NASHVILLE, TENN. – At the University of North Carolina at Chapel Hill, many infants who would previously have been transferred to the NICU for asymptomatic hypoglycemia now are staying with their moms, thanks to a new protocol that holds off on blood glucose testing until infants are fed for the first time and glucose homeostasis can begin.

Not too long ago, the university realized it had a problem that’s probably familiar to other institutions: Its system to monitor newborns at risk for hypoglycemia – those born to diabetic mothers, or who are small or large for gestational age – put too many infants with asymptomatic hypoglycemia into the NICU when they didn’t really need to be there.

Nurse practitioners “were tired of transferring babies they felt were responsive to feeding and did not actually require NICU care,” and “a growing number of families were unhappy with being separated from infants that were well-appearing and feeding well at a time when moms were trying to establish breast feeding and bonding. There was frustration with our protocol,” which “seemed rigid and outdated,” said Ashley Sutton, MD, a pediatric hospitalist at the university.

[email protected]

NASHVILLE, TENN. – At the University of North Carolina at Chapel Hill, many infants who would previously have been transferred to the NICU for asymptomatic hypoglycemia now are staying with their moms, thanks to a new protocol that holds off on blood glucose testing until infants are fed for the first time and glucose homeostasis can begin.

Not too long ago, the university realized it had a problem that’s probably familiar to other institutions: Its system to monitor newborns at risk for hypoglycemia – those born to diabetic mothers, or who are small or large for gestational age – put too many infants with asymptomatic hypoglycemia into the NICU when they didn’t really need to be there.

Nurse practitioners “were tired of transferring babies they felt were responsive to feeding and did not actually require NICU care,” and “a growing number of families were unhappy with being separated from infants that were well-appearing and feeding well at a time when moms were trying to establish breast feeding and bonding. There was frustration with our protocol,” which “seemed rigid and outdated,” said Ashley Sutton, MD, a pediatric hospitalist at the university.

[email protected]

NASHVILLE, TENN. – At the University of North Carolina at Chapel Hill, many infants who would previously have been transferred to the NICU for asymptomatic hypoglycemia now are staying with their moms, thanks to a new protocol that holds off on blood glucose testing until infants are fed for the first time and glucose homeostasis can begin.

Not too long ago, the university realized it had a problem that’s probably familiar to other institutions: Its system to monitor newborns at risk for hypoglycemia – those born to diabetic mothers, or who are small or large for gestational age – put too many infants with asymptomatic hypoglycemia into the NICU when they didn’t really need to be there.

Nurse practitioners “were tired of transferring babies they felt were responsive to feeding and did not actually require NICU care,” and “a growing number of families were unhappy with being separated from infants that were well-appearing and feeding well at a time when moms were trying to establish breast feeding and bonding. There was frustration with our protocol,” which “seemed rigid and outdated,” said Ashley Sutton, MD, a pediatric hospitalist at the university.

[email protected]

The mobile companion app (Apple products only) for VESAP4 is expected to be released by mid-September. The app permits users to access the program offline anywhere and sync up with the desktop app when later connected to the Internet.

It will be available on the iTunes store and is free to VESAP4 purchasers. Learn more about the fourth edition of the Vascular Education and Self-Assessment Program (VESAP4) here.

The mobile companion app (Apple products only) for VESAP4 is expected to be released by mid-September. The app permits users to access the program offline anywhere and sync up with the desktop app when later connected to the Internet.

It will be available on the iTunes store and is free to VESAP4 purchasers. Learn more about the fourth edition of the Vascular Education and Self-Assessment Program (VESAP4) here.

The mobile companion app (Apple products only) for VESAP4 is expected to be released by mid-September. The app permits users to access the program offline anywhere and sync up with the desktop app when later connected to the Internet.

It will be available on the iTunes store and is free to VESAP4 purchasers. Learn more about the fourth edition of the Vascular Education and Self-Assessment Program (VESAP4) here.

SVS is seeking proposals for invited sessions from internal committees and members alike for the 2018 Vascular Annual Meeting, June 20-23 (exhibits: June 21 to 22; plenaries: June 21 to 23) in Boston, Mass.

Invited sessions consist of postgraduate courses, breakfast sessions, concurrent sessions and workshops/small-group sessions. Submitters will be asked to address educational needs, provide objectives, indicate proposed formats and identify target audiences.

The deadline is 3 p.m. Central Daylight Time, Friday, Sept. 15. Submitters will be notified the week of Sept. 25 if their proposals have been selected for further development. Contact [email protected] or call 312-334-2327 with questions.

SVS is seeking proposals for invited sessions from internal committees and members alike for the 2018 Vascular Annual Meeting, June 20-23 (exhibits: June 21 to 22; plenaries: June 21 to 23) in Boston, Mass.

Invited sessions consist of postgraduate courses, breakfast sessions, concurrent sessions and workshops/small-group sessions. Submitters will be asked to address educational needs, provide objectives, indicate proposed formats and identify target audiences.

The deadline is 3 p.m. Central Daylight Time, Friday, Sept. 15. Submitters will be notified the week of Sept. 25 if their proposals have been selected for further development. Contact [email protected] or call 312-334-2327 with questions.

SVS is seeking proposals for invited sessions from internal committees and members alike for the 2018 Vascular Annual Meeting, June 20-23 (exhibits: June 21 to 22; plenaries: June 21 to 23) in Boston, Mass.

Invited sessions consist of postgraduate courses, breakfast sessions, concurrent sessions and workshops/small-group sessions. Submitters will be asked to address educational needs, provide objectives, indicate proposed formats and identify target audiences.

The deadline is 3 p.m. Central Daylight Time, Friday, Sept. 15. Submitters will be notified the week of Sept. 25 if their proposals have been selected for further development. Contact [email protected] or call 312-334-2327 with questions.

The immune-related adverse effects of inhibitors of programmed cell death protein 1 (PD-1) and its ligand varied by tumor type in a large systematic review and meta-analysis.

Patients with melanoma were significantly more likely to develop colitis (odds ratio, 4.2; 95% confidence interval, 1.3 to 14.0), diarrhea (OR, 1.9), pruritus (OR, 2.4), and rash (OR, 1.8) compared with patients with non–small cell lung cancer, who were significantly more likely to develop pneumonitis, reported Leila Khoja, MBChB, PhD, of AstraZeneca UK, Melbourn, England, and associates. Patients with melanoma also were significantly more likely to develop arthralgia, hypothyroidism, rash, pruritus, and diarrhea compared with patients with renal cell carcinoma, who were more likely to develop pneumonitis and dyspnea.

“In light of this study, we should be mindful that different tumor types may have different immune-related adverse effect patterns when treated with the same immune checkpoint inhibitor,” the reviewers noted (Ann Oncol. 2017 Aug 8. doi: 10.1093/annonc/mdx286).

The review included 48 trials of nearly 7,000 patients with solid tumors who received CTLA-4 inhibitors (26 studies), PD-1 inhibitors (17 studies), PD-1 ligand (PD-L1) inhibitors (two trials), or both CTLA-4 and PD-1 inhibitors (three trials). The reviewers identified the studies by searching the Medline, EMBASE, and COCHRANE databases for prospective trials published from 2003 through November 2015.

Severe or life-threatening immune-related adverse effects developed in 31% of patients who received CTLA-4 inhibitors and 10% of patients who received PD-1 inhibitors. Inhibitors of CTLA-4 were significantly more likely to cause all grades of colitis (OR, 8.7), hypophysitis (OR, 6.5), and rash (OR, 2.0), while PD-1 inhibitors were more strongly linked with pneumonitis (OR 6.4), hypothyroidism (OR 4.3), arthralgia (OR, 3.5), and vitiligo (OR, 3.5).

The reviewers also looked for significant predictors of immune-related colitis and pneumonitis, because these are potentially fatal. They found that pneumonitis was significantly linked to PD-1/PD-L1 inhibitor therapy (P less than .001) and colitis to CTLA-4 treatment (P = .04), even after accounting for therapeutic dose and tumor type. No other factors reached significance in this multivariable model.

“Clearly, a more thorough understanding of the mechanisms of immune-related adverse effects is needed, which may lead to the identification of biomarkers to predict the occurrence of toxicity in patients or predict those who have immune-related adverse effects that are unlikely to respond to corticosteroids,” the reviewers concluded. Researchers should also study whether clinical factors such as treatment history or comorbidities affect the risk of immune-related adverse effects from immune checkpoint inhibitors, they said.

The reviewers reported having no funding sources and no relevant conflicts of interest.

The immune-related adverse effects of inhibitors of programmed cell death protein 1 (PD-1) and its ligand varied by tumor type in a large systematic review and meta-analysis.

Patients with melanoma were significantly more likely to develop colitis (odds ratio, 4.2; 95% confidence interval, 1.3 to 14.0), diarrhea (OR, 1.9), pruritus (OR, 2.4), and rash (OR, 1.8) compared with patients with non–small cell lung cancer, who were significantly more likely to develop pneumonitis, reported Leila Khoja, MBChB, PhD, of AstraZeneca UK, Melbourn, England, and associates. Patients with melanoma also were significantly more likely to develop arthralgia, hypothyroidism, rash, pruritus, and diarrhea compared with patients with renal cell carcinoma, who were more likely to develop pneumonitis and dyspnea.

“In light of this study, we should be mindful that different tumor types may have different immune-related adverse effect patterns when treated with the same immune checkpoint inhibitor,” the reviewers noted (Ann Oncol. 2017 Aug 8. doi: 10.1093/annonc/mdx286).

The review included 48 trials of nearly 7,000 patients with solid tumors who received CTLA-4 inhibitors (26 studies), PD-1 inhibitors (17 studies), PD-1 ligand (PD-L1) inhibitors (two trials), or both CTLA-4 and PD-1 inhibitors (three trials). The reviewers identified the studies by searching the Medline, EMBASE, and COCHRANE databases for prospective trials published from 2003 through November 2015.

Severe or life-threatening immune-related adverse effects developed in 31% of patients who received CTLA-4 inhibitors and 10% of patients who received PD-1 inhibitors. Inhibitors of CTLA-4 were significantly more likely to cause all grades of colitis (OR, 8.7), hypophysitis (OR, 6.5), and rash (OR, 2.0), while PD-1 inhibitors were more strongly linked with pneumonitis (OR 6.4), hypothyroidism (OR 4.3), arthralgia (OR, 3.5), and vitiligo (OR, 3.5).

The reviewers also looked for significant predictors of immune-related colitis and pneumonitis, because these are potentially fatal. They found that pneumonitis was significantly linked to PD-1/PD-L1 inhibitor therapy (P less than .001) and colitis to CTLA-4 treatment (P = .04), even after accounting for therapeutic dose and tumor type. No other factors reached significance in this multivariable model.

“Clearly, a more thorough understanding of the mechanisms of immune-related adverse effects is needed, which may lead to the identification of biomarkers to predict the occurrence of toxicity in patients or predict those who have immune-related adverse effects that are unlikely to respond to corticosteroids,” the reviewers concluded. Researchers should also study whether clinical factors such as treatment history or comorbidities affect the risk of immune-related adverse effects from immune checkpoint inhibitors, they said.

The reviewers reported having no funding sources and no relevant conflicts of interest.

The immune-related adverse effects of inhibitors of programmed cell death protein 1 (PD-1) and its ligand varied by tumor type in a large systematic review and meta-analysis.

Patients with melanoma were significantly more likely to develop colitis (odds ratio, 4.2; 95% confidence interval, 1.3 to 14.0), diarrhea (OR, 1.9), pruritus (OR, 2.4), and rash (OR, 1.8) compared with patients with non–small cell lung cancer, who were significantly more likely to develop pneumonitis, reported Leila Khoja, MBChB, PhD, of AstraZeneca UK, Melbourn, England, and associates. Patients with melanoma also were significantly more likely to develop arthralgia, hypothyroidism, rash, pruritus, and diarrhea compared with patients with renal cell carcinoma, who were more likely to develop pneumonitis and dyspnea.

“In light of this study, we should be mindful that different tumor types may have different immune-related adverse effect patterns when treated with the same immune checkpoint inhibitor,” the reviewers noted (Ann Oncol. 2017 Aug 8. doi: 10.1093/annonc/mdx286).

The review included 48 trials of nearly 7,000 patients with solid tumors who received CTLA-4 inhibitors (26 studies), PD-1 inhibitors (17 studies), PD-1 ligand (PD-L1) inhibitors (two trials), or both CTLA-4 and PD-1 inhibitors (three trials). The reviewers identified the studies by searching the Medline, EMBASE, and COCHRANE databases for prospective trials published from 2003 through November 2015.

Severe or life-threatening immune-related adverse effects developed in 31% of patients who received CTLA-4 inhibitors and 10% of patients who received PD-1 inhibitors. Inhibitors of CTLA-4 were significantly more likely to cause all grades of colitis (OR, 8.7), hypophysitis (OR, 6.5), and rash (OR, 2.0), while PD-1 inhibitors were more strongly linked with pneumonitis (OR 6.4), hypothyroidism (OR 4.3), arthralgia (OR, 3.5), and vitiligo (OR, 3.5).

The reviewers also looked for significant predictors of immune-related colitis and pneumonitis, because these are potentially fatal. They found that pneumonitis was significantly linked to PD-1/PD-L1 inhibitor therapy (P less than .001) and colitis to CTLA-4 treatment (P = .04), even after accounting for therapeutic dose and tumor type. No other factors reached significance in this multivariable model.

“Clearly, a more thorough understanding of the mechanisms of immune-related adverse effects is needed, which may lead to the identification of biomarkers to predict the occurrence of toxicity in patients or predict those who have immune-related adverse effects that are unlikely to respond to corticosteroids,” the reviewers concluded. Researchers should also study whether clinical factors such as treatment history or comorbidities affect the risk of immune-related adverse effects from immune checkpoint inhibitors, they said.

The reviewers reported having no funding sources and no relevant conflicts of interest.

Enasidenib was a well-tolerated, efficacious alternative to cytotoxic chemotherapy for patients with IDH2-mutated relapsed or refractory acute myeloid leukemia (AML), the results of a phase 1/2 study showed.

The Food and Drug Administration recently approved enasidenib (Idhifa, formerly AG-221; Celgene) for the treatment of adult patients with relapsed or refractory AML having an IDH2 mutation as detected by a companion diagnostic test (RealTime IDH2 Assay; Abbott Molecular Inc.). The drug was generally safe and well tolerated, according to reported trial results (Blood. 2017 Aug. 10;130[6]:722-31). The main grade 3-4 enasidenib-related adverse events were hyperbilirubinemia (12%) and IDH inhibitor–associated differentiation syndrome (6%).

The drug is an oral selective inhibitor of mutant isocitrate dehydrogenase 2 (IDH2) enzymes that is not myeloablative. Although enasidenib appears to work by inducing myeloblast differentiation, predictors of response to the drug generally remain elusive, according to Eytan M. Stein, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, New York, and his coauthors.

About 12% of patients with AML have an IDH2 mutation. This genetic defect leads to accumulation of the metabolite 2-hydroxyglutarate (2-HG), causing DNA and histone hypermethylation. Hypermethylation, in turn, blocks hematopoietic cellular differentiation.

In a phase 1/2 trial sponsored by Celgene and Agios Pharmaceuticals, the investigators tested daily enasidenib monotherapy among 239 patients with IDH2-mutated advanced myeloid malignancies.

Among the 176 patients with relapsed or refractory AML (more than half of whom had already received at least two regimens directed against the disease), the overall response rate was 40.3%, and the complete response/remission rate was 19.3%. The median duration of response was 5.8 months.

Evaluation of serial bone marrow aspirates showed that responses were associated with myeloid cellular differentiation and maturation, generally without evidence of aplasia or hypoplasia.

With a median follow-up of 7.7 months, median overall survival was 9.3 months in the entire AML cohort and 19.7 months in the subset achieving complete response/remission. Ten percent of patients went on to allogeneic stem cell transplantation.

Although nearly all patients had a marked reduction in plasma levels of 2-HG, the extent of reduction did not predict response, suggesting that this metabolite is not a biomarker for benefit, and additional mechanisms are at play.

“Continuous daily enasidenib treatment was generally well tolerated and induced hematologic responses in patients for whom prior AML therapy had failed,” Dr. Stein and his coinvestigators wrote. “Inducing differentiation of myeloblasts, not cytotoxicity, seems to drive the clinical efficacy of enasidenib.”

They noted that an ongoing multicenter, randomized phase 3 trial, called IDHENTIFY (NCT02577406), is testing enasidenib against conventional regimens in older adults with late-stage AML harboring an IDH2 mutation.

In a companion translational study, investigators led by Michael D. Amatangelo, PhD, a scientist with Celgene in Summit, N.J., further explored mechanisms of enasidenib response and sought to identify alternative biomarkers for benefit in the AML cohort. They measured 2-HG levels, mutant IDH2 allele burden, and co-occurring somatic mutations in samples serially collected during the trial, and used flow cytometry to assess inhibition of mutant IDH2 on hematopoietic differentiation.

Enasidenib therapy induced 2-HG suppression regardless of whether patients’ IDH2 mutation affected the R140 or the R172 residue, according to reported results (Blood. 2017 Aug. 10;130[6]:732-41). However, analyses confirmed that 2-HG suppression alone did not predict response, as most nonresponders also had suppression.

In some patients with complete remission, mutant IDH2 persisted, but there was normalization of hematopoietic stem and progenitor compartments, and emergence of functional neutrophils having the IDH2 mutation. And some patients saw a reduction in mutant IDH2 allele burden, with levels remaining undetectable during response.

Analyses failed to identify any single mutation predictive of response to enasidenib. However, patients who did not achieve a response more commonly had mutations in NRAS and other MAPK pathway effectors, suggesting that RAS signaling plays a role in primary resistance to the drug.

“Although this is only a subgroup analysis of a large single-arm experience, taken together, the clinical response and translational data demonstrate that single-agent [mutant IDH2] inhibition by enasidenib in [relapsed or refractory AML] represents a critical and novel differentiation therapy,” Dr. Amatangelo and his coinvestigators wrote.

“Although enasidenib responses are clinically durable, the genetic heterogeneity observed in our patients suggests that combination with other therapies may be required to achieve long-term disease remission in more patients,” they added. “Current clinical studies combining enasidenib with combination chemotherapy or azacitidine (NCT02677922 and NCT02632708) and future orthogonal targeted therapies will address this question.”

Dr. Stein disclosed that he received grants and personal fees from Celgene and Agios Pharmaceuticals. Dr. Amatangelo disclosed that he is employed by and owns equity in Celgene.

Enasidenib was a well-tolerated, efficacious alternative to cytotoxic chemotherapy for patients with IDH2-mutated relapsed or refractory acute myeloid leukemia (AML), the results of a phase 1/2 study showed.

The Food and Drug Administration recently approved enasidenib (Idhifa, formerly AG-221; Celgene) for the treatment of adult patients with relapsed or refractory AML having an IDH2 mutation as detected by a companion diagnostic test (RealTime IDH2 Assay; Abbott Molecular Inc.). The drug was generally safe and well tolerated, according to reported trial results (Blood. 2017 Aug. 10;130[6]:722-31). The main grade 3-4 enasidenib-related adverse events were hyperbilirubinemia (12%) and IDH inhibitor–associated differentiation syndrome (6%).

The drug is an oral selective inhibitor of mutant isocitrate dehydrogenase 2 (IDH2) enzymes that is not myeloablative. Although enasidenib appears to work by inducing myeloblast differentiation, predictors of response to the drug generally remain elusive, according to Eytan M. Stein, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, New York, and his coauthors.

About 12% of patients with AML have an IDH2 mutation. This genetic defect leads to accumulation of the metabolite 2-hydroxyglutarate (2-HG), causing DNA and histone hypermethylation. Hypermethylation, in turn, blocks hematopoietic cellular differentiation.

In a phase 1/2 trial sponsored by Celgene and Agios Pharmaceuticals, the investigators tested daily enasidenib monotherapy among 239 patients with IDH2-mutated advanced myeloid malignancies.

Among the 176 patients with relapsed or refractory AML (more than half of whom had already received at least two regimens directed against the disease), the overall response rate was 40.3%, and the complete response/remission rate was 19.3%. The median duration of response was 5.8 months.

Evaluation of serial bone marrow aspirates showed that responses were associated with myeloid cellular differentiation and maturation, generally without evidence of aplasia or hypoplasia.

With a median follow-up of 7.7 months, median overall survival was 9.3 months in the entire AML cohort and 19.7 months in the subset achieving complete response/remission. Ten percent of patients went on to allogeneic stem cell transplantation.

Although nearly all patients had a marked reduction in plasma levels of 2-HG, the extent of reduction did not predict response, suggesting that this metabolite is not a biomarker for benefit, and additional mechanisms are at play.

“Continuous daily enasidenib treatment was generally well tolerated and induced hematologic responses in patients for whom prior AML therapy had failed,” Dr. Stein and his coinvestigators wrote. “Inducing differentiation of myeloblasts, not cytotoxicity, seems to drive the clinical efficacy of enasidenib.”

They noted that an ongoing multicenter, randomized phase 3 trial, called IDHENTIFY (NCT02577406), is testing enasidenib against conventional regimens in older adults with late-stage AML harboring an IDH2 mutation.

In a companion translational study, investigators led by Michael D. Amatangelo, PhD, a scientist with Celgene in Summit, N.J., further explored mechanisms of enasidenib response and sought to identify alternative biomarkers for benefit in the AML cohort. They measured 2-HG levels, mutant IDH2 allele burden, and co-occurring somatic mutations in samples serially collected during the trial, and used flow cytometry to assess inhibition of mutant IDH2 on hematopoietic differentiation.

Enasidenib therapy induced 2-HG suppression regardless of whether patients’ IDH2 mutation affected the R140 or the R172 residue, according to reported results (Blood. 2017 Aug. 10;130[6]:732-41). However, analyses confirmed that 2-HG suppression alone did not predict response, as most nonresponders also had suppression.

In some patients with complete remission, mutant IDH2 persisted, but there was normalization of hematopoietic stem and progenitor compartments, and emergence of functional neutrophils having the IDH2 mutation. And some patients saw a reduction in mutant IDH2 allele burden, with levels remaining undetectable during response.

Analyses failed to identify any single mutation predictive of response to enasidenib. However, patients who did not achieve a response more commonly had mutations in NRAS and other MAPK pathway effectors, suggesting that RAS signaling plays a role in primary resistance to the drug.

“Although this is only a subgroup analysis of a large single-arm experience, taken together, the clinical response and translational data demonstrate that single-agent [mutant IDH2] inhibition by enasidenib in [relapsed or refractory AML] represents a critical and novel differentiation therapy,” Dr. Amatangelo and his coinvestigators wrote.

“Although enasidenib responses are clinically durable, the genetic heterogeneity observed in our patients suggests that combination with other therapies may be required to achieve long-term disease remission in more patients,” they added. “Current clinical studies combining enasidenib with combination chemotherapy or azacitidine (NCT02677922 and NCT02632708) and future orthogonal targeted therapies will address this question.”

Dr. Stein disclosed that he received grants and personal fees from Celgene and Agios Pharmaceuticals. Dr. Amatangelo disclosed that he is employed by and owns equity in Celgene.

Enasidenib was a well-tolerated, efficacious alternative to cytotoxic chemotherapy for patients with IDH2-mutated relapsed or refractory acute myeloid leukemia (AML), the results of a phase 1/2 study showed.

The Food and Drug Administration recently approved enasidenib (Idhifa, formerly AG-221; Celgene) for the treatment of adult patients with relapsed or refractory AML having an IDH2 mutation as detected by a companion diagnostic test (RealTime IDH2 Assay; Abbott Molecular Inc.). The drug was generally safe and well tolerated, according to reported trial results (Blood. 2017 Aug. 10;130[6]:722-31). The main grade 3-4 enasidenib-related adverse events were hyperbilirubinemia (12%) and IDH inhibitor–associated differentiation syndrome (6%).

The drug is an oral selective inhibitor of mutant isocitrate dehydrogenase 2 (IDH2) enzymes that is not myeloablative. Although enasidenib appears to work by inducing myeloblast differentiation, predictors of response to the drug generally remain elusive, according to Eytan M. Stein, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, New York, and his coauthors.

About 12% of patients with AML have an IDH2 mutation. This genetic defect leads to accumulation of the metabolite 2-hydroxyglutarate (2-HG), causing DNA and histone hypermethylation. Hypermethylation, in turn, blocks hematopoietic cellular differentiation.

In a phase 1/2 trial sponsored by Celgene and Agios Pharmaceuticals, the investigators tested daily enasidenib monotherapy among 239 patients with IDH2-mutated advanced myeloid malignancies.

Among the 176 patients with relapsed or refractory AML (more than half of whom had already received at least two regimens directed against the disease), the overall response rate was 40.3%, and the complete response/remission rate was 19.3%. The median duration of response was 5.8 months.

Evaluation of serial bone marrow aspirates showed that responses were associated with myeloid cellular differentiation and maturation, generally without evidence of aplasia or hypoplasia.

With a median follow-up of 7.7 months, median overall survival was 9.3 months in the entire AML cohort and 19.7 months in the subset achieving complete response/remission. Ten percent of patients went on to allogeneic stem cell transplantation.

Although nearly all patients had a marked reduction in plasma levels of 2-HG, the extent of reduction did not predict response, suggesting that this metabolite is not a biomarker for benefit, and additional mechanisms are at play.

“Continuous daily enasidenib treatment was generally well tolerated and induced hematologic responses in patients for whom prior AML therapy had failed,” Dr. Stein and his coinvestigators wrote. “Inducing differentiation of myeloblasts, not cytotoxicity, seems to drive the clinical efficacy of enasidenib.”

They noted that an ongoing multicenter, randomized phase 3 trial, called IDHENTIFY (NCT02577406), is testing enasidenib against conventional regimens in older adults with late-stage AML harboring an IDH2 mutation.

In a companion translational study, investigators led by Michael D. Amatangelo, PhD, a scientist with Celgene in Summit, N.J., further explored mechanisms of enasidenib response and sought to identify alternative biomarkers for benefit in the AML cohort. They measured 2-HG levels, mutant IDH2 allele burden, and co-occurring somatic mutations in samples serially collected during the trial, and used flow cytometry to assess inhibition of mutant IDH2 on hematopoietic differentiation.

Enasidenib therapy induced 2-HG suppression regardless of whether patients’ IDH2 mutation affected the R140 or the R172 residue, according to reported results (Blood. 2017 Aug. 10;130[6]:732-41). However, analyses confirmed that 2-HG suppression alone did not predict response, as most nonresponders also had suppression.

In some patients with complete remission, mutant IDH2 persisted, but there was normalization of hematopoietic stem and progenitor compartments, and emergence of functional neutrophils having the IDH2 mutation. And some patients saw a reduction in mutant IDH2 allele burden, with levels remaining undetectable during response.

Analyses failed to identify any single mutation predictive of response to enasidenib. However, patients who did not achieve a response more commonly had mutations in NRAS and other MAPK pathway effectors, suggesting that RAS signaling plays a role in primary resistance to the drug.

“Although this is only a subgroup analysis of a large single-arm experience, taken together, the clinical response and translational data demonstrate that single-agent [mutant IDH2] inhibition by enasidenib in [relapsed or refractory AML] represents a critical and novel differentiation therapy,” Dr. Amatangelo and his coinvestigators wrote.

“Although enasidenib responses are clinically durable, the genetic heterogeneity observed in our patients suggests that combination with other therapies may be required to achieve long-term disease remission in more patients,” they added. “Current clinical studies combining enasidenib with combination chemotherapy or azacitidine (NCT02677922 and NCT02632708) and future orthogonal targeted therapies will address this question.”

Dr. Stein disclosed that he received grants and personal fees from Celgene and Agios Pharmaceuticals. Dr. Amatangelo disclosed that he is employed by and owns equity in Celgene.

Statin Prescription Varies in Stroke Belt

Less than half of patients with stroke discharged from the hospital receive a prescription for statins, and the likelihood of a prescription varies by patients’ location, sex, age, and race, according to a study published August 2 in the Journal of the American Heart Association. Researchers analyzed discharge medications for 323 participants hospitalized for an ischemic stroke during follow-up of the Reasons for Geographic and Racial Differences in Stroke study. In the Stroke Belt, participants ages 65 and older were 47% less likely to be discharged on a statin, compared with people younger than 65. Compared with women, men in the Stroke Belt were 31% less likely to be discharged on a statin, while men outside the Stroke Belt were more likely to be discharged on a statin.

Albright KC, Howard VJ, Howard G, et al. Age and sex disparities in discharge statin prescribing in the stroke belt: evidence from the Reasons for Geographic and Racial Differences in Stroke Study. J Am Heart Assoc. 2017;6(8).

Midlife Vascular Risk Factors Increase Risk of Dementia

Midlife vascular risk factors are associated with increased risk of dementia in blacks and whites, according to a study published online ahead of print August 7 in JAMA Neurology. In the Atherosclerosis Risk in Communities study, investigators measured demographic and vascular risk factors at baseline (ie, obesity, smoking, diabetes, prehypertension, hypertension, and hypercholesterolemia), along with the presence of the APOE ε4 genotype. After the baseline visit, participants had four additional in-person visits. In all, 1,516 cases of dementia (57.0% female and 34.9% black, with a mean age at visit 1 of 57.4) were identified among 15,744 participants. Black race, older age, lower educational attainment, and APOE ε4 genotype were associated with increased risk of dementia, as were midlife smoking, diabetes, prehypertension, and hypertension.

Gottesman RF, Albert MS, Alonso A, et al. Associations between midlife vascular risk factors and 25-year incident dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort. JAMA Neurol. 2017 August 7 [Epub ahead of print].

Resistance Training May Slow the Progression of MS

Progressive resistance training may have a neuroprotective or neuroregenerative effect in relapsing-remitting multiple sclerosis (MS), according to a study published online ahead of print July 1 in Multiple Sclerosis Journal. This study was a 24-week randomized controlled crossover trial. Participants were assigned to training or to a wait list. Assessments included disability measures and MRI. The MS Functional Composite score improved in the training group, but disability, lesion load, and global brain volumes did not differ between groups. The researchers noted higher absolute cortical thickness values in 19 of 74 investigated cortical regions after progressive resistance training. Observed changes were confirmed and reproduced when comparing relative cortical thickness changes between groups in the anterior cingulate gyrus, temporal pole, orbital sulcus, and inferior temporal sulcus.

Kjølhede T, Siemonsen S, Wenzel D, et al. Can resistance training impact MRI outcomes in relapsing-remitting multiple sclerosis? Mult Scler. 2017 Jul 1 [Epub ahead of print].

Noninvasive Device Measures Intracranial Pressure

A noninvasive device measures intracranial pressure (ICP) accurately, according to research published online ahead of print August 8 in the Journal of Neurosurgery. In patients with traumatic brain injury and subarachnoid hemorrhage who were undergoing treatment in a neurocritical intensive care unit, researchers recorded ICP using the gold-standard method of invasive external ventricular drainage or intraparenchymal monitoring. In addition, the authors simultaneously measured ICP noninvasively with a device that uses advanced signal-analysis algorithms for acoustic signals propagating through the cranium. Data were collected in 14 patients, yielding 2,543 data points of continuous parallel ICP values. For measurements at the ≥ 17-mm Hg cutoff, the sensitivity and specificity of the noninvasive device were 0.7541 and 0.8887, respectively. ICP values obtained using noninvasive and invasive monitoring methods correlated well.

Ganslandt O, Mourtzoukos S, Stadlbauer A, et al. Evaluation of a novel noninvasive ICP monitoring device in patients undergoing invasive ICP monitoring: preliminary results. J Neurosurg. 2017 Aug 8 [Epub ahead of print].

Strokes Decline Among Men, But Not Women

The rate of stroke in the US has declined among men, but not among women, according to a study published online ahead of print August 9 in Neurology. Researchers collected data on 1.3 million adults in Ohio and Kentucky between 1993 and 2010. They used medical records to identify first-ever strokes during four one-year periods. The researchers observed 7,710 incident strokes in the four periods, and 57% of them were among women. The incidence of all strokes decreased over time in men (263 to 192), but not in women (217 to 198). The researchers found a similar sex difference in the change in the rate of ischemic stroke (ie, a decline from 238 to 165 among men, and a change from 193 to 173 among women).

Madsen TE, Khoury J, Alwell K, et al. Sex-specific stroke incidence over time in the Greater Cincinnati/Northern Kentucky Stroke Study. Neurology. 2017 Aug 9 [Epub ahead of print].

Link Between Alcohol Intake and Cognitively Healthy Longevity

Older adults who consume alcohol moderately on a regular basis are more likely to live to age 85 without dementia or other cognitive impairments than nondrinkers, according to a study published in the August issue of the Journal of Alzheimer’s Disease. Researchers examined 1,344 older community-dwelling adults and assessed alcohol intake by questionnaire in 1984–1987. They evaluated cognitive function in approximately four-year intervals between 1988 and 2009. About 49% of participants reported moderate alcohol intake, and 48% reported drinking almost daily. Relative to nondrinkers, moderate and heavy drinkers had significantly higher adjusted odds of survival to age 85 without cognitive impairment. Near-daily drinkers had two- to threefold higher adjusted odds of cognitively healthy longevity versus living to at least age 85 with cognitive impairment or death before age 85.

Richard EL, Kritz-Silverstein D, Laughlin GA, et al. Alcohol intake and cognitively healthy longevity in community-dwelling adults: The Rancho Bernardo Study. J Alzheimers Dis. 2017;59(3):803-814.

MRI Shows Brain Differences in Genetic Autism

In two genetically related cohorts at high risk for autism, reciprocal neuroanatomic abnormalities were associated with cognitive and behavioral impairments, according to a study published online ahead of print August 8 in Radiology. Researchers performed MRI on 79 carriers of a deletion at 16p11.2, 79 carriers of a duplication at 16p11.2, 64 unaffected family members, and 109 controls. The participants completed cognitive and behavioral tests, and neuroradiologists reviewed the images for development-related abnormalities. The researchers found differences in the brain structures of deletion and duplication carriers, compared with noncarriers. Deletion carriers had brain overgrowth, and duplication carriers had brain undergrowth. When investigators compared cognitive assessments to imaging findings, they found that any imaging feature associated with the deletion carriers indicated worse daily living, communication, and social skills.

Owen JP, Bukshpun P, Pojman N, et al. Brain MR imaging findings and associated outcomes in carriers of the reciprocal copy number variation at 16p11.2. Radiology. 2017 Aug 8 [Epub ahead of print].

FDA Clears Stimpod NMS460 for Relief of Chronic Pain

The FDA has cleared Stimpod NMS460, a noninvasive neuromodulation device, for the symptomatic relief and management of chronic intractable pain. The unit also can be used for the adjunctive treatment of postsurgical pain, posttraumatic acute pain, and pain control due to rehabilitation. The device has a pulsed radio frequency waveform that creates electromagnetic effects similar to those of invasive pulsed radio frequency treatments. Treatment is applied transcutaneously. Case studies have shown quick and notable relief of chronic intractable pain. The treatment has no known side effects. The Stimpod NMS460 also incorporates nerve-locating technology that includes a nerve-mapping probe that enables practitioners to evaluate the treatment progress of damaged nerves. Xavant Technology, which markets Stimpod NMS460, is headquartered in Pretoria, South Africa.

Longer Sleep Is Associated With Lower BMI

Adults who have poor sleep patterns are more likely to be overweight or obese and have poorer metabolic health, according to a study published July 27 in PLoS One. Researchers analyzed associations between sleep duration and adiposity, selected metabolic health markers, and diet using National Diet and Nutrition Survey data. In all, 1,615 adults (57.1% female) between ages 19 and 65 completed questions about sleep duration and three to four days of food diaries. Investigators recorded blood pressure and waist circumference. Fasting blood lipids, glucose, glycated hemoglobin, thyroid hormones, and high-sensitivity C-reactive protein were measured in a subset of participants. After adjusting for age, ethnicity, sex, smoking, and socioeconomic status, sleep duration was negatively associated with BMI and waist circumference. Sleep duration was positively associated with high-density lipoprotein cholesterol.

Potter GDM, Cade JE, Hardie LJ. Longer sleep is associated with lower BMI and favorable metabolic profiles in UK adults: findings from the National Diet and Nutrition Survey. PLoS One. 2017; 12(7):e0182195.

Can Bleeding Risk After Stroke Be Predicted?

The S2TOP-BLEED score can estimate three-year major bleeding risk in patients with transient ischemic attack (TIA) or ischemic stroke who use antiplatelet agents, according to a study published online ahead of print August 2 in Neurology. To develop this prediction model, researchers combined data from six trials investigating antiplatelet therapy after TIA or ischemic stroke. They performed Cox regression analyses stratified by trial to study the association between predictors and major bleeding. Major bleeding occurred in 1,530 of the 43,112 patients during 94,833 person-years of follow-up. The observed three-year risk of major bleeding was 4.6%. The investigators identified male sex, smoking, type of antiplatelet agents, outcome on modified Rankin Scale ≥ 3, prior stroke, high blood pressure, lower BMI, elderly status, Asian ethnicity, and diabetes as predictors of major bleeding.

Hilkens NA, Algra A, Diener HC, et al. Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets: S2TOP-BLEED. Neurology. 2017 Aug 2 [Epub ahead of print].

Questionnaires Predict Survival in MS

The way patients with multiple sclerosis (MS) answer questionnaires could help to predict their survival rate from the disease, according to a study published July 10 in PLoS Medicine. From July 15, 2004, onward, 2,126 people with MS completed MS Impact Scale-29 (MSIS-29) questionnaires. By 2014, 264 participants had died. Higher baseline MSIS-29 physical score and higher baseline MSIS-29 psychologic score were associated with reduced survival time. In participants with high baseline MSIS-29 scores, mortality risk was greater if the MSIS-29 score worsened over one year. MSIS-29 physical scores were associated with survival time, independent of age, sex, and patient-reported Expanded Disability Status Scale score in a Cox regression analysis.

Raffel J, Wallace A, Gveric D, et al. Patient-reported outcomes and survival in multiple sclerosis: a 10-year retrospective cohort study using the Multiple Sclerosis Impact Scale-29. PLoS Med. 2017;14(7):e1002346.

—Kimberly Williams

Statin Prescription Varies in Stroke Belt

Less than half of patients with stroke discharged from the hospital receive a prescription for statins, and the likelihood of a prescription varies by patients’ location, sex, age, and race, according to a study published August 2 in the Journal of the American Heart Association. Researchers analyzed discharge medications for 323 participants hospitalized for an ischemic stroke during follow-up of the Reasons for Geographic and Racial Differences in Stroke study. In the Stroke Belt, participants ages 65 and older were 47% less likely to be discharged on a statin, compared with people younger than 65. Compared with women, men in the Stroke Belt were 31% less likely to be discharged on a statin, while men outside the Stroke Belt were more likely to be discharged on a statin.

Albright KC, Howard VJ, Howard G, et al. Age and sex disparities in discharge statin prescribing in the stroke belt: evidence from the Reasons for Geographic and Racial Differences in Stroke Study. J Am Heart Assoc. 2017;6(8).

Midlife Vascular Risk Factors Increase Risk of Dementia

Midlife vascular risk factors are associated with increased risk of dementia in blacks and whites, according to a study published online ahead of print August 7 in JAMA Neurology. In the Atherosclerosis Risk in Communities study, investigators measured demographic and vascular risk factors at baseline (ie, obesity, smoking, diabetes, prehypertension, hypertension, and hypercholesterolemia), along with the presence of the APOE ε4 genotype. After the baseline visit, participants had four additional in-person visits. In all, 1,516 cases of dementia (57.0% female and 34.9% black, with a mean age at visit 1 of 57.4) were identified among 15,744 participants. Black race, older age, lower educational attainment, and APOE ε4 genotype were associated with increased risk of dementia, as were midlife smoking, diabetes, prehypertension, and hypertension.

Gottesman RF, Albert MS, Alonso A, et al. Associations between midlife vascular risk factors and 25-year incident dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort. JAMA Neurol. 2017 August 7 [Epub ahead of print].

Resistance Training May Slow the Progression of MS

Progressive resistance training may have a neuroprotective or neuroregenerative effect in relapsing-remitting multiple sclerosis (MS), according to a study published online ahead of print July 1 in Multiple Sclerosis Journal. This study was a 24-week randomized controlled crossover trial. Participants were assigned to training or to a wait list. Assessments included disability measures and MRI. The MS Functional Composite score improved in the training group, but disability, lesion load, and global brain volumes did not differ between groups. The researchers noted higher absolute cortical thickness values in 19 of 74 investigated cortical regions after progressive resistance training. Observed changes were confirmed and reproduced when comparing relative cortical thickness changes between groups in the anterior cingulate gyrus, temporal pole, orbital sulcus, and inferior temporal sulcus.

Kjølhede T, Siemonsen S, Wenzel D, et al. Can resistance training impact MRI outcomes in relapsing-remitting multiple sclerosis? Mult Scler. 2017 Jul 1 [Epub ahead of print].

Noninvasive Device Measures Intracranial Pressure

A noninvasive device measures intracranial pressure (ICP) accurately, according to research published online ahead of print August 8 in the Journal of Neurosurgery. In patients with traumatic brain injury and subarachnoid hemorrhage who were undergoing treatment in a neurocritical intensive care unit, researchers recorded ICP using the gold-standard method of invasive external ventricular drainage or intraparenchymal monitoring. In addition, the authors simultaneously measured ICP noninvasively with a device that uses advanced signal-analysis algorithms for acoustic signals propagating through the cranium. Data were collected in 14 patients, yielding 2,543 data points of continuous parallel ICP values. For measurements at the ≥ 17-mm Hg cutoff, the sensitivity and specificity of the noninvasive device were 0.7541 and 0.8887, respectively. ICP values obtained using noninvasive and invasive monitoring methods correlated well.

Ganslandt O, Mourtzoukos S, Stadlbauer A, et al. Evaluation of a novel noninvasive ICP monitoring device in patients undergoing invasive ICP monitoring: preliminary results. J Neurosurg. 2017 Aug 8 [Epub ahead of print].

Strokes Decline Among Men, But Not Women

The rate of stroke in the US has declined among men, but not among women, according to a study published online ahead of print August 9 in Neurology. Researchers collected data on 1.3 million adults in Ohio and Kentucky between 1993 and 2010. They used medical records to identify first-ever strokes during four one-year periods. The researchers observed 7,710 incident strokes in the four periods, and 57% of them were among women. The incidence of all strokes decreased over time in men (263 to 192), but not in women (217 to 198). The researchers found a similar sex difference in the change in the rate of ischemic stroke (ie, a decline from 238 to 165 among men, and a change from 193 to 173 among women).

Madsen TE, Khoury J, Alwell K, et al. Sex-specific stroke incidence over time in the Greater Cincinnati/Northern Kentucky Stroke Study. Neurology. 2017 Aug 9 [Epub ahead of print].

Link Between Alcohol Intake and Cognitively Healthy Longevity

Older adults who consume alcohol moderately on a regular basis are more likely to live to age 85 without dementia or other cognitive impairments than nondrinkers, according to a study published in the August issue of the Journal of Alzheimer’s Disease. Researchers examined 1,344 older community-dwelling adults and assessed alcohol intake by questionnaire in 1984–1987. They evaluated cognitive function in approximately four-year intervals between 1988 and 2009. About 49% of participants reported moderate alcohol intake, and 48% reported drinking almost daily. Relative to nondrinkers, moderate and heavy drinkers had significantly higher adjusted odds of survival to age 85 without cognitive impairment. Near-daily drinkers had two- to threefold higher adjusted odds of cognitively healthy longevity versus living to at least age 85 with cognitive impairment or death before age 85.

Richard EL, Kritz-Silverstein D, Laughlin GA, et al. Alcohol intake and cognitively healthy longevity in community-dwelling adults: The Rancho Bernardo Study. J Alzheimers Dis. 2017;59(3):803-814.

MRI Shows Brain Differences in Genetic Autism

In two genetically related cohorts at high risk for autism, reciprocal neuroanatomic abnormalities were associated with cognitive and behavioral impairments, according to a study published online ahead of print August 8 in Radiology. Researchers performed MRI on 79 carriers of a deletion at 16p11.2, 79 carriers of a duplication at 16p11.2, 64 unaffected family members, and 109 controls. The participants completed cognitive and behavioral tests, and neuroradiologists reviewed the images for development-related abnormalities. The researchers found differences in the brain structures of deletion and duplication carriers, compared with noncarriers. Deletion carriers had brain overgrowth, and duplication carriers had brain undergrowth. When investigators compared cognitive assessments to imaging findings, they found that any imaging feature associated with the deletion carriers indicated worse daily living, communication, and social skills.

Owen JP, Bukshpun P, Pojman N, et al. Brain MR imaging findings and associated outcomes in carriers of the reciprocal copy number variation at 16p11.2. Radiology. 2017 Aug 8 [Epub ahead of print].

FDA Clears Stimpod NMS460 for Relief of Chronic Pain

The FDA has cleared Stimpod NMS460, a noninvasive neuromodulation device, for the symptomatic relief and management of chronic intractable pain. The unit also can be used for the adjunctive treatment of postsurgical pain, posttraumatic acute pain, and pain control due to rehabilitation. The device has a pulsed radio frequency waveform that creates electromagnetic effects similar to those of invasive pulsed radio frequency treatments. Treatment is applied transcutaneously. Case studies have shown quick and notable relief of chronic intractable pain. The treatment has no known side effects. The Stimpod NMS460 also incorporates nerve-locating technology that includes a nerve-mapping probe that enables practitioners to evaluate the treatment progress of damaged nerves. Xavant Technology, which markets Stimpod NMS460, is headquartered in Pretoria, South Africa.

Longer Sleep Is Associated With Lower BMI

Adults who have poor sleep patterns are more likely to be overweight or obese and have poorer metabolic health, according to a study published July 27 in PLoS One. Researchers analyzed associations between sleep duration and adiposity, selected metabolic health markers, and diet using National Diet and Nutrition Survey data. In all, 1,615 adults (57.1% female) between ages 19 and 65 completed questions about sleep duration and three to four days of food diaries. Investigators recorded blood pressure and waist circumference. Fasting blood lipids, glucose, glycated hemoglobin, thyroid hormones, and high-sensitivity C-reactive protein were measured in a subset of participants. After adjusting for age, ethnicity, sex, smoking, and socioeconomic status, sleep duration was negatively associated with BMI and waist circumference. Sleep duration was positively associated with high-density lipoprotein cholesterol.

Potter GDM, Cade JE, Hardie LJ. Longer sleep is associated with lower BMI and favorable metabolic profiles in UK adults: findings from the National Diet and Nutrition Survey. PLoS One. 2017; 12(7):e0182195.

Can Bleeding Risk After Stroke Be Predicted?

The S2TOP-BLEED score can estimate three-year major bleeding risk in patients with transient ischemic attack (TIA) or ischemic stroke who use antiplatelet agents, according to a study published online ahead of print August 2 in Neurology. To develop this prediction model, researchers combined data from six trials investigating antiplatelet therapy after TIA or ischemic stroke. They performed Cox regression analyses stratified by trial to study the association between predictors and major bleeding. Major bleeding occurred in 1,530 of the 43,112 patients during 94,833 person-years of follow-up. The observed three-year risk of major bleeding was 4.6%. The investigators identified male sex, smoking, type of antiplatelet agents, outcome on modified Rankin Scale ≥ 3, prior stroke, high blood pressure, lower BMI, elderly status, Asian ethnicity, and diabetes as predictors of major bleeding.

Hilkens NA, Algra A, Diener HC, et al. Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets: S2TOP-BLEED. Neurology. 2017 Aug 2 [Epub ahead of print].

Questionnaires Predict Survival in MS

The way patients with multiple sclerosis (MS) answer questionnaires could help to predict their survival rate from the disease, according to a study published July 10 in PLoS Medicine. From July 15, 2004, onward, 2,126 people with MS completed MS Impact Scale-29 (MSIS-29) questionnaires. By 2014, 264 participants had died. Higher baseline MSIS-29 physical score and higher baseline MSIS-29 psychologic score were associated with reduced survival time. In participants with high baseline MSIS-29 scores, mortality risk was greater if the MSIS-29 score worsened over one year. MSIS-29 physical scores were associated with survival time, independent of age, sex, and patient-reported Expanded Disability Status Scale score in a Cox regression analysis.

Raffel J, Wallace A, Gveric D, et al. Patient-reported outcomes and survival in multiple sclerosis: a 10-year retrospective cohort study using the Multiple Sclerosis Impact Scale-29. PLoS Med. 2017;14(7):e1002346.

—Kimberly Williams

Statin Prescription Varies in Stroke Belt

Less than half of patients with stroke discharged from the hospital receive a prescription for statins, and the likelihood of a prescription varies by patients’ location, sex, age, and race, according to a study published August 2 in the Journal of the American Heart Association. Researchers analyzed discharge medications for 323 participants hospitalized for an ischemic stroke during follow-up of the Reasons for Geographic and Racial Differences in Stroke study. In the Stroke Belt, participants ages 65 and older were 47% less likely to be discharged on a statin, compared with people younger than 65. Compared with women, men in the Stroke Belt were 31% less likely to be discharged on a statin, while men outside the Stroke Belt were more likely to be discharged on a statin.

Albright KC, Howard VJ, Howard G, et al. Age and sex disparities in discharge statin prescribing in the stroke belt: evidence from the Reasons for Geographic and Racial Differences in Stroke Study. J Am Heart Assoc. 2017;6(8).

Midlife Vascular Risk Factors Increase Risk of Dementia

Midlife vascular risk factors are associated with increased risk of dementia in blacks and whites, according to a study published online ahead of print August 7 in JAMA Neurology. In the Atherosclerosis Risk in Communities study, investigators measured demographic and vascular risk factors at baseline (ie, obesity, smoking, diabetes, prehypertension, hypertension, and hypercholesterolemia), along with the presence of the APOE ε4 genotype. After the baseline visit, participants had four additional in-person visits. In all, 1,516 cases of dementia (57.0% female and 34.9% black, with a mean age at visit 1 of 57.4) were identified among 15,744 participants. Black race, older age, lower educational attainment, and APOE ε4 genotype were associated with increased risk of dementia, as were midlife smoking, diabetes, prehypertension, and hypertension.

Gottesman RF, Albert MS, Alonso A, et al. Associations between midlife vascular risk factors and 25-year incident dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort. JAMA Neurol. 2017 August 7 [Epub ahead of print].

Resistance Training May Slow the Progression of MS

Progressive resistance training may have a neuroprotective or neuroregenerative effect in relapsing-remitting multiple sclerosis (MS), according to a study published online ahead of print July 1 in Multiple Sclerosis Journal. This study was a 24-week randomized controlled crossover trial. Participants were assigned to training or to a wait list. Assessments included disability measures and MRI. The MS Functional Composite score improved in the training group, but disability, lesion load, and global brain volumes did not differ between groups. The researchers noted higher absolute cortical thickness values in 19 of 74 investigated cortical regions after progressive resistance training. Observed changes were confirmed and reproduced when comparing relative cortical thickness changes between groups in the anterior cingulate gyrus, temporal pole, orbital sulcus, and inferior temporal sulcus.

Kjølhede T, Siemonsen S, Wenzel D, et al. Can resistance training impact MRI outcomes in relapsing-remitting multiple sclerosis? Mult Scler. 2017 Jul 1 [Epub ahead of print].

Noninvasive Device Measures Intracranial Pressure

A noninvasive device measures intracranial pressure (ICP) accurately, according to research published online ahead of print August 8 in the Journal of Neurosurgery. In patients with traumatic brain injury and subarachnoid hemorrhage who were undergoing treatment in a neurocritical intensive care unit, researchers recorded ICP using the gold-standard method of invasive external ventricular drainage or intraparenchymal monitoring. In addition, the authors simultaneously measured ICP noninvasively with a device that uses advanced signal-analysis algorithms for acoustic signals propagating through the cranium. Data were collected in 14 patients, yielding 2,543 data points of continuous parallel ICP values. For measurements at the ≥ 17-mm Hg cutoff, the sensitivity and specificity of the noninvasive device were 0.7541 and 0.8887, respectively. ICP values obtained using noninvasive and invasive monitoring methods correlated well.

Ganslandt O, Mourtzoukos S, Stadlbauer A, et al. Evaluation of a novel noninvasive ICP monitoring device in patients undergoing invasive ICP monitoring: preliminary results. J Neurosurg. 2017 Aug 8 [Epub ahead of print].

Strokes Decline Among Men, But Not Women

The rate of stroke in the US has declined among men, but not among women, according to a study published online ahead of print August 9 in Neurology. Researchers collected data on 1.3 million adults in Ohio and Kentucky between 1993 and 2010. They used medical records to identify first-ever strokes during four one-year periods. The researchers observed 7,710 incident strokes in the four periods, and 57% of them were among women. The incidence of all strokes decreased over time in men (263 to 192), but not in women (217 to 198). The researchers found a similar sex difference in the change in the rate of ischemic stroke (ie, a decline from 238 to 165 among men, and a change from 193 to 173 among women).

Madsen TE, Khoury J, Alwell K, et al. Sex-specific stroke incidence over time in the Greater Cincinnati/Northern Kentucky Stroke Study. Neurology. 2017 Aug 9 [Epub ahead of print].

Link Between Alcohol Intake and Cognitively Healthy Longevity

Older adults who consume alcohol moderately on a regular basis are more likely to live to age 85 without dementia or other cognitive impairments than nondrinkers, according to a study published in the August issue of the Journal of Alzheimer’s Disease. Researchers examined 1,344 older community-dwelling adults and assessed alcohol intake by questionnaire in 1984–1987. They evaluated cognitive function in approximately four-year intervals between 1988 and 2009. About 49% of participants reported moderate alcohol intake, and 48% reported drinking almost daily. Relative to nondrinkers, moderate and heavy drinkers had significantly higher adjusted odds of survival to age 85 without cognitive impairment. Near-daily drinkers had two- to threefold higher adjusted odds of cognitively healthy longevity versus living to at least age 85 with cognitive impairment or death before age 85.

Richard EL, Kritz-Silverstein D, Laughlin GA, et al. Alcohol intake and cognitively healthy longevity in community-dwelling adults: The Rancho Bernardo Study. J Alzheimers Dis. 2017;59(3):803-814.

MRI Shows Brain Differences in Genetic Autism

In two genetically related cohorts at high risk for autism, reciprocal neuroanatomic abnormalities were associated with cognitive and behavioral impairments, according to a study published online ahead of print August 8 in Radiology. Researchers performed MRI on 79 carriers of a deletion at 16p11.2, 79 carriers of a duplication at 16p11.2, 64 unaffected family members, and 109 controls. The participants completed cognitive and behavioral tests, and neuroradiologists reviewed the images for development-related abnormalities. The researchers found differences in the brain structures of deletion and duplication carriers, compared with noncarriers. Deletion carriers had brain overgrowth, and duplication carriers had brain undergrowth. When investigators compared cognitive assessments to imaging findings, they found that any imaging feature associated with the deletion carriers indicated worse daily living, communication, and social skills.

Owen JP, Bukshpun P, Pojman N, et al. Brain MR imaging findings and associated outcomes in carriers of the reciprocal copy number variation at 16p11.2. Radiology. 2017 Aug 8 [Epub ahead of print].

FDA Clears Stimpod NMS460 for Relief of Chronic Pain

The FDA has cleared Stimpod NMS460, a noninvasive neuromodulation device, for the symptomatic relief and management of chronic intractable pain. The unit also can be used for the adjunctive treatment of postsurgical pain, posttraumatic acute pain, and pain control due to rehabilitation. The device has a pulsed radio frequency waveform that creates electromagnetic effects similar to those of invasive pulsed radio frequency treatments. Treatment is applied transcutaneously. Case studies have shown quick and notable relief of chronic intractable pain. The treatment has no known side effects. The Stimpod NMS460 also incorporates nerve-locating technology that includes a nerve-mapping probe that enables practitioners to evaluate the treatment progress of damaged nerves. Xavant Technology, which markets Stimpod NMS460, is headquartered in Pretoria, South Africa.

Longer Sleep Is Associated With Lower BMI

Adults who have poor sleep patterns are more likely to be overweight or obese and have poorer metabolic health, according to a study published July 27 in PLoS One. Researchers analyzed associations between sleep duration and adiposity, selected metabolic health markers, and diet using National Diet and Nutrition Survey data. In all, 1,615 adults (57.1% female) between ages 19 and 65 completed questions about sleep duration and three to four days of food diaries. Investigators recorded blood pressure and waist circumference. Fasting blood lipids, glucose, glycated hemoglobin, thyroid hormones, and high-sensitivity C-reactive protein were measured in a subset of participants. After adjusting for age, ethnicity, sex, smoking, and socioeconomic status, sleep duration was negatively associated with BMI and waist circumference. Sleep duration was positively associated with high-density lipoprotein cholesterol.

Potter GDM, Cade JE, Hardie LJ. Longer sleep is associated with lower BMI and favorable metabolic profiles in UK adults: findings from the National Diet and Nutrition Survey. PLoS One. 2017; 12(7):e0182195.

Can Bleeding Risk After Stroke Be Predicted?

The S2TOP-BLEED score can estimate three-year major bleeding risk in patients with transient ischemic attack (TIA) or ischemic stroke who use antiplatelet agents, according to a study published online ahead of print August 2 in Neurology. To develop this prediction model, researchers combined data from six trials investigating antiplatelet therapy after TIA or ischemic stroke. They performed Cox regression analyses stratified by trial to study the association between predictors and major bleeding. Major bleeding occurred in 1,530 of the 43,112 patients during 94,833 person-years of follow-up. The observed three-year risk of major bleeding was 4.6%. The investigators identified male sex, smoking, type of antiplatelet agents, outcome on modified Rankin Scale ≥ 3, prior stroke, high blood pressure, lower BMI, elderly status, Asian ethnicity, and diabetes as predictors of major bleeding.

Hilkens NA, Algra A, Diener HC, et al. Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets: S2TOP-BLEED. Neurology. 2017 Aug 2 [Epub ahead of print].

Questionnaires Predict Survival in MS

The way patients with multiple sclerosis (MS) answer questionnaires could help to predict their survival rate from the disease, according to a study published July 10 in PLoS Medicine. From July 15, 2004, onward, 2,126 people with MS completed MS Impact Scale-29 (MSIS-29) questionnaires. By 2014, 264 participants had died. Higher baseline MSIS-29 physical score and higher baseline MSIS-29 psychologic score were associated with reduced survival time. In participants with high baseline MSIS-29 scores, mortality risk was greater if the MSIS-29 score worsened over one year. MSIS-29 physical scores were associated with survival time, independent of age, sex, and patient-reported Expanded Disability Status Scale score in a Cox regression analysis.

Raffel J, Wallace A, Gveric D, et al. Patient-reported outcomes and survival in multiple sclerosis: a 10-year retrospective cohort study using the Multiple Sclerosis Impact Scale-29. PLoS Med. 2017;14(7):e1002346.

—Kimberly Williams

Annual mammograms starting at age 40 and continuing until age 84 will achieve the greatest reductions in breast cancer deaths, according to a modeling study published in Cancer.

Researchers used Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer models to compare three current mammography-based screening approaches for women at average risk of breast cancer. The first approach is for annual screening from ages 40-84 years, the second is a hybrid approach with annual screening from ages 45 to 54 then biennial screening from ages 55 to 79, and the third approach involves biennial mammograms from ages 50 to 74.

The modeling suggested that the largest mean reduction in mortality – 36.9% – was associated with annual screening starting at age 40. The second largest reduction of 30.8% occurred with the hybrid screening approach starting at age 45, while the smallest reduction in mortality – 23.2% – occurred with biennial screening starting at age 50 (Cancer 2017 Aug 21. doi: 10.1002/cncr.30842).

Annual screening also averted the most deaths from breast cancer – 11.9 per 1,000 women screened – and gained the most life-years (189 per 1,000 women screened, compared with 149 for the hybrid approach and 110 for biennial screening), reported Elizabeth K. Arleo, MD, of Weill Cornell Imaging at New York–Presbyterian, New York, and her coauthors.

copyright John Foxx/Thinkstock

Annual mammograms starting at age 40 and continuing until age 84 will achieve the greatest reductions in breast cancer deaths, according to a modeling study published in Cancer.

Researchers used Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer models to compare three current mammography-based screening approaches for women at average risk of breast cancer. The first approach is for annual screening from ages 40-84 years, the second is a hybrid approach with annual screening from ages 45 to 54 then biennial screening from ages 55 to 79, and the third approach involves biennial mammograms from ages 50 to 74.

The modeling suggested that the largest mean reduction in mortality – 36.9% – was associated with annual screening starting at age 40. The second largest reduction of 30.8% occurred with the hybrid screening approach starting at age 45, while the smallest reduction in mortality – 23.2% – occurred with biennial screening starting at age 50 (Cancer 2017 Aug 21. doi: 10.1002/cncr.30842).

Annual screening also averted the most deaths from breast cancer – 11.9 per 1,000 women screened – and gained the most life-years (189 per 1,000 women screened, compared with 149 for the hybrid approach and 110 for biennial screening), reported Elizabeth K. Arleo, MD, of Weill Cornell Imaging at New York–Presbyterian, New York, and her coauthors.

copyright John Foxx/Thinkstock

Annual mammograms starting at age 40 and continuing until age 84 will achieve the greatest reductions in breast cancer deaths, according to a modeling study published in Cancer.

Researchers used Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer models to compare three current mammography-based screening approaches for women at average risk of breast cancer. The first approach is for annual screening from ages 40-84 years, the second is a hybrid approach with annual screening from ages 45 to 54 then biennial screening from ages 55 to 79, and the third approach involves biennial mammograms from ages 50 to 74.

The modeling suggested that the largest mean reduction in mortality – 36.9% – was associated with annual screening starting at age 40. The second largest reduction of 30.8% occurred with the hybrid screening approach starting at age 45, while the smallest reduction in mortality – 23.2% – occurred with biennial screening starting at age 50 (Cancer 2017 Aug 21. doi: 10.1002/cncr.30842).

Annual screening also averted the most deaths from breast cancer – 11.9 per 1,000 women screened – and gained the most life-years (189 per 1,000 women screened, compared with 149 for the hybrid approach and 110 for biennial screening), reported Elizabeth K. Arleo, MD, of Weill Cornell Imaging at New York–Presbyterian, New York, and her coauthors.

copyright John Foxx/Thinkstock

The U.S. opioid crisis and ongoing epidemic of chronic pain are inextricably intertwined, and psychiatrists are increasingly being called upon to intervene.

In a June 2016 blog post penned in the wake of new Centers for Disease Control and Prevention prescribing guidelines calling for a move away from opioids as the first-line treatment for many types of chronic noncancer pain, National Institute on Drug Abuse (NIDA) Director Nora D. Volkow, MD, decried the absence of psychiatrists on the front lines.

“Thus far, psychiatrists have not taken an active role in addressing the problem of chronic pain, but they have an important role to play here, for multiple reasons,” she wrote.

Chronic pain is closely linked to multiple psychiatric problems, she explained.

Power of hypnosis

“The brain has a whole lot to do with pain perception, and there’s a lot you can do to control it,” said Dr. Spiegel, the Jack, Samuel, and Lulu Willson Professor in Medicine in the department of psychiatry and behavioral sciences at Stanford (Calif.) University and a member of the Institute of Medicine.

And despite what many patients and physicians believe, it’s simply not true that if you’re not using a drug, you can’t actually control pain, he added.

Other approaches to pain management

For the one in three adults who are not hypnotizable, Dr. Spiegel teaches distraction techniques, and sometimes recommends acupuncture, which can be helpful for some patients. Exercise and physical therapy also can be of benefit for chronic pain.

“You can have very real pain that you can learn to deal with as people did throughout history. That doesn’t mean you should suffer unnecessarily; there is a time and place for opiates and other [pharmacologic] strategies, but they should be one among an array of choices,” he said, adding that for chronic pain, opioids can be more of a problem than a solution, and learning these techniques “can really help people safely deal with pain.”

Jeffrey Borckardt, PhD, professor and director of the division of biobehavioral medicine at the Medical University of South Carolina (MUSC), Charleston, agreed that hypnosis is a well-researched and effective treatment for pain, despite being better known for weight loss and smoking cessation. Another, lesser-known treatment that has been shown to have some effect for pain is acceptance and commitment therapy, or ACT, which incorporates the practice of mindfulness.

CBT and ‘360’ programs

CBT also was mentioned by Dr. Volkow in her June 2016 blog post. She called it “one of the most effective pain treatments,” and said that “assisting patients in learning to change their pain-related thoughts, emotions, and behaviors is going to help with their condition, regardless of other pharmacological interventions.”

Dr. Borckardt said it is particularly effective in the context of programs that provide what he called “a 360 approach.” These multifaceted treatment programs aim to help chronic pain patients taper off of opioid medications and to find other approaches to managing pain.

Only a handful of such comprehensive, intensive outpatient programs exist across the United States, but the concept is taking hold, driven in part by the opioid crisis, and more centers are opening. In fact, Dr. Borckardt is helping to develop such a program at MUSC. The program will likely be housed in the MUSC Wellness Center, and much like the Mayo Clinic’s Pain Rehabilitation Center, which opened in 1974 and was one of the first such programs in the world, the MUSC program will involve an integrated team of health care professionals that provide CBT for pain, physical therapy, occupational therapy, and other programs designed to help patients living with pain.

This is widely accepted as being the best approach for pain rehabilitation, Dr. Borckardt said.

TMS and TDCS

Dr. Borckardt also has worked with some more cutting-edge approaches to pain management. Transcranial magnetic stimulation (TMS), which is approved for the treatment of depression, also has shown promise for treating pain. TMS can target areas in the brain involved with specific functioning, such as emotional regulation. The high-frequency stimulation is believed to enhance that particular area and produce a clinical effect.

“Pain is a subjective, largely psychological experience, and it involves an emotional component,” he said, explaining that the rationale for the use of TMS for pain is that the emotional component of the pain experience can be targeted along with the sensory and cognitive aspects of the pain experience.

TMS is being used in various studies, and has been used off label for pain management, but the out-of-pocket cost is high because it is not currently approved for pain and is therefore not covered by insurance, he said.

For depression, TMS typically is used 5 days per week for 3 weeks – at a cost ranging anywhere from $100 to $500 per session. It remains unclear how many sessions would be required for pain treatment to produce a sustained effect, but it would likely be similar to the requirements for depression treatment, and may also require follow-up treatments, Dr. Borckardt said.

“We do know with reasonable confidence that it impacts pain perception and can impact sensory or emotional components of pain, depending on the part of the brain treated. But we don’t know how long we have to treat, how often, or how durable the effects are,” he said, noting that several groups are studying TMS for pain.

Notably, there is also some very preliminary evidence that TMS may be useful for treating addiction by affecting cravings for substances such as opiates, nicotine, and alcohol. If that effect is confirmed, TMS could help chronic pain patients reduce their need for higher opioid doses, thereby lowering the risk of overdose, which is an important factor in the opioid crisis; most patients who use opioids don’t become addicted, but they can be at risk for overdose because of the need for high doses to control their pain, he explained.

In one study, the use of TMS postoperatively reduced the amount of in-hospital drug use by 40%, he said, noting that the reduction could convert to a reduction in the use of pain medication after discharge as well.

A related treatment, transcranial direct current stimulation, or tDCS, involves placement of electrodes directly on the scalp to run weak electrical currents through the brain, again trying to alter areas associated with pain perception. Ongoing studies are looking at combining tDCS and CBT with the hope that the two will have synergistic effects, including one in veterans with low back pain and opioid misuse. Another small pilot study in patients with fibromyalgia recently concluded and had some promising results.

These and other nonpharmacologic approaches to pain management could play an important role in the effort to reduce opioid prescribing. Currently, about 90 Americans die each day after overdosing on opioids, according to NIDA, and the CDC estimates that prescription opioid misuse alone in the United States costs $78.5 billion per year in health care, lost productivity, addiction treatment, and criminal justice involvement.

In her plea to psychiatrists to take action to intervene, Dr. Volkow underscored the value that they bring to the table.

“It is crucial that we not lose sight of the reality and complexity of chronic pain as management of chronic noncancer pain moves toward greater caution around opioid medication. This should not be solely an issue for primary care medicine or neurology, but also for specialties such as psychiatry that have much to offer people who are suffering from complex disorders in which physical symptoms merge with psychological distress,” she wrote.

Dr. Volkow has written hundreds of peer-reviewed articles, including analyses of the opioid crisis (N Engl J Med. 2017 Jul 27;377[4]:391-4) and (Neuron. 2016 Oct 19[2]:294-7). Dr. Spiegel is coauthor of Trance and Treatment: Clinical Uses of Hypnosis (Washington: American Psychiatric Association Publishing, 2004), a textbook written to help psychiatrists and other physicians learn to use hypnosis. Dr. Borckardt receives research funding from the National Institutes of Health.

[email protected]

The U.S. opioid crisis and ongoing epidemic of chronic pain are inextricably intertwined, and psychiatrists are increasingly being called upon to intervene.

In a June 2016 blog post penned in the wake of new Centers for Disease Control and Prevention prescribing guidelines calling for a move away from opioids as the first-line treatment for many types of chronic noncancer pain, National Institute on Drug Abuse (NIDA) Director Nora D. Volkow, MD, decried the absence of psychiatrists on the front lines.

“Thus far, psychiatrists have not taken an active role in addressing the problem of chronic pain, but they have an important role to play here, for multiple reasons,” she wrote.

Chronic pain is closely linked to multiple psychiatric problems, she explained.

Power of hypnosis

“The brain has a whole lot to do with pain perception, and there’s a lot you can do to control it,” said Dr. Spiegel, the Jack, Samuel, and Lulu Willson Professor in Medicine in the department of psychiatry and behavioral sciences at Stanford (Calif.) University and a member of the Institute of Medicine.

And despite what many patients and physicians believe, it’s simply not true that if you’re not using a drug, you can’t actually control pain, he added.

Other approaches to pain management

For the one in three adults who are not hypnotizable, Dr. Spiegel teaches distraction techniques, and sometimes recommends acupuncture, which can be helpful for some patients. Exercise and physical therapy also can be of benefit for chronic pain.

“You can have very real pain that you can learn to deal with as people did throughout history. That doesn’t mean you should suffer unnecessarily; there is a time and place for opiates and other [pharmacologic] strategies, but they should be one among an array of choices,” he said, adding that for chronic pain, opioids can be more of a problem than a solution, and learning these techniques “can really help people safely deal with pain.”

Jeffrey Borckardt, PhD, professor and director of the division of biobehavioral medicine at the Medical University of South Carolina (MUSC), Charleston, agreed that hypnosis is a well-researched and effective treatment for pain, despite being better known for weight loss and smoking cessation. Another, lesser-known treatment that has been shown to have some effect for pain is acceptance and commitment therapy, or ACT, which incorporates the practice of mindfulness.

CBT and ‘360’ programs

CBT also was mentioned by Dr. Volkow in her June 2016 blog post. She called it “one of the most effective pain treatments,” and said that “assisting patients in learning to change their pain-related thoughts, emotions, and behaviors is going to help with their condition, regardless of other pharmacological interventions.”

Dr. Borckardt said it is particularly effective in the context of programs that provide what he called “a 360 approach.” These multifaceted treatment programs aim to help chronic pain patients taper off of opioid medications and to find other approaches to managing pain.

Only a handful of such comprehensive, intensive outpatient programs exist across the United States, but the concept is taking hold, driven in part by the opioid crisis, and more centers are opening. In fact, Dr. Borckardt is helping to develop such a program at MUSC. The program will likely be housed in the MUSC Wellness Center, and much like the Mayo Clinic’s Pain Rehabilitation Center, which opened in 1974 and was one of the first such programs in the world, the MUSC program will involve an integrated team of health care professionals that provide CBT for pain, physical therapy, occupational therapy, and other programs designed to help patients living with pain.

This is widely accepted as being the best approach for pain rehabilitation, Dr. Borckardt said.

TMS and TDCS

Dr. Borckardt also has worked with some more cutting-edge approaches to pain management. Transcranial magnetic stimulation (TMS), which is approved for the treatment of depression, also has shown promise for treating pain. TMS can target areas in the brain involved with specific functioning, such as emotional regulation. The high-frequency stimulation is believed to enhance that particular area and produce a clinical effect.

“Pain is a subjective, largely psychological experience, and it involves an emotional component,” he said, explaining that the rationale for the use of TMS for pain is that the emotional component of the pain experience can be targeted along with the sensory and cognitive aspects of the pain experience.

TMS is being used in various studies, and has been used off label for pain management, but the out-of-pocket cost is high because it is not currently approved for pain and is therefore not covered by insurance, he said.

For depression, TMS typically is used 5 days per week for 3 weeks – at a cost ranging anywhere from $100 to $500 per session. It remains unclear how many sessions would be required for pain treatment to produce a sustained effect, but it would likely be similar to the requirements for depression treatment, and may also require follow-up treatments, Dr. Borckardt said.

“We do know with reasonable confidence that it impacts pain perception and can impact sensory or emotional components of pain, depending on the part of the brain treated. But we don’t know how long we have to treat, how often, or how durable the effects are,” he said, noting that several groups are studying TMS for pain.

Notably, there is also some very preliminary evidence that TMS may be useful for treating addiction by affecting cravings for substances such as opiates, nicotine, and alcohol. If that effect is confirmed, TMS could help chronic pain patients reduce their need for higher opioid doses, thereby lowering the risk of overdose, which is an important factor in the opioid crisis; most patients who use opioids don’t become addicted, but they can be at risk for overdose because of the need for high doses to control their pain, he explained.

In one study, the use of TMS postoperatively reduced the amount of in-hospital drug use by 40%, he said, noting that the reduction could convert to a reduction in the use of pain medication after discharge as well.

A related treatment, transcranial direct current stimulation, or tDCS, involves placement of electrodes directly on the scalp to run weak electrical currents through the brain, again trying to alter areas associated with pain perception. Ongoing studies are looking at combining tDCS and CBT with the hope that the two will have synergistic effects, including one in veterans with low back pain and opioid misuse. Another small pilot study in patients with fibromyalgia recently concluded and had some promising results.

These and other nonpharmacologic approaches to pain management could play an important role in the effort to reduce opioid prescribing. Currently, about 90 Americans die each day after overdosing on opioids, according to NIDA, and the CDC estimates that prescription opioid misuse alone in the United States costs $78.5 billion per year in health care, lost productivity, addiction treatment, and criminal justice involvement.

In her plea to psychiatrists to take action to intervene, Dr. Volkow underscored the value that they bring to the table.

“It is crucial that we not lose sight of the reality and complexity of chronic pain as management of chronic noncancer pain moves toward greater caution around opioid medication. This should not be solely an issue for primary care medicine or neurology, but also for specialties such as psychiatry that have much to offer people who are suffering from complex disorders in which physical symptoms merge with psychological distress,” she wrote.

Dr. Volkow has written hundreds of peer-reviewed articles, including analyses of the opioid crisis (N Engl J Med. 2017 Jul 27;377[4]:391-4) and (Neuron. 2016 Oct 19[2]:294-7). Dr. Spiegel is coauthor of Trance and Treatment: Clinical Uses of Hypnosis (Washington: American Psychiatric Association Publishing, 2004), a textbook written to help psychiatrists and other physicians learn to use hypnosis. Dr. Borckardt receives research funding from the National Institutes of Health.

[email protected]

The U.S. opioid crisis and ongoing epidemic of chronic pain are inextricably intertwined, and psychiatrists are increasingly being called upon to intervene.

In a June 2016 blog post penned in the wake of new Centers for Disease Control and Prevention prescribing guidelines calling for a move away from opioids as the first-line treatment for many types of chronic noncancer pain, National Institute on Drug Abuse (NIDA) Director Nora D. Volkow, MD, decried the absence of psychiatrists on the front lines.

“Thus far, psychiatrists have not taken an active role in addressing the problem of chronic pain, but they have an important role to play here, for multiple reasons,” she wrote.

Chronic pain is closely linked to multiple psychiatric problems, she explained.

Power of hypnosis

“The brain has a whole lot to do with pain perception, and there’s a lot you can do to control it,” said Dr. Spiegel, the Jack, Samuel, and Lulu Willson Professor in Medicine in the department of psychiatry and behavioral sciences at Stanford (Calif.) University and a member of the Institute of Medicine.

And despite what many patients and physicians believe, it’s simply not true that if you’re not using a drug, you can’t actually control pain, he added.

Other approaches to pain management

For the one in three adults who are not hypnotizable, Dr. Spiegel teaches distraction techniques, and sometimes recommends acupuncture, which can be helpful for some patients. Exercise and physical therapy also can be of benefit for chronic pain.

“You can have very real pain that you can learn to deal with as people did throughout history. That doesn’t mean you should suffer unnecessarily; there is a time and place for opiates and other [pharmacologic] strategies, but they should be one among an array of choices,” he said, adding that for chronic pain, opioids can be more of a problem than a solution, and learning these techniques “can really help people safely deal with pain.”

Jeffrey Borckardt, PhD, professor and director of the division of biobehavioral medicine at the Medical University of South Carolina (MUSC), Charleston, agreed that hypnosis is a well-researched and effective treatment for pain, despite being better known for weight loss and smoking cessation. Another, lesser-known treatment that has been shown to have some effect for pain is acceptance and commitment therapy, or ACT, which incorporates the practice of mindfulness.

CBT and ‘360’ programs

CBT also was mentioned by Dr. Volkow in her June 2016 blog post. She called it “one of the most effective pain treatments,” and said that “assisting patients in learning to change their pain-related thoughts, emotions, and behaviors is going to help with their condition, regardless of other pharmacological interventions.”

Dr. Borckardt said it is particularly effective in the context of programs that provide what he called “a 360 approach.” These multifaceted treatment programs aim to help chronic pain patients taper off of opioid medications and to find other approaches to managing pain.

Only a handful of such comprehensive, intensive outpatient programs exist across the United States, but the concept is taking hold, driven in part by the opioid crisis, and more centers are opening. In fact, Dr. Borckardt is helping to develop such a program at MUSC. The program will likely be housed in the MUSC Wellness Center, and much like the Mayo Clinic’s Pain Rehabilitation Center, which opened in 1974 and was one of the first such programs in the world, the MUSC program will involve an integrated team of health care professionals that provide CBT for pain, physical therapy, occupational therapy, and other programs designed to help patients living with pain.

This is widely accepted as being the best approach for pain rehabilitation, Dr. Borckardt said.

TMS and TDCS

Dr. Borckardt also has worked with some more cutting-edge approaches to pain management. Transcranial magnetic stimulation (TMS), which is approved for the treatment of depression, also has shown promise for treating pain. TMS can target areas in the brain involved with specific functioning, such as emotional regulation. The high-frequency stimulation is believed to enhance that particular area and produce a clinical effect.

“Pain is a subjective, largely psychological experience, and it involves an emotional component,” he said, explaining that the rationale for the use of TMS for pain is that the emotional component of the pain experience can be targeted along with the sensory and cognitive aspects of the pain experience.

TMS is being used in various studies, and has been used off label for pain management, but the out-of-pocket cost is high because it is not currently approved for pain and is therefore not covered by insurance, he said.

For depression, TMS typically is used 5 days per week for 3 weeks – at a cost ranging anywhere from $100 to $500 per session. It remains unclear how many sessions would be required for pain treatment to produce a sustained effect, but it would likely be similar to the requirements for depression treatment, and may also require follow-up treatments, Dr. Borckardt said.

“We do know with reasonable confidence that it impacts pain perception and can impact sensory or emotional components of pain, depending on the part of the brain treated. But we don’t know how long we have to treat, how often, or how durable the effects are,” he said, noting that several groups are studying TMS for pain.

Notably, there is also some very preliminary evidence that TMS may be useful for treating addiction by affecting cravings for substances such as opiates, nicotine, and alcohol. If that effect is confirmed, TMS could help chronic pain patients reduce their need for higher opioid doses, thereby lowering the risk of overdose, which is an important factor in the opioid crisis; most patients who use opioids don’t become addicted, but they can be at risk for overdose because of the need for high doses to control their pain, he explained.

In one study, the use of TMS postoperatively reduced the amount of in-hospital drug use by 40%, he said, noting that the reduction could convert to a reduction in the use of pain medication after discharge as well.

A related treatment, transcranial direct current stimulation, or tDCS, involves placement of electrodes directly on the scalp to run weak electrical currents through the brain, again trying to alter areas associated with pain perception. Ongoing studies are looking at combining tDCS and CBT with the hope that the two will have synergistic effects, including one in veterans with low back pain and opioid misuse. Another small pilot study in patients with fibromyalgia recently concluded and had some promising results.

These and other nonpharmacologic approaches to pain management could play an important role in the effort to reduce opioid prescribing. Currently, about 90 Americans die each day after overdosing on opioids, according to NIDA, and the CDC estimates that prescription opioid misuse alone in the United States costs $78.5 billion per year in health care, lost productivity, addiction treatment, and criminal justice involvement.

In her plea to psychiatrists to take action to intervene, Dr. Volkow underscored the value that they bring to the table.

“It is crucial that we not lose sight of the reality and complexity of chronic pain as management of chronic noncancer pain moves toward greater caution around opioid medication. This should not be solely an issue for primary care medicine or neurology, but also for specialties such as psychiatry that have much to offer people who are suffering from complex disorders in which physical symptoms merge with psychological distress,” she wrote.

Dr. Volkow has written hundreds of peer-reviewed articles, including analyses of the opioid crisis (N Engl J Med. 2017 Jul 27;377[4]:391-4) and (Neuron. 2016 Oct 19[2]:294-7). Dr. Spiegel is coauthor of Trance and Treatment: Clinical Uses of Hypnosis (Washington: American Psychiatric Association Publishing, 2004), a textbook written to help psychiatrists and other physicians learn to use hypnosis. Dr. Borckardt receives research funding from the National Institutes of Health.

[email protected]

BARCELONA – Combined treatment with a very low dosage of the anticoagulant rivaroxaban plus low-dose aspirin produced significant cuts in major adverse coronary, cerebral, and peripheral artery disease events with just a modest rise in major bleeding events in patients with stable disease in the COMPASS pivotal, randomized trial with more than 27,000 patients.

The benefits from the rivaroxaban plus aspirin regimen included a statistically significant 24% relative risk reduction in the study’s primary, combined endpoint, and a significant 18% relative risk reduction in all-cause death compared with a standard regimen of aspirin only, John W. Eikelboom, MD, said at the annual congress of the European Society of Cardiology. In addition, analysis of the net clinical benefit from treatment that took into account both the major adverse cardiovascular events prevented and major bleeding events induced, showed that the rivaroxaban-plus-aspirin regimen cut these by a statistically significant 20%, compared with aspirin alone.

Other notable benefits documented by the findings included a statistically significant 42% relative risk reduction for stroke and a statistically significant 46% relative risk reduction in the incidence of major adverse limb events among the roughly one-quarter of enrolled patients who entered the study with evidence of peripheral artery disease.

These risk reductions are similar in magnitude to the secondary-prevention benefits produced by controlling hypertension or dyslipidemia, noted Dr. Eikelboom, a researcher at McMaster University in Hamilton, Ont. “In the future, rivaroxaban will take its place among the other foundational treatments for long-term, secondary prevention,” he predicted in a video interview.

The COMPASS trial produced “unambiguous results that should change guidelines and the management of stable coronary artery disease,” commented Eugene Braunwald, MD, designated discussant for Dr. Eikelboom’s report. The results are “an important step for thrombocardiology,” said Dr. Braunwald, professor of medicine at Harvard Medical School in Boston.

Concurrently with Dr. Eikelboom’s report the results appeared in an article published online (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1709118). This publication also include an editorial by Dr. Braunwald (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMe1710241).

Mitchel L. Zoler/Frontline Medical News

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

BARCELONA – Combined treatment with a very low dosage of the anticoagulant rivaroxaban plus low-dose aspirin produced significant cuts in major adverse coronary, cerebral, and peripheral artery disease events with just a modest rise in major bleeding events in patients with stable disease in the COMPASS pivotal, randomized trial with more than 27,000 patients.

The benefits from the rivaroxaban plus aspirin regimen included a statistically significant 24% relative risk reduction in the study’s primary, combined endpoint, and a significant 18% relative risk reduction in all-cause death compared with a standard regimen of aspirin only, John W. Eikelboom, MD, said at the annual congress of the European Society of Cardiology. In addition, analysis of the net clinical benefit from treatment that took into account both the major adverse cardiovascular events prevented and major bleeding events induced, showed that the rivaroxaban-plus-aspirin regimen cut these by a statistically significant 20%, compared with aspirin alone.

Other notable benefits documented by the findings included a statistically significant 42% relative risk reduction for stroke and a statistically significant 46% relative risk reduction in the incidence of major adverse limb events among the roughly one-quarter of enrolled patients who entered the study with evidence of peripheral artery disease.

These risk reductions are similar in magnitude to the secondary-prevention benefits produced by controlling hypertension or dyslipidemia, noted Dr. Eikelboom, a researcher at McMaster University in Hamilton, Ont. “In the future, rivaroxaban will take its place among the other foundational treatments for long-term, secondary prevention,” he predicted in a video interview.

The COMPASS trial produced “unambiguous results that should change guidelines and the management of stable coronary artery disease,” commented Eugene Braunwald, MD, designated discussant for Dr. Eikelboom’s report. The results are “an important step for thrombocardiology,” said Dr. Braunwald, professor of medicine at Harvard Medical School in Boston.

Concurrently with Dr. Eikelboom’s report the results appeared in an article published online (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1709118). This publication also include an editorial by Dr. Braunwald (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMe1710241).

Mitchel L. Zoler/Frontline Medical News

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

BARCELONA – Combined treatment with a very low dosage of the anticoagulant rivaroxaban plus low-dose aspirin produced significant cuts in major adverse coronary, cerebral, and peripheral artery disease events with just a modest rise in major bleeding events in patients with stable disease in the COMPASS pivotal, randomized trial with more than 27,000 patients.

The benefits from the rivaroxaban plus aspirin regimen included a statistically significant 24% relative risk reduction in the study’s primary, combined endpoint, and a significant 18% relative risk reduction in all-cause death compared with a standard regimen of aspirin only, John W. Eikelboom, MD, said at the annual congress of the European Society of Cardiology. In addition, analysis of the net clinical benefit from treatment that took into account both the major adverse cardiovascular events prevented and major bleeding events induced, showed that the rivaroxaban-plus-aspirin regimen cut these by a statistically significant 20%, compared with aspirin alone.

Other notable benefits documented by the findings included a statistically significant 42% relative risk reduction for stroke and a statistically significant 46% relative risk reduction in the incidence of major adverse limb events among the roughly one-quarter of enrolled patients who entered the study with evidence of peripheral artery disease.

These risk reductions are similar in magnitude to the secondary-prevention benefits produced by controlling hypertension or dyslipidemia, noted Dr. Eikelboom, a researcher at McMaster University in Hamilton, Ont. “In the future, rivaroxaban will take its place among the other foundational treatments for long-term, secondary prevention,” he predicted in a video interview.

The COMPASS trial produced “unambiguous results that should change guidelines and the management of stable coronary artery disease,” commented Eugene Braunwald, MD, designated discussant for Dr. Eikelboom’s report. The results are “an important step for thrombocardiology,” said Dr. Braunwald, professor of medicine at Harvard Medical School in Boston.

Concurrently with Dr. Eikelboom’s report the results appeared in an article published online (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1709118). This publication also include an editorial by Dr. Braunwald (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMe1710241).

Mitchel L. Zoler/Frontline Medical News

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

VANCOUVER—Standard clinical assessments of Parkinson’s disease psychosis may miss more than half of psychotic symptoms, according to research presented at the 21st International Congress of Parkinson’s Disease and Movement Disorders. Among 182 patients with Parkinson’s disease, a structured clinical interview with prompts about delusions and olfactory, tactile, gustatory, and minor hallucinations detected more symptoms than standard assessments did.

“There is need for Parkinson’s disease psychosis scales such as our structured clinical interview that have greater sensitivity, particularly for delusions and olfactory, tactile, gustatory, and minor hallucinations,” said Catherine V. Kulick, a researcher at the Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders at New York University School of Medicine, and colleagues. “Even isolated minor hallucinations were associated with reduced quality of life and higher prevalence of other nonmotor symptoms.”

As an alternative to standard rating scales for Parkinson’s disease psychosis, which focus on visual and auditory hallucinations and specific delusions, researchers developed a structured clinical interview based on the Parkinson’s disease–specific Scale for Assessment of Positive Symptoms with additional prompts for delusions and olfactory, tactile, gustatory, and minor hallucinations. To evaluate the new tool, the investigators conducted a cross-sectional analysis of 182 consecutive outpatients with Parkinson’s disease (mean age, 67). They evaluated patients with the structured clinical interview as well as a standardized battery of motor, psychiatric, and quality of life scales. Based on the results of the structured clinical interview, investigators classified patients has having major, minor, or no psychotic symptoms.

The structured clinical interview identified 52 patients (28.5%) with psychotic symptoms. Twenty-four patients had major symptoms, and 28 patients had minor symptoms.

A combination of clinical impression, the Unified Parkinson’s Disease Rating Scale (question 2), and the Nonmotor Symptoms Questionnaire (questions 14 and 30) identified 58% of the major psychotic symptoms and 17% of the isolated minor hallucinations that were detected during the structured clinical interview.

About 10% of patients reported major hallucinations, and more patients had major olfactory hallucinations (about 5% of patients) than had major visual, somatic, auditory, and gustatory hallucinations.

—Jake Remaly

Suggested Reading

Pagonabarraga J, Martinez-Horta S, Fernández de Bobadilla R, et al. Minor hallucinations occur in drug-naive Parkinson’s disease patients, even from the premotor phase. Mov Disord. 2016;31(1):45-52.

Voss T, Bahr D, Cummings J, et al. Performance of a shortened Scale for Assessment of Positive Symptoms for Parkinson’s disease psychosis. Parkinsonism Relat Disord. 2013;19(3):295-299.

VANCOUVER—Standard clinical assessments of Parkinson’s disease psychosis may miss more than half of psychotic symptoms, according to research presented at the 21st International Congress of Parkinson’s Disease and Movement Disorders. Among 182 patients with Parkinson’s disease, a structured clinical interview with prompts about delusions and olfactory, tactile, gustatory, and minor hallucinations detected more symptoms than standard assessments did.

“There is need for Parkinson’s disease psychosis scales such as our structured clinical interview that have greater sensitivity, particularly for delusions and olfactory, tactile, gustatory, and minor hallucinations,” said Catherine V. Kulick, a researcher at the Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders at New York University School of Medicine, and colleagues. “Even isolated minor hallucinations were associated with reduced quality of life and higher prevalence of other nonmotor symptoms.”

As an alternative to standard rating scales for Parkinson’s disease psychosis, which focus on visual and auditory hallucinations and specific delusions, researchers developed a structured clinical interview based on the Parkinson’s disease–specific Scale for Assessment of Positive Symptoms with additional prompts for delusions and olfactory, tactile, gustatory, and minor hallucinations. To evaluate the new tool, the investigators conducted a cross-sectional analysis of 182 consecutive outpatients with Parkinson’s disease (mean age, 67). They evaluated patients with the structured clinical interview as well as a standardized battery of motor, psychiatric, and quality of life scales. Based on the results of the structured clinical interview, investigators classified patients has having major, minor, or no psychotic symptoms.

The structured clinical interview identified 52 patients (28.5%) with psychotic symptoms. Twenty-four patients had major symptoms, and 28 patients had minor symptoms.

A combination of clinical impression, the Unified Parkinson’s Disease Rating Scale (question 2), and the Nonmotor Symptoms Questionnaire (questions 14 and 30) identified 58% of the major psychotic symptoms and 17% of the isolated minor hallucinations that were detected during the structured clinical interview.

About 10% of patients reported major hallucinations, and more patients had major olfactory hallucinations (about 5% of patients) than had major visual, somatic, auditory, and gustatory hallucinations.

—Jake Remaly

Suggested Reading

Pagonabarraga J, Martinez-Horta S, Fernández de Bobadilla R, et al. Minor hallucinations occur in drug-naive Parkinson’s disease patients, even from the premotor phase. Mov Disord. 2016;31(1):45-52.

Voss T, Bahr D, Cummings J, et al. Performance of a shortened Scale for Assessment of Positive Symptoms for Parkinson’s disease psychosis. Parkinsonism Relat Disord. 2013;19(3):295-299.

VANCOUVER—Standard clinical assessments of Parkinson’s disease psychosis may miss more than half of psychotic symptoms, according to research presented at the 21st International Congress of Parkinson’s Disease and Movement Disorders. Among 182 patients with Parkinson’s disease, a structured clinical interview with prompts about delusions and olfactory, tactile, gustatory, and minor hallucinations detected more symptoms than standard assessments did.

“There is need for Parkinson’s disease psychosis scales such as our structured clinical interview that have greater sensitivity, particularly for delusions and olfactory, tactile, gustatory, and minor hallucinations,” said Catherine V. Kulick, a researcher at the Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders at New York University School of Medicine, and colleagues. “Even isolated minor hallucinations were associated with reduced quality of life and higher prevalence of other nonmotor symptoms.”

As an alternative to standard rating scales for Parkinson’s disease psychosis, which focus on visual and auditory hallucinations and specific delusions, researchers developed a structured clinical interview based on the Parkinson’s disease–specific Scale for Assessment of Positive Symptoms with additional prompts for delusions and olfactory, tactile, gustatory, and minor hallucinations. To evaluate the new tool, the investigators conducted a cross-sectional analysis of 182 consecutive outpatients with Parkinson’s disease (mean age, 67). They evaluated patients with the structured clinical interview as well as a standardized battery of motor, psychiatric, and quality of life scales. Based on the results of the structured clinical interview, investigators classified patients has having major, minor, or no psychotic symptoms.

The structured clinical interview identified 52 patients (28.5%) with psychotic symptoms. Twenty-four patients had major symptoms, and 28 patients had minor symptoms.

A combination of clinical impression, the Unified Parkinson’s Disease Rating Scale (question 2), and the Nonmotor Symptoms Questionnaire (questions 14 and 30) identified 58% of the major psychotic symptoms and 17% of the isolated minor hallucinations that were detected during the structured clinical interview.

About 10% of patients reported major hallucinations, and more patients had major olfactory hallucinations (about 5% of patients) than had major visual, somatic, auditory, and gustatory hallucinations.

—Jake Remaly

Suggested Reading

Pagonabarraga J, Martinez-Horta S, Fernández de Bobadilla R, et al. Minor hallucinations occur in drug-naive Parkinson’s disease patients, even from the premotor phase. Mov Disord. 2016;31(1):45-52.

Voss T, Bahr D, Cummings J, et al. Performance of a shortened Scale for Assessment of Positive Symptoms for Parkinson’s disease psychosis. Parkinsonism Relat Disord. 2013;19(3):295-299.