform about half the time, according to investigators.

In the first study of its kind, involving 10 Chinese oncologists, recommendation concordance with the Watson for Oncology treatment advisory tool (WfO) was generally lower for hormone receptor–positive and metastatic cancers than hormone receptor–negative and nonmetastatic cases, reported Fengrui Xu, MD, of the Academy of Military Medical Sciences in Beijing, and colleagues. Refinement could enable broad use of Watson, not to dictate treatment decisions, but instead to propose alternate treatment approaches and offer point-of-care access to relevant evidence.

“[WfO] is an example of a quantitative oncology clinical decision support that leverages the clinical expertise of oncologists at Memorial Sloan Kettering Cancer Center [MSKCC],” the investigators wrote in JCO Clinical Cancer Informatics. The platform uses machine-learning software to interpret patient scenarios in light from MSKCC training cases, MSKCC treatment guidelines, and more than 300 medical textbooks and journals.

To compare WfO with real-world decision makers, the investigators recruited three chief physicians, four attending physicians, and three fellows to provide treatment recommendations for 1,977 patients with complex breast cancer who were treated at 10 hospitals in China. Participating physicians shared the workload; each evaluated an average of 198 different cases.

On average, oncologists and WfO made the same treatment recommendations 56% of the time. Out of the different types of physicians, fellows were most likely to agree with WfO, based on a 68% concordance rate, compared with 54% for chief physicians and 49% for attending physicians. Including all physicians, concordance was lowest for hormone receptor–positive/HER2-positive disease (48%) and highest for triple-negative cases (71%). Adjuvant and metastatic therapies were also evaluated, with high concordance for adjuvant endocrine (78%) and targeted therapy (100%), compared with moderate concordance for first- (52%) and second-line metastatic therapy (50%). The investigators described concordance results as generally “modest;” however, they noted that such levels are promising.

“This degree of concordance is encouraging because therapeutic decisions in these cases are often difficult as a result of the current limits of medical knowledge for treating complex breast cancers and the presence of local contextual factors that affect physician treatment choices,” the investigators wrote. “It is important to note that nonconcordance does not imply that one treatment is correct for a given patient and another is not, nor does it necessarily diminish the potential value of a decision support system that provides access to supporting evidence and insight into its reasoning process.”

The study was funded by Zefei Jiang. The investigators reported affiliations with IBM Watson Health, Pharmaceutical Manufacturer Institution, Merck, and others.

SOURCE: Xu F et al. JCO Clin Cancer Inform. 2019 Aug 16. doi: 10.1200/CCI.18.00159.

When it comes to treatment recommendations for high-risk breast cancer, oncologists agree with a leading artificial intelligence platform about half the time, according to investigators.

In the first study of its kind, involving 10 Chinese oncologists, recommendation concordance with the Watson for Oncology treatment advisory tool (WfO) was generally lower for hormone receptor–positive and metastatic cancers than hormone receptor–negative and nonmetastatic cases, reported Fengrui Xu, MD, of the Academy of Military Medical Sciences in Beijing, and colleagues. Refinement could enable broad use of Watson, not to dictate treatment decisions, but instead to propose alternate treatment approaches and offer point-of-care access to relevant evidence.

“[WfO] is an example of a quantitative oncology clinical decision support that leverages the clinical expertise of oncologists at Memorial Sloan Kettering Cancer Center [MSKCC],” the investigators wrote in JCO Clinical Cancer Informatics. The platform uses machine-learning software to interpret patient scenarios in light from MSKCC training cases, MSKCC treatment guidelines, and more than 300 medical textbooks and journals.

To compare WfO with real-world decision makers, the investigators recruited three chief physicians, four attending physicians, and three fellows to provide treatment recommendations for 1,977 patients with complex breast cancer who were treated at 10 hospitals in China. Participating physicians shared the workload; each evaluated an average of 198 different cases.

On average, oncologists and WfO made the same treatment recommendations 56% of the time. Out of the different types of physicians, fellows were most likely to agree with WfO, based on a 68% concordance rate, compared with 54% for chief physicians and 49% for attending physicians. Including all physicians, concordance was lowest for hormone receptor–positive/HER2-positive disease (48%) and highest for triple-negative cases (71%). Adjuvant and metastatic therapies were also evaluated, with high concordance for adjuvant endocrine (78%) and targeted therapy (100%), compared with moderate concordance for first- (52%) and second-line metastatic therapy (50%). The investigators described concordance results as generally “modest;” however, they noted that such levels are promising.

“This degree of concordance is encouraging because therapeutic decisions in these cases are often difficult as a result of the current limits of medical knowledge for treating complex breast cancers and the presence of local contextual factors that affect physician treatment choices,” the investigators wrote. “It is important to note that nonconcordance does not imply that one treatment is correct for a given patient and another is not, nor does it necessarily diminish the potential value of a decision support system that provides access to supporting evidence and insight into its reasoning process.”

The study was funded by Zefei Jiang. The investigators reported affiliations with IBM Watson Health, Pharmaceutical Manufacturer Institution, Merck, and others.

SOURCE: Xu F et al. JCO Clin Cancer Inform. 2019 Aug 16. doi: 10.1200/CCI.18.00159.

When it comes to treatment recommendations for high-risk breast cancer, oncologists agree with a leading artificial intelligence platform about half the time, according to investigators.

In the first study of its kind, involving 10 Chinese oncologists, recommendation concordance with the Watson for Oncology treatment advisory tool (WfO) was generally lower for hormone receptor–positive and metastatic cancers than hormone receptor–negative and nonmetastatic cases, reported Fengrui Xu, MD, of the Academy of Military Medical Sciences in Beijing, and colleagues. Refinement could enable broad use of Watson, not to dictate treatment decisions, but instead to propose alternate treatment approaches and offer point-of-care access to relevant evidence.

“[WfO] is an example of a quantitative oncology clinical decision support that leverages the clinical expertise of oncologists at Memorial Sloan Kettering Cancer Center [MSKCC],” the investigators wrote in JCO Clinical Cancer Informatics. The platform uses machine-learning software to interpret patient scenarios in light from MSKCC training cases, MSKCC treatment guidelines, and more than 300 medical textbooks and journals.

To compare WfO with real-world decision makers, the investigators recruited three chief physicians, four attending physicians, and three fellows to provide treatment recommendations for 1,977 patients with complex breast cancer who were treated at 10 hospitals in China. Participating physicians shared the workload; each evaluated an average of 198 different cases.

On average, oncologists and WfO made the same treatment recommendations 56% of the time. Out of the different types of physicians, fellows were most likely to agree with WfO, based on a 68% concordance rate, compared with 54% for chief physicians and 49% for attending physicians. Including all physicians, concordance was lowest for hormone receptor–positive/HER2-positive disease (48%) and highest for triple-negative cases (71%). Adjuvant and metastatic therapies were also evaluated, with high concordance for adjuvant endocrine (78%) and targeted therapy (100%), compared with moderate concordance for first- (52%) and second-line metastatic therapy (50%). The investigators described concordance results as generally “modest;” however, they noted that such levels are promising.

“This degree of concordance is encouraging because therapeutic decisions in these cases are often difficult as a result of the current limits of medical knowledge for treating complex breast cancers and the presence of local contextual factors that affect physician treatment choices,” the investigators wrote. “It is important to note that nonconcordance does not imply that one treatment is correct for a given patient and another is not, nor does it necessarily diminish the potential value of a decision support system that provides access to supporting evidence and insight into its reasoning process.”

The study was funded by Zefei Jiang. The investigators reported affiliations with IBM Watson Health, Pharmaceutical Manufacturer Institution, Merck, and others.

SOURCE: Xu F et al. JCO Clin Cancer Inform. 2019 Aug 16. doi: 10.1200/CCI.18.00159.

PHILADELPHIA – In patients with migraine and medication overuse, galcanezumab reduces the number of mean monthly migraine headache days, according to research presented at the annual meeting of the American Headache Society. Furthermore, galcanezumab is associated with a reduction in medication overuse, compared with placebo, in this population.

“When you have targeted preventive treatment and you reduce the burden of illness, medication overuse seems to be reduced as well,” said Sheena Aurora, MD, adjunct clinical associate professor of anesthesiology and perioperative and pain medicine at Stanford (Calif.) Health Care. Dr. Aurora also is a medical fellow and global launch leader for galcanezumab at Eli Lilly, which has developed the treatment.

Galcanezumab is a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide. The phase 3 EVOLVE-1, EVOLVE-2, and REGAIN studies indicated galcanezumab’s superiority to placebo in preventing episodic and chronic migraine.
 

A post hoc analysis of phase 3 data

Dr. Aurora and colleagues conducted a post hoc analysis of data from the three phase 3 studies to examine galcanezumab’s effect in patients with medication overuse. EVOLVE-1 and EVOLVE-2 included patients with episodic migraine, and REGAIN included patients with chronic migraine. All participants were randomized to monthly subcutaneous injections of placebo or galcanezumab (120 mg/month or 240 mg/month) for 3-6 months. Based on information obtained through electronic patient-reported outcome diaries, investigators determined headache medication overuse using criteria adapted from the International Classification of Headache Disorders, third edition. They estimated mean changes in monthly headache days and the proportion of patients with medication overuse after randomization using mixed modeling.

The demographic characteristics of the three study populations were similar to those reported in epidemiologic studies of migraine, said Dr. Aurora. Most participants were women, and most patients were between ages 40 and 49 years. At baseline, the mean number of monthly migraine headache days was 20 among patients with chronic migraine and 9 among patients with episodic migraine.

The rate of medication overuse was higher in the combined study population than in the literature. Patients with medication overuse had greater disability and greater health care resource utilization, compared with patients without medication overuse. Among patients with chronic migraine, participants who overused medication were not significantly different from those who did not. But among patients with episodic migraine, participants who overused medication had higher headache frequency than those who did not.

In the EVOLVE trials, the proportion of patients with baseline medication overuse was 19.3% in the placebo arm, 17.0% in the galcanezumab 120-mg arm, and 19.2% in the galcanezumab 240-mg arm. In REGAIN, the proportion of patients with baseline medication overuse was 63.4% in the placebo arm, 64.3% in the galcanezumab 120-mg arm, and 64.1% in the galcanezumab 240-mg arm.

Galcanezumab reduced medication overuse

Compared with placebo, both doses of galcanezumab significantly decreased mean monthly migraine headache days in patients with baseline medication overuse. In the EVOLVE studies, this endpoint decreased by 2.71 in the placebo group, 6.26 in the galcanezumab 120-mg group, and 5.77 in the galcanezumab 240-mg group. In REGAIN, the reductions were 2.25 in the placebo group, 4.78 in the galcanezumab 120-mg group, and 4.51 in the galcanezumab 240-mg group. The effect size was higher in patients who were overusing medications, compared with those who were not, said Dr. Aurora. “This is clinically relevant, because most of us ... had this belief that patients who were overusing medications may be more treatment-resistant to prevention.”

In addition, galcanezumab was associated with significantly lower rates of average monthly medication overuse, compared with placebo. In the EVOLVE studies, the average rate of monthly medication overuse was 15.9% for the placebo group, 6.2% for the galcanezumab 120-mg group, and 7.9% for the galcanezumab 240-mg group. In REGAIN, the average rate of monthly medication overuse was 40.6% in the placebo group, 24.3% in the galcanezumab 120-mg group, and 23.1% in the galcanezumab 240-mg group. About 85% of patients with episodic migraine and medication overuse had a reduction in medication overuse, and approximately 50% of patients with chronic migraine and medication overuse had a reduction in medication overuse, said Dr. Aurora.

Dr. Aurora and coinvestigators are employees of Eli Lilly, which developed galcanezumab and funded the EVOLVE and REGAIN studies.

[email protected]

SOURCE: Aurora S et al. AHS 2019. Abstract IOR07.

PHILADELPHIA – In patients with migraine and medication overuse, galcanezumab reduces the number of mean monthly migraine headache days, according to research presented at the annual meeting of the American Headache Society. Furthermore, galcanezumab is associated with a reduction in medication overuse, compared with placebo, in this population.

“When you have targeted preventive treatment and you reduce the burden of illness, medication overuse seems to be reduced as well,” said Sheena Aurora, MD, adjunct clinical associate professor of anesthesiology and perioperative and pain medicine at Stanford (Calif.) Health Care. Dr. Aurora also is a medical fellow and global launch leader for galcanezumab at Eli Lilly, which has developed the treatment.

Galcanezumab is a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide. The phase 3 EVOLVE-1, EVOLVE-2, and REGAIN studies indicated galcanezumab’s superiority to placebo in preventing episodic and chronic migraine.
 

A post hoc analysis of phase 3 data

Dr. Aurora and colleagues conducted a post hoc analysis of data from the three phase 3 studies to examine galcanezumab’s effect in patients with medication overuse. EVOLVE-1 and EVOLVE-2 included patients with episodic migraine, and REGAIN included patients with chronic migraine. All participants were randomized to monthly subcutaneous injections of placebo or galcanezumab (120 mg/month or 240 mg/month) for 3-6 months. Based on information obtained through electronic patient-reported outcome diaries, investigators determined headache medication overuse using criteria adapted from the International Classification of Headache Disorders, third edition. They estimated mean changes in monthly headache days and the proportion of patients with medication overuse after randomization using mixed modeling.

The demographic characteristics of the three study populations were similar to those reported in epidemiologic studies of migraine, said Dr. Aurora. Most participants were women, and most patients were between ages 40 and 49 years. At baseline, the mean number of monthly migraine headache days was 20 among patients with chronic migraine and 9 among patients with episodic migraine.

The rate of medication overuse was higher in the combined study population than in the literature. Patients with medication overuse had greater disability and greater health care resource utilization, compared with patients without medication overuse. Among patients with chronic migraine, participants who overused medication were not significantly different from those who did not. But among patients with episodic migraine, participants who overused medication had higher headache frequency than those who did not.

In the EVOLVE trials, the proportion of patients with baseline medication overuse was 19.3% in the placebo arm, 17.0% in the galcanezumab 120-mg arm, and 19.2% in the galcanezumab 240-mg arm. In REGAIN, the proportion of patients with baseline medication overuse was 63.4% in the placebo arm, 64.3% in the galcanezumab 120-mg arm, and 64.1% in the galcanezumab 240-mg arm.

Galcanezumab reduced medication overuse

Compared with placebo, both doses of galcanezumab significantly decreased mean monthly migraine headache days in patients with baseline medication overuse. In the EVOLVE studies, this endpoint decreased by 2.71 in the placebo group, 6.26 in the galcanezumab 120-mg group, and 5.77 in the galcanezumab 240-mg group. In REGAIN, the reductions were 2.25 in the placebo group, 4.78 in the galcanezumab 120-mg group, and 4.51 in the galcanezumab 240-mg group. The effect size was higher in patients who were overusing medications, compared with those who were not, said Dr. Aurora. “This is clinically relevant, because most of us ... had this belief that patients who were overusing medications may be more treatment-resistant to prevention.”

In addition, galcanezumab was associated with significantly lower rates of average monthly medication overuse, compared with placebo. In the EVOLVE studies, the average rate of monthly medication overuse was 15.9% for the placebo group, 6.2% for the galcanezumab 120-mg group, and 7.9% for the galcanezumab 240-mg group. In REGAIN, the average rate of monthly medication overuse was 40.6% in the placebo group, 24.3% in the galcanezumab 120-mg group, and 23.1% in the galcanezumab 240-mg group. About 85% of patients with episodic migraine and medication overuse had a reduction in medication overuse, and approximately 50% of patients with chronic migraine and medication overuse had a reduction in medication overuse, said Dr. Aurora.

Dr. Aurora and coinvestigators are employees of Eli Lilly, which developed galcanezumab and funded the EVOLVE and REGAIN studies.

[email protected]

SOURCE: Aurora S et al. AHS 2019. Abstract IOR07.

PHILADELPHIA – In patients with migraine and medication overuse, galcanezumab reduces the number of mean monthly migraine headache days, according to research presented at the annual meeting of the American Headache Society. Furthermore, galcanezumab is associated with a reduction in medication overuse, compared with placebo, in this population.

“When you have targeted preventive treatment and you reduce the burden of illness, medication overuse seems to be reduced as well,” said Sheena Aurora, MD, adjunct clinical associate professor of anesthesiology and perioperative and pain medicine at Stanford (Calif.) Health Care. Dr. Aurora also is a medical fellow and global launch leader for galcanezumab at Eli Lilly, which has developed the treatment.

Galcanezumab is a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide. The phase 3 EVOLVE-1, EVOLVE-2, and REGAIN studies indicated galcanezumab’s superiority to placebo in preventing episodic and chronic migraine.
 

A post hoc analysis of phase 3 data

Dr. Aurora and colleagues conducted a post hoc analysis of data from the three phase 3 studies to examine galcanezumab’s effect in patients with medication overuse. EVOLVE-1 and EVOLVE-2 included patients with episodic migraine, and REGAIN included patients with chronic migraine. All participants were randomized to monthly subcutaneous injections of placebo or galcanezumab (120 mg/month or 240 mg/month) for 3-6 months. Based on information obtained through electronic patient-reported outcome diaries, investigators determined headache medication overuse using criteria adapted from the International Classification of Headache Disorders, third edition. They estimated mean changes in monthly headache days and the proportion of patients with medication overuse after randomization using mixed modeling.

The demographic characteristics of the three study populations were similar to those reported in epidemiologic studies of migraine, said Dr. Aurora. Most participants were women, and most patients were between ages 40 and 49 years. At baseline, the mean number of monthly migraine headache days was 20 among patients with chronic migraine and 9 among patients with episodic migraine.

The rate of medication overuse was higher in the combined study population than in the literature. Patients with medication overuse had greater disability and greater health care resource utilization, compared with patients without medication overuse. Among patients with chronic migraine, participants who overused medication were not significantly different from those who did not. But among patients with episodic migraine, participants who overused medication had higher headache frequency than those who did not.

In the EVOLVE trials, the proportion of patients with baseline medication overuse was 19.3% in the placebo arm, 17.0% in the galcanezumab 120-mg arm, and 19.2% in the galcanezumab 240-mg arm. In REGAIN, the proportion of patients with baseline medication overuse was 63.4% in the placebo arm, 64.3% in the galcanezumab 120-mg arm, and 64.1% in the galcanezumab 240-mg arm.

Galcanezumab reduced medication overuse

Compared with placebo, both doses of galcanezumab significantly decreased mean monthly migraine headache days in patients with baseline medication overuse. In the EVOLVE studies, this endpoint decreased by 2.71 in the placebo group, 6.26 in the galcanezumab 120-mg group, and 5.77 in the galcanezumab 240-mg group. In REGAIN, the reductions were 2.25 in the placebo group, 4.78 in the galcanezumab 120-mg group, and 4.51 in the galcanezumab 240-mg group. The effect size was higher in patients who were overusing medications, compared with those who were not, said Dr. Aurora. “This is clinically relevant, because most of us ... had this belief that patients who were overusing medications may be more treatment-resistant to prevention.”

In addition, galcanezumab was associated with significantly lower rates of average monthly medication overuse, compared with placebo. In the EVOLVE studies, the average rate of monthly medication overuse was 15.9% for the placebo group, 6.2% for the galcanezumab 120-mg group, and 7.9% for the galcanezumab 240-mg group. In REGAIN, the average rate of monthly medication overuse was 40.6% in the placebo group, 24.3% in the galcanezumab 120-mg group, and 23.1% in the galcanezumab 240-mg group. About 85% of patients with episodic migraine and medication overuse had a reduction in medication overuse, and approximately 50% of patients with chronic migraine and medication overuse had a reduction in medication overuse, said Dr. Aurora.

Dr. Aurora and coinvestigators are employees of Eli Lilly, which developed galcanezumab and funded the EVOLVE and REGAIN studies.

[email protected]

SOURCE: Aurora S et al. AHS 2019. Abstract IOR07.

The patient was given a diagnosis of green nail syndrome (GNS), an infection of the nail bed caused by Pseudomonas aeruginosa. These bacteria produce pyocyanin, a blue-green pigment that discolors the nail. GNS often occurs in patients with prior nail problems, such as onychomycosis, onycholysis, trauma, chronic paronychia, or psoriasis.

Nail disease disrupts the integumentary barrier and allows a portal of entry for bacteria. Scanning electron microscopy of patients with GNS has shown that fungal infections create tunnel-like structures in the nail keratin, and P aeruginosa can grow in these spaces. Nails with prior nail disease that are chronically exposed to moisture are at greatest risk of developing GNS, and it is typical for only one nail to be involved.

It’s likely that this patient’s earlier nail problem had been a case of onycholysis, based on her description of a “spongy” nail bed and loose nail. This created a favorable environment for an infection by allowing moisture and bacteria to infiltrate the space. The patient also acknowledged that she washed dishes by hand and bathed her young children. This frequent soaking of her hands likely helped to provide a moist environment in which P aeruginosa could thrive. In addition, onycholysis is associated with hypothyroidism, which the patient also had.

GNS can be diagnosed by clinical observation and characteristic pigmentation along with an appropriate patient history. Nail discoloration, or chromonychia, can present in a variety of colors. Nail findings may represent an isolated disease or provide an important clinical clue to other systemic diseases. The specific shade of discoloration helps to differentiate the underlying pathology. Culture of the nail bed may be helpful if bacterial resistance or co-infection with fungal organisms is suspected. GNS is often painless, but may be accompanied by mild tenderness of the nail.

The patient was prescribed ciprofloxacin 500 mg twice a day for 10 days, plus bleach soaks (1 part bleach to 4 parts water) twice a day. She also was advised to wear gloves for household tasks that involved immersing her hands in water, and to dry her finger with a hair dryer after bathing.

‌

This case was adapted from: Gish D, Romero BJ. Green fingernail. J Fam Pract. 2017;66:E7-E9.

The patient was given a diagnosis of green nail syndrome (GNS), an infection of the nail bed caused by Pseudomonas aeruginosa. These bacteria produce pyocyanin, a blue-green pigment that discolors the nail. GNS often occurs in patients with prior nail problems, such as onychomycosis, onycholysis, trauma, chronic paronychia, or psoriasis.

Nail disease disrupts the integumentary barrier and allows a portal of entry for bacteria. Scanning electron microscopy of patients with GNS has shown that fungal infections create tunnel-like structures in the nail keratin, and P aeruginosa can grow in these spaces. Nails with prior nail disease that are chronically exposed to moisture are at greatest risk of developing GNS, and it is typical for only one nail to be involved.

It’s likely that this patient’s earlier nail problem had been a case of onycholysis, based on her description of a “spongy” nail bed and loose nail. This created a favorable environment for an infection by allowing moisture and bacteria to infiltrate the space. The patient also acknowledged that she washed dishes by hand and bathed her young children. This frequent soaking of her hands likely helped to provide a moist environment in which P aeruginosa could thrive. In addition, onycholysis is associated with hypothyroidism, which the patient also had.

GNS can be diagnosed by clinical observation and characteristic pigmentation along with an appropriate patient history. Nail discoloration, or chromonychia, can present in a variety of colors. Nail findings may represent an isolated disease or provide an important clinical clue to other systemic diseases. The specific shade of discoloration helps to differentiate the underlying pathology. Culture of the nail bed may be helpful if bacterial resistance or co-infection with fungal organisms is suspected. GNS is often painless, but may be accompanied by mild tenderness of the nail.

The patient was prescribed ciprofloxacin 500 mg twice a day for 10 days, plus bleach soaks (1 part bleach to 4 parts water) twice a day. She also was advised to wear gloves for household tasks that involved immersing her hands in water, and to dry her finger with a hair dryer after bathing.

‌

This case was adapted from: Gish D, Romero BJ. Green fingernail. J Fam Pract. 2017;66:E7-E9.

The patient was given a diagnosis of green nail syndrome (GNS), an infection of the nail bed caused by Pseudomonas aeruginosa. These bacteria produce pyocyanin, a blue-green pigment that discolors the nail. GNS often occurs in patients with prior nail problems, such as onychomycosis, onycholysis, trauma, chronic paronychia, or psoriasis.

Nail disease disrupts the integumentary barrier and allows a portal of entry for bacteria. Scanning electron microscopy of patients with GNS has shown that fungal infections create tunnel-like structures in the nail keratin, and P aeruginosa can grow in these spaces. Nails with prior nail disease that are chronically exposed to moisture are at greatest risk of developing GNS, and it is typical for only one nail to be involved.

It’s likely that this patient’s earlier nail problem had been a case of onycholysis, based on her description of a “spongy” nail bed and loose nail. This created a favorable environment for an infection by allowing moisture and bacteria to infiltrate the space. The patient also acknowledged that she washed dishes by hand and bathed her young children. This frequent soaking of her hands likely helped to provide a moist environment in which P aeruginosa could thrive. In addition, onycholysis is associated with hypothyroidism, which the patient also had.

GNS can be diagnosed by clinical observation and characteristic pigmentation along with an appropriate patient history. Nail discoloration, or chromonychia, can present in a variety of colors. Nail findings may represent an isolated disease or provide an important clinical clue to other systemic diseases. The specific shade of discoloration helps to differentiate the underlying pathology. Culture of the nail bed may be helpful if bacterial resistance or co-infection with fungal organisms is suspected. GNS is often painless, but may be accompanied by mild tenderness of the nail.

The patient was prescribed ciprofloxacin 500 mg twice a day for 10 days, plus bleach soaks (1 part bleach to 4 parts water) twice a day. She also was advised to wear gloves for household tasks that involved immersing her hands in water, and to dry her finger with a hair dryer after bathing.

‌

This case was adapted from: Gish D, Romero BJ. Green fingernail. J Fam Pract. 2017;66:E7-E9.

Veterans with a clinically meaningful reduction in symptoms of PTSD are less likely to develop type 2 diabetes, research from a retrospective study shows.

“We cautiously speculate that normalization of hypothalamic-pituitary-adrenal axis and cortisol levels could be one mechanism behind our results,” wrote Jeffrey F. Scherrer, PhD, and colleagues. “PTSD is associated with inflammation, which may in turn be associated with increased risk for [type 2 diabetes].” The study was published in JAMA Psychiatry.

Using medical record data from the Veterans Health Administration, Dr. Scherrer and colleagues identified 5,916 patients with PTSD who visited a VHA medical center between 2008 and 2012, and scored at least 50 points or higher on the PTSD Checklist (PCL) followed by another PCL score at least 8 months after the previous score. The mean age of patients in the study was 42.1 years, the cohort consisted of 84.3% men, and 66.3% patients were white. PCL score reduction was deemed clinically meaningful if there was a decrease of 20 points or more in the score, reported Dr. Scherrer of the department of family and community medicine at Saint Louis University and colleagues.

Patients who were older (mean 43.6 years vs. mean 41.7 years; P = .02) and those who underwent minimally adequate duration of PTSD psychotherapy (P less than .001) were significantly more likely to have a clinically meaningful decrease in PCL scores. Patients who received antidepressants (P = .004) or antipsychotics (P less than .001) were significantly more likely to have less than clinically meaningful decreases in PCL scores. Factors that put patients at significantly higher risk of developing type 2 diabetes included older age (hazard ratio, 1.05; 95% confidence interval, 1.04-1.07; P less than .001), black race/ethnicity (HR, 1.86; 95% CI, 1.23-2.83; P = .004), hypertension (HR, 3.46; 95% CI, 2.33-5.16), hyperlipidemia (HR, 2.82; 95% CI, 1.91-4.16), and obesity (HR, 3.32; 95% CI, 2.12-5.21) (all P less than .001).

Minimally adequate duration of PTSD psychotherapy and high use of primary care health services also were associated with developing type 2 diabetes.

In a Cox proportional hazards regression model, patients with clinically meaningful decreases in PCL scores had significantly lower risk of developing type 2 diabetes, and those results remained consistent after adjusting for age, calculating the results using weighted data, and factoring in hypertension, obesity, and hyperlipidemia.

“This result was independent of numerous demographics and psychiatric and physical comorbidities,” said Dr. Scherrer and colleagues. “The association was also independent of the number of PTSD psychotherapy sessions used, suggesting that a healthy adherer effect, or a general orientation to improve health, is unlikely to explain our observations.”

Dr. Scherrer and colleagues cited several limitations, such as unmeasured confounding and the difficulty of generalizing the results beyond PTSD patients in a VHA setting. In addition, the researchers were unable to calculate the lifetime effect of reduced PTSD symptoms and incidence of type 2 diabetes.

This study was funded in part by a grant from the National Heart, Lung, and Blood Institute. Four authors reported receiving one or more grants from the National Heart, Lung, and Blood Institute during the study period. Some authors reported receiving other support from Noblis Therapeutics and Saint Louis University both during and outside the study period. The other authors reported no relevant conflicts of interest.

SOURCE: Scherrer JF et al. JAMA Psychiatry. 2019 Aug 21. doi: 10.1001/jamapsychiatry.2019.2096.

Veterans with a clinically meaningful reduction in symptoms of PTSD are less likely to develop type 2 diabetes, research from a retrospective study shows.

“We cautiously speculate that normalization of hypothalamic-pituitary-adrenal axis and cortisol levels could be one mechanism behind our results,” wrote Jeffrey F. Scherrer, PhD, and colleagues. “PTSD is associated with inflammation, which may in turn be associated with increased risk for [type 2 diabetes].” The study was published in JAMA Psychiatry.

Using medical record data from the Veterans Health Administration, Dr. Scherrer and colleagues identified 5,916 patients with PTSD who visited a VHA medical center between 2008 and 2012, and scored at least 50 points or higher on the PTSD Checklist (PCL) followed by another PCL score at least 8 months after the previous score. The mean age of patients in the study was 42.1 years, the cohort consisted of 84.3% men, and 66.3% patients were white. PCL score reduction was deemed clinically meaningful if there was a decrease of 20 points or more in the score, reported Dr. Scherrer of the department of family and community medicine at Saint Louis University and colleagues.

Patients who were older (mean 43.6 years vs. mean 41.7 years; P = .02) and those who underwent minimally adequate duration of PTSD psychotherapy (P less than .001) were significantly more likely to have a clinically meaningful decrease in PCL scores. Patients who received antidepressants (P = .004) or antipsychotics (P less than .001) were significantly more likely to have less than clinically meaningful decreases in PCL scores. Factors that put patients at significantly higher risk of developing type 2 diabetes included older age (hazard ratio, 1.05; 95% confidence interval, 1.04-1.07; P less than .001), black race/ethnicity (HR, 1.86; 95% CI, 1.23-2.83; P = .004), hypertension (HR, 3.46; 95% CI, 2.33-5.16), hyperlipidemia (HR, 2.82; 95% CI, 1.91-4.16), and obesity (HR, 3.32; 95% CI, 2.12-5.21) (all P less than .001).

Minimally adequate duration of PTSD psychotherapy and high use of primary care health services also were associated with developing type 2 diabetes.

In a Cox proportional hazards regression model, patients with clinically meaningful decreases in PCL scores had significantly lower risk of developing type 2 diabetes, and those results remained consistent after adjusting for age, calculating the results using weighted data, and factoring in hypertension, obesity, and hyperlipidemia.

“This result was independent of numerous demographics and psychiatric and physical comorbidities,” said Dr. Scherrer and colleagues. “The association was also independent of the number of PTSD psychotherapy sessions used, suggesting that a healthy adherer effect, or a general orientation to improve health, is unlikely to explain our observations.”

Dr. Scherrer and colleagues cited several limitations, such as unmeasured confounding and the difficulty of generalizing the results beyond PTSD patients in a VHA setting. In addition, the researchers were unable to calculate the lifetime effect of reduced PTSD symptoms and incidence of type 2 diabetes.

This study was funded in part by a grant from the National Heart, Lung, and Blood Institute. Four authors reported receiving one or more grants from the National Heart, Lung, and Blood Institute during the study period. Some authors reported receiving other support from Noblis Therapeutics and Saint Louis University both during and outside the study period. The other authors reported no relevant conflicts of interest.

SOURCE: Scherrer JF et al. JAMA Psychiatry. 2019 Aug 21. doi: 10.1001/jamapsychiatry.2019.2096.

Veterans with a clinically meaningful reduction in symptoms of PTSD are less likely to develop type 2 diabetes, research from a retrospective study shows.

“We cautiously speculate that normalization of hypothalamic-pituitary-adrenal axis and cortisol levels could be one mechanism behind our results,” wrote Jeffrey F. Scherrer, PhD, and colleagues. “PTSD is associated with inflammation, which may in turn be associated with increased risk for [type 2 diabetes].” The study was published in JAMA Psychiatry.

Using medical record data from the Veterans Health Administration, Dr. Scherrer and colleagues identified 5,916 patients with PTSD who visited a VHA medical center between 2008 and 2012, and scored at least 50 points or higher on the PTSD Checklist (PCL) followed by another PCL score at least 8 months after the previous score. The mean age of patients in the study was 42.1 years, the cohort consisted of 84.3% men, and 66.3% patients were white. PCL score reduction was deemed clinically meaningful if there was a decrease of 20 points or more in the score, reported Dr. Scherrer of the department of family and community medicine at Saint Louis University and colleagues.

Patients who were older (mean 43.6 years vs. mean 41.7 years; P = .02) and those who underwent minimally adequate duration of PTSD psychotherapy (P less than .001) were significantly more likely to have a clinically meaningful decrease in PCL scores. Patients who received antidepressants (P = .004) or antipsychotics (P less than .001) were significantly more likely to have less than clinically meaningful decreases in PCL scores. Factors that put patients at significantly higher risk of developing type 2 diabetes included older age (hazard ratio, 1.05; 95% confidence interval, 1.04-1.07; P less than .001), black race/ethnicity (HR, 1.86; 95% CI, 1.23-2.83; P = .004), hypertension (HR, 3.46; 95% CI, 2.33-5.16), hyperlipidemia (HR, 2.82; 95% CI, 1.91-4.16), and obesity (HR, 3.32; 95% CI, 2.12-5.21) (all P less than .001).

Minimally adequate duration of PTSD psychotherapy and high use of primary care health services also were associated with developing type 2 diabetes.

In a Cox proportional hazards regression model, patients with clinically meaningful decreases in PCL scores had significantly lower risk of developing type 2 diabetes, and those results remained consistent after adjusting for age, calculating the results using weighted data, and factoring in hypertension, obesity, and hyperlipidemia.

“This result was independent of numerous demographics and psychiatric and physical comorbidities,” said Dr. Scherrer and colleagues. “The association was also independent of the number of PTSD psychotherapy sessions used, suggesting that a healthy adherer effect, or a general orientation to improve health, is unlikely to explain our observations.”

Dr. Scherrer and colleagues cited several limitations, such as unmeasured confounding and the difficulty of generalizing the results beyond PTSD patients in a VHA setting. In addition, the researchers were unable to calculate the lifetime effect of reduced PTSD symptoms and incidence of type 2 diabetes.

This study was funded in part by a grant from the National Heart, Lung, and Blood Institute. Four authors reported receiving one or more grants from the National Heart, Lung, and Blood Institute during the study period. Some authors reported receiving other support from Noblis Therapeutics and Saint Louis University both during and outside the study period. The other authors reported no relevant conflicts of interest.

SOURCE: Scherrer JF et al. JAMA Psychiatry. 2019 Aug 21. doi: 10.1001/jamapsychiatry.2019.2096.

More than 150 cases of severe lung illness possibly related to e-cigarette use in adolescents and young adults have been reported in 16 states, according to an Aug. 21 update from officials at the Centers for Disease Control and Prevention.

licsiren/iStock/Getty Images

Officials from the CDC and the Food and Drug Administration are working with state health officials to gather information on the cases as well as any products or substances that might be involved.

A total of 153 potential cases were reported between June 28 and Aug. 20 in 16 states – California, Connecticut, Florida, Illinois, Indiana, Iowa, Michigan, Minnesota, New Jersey, New Mexico, New York, North Carolina, Pennsylvania, Texas, Utah, and Wisconsin.

Health officials have yet to find a cause for these illnesses; however, all patients have reported e-cigarette use or vaping, according to a CDC statement. Evidence to date does not seem to indicate that an infectious agent is the cause.

In general, patients have reported a gradual onset of symptoms including shortness of breath and/or chest pain that increased over days or weeks before hospital admission. Gastrointestinal symptoms including vomiting, diarrhea, and fatigue have been reported by some.

Many patients reported using products containing tetrahydrocannabinol, though no specific or consistent product has been linked definitively.

While cases reported across the country seem to be similar, there is no evidence currently indicating they have a common cause, according to the CDC statement.

The CDC is urging health care professionals to report possible cases to their state or local health department and the FDA is urging the public to provide detailed reports of any unusual or unexpected health concerns related to tobacco use or e-cigarette use through its Safety Reporting Portal.

[email protected]

More than 150 cases of severe lung illness possibly related to e-cigarette use in adolescents and young adults have been reported in 16 states, according to an Aug. 21 update from officials at the Centers for Disease Control and Prevention.

licsiren/iStock/Getty Images

Officials from the CDC and the Food and Drug Administration are working with state health officials to gather information on the cases as well as any products or substances that might be involved.

A total of 153 potential cases were reported between June 28 and Aug. 20 in 16 states – California, Connecticut, Florida, Illinois, Indiana, Iowa, Michigan, Minnesota, New Jersey, New Mexico, New York, North Carolina, Pennsylvania, Texas, Utah, and Wisconsin.

Health officials have yet to find a cause for these illnesses; however, all patients have reported e-cigarette use or vaping, according to a CDC statement. Evidence to date does not seem to indicate that an infectious agent is the cause.

In general, patients have reported a gradual onset of symptoms including shortness of breath and/or chest pain that increased over days or weeks before hospital admission. Gastrointestinal symptoms including vomiting, diarrhea, and fatigue have been reported by some.

Many patients reported using products containing tetrahydrocannabinol, though no specific or consistent product has been linked definitively.

While cases reported across the country seem to be similar, there is no evidence currently indicating they have a common cause, according to the CDC statement.

The CDC is urging health care professionals to report possible cases to their state or local health department and the FDA is urging the public to provide detailed reports of any unusual or unexpected health concerns related to tobacco use or e-cigarette use through its Safety Reporting Portal.

[email protected]

More than 150 cases of severe lung illness possibly related to e-cigarette use in adolescents and young adults have been reported in 16 states, according to an Aug. 21 update from officials at the Centers for Disease Control and Prevention.

licsiren/iStock/Getty Images

Officials from the CDC and the Food and Drug Administration are working with state health officials to gather information on the cases as well as any products or substances that might be involved.

A total of 153 potential cases were reported between June 28 and Aug. 20 in 16 states – California, Connecticut, Florida, Illinois, Indiana, Iowa, Michigan, Minnesota, New Jersey, New Mexico, New York, North Carolina, Pennsylvania, Texas, Utah, and Wisconsin.

Health officials have yet to find a cause for these illnesses; however, all patients have reported e-cigarette use or vaping, according to a CDC statement. Evidence to date does not seem to indicate that an infectious agent is the cause.

In general, patients have reported a gradual onset of symptoms including shortness of breath and/or chest pain that increased over days or weeks before hospital admission. Gastrointestinal symptoms including vomiting, diarrhea, and fatigue have been reported by some.

Many patients reported using products containing tetrahydrocannabinol, though no specific or consistent product has been linked definitively.

While cases reported across the country seem to be similar, there is no evidence currently indicating they have a common cause, according to the CDC statement.

The CDC is urging health care professionals to report possible cases to their state or local health department and the FDA is urging the public to provide detailed reports of any unusual or unexpected health concerns related to tobacco use or e-cigarette use through its Safety Reporting Portal.

[email protected]

Regardless of where people live in the world, air pollution is linked to increased rates of cardiovascular disease, respiratory problems, and all-cause mortality, according to one of the largest studies ever to assess the effects of inhalable particulate matter (PM), published Aug. 21 in the New England Journal of Medicine.

“These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies,” reported Cong Liu of the Huazhong University of Science and Technology in Wuhan, China, and an international team of researchers.

“Many people are experiencing worse allergy and asthma symptoms in the setting of increased heat and worse air quality,” Caren G. Solomon, MD, of Harvard Medical School, Boston, said in an interview. “It is often not appreciated that these are complications of climate change.”

Other such complications include heat-related illnesses and severe weather events, as well as the less visible manifestations, such as shifts in the epidemiology of vector-borne infectious disease, Dr. Solomon and colleagues wrote in an editorial accompanying Mr. Liu’s study.

“The stark reality is that high levels of greenhouse gases caused by the combustion of fossil fuels – and the resulting rise in temperature and sea levels and intensification of extreme weather – are having profound consequences for human health and health systems,” Dr. Solomon and colleagues wrote (N Engl J Med. 2019;381:773-4.).

In the new air pollution study, Mr. Liu and colleagues analyzed 59.6 million deaths from 652 cities across 24 countries, “thereby greatly increasing the generalizability of the association and decreasing the likelihood that the reported associations are subject to confounding bias,” wrote John R. Balmes, MD, of the University of California, San Francisco, and the University of California, Berkeley, in an editorial about the study (N Engl J Med. 2019;381:774-6).

The researchers compared air pollution data from 1986-2015 from the Multi-City Multi-Country (MCC) Collaborative Research Network to mortality data reported from individual countries. They assessed PM with an aerodynamic diameter of 10 mcg or less (PM10; n = 598 cities) and PM with an aerodynamic diameter of 2.5 mcg or less (PM_2.5; n=499 cities).

Mr. Liu’s team used a time-series analysis – a standard upon which the majority of air pollution research relies. These studies “include daily measures of health events (e.g., daily mortality), regressed against concentrations of PM (e.g., 24-hour average PM_2.5) and weather variables (e.g., daily average temperature) for a given geographic area,” Dr. Balmes wrote. “The population serves as its own control, and confounding by population characteristics is negligible because these are stable over short time frames.”

The researchers found a 0.44% increase in daily all-cause mortality for each 10-mcg/m³ increase in the 2-day moving average (current and previous day) of PM₁₀. The same increase was linked to a 0.36% increase in daily cardiovascular mortality and a 0.47% increase in daily respiratory mortality. Similarly, a 10-mcg/m³ increase in the PM_2.5 average was linked to 0.68% increase in all-cause mortality, a 0.55% increase in cardiovascular mortality, and 0.74% increase in respiratory mortality.

Locations with higher annual mean temperatures showed stronger associations, and all these associations remained statistically significant after the researchers adjusted for gaseous pollutants.

Although the majority of countries and cities included in the study came from the northern hemisphere, the researchers noted that the magnitude of effect they found, particularly for PM₁₀ concentrations, matched up with that seen in previous studies of multiple cities or countries.

Still, they found “significant evidence of spatial heterogeneity in the associations between PM concentration and daily mortality across countries and regions.” Among the factors that could contribute to those variations are “different PM components, long-term air pollution levels, population susceptibility, and different lengths of study periods,” they speculated.

What makes this study remarkable – despite decades of previous similar studies – is its size and the implications of a curvilinear shape in its concentration-response relation, according to Dr. Balmes.

“The current study of PM data from many regions around the world provides the strongest evidence to date that higher levels of exposure may be associated with a lower per-unit risk,” Dr. Balmes wrote. “Regions that have lower exposures had a higher per-unit risk. This finding has profound policy implications, especially given that no threshold of effect was found. Even high-income countries, such as the United States, with relatively good air quality could still see public health benefits from further reduction of ambient PM concentrations.”

The policy implications, however, extend well beyond clean air regulations because the findings represent just one aspect of climate change’s negative effects on health, which are “frighteningly broad,” Dr. Solomon and colleagues wrote.

“As climate change continues to alter disease patterns and disrupt health systems, its effects on human health will become harder to ignore,” they wrote. “We, as a medical community, have the responsibility and the opportunity to mobilize the urgent, large-scale climate action required to protect health – as well as the ingenuity to develop novel and bold interventions to avert the most catastrophic outcomes.”

The new research and associated commentary marked the introduction of a new NEJM topic on climate change effects on health and health systems.
 

SOURCE: Liu C et al. N Engl J Med. 2019;381:705-15.

This article was updated 8/22/19.

Regardless of where people live in the world, air pollution is linked to increased rates of cardiovascular disease, respiratory problems, and all-cause mortality, according to one of the largest studies ever to assess the effects of inhalable particulate matter (PM), published Aug. 21 in the New England Journal of Medicine.

“These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies,” reported Cong Liu of the Huazhong University of Science and Technology in Wuhan, China, and an international team of researchers.

“Many people are experiencing worse allergy and asthma symptoms in the setting of increased heat and worse air quality,” Caren G. Solomon, MD, of Harvard Medical School, Boston, said in an interview. “It is often not appreciated that these are complications of climate change.”

Other such complications include heat-related illnesses and severe weather events, as well as the less visible manifestations, such as shifts in the epidemiology of vector-borne infectious disease, Dr. Solomon and colleagues wrote in an editorial accompanying Mr. Liu’s study.

“The stark reality is that high levels of greenhouse gases caused by the combustion of fossil fuels – and the resulting rise in temperature and sea levels and intensification of extreme weather – are having profound consequences for human health and health systems,” Dr. Solomon and colleagues wrote (N Engl J Med. 2019;381:773-4.).

In the new air pollution study, Mr. Liu and colleagues analyzed 59.6 million deaths from 652 cities across 24 countries, “thereby greatly increasing the generalizability of the association and decreasing the likelihood that the reported associations are subject to confounding bias,” wrote John R. Balmes, MD, of the University of California, San Francisco, and the University of California, Berkeley, in an editorial about the study (N Engl J Med. 2019;381:774-6).

The researchers compared air pollution data from 1986-2015 from the Multi-City Multi-Country (MCC) Collaborative Research Network to mortality data reported from individual countries. They assessed PM with an aerodynamic diameter of 10 mcg or less (PM10; n = 598 cities) and PM with an aerodynamic diameter of 2.5 mcg or less (PM_2.5; n=499 cities).

Mr. Liu’s team used a time-series analysis – a standard upon which the majority of air pollution research relies. These studies “include daily measures of health events (e.g., daily mortality), regressed against concentrations of PM (e.g., 24-hour average PM_2.5) and weather variables (e.g., daily average temperature) for a given geographic area,” Dr. Balmes wrote. “The population serves as its own control, and confounding by population characteristics is negligible because these are stable over short time frames.”

The researchers found a 0.44% increase in daily all-cause mortality for each 10-mcg/m³ increase in the 2-day moving average (current and previous day) of PM₁₀. The same increase was linked to a 0.36% increase in daily cardiovascular mortality and a 0.47% increase in daily respiratory mortality. Similarly, a 10-mcg/m³ increase in the PM_2.5 average was linked to 0.68% increase in all-cause mortality, a 0.55% increase in cardiovascular mortality, and 0.74% increase in respiratory mortality.

Locations with higher annual mean temperatures showed stronger associations, and all these associations remained statistically significant after the researchers adjusted for gaseous pollutants.

Although the majority of countries and cities included in the study came from the northern hemisphere, the researchers noted that the magnitude of effect they found, particularly for PM₁₀ concentrations, matched up with that seen in previous studies of multiple cities or countries.

Still, they found “significant evidence of spatial heterogeneity in the associations between PM concentration and daily mortality across countries and regions.” Among the factors that could contribute to those variations are “different PM components, long-term air pollution levels, population susceptibility, and different lengths of study periods,” they speculated.

What makes this study remarkable – despite decades of previous similar studies – is its size and the implications of a curvilinear shape in its concentration-response relation, according to Dr. Balmes.

“The current study of PM data from many regions around the world provides the strongest evidence to date that higher levels of exposure may be associated with a lower per-unit risk,” Dr. Balmes wrote. “Regions that have lower exposures had a higher per-unit risk. This finding has profound policy implications, especially given that no threshold of effect was found. Even high-income countries, such as the United States, with relatively good air quality could still see public health benefits from further reduction of ambient PM concentrations.”

The policy implications, however, extend well beyond clean air regulations because the findings represent just one aspect of climate change’s negative effects on health, which are “frighteningly broad,” Dr. Solomon and colleagues wrote.

“As climate change continues to alter disease patterns and disrupt health systems, its effects on human health will become harder to ignore,” they wrote. “We, as a medical community, have the responsibility and the opportunity to mobilize the urgent, large-scale climate action required to protect health – as well as the ingenuity to develop novel and bold interventions to avert the most catastrophic outcomes.”

The new research and associated commentary marked the introduction of a new NEJM topic on climate change effects on health and health systems.
 

SOURCE: Liu C et al. N Engl J Med. 2019;381:705-15.

This article was updated 8/22/19.

Regardless of where people live in the world, air pollution is linked to increased rates of cardiovascular disease, respiratory problems, and all-cause mortality, according to one of the largest studies ever to assess the effects of inhalable particulate matter (PM), published Aug. 21 in the New England Journal of Medicine.

“These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies,” reported Cong Liu of the Huazhong University of Science and Technology in Wuhan, China, and an international team of researchers.

“Many people are experiencing worse allergy and asthma symptoms in the setting of increased heat and worse air quality,” Caren G. Solomon, MD, of Harvard Medical School, Boston, said in an interview. “It is often not appreciated that these are complications of climate change.”

Other such complications include heat-related illnesses and severe weather events, as well as the less visible manifestations, such as shifts in the epidemiology of vector-borne infectious disease, Dr. Solomon and colleagues wrote in an editorial accompanying Mr. Liu’s study.

“The stark reality is that high levels of greenhouse gases caused by the combustion of fossil fuels – and the resulting rise in temperature and sea levels and intensification of extreme weather – are having profound consequences for human health and health systems,” Dr. Solomon and colleagues wrote (N Engl J Med. 2019;381:773-4.).

In the new air pollution study, Mr. Liu and colleagues analyzed 59.6 million deaths from 652 cities across 24 countries, “thereby greatly increasing the generalizability of the association and decreasing the likelihood that the reported associations are subject to confounding bias,” wrote John R. Balmes, MD, of the University of California, San Francisco, and the University of California, Berkeley, in an editorial about the study (N Engl J Med. 2019;381:774-6).

The researchers compared air pollution data from 1986-2015 from the Multi-City Multi-Country (MCC) Collaborative Research Network to mortality data reported from individual countries. They assessed PM with an aerodynamic diameter of 10 mcg or less (PM10; n = 598 cities) and PM with an aerodynamic diameter of 2.5 mcg or less (PM_2.5; n=499 cities).

Mr. Liu’s team used a time-series analysis – a standard upon which the majority of air pollution research relies. These studies “include daily measures of health events (e.g., daily mortality), regressed against concentrations of PM (e.g., 24-hour average PM_2.5) and weather variables (e.g., daily average temperature) for a given geographic area,” Dr. Balmes wrote. “The population serves as its own control, and confounding by population characteristics is negligible because these are stable over short time frames.”

The researchers found a 0.44% increase in daily all-cause mortality for each 10-mcg/m³ increase in the 2-day moving average (current and previous day) of PM₁₀. The same increase was linked to a 0.36% increase in daily cardiovascular mortality and a 0.47% increase in daily respiratory mortality. Similarly, a 10-mcg/m³ increase in the PM_2.5 average was linked to 0.68% increase in all-cause mortality, a 0.55% increase in cardiovascular mortality, and 0.74% increase in respiratory mortality.

Locations with higher annual mean temperatures showed stronger associations, and all these associations remained statistically significant after the researchers adjusted for gaseous pollutants.

Although the majority of countries and cities included in the study came from the northern hemisphere, the researchers noted that the magnitude of effect they found, particularly for PM₁₀ concentrations, matched up with that seen in previous studies of multiple cities or countries.

Still, they found “significant evidence of spatial heterogeneity in the associations between PM concentration and daily mortality across countries and regions.” Among the factors that could contribute to those variations are “different PM components, long-term air pollution levels, population susceptibility, and different lengths of study periods,” they speculated.

What makes this study remarkable – despite decades of previous similar studies – is its size and the implications of a curvilinear shape in its concentration-response relation, according to Dr. Balmes.

“The current study of PM data from many regions around the world provides the strongest evidence to date that higher levels of exposure may be associated with a lower per-unit risk,” Dr. Balmes wrote. “Regions that have lower exposures had a higher per-unit risk. This finding has profound policy implications, especially given that no threshold of effect was found. Even high-income countries, such as the United States, with relatively good air quality could still see public health benefits from further reduction of ambient PM concentrations.”

The policy implications, however, extend well beyond clean air regulations because the findings represent just one aspect of climate change’s negative effects on health, which are “frighteningly broad,” Dr. Solomon and colleagues wrote.

“As climate change continues to alter disease patterns and disrupt health systems, its effects on human health will become harder to ignore,” they wrote. “We, as a medical community, have the responsibility and the opportunity to mobilize the urgent, large-scale climate action required to protect health – as well as the ingenuity to develop novel and bold interventions to avert the most catastrophic outcomes.”

The new research and associated commentary marked the introduction of a new NEJM topic on climate change effects on health and health systems.
 

SOURCE: Liu C et al. N Engl J Med. 2019;381:705-15.

This article was updated 8/22/19.

Selinexor plus low-dose dexamethasone can produce responses in patients with triple-class refractory multiple myeloma, according to the phase 2 STORM trial.

Wikimedia Commons/KGH/Creative Commons License

The combination produced a response rate of 26% in patients who were refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab.

The most common grade 3/4 adverse events in this trial were thrombocytopenia (59%), anemia (44%), hyponatremia (22%), and neutropenia (21%).

Ajai Chari, MD, of the Mount Sinai School of Medicine, New York, and colleagues reported these results in the New England Journal of Medicine.

The STORM trial included 123 patients with multiple myeloma who had previously received bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent. Their disease was refractory to at least one proteasome inhibitor, one immunomodulatory drug, and daratumumab.

The patients had received a median of 7 (range, 3-18) prior treatment regimens, and their median time since diagnosis was 6.6 years (range, 1.1-23.4 years). The median age at baseline was 65.2 years (range, 40-86 years), 58% of patients were men, and 53% had high-risk cytogenetics. In addition, 36% of patients had thrombocytopenia and 16% had neutropenia at baseline.

The patients received oral selinexor at 80 mg twice weekly plus dexamethasone at 20 mg twice weekly until disease progression, death, or discontinuation. Doses were modified in response to adverse events.

Results

In total, 96% of patients (118/123) discontinued treatment. The most common reasons for discontinuation were disease progression (n = 65) and adverse events (n = 38).

Of the 122 patients evaluable for efficacy, 26% achieved a partial response or better, and 39% had a minimal response or better. There were 24 partial responses, 16 minimal responses, 6 very good partial responses, and 2 stringent complete responses. Forty-eight patients had stable disease.

The median duration of response was 4.4 months, the median progression-free survival was 3.7 months, and the median overall survival was 8.6 months.

The median overall survival was 15.6 months in responders, 5.9 months in patients with stable disease, and 1.7 months in those who progressed.

All 123 patients were evaluable for safety, and 63% of them experienced serious adverse events. Pneumonia (11%) and sepsis (9%) were the most common serious events.

The most common treatment-emergent nonhematologic adverse events were fatigue (73%), nausea (72%), decreased appetite (56%), decreased weight (50%), diarrhea (46%), vomiting (38%), hyponatremia (37%), upper respiratory tract infection (23%), constipation (22%), and dyspnea (22%).

Treatment-emergent hematologic adverse events included thrombocytopenia (73%), anemia (67%), neutropenia (40%), leukopenia (33%), and lymphopenia (16%).

Eighty percent of patients had adverse events leading to dose modification or interruption. The most common of these were thrombocytopenia (43%), fatigue (16%), and neutropenia (11%).

“Because most patients involved in the study were older and frail, with limited end-organ reserve and at increased risk for adverse events, dose modifications were anticipated and were specified along with supportive care in the protocol,” the researchers wrote.


“The adverse events that were observed in the study were a function of dose, schedule, and baseline clinical characteristics (e.g., cytopenias). Thrombocytopenia … was reversible and was managed with dose interruptions and thrombopoietin-receptor agonists.”

There were 28 deaths on study, with 16 patients dying of disease progression and 12 dying from an adverse event. Two of the fatal adverse events were considered treatment related – sepsis in one patient and pneumonia with concurrent disease progression in another patient.

The researchers reported ties with Karyopharm Therapeutics, which sponsored the study, and many other companies.

[email protected]

SOURCE: Chari A et al. N Engl J Med 2019;381:727-38.

Selinexor plus low-dose dexamethasone can produce responses in patients with triple-class refractory multiple myeloma, according to the phase 2 STORM trial.

Wikimedia Commons/KGH/Creative Commons License

The combination produced a response rate of 26% in patients who were refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab.

The most common grade 3/4 adverse events in this trial were thrombocytopenia (59%), anemia (44%), hyponatremia (22%), and neutropenia (21%).

Ajai Chari, MD, of the Mount Sinai School of Medicine, New York, and colleagues reported these results in the New England Journal of Medicine.

The STORM trial included 123 patients with multiple myeloma who had previously received bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent. Their disease was refractory to at least one proteasome inhibitor, one immunomodulatory drug, and daratumumab.

The patients had received a median of 7 (range, 3-18) prior treatment regimens, and their median time since diagnosis was 6.6 years (range, 1.1-23.4 years). The median age at baseline was 65.2 years (range, 40-86 years), 58% of patients were men, and 53% had high-risk cytogenetics. In addition, 36% of patients had thrombocytopenia and 16% had neutropenia at baseline.

The patients received oral selinexor at 80 mg twice weekly plus dexamethasone at 20 mg twice weekly until disease progression, death, or discontinuation. Doses were modified in response to adverse events.

Results

In total, 96% of patients (118/123) discontinued treatment. The most common reasons for discontinuation were disease progression (n = 65) and adverse events (n = 38).

Of the 122 patients evaluable for efficacy, 26% achieved a partial response or better, and 39% had a minimal response or better. There were 24 partial responses, 16 minimal responses, 6 very good partial responses, and 2 stringent complete responses. Forty-eight patients had stable disease.

The median duration of response was 4.4 months, the median progression-free survival was 3.7 months, and the median overall survival was 8.6 months.

The median overall survival was 15.6 months in responders, 5.9 months in patients with stable disease, and 1.7 months in those who progressed.

All 123 patients were evaluable for safety, and 63% of them experienced serious adverse events. Pneumonia (11%) and sepsis (9%) were the most common serious events.

The most common treatment-emergent nonhematologic adverse events were fatigue (73%), nausea (72%), decreased appetite (56%), decreased weight (50%), diarrhea (46%), vomiting (38%), hyponatremia (37%), upper respiratory tract infection (23%), constipation (22%), and dyspnea (22%).

Treatment-emergent hematologic adverse events included thrombocytopenia (73%), anemia (67%), neutropenia (40%), leukopenia (33%), and lymphopenia (16%).

Eighty percent of patients had adverse events leading to dose modification or interruption. The most common of these were thrombocytopenia (43%), fatigue (16%), and neutropenia (11%).

“Because most patients involved in the study were older and frail, with limited end-organ reserve and at increased risk for adverse events, dose modifications were anticipated and were specified along with supportive care in the protocol,” the researchers wrote.


“The adverse events that were observed in the study were a function of dose, schedule, and baseline clinical characteristics (e.g., cytopenias). Thrombocytopenia … was reversible and was managed with dose interruptions and thrombopoietin-receptor agonists.”

There were 28 deaths on study, with 16 patients dying of disease progression and 12 dying from an adverse event. Two of the fatal adverse events were considered treatment related – sepsis in one patient and pneumonia with concurrent disease progression in another patient.

The researchers reported ties with Karyopharm Therapeutics, which sponsored the study, and many other companies.

[email protected]

SOURCE: Chari A et al. N Engl J Med 2019;381:727-38.

Selinexor plus low-dose dexamethasone can produce responses in patients with triple-class refractory multiple myeloma, according to the phase 2 STORM trial.

Wikimedia Commons/KGH/Creative Commons License

The combination produced a response rate of 26% in patients who were refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab.

The most common grade 3/4 adverse events in this trial were thrombocytopenia (59%), anemia (44%), hyponatremia (22%), and neutropenia (21%).

Ajai Chari, MD, of the Mount Sinai School of Medicine, New York, and colleagues reported these results in the New England Journal of Medicine.

The STORM trial included 123 patients with multiple myeloma who had previously received bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent. Their disease was refractory to at least one proteasome inhibitor, one immunomodulatory drug, and daratumumab.

The patients had received a median of 7 (range, 3-18) prior treatment regimens, and their median time since diagnosis was 6.6 years (range, 1.1-23.4 years). The median age at baseline was 65.2 years (range, 40-86 years), 58% of patients were men, and 53% had high-risk cytogenetics. In addition, 36% of patients had thrombocytopenia and 16% had neutropenia at baseline.

The patients received oral selinexor at 80 mg twice weekly plus dexamethasone at 20 mg twice weekly until disease progression, death, or discontinuation. Doses were modified in response to adverse events.

Results

In total, 96% of patients (118/123) discontinued treatment. The most common reasons for discontinuation were disease progression (n = 65) and adverse events (n = 38).

Of the 122 patients evaluable for efficacy, 26% achieved a partial response or better, and 39% had a minimal response or better. There were 24 partial responses, 16 minimal responses, 6 very good partial responses, and 2 stringent complete responses. Forty-eight patients had stable disease.

The median duration of response was 4.4 months, the median progression-free survival was 3.7 months, and the median overall survival was 8.6 months.

The median overall survival was 15.6 months in responders, 5.9 months in patients with stable disease, and 1.7 months in those who progressed.

All 123 patients were evaluable for safety, and 63% of them experienced serious adverse events. Pneumonia (11%) and sepsis (9%) were the most common serious events.

The most common treatment-emergent nonhematologic adverse events were fatigue (73%), nausea (72%), decreased appetite (56%), decreased weight (50%), diarrhea (46%), vomiting (38%), hyponatremia (37%), upper respiratory tract infection (23%), constipation (22%), and dyspnea (22%).

Treatment-emergent hematologic adverse events included thrombocytopenia (73%), anemia (67%), neutropenia (40%), leukopenia (33%), and lymphopenia (16%).

Eighty percent of patients had adverse events leading to dose modification or interruption. The most common of these were thrombocytopenia (43%), fatigue (16%), and neutropenia (11%).

“Because most patients involved in the study were older and frail, with limited end-organ reserve and at increased risk for adverse events, dose modifications were anticipated and were specified along with supportive care in the protocol,” the researchers wrote.


“The adverse events that were observed in the study were a function of dose, schedule, and baseline clinical characteristics (e.g., cytopenias). Thrombocytopenia … was reversible and was managed with dose interruptions and thrombopoietin-receptor agonists.”

There were 28 deaths on study, with 16 patients dying of disease progression and 12 dying from an adverse event. Two of the fatal adverse events were considered treatment related – sepsis in one patient and pneumonia with concurrent disease progression in another patient.

The researchers reported ties with Karyopharm Therapeutics, which sponsored the study, and many other companies.

[email protected]

SOURCE: Chari A et al. N Engl J Med 2019;381:727-38.

This supplement to Neurology Reviews compiles MS-related news briefs from the 2019 annual meetings the American Academy of Neurology, held in Philadelphia in early May, and the Consortium of Multiple Sclerosis Centers, held in Seattle in late May.  

Click here to read the supplement.

This supplement to Neurology Reviews compiles MS-related news briefs from the 2019 annual meetings the American Academy of Neurology, held in Philadelphia in early May, and the Consortium of Multiple Sclerosis Centers, held in Seattle in late May.  

Click here to read the supplement.

This supplement to Neurology Reviews compiles MS-related news briefs from the 2019 annual meetings the American Academy of Neurology, held in Philadelphia in early May, and the Consortium of Multiple Sclerosis Centers, held in Seattle in late May.  

Click here to read the supplement.