SAN DIEGO – Whatever you do, don’t order a 24-hour urine test. Do encourage “pork holidays.” And choose between an ACE inhibitor and an ARB – don’t give them both to a single patient, according to Kim Zuber, PA-C, MS, a nephrology physician assistant from St. Petersburg, Fla., in a presentation about kidney disease, hypertension, and diabetes at the Metabolic & Endocrine Disease Summit, sponsored by Global Academy for Medical Education.

Ms. Zuber, who is the executive director of the American Academy of Nephrology PAs and the outreach chair of the National Kidney Foundation, outlined some approaches for the diagnosis, management, and treatment of chronic kidney disease (CKD) with comorbid hypertension and diabetes.

• Use the right urine test. Urine albumin testing, which detects albuminuria, is vital in patients who are at risk of chronic kidney disease, Ms. Zuber said, although it’s often not performed. In fact, research suggests that most Medicare patients with diabetes, hypertension, or both do not have this test, she said. Order a urine albumin-to-creatinine ratio (UACR) test at least once a year in at-risk patients, she recommended, and more frequently if they show signs of abnormal values. But be aware, she said, some labs might refer to the test as microalbuminuria instead of UACR, and be prepared to calculate the UACR yourself if your institution provides only albumin and creatinine levels. Also watch out for mix-ups regarding UACR measurements. Nephrotic-range proteinuria starts at 3 g/dL or 3,000 mg/dL, she said, and residents often confuse those two sets of units. “Many have gotten in trouble with that,” she said.
• Don’t go near a 24-hour urine test. Thinking about ordering a 24-hour urine test that requires a patients to collect all their urine for a day? Think again. “We’ve been telling you almost 20 years not to do this,” Ms. Zuber said. These tests “are unreliable, and they don’t work.”
• Don’t focus on tight blood pressure control. Studies provide little insight into the ideal blood pressure readings for patients with diabetes and CKD, according to Ms. Zuber, but some findings suggest that tight control can be harmful to the kidneys. She urges her patients to treat hypertension in part by embracing lifestyle change. “I tell them that if you improve your lifestyle, you can give up one of your drugs. When they average 15 drugs a day, that becomes popular.” Physical activity, the DASH diet, salt restriction, moderate alcohol consumption, weight loss, stress reduction, and smoking cessation can all lower blood pressure, she added.
• Talk up the “pork holiday.” For patients with hypertension, “sodium restriction is huge,” Ms. Zuber said, especially among black patients. She urges her patients to take “pork holidays”, that is, eat pork only four times a year, on holidays such as the Fourth of July. She also urges them to prepare food in ways that begin with B, as in bake, boil, and barbecue. “You’ll notice that ‘fry’ doesn’t start with a B.”
• Try an ACE inhibitor or an ARB, but not both. In patients with hypertension plus diabetes and/or CKD, Ms. Zuber suggests using an angiotensin-converting enzyme inhibitor or angiotensin receptor blockers, but not both. One or the other can improve albuminuria, she said, but together they can boost risk of CKD, hyperkalemia, and hypotension.

Consider factors such as formularies and personal experience when trying to decide which drug to use, she said. If a patient still has hypertension, consider a diuretic and then move to a calcium channel or beta blocker. However, she cautioned, although beta blockers, they can cause erectile dysfunction.

Global Academy for Medical Education and this news organization are owned by the same parent company. Ms. Zuber reported no disclosures.

SAN DIEGO – Whatever you do, don’t order a 24-hour urine test. Do encourage “pork holidays.” And choose between an ACE inhibitor and an ARB – don’t give them both to a single patient, according to Kim Zuber, PA-C, MS, a nephrology physician assistant from St. Petersburg, Fla., in a presentation about kidney disease, hypertension, and diabetes at the Metabolic & Endocrine Disease Summit, sponsored by Global Academy for Medical Education.

Ms. Zuber, who is the executive director of the American Academy of Nephrology PAs and the outreach chair of the National Kidney Foundation, outlined some approaches for the diagnosis, management, and treatment of chronic kidney disease (CKD) with comorbid hypertension and diabetes.

• Use the right urine test. Urine albumin testing, which detects albuminuria, is vital in patients who are at risk of chronic kidney disease, Ms. Zuber said, although it’s often not performed. In fact, research suggests that most Medicare patients with diabetes, hypertension, or both do not have this test, she said. Order a urine albumin-to-creatinine ratio (UACR) test at least once a year in at-risk patients, she recommended, and more frequently if they show signs of abnormal values. But be aware, she said, some labs might refer to the test as microalbuminuria instead of UACR, and be prepared to calculate the UACR yourself if your institution provides only albumin and creatinine levels. Also watch out for mix-ups regarding UACR measurements. Nephrotic-range proteinuria starts at 3 g/dL or 3,000 mg/dL, she said, and residents often confuse those two sets of units. “Many have gotten in trouble with that,” she said.
• Don’t go near a 24-hour urine test. Thinking about ordering a 24-hour urine test that requires a patients to collect all their urine for a day? Think again. “We’ve been telling you almost 20 years not to do this,” Ms. Zuber said. These tests “are unreliable, and they don’t work.”
• Don’t focus on tight blood pressure control. Studies provide little insight into the ideal blood pressure readings for patients with diabetes and CKD, according to Ms. Zuber, but some findings suggest that tight control can be harmful to the kidneys. She urges her patients to treat hypertension in part by embracing lifestyle change. “I tell them that if you improve your lifestyle, you can give up one of your drugs. When they average 15 drugs a day, that becomes popular.” Physical activity, the DASH diet, salt restriction, moderate alcohol consumption, weight loss, stress reduction, and smoking cessation can all lower blood pressure, she added.
• Talk up the “pork holiday.” For patients with hypertension, “sodium restriction is huge,” Ms. Zuber said, especially among black patients. She urges her patients to take “pork holidays”, that is, eat pork only four times a year, on holidays such as the Fourth of July. She also urges them to prepare food in ways that begin with B, as in bake, boil, and barbecue. “You’ll notice that ‘fry’ doesn’t start with a B.”
• Try an ACE inhibitor or an ARB, but not both. In patients with hypertension plus diabetes and/or CKD, Ms. Zuber suggests using an angiotensin-converting enzyme inhibitor or angiotensin receptor blockers, but not both. One or the other can improve albuminuria, she said, but together they can boost risk of CKD, hyperkalemia, and hypotension.

Consider factors such as formularies and personal experience when trying to decide which drug to use, she said. If a patient still has hypertension, consider a diuretic and then move to a calcium channel or beta blocker. However, she cautioned, although beta blockers, they can cause erectile dysfunction.

Global Academy for Medical Education and this news organization are owned by the same parent company. Ms. Zuber reported no disclosures.

SAN DIEGO – Whatever you do, don’t order a 24-hour urine test. Do encourage “pork holidays.” And choose between an ACE inhibitor and an ARB – don’t give them both to a single patient, according to Kim Zuber, PA-C, MS, a nephrology physician assistant from St. Petersburg, Fla., in a presentation about kidney disease, hypertension, and diabetes at the Metabolic & Endocrine Disease Summit, sponsored by Global Academy for Medical Education.

Ms. Zuber, who is the executive director of the American Academy of Nephrology PAs and the outreach chair of the National Kidney Foundation, outlined some approaches for the diagnosis, management, and treatment of chronic kidney disease (CKD) with comorbid hypertension and diabetes.

• Use the right urine test. Urine albumin testing, which detects albuminuria, is vital in patients who are at risk of chronic kidney disease, Ms. Zuber said, although it’s often not performed. In fact, research suggests that most Medicare patients with diabetes, hypertension, or both do not have this test, she said. Order a urine albumin-to-creatinine ratio (UACR) test at least once a year in at-risk patients, she recommended, and more frequently if they show signs of abnormal values. But be aware, she said, some labs might refer to the test as microalbuminuria instead of UACR, and be prepared to calculate the UACR yourself if your institution provides only albumin and creatinine levels. Also watch out for mix-ups regarding UACR measurements. Nephrotic-range proteinuria starts at 3 g/dL or 3,000 mg/dL, she said, and residents often confuse those two sets of units. “Many have gotten in trouble with that,” she said.
• Don’t go near a 24-hour urine test. Thinking about ordering a 24-hour urine test that requires a patients to collect all their urine for a day? Think again. “We’ve been telling you almost 20 years not to do this,” Ms. Zuber said. These tests “are unreliable, and they don’t work.”
• Don’t focus on tight blood pressure control. Studies provide little insight into the ideal blood pressure readings for patients with diabetes and CKD, according to Ms. Zuber, but some findings suggest that tight control can be harmful to the kidneys. She urges her patients to treat hypertension in part by embracing lifestyle change. “I tell them that if you improve your lifestyle, you can give up one of your drugs. When they average 15 drugs a day, that becomes popular.” Physical activity, the DASH diet, salt restriction, moderate alcohol consumption, weight loss, stress reduction, and smoking cessation can all lower blood pressure, she added.
• Talk up the “pork holiday.” For patients with hypertension, “sodium restriction is huge,” Ms. Zuber said, especially among black patients. She urges her patients to take “pork holidays”, that is, eat pork only four times a year, on holidays such as the Fourth of July. She also urges them to prepare food in ways that begin with B, as in bake, boil, and barbecue. “You’ll notice that ‘fry’ doesn’t start with a B.”
• Try an ACE inhibitor or an ARB, but not both. In patients with hypertension plus diabetes and/or CKD, Ms. Zuber suggests using an angiotensin-converting enzyme inhibitor or angiotensin receptor blockers, but not both. One or the other can improve albuminuria, she said, but together they can boost risk of CKD, hyperkalemia, and hypotension.

Consider factors such as formularies and personal experience when trying to decide which drug to use, she said. If a patient still has hypertension, consider a diuretic and then move to a calcium channel or beta blocker. However, she cautioned, although beta blockers, they can cause erectile dysfunction.

Global Academy for Medical Education and this news organization are owned by the same parent company. Ms. Zuber reported no disclosures.

Low-dose radiation therapy – with or without concurrent chemotherapy – appears promising as a treatment for patients with relapsed or refractory mantle cell lymphoma (MCL) or at least a bridge to subsequent therapy, according to findings published in Blood Advances.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

Matthew S. Ning, MD, of the department of radiation oncology at the University of Texas MD Anderson Cancer Center, Houston, and colleagues, said this is the first study to evaluate low-dose radiation therapy (LDRT) with chemotherapy as a treatment modality outside of palliative care for relapsed, multiple refractory MCL patients.

“Our findings indicate that LDRT imparts excellent [local control], minimal toxicity, and favorable outcomes in this setting,” the researchers said.

The study included 19 patients with a total of 98 sites of relapsed, refractory MCL who were treated from 2014 to 2018. The median follow-up was 51.3 months from initial diagnosis and 15.4 months from initial treatment with low-dose radiation therapy, given at a dose of 4 Gy.

These were hard-to-treat patients who had received multiple prior therapies since diagnosis, including carfilzomib, ibrutinib, bortezomib, anthracycline, and rituximab. In total, 8 of the patients had previously undergone autologous stem cell transplant and 11 were refractory to ibrutinib by the time of initial radiation therapy.

Median age of the patients was 69 years; 15 patients had classical histology and 4 had blastoid variant. Among the 98 tumor sites treated, the median tumor size was 2.8 cm.

In all, 14 patients received initial LDRT that was concurrent with chemotherapy. The remaining 5 patients had stopped chemotherapy prior to starting LDRT.

LDRT was given in 1-2 daily fractions via 3-dimensional conformal radiation therapy or electron beam.

Of the 98 tumor sites treated, complete response was achieved for 79 sites (81%) and the median time to complete response was 2.7 months after the start of LDRT. The researchers removed one patient who was an outlier with 27 tumor sites treated, and that dropped the complete response rate down to 76%. The overall response rate, which include an additional five sites with partial response, was 86%.

The researchers found links between complete response and soft tissue site versus non–soft tissue site (hazard ratio, 1.80; 1.12-2.90, P = .02). However, there were no associations between response and chemo-refractory status, ibrutinib-refractory status, prior chemotherapy courts, receipt of concurrent chemotherapy, tumor size, number of fractions, lesions treated per course, or blastoid variant.

The overall survival at 1 year after LDRT initiation was 90% and the 1-year progression-free survival was 55%. All five patients who died were refractory to ibrutinib.

The researchers reported finding no radiation therapy–related toxicities, even when patients received concurrent chemotherapy.

The use of LDRT has the potential to bridge refractory patients to subsequent therapies or to provide treatment breaks as patients recover from toxicities, the researchers said. However, they called for additional studies to confirm that this approach improves progression-free survival over chemotherapy alone.

The study was supported in part by a grant from the National Cancer Institute. The researchers reported having no competing financial interests.

mschneider@mdedge.com

SOURCE: Ning MS et al. Blood Adv. 2019. Jul 9;3(13):2035-9.

Low-dose radiation therapy – with or without concurrent chemotherapy – appears promising as a treatment for patients with relapsed or refractory mantle cell lymphoma (MCL) or at least a bridge to subsequent therapy, according to findings published in Blood Advances.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

Matthew S. Ning, MD, of the department of radiation oncology at the University of Texas MD Anderson Cancer Center, Houston, and colleagues, said this is the first study to evaluate low-dose radiation therapy (LDRT) with chemotherapy as a treatment modality outside of palliative care for relapsed, multiple refractory MCL patients.

“Our findings indicate that LDRT imparts excellent [local control], minimal toxicity, and favorable outcomes in this setting,” the researchers said.

The study included 19 patients with a total of 98 sites of relapsed, refractory MCL who were treated from 2014 to 2018. The median follow-up was 51.3 months from initial diagnosis and 15.4 months from initial treatment with low-dose radiation therapy, given at a dose of 4 Gy.

These were hard-to-treat patients who had received multiple prior therapies since diagnosis, including carfilzomib, ibrutinib, bortezomib, anthracycline, and rituximab. In total, 8 of the patients had previously undergone autologous stem cell transplant and 11 were refractory to ibrutinib by the time of initial radiation therapy.

Median age of the patients was 69 years; 15 patients had classical histology and 4 had blastoid variant. Among the 98 tumor sites treated, the median tumor size was 2.8 cm.

In all, 14 patients received initial LDRT that was concurrent with chemotherapy. The remaining 5 patients had stopped chemotherapy prior to starting LDRT.

LDRT was given in 1-2 daily fractions via 3-dimensional conformal radiation therapy or electron beam.

Of the 98 tumor sites treated, complete response was achieved for 79 sites (81%) and the median time to complete response was 2.7 months after the start of LDRT. The researchers removed one patient who was an outlier with 27 tumor sites treated, and that dropped the complete response rate down to 76%. The overall response rate, which include an additional five sites with partial response, was 86%.

The researchers found links between complete response and soft tissue site versus non–soft tissue site (hazard ratio, 1.80; 1.12-2.90, P = .02). However, there were no associations between response and chemo-refractory status, ibrutinib-refractory status, prior chemotherapy courts, receipt of concurrent chemotherapy, tumor size, number of fractions, lesions treated per course, or blastoid variant.

The overall survival at 1 year after LDRT initiation was 90% and the 1-year progression-free survival was 55%. All five patients who died were refractory to ibrutinib.

The researchers reported finding no radiation therapy–related toxicities, even when patients received concurrent chemotherapy.

The use of LDRT has the potential to bridge refractory patients to subsequent therapies or to provide treatment breaks as patients recover from toxicities, the researchers said. However, they called for additional studies to confirm that this approach improves progression-free survival over chemotherapy alone.

The study was supported in part by a grant from the National Cancer Institute. The researchers reported having no competing financial interests.

mschneider@mdedge.com

SOURCE: Ning MS et al. Blood Adv. 2019. Jul 9;3(13):2035-9.

Low-dose radiation therapy – with or without concurrent chemotherapy – appears promising as a treatment for patients with relapsed or refractory mantle cell lymphoma (MCL) or at least a bridge to subsequent therapy, according to findings published in Blood Advances.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

Matthew S. Ning, MD, of the department of radiation oncology at the University of Texas MD Anderson Cancer Center, Houston, and colleagues, said this is the first study to evaluate low-dose radiation therapy (LDRT) with chemotherapy as a treatment modality outside of palliative care for relapsed, multiple refractory MCL patients.

“Our findings indicate that LDRT imparts excellent [local control], minimal toxicity, and favorable outcomes in this setting,” the researchers said.

The study included 19 patients with a total of 98 sites of relapsed, refractory MCL who were treated from 2014 to 2018. The median follow-up was 51.3 months from initial diagnosis and 15.4 months from initial treatment with low-dose radiation therapy, given at a dose of 4 Gy.

These were hard-to-treat patients who had received multiple prior therapies since diagnosis, including carfilzomib, ibrutinib, bortezomib, anthracycline, and rituximab. In total, 8 of the patients had previously undergone autologous stem cell transplant and 11 were refractory to ibrutinib by the time of initial radiation therapy.

Median age of the patients was 69 years; 15 patients had classical histology and 4 had blastoid variant. Among the 98 tumor sites treated, the median tumor size was 2.8 cm.

In all, 14 patients received initial LDRT that was concurrent with chemotherapy. The remaining 5 patients had stopped chemotherapy prior to starting LDRT.

LDRT was given in 1-2 daily fractions via 3-dimensional conformal radiation therapy or electron beam.

Of the 98 tumor sites treated, complete response was achieved for 79 sites (81%) and the median time to complete response was 2.7 months after the start of LDRT. The researchers removed one patient who was an outlier with 27 tumor sites treated, and that dropped the complete response rate down to 76%. The overall response rate, which include an additional five sites with partial response, was 86%.

The researchers found links between complete response and soft tissue site versus non–soft tissue site (hazard ratio, 1.80; 1.12-2.90, P = .02). However, there were no associations between response and chemo-refractory status, ibrutinib-refractory status, prior chemotherapy courts, receipt of concurrent chemotherapy, tumor size, number of fractions, lesions treated per course, or blastoid variant.

The overall survival at 1 year after LDRT initiation was 90% and the 1-year progression-free survival was 55%. All five patients who died were refractory to ibrutinib.

The researchers reported finding no radiation therapy–related toxicities, even when patients received concurrent chemotherapy.

The use of LDRT has the potential to bridge refractory patients to subsequent therapies or to provide treatment breaks as patients recover from toxicities, the researchers said. However, they called for additional studies to confirm that this approach improves progression-free survival over chemotherapy alone.

The study was supported in part by a grant from the National Cancer Institute. The researchers reported having no competing financial interests.

mschneider@mdedge.com

SOURCE: Ning MS et al. Blood Adv. 2019. Jul 9;3(13):2035-9.

Single-agent therapy with either bevacizumab or pemetrexed is efficacious as maintenance therapy for patients with advanced nonsquamous non–small cell lung cancer (NSCLC), but the combination of the two agents offers no survival benefit and is more toxic, results of the randomized ECOG-ACRIN 5508 study show.

Neil Osterweil/MDedge News

For patients with no disease progression after four cycles of induction chemotherapy who were assigned to one of three maintenance therapy strategies, there were no differences in overall survival between those randomized to monotherapy with pemetrexed or bevacizumab or to a combination of the two agents, although progression-free survival (PFS) was better with the combination, reported Suresh S. Ramalingam, MD, from the Winship Cancer Institute of Emory University, Atlanta, and colleagues.

The incidence of grade 3 or greater adverse events was also significantly higher with the combination, compared with bevacizumab monotherapy.

Even in the age of immune checkpoint inhibitor therapy in the front line, “[i]t is clear that maintenance therapy will remain an integral part of the treatment approach to advanced nonsquamous NSCLC. The results of ECOG-ACRIN 5508 support the use of either pemetrexed or bevacizumab as a single agent in this setting,” the investigators wrote in the Journal of Clinical Oncology.

Although the combination of bevacizumab and pemetrexed was associated with a significant improvement in PFS in a randomized trial, the three maintenance strategies have never before been directly compared, Dr. Ramalingam and associates noted.

­In ECOG-ACRIN 5508, 1,516 patients with advanced nonsquamous NSCLC who had not received prior systemic therapy were given standard induction chemotherapy, consisting of carboplatin to an area under the curve of 6, paclitaxel 200 mg/m², and bevacizumab 15 mg/kg for up to four cycles.

Patients without progression after four cycles (874) were randomly assigned to maintenance therapy with bevacizumab at 15 mg/kg , pemetrexed 500 mg/m², or a combination of the two agents.

For the primary endpoint of overall survival, with bevacizumab serving as the control group for comparison, the investigators found that, at a median follow-up of 50.6 months, median survival was 15.9 months with pemetrexed, compared with 14.4 months with bevacizumab, a difference that was not statistically significant. Median survival with the combination was 16.4 months and was also not significantly different from bevacizumab.

Median PFS was 4.2 months and 5.1 months for the pemetrexed and bevacizumab groups, respectively, with no significant difference. In contrast, median was 7.5 months with the combination, which was significantly better than controls, with a hazard ratio of 0.67 (P less than .001).

Patients received a median of six maintenance therapy cycles for each of the single agents, and a median of eight for the combinations. The incidence of grade 3-4 toxicity was 29% with bevacizumab, 37% with pemetrexed, and 51% with the combination. The combination was associated with a significantly greater incidence of toxicities, compared with bevacizumab (P less than .001).

The study was supported by grants from the National Cancer Institute. Dr. Ramalingam reported a consulting/advisory role for bevacizumab maker Genentech/Roche and others. Multiple coauthors reported similar disclosures.

SOURCE: Ramalingam SS et al. J Clin Oncol. 2019 Jul 30. doi: 10.1200/JCO.19.01006.

Single-agent therapy with either bevacizumab or pemetrexed is efficacious as maintenance therapy for patients with advanced nonsquamous non–small cell lung cancer (NSCLC), but the combination of the two agents offers no survival benefit and is more toxic, results of the randomized ECOG-ACRIN 5508 study show.

Neil Osterweil/MDedge News

For patients with no disease progression after four cycles of induction chemotherapy who were assigned to one of three maintenance therapy strategies, there were no differences in overall survival between those randomized to monotherapy with pemetrexed or bevacizumab or to a combination of the two agents, although progression-free survival (PFS) was better with the combination, reported Suresh S. Ramalingam, MD, from the Winship Cancer Institute of Emory University, Atlanta, and colleagues.

The incidence of grade 3 or greater adverse events was also significantly higher with the combination, compared with bevacizumab monotherapy.

Even in the age of immune checkpoint inhibitor therapy in the front line, “[i]t is clear that maintenance therapy will remain an integral part of the treatment approach to advanced nonsquamous NSCLC. The results of ECOG-ACRIN 5508 support the use of either pemetrexed or bevacizumab as a single agent in this setting,” the investigators wrote in the Journal of Clinical Oncology.

Although the combination of bevacizumab and pemetrexed was associated with a significant improvement in PFS in a randomized trial, the three maintenance strategies have never before been directly compared, Dr. Ramalingam and associates noted.

­In ECOG-ACRIN 5508, 1,516 patients with advanced nonsquamous NSCLC who had not received prior systemic therapy were given standard induction chemotherapy, consisting of carboplatin to an area under the curve of 6, paclitaxel 200 mg/m², and bevacizumab 15 mg/kg for up to four cycles.

Patients without progression after four cycles (874) were randomly assigned to maintenance therapy with bevacizumab at 15 mg/kg , pemetrexed 500 mg/m², or a combination of the two agents.

For the primary endpoint of overall survival, with bevacizumab serving as the control group for comparison, the investigators found that, at a median follow-up of 50.6 months, median survival was 15.9 months with pemetrexed, compared with 14.4 months with bevacizumab, a difference that was not statistically significant. Median survival with the combination was 16.4 months and was also not significantly different from bevacizumab.

Median PFS was 4.2 months and 5.1 months for the pemetrexed and bevacizumab groups, respectively, with no significant difference. In contrast, median was 7.5 months with the combination, which was significantly better than controls, with a hazard ratio of 0.67 (P less than .001).

Patients received a median of six maintenance therapy cycles for each of the single agents, and a median of eight for the combinations. The incidence of grade 3-4 toxicity was 29% with bevacizumab, 37% with pemetrexed, and 51% with the combination. The combination was associated with a significantly greater incidence of toxicities, compared with bevacizumab (P less than .001).

The study was supported by grants from the National Cancer Institute. Dr. Ramalingam reported a consulting/advisory role for bevacizumab maker Genentech/Roche and others. Multiple coauthors reported similar disclosures.

SOURCE: Ramalingam SS et al. J Clin Oncol. 2019 Jul 30. doi: 10.1200/JCO.19.01006.

Single-agent therapy with either bevacizumab or pemetrexed is efficacious as maintenance therapy for patients with advanced nonsquamous non–small cell lung cancer (NSCLC), but the combination of the two agents offers no survival benefit and is more toxic, results of the randomized ECOG-ACRIN 5508 study show.

Neil Osterweil/MDedge News

For patients with no disease progression after four cycles of induction chemotherapy who were assigned to one of three maintenance therapy strategies, there were no differences in overall survival between those randomized to monotherapy with pemetrexed or bevacizumab or to a combination of the two agents, although progression-free survival (PFS) was better with the combination, reported Suresh S. Ramalingam, MD, from the Winship Cancer Institute of Emory University, Atlanta, and colleagues.

The incidence of grade 3 or greater adverse events was also significantly higher with the combination, compared with bevacizumab monotherapy.

Even in the age of immune checkpoint inhibitor therapy in the front line, “[i]t is clear that maintenance therapy will remain an integral part of the treatment approach to advanced nonsquamous NSCLC. The results of ECOG-ACRIN 5508 support the use of either pemetrexed or bevacizumab as a single agent in this setting,” the investigators wrote in the Journal of Clinical Oncology.

Although the combination of bevacizumab and pemetrexed was associated with a significant improvement in PFS in a randomized trial, the three maintenance strategies have never before been directly compared, Dr. Ramalingam and associates noted.

­In ECOG-ACRIN 5508, 1,516 patients with advanced nonsquamous NSCLC who had not received prior systemic therapy were given standard induction chemotherapy, consisting of carboplatin to an area under the curve of 6, paclitaxel 200 mg/m², and bevacizumab 15 mg/kg for up to four cycles.

Patients without progression after four cycles (874) were randomly assigned to maintenance therapy with bevacizumab at 15 mg/kg , pemetrexed 500 mg/m², or a combination of the two agents.

For the primary endpoint of overall survival, with bevacizumab serving as the control group for comparison, the investigators found that, at a median follow-up of 50.6 months, median survival was 15.9 months with pemetrexed, compared with 14.4 months with bevacizumab, a difference that was not statistically significant. Median survival with the combination was 16.4 months and was also not significantly different from bevacizumab.

Median PFS was 4.2 months and 5.1 months for the pemetrexed and bevacizumab groups, respectively, with no significant difference. In contrast, median was 7.5 months with the combination, which was significantly better than controls, with a hazard ratio of 0.67 (P less than .001).

Patients received a median of six maintenance therapy cycles for each of the single agents, and a median of eight for the combinations. The incidence of grade 3-4 toxicity was 29% with bevacizumab, 37% with pemetrexed, and 51% with the combination. The combination was associated with a significantly greater incidence of toxicities, compared with bevacizumab (P less than .001).

The study was supported by grants from the National Cancer Institute. Dr. Ramalingam reported a consulting/advisory role for bevacizumab maker Genentech/Roche and others. Multiple coauthors reported similar disclosures.

SOURCE: Ramalingam SS et al. J Clin Oncol. 2019 Jul 30. doi: 10.1200/JCO.19.01006.

A significant proportion of the increased cardiovascular disease (CVD) risk seen in people with osteoarthritis could be attributable to NSAIDs, new research has suggested.

Denise Fulton/MDedge News

Writing in Arthritis & Rheumatology, researchers reported the outcomes of a longitudinal, population-based cohort study of 7,743 individuals with osteoarthritis patients and 23,229 age- and sex-matched controls without osteoarthritis.

“The prevailing hypothesis in the OA to CVD relationship has been that OA patients frequently take NSAIDs to control their pain and inflammation and that this may lead to them developing CVD,” wrote Mohammad Atiquzzaman, a PhD student at the University of British Columbia, Vancouver, and his coauthors. However they commented that no studies had so far examined this directly in patients with osteoarthritis.

Overall, people with osteoarthritis had a significant 23% higher risk of cardiovascular disease, compared with controls, after adjustment for factors such body mass index, hypertension, diabetes, hyperlipidemia, and socioeconomic status. They also had a 42% higher risk of congestive heart failure, 17% higher risk of ischemic heart disease, and 14% higher risk of stroke.

NSAID use was five times more common among people with osteoarthritis, and NSAIDs alone were associated with a greater than fourfold higher risk of cardiovascular disease, after adjusting for osteoarthritis and other potential confounders.

When the authors performed modeling to break down the effect of osteoarthritis on CVD risk into the direct effect of osteoarthritis itself and the indirect effect mediated by NSAID use, they concluded that 41% of the total effect of osteoarthritis on cardiovascular risk was mediated by NSAIDs. The effect of NSAIDs was particularly pronounced for stroke, in which cases they estimated that the drugs contributed to 64% of the increased in risk, and in ischemic heart disease, in which they contributed to 56% of the increased risk.

Subgroup analysis suggested that conventional NSAIDs were responsible for around 29% of the total increased risk of cardiovascular disease, while selective COX-2 inhibitors, or coxibs, such as celecoxib, lumiracoxib, rofecoxib, and valdecoxib mediated around 21%. For ischemic heart disease, conventional NSAIDs explained around 45% of the increased risk, while selective coxibs explained around 32% of the risk. Similarly, with congestive heart failure and stroke, the proportion of risk mediated by NSAIDs was higher for conventional NSAIDs, compared with coxibs.


The authors noted that while a number of previous studies have found osteoarthritis is an independent risk factor for cardiovascular disease, theirs was the first study to specifically examine the role that NSAIDs play in that increased risk.

However, they noted that their information on NSAID use was gleaned from prescription claims data, which did not include information on over-the-counter NSAID use. Their analysis was also unable to include information on family history of cardiovascular disease, smoking, and physical activity, which are important cardiovascular disease risk factors. They did observe that the rates of obesity were higher among the osteoarthritis group when compared with controls (29% vs. 20%), and hypertension and COPD were also more common among individuals with osteoarthritis.

There was no outside funding for the study, and the authors had no conflicts of interest to declare.

SOURCE: Atiquzzaman M et al. Arthritis Rheumatol. 2019 Aug 6. doi: 10.1002/art.41027

A significant proportion of the increased cardiovascular disease (CVD) risk seen in people with osteoarthritis could be attributable to NSAIDs, new research has suggested.

Denise Fulton/MDedge News

Writing in Arthritis & Rheumatology, researchers reported the outcomes of a longitudinal, population-based cohort study of 7,743 individuals with osteoarthritis patients and 23,229 age- and sex-matched controls without osteoarthritis.

“The prevailing hypothesis in the OA to CVD relationship has been that OA patients frequently take NSAIDs to control their pain and inflammation and that this may lead to them developing CVD,” wrote Mohammad Atiquzzaman, a PhD student at the University of British Columbia, Vancouver, and his coauthors. However they commented that no studies had so far examined this directly in patients with osteoarthritis.

Overall, people with osteoarthritis had a significant 23% higher risk of cardiovascular disease, compared with controls, after adjustment for factors such body mass index, hypertension, diabetes, hyperlipidemia, and socioeconomic status. They also had a 42% higher risk of congestive heart failure, 17% higher risk of ischemic heart disease, and 14% higher risk of stroke.

NSAID use was five times more common among people with osteoarthritis, and NSAIDs alone were associated with a greater than fourfold higher risk of cardiovascular disease, after adjusting for osteoarthritis and other potential confounders.

When the authors performed modeling to break down the effect of osteoarthritis on CVD risk into the direct effect of osteoarthritis itself and the indirect effect mediated by NSAID use, they concluded that 41% of the total effect of osteoarthritis on cardiovascular risk was mediated by NSAIDs. The effect of NSAIDs was particularly pronounced for stroke, in which cases they estimated that the drugs contributed to 64% of the increased in risk, and in ischemic heart disease, in which they contributed to 56% of the increased risk.

Subgroup analysis suggested that conventional NSAIDs were responsible for around 29% of the total increased risk of cardiovascular disease, while selective COX-2 inhibitors, or coxibs, such as celecoxib, lumiracoxib, rofecoxib, and valdecoxib mediated around 21%. For ischemic heart disease, conventional NSAIDs explained around 45% of the increased risk, while selective coxibs explained around 32% of the risk. Similarly, with congestive heart failure and stroke, the proportion of risk mediated by NSAIDs was higher for conventional NSAIDs, compared with coxibs.


The authors noted that while a number of previous studies have found osteoarthritis is an independent risk factor for cardiovascular disease, theirs was the first study to specifically examine the role that NSAIDs play in that increased risk.

However, they noted that their information on NSAID use was gleaned from prescription claims data, which did not include information on over-the-counter NSAID use. Their analysis was also unable to include information on family history of cardiovascular disease, smoking, and physical activity, which are important cardiovascular disease risk factors. They did observe that the rates of obesity were higher among the osteoarthritis group when compared with controls (29% vs. 20%), and hypertension and COPD were also more common among individuals with osteoarthritis.

There was no outside funding for the study, and the authors had no conflicts of interest to declare.

SOURCE: Atiquzzaman M et al. Arthritis Rheumatol. 2019 Aug 6. doi: 10.1002/art.41027

A significant proportion of the increased cardiovascular disease (CVD) risk seen in people with osteoarthritis could be attributable to NSAIDs, new research has suggested.

Denise Fulton/MDedge News

Writing in Arthritis & Rheumatology, researchers reported the outcomes of a longitudinal, population-based cohort study of 7,743 individuals with osteoarthritis patients and 23,229 age- and sex-matched controls without osteoarthritis.

“The prevailing hypothesis in the OA to CVD relationship has been that OA patients frequently take NSAIDs to control their pain and inflammation and that this may lead to them developing CVD,” wrote Mohammad Atiquzzaman, a PhD student at the University of British Columbia, Vancouver, and his coauthors. However they commented that no studies had so far examined this directly in patients with osteoarthritis.

Overall, people with osteoarthritis had a significant 23% higher risk of cardiovascular disease, compared with controls, after adjustment for factors such body mass index, hypertension, diabetes, hyperlipidemia, and socioeconomic status. They also had a 42% higher risk of congestive heart failure, 17% higher risk of ischemic heart disease, and 14% higher risk of stroke.

NSAID use was five times more common among people with osteoarthritis, and NSAIDs alone were associated with a greater than fourfold higher risk of cardiovascular disease, after adjusting for osteoarthritis and other potential confounders.

When the authors performed modeling to break down the effect of osteoarthritis on CVD risk into the direct effect of osteoarthritis itself and the indirect effect mediated by NSAID use, they concluded that 41% of the total effect of osteoarthritis on cardiovascular risk was mediated by NSAIDs. The effect of NSAIDs was particularly pronounced for stroke, in which cases they estimated that the drugs contributed to 64% of the increased in risk, and in ischemic heart disease, in which they contributed to 56% of the increased risk.

Subgroup analysis suggested that conventional NSAIDs were responsible for around 29% of the total increased risk of cardiovascular disease, while selective COX-2 inhibitors, or coxibs, such as celecoxib, lumiracoxib, rofecoxib, and valdecoxib mediated around 21%. For ischemic heart disease, conventional NSAIDs explained around 45% of the increased risk, while selective coxibs explained around 32% of the risk. Similarly, with congestive heart failure and stroke, the proportion of risk mediated by NSAIDs was higher for conventional NSAIDs, compared with coxibs.


The authors noted that while a number of previous studies have found osteoarthritis is an independent risk factor for cardiovascular disease, theirs was the first study to specifically examine the role that NSAIDs play in that increased risk.

However, they noted that their information on NSAID use was gleaned from prescription claims data, which did not include information on over-the-counter NSAID use. Their analysis was also unable to include information on family history of cardiovascular disease, smoking, and physical activity, which are important cardiovascular disease risk factors. They did observe that the rates of obesity were higher among the osteoarthritis group when compared with controls (29% vs. 20%), and hypertension and COPD were also more common among individuals with osteoarthritis.

There was no outside funding for the study, and the authors had no conflicts of interest to declare.

SOURCE: Atiquzzaman M et al. Arthritis Rheumatol. 2019 Aug 6. doi: 10.1002/art.41027

Over the past 2 decades, hospital medicine has grown from a nascent collection of hospitalists to one of the fastest growing specialties, with more than 60,000 active practitioners today.

Ten years ago, the need for mentoring and growth of a new generation of young academic faculty led to the development of the first Academic Hospitalist Academy (AHA) through the coordinated efforts of the Society of Hospital Medicine, the Society of General Internal Medicine, and the Association of Clinical Leaders of General Internal Medicine.

As modern medicine moves at an increasing pace, the intersection of patient care, research, and education has opened further opportunities for fostering the expertise of hospital medicine practitioners. The next level of training is now available with the advent of AHA’s Level 2 course.

Ever wonder why the new clinical service you’ve designed to improve physician and patient efficiency isn’t functioning like it did in the beginning? Patients are staying longer in the hospital, and physicians are working harder. The principles of change management, personal leadership styles, and adult learning will be covered in the AHA Level 2 course. How do I get my project funded and then what do I do with the results? Keys to negotiating for time and resources as well as the skills to write and disseminate your work are integrated into the curriculum.

Participants will be engaged in an interactive course designed around the challenges of practicing and leading in an academic environment. AHA Level 2 aims to help attendees – regardless of their areas of interest – identify and acquire the skills necessary to advance their career, describe the business and cultural landscape of academic health systems, and learn how to leverage that knowledge; to list resources and techniques to continue to further build their skills, and identify and pursue their unique scholarly niche.

Based on the success of AHA’s Level 1 course and the feedback from the almost 1,000 participants who have attended, AHA Level 2 is a 2.5-day course that will allow for the exchange of ideas and skills from nationally regarded faculty and fellow attendees. Through plenary sessions, workshops, small groups, and networking opportunities, attendees will be immersed in the realm of modern academic hospital medicine. The new course is offered in parallel with AHA Level 1 at the Inverness Resort, outside of Denver, on Sept. 10-12, 2019.

The course will leave attendees with an individualized career plan and enhance their area of expertise. The lessons learned and shared will allow participants to return to their institutions and continue to lead in the areas of patient care, financial resourcefulness, and the education of current and future generations of hospital medicine specialists.

Dr. O’Dorisio is a Med-Peds hospitalist at the Ohio State University, Columbus.

Over the past 2 decades, hospital medicine has grown from a nascent collection of hospitalists to one of the fastest growing specialties, with more than 60,000 active practitioners today.

Ten years ago, the need for mentoring and growth of a new generation of young academic faculty led to the development of the first Academic Hospitalist Academy (AHA) through the coordinated efforts of the Society of Hospital Medicine, the Society of General Internal Medicine, and the Association of Clinical Leaders of General Internal Medicine.

As modern medicine moves at an increasing pace, the intersection of patient care, research, and education has opened further opportunities for fostering the expertise of hospital medicine practitioners. The next level of training is now available with the advent of AHA’s Level 2 course.

Ever wonder why the new clinical service you’ve designed to improve physician and patient efficiency isn’t functioning like it did in the beginning? Patients are staying longer in the hospital, and physicians are working harder. The principles of change management, personal leadership styles, and adult learning will be covered in the AHA Level 2 course. How do I get my project funded and then what do I do with the results? Keys to negotiating for time and resources as well as the skills to write and disseminate your work are integrated into the curriculum.

Participants will be engaged in an interactive course designed around the challenges of practicing and leading in an academic environment. AHA Level 2 aims to help attendees – regardless of their areas of interest – identify and acquire the skills necessary to advance their career, describe the business and cultural landscape of academic health systems, and learn how to leverage that knowledge; to list resources and techniques to continue to further build their skills, and identify and pursue their unique scholarly niche.

Based on the success of AHA’s Level 1 course and the feedback from the almost 1,000 participants who have attended, AHA Level 2 is a 2.5-day course that will allow for the exchange of ideas and skills from nationally regarded faculty and fellow attendees. Through plenary sessions, workshops, small groups, and networking opportunities, attendees will be immersed in the realm of modern academic hospital medicine. The new course is offered in parallel with AHA Level 1 at the Inverness Resort, outside of Denver, on Sept. 10-12, 2019.

The course will leave attendees with an individualized career plan and enhance their area of expertise. The lessons learned and shared will allow participants to return to their institutions and continue to lead in the areas of patient care, financial resourcefulness, and the education of current and future generations of hospital medicine specialists.

Dr. O’Dorisio is a Med-Peds hospitalist at the Ohio State University, Columbus.

Over the past 2 decades, hospital medicine has grown from a nascent collection of hospitalists to one of the fastest growing specialties, with more than 60,000 active practitioners today.

Ten years ago, the need for mentoring and growth of a new generation of young academic faculty led to the development of the first Academic Hospitalist Academy (AHA) through the coordinated efforts of the Society of Hospital Medicine, the Society of General Internal Medicine, and the Association of Clinical Leaders of General Internal Medicine.

As modern medicine moves at an increasing pace, the intersection of patient care, research, and education has opened further opportunities for fostering the expertise of hospital medicine practitioners. The next level of training is now available with the advent of AHA’s Level 2 course.

Ever wonder why the new clinical service you’ve designed to improve physician and patient efficiency isn’t functioning like it did in the beginning? Patients are staying longer in the hospital, and physicians are working harder. The principles of change management, personal leadership styles, and adult learning will be covered in the AHA Level 2 course. How do I get my project funded and then what do I do with the results? Keys to negotiating for time and resources as well as the skills to write and disseminate your work are integrated into the curriculum.

Participants will be engaged in an interactive course designed around the challenges of practicing and leading in an academic environment. AHA Level 2 aims to help attendees – regardless of their areas of interest – identify and acquire the skills necessary to advance their career, describe the business and cultural landscape of academic health systems, and learn how to leverage that knowledge; to list resources and techniques to continue to further build their skills, and identify and pursue their unique scholarly niche.

Based on the success of AHA’s Level 1 course and the feedback from the almost 1,000 participants who have attended, AHA Level 2 is a 2.5-day course that will allow for the exchange of ideas and skills from nationally regarded faculty and fellow attendees. Through plenary sessions, workshops, small groups, and networking opportunities, attendees will be immersed in the realm of modern academic hospital medicine. The new course is offered in parallel with AHA Level 1 at the Inverness Resort, outside of Denver, on Sept. 10-12, 2019.

The course will leave attendees with an individualized career plan and enhance their area of expertise. The lessons learned and shared will allow participants to return to their institutions and continue to lead in the areas of patient care, financial resourcefulness, and the education of current and future generations of hospital medicine specialists.

Dr. O’Dorisio is a Med-Peds hospitalist at the Ohio State University, Columbus.

Biologics improved coronary inflammation as well as psoriasis symptoms, according to data from the perivascular fat attenuation index in 134 adults identified using coronary CT angiography.

Oxford Academic Cardiovascular CT Core Lab and Lab of Inflammation and Cardiometabolic Diseases at NHLBI

“The perivascular fat attenuation index [FAI] is a [CT]-based, novel, noninvasive imaging technique that allows for direct visualization and quantification of coronary inflammation using differential mapping of attenuation gradients in pericoronary fat,” wrote Youssef A. Elnabawi, MD, of the National Heart, Lung, and Blood Institute and colleagues. Biologics have been associated with reduced noncalcified coronary plaques in psoriasis patients, which suggests possible reduction in coronary inflammation as well.

In a study published in JAMA Cardiology, the researchers analyzed data from 134 adults with moderate to severe psoriasis who received no biologic therapy for at least 3 months before starting the study. Of these, 52 chose not to receive biologics, and served as controls while being treated with topical or light therapies. The participants are part of the Psoriasis Atherosclerosis Cardiometabolic Initiative, an ongoing, prospective cohort study. The average age of the patients was 51 years, and 63% were male.

The 82 patients given biologics received anti–tumor necrosis factor–alpha, anti–interleukin-12/23, or anti-IL-17 for 1 year. Overall, patients on biologics showed a significant decrease in FAI from a median of –71.22 Hounsfield units (HU) at baseline to a median of –76.06 at 1 year. These patients also showed significant improvement in Psoriasis Area and Severity Index scores, from a median of 7.7 at baseline to a median of 3.2 at 1 year. The control patients not on biologics showed no significant changes in FAI, with a median of –71.98 HU at baseline and –72.66 HU at 1 year.

The changes were consistent among the various biologics used, and The median FAI for patients on anti–tumor necrosis factor–alpha changed from –71.25 at baseline to –75.49 at 1 year; median FAI for both IL-12/23 and anti-IL-17 treatment groups changed from –71.18 HU at baseline to –76.92 at 1 year.

In addition, only patients treated with biologics showed a significant reduction in median C-reactive protein levels from baseline (2.2 mg/L vs. 1.3 mg/L). The changes in FAI were not associated with the presence of coronary plaques, the researchers noted.

The study findings were limited by several factors, including the observational design, small size, and lack of data on cardiovascular endpoints. “Future studies will be needed to explore whether the residual CV risk detected by perivascular FAI can be attenuated using targeted anti-inflammatory interventions,” they wrote.

However, the results suggest that biologics impact coronary vasculature at the microenvironmental level, and that FAI can be a noninvasive, cost-effective way to stratify patients at increased risk for cardiovascular disease, the researchers noted.


“We believe that the strength of perivascular FAI in risk stratifying patients with increased coronary inflammation will allow for better identification of patients at increased risk of future myocardial events that are not captured by traditional CV risk factors,” they wrote.

The study was funded by the National Institutes of Health, several research foundations, Elsevier, Colgate-Palmolive, and Genentech. Dr. Elnabawi had no financial conflicts to disclose; several coauthors reported relationships with multiple companies. One coauthor disclosed a pending and licensed patent to a novel tool for cardiovascular risk stratification based on the CT attenuation of perivascular tissue (OxScore) and a pending and licensed patent to perivascular texture index.

SOURCE: Elnabawi YA et al. JAMA Cardiol. 2019 Jul 31. doi: 10.1001/jamacardio.2019.2589.

Biologics improved coronary inflammation as well as psoriasis symptoms, according to data from the perivascular fat attenuation index in 134 adults identified using coronary CT angiography.

Oxford Academic Cardiovascular CT Core Lab and Lab of Inflammation and Cardiometabolic Diseases at NHLBI

“The perivascular fat attenuation index [FAI] is a [CT]-based, novel, noninvasive imaging technique that allows for direct visualization and quantification of coronary inflammation using differential mapping of attenuation gradients in pericoronary fat,” wrote Youssef A. Elnabawi, MD, of the National Heart, Lung, and Blood Institute and colleagues. Biologics have been associated with reduced noncalcified coronary plaques in psoriasis patients, which suggests possible reduction in coronary inflammation as well.

In a study published in JAMA Cardiology, the researchers analyzed data from 134 adults with moderate to severe psoriasis who received no biologic therapy for at least 3 months before starting the study. Of these, 52 chose not to receive biologics, and served as controls while being treated with topical or light therapies. The participants are part of the Psoriasis Atherosclerosis Cardiometabolic Initiative, an ongoing, prospective cohort study. The average age of the patients was 51 years, and 63% were male.

The 82 patients given biologics received anti–tumor necrosis factor–alpha, anti–interleukin-12/23, or anti-IL-17 for 1 year. Overall, patients on biologics showed a significant decrease in FAI from a median of –71.22 Hounsfield units (HU) at baseline to a median of –76.06 at 1 year. These patients also showed significant improvement in Psoriasis Area and Severity Index scores, from a median of 7.7 at baseline to a median of 3.2 at 1 year. The control patients not on biologics showed no significant changes in FAI, with a median of –71.98 HU at baseline and –72.66 HU at 1 year.

The changes were consistent among the various biologics used, and The median FAI for patients on anti–tumor necrosis factor–alpha changed from –71.25 at baseline to –75.49 at 1 year; median FAI for both IL-12/23 and anti-IL-17 treatment groups changed from –71.18 HU at baseline to –76.92 at 1 year.

In addition, only patients treated with biologics showed a significant reduction in median C-reactive protein levels from baseline (2.2 mg/L vs. 1.3 mg/L). The changes in FAI were not associated with the presence of coronary plaques, the researchers noted.

The study findings were limited by several factors, including the observational design, small size, and lack of data on cardiovascular endpoints. “Future studies will be needed to explore whether the residual CV risk detected by perivascular FAI can be attenuated using targeted anti-inflammatory interventions,” they wrote.

However, the results suggest that biologics impact coronary vasculature at the microenvironmental level, and that FAI can be a noninvasive, cost-effective way to stratify patients at increased risk for cardiovascular disease, the researchers noted.


“We believe that the strength of perivascular FAI in risk stratifying patients with increased coronary inflammation will allow for better identification of patients at increased risk of future myocardial events that are not captured by traditional CV risk factors,” they wrote.

The study was funded by the National Institutes of Health, several research foundations, Elsevier, Colgate-Palmolive, and Genentech. Dr. Elnabawi had no financial conflicts to disclose; several coauthors reported relationships with multiple companies. One coauthor disclosed a pending and licensed patent to a novel tool for cardiovascular risk stratification based on the CT attenuation of perivascular tissue (OxScore) and a pending and licensed patent to perivascular texture index.

SOURCE: Elnabawi YA et al. JAMA Cardiol. 2019 Jul 31. doi: 10.1001/jamacardio.2019.2589.

Biologics improved coronary inflammation as well as psoriasis symptoms, according to data from the perivascular fat attenuation index in 134 adults identified using coronary CT angiography.

Oxford Academic Cardiovascular CT Core Lab and Lab of Inflammation and Cardiometabolic Diseases at NHLBI

“The perivascular fat attenuation index [FAI] is a [CT]-based, novel, noninvasive imaging technique that allows for direct visualization and quantification of coronary inflammation using differential mapping of attenuation gradients in pericoronary fat,” wrote Youssef A. Elnabawi, MD, of the National Heart, Lung, and Blood Institute and colleagues. Biologics have been associated with reduced noncalcified coronary plaques in psoriasis patients, which suggests possible reduction in coronary inflammation as well.

In a study published in JAMA Cardiology, the researchers analyzed data from 134 adults with moderate to severe psoriasis who received no biologic therapy for at least 3 months before starting the study. Of these, 52 chose not to receive biologics, and served as controls while being treated with topical or light therapies. The participants are part of the Psoriasis Atherosclerosis Cardiometabolic Initiative, an ongoing, prospective cohort study. The average age of the patients was 51 years, and 63% were male.

The 82 patients given biologics received anti–tumor necrosis factor–alpha, anti–interleukin-12/23, or anti-IL-17 for 1 year. Overall, patients on biologics showed a significant decrease in FAI from a median of –71.22 Hounsfield units (HU) at baseline to a median of –76.06 at 1 year. These patients also showed significant improvement in Psoriasis Area and Severity Index scores, from a median of 7.7 at baseline to a median of 3.2 at 1 year. The control patients not on biologics showed no significant changes in FAI, with a median of –71.98 HU at baseline and –72.66 HU at 1 year.

The changes were consistent among the various biologics used, and The median FAI for patients on anti–tumor necrosis factor–alpha changed from –71.25 at baseline to –75.49 at 1 year; median FAI for both IL-12/23 and anti-IL-17 treatment groups changed from –71.18 HU at baseline to –76.92 at 1 year.

In addition, only patients treated with biologics showed a significant reduction in median C-reactive protein levels from baseline (2.2 mg/L vs. 1.3 mg/L). The changes in FAI were not associated with the presence of coronary plaques, the researchers noted.

The study findings were limited by several factors, including the observational design, small size, and lack of data on cardiovascular endpoints. “Future studies will be needed to explore whether the residual CV risk detected by perivascular FAI can be attenuated using targeted anti-inflammatory interventions,” they wrote.

However, the results suggest that biologics impact coronary vasculature at the microenvironmental level, and that FAI can be a noninvasive, cost-effective way to stratify patients at increased risk for cardiovascular disease, the researchers noted.


“We believe that the strength of perivascular FAI in risk stratifying patients with increased coronary inflammation will allow for better identification of patients at increased risk of future myocardial events that are not captured by traditional CV risk factors,” they wrote.

The study was funded by the National Institutes of Health, several research foundations, Elsevier, Colgate-Palmolive, and Genentech. Dr. Elnabawi had no financial conflicts to disclose; several coauthors reported relationships with multiple companies. One coauthor disclosed a pending and licensed patent to a novel tool for cardiovascular risk stratification based on the CT attenuation of perivascular tissue (OxScore) and a pending and licensed patent to perivascular texture index.

SOURCE: Elnabawi YA et al. JAMA Cardiol. 2019 Jul 31. doi: 10.1001/jamacardio.2019.2589.

LOS ANGELES – While a large number of older adults take prescription and nonprescription medications to help them sleep, the effect of these medications on dementia risk is unclear, with most researchers advocating a cautious and conservative approach to prescribing.

Nastasic/iStockphoto.com

Research is increasingly revealing a bidirectional relationship between sleep and dementia. Poor sleep – especially from insomnia, sleep deprivation, or obstructive sleep apnea – is known to increase dementia risk. Dementias, meanwhile, are associated with serious circadian rhythm disturbances, leading to nighttime sleep loss and increasing the likelihood of institutionalization.

At the Alzheimer’s Association International Conference, researchers presented findings assessing the links between sleep medication use and dementia and also what agents or approaches might safely improve sleep in people with sleep disorders who are at risk for dementia or who have been diagnosed with dementia.
 

Sex- and race-based differences in risk

Yue Leng, PhD, of the University of California, San Francisco, reported a link between frequent sleep medication use and later dementia – but only in white adults. Dr. Leng presented findings from the National Institutes of Health–funded Health, Aging, and Body Composition Study, which recruited 3,068 subjects aged 70-79 and followed them for 15 years. At baseline, 2.7% of African Americans and 7.7% of whites in the study reported taking sleep medications “often” or “almost always.”

Dr. Leng and her colleagues found that white subjects who reported taking sleep aids five or more times a month at baseline had a nearly 80% higher risk of developing dementia during the course of the study (hazard ratio, 1.79; 95% confidence interval, 1.21-2.66), compared with people who reported never taking sleep aids or taking them less frequently.

The researchers saw no between-sex differences for this finding, and adjusted for a variety of genetic and lifestyle confounders. Importantly, no significant increase in dementia risk was seen for black subjects, who made up more than one-third of the cohort.

Dr. Leng told the conference that the researchers could not explain why black participants did not see similarly increased dementia risk. Also, she noted, researchers did not have information on the specific sleep medications people used: benzodiazepines, antihistamines, antidepressants, or other types of drugs. Nonetheless, she told the conference, the findings ratified the cautious approach many dementia experts are already stressing.


“Do we really need to prescribe so many sleep meds to older adults who are already at risk for cognitive impairment?” Dr. Leng said, adding: “I am a big advocate of behavioral sleep interventions.” People with clinical sleep problems “should be referred to sleep centers” for a fuller assessment before medication is prescribed, she said.

Findings from another cohort study, meanwhile, suggest that there could be sex-related differences in how sleep aids affect dementia risk. Investigators at Utah State University in Logan used data from some 3,656 older adults in the Cache County Study on Memory and Aging, an NIH-backed cohort study of white adults in Utah without dementia at baseline who were followed for 12 years.

The investigators, led by doctoral student Elizabeth Vernon, found that men reporting use of sleep medication saw more than threefold higher risk of developing Alzheimer’s disease than did men who did not use sleep aids (HR, 3.604; P = .0001).

Women who did not report having sleep disturbance but used sleep-inducing medications were at nearly fourfold greater risk for developing Alzheimer’s disease (HR, 3.916; P = .0001). Women who self-reported sleep disturbances at baseline, meanwhile, saw a reduction in Alzheimer’s risk of about one-third associated with the use of sleep medications.

Ms. Vernon told the conference that, despite the finding of risk reduction for this particular group of women, caution in prescribing sleep aids was warranted.

Common sleep drugs linked to cognitive aging

Chris Fox, MD, a researcher at the University of East Anglia in Norwich, England, and his colleagues demonstrated in 2018 that long-term exposure to anticholinergic drugs, a class that includes some antidepressants and antihistamines used to promote sleep, was associated with a higher risk of dementia, while use of benzodiazepines, a class of sedatives used commonly in older people as sleep aids, was not. (Whether benzodiazepine exposure relates to dementia remains controversial.)

At AAIC 2019, Dr. Fox presented findings from a study of 337 brains in a U.K. brain bank, of which 17% and 21% came from users of benzodiazepines and anticholinergic drugs, whose usage history was well documented. Dr. Fox and his colleagues found that, while neither anticholinergic nor benzodiazepine exposure was associated with brain pathology specific to that seen in Alzheimer’s disease, both classes of drugs were associated with “slight signals in neuronal loss” in one brain region, the nucleus basalis of Meynert. Dr. Fox described the drugs as causing “an increase in cognitive aging” which could bear on Alzheimer’s risk without being directly causative.
 

Newer sleep drugs may help Alzheimer’s patients

Scientists working for drug manufacturers presented findings on agents to counter the circadian rhythm disturbances seen in people with Alzheimer’s disease. Margaret Moline, PhD, of Eisai in Woodcliff Lake, N.J., showed some results from a phase 2, dose-ranging, placebo-controlled study of the experimental agent lemborexant in 62 subjects aged 60-90 with mild to moderate Alzheimer’s disease and sleep disturbances. (Lemborexant, an orexin receptor agonist that acts to regulate wakefulness, is being investigated in a broad range of sleep disorders.) Patients were randomized to one of four doses of lemborexant or placebo and wore a device for sleep monitoring. Nighttime activity indicating arousal was significantly lower for people in two dosage arms, 5 mg and 10 mg, compared with placebo, and treatment groups saw trends toward less sleep fragmentation and higher total sleep time, Dr. Moline told the conference.

Suvorexant (Belsomra), the only orexin receptor antagonist currently licensed as a sleep aid, is also being tested in people with Alzheimer’s disease. At AAIC 2019, Joseph Herring, MD, PhD, of Merck in Kenilworth, N.J., presented results from a placebo-controlled trial of 277 patients with Alzheimer’s disease and insomnia, and reported that treatment with 10 or 20 mg of suvorexant over 4 weeks was associated with about an extra half hour of total nightly sleep, with a 73-minute mean increase from baseline, compared with 45 minutes for patients receiving placebo (95% CI, 11-45; P less than .005).
 

Trazodone linked to slower cognitive decline

An inexpensive antidepressant used in low doses as a sleep aid, including in people with Alzheimer’s disease, was associated with a delay in cognitive decline in older adults, according to results from a retrospective study. Elissaios Karageorgiou, MD, PhD, of the University of California, San Francisco, and the Neurological Institute of Athens presented results derived from two cohorts: patients enrolled at the UCSF Memory and Aging Center and women enrolled in the Study for Osteoporotic Fractures (SOF) in Women. The investigators were able to identify trazodone users in the studies (with two or more contiguous study visits reporting trazodone use) and match them with control patients from the same cohorts who did not use trazodone.

Trazodone was studied because previous research suggests it increases total sleep time in patients with Alzheimer’s disease without affecting next-day cognitive performance.

Trazodone-using patients in the UCSF cohort (n = 25) saw significantly less decline in Mini Mental State Exam (MMSE) scores over 4 years, compared with nonusers (0.27 vs. 0.70 points per year; P = .023), an effect that remained statistically significant even after adjusting for sedative and stimulant use and the expected progression of Alzheimer’s disease pathology. Importantly, the slower decline was seen only among subjects with sleep complaints at baseline and especially those whose sleep improved over time, suggesting that the cognitive benefit was mediated by improved sleep.

In the SOF cohort of 46 trazodone users matched with 148 nonusers, no significant protective or negative effect related to long-term trazodone use was found using the MMSE or the Trails Making Test. In this analysis, however, baseline and longitudinal sleep quality was not captured in the group-matching process, neither was the use of other medications. The patient group was slightly older, and all patients were women.

Dr. Karageorgiou said in an interview that the link between improved sleep, trazodone, and cognition needs to be validated in prospective intervention studies. Trazodone, he said, appears to work best in people with a specific type of insomnia characterized by cortical and behavioral hyperarousal, and its cognitive effect appears limited to people whose sleep improves with treatment. “You’re not going to see long-term cognitive benefits if it’s not improving your sleep,” Dr. Karageorgiou said. “So, whether trazodone improves sleep or not in a patient after a few months can be an early indicator for the clinician to continue using it or suspend it, because it is unlikely to help their cognition otherwise.”

He stressed that physicians need to be broadly focused on improving sleep to help patients with, or at risk for, dementia by consolidating their sleep rhythms.

“Trazodone is not the magic bullet, and I don’t think we will ever have a magic bullet,” Dr. Karageorgiou said. “Because when our brain degenerates, it’s not just one chemical, or one system, it’s many. And our body changes as well. The important thing is to help the patient consolidate their rhythms, whether through light therapy, daily exercise, cognitive behavioral therapy for insomnia, or other evidence-based interventions and their combination. The same applies for a person with dementia as for the rest of us.”

None of the investigators outside of the industry-sponsored studies had relevant disclosures.

LOS ANGELES – While a large number of older adults take prescription and nonprescription medications to help them sleep, the effect of these medications on dementia risk is unclear, with most researchers advocating a cautious and conservative approach to prescribing.

Nastasic/iStockphoto.com

Research is increasingly revealing a bidirectional relationship between sleep and dementia. Poor sleep – especially from insomnia, sleep deprivation, or obstructive sleep apnea – is known to increase dementia risk. Dementias, meanwhile, are associated with serious circadian rhythm disturbances, leading to nighttime sleep loss and increasing the likelihood of institutionalization.

At the Alzheimer’s Association International Conference, researchers presented findings assessing the links between sleep medication use and dementia and also what agents or approaches might safely improve sleep in people with sleep disorders who are at risk for dementia or who have been diagnosed with dementia.
 

Sex- and race-based differences in risk

Yue Leng, PhD, of the University of California, San Francisco, reported a link between frequent sleep medication use and later dementia – but only in white adults. Dr. Leng presented findings from the National Institutes of Health–funded Health, Aging, and Body Composition Study, which recruited 3,068 subjects aged 70-79 and followed them for 15 years. At baseline, 2.7% of African Americans and 7.7% of whites in the study reported taking sleep medications “often” or “almost always.”

Dr. Leng and her colleagues found that white subjects who reported taking sleep aids five or more times a month at baseline had a nearly 80% higher risk of developing dementia during the course of the study (hazard ratio, 1.79; 95% confidence interval, 1.21-2.66), compared with people who reported never taking sleep aids or taking them less frequently.

The researchers saw no between-sex differences for this finding, and adjusted for a variety of genetic and lifestyle confounders. Importantly, no significant increase in dementia risk was seen for black subjects, who made up more than one-third of the cohort.

Dr. Leng told the conference that the researchers could not explain why black participants did not see similarly increased dementia risk. Also, she noted, researchers did not have information on the specific sleep medications people used: benzodiazepines, antihistamines, antidepressants, or other types of drugs. Nonetheless, she told the conference, the findings ratified the cautious approach many dementia experts are already stressing.


“Do we really need to prescribe so many sleep meds to older adults who are already at risk for cognitive impairment?” Dr. Leng said, adding: “I am a big advocate of behavioral sleep interventions.” People with clinical sleep problems “should be referred to sleep centers” for a fuller assessment before medication is prescribed, she said.

Findings from another cohort study, meanwhile, suggest that there could be sex-related differences in how sleep aids affect dementia risk. Investigators at Utah State University in Logan used data from some 3,656 older adults in the Cache County Study on Memory and Aging, an NIH-backed cohort study of white adults in Utah without dementia at baseline who were followed for 12 years.

The investigators, led by doctoral student Elizabeth Vernon, found that men reporting use of sleep medication saw more than threefold higher risk of developing Alzheimer’s disease than did men who did not use sleep aids (HR, 3.604; P = .0001).

Women who did not report having sleep disturbance but used sleep-inducing medications were at nearly fourfold greater risk for developing Alzheimer’s disease (HR, 3.916; P = .0001). Women who self-reported sleep disturbances at baseline, meanwhile, saw a reduction in Alzheimer’s risk of about one-third associated with the use of sleep medications.

Ms. Vernon told the conference that, despite the finding of risk reduction for this particular group of women, caution in prescribing sleep aids was warranted.

Common sleep drugs linked to cognitive aging

Chris Fox, MD, a researcher at the University of East Anglia in Norwich, England, and his colleagues demonstrated in 2018 that long-term exposure to anticholinergic drugs, a class that includes some antidepressants and antihistamines used to promote sleep, was associated with a higher risk of dementia, while use of benzodiazepines, a class of sedatives used commonly in older people as sleep aids, was not. (Whether benzodiazepine exposure relates to dementia remains controversial.)

At AAIC 2019, Dr. Fox presented findings from a study of 337 brains in a U.K. brain bank, of which 17% and 21% came from users of benzodiazepines and anticholinergic drugs, whose usage history was well documented. Dr. Fox and his colleagues found that, while neither anticholinergic nor benzodiazepine exposure was associated with brain pathology specific to that seen in Alzheimer’s disease, both classes of drugs were associated with “slight signals in neuronal loss” in one brain region, the nucleus basalis of Meynert. Dr. Fox described the drugs as causing “an increase in cognitive aging” which could bear on Alzheimer’s risk without being directly causative.
 

Newer sleep drugs may help Alzheimer’s patients

Scientists working for drug manufacturers presented findings on agents to counter the circadian rhythm disturbances seen in people with Alzheimer’s disease. Margaret Moline, PhD, of Eisai in Woodcliff Lake, N.J., showed some results from a phase 2, dose-ranging, placebo-controlled study of the experimental agent lemborexant in 62 subjects aged 60-90 with mild to moderate Alzheimer’s disease and sleep disturbances. (Lemborexant, an orexin receptor agonist that acts to regulate wakefulness, is being investigated in a broad range of sleep disorders.) Patients were randomized to one of four doses of lemborexant or placebo and wore a device for sleep monitoring. Nighttime activity indicating arousal was significantly lower for people in two dosage arms, 5 mg and 10 mg, compared with placebo, and treatment groups saw trends toward less sleep fragmentation and higher total sleep time, Dr. Moline told the conference.

Suvorexant (Belsomra), the only orexin receptor antagonist currently licensed as a sleep aid, is also being tested in people with Alzheimer’s disease. At AAIC 2019, Joseph Herring, MD, PhD, of Merck in Kenilworth, N.J., presented results from a placebo-controlled trial of 277 patients with Alzheimer’s disease and insomnia, and reported that treatment with 10 or 20 mg of suvorexant over 4 weeks was associated with about an extra half hour of total nightly sleep, with a 73-minute mean increase from baseline, compared with 45 minutes for patients receiving placebo (95% CI, 11-45; P less than .005).
 

Trazodone linked to slower cognitive decline

An inexpensive antidepressant used in low doses as a sleep aid, including in people with Alzheimer’s disease, was associated with a delay in cognitive decline in older adults, according to results from a retrospective study. Elissaios Karageorgiou, MD, PhD, of the University of California, San Francisco, and the Neurological Institute of Athens presented results derived from two cohorts: patients enrolled at the UCSF Memory and Aging Center and women enrolled in the Study for Osteoporotic Fractures (SOF) in Women. The investigators were able to identify trazodone users in the studies (with two or more contiguous study visits reporting trazodone use) and match them with control patients from the same cohorts who did not use trazodone.

Trazodone was studied because previous research suggests it increases total sleep time in patients with Alzheimer’s disease without affecting next-day cognitive performance.

Trazodone-using patients in the UCSF cohort (n = 25) saw significantly less decline in Mini Mental State Exam (MMSE) scores over 4 years, compared with nonusers (0.27 vs. 0.70 points per year; P = .023), an effect that remained statistically significant even after adjusting for sedative and stimulant use and the expected progression of Alzheimer’s disease pathology. Importantly, the slower decline was seen only among subjects with sleep complaints at baseline and especially those whose sleep improved over time, suggesting that the cognitive benefit was mediated by improved sleep.

In the SOF cohort of 46 trazodone users matched with 148 nonusers, no significant protective or negative effect related to long-term trazodone use was found using the MMSE or the Trails Making Test. In this analysis, however, baseline and longitudinal sleep quality was not captured in the group-matching process, neither was the use of other medications. The patient group was slightly older, and all patients were women.

Dr. Karageorgiou said in an interview that the link between improved sleep, trazodone, and cognition needs to be validated in prospective intervention studies. Trazodone, he said, appears to work best in people with a specific type of insomnia characterized by cortical and behavioral hyperarousal, and its cognitive effect appears limited to people whose sleep improves with treatment. “You’re not going to see long-term cognitive benefits if it’s not improving your sleep,” Dr. Karageorgiou said. “So, whether trazodone improves sleep or not in a patient after a few months can be an early indicator for the clinician to continue using it or suspend it, because it is unlikely to help their cognition otherwise.”

He stressed that physicians need to be broadly focused on improving sleep to help patients with, or at risk for, dementia by consolidating their sleep rhythms.

“Trazodone is not the magic bullet, and I don’t think we will ever have a magic bullet,” Dr. Karageorgiou said. “Because when our brain degenerates, it’s not just one chemical, or one system, it’s many. And our body changes as well. The important thing is to help the patient consolidate their rhythms, whether through light therapy, daily exercise, cognitive behavioral therapy for insomnia, or other evidence-based interventions and their combination. The same applies for a person with dementia as for the rest of us.”

None of the investigators outside of the industry-sponsored studies had relevant disclosures.

LOS ANGELES – While a large number of older adults take prescription and nonprescription medications to help them sleep, the effect of these medications on dementia risk is unclear, with most researchers advocating a cautious and conservative approach to prescribing.

Nastasic/iStockphoto.com

Research is increasingly revealing a bidirectional relationship between sleep and dementia. Poor sleep – especially from insomnia, sleep deprivation, or obstructive sleep apnea – is known to increase dementia risk. Dementias, meanwhile, are associated with serious circadian rhythm disturbances, leading to nighttime sleep loss and increasing the likelihood of institutionalization.

At the Alzheimer’s Association International Conference, researchers presented findings assessing the links between sleep medication use and dementia and also what agents or approaches might safely improve sleep in people with sleep disorders who are at risk for dementia or who have been diagnosed with dementia.
 

Sex- and race-based differences in risk

Yue Leng, PhD, of the University of California, San Francisco, reported a link between frequent sleep medication use and later dementia – but only in white adults. Dr. Leng presented findings from the National Institutes of Health–funded Health, Aging, and Body Composition Study, which recruited 3,068 subjects aged 70-79 and followed them for 15 years. At baseline, 2.7% of African Americans and 7.7% of whites in the study reported taking sleep medications “often” or “almost always.”

Dr. Leng and her colleagues found that white subjects who reported taking sleep aids five or more times a month at baseline had a nearly 80% higher risk of developing dementia during the course of the study (hazard ratio, 1.79; 95% confidence interval, 1.21-2.66), compared with people who reported never taking sleep aids or taking them less frequently.

The researchers saw no between-sex differences for this finding, and adjusted for a variety of genetic and lifestyle confounders. Importantly, no significant increase in dementia risk was seen for black subjects, who made up more than one-third of the cohort.

Dr. Leng told the conference that the researchers could not explain why black participants did not see similarly increased dementia risk. Also, she noted, researchers did not have information on the specific sleep medications people used: benzodiazepines, antihistamines, antidepressants, or other types of drugs. Nonetheless, she told the conference, the findings ratified the cautious approach many dementia experts are already stressing.


“Do we really need to prescribe so many sleep meds to older adults who are already at risk for cognitive impairment?” Dr. Leng said, adding: “I am a big advocate of behavioral sleep interventions.” People with clinical sleep problems “should be referred to sleep centers” for a fuller assessment before medication is prescribed, she said.

Findings from another cohort study, meanwhile, suggest that there could be sex-related differences in how sleep aids affect dementia risk. Investigators at Utah State University in Logan used data from some 3,656 older adults in the Cache County Study on Memory and Aging, an NIH-backed cohort study of white adults in Utah without dementia at baseline who were followed for 12 years.

The investigators, led by doctoral student Elizabeth Vernon, found that men reporting use of sleep medication saw more than threefold higher risk of developing Alzheimer’s disease than did men who did not use sleep aids (HR, 3.604; P = .0001).

Women who did not report having sleep disturbance but used sleep-inducing medications were at nearly fourfold greater risk for developing Alzheimer’s disease (HR, 3.916; P = .0001). Women who self-reported sleep disturbances at baseline, meanwhile, saw a reduction in Alzheimer’s risk of about one-third associated with the use of sleep medications.

Ms. Vernon told the conference that, despite the finding of risk reduction for this particular group of women, caution in prescribing sleep aids was warranted.

Common sleep drugs linked to cognitive aging

Chris Fox, MD, a researcher at the University of East Anglia in Norwich, England, and his colleagues demonstrated in 2018 that long-term exposure to anticholinergic drugs, a class that includes some antidepressants and antihistamines used to promote sleep, was associated with a higher risk of dementia, while use of benzodiazepines, a class of sedatives used commonly in older people as sleep aids, was not. (Whether benzodiazepine exposure relates to dementia remains controversial.)

At AAIC 2019, Dr. Fox presented findings from a study of 337 brains in a U.K. brain bank, of which 17% and 21% came from users of benzodiazepines and anticholinergic drugs, whose usage history was well documented. Dr. Fox and his colleagues found that, while neither anticholinergic nor benzodiazepine exposure was associated with brain pathology specific to that seen in Alzheimer’s disease, both classes of drugs were associated with “slight signals in neuronal loss” in one brain region, the nucleus basalis of Meynert. Dr. Fox described the drugs as causing “an increase in cognitive aging” which could bear on Alzheimer’s risk without being directly causative.
 

Newer sleep drugs may help Alzheimer’s patients

Scientists working for drug manufacturers presented findings on agents to counter the circadian rhythm disturbances seen in people with Alzheimer’s disease. Margaret Moline, PhD, of Eisai in Woodcliff Lake, N.J., showed some results from a phase 2, dose-ranging, placebo-controlled study of the experimental agent lemborexant in 62 subjects aged 60-90 with mild to moderate Alzheimer’s disease and sleep disturbances. (Lemborexant, an orexin receptor agonist that acts to regulate wakefulness, is being investigated in a broad range of sleep disorders.) Patients were randomized to one of four doses of lemborexant or placebo and wore a device for sleep monitoring. Nighttime activity indicating arousal was significantly lower for people in two dosage arms, 5 mg and 10 mg, compared with placebo, and treatment groups saw trends toward less sleep fragmentation and higher total sleep time, Dr. Moline told the conference.

Suvorexant (Belsomra), the only orexin receptor antagonist currently licensed as a sleep aid, is also being tested in people with Alzheimer’s disease. At AAIC 2019, Joseph Herring, MD, PhD, of Merck in Kenilworth, N.J., presented results from a placebo-controlled trial of 277 patients with Alzheimer’s disease and insomnia, and reported that treatment with 10 or 20 mg of suvorexant over 4 weeks was associated with about an extra half hour of total nightly sleep, with a 73-minute mean increase from baseline, compared with 45 minutes for patients receiving placebo (95% CI, 11-45; P less than .005).
 

Trazodone linked to slower cognitive decline

An inexpensive antidepressant used in low doses as a sleep aid, including in people with Alzheimer’s disease, was associated with a delay in cognitive decline in older adults, according to results from a retrospective study. Elissaios Karageorgiou, MD, PhD, of the University of California, San Francisco, and the Neurological Institute of Athens presented results derived from two cohorts: patients enrolled at the UCSF Memory and Aging Center and women enrolled in the Study for Osteoporotic Fractures (SOF) in Women. The investigators were able to identify trazodone users in the studies (with two or more contiguous study visits reporting trazodone use) and match them with control patients from the same cohorts who did not use trazodone.

Trazodone was studied because previous research suggests it increases total sleep time in patients with Alzheimer’s disease without affecting next-day cognitive performance.

Trazodone-using patients in the UCSF cohort (n = 25) saw significantly less decline in Mini Mental State Exam (MMSE) scores over 4 years, compared with nonusers (0.27 vs. 0.70 points per year; P = .023), an effect that remained statistically significant even after adjusting for sedative and stimulant use and the expected progression of Alzheimer’s disease pathology. Importantly, the slower decline was seen only among subjects with sleep complaints at baseline and especially those whose sleep improved over time, suggesting that the cognitive benefit was mediated by improved sleep.

In the SOF cohort of 46 trazodone users matched with 148 nonusers, no significant protective or negative effect related to long-term trazodone use was found using the MMSE or the Trails Making Test. In this analysis, however, baseline and longitudinal sleep quality was not captured in the group-matching process, neither was the use of other medications. The patient group was slightly older, and all patients were women.

Dr. Karageorgiou said in an interview that the link between improved sleep, trazodone, and cognition needs to be validated in prospective intervention studies. Trazodone, he said, appears to work best in people with a specific type of insomnia characterized by cortical and behavioral hyperarousal, and its cognitive effect appears limited to people whose sleep improves with treatment. “You’re not going to see long-term cognitive benefits if it’s not improving your sleep,” Dr. Karageorgiou said. “So, whether trazodone improves sleep or not in a patient after a few months can be an early indicator for the clinician to continue using it or suspend it, because it is unlikely to help their cognition otherwise.”

He stressed that physicians need to be broadly focused on improving sleep to help patients with, or at risk for, dementia by consolidating their sleep rhythms.

“Trazodone is not the magic bullet, and I don’t think we will ever have a magic bullet,” Dr. Karageorgiou said. “Because when our brain degenerates, it’s not just one chemical, or one system, it’s many. And our body changes as well. The important thing is to help the patient consolidate their rhythms, whether through light therapy, daily exercise, cognitive behavioral therapy for insomnia, or other evidence-based interventions and their combination. The same applies for a person with dementia as for the rest of us.”

None of the investigators outside of the industry-sponsored studies had relevant disclosures.

LJUBLJANA, SLOVENIA – Encouraging safety and immunogenicity results reported from phase 1 studies of the first mRNA vaccines against the potentially pandemic H10N8 avian influenza and H7N9 influenza viruses suggest a bright future for what appears to be a breakthrough technology in vaccine development.

Bruce Jancin/MDedge News

“We have developed an mRNA platform that has the potential to be quite applicable to the vaccine space. It’s an agile platform with the potential for relatively rapid development of vaccine antigen without the use of dedicated facilities, or growth in eggs, or insects, or mammalian cells,” Lori Panther, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

“We now have a platform that is relatively plug and play. If one has the mRNA sequence that you’re after to produce the protein that you’re after, it is a relatively repetitive process somewhat irrespective of the goal of the protein that you’re going to manufacture. We’re introducing an mRNA into our cellular machinery – the destination is the cellular ribosome – where it hopefully is able to be translated with fidelity into the target protein. Essentially it’s like the biological equivalent of a software hack for our own cells,” explained Dr. Panther, who is director of clinical development for infectious diseases at Moderna, in Cambridge, Mass.

Indeed, Moderna has numerous ongoing or recently completed phase 1 clinical trials of mRNA vaccines developed to protect against a raft of viral infections: respiratory syncytial virus, cytomegalovirus (NCT03382405), zika, chikungunya (NCT03829384), human metapneumovirus, and parainfluenza virus 3, as well as the aforementioned H10N8 and H7N9 influenza viruses. And an mRNA varicella zoster virus vaccine is in preclinical studies.

The mRNA vaccines closely mimic native viral infections, eliciting both B- and T-cell responses.

Moreover, the company also has ongoing phase 1 studies of mRNA-based cancer vaccines – therapies targeting solid tumors and lymphomas – as well as mRNA-directed increased production of relaxin as a treatment for heart failure and of vascular endothelial growth factor to treat myocardial ischemia.

“For the purposes of my company, the desired protein at this juncture could be an antibody, it could be a tumor antigen, it could be an enzyme that will replace an enzyme that’s lacking in somebody with an inborn error of metabolism. Or it could be a vaccine antigen target,” Dr. Panther said.

In addition to highlighting the results of the two phase 1 proof-of-concept studies of mRNA vaccines targeting the feared H10N8 and H7N9 influenza viruses, she presented interim results of an ongoing 1-year study of an mRNA vaccine that contains two antigens simultaneously targeting human metapneumovirus (hMPV) and parainfluenza virus 3 (PIV3).

“The rationale behind this study is that, taken together, these are two viruses that are responsible for a fair bit of disease burden in terms of lower respiratory tract infections and hospitalizations in children [younger] than 12 months of age, which will be the target population,” the infectious disease specialist noted.

The early positive results of the mRNA influenza vaccine studies were of particular interest to her audience of pediatric infectious disease specialists. Since the first human H7N9 infections were reported in China in 2013, five outbreaks have occurred involving more than 1,500 documented infections, resulting in more than 600 deaths. And ever since the virulent H10N8 avian influenza virus popped up on the radar in 2013, infectious disease physicians the world over have been waiting for the other shoe to drop.

There is obvious appeal to a novel, precise, and rapidly scalable technology such as that promised by intracellular delivery of mRNA in order to ramp up high-volume production of effective vaccines in the face of a looming pandemic threat. Elsewhere at the meeting, it was noted that, during the H1N1 pandemic of 2009, it took 6 months for the first vaccine doses to become available using current antiquated egg-based production methods. Another 2 months elapsed before the necessary millions of doses were produced.

The details of the two phase 1 studies of the mRNA vaccines against H7N9 and H10N8 influenza have recently been published (Vaccine. 2019 May 31;37[25]:3326-34). The vaccines, delivered in the conventional manner via injection into the deltoid muscle, were well tolerated, with the most common adverse events being the familiar ones: injection site pain, erythema, headache, fatigue, and myalgia. The immune response was robust and durable.

In response to an audience question, Dr. Panther said the mRNA vaccines are amenable to development as intranasal formulations.

The ongoing 12-month, phase 1, dose-ranging study of the mRNA hMPV/PIV3 virus vaccine includes 124 healthy adults at three U.S. sites who received two vaccinations on days 1 and 28. One month after a single vaccination, hMPV neutralizing antibody titers were 6.2-6.4 times those in the placebo arm; PIV3 neutralization titers were increased 3.3-fold. The second injection didn’t further boost antibody titers, suggesting that, at least in this study population of preexposed adults, a single vaccination is sufficient.

The use of mRNA technology has been a long time in coming. Dr. Panther explained why: “It’s a big trick to take an mRNA that by its own nature is a pretty fragile molecule and to get it past the degrading enzymes, like RNAses, that are out to chew it up immediately, and then to sneak it across the cellular membrane and into the cytoplasm, all the while avoiding the innate immune responses that exist solely to recognize RNA that looks foreign and chew it up.”

Moderna has accomplished this using a proprietary lipid nanoparticle delivery system.

“Essentially it’s a lipid shield that surrounds the mRNAs and ushers them past those enzymes and past the innate immune response that would otherwise destroy them,” according to Dr. Panther.

She and her colleagues believe they may eventually be able to change the nucleotide sequence of their manufactured mRNAs in order to expand the immunogenicity epitope and achieve a stronger immune response than would result from natural infection.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – Encouraging safety and immunogenicity results reported from phase 1 studies of the first mRNA vaccines against the potentially pandemic H10N8 avian influenza and H7N9 influenza viruses suggest a bright future for what appears to be a breakthrough technology in vaccine development.

Bruce Jancin/MDedge News

“We have developed an mRNA platform that has the potential to be quite applicable to the vaccine space. It’s an agile platform with the potential for relatively rapid development of vaccine antigen without the use of dedicated facilities, or growth in eggs, or insects, or mammalian cells,” Lori Panther, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

“We now have a platform that is relatively plug and play. If one has the mRNA sequence that you’re after to produce the protein that you’re after, it is a relatively repetitive process somewhat irrespective of the goal of the protein that you’re going to manufacture. We’re introducing an mRNA into our cellular machinery – the destination is the cellular ribosome – where it hopefully is able to be translated with fidelity into the target protein. Essentially it’s like the biological equivalent of a software hack for our own cells,” explained Dr. Panther, who is director of clinical development for infectious diseases at Moderna, in Cambridge, Mass.

Indeed, Moderna has numerous ongoing or recently completed phase 1 clinical trials of mRNA vaccines developed to protect against a raft of viral infections: respiratory syncytial virus, cytomegalovirus (NCT03382405), zika, chikungunya (NCT03829384), human metapneumovirus, and parainfluenza virus 3, as well as the aforementioned H10N8 and H7N9 influenza viruses. And an mRNA varicella zoster virus vaccine is in preclinical studies.

The mRNA vaccines closely mimic native viral infections, eliciting both B- and T-cell responses.

Moreover, the company also has ongoing phase 1 studies of mRNA-based cancer vaccines – therapies targeting solid tumors and lymphomas – as well as mRNA-directed increased production of relaxin as a treatment for heart failure and of vascular endothelial growth factor to treat myocardial ischemia.

“For the purposes of my company, the desired protein at this juncture could be an antibody, it could be a tumor antigen, it could be an enzyme that will replace an enzyme that’s lacking in somebody with an inborn error of metabolism. Or it could be a vaccine antigen target,” Dr. Panther said.

In addition to highlighting the results of the two phase 1 proof-of-concept studies of mRNA vaccines targeting the feared H10N8 and H7N9 influenza viruses, she presented interim results of an ongoing 1-year study of an mRNA vaccine that contains two antigens simultaneously targeting human metapneumovirus (hMPV) and parainfluenza virus 3 (PIV3).

“The rationale behind this study is that, taken together, these are two viruses that are responsible for a fair bit of disease burden in terms of lower respiratory tract infections and hospitalizations in children [younger] than 12 months of age, which will be the target population,” the infectious disease specialist noted.

The early positive results of the mRNA influenza vaccine studies were of particular interest to her audience of pediatric infectious disease specialists. Since the first human H7N9 infections were reported in China in 2013, five outbreaks have occurred involving more than 1,500 documented infections, resulting in more than 600 deaths. And ever since the virulent H10N8 avian influenza virus popped up on the radar in 2013, infectious disease physicians the world over have been waiting for the other shoe to drop.

There is obvious appeal to a novel, precise, and rapidly scalable technology such as that promised by intracellular delivery of mRNA in order to ramp up high-volume production of effective vaccines in the face of a looming pandemic threat. Elsewhere at the meeting, it was noted that, during the H1N1 pandemic of 2009, it took 6 months for the first vaccine doses to become available using current antiquated egg-based production methods. Another 2 months elapsed before the necessary millions of doses were produced.

The details of the two phase 1 studies of the mRNA vaccines against H7N9 and H10N8 influenza have recently been published (Vaccine. 2019 May 31;37[25]:3326-34). The vaccines, delivered in the conventional manner via injection into the deltoid muscle, were well tolerated, with the most common adverse events being the familiar ones: injection site pain, erythema, headache, fatigue, and myalgia. The immune response was robust and durable.

In response to an audience question, Dr. Panther said the mRNA vaccines are amenable to development as intranasal formulations.

The ongoing 12-month, phase 1, dose-ranging study of the mRNA hMPV/PIV3 virus vaccine includes 124 healthy adults at three U.S. sites who received two vaccinations on days 1 and 28. One month after a single vaccination, hMPV neutralizing antibody titers were 6.2-6.4 times those in the placebo arm; PIV3 neutralization titers were increased 3.3-fold. The second injection didn’t further boost antibody titers, suggesting that, at least in this study population of preexposed adults, a single vaccination is sufficient.

The use of mRNA technology has been a long time in coming. Dr. Panther explained why: “It’s a big trick to take an mRNA that by its own nature is a pretty fragile molecule and to get it past the degrading enzymes, like RNAses, that are out to chew it up immediately, and then to sneak it across the cellular membrane and into the cytoplasm, all the while avoiding the innate immune responses that exist solely to recognize RNA that looks foreign and chew it up.”

Moderna has accomplished this using a proprietary lipid nanoparticle delivery system.

“Essentially it’s a lipid shield that surrounds the mRNAs and ushers them past those enzymes and past the innate immune response that would otherwise destroy them,” according to Dr. Panther.

She and her colleagues believe they may eventually be able to change the nucleotide sequence of their manufactured mRNAs in order to expand the immunogenicity epitope and achieve a stronger immune response than would result from natural infection.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – Encouraging safety and immunogenicity results reported from phase 1 studies of the first mRNA vaccines against the potentially pandemic H10N8 avian influenza and H7N9 influenza viruses suggest a bright future for what appears to be a breakthrough technology in vaccine development.

Bruce Jancin/MDedge News

“We have developed an mRNA platform that has the potential to be quite applicable to the vaccine space. It’s an agile platform with the potential for relatively rapid development of vaccine antigen without the use of dedicated facilities, or growth in eggs, or insects, or mammalian cells,” Lori Panther, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

“We now have a platform that is relatively plug and play. If one has the mRNA sequence that you’re after to produce the protein that you’re after, it is a relatively repetitive process somewhat irrespective of the goal of the protein that you’re going to manufacture. We’re introducing an mRNA into our cellular machinery – the destination is the cellular ribosome – where it hopefully is able to be translated with fidelity into the target protein. Essentially it’s like the biological equivalent of a software hack for our own cells,” explained Dr. Panther, who is director of clinical development for infectious diseases at Moderna, in Cambridge, Mass.

Indeed, Moderna has numerous ongoing or recently completed phase 1 clinical trials of mRNA vaccines developed to protect against a raft of viral infections: respiratory syncytial virus, cytomegalovirus (NCT03382405), zika, chikungunya (NCT03829384), human metapneumovirus, and parainfluenza virus 3, as well as the aforementioned H10N8 and H7N9 influenza viruses. And an mRNA varicella zoster virus vaccine is in preclinical studies.

The mRNA vaccines closely mimic native viral infections, eliciting both B- and T-cell responses.

Moreover, the company also has ongoing phase 1 studies of mRNA-based cancer vaccines – therapies targeting solid tumors and lymphomas – as well as mRNA-directed increased production of relaxin as a treatment for heart failure and of vascular endothelial growth factor to treat myocardial ischemia.

“For the purposes of my company, the desired protein at this juncture could be an antibody, it could be a tumor antigen, it could be an enzyme that will replace an enzyme that’s lacking in somebody with an inborn error of metabolism. Or it could be a vaccine antigen target,” Dr. Panther said.

In addition to highlighting the results of the two phase 1 proof-of-concept studies of mRNA vaccines targeting the feared H10N8 and H7N9 influenza viruses, she presented interim results of an ongoing 1-year study of an mRNA vaccine that contains two antigens simultaneously targeting human metapneumovirus (hMPV) and parainfluenza virus 3 (PIV3).

“The rationale behind this study is that, taken together, these are two viruses that are responsible for a fair bit of disease burden in terms of lower respiratory tract infections and hospitalizations in children [younger] than 12 months of age, which will be the target population,” the infectious disease specialist noted.

The early positive results of the mRNA influenza vaccine studies were of particular interest to her audience of pediatric infectious disease specialists. Since the first human H7N9 infections were reported in China in 2013, five outbreaks have occurred involving more than 1,500 documented infections, resulting in more than 600 deaths. And ever since the virulent H10N8 avian influenza virus popped up on the radar in 2013, infectious disease physicians the world over have been waiting for the other shoe to drop.

There is obvious appeal to a novel, precise, and rapidly scalable technology such as that promised by intracellular delivery of mRNA in order to ramp up high-volume production of effective vaccines in the face of a looming pandemic threat. Elsewhere at the meeting, it was noted that, during the H1N1 pandemic of 2009, it took 6 months for the first vaccine doses to become available using current antiquated egg-based production methods. Another 2 months elapsed before the necessary millions of doses were produced.

The details of the two phase 1 studies of the mRNA vaccines against H7N9 and H10N8 influenza have recently been published (Vaccine. 2019 May 31;37[25]:3326-34). The vaccines, delivered in the conventional manner via injection into the deltoid muscle, were well tolerated, with the most common adverse events being the familiar ones: injection site pain, erythema, headache, fatigue, and myalgia. The immune response was robust and durable.

In response to an audience question, Dr. Panther said the mRNA vaccines are amenable to development as intranasal formulations.

The ongoing 12-month, phase 1, dose-ranging study of the mRNA hMPV/PIV3 virus vaccine includes 124 healthy adults at three U.S. sites who received two vaccinations on days 1 and 28. One month after a single vaccination, hMPV neutralizing antibody titers were 6.2-6.4 times those in the placebo arm; PIV3 neutralization titers were increased 3.3-fold. The second injection didn’t further boost antibody titers, suggesting that, at least in this study population of preexposed adults, a single vaccination is sufficient.

The use of mRNA technology has been a long time in coming. Dr. Panther explained why: “It’s a big trick to take an mRNA that by its own nature is a pretty fragile molecule and to get it past the degrading enzymes, like RNAses, that are out to chew it up immediately, and then to sneak it across the cellular membrane and into the cytoplasm, all the while avoiding the innate immune responses that exist solely to recognize RNA that looks foreign and chew it up.”

Moderna has accomplished this using a proprietary lipid nanoparticle delivery system.

“Essentially it’s a lipid shield that surrounds the mRNAs and ushers them past those enzymes and past the innate immune response that would otherwise destroy them,” according to Dr. Panther.

She and her colleagues believe they may eventually be able to change the nucleotide sequence of their manufactured mRNAs in order to expand the immunogenicity epitope and achieve a stronger immune response than would result from natural infection.

bjancin@mdedge.com

A study modeling outcomes for women with estrogen receptor–positive, HER2-negative breast cancer indicates that those with the highest score on a clinicomolecular test would be most likely to benefit from chemotherapy to reduce the risk of distant recurrence.

The model, created by William Gradishar, MD, from the Robert H. Lurie Comprehensive Cancer Center in Chicago, and colleagues, uses validated 10-year risk of distant breast recurrences as a function of the EndoPredict (EPclin) 12-gene clinicomolecular assay score.

The model suggests that for patients with a low EPclin score, chemotherapy would offer no additional benefit over endocrine therapy, whereas those with high scores would have an increase in recurrence-free survival with chemotherapy.

“Overall, this demonstrates that EndoPredict provides guidance on the expected absolute benefit from adjuvant chemotherapy in addition to prognostic information for patients with ER-positive, HER2-negative early-stage breast cancer. Therefore, EndoPredict can identify patients likely to benefit sufficiently from adjuvant chemotherapy to justify associated toxicities,” Dr. Gradishar and associates wrote in Precision Oncology.

The assay has previously been shown to accurately predict the risk of distant metastases in patients with estrogen receptor–positive, human epidermal growth factor receptor–2 negative (ER+/HER2–) breast cancer, but the ability to predict absolute benefit of chemotherapy is less clear, and it would be unethical to conduct a randomized trial with a no-chemotherapy arm, the investigators noted.

Instead, the investigators created a mathematical model to try to answer the question. They determined the average relative benefit of chemotherapy for reducing distant recurrence using a published meta-analysis from the Early Breast Cancer Trialists’ Collaborative Group, and they estimated absolute chemotherapy benefit differences across a range of interaction strengths between relative chemotherapy benefit and the EPclin score. Finally, they calculated average absolute benefit for patients with high and low EPclin scores using the distribution of scores in 2,185 samples tested by Myriad Genetics, maker of the assay.

They found that the average expected absolute benefit of chemotherapy treatment for patients with a low EPclin score was 1.8% assuming no interaction between prognostic factors and chemotherapy benefit, and 1.5% for maximal interaction, suggesting no significant added benefit from chemotherapy.

In contrast, for patients with a high EPclin score, the absolute benefit assuming no interaction was 5.3% and the benefit assuming maximal interaction was 7.3%.

“Overall, these data demonstrate that high EPclin scores are associated with maximal predicted chemotherapy benefit, and low EPclin scores are associated with no clinically meaningful benefit. This association is irrespective of interaction strength between EPclin and predicted chemotherapy benefit, and the impact of any interaction on absolute benefit is much smaller than the ability to accurately estimate absolute risk,” they wrote.

The study was supported by Myriad Genetics. Dr. Gradishar disclosed consulting or advisory roles with Genentech and Roche. Five of the coauthors are employees of Myriad Genetics or Myriad International.

SOURCE: Gradishar W et al. Precision Oncology. 2016 Aug. 6. doi: 10.1200/PO.18.00361.

A study modeling outcomes for women with estrogen receptor–positive, HER2-negative breast cancer indicates that those with the highest score on a clinicomolecular test would be most likely to benefit from chemotherapy to reduce the risk of distant recurrence.

The model, created by William Gradishar, MD, from the Robert H. Lurie Comprehensive Cancer Center in Chicago, and colleagues, uses validated 10-year risk of distant breast recurrences as a function of the EndoPredict (EPclin) 12-gene clinicomolecular assay score.

The model suggests that for patients with a low EPclin score, chemotherapy would offer no additional benefit over endocrine therapy, whereas those with high scores would have an increase in recurrence-free survival with chemotherapy.

“Overall, this demonstrates that EndoPredict provides guidance on the expected absolute benefit from adjuvant chemotherapy in addition to prognostic information for patients with ER-positive, HER2-negative early-stage breast cancer. Therefore, EndoPredict can identify patients likely to benefit sufficiently from adjuvant chemotherapy to justify associated toxicities,” Dr. Gradishar and associates wrote in Precision Oncology.

The assay has previously been shown to accurately predict the risk of distant metastases in patients with estrogen receptor–positive, human epidermal growth factor receptor–2 negative (ER+/HER2–) breast cancer, but the ability to predict absolute benefit of chemotherapy is less clear, and it would be unethical to conduct a randomized trial with a no-chemotherapy arm, the investigators noted.

Instead, the investigators created a mathematical model to try to answer the question. They determined the average relative benefit of chemotherapy for reducing distant recurrence using a published meta-analysis from the Early Breast Cancer Trialists’ Collaborative Group, and they estimated absolute chemotherapy benefit differences across a range of interaction strengths between relative chemotherapy benefit and the EPclin score. Finally, they calculated average absolute benefit for patients with high and low EPclin scores using the distribution of scores in 2,185 samples tested by Myriad Genetics, maker of the assay.

They found that the average expected absolute benefit of chemotherapy treatment for patients with a low EPclin score was 1.8% assuming no interaction between prognostic factors and chemotherapy benefit, and 1.5% for maximal interaction, suggesting no significant added benefit from chemotherapy.

In contrast, for patients with a high EPclin score, the absolute benefit assuming no interaction was 5.3% and the benefit assuming maximal interaction was 7.3%.

“Overall, these data demonstrate that high EPclin scores are associated with maximal predicted chemotherapy benefit, and low EPclin scores are associated with no clinically meaningful benefit. This association is irrespective of interaction strength between EPclin and predicted chemotherapy benefit, and the impact of any interaction on absolute benefit is much smaller than the ability to accurately estimate absolute risk,” they wrote.

The study was supported by Myriad Genetics. Dr. Gradishar disclosed consulting or advisory roles with Genentech and Roche. Five of the coauthors are employees of Myriad Genetics or Myriad International.

SOURCE: Gradishar W et al. Precision Oncology. 2016 Aug. 6. doi: 10.1200/PO.18.00361.

A study modeling outcomes for women with estrogen receptor–positive, HER2-negative breast cancer indicates that those with the highest score on a clinicomolecular test would be most likely to benefit from chemotherapy to reduce the risk of distant recurrence.

The model, created by William Gradishar, MD, from the Robert H. Lurie Comprehensive Cancer Center in Chicago, and colleagues, uses validated 10-year risk of distant breast recurrences as a function of the EndoPredict (EPclin) 12-gene clinicomolecular assay score.

The model suggests that for patients with a low EPclin score, chemotherapy would offer no additional benefit over endocrine therapy, whereas those with high scores would have an increase in recurrence-free survival with chemotherapy.

“Overall, this demonstrates that EndoPredict provides guidance on the expected absolute benefit from adjuvant chemotherapy in addition to prognostic information for patients with ER-positive, HER2-negative early-stage breast cancer. Therefore, EndoPredict can identify patients likely to benefit sufficiently from adjuvant chemotherapy to justify associated toxicities,” Dr. Gradishar and associates wrote in Precision Oncology.

The assay has previously been shown to accurately predict the risk of distant metastases in patients with estrogen receptor–positive, human epidermal growth factor receptor–2 negative (ER+/HER2–) breast cancer, but the ability to predict absolute benefit of chemotherapy is less clear, and it would be unethical to conduct a randomized trial with a no-chemotherapy arm, the investigators noted.

Instead, the investigators created a mathematical model to try to answer the question. They determined the average relative benefit of chemotherapy for reducing distant recurrence using a published meta-analysis from the Early Breast Cancer Trialists’ Collaborative Group, and they estimated absolute chemotherapy benefit differences across a range of interaction strengths between relative chemotherapy benefit and the EPclin score. Finally, they calculated average absolute benefit for patients with high and low EPclin scores using the distribution of scores in 2,185 samples tested by Myriad Genetics, maker of the assay.

They found that the average expected absolute benefit of chemotherapy treatment for patients with a low EPclin score was 1.8% assuming no interaction between prognostic factors and chemotherapy benefit, and 1.5% for maximal interaction, suggesting no significant added benefit from chemotherapy.

In contrast, for patients with a high EPclin score, the absolute benefit assuming no interaction was 5.3% and the benefit assuming maximal interaction was 7.3%.

“Overall, these data demonstrate that high EPclin scores are associated with maximal predicted chemotherapy benefit, and low EPclin scores are associated with no clinically meaningful benefit. This association is irrespective of interaction strength between EPclin and predicted chemotherapy benefit, and the impact of any interaction on absolute benefit is much smaller than the ability to accurately estimate absolute risk,” they wrote.

The study was supported by Myriad Genetics. Dr. Gradishar disclosed consulting or advisory roles with Genentech and Roche. Five of the coauthors are employees of Myriad Genetics or Myriad International.

SOURCE: Gradishar W et al. Precision Oncology. 2016 Aug. 6. doi: 10.1200/PO.18.00361.

ORLANDO – Regular education of patients with asthma and their loved ones about how to manage the disease is critical to successful treatment, according to a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.

“Every contact with them is a teachable moment,” Mary Lou Hayden, RN, MS, FNP-BC, AE-C, a board-certified nurse practitioner and asthma educator, said in her presentation. “You want to make sure you’re involving the important people in their lives to help them.”

Education for asthma includes teaching patients and their families the difference between long-term control and reliever medications; the proper timing and technique with the medications, as well as the importance of adherence; how to recognize and avoid triggers for asthma; how to self-monitor their asthma and control the disease; and when to seek medication care, she said.

“We review their inhaler technique every time they come in,” she added.

According to the American Lung Association, patients learn in visual, auditory, and kinesthetic styles. Teaching patients in a kinesthetic style by actually showing the patient how to take the medication through example will help the patient learn through feeling, or muscle memory. This also method works even if patients do not have the medication with them at the time, said Ms. Hayden.

“Let’s say, you don’t have [the medication], but you prescribe it,” she said. “When they come back, tell them to bring their bag of medications and make sure you go back through because if they can kinesthetically use it correctly, they’ve already mastered the visual and the auditory piece.

Written action plans are also important to successful asthma management. The plan should be tailored to the patient’s disease severity, loss of control, and include information like the peak expiratory flow and medication types, dosages, and frequencies. The action plan should also be available at home, daycare, and school. “You want them to know how to recognize their symptoms, what to do about their symptoms, and when to contact you or go to urgent care or [the emergency room],” said Ms. Hayden.

To simplify the plan, Ms. Hayden recommended zoning actions based on color, like the asthma action plan provided by the American Academy of Allergy, Asthma & Immunology. The AAAAI plan uses traffic colors to signify how well controlled a patient’s asthma is, with green indicating well-controlled disease, yellow denoting worsening asthma, and red indicating that the asthma needs to be treated right away.

Action plans should also address a patient’s health literacy level and culture. “Think about who’s going to be using it,” said Ms. Hayden.

The goal of asthma therapy is to prevent chronic or problematic symptoms, lower use of short-acting beta-agonists, maintain good pulmonary function, normalize activity levels at school and work, prevent exacerbations and hospitalizations, and meet the patient’s expectations, as well as those of their family. “If you’re thinking only severe patients have exacerbations that are near fatal or fatal, that’s not true,” she said. It’s “very common for somebody with a very mild and intermittent asthma to go to severe in a very short period of time.”

When properly implemented, patient education is performed at the time of diagnosis, is done according to a plan, is integrated into care, reinforces important information, improves adherence, is individualized to the patient and addresses their needs, and builds a partnership between provider and patient.

“We really are thinking of the team concept: us, the patient and the important people the patient’s lives, and other clinicians that might be involved with other diseases to care for the patient,” said Ms. Hayden.

Ms. Hayden reports no relevant conflicts of interest. Global Academy for Medical Education and this news organization are owned by the same parent company.

ORLANDO – Regular education of patients with asthma and their loved ones about how to manage the disease is critical to successful treatment, according to a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.

“Every contact with them is a teachable moment,” Mary Lou Hayden, RN, MS, FNP-BC, AE-C, a board-certified nurse practitioner and asthma educator, said in her presentation. “You want to make sure you’re involving the important people in their lives to help them.”

Education for asthma includes teaching patients and their families the difference between long-term control and reliever medications; the proper timing and technique with the medications, as well as the importance of adherence; how to recognize and avoid triggers for asthma; how to self-monitor their asthma and control the disease; and when to seek medication care, she said.

“We review their inhaler technique every time they come in,” she added.

According to the American Lung Association, patients learn in visual, auditory, and kinesthetic styles. Teaching patients in a kinesthetic style by actually showing the patient how to take the medication through example will help the patient learn through feeling, or muscle memory. This also method works even if patients do not have the medication with them at the time, said Ms. Hayden.

“Let’s say, you don’t have [the medication], but you prescribe it,” she said. “When they come back, tell them to bring their bag of medications and make sure you go back through because if they can kinesthetically use it correctly, they’ve already mastered the visual and the auditory piece.

Written action plans are also important to successful asthma management. The plan should be tailored to the patient’s disease severity, loss of control, and include information like the peak expiratory flow and medication types, dosages, and frequencies. The action plan should also be available at home, daycare, and school. “You want them to know how to recognize their symptoms, what to do about their symptoms, and when to contact you or go to urgent care or [the emergency room],” said Ms. Hayden.

To simplify the plan, Ms. Hayden recommended zoning actions based on color, like the asthma action plan provided by the American Academy of Allergy, Asthma & Immunology. The AAAAI plan uses traffic colors to signify how well controlled a patient’s asthma is, with green indicating well-controlled disease, yellow denoting worsening asthma, and red indicating that the asthma needs to be treated right away.

Action plans should also address a patient’s health literacy level and culture. “Think about who’s going to be using it,” said Ms. Hayden.

The goal of asthma therapy is to prevent chronic or problematic symptoms, lower use of short-acting beta-agonists, maintain good pulmonary function, normalize activity levels at school and work, prevent exacerbations and hospitalizations, and meet the patient’s expectations, as well as those of their family. “If you’re thinking only severe patients have exacerbations that are near fatal or fatal, that’s not true,” she said. It’s “very common for somebody with a very mild and intermittent asthma to go to severe in a very short period of time.”

When properly implemented, patient education is performed at the time of diagnosis, is done according to a plan, is integrated into care, reinforces important information, improves adherence, is individualized to the patient and addresses their needs, and builds a partnership between provider and patient.

“We really are thinking of the team concept: us, the patient and the important people the patient’s lives, and other clinicians that might be involved with other diseases to care for the patient,” said Ms. Hayden.

Ms. Hayden reports no relevant conflicts of interest. Global Academy for Medical Education and this news organization are owned by the same parent company.

ORLANDO – Regular education of patients with asthma and their loved ones about how to manage the disease is critical to successful treatment, according to a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.

“Every contact with them is a teachable moment,” Mary Lou Hayden, RN, MS, FNP-BC, AE-C, a board-certified nurse practitioner and asthma educator, said in her presentation. “You want to make sure you’re involving the important people in their lives to help them.”

Education for asthma includes teaching patients and their families the difference between long-term control and reliever medications; the proper timing and technique with the medications, as well as the importance of adherence; how to recognize and avoid triggers for asthma; how to self-monitor their asthma and control the disease; and when to seek medication care, she said.

“We review their inhaler technique every time they come in,” she added.

According to the American Lung Association, patients learn in visual, auditory, and kinesthetic styles. Teaching patients in a kinesthetic style by actually showing the patient how to take the medication through example will help the patient learn through feeling, or muscle memory. This also method works even if patients do not have the medication with them at the time, said Ms. Hayden.

“Let’s say, you don’t have [the medication], but you prescribe it,” she said. “When they come back, tell them to bring their bag of medications and make sure you go back through because if they can kinesthetically use it correctly, they’ve already mastered the visual and the auditory piece.

Written action plans are also important to successful asthma management. The plan should be tailored to the patient’s disease severity, loss of control, and include information like the peak expiratory flow and medication types, dosages, and frequencies. The action plan should also be available at home, daycare, and school. “You want them to know how to recognize their symptoms, what to do about their symptoms, and when to contact you or go to urgent care or [the emergency room],” said Ms. Hayden.

To simplify the plan, Ms. Hayden recommended zoning actions based on color, like the asthma action plan provided by the American Academy of Allergy, Asthma & Immunology. The AAAAI plan uses traffic colors to signify how well controlled a patient’s asthma is, with green indicating well-controlled disease, yellow denoting worsening asthma, and red indicating that the asthma needs to be treated right away.

Action plans should also address a patient’s health literacy level and culture. “Think about who’s going to be using it,” said Ms. Hayden.

The goal of asthma therapy is to prevent chronic or problematic symptoms, lower use of short-acting beta-agonists, maintain good pulmonary function, normalize activity levels at school and work, prevent exacerbations and hospitalizations, and meet the patient’s expectations, as well as those of their family. “If you’re thinking only severe patients have exacerbations that are near fatal or fatal, that’s not true,” she said. It’s “very common for somebody with a very mild and intermittent asthma to go to severe in a very short period of time.”

When properly implemented, patient education is performed at the time of diagnosis, is done according to a plan, is integrated into care, reinforces important information, improves adherence, is individualized to the patient and addresses their needs, and builds a partnership between provider and patient.

“We really are thinking of the team concept: us, the patient and the important people the patient’s lives, and other clinicians that might be involved with other diseases to care for the patient,” said Ms. Hayden.

Ms. Hayden reports no relevant conflicts of interest. Global Academy for Medical Education and this news organization are owned by the same parent company.