SAN FRANCISCO – Type 2 diabetes is much more aggressive in adolescents than in adults, and by the time those with youth-onset diabetes reach their early 20s, they are beset with disease-related complications usually seen in older populations, findings from the RISE and TODAY2 studies have demonstrated.

M. Alexander Otto/Mdedge News

“Additional research is urgently needed to better understand the reasons for this more serious trajectory,” Philip Zeitler, MD, PhD, of Children’s Hospital Colorado, Aurora, said at the annual scientific sessions of the American Diabetes Association. The hope is to identify at-risk children and prevent the disease, but at this point “we don’t know the answer.”

In the meantime, “we are getting more aggressive with bariatric surgery at our center, because nothing else is working as well. It would be nice to move away from that, but these kids are going to die,” he added.

Steven Kahn, MD, of the diabetes Research Center at the University of Washington, Seattle, presented the findings from a comparison of outcomes from the Restoring Insulin Secretion (RISE) studies in adolescents aged 10-19 years and in adults. The RISE Pediatric Medication Study (Diabetes Care. 2018; 41[8]:1717-25) and RISE Adult Medication Study were parallel investigations treatments to preserve or improve beta-cell function.

M. Alexander Otto/MDedge News

“This is the first-ever true comparison of outcomes in youth versus adults,” he said. Both arms had the same design and lab measurements, but the differences in outcomes were “very scary,” he added. “The disease is much more aggressive in youth than in adults.”

Among other things, the RISE youth-versus-adult study compared the outcomes after 3 months of insulin glargine followed by 9 months of metformin, or 12 months of metformin in 132 obese adults and 91 obese adolescents with impaired glucose tolerance or recently diagnosed type 2 diabetes. The treatments were stopped after 12 months, and the participants were reevaluated at 15 months. Hyperglycemic clamps were conducted at baseline, 12 months, and 3 months after treatment cessation (Diabetes. 2019 Jun 9. doi: 10.2337/db19-0299).

In adults, treatment improved insulin sensitivity and beta-cell response, but after treatment cessation, they reverted to baseline by the 15-month evaluation. However, there was no improvement in insulin sensitivity and beta-cell response in adolescents, either during treatment or after cessation, and in fact, they were worse off at 15 months than they had been at baseline, with lower insulin secretion and higher hemoglobin A_1c.

Those stark differences in outcomes between the adolescents and adults were indicative of a more aggressive disease trajectory for younger patients.

Compliance was not the issue, with more than 80% of both adults and children taking more than 80% of their medications, Dr. Kahn said.

He suggested that adolescents might have a different underlying pathology that makes it worse to develop diabetes during puberty, which is already an insulin-resistant state. But, whatever the case, there is an “urgent need” to better understand the differences between adolescents and adults and to find better treatments for younger patients with diabetes, he said.

In regard to using weight loss as a means of treatment or prevention, Dr. Zeitler emphasized that type 2 diabetes in younger patients “occurs in a context of very low socioeconomic status, family dysfunction, and a great deal of stress and [family] illness. It’s often a complex situation and it’s difficult to accomplish effective lifestyle change when families are struggling to have afford quality food, facing challenges of family and neighborhood violence, and working multiple jobs.”

The RISE findings of a more aggressive deterioration in beta-cell function for younger patients were reflected in outcomes in the TODAY2 study, which found that adolescents who are diagnosed with type 2 diabetes face severe renal, cardiovascular, eye, and nerve complications by the time they reach their early 20s.

TODAY2 was an 8-year follow-up to the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial published in 2012 (N Engl J Med. 2012;366:2247-56). Data from the original study of patients aged 10-17 years with type 2 diabetes showed that after a roughly 4-year follow-up, almost half of all participants had experienced loss of glycemic control on their original treatment assignment, a rate much higher than that reported in adults. Metformin plus rosiglitazone was superior to metformin alone in maintaining durable glycemic control and metformin plus an intensive lifestyle intervention was intermediate to the other groups, but not significantly different from them. In addition, metformin alone was found to be least effective in non-Hispanic black patients, metformin and rosiglitazone was most effective in girls.

Overall, 517 participants of the original study’s 669 participants are still being followed as part of the TODAY2 trial. They are managed in community practices now and are in their early 20s, on average.

But, less than 10 years down the road from TODAY, the young adults “have problems you’d expect in your grandparents. Target-organ damage is already evident, and serious cardiovascular events are occurring,” Dr. Zeitler said.
 

Cardiovascular complications

The cardiovascular event rate in TODAY 2 was about the same as is seen in older adults with type 1 diabetes. Overall, there were 38 cardiovascular events in 19 patients for an event rate of 6.4/1,000 patients per year. Those events included heart failure, arrhythmia, coronary artery disease or myocardial infarction, deep venous thrombosis, stroke or transient ischemic attack, and vascular insufficiency.

Over that time, the cumulative incidence of elevated LDL cholesterol increased from 3% in the TODAY report to 26% for TODAY2, and for triglycerides, it went from 18% to 35%. The cumulative incidence of hypertension increased from 19% to 55%.
 

Decline renal function

In regard to renal complications, the cumulative incident curve for microalbuminuria went from 8% at baseline to 40% at 12 years, while macroalbuminuria prevalence increased from 1.5% to 11% during the same time. The cumulative incidence of hyperfiltration increased from 12% to 48%. Risk factors for hyperfiltration included female sex, Hispanic ethnicity, loss of glycemic control, and hypertension, although body mass index was actually associated with lower risk.

So far, there have been four renal events in two patients, who both had chronic kidney disease and end-stage renal failure, for an event rate of 0.7/1,000 patients per year.
 

Pregnancy outcomes

Women in the cohort – about two-thirds of the study population – have had high rates of maternal complications, and their offspring also face complications after birth.

There were 306 pregnancies reported, of which there are known outcomes for 53 (TODAY) and 236 (TODAY2). In all, 5% of the total cohort had voluntary elective termination; 9% and 12% of patients, respectively, suffered a miscarriage before 20 weeks; and 4% of pregnancies in the total cohort ended in stillbirth.

Preterm live births more than doubled from 11% to 24%, and full-term deliveries decreased from 62% to 46% in the TODAY2 patients.

In regard to offspring characteristics, average birth weight in the total cohort was just over 4.5 pounds (national average, 7.3 pounds), and the prevalence of very low birth weight more than doubled from 8% to 16% at the 12-year mark. The prevalence of macrosomia was 19% for the cohort, more than double the national average of 8%. In all, 5% and 7% of offspring were small for gestational age, whereas 22% and 26% of offspring were large for gestational age.

Among other complications, respiratory distress occurred in 8% and 14% of offspring, and cardiac anomalies occurred in 10% and 9%, which, although they held steady across the cohorts, were significantly higher than the national average of 1%. Similarly, neonatal hypoglycemia occurred in 17% and 29% of offspring, again, notably higher than the national average of 2%. Offspring outcomes were worse in mothers with loss of glycemic control.

In regard to maternal pregnancy complications, the rate of hospitalization before delivery increased from 25% to 36%; hypertension increased in prevalence from 19% to 36%; and while macroalbuminuria held steady at 9.4%, microalbuminuria increased from 6% to 8%. Thirty-three percent of the TODAY2 cohort had a hemoglobin A_1c level of more than 8%.
 

Retinopathy

Serious eye problems were common, with notable progression seen in diabetic retinopathy in patients who had fundus photos taken in 2011 (TODAY) and 2018 (TODAY2). Among the patients, 86% and 51%, respectively, of 371 patients had no definitive diabetic retinopathy; 14% and 22% of patients had very mild nonproliferative diabetic retinopathy (NPDR); and 0% and 16% of patients had mild NPDR. None of the TODAY patients had early or high-risk proliferative diabetic retinopathy, compared with 3% and 1%, respectively, in TODAY2. Risk factors included loss of glycemic control (hazard ratio, 19.23; 95% confidence interval, 4.62-80.07).

None of the TODAY patients had macular edema, whereas it occurred in 4% of TODAY2 patients. In all, there were 142 adjudicated eye-related events reported for 92 patients, for an event rate of 15.5/1,000 patients per year. The events included NPDR, proliferative diabetic retinopathy, macular edema, cataracts, glaucoma, and vitreous hemorrhage).
 

Neuropathy

The prevalence of diabetic neuropathy also increased over the duration of follow-up, rising to 28%-33% based on Michigan Neuropathy Screening Instrument scores. There were 14 adjudicated events reported for 12 patients (2.4 events/1,000 patients per year), including peripheral diabetic neuropathy, autonomic neuropathy, and diabetic mononeuropathy.

“We’ve had a number of amputations; quite a number of toes are now missing in this group of kids,” Dr. Zeitler said.

There have been five deaths so far: one heart attack, one renal failure, one overwhelming sepsis, one postop cardiac arrest, and a drug overdose.

Dr. Zeitler was the senior author on 2018 updated ADA guidelines for managing youth-onset type 2 diabetes. The recommendations where extensively shaped by the TODAY findings and were more aggressive than those previously put forward, suggesting, among other things, hemoglobin A_1c targets of 6.5%-7%; earlier treatment with insulin; and stricter management of hypertension, dyslipidemia, and proteinuria (Diabetes Care. 2018;41[12]:2648-68).

The National Institute of Diabetes & Kidney disease funded the studies. The presenters reported no relevant disclosures or conflicts of interest.

[email protected]

This article was updated 7/22/19.

SAN FRANCISCO – Type 2 diabetes is much more aggressive in adolescents than in adults, and by the time those with youth-onset diabetes reach their early 20s, they are beset with disease-related complications usually seen in older populations, findings from the RISE and TODAY2 studies have demonstrated.

M. Alexander Otto/Mdedge News

“Additional research is urgently needed to better understand the reasons for this more serious trajectory,” Philip Zeitler, MD, PhD, of Children’s Hospital Colorado, Aurora, said at the annual scientific sessions of the American Diabetes Association. The hope is to identify at-risk children and prevent the disease, but at this point “we don’t know the answer.”

In the meantime, “we are getting more aggressive with bariatric surgery at our center, because nothing else is working as well. It would be nice to move away from that, but these kids are going to die,” he added.

Steven Kahn, MD, of the diabetes Research Center at the University of Washington, Seattle, presented the findings from a comparison of outcomes from the Restoring Insulin Secretion (RISE) studies in adolescents aged 10-19 years and in adults. The RISE Pediatric Medication Study (Diabetes Care. 2018; 41[8]:1717-25) and RISE Adult Medication Study were parallel investigations treatments to preserve or improve beta-cell function.

M. Alexander Otto/MDedge News

“This is the first-ever true comparison of outcomes in youth versus adults,” he said. Both arms had the same design and lab measurements, but the differences in outcomes were “very scary,” he added. “The disease is much more aggressive in youth than in adults.”

Among other things, the RISE youth-versus-adult study compared the outcomes after 3 months of insulin glargine followed by 9 months of metformin, or 12 months of metformin in 132 obese adults and 91 obese adolescents with impaired glucose tolerance or recently diagnosed type 2 diabetes. The treatments were stopped after 12 months, and the participants were reevaluated at 15 months. Hyperglycemic clamps were conducted at baseline, 12 months, and 3 months after treatment cessation (Diabetes. 2019 Jun 9. doi: 10.2337/db19-0299).

In adults, treatment improved insulin sensitivity and beta-cell response, but after treatment cessation, they reverted to baseline by the 15-month evaluation. However, there was no improvement in insulin sensitivity and beta-cell response in adolescents, either during treatment or after cessation, and in fact, they were worse off at 15 months than they had been at baseline, with lower insulin secretion and higher hemoglobin A_1c.

Those stark differences in outcomes between the adolescents and adults were indicative of a more aggressive disease trajectory for younger patients.

Compliance was not the issue, with more than 80% of both adults and children taking more than 80% of their medications, Dr. Kahn said.

He suggested that adolescents might have a different underlying pathology that makes it worse to develop diabetes during puberty, which is already an insulin-resistant state. But, whatever the case, there is an “urgent need” to better understand the differences between adolescents and adults and to find better treatments for younger patients with diabetes, he said.

In regard to using weight loss as a means of treatment or prevention, Dr. Zeitler emphasized that type 2 diabetes in younger patients “occurs in a context of very low socioeconomic status, family dysfunction, and a great deal of stress and [family] illness. It’s often a complex situation and it’s difficult to accomplish effective lifestyle change when families are struggling to have afford quality food, facing challenges of family and neighborhood violence, and working multiple jobs.”

The RISE findings of a more aggressive deterioration in beta-cell function for younger patients were reflected in outcomes in the TODAY2 study, which found that adolescents who are diagnosed with type 2 diabetes face severe renal, cardiovascular, eye, and nerve complications by the time they reach their early 20s.

TODAY2 was an 8-year follow-up to the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial published in 2012 (N Engl J Med. 2012;366:2247-56). Data from the original study of patients aged 10-17 years with type 2 diabetes showed that after a roughly 4-year follow-up, almost half of all participants had experienced loss of glycemic control on their original treatment assignment, a rate much higher than that reported in adults. Metformin plus rosiglitazone was superior to metformin alone in maintaining durable glycemic control and metformin plus an intensive lifestyle intervention was intermediate to the other groups, but not significantly different from them. In addition, metformin alone was found to be least effective in non-Hispanic black patients, metformin and rosiglitazone was most effective in girls.

Overall, 517 participants of the original study’s 669 participants are still being followed as part of the TODAY2 trial. They are managed in community practices now and are in their early 20s, on average.

But, less than 10 years down the road from TODAY, the young adults “have problems you’d expect in your grandparents. Target-organ damage is already evident, and serious cardiovascular events are occurring,” Dr. Zeitler said.
 

Cardiovascular complications

The cardiovascular event rate in TODAY 2 was about the same as is seen in older adults with type 1 diabetes. Overall, there were 38 cardiovascular events in 19 patients for an event rate of 6.4/1,000 patients per year. Those events included heart failure, arrhythmia, coronary artery disease or myocardial infarction, deep venous thrombosis, stroke or transient ischemic attack, and vascular insufficiency.

Over that time, the cumulative incidence of elevated LDL cholesterol increased from 3% in the TODAY report to 26% for TODAY2, and for triglycerides, it went from 18% to 35%. The cumulative incidence of hypertension increased from 19% to 55%.
 

Decline renal function

In regard to renal complications, the cumulative incident curve for microalbuminuria went from 8% at baseline to 40% at 12 years, while macroalbuminuria prevalence increased from 1.5% to 11% during the same time. The cumulative incidence of hyperfiltration increased from 12% to 48%. Risk factors for hyperfiltration included female sex, Hispanic ethnicity, loss of glycemic control, and hypertension, although body mass index was actually associated with lower risk.

So far, there have been four renal events in two patients, who both had chronic kidney disease and end-stage renal failure, for an event rate of 0.7/1,000 patients per year.
 

Pregnancy outcomes

Women in the cohort – about two-thirds of the study population – have had high rates of maternal complications, and their offspring also face complications after birth.

There were 306 pregnancies reported, of which there are known outcomes for 53 (TODAY) and 236 (TODAY2). In all, 5% of the total cohort had voluntary elective termination; 9% and 12% of patients, respectively, suffered a miscarriage before 20 weeks; and 4% of pregnancies in the total cohort ended in stillbirth.

Preterm live births more than doubled from 11% to 24%, and full-term deliveries decreased from 62% to 46% in the TODAY2 patients.

In regard to offspring characteristics, average birth weight in the total cohort was just over 4.5 pounds (national average, 7.3 pounds), and the prevalence of very low birth weight more than doubled from 8% to 16% at the 12-year mark. The prevalence of macrosomia was 19% for the cohort, more than double the national average of 8%. In all, 5% and 7% of offspring were small for gestational age, whereas 22% and 26% of offspring were large for gestational age.

Among other complications, respiratory distress occurred in 8% and 14% of offspring, and cardiac anomalies occurred in 10% and 9%, which, although they held steady across the cohorts, were significantly higher than the national average of 1%. Similarly, neonatal hypoglycemia occurred in 17% and 29% of offspring, again, notably higher than the national average of 2%. Offspring outcomes were worse in mothers with loss of glycemic control.

In regard to maternal pregnancy complications, the rate of hospitalization before delivery increased from 25% to 36%; hypertension increased in prevalence from 19% to 36%; and while macroalbuminuria held steady at 9.4%, microalbuminuria increased from 6% to 8%. Thirty-three percent of the TODAY2 cohort had a hemoglobin A_1c level of more than 8%.
 

Retinopathy

Serious eye problems were common, with notable progression seen in diabetic retinopathy in patients who had fundus photos taken in 2011 (TODAY) and 2018 (TODAY2). Among the patients, 86% and 51%, respectively, of 371 patients had no definitive diabetic retinopathy; 14% and 22% of patients had very mild nonproliferative diabetic retinopathy (NPDR); and 0% and 16% of patients had mild NPDR. None of the TODAY patients had early or high-risk proliferative diabetic retinopathy, compared with 3% and 1%, respectively, in TODAY2. Risk factors included loss of glycemic control (hazard ratio, 19.23; 95% confidence interval, 4.62-80.07).

None of the TODAY patients had macular edema, whereas it occurred in 4% of TODAY2 patients. In all, there were 142 adjudicated eye-related events reported for 92 patients, for an event rate of 15.5/1,000 patients per year. The events included NPDR, proliferative diabetic retinopathy, macular edema, cataracts, glaucoma, and vitreous hemorrhage).
 

Neuropathy

The prevalence of diabetic neuropathy also increased over the duration of follow-up, rising to 28%-33% based on Michigan Neuropathy Screening Instrument scores. There were 14 adjudicated events reported for 12 patients (2.4 events/1,000 patients per year), including peripheral diabetic neuropathy, autonomic neuropathy, and diabetic mononeuropathy.

“We’ve had a number of amputations; quite a number of toes are now missing in this group of kids,” Dr. Zeitler said.

There have been five deaths so far: one heart attack, one renal failure, one overwhelming sepsis, one postop cardiac arrest, and a drug overdose.

Dr. Zeitler was the senior author on 2018 updated ADA guidelines for managing youth-onset type 2 diabetes. The recommendations where extensively shaped by the TODAY findings and were more aggressive than those previously put forward, suggesting, among other things, hemoglobin A_1c targets of 6.5%-7%; earlier treatment with insulin; and stricter management of hypertension, dyslipidemia, and proteinuria (Diabetes Care. 2018;41[12]:2648-68).

The National Institute of Diabetes & Kidney disease funded the studies. The presenters reported no relevant disclosures or conflicts of interest.

[email protected]

This article was updated 7/22/19.

SAN FRANCISCO – Type 2 diabetes is much more aggressive in adolescents than in adults, and by the time those with youth-onset diabetes reach their early 20s, they are beset with disease-related complications usually seen in older populations, findings from the RISE and TODAY2 studies have demonstrated.

M. Alexander Otto/Mdedge News

“Additional research is urgently needed to better understand the reasons for this more serious trajectory,” Philip Zeitler, MD, PhD, of Children’s Hospital Colorado, Aurora, said at the annual scientific sessions of the American Diabetes Association. The hope is to identify at-risk children and prevent the disease, but at this point “we don’t know the answer.”

In the meantime, “we are getting more aggressive with bariatric surgery at our center, because nothing else is working as well. It would be nice to move away from that, but these kids are going to die,” he added.

Steven Kahn, MD, of the diabetes Research Center at the University of Washington, Seattle, presented the findings from a comparison of outcomes from the Restoring Insulin Secretion (RISE) studies in adolescents aged 10-19 years and in adults. The RISE Pediatric Medication Study (Diabetes Care. 2018; 41[8]:1717-25) and RISE Adult Medication Study were parallel investigations treatments to preserve or improve beta-cell function.

M. Alexander Otto/MDedge News

“This is the first-ever true comparison of outcomes in youth versus adults,” he said. Both arms had the same design and lab measurements, but the differences in outcomes were “very scary,” he added. “The disease is much more aggressive in youth than in adults.”

Among other things, the RISE youth-versus-adult study compared the outcomes after 3 months of insulin glargine followed by 9 months of metformin, or 12 months of metformin in 132 obese adults and 91 obese adolescents with impaired glucose tolerance or recently diagnosed type 2 diabetes. The treatments were stopped after 12 months, and the participants were reevaluated at 15 months. Hyperglycemic clamps were conducted at baseline, 12 months, and 3 months after treatment cessation (Diabetes. 2019 Jun 9. doi: 10.2337/db19-0299).

In adults, treatment improved insulin sensitivity and beta-cell response, but after treatment cessation, they reverted to baseline by the 15-month evaluation. However, there was no improvement in insulin sensitivity and beta-cell response in adolescents, either during treatment or after cessation, and in fact, they were worse off at 15 months than they had been at baseline, with lower insulin secretion and higher hemoglobin A_1c.

Those stark differences in outcomes between the adolescents and adults were indicative of a more aggressive disease trajectory for younger patients.

Compliance was not the issue, with more than 80% of both adults and children taking more than 80% of their medications, Dr. Kahn said.

He suggested that adolescents might have a different underlying pathology that makes it worse to develop diabetes during puberty, which is already an insulin-resistant state. But, whatever the case, there is an “urgent need” to better understand the differences between adolescents and adults and to find better treatments for younger patients with diabetes, he said.

In regard to using weight loss as a means of treatment or prevention, Dr. Zeitler emphasized that type 2 diabetes in younger patients “occurs in a context of very low socioeconomic status, family dysfunction, and a great deal of stress and [family] illness. It’s often a complex situation and it’s difficult to accomplish effective lifestyle change when families are struggling to have afford quality food, facing challenges of family and neighborhood violence, and working multiple jobs.”

The RISE findings of a more aggressive deterioration in beta-cell function for younger patients were reflected in outcomes in the TODAY2 study, which found that adolescents who are diagnosed with type 2 diabetes face severe renal, cardiovascular, eye, and nerve complications by the time they reach their early 20s.

TODAY2 was an 8-year follow-up to the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial published in 2012 (N Engl J Med. 2012;366:2247-56). Data from the original study of patients aged 10-17 years with type 2 diabetes showed that after a roughly 4-year follow-up, almost half of all participants had experienced loss of glycemic control on their original treatment assignment, a rate much higher than that reported in adults. Metformin plus rosiglitazone was superior to metformin alone in maintaining durable glycemic control and metformin plus an intensive lifestyle intervention was intermediate to the other groups, but not significantly different from them. In addition, metformin alone was found to be least effective in non-Hispanic black patients, metformin and rosiglitazone was most effective in girls.

Overall, 517 participants of the original study’s 669 participants are still being followed as part of the TODAY2 trial. They are managed in community practices now and are in their early 20s, on average.

But, less than 10 years down the road from TODAY, the young adults “have problems you’d expect in your grandparents. Target-organ damage is already evident, and serious cardiovascular events are occurring,” Dr. Zeitler said.
 

Cardiovascular complications

The cardiovascular event rate in TODAY 2 was about the same as is seen in older adults with type 1 diabetes. Overall, there were 38 cardiovascular events in 19 patients for an event rate of 6.4/1,000 patients per year. Those events included heart failure, arrhythmia, coronary artery disease or myocardial infarction, deep venous thrombosis, stroke or transient ischemic attack, and vascular insufficiency.

Over that time, the cumulative incidence of elevated LDL cholesterol increased from 3% in the TODAY report to 26% for TODAY2, and for triglycerides, it went from 18% to 35%. The cumulative incidence of hypertension increased from 19% to 55%.
 

Decline renal function

In regard to renal complications, the cumulative incident curve for microalbuminuria went from 8% at baseline to 40% at 12 years, while macroalbuminuria prevalence increased from 1.5% to 11% during the same time. The cumulative incidence of hyperfiltration increased from 12% to 48%. Risk factors for hyperfiltration included female sex, Hispanic ethnicity, loss of glycemic control, and hypertension, although body mass index was actually associated with lower risk.

So far, there have been four renal events in two patients, who both had chronic kidney disease and end-stage renal failure, for an event rate of 0.7/1,000 patients per year.
 

Pregnancy outcomes

Women in the cohort – about two-thirds of the study population – have had high rates of maternal complications, and their offspring also face complications after birth.

There were 306 pregnancies reported, of which there are known outcomes for 53 (TODAY) and 236 (TODAY2). In all, 5% of the total cohort had voluntary elective termination; 9% and 12% of patients, respectively, suffered a miscarriage before 20 weeks; and 4% of pregnancies in the total cohort ended in stillbirth.

Preterm live births more than doubled from 11% to 24%, and full-term deliveries decreased from 62% to 46% in the TODAY2 patients.

In regard to offspring characteristics, average birth weight in the total cohort was just over 4.5 pounds (national average, 7.3 pounds), and the prevalence of very low birth weight more than doubled from 8% to 16% at the 12-year mark. The prevalence of macrosomia was 19% for the cohort, more than double the national average of 8%. In all, 5% and 7% of offspring were small for gestational age, whereas 22% and 26% of offspring were large for gestational age.

Among other complications, respiratory distress occurred in 8% and 14% of offspring, and cardiac anomalies occurred in 10% and 9%, which, although they held steady across the cohorts, were significantly higher than the national average of 1%. Similarly, neonatal hypoglycemia occurred in 17% and 29% of offspring, again, notably higher than the national average of 2%. Offspring outcomes were worse in mothers with loss of glycemic control.

In regard to maternal pregnancy complications, the rate of hospitalization before delivery increased from 25% to 36%; hypertension increased in prevalence from 19% to 36%; and while macroalbuminuria held steady at 9.4%, microalbuminuria increased from 6% to 8%. Thirty-three percent of the TODAY2 cohort had a hemoglobin A_1c level of more than 8%.
 

Retinopathy

Serious eye problems were common, with notable progression seen in diabetic retinopathy in patients who had fundus photos taken in 2011 (TODAY) and 2018 (TODAY2). Among the patients, 86% and 51%, respectively, of 371 patients had no definitive diabetic retinopathy; 14% and 22% of patients had very mild nonproliferative diabetic retinopathy (NPDR); and 0% and 16% of patients had mild NPDR. None of the TODAY patients had early or high-risk proliferative diabetic retinopathy, compared with 3% and 1%, respectively, in TODAY2. Risk factors included loss of glycemic control (hazard ratio, 19.23; 95% confidence interval, 4.62-80.07).

None of the TODAY patients had macular edema, whereas it occurred in 4% of TODAY2 patients. In all, there were 142 adjudicated eye-related events reported for 92 patients, for an event rate of 15.5/1,000 patients per year. The events included NPDR, proliferative diabetic retinopathy, macular edema, cataracts, glaucoma, and vitreous hemorrhage).
 

Neuropathy

The prevalence of diabetic neuropathy also increased over the duration of follow-up, rising to 28%-33% based on Michigan Neuropathy Screening Instrument scores. There were 14 adjudicated events reported for 12 patients (2.4 events/1,000 patients per year), including peripheral diabetic neuropathy, autonomic neuropathy, and diabetic mononeuropathy.

“We’ve had a number of amputations; quite a number of toes are now missing in this group of kids,” Dr. Zeitler said.

There have been five deaths so far: one heart attack, one renal failure, one overwhelming sepsis, one postop cardiac arrest, and a drug overdose.

Dr. Zeitler was the senior author on 2018 updated ADA guidelines for managing youth-onset type 2 diabetes. The recommendations where extensively shaped by the TODAY findings and were more aggressive than those previously put forward, suggesting, among other things, hemoglobin A_1c targets of 6.5%-7%; earlier treatment with insulin; and stricter management of hypertension, dyslipidemia, and proteinuria (Diabetes Care. 2018;41[12]:2648-68).

The National Institute of Diabetes & Kidney disease funded the studies. The presenters reported no relevant disclosures or conflicts of interest.

[email protected]

This article was updated 7/22/19.

LUGANO, Switzerland – Adding the immunomodulator lenalidomide (Revlimid) to standard chemotherapy for patients with newly diagnosed ABC-type diffuse large B-cell lymphoma (DLBCL) – the so-called R2-CHOP regimen – did not significantly improve either progression-free or overall survival, compared with R-CHOP alone, investigators in the phase 3 ROBUST trial found.

Among 570 patients with activated B-cell (ABC) type DLBCL followed for a median of 27.1 months, median progression-free survival (PFS) – the primary endpoint – had not been reached either for patients randomized to R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone) plus lenalidomide (R2-CHOP) or R-CHOP plus placebo.

The 1-year and 2-year PFS rate with R2-CHOP was 77%, compared with 75% for R-CHOP, and 2-year PFS rates were 67% and 64%, respectively, and neither comparison was statistically significant reported Umberto Vitolo, MD, from the Citta della Salute e della Scienzia Hospital and University in Turin, Italy.“The future direction is that promising preclinical data with next-generation immunomodulatory agents will be evaluated in future DLBCL clinical trials,” he said at the International Conference on Malignant Lymphoma.

The ROBUST trial is the latest in a long line of studies that failed to show improvement in outcomes with the addition of a novel agent to R-CHOP.

The rationale for adding lenalidomide to R-CHOP came from in-vitro studies showing antiproliferative and immunomodulatory action of lenalidomide against DLBCL, as well as two proof-of-concept clinical studies (REAL07 and MC078E) indicating efficacy against non–germinal center–like B (GCB) type DLBCL, Dr. Vitolo said.

In the ROBUST trial, investigators across 257 global sites enrolled 570 patients with ABC-type DLBCL, stratified them by International Prognostic Index (IPI) score (2 vs. 3 or greater), bulky disease (less than 7 cm vs. 7 cm or more), and age (younger than 65 years vs. 65 years and older) and randomly assigned them to receive R-CHOP with either oral lenalidomide 15 mg or placebo daily on days 1-14 of each 21-day cycle for six cycles.

All patients were required to have neutropenia prophylaxis according to local practice, with either a granulocyte- or granulocyte-macrophage colony-stimulating factor.

The efficacy analysis was by intention-to-treat and included 285 patients in each arm.

The investigators found no significant difference in the primary endpoint of PFS. Overall response rates (ORR) and complete response (CR) rates were high in both arms. The ORR was 91% in each arm, and the CR rate was 69% for R2-CHOP and 65% for R-CHOP.

Event-free survival (EFS) – a composite of first disease progression, death, or relapse after CR or start of second-line therapy – also did not differ significantly between the groups. The 1-year and 2-year EFS rates were 68% vs. 71% and 59% vs. 61%, respectively. The median EFS was not reached in either arm.

Similarly, overall survival did not differ between the groups. At 48 months of follow-up, 57 patients in the R2-CHOP arm and 62 patients in the R-CHOP arm had died. Respective 1- and 2-year overall survival rates were 91% vs. 90%, and 79% vs. 80%.

In the safety analysis, which included 283 patients in the R2-CHOP arm and 284 in the placebo/R-CHOP arm, there were no new safety signals observed. In all, 78% of patients in the lenalidomide arm and 71% in the placebo arm had at least one grade 3 or greater adverse events. The most common adverse events were hematologic, including neutropenia, febrile neutropenia, anemia, thrombocytopenia, and leukopenia.

The ROBUST study was funded by Celgene. Dr. Vitolo reported consulting and speaker’s bureau fees and research funding from the company.

SOURCE: Vitolo U et al. 15-ICML, Abstract 005.

LUGANO, Switzerland – Adding the immunomodulator lenalidomide (Revlimid) to standard chemotherapy for patients with newly diagnosed ABC-type diffuse large B-cell lymphoma (DLBCL) – the so-called R2-CHOP regimen – did not significantly improve either progression-free or overall survival, compared with R-CHOP alone, investigators in the phase 3 ROBUST trial found.

Among 570 patients with activated B-cell (ABC) type DLBCL followed for a median of 27.1 months, median progression-free survival (PFS) – the primary endpoint – had not been reached either for patients randomized to R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone) plus lenalidomide (R2-CHOP) or R-CHOP plus placebo.

The 1-year and 2-year PFS rate with R2-CHOP was 77%, compared with 75% for R-CHOP, and 2-year PFS rates were 67% and 64%, respectively, and neither comparison was statistically significant reported Umberto Vitolo, MD, from the Citta della Salute e della Scienzia Hospital and University in Turin, Italy.“The future direction is that promising preclinical data with next-generation immunomodulatory agents will be evaluated in future DLBCL clinical trials,” he said at the International Conference on Malignant Lymphoma.

The ROBUST trial is the latest in a long line of studies that failed to show improvement in outcomes with the addition of a novel agent to R-CHOP.

The rationale for adding lenalidomide to R-CHOP came from in-vitro studies showing antiproliferative and immunomodulatory action of lenalidomide against DLBCL, as well as two proof-of-concept clinical studies (REAL07 and MC078E) indicating efficacy against non–germinal center–like B (GCB) type DLBCL, Dr. Vitolo said.

In the ROBUST trial, investigators across 257 global sites enrolled 570 patients with ABC-type DLBCL, stratified them by International Prognostic Index (IPI) score (2 vs. 3 or greater), bulky disease (less than 7 cm vs. 7 cm or more), and age (younger than 65 years vs. 65 years and older) and randomly assigned them to receive R-CHOP with either oral lenalidomide 15 mg or placebo daily on days 1-14 of each 21-day cycle for six cycles.

All patients were required to have neutropenia prophylaxis according to local practice, with either a granulocyte- or granulocyte-macrophage colony-stimulating factor.

The efficacy analysis was by intention-to-treat and included 285 patients in each arm.

The investigators found no significant difference in the primary endpoint of PFS. Overall response rates (ORR) and complete response (CR) rates were high in both arms. The ORR was 91% in each arm, and the CR rate was 69% for R2-CHOP and 65% for R-CHOP.

Event-free survival (EFS) – a composite of first disease progression, death, or relapse after CR or start of second-line therapy – also did not differ significantly between the groups. The 1-year and 2-year EFS rates were 68% vs. 71% and 59% vs. 61%, respectively. The median EFS was not reached in either arm.

Similarly, overall survival did not differ between the groups. At 48 months of follow-up, 57 patients in the R2-CHOP arm and 62 patients in the R-CHOP arm had died. Respective 1- and 2-year overall survival rates were 91% vs. 90%, and 79% vs. 80%.

In the safety analysis, which included 283 patients in the R2-CHOP arm and 284 in the placebo/R-CHOP arm, there were no new safety signals observed. In all, 78% of patients in the lenalidomide arm and 71% in the placebo arm had at least one grade 3 or greater adverse events. The most common adverse events were hematologic, including neutropenia, febrile neutropenia, anemia, thrombocytopenia, and leukopenia.

The ROBUST study was funded by Celgene. Dr. Vitolo reported consulting and speaker’s bureau fees and research funding from the company.

SOURCE: Vitolo U et al. 15-ICML, Abstract 005.

LUGANO, Switzerland – Adding the immunomodulator lenalidomide (Revlimid) to standard chemotherapy for patients with newly diagnosed ABC-type diffuse large B-cell lymphoma (DLBCL) – the so-called R2-CHOP regimen – did not significantly improve either progression-free or overall survival, compared with R-CHOP alone, investigators in the phase 3 ROBUST trial found.

Among 570 patients with activated B-cell (ABC) type DLBCL followed for a median of 27.1 months, median progression-free survival (PFS) – the primary endpoint – had not been reached either for patients randomized to R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone) plus lenalidomide (R2-CHOP) or R-CHOP plus placebo.

The 1-year and 2-year PFS rate with R2-CHOP was 77%, compared with 75% for R-CHOP, and 2-year PFS rates were 67% and 64%, respectively, and neither comparison was statistically significant reported Umberto Vitolo, MD, from the Citta della Salute e della Scienzia Hospital and University in Turin, Italy.“The future direction is that promising preclinical data with next-generation immunomodulatory agents will be evaluated in future DLBCL clinical trials,” he said at the International Conference on Malignant Lymphoma.

The ROBUST trial is the latest in a long line of studies that failed to show improvement in outcomes with the addition of a novel agent to R-CHOP.

The rationale for adding lenalidomide to R-CHOP came from in-vitro studies showing antiproliferative and immunomodulatory action of lenalidomide against DLBCL, as well as two proof-of-concept clinical studies (REAL07 and MC078E) indicating efficacy against non–germinal center–like B (GCB) type DLBCL, Dr. Vitolo said.

In the ROBUST trial, investigators across 257 global sites enrolled 570 patients with ABC-type DLBCL, stratified them by International Prognostic Index (IPI) score (2 vs. 3 or greater), bulky disease (less than 7 cm vs. 7 cm or more), and age (younger than 65 years vs. 65 years and older) and randomly assigned them to receive R-CHOP with either oral lenalidomide 15 mg or placebo daily on days 1-14 of each 21-day cycle for six cycles.

All patients were required to have neutropenia prophylaxis according to local practice, with either a granulocyte- or granulocyte-macrophage colony-stimulating factor.

The efficacy analysis was by intention-to-treat and included 285 patients in each arm.

The investigators found no significant difference in the primary endpoint of PFS. Overall response rates (ORR) and complete response (CR) rates were high in both arms. The ORR was 91% in each arm, and the CR rate was 69% for R2-CHOP and 65% for R-CHOP.

Event-free survival (EFS) – a composite of first disease progression, death, or relapse after CR or start of second-line therapy – also did not differ significantly between the groups. The 1-year and 2-year EFS rates were 68% vs. 71% and 59% vs. 61%, respectively. The median EFS was not reached in either arm.

Similarly, overall survival did not differ between the groups. At 48 months of follow-up, 57 patients in the R2-CHOP arm and 62 patients in the R-CHOP arm had died. Respective 1- and 2-year overall survival rates were 91% vs. 90%, and 79% vs. 80%.

In the safety analysis, which included 283 patients in the R2-CHOP arm and 284 in the placebo/R-CHOP arm, there were no new safety signals observed. In all, 78% of patients in the lenalidomide arm and 71% in the placebo arm had at least one grade 3 or greater adverse events. The most common adverse events were hematologic, including neutropenia, febrile neutropenia, anemia, thrombocytopenia, and leukopenia.

The ROBUST study was funded by Celgene. Dr. Vitolo reported consulting and speaker’s bureau fees and research funding from the company.

SOURCE: Vitolo U et al. 15-ICML, Abstract 005.

Higher levels of eicosapentaenoic acid, a type of omega-3 polyunsaturated fatty acid, were associated with a significantly reduced risk of heart failure in a large, multi-ethnic cohort of adults in the United States.

Despite the potential benefits of omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for heart health, their use has been controversial, although data in a mouse model showed that dietary EPA was protective against heart failure, wrote Robert C. Block, MD, of the University of Rochester (N.Y.), and colleagues. Their report is in the Journal of the American College of Cardiology.

To examine the impact of EPA on heart failure in humans, the researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA), a longitudinal cohort study of U.S. adults, including those who are African American, Hispanic, Asian, and white.

The researchers included 6,562 MESA participants aged 45-84 years from six communities. Participants underwent a baseline exam between July 2000 and July 2002 that included phospholipid measurements used to identify plasma EPA percentage, and they completed study visits approximately every other year for a median follow-up of 13 years.

A total of 292 heart failure events occurred during the follow-up period: 128 with reduced ejection fraction (EF less than 45%), 110 with preserved ejection fraction (EF at least 45%), and 54 with unknown EF status.

The percent EPA for individuals without heart failure was significantly higher compared with those with heart failure (0.76% vs. 0.69%, P =.005). The association remained significant after the researchers controlled for age, sex, race, body mass index, smoking, diabetes, blood pressure, lipids and lipid-lowering drugs, albuminuria, and the lead fatty acid (defined as the fatty acid with the largest in-cluster correlation).


An EPA level greater than 2.5% was considered sufficient to prevent heart failure based on prior definitions. A total of 73% of the participants had insufficient EPA (less than 1.0%), 2.4% had marginal levels (1.0%-2.5%), and 4.5% had sufficient levels. However, given that EPA levels can be easily and safely increased with the consumption of seafood or fish oil capsules, increasing EPA is a feasible heart failure prevention strategy, the researchers said.

The study included 2,532 white, 1,794 black, 1,442 Hispanic, and 794 Chinese participants. Overall, the fewest Hispanic participants met the criteria for sufficient EPA (1.4%), followed by black (4.4%), white (4.9%), and Chinese participants (9.8%).

The study findings were limited by several factors, including relatively few participants with preserved ejection fractions and sufficient EPA levels, as well as the inability to account for changes in omega-3 levels and other risk factors over time, the researchers noted.

“We consider this study to strongly determine a benefit of EPA exists, but insufficient to determine whether a threshold for %EPA exists near 3%,” they said. They proposed a follow-up study including individuals with higher levels of EPA to better detect a protective effect.

Lead author Dr. Block had no financial conflicts to disclose. Several coauthors received honoraria from Amarin Pharmaceuticals. The study was funded in part by the National Heart, Lung, and Blood Institute.

Higher levels of eicosapentaenoic acid, a type of omega-3 polyunsaturated fatty acid, were associated with a significantly reduced risk of heart failure in a large, multi-ethnic cohort of adults in the United States.

Despite the potential benefits of omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for heart health, their use has been controversial, although data in a mouse model showed that dietary EPA was protective against heart failure, wrote Robert C. Block, MD, of the University of Rochester (N.Y.), and colleagues. Their report is in the Journal of the American College of Cardiology.

To examine the impact of EPA on heart failure in humans, the researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA), a longitudinal cohort study of U.S. adults, including those who are African American, Hispanic, Asian, and white.

The researchers included 6,562 MESA participants aged 45-84 years from six communities. Participants underwent a baseline exam between July 2000 and July 2002 that included phospholipid measurements used to identify plasma EPA percentage, and they completed study visits approximately every other year for a median follow-up of 13 years.

A total of 292 heart failure events occurred during the follow-up period: 128 with reduced ejection fraction (EF less than 45%), 110 with preserved ejection fraction (EF at least 45%), and 54 with unknown EF status.

The percent EPA for individuals without heart failure was significantly higher compared with those with heart failure (0.76% vs. 0.69%, P =.005). The association remained significant after the researchers controlled for age, sex, race, body mass index, smoking, diabetes, blood pressure, lipids and lipid-lowering drugs, albuminuria, and the lead fatty acid (defined as the fatty acid with the largest in-cluster correlation).


An EPA level greater than 2.5% was considered sufficient to prevent heart failure based on prior definitions. A total of 73% of the participants had insufficient EPA (less than 1.0%), 2.4% had marginal levels (1.0%-2.5%), and 4.5% had sufficient levels. However, given that EPA levels can be easily and safely increased with the consumption of seafood or fish oil capsules, increasing EPA is a feasible heart failure prevention strategy, the researchers said.

The study included 2,532 white, 1,794 black, 1,442 Hispanic, and 794 Chinese participants. Overall, the fewest Hispanic participants met the criteria for sufficient EPA (1.4%), followed by black (4.4%), white (4.9%), and Chinese participants (9.8%).

The study findings were limited by several factors, including relatively few participants with preserved ejection fractions and sufficient EPA levels, as well as the inability to account for changes in omega-3 levels and other risk factors over time, the researchers noted.

“We consider this study to strongly determine a benefit of EPA exists, but insufficient to determine whether a threshold for %EPA exists near 3%,” they said. They proposed a follow-up study including individuals with higher levels of EPA to better detect a protective effect.

Lead author Dr. Block had no financial conflicts to disclose. Several coauthors received honoraria from Amarin Pharmaceuticals. The study was funded in part by the National Heart, Lung, and Blood Institute.

Higher levels of eicosapentaenoic acid, a type of omega-3 polyunsaturated fatty acid, were associated with a significantly reduced risk of heart failure in a large, multi-ethnic cohort of adults in the United States.

Despite the potential benefits of omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for heart health, their use has been controversial, although data in a mouse model showed that dietary EPA was protective against heart failure, wrote Robert C. Block, MD, of the University of Rochester (N.Y.), and colleagues. Their report is in the Journal of the American College of Cardiology.

To examine the impact of EPA on heart failure in humans, the researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA), a longitudinal cohort study of U.S. adults, including those who are African American, Hispanic, Asian, and white.

The researchers included 6,562 MESA participants aged 45-84 years from six communities. Participants underwent a baseline exam between July 2000 and July 2002 that included phospholipid measurements used to identify plasma EPA percentage, and they completed study visits approximately every other year for a median follow-up of 13 years.

A total of 292 heart failure events occurred during the follow-up period: 128 with reduced ejection fraction (EF less than 45%), 110 with preserved ejection fraction (EF at least 45%), and 54 with unknown EF status.

The percent EPA for individuals without heart failure was significantly higher compared with those with heart failure (0.76% vs. 0.69%, P =.005). The association remained significant after the researchers controlled for age, sex, race, body mass index, smoking, diabetes, blood pressure, lipids and lipid-lowering drugs, albuminuria, and the lead fatty acid (defined as the fatty acid with the largest in-cluster correlation).


An EPA level greater than 2.5% was considered sufficient to prevent heart failure based on prior definitions. A total of 73% of the participants had insufficient EPA (less than 1.0%), 2.4% had marginal levels (1.0%-2.5%), and 4.5% had sufficient levels. However, given that EPA levels can be easily and safely increased with the consumption of seafood or fish oil capsules, increasing EPA is a feasible heart failure prevention strategy, the researchers said.

The study included 2,532 white, 1,794 black, 1,442 Hispanic, and 794 Chinese participants. Overall, the fewest Hispanic participants met the criteria for sufficient EPA (1.4%), followed by black (4.4%), white (4.9%), and Chinese participants (9.8%).

The study findings were limited by several factors, including relatively few participants with preserved ejection fractions and sufficient EPA levels, as well as the inability to account for changes in omega-3 levels and other risk factors over time, the researchers noted.

“We consider this study to strongly determine a benefit of EPA exists, but insufficient to determine whether a threshold for %EPA exists near 3%,” they said. They proposed a follow-up study including individuals with higher levels of EPA to better detect a protective effect.

Lead author Dr. Block had no financial conflicts to disclose. Several coauthors received honoraria from Amarin Pharmaceuticals. The study was funded in part by the National Heart, Lung, and Blood Institute.

Louisiana physicians who treat Medicaid patients for hepatitis C will see less administrative burden under an arrangement approved by the Centers for Medicare & Medicaid Services.

Dynamic Graphics/Thinkstockphotos

Beginning July 15, physicians will no longer have to seek prior authorization or preauthorization to prescribe the authorized generic version of Epclusa (sofosbuvir/velpatasvir) to any Medicaid patient with hepatitis C. There will be no forms to file.

The change comes as part of a supplemental rebate agreement approved June 26 by CMS. That same day, Louisiana announced a deal with Asegua Therapeutics, a wholly owned subsidiary of Epclusa maker Gilead, that essentially caps the annual cost to the state for treating hepatitis C in incarcerated patients and Medicaid recipients.

State officials estimate about 39,000 Louisianans fit those criteria; the goal of the program is to cure at least 31,000 of them by the time the 5-year agreement expires.

“This new model has the potential to save many lives and improve the health of our citizens,” Louisiana Gov. John Bel Edwards (D) said in a statement. “Asegua was willing to come to the table to work with us to help Louisiana residents and we are pleased to initiate this 5-year partnership. Ultimately our goal is to eliminate this disease in Louisiana, and we have taken a big step forward in that effort.”

The agreement was designed to change very little in terms of the mechanics of how Medicaid managed care organizations, which cover most of the state’s Medicaid population and handle coverage and claims. The biggest change is that, when a spending cap is reached, Asegua will rebate 100% excess costs to the state. Louisiana officials did not disclose what the annual financial caps were as part of the agreement.

“We really thought it was important to leave the system – as much as possible – intact because we think that is going to make us most successful,” Alex Billioux, MD, of the Louisiana Department of Health said in an interview. “We think it leverages existing patient relationships and existing [Medicaid managed care organization] care management responsibilities.”

He added that, by keeping current processes unchanged, “it takes what is an otherwise very complicated arrangement with the state and makes it a little simpler.”

Patients will see no change in terms of copayments for the approved generic topping out at $3 depending on income level as they would have prior to the agreement. The biggest difference for them is that “people who couldn’t be treated are now going to have access to those prescriptions,” Dr. Billioux said.

Some cautious optimism surrounds this kind of arrangement and the potential effect it can have on the affected population.

“Innovation geared to improve access to hepatitis C treatment is critical, particularly in areas like Louisiana where treatment rates for Medicaid patients have been very low,” Robert Brown, MD, member of the American Liver Foundation’s National Medical Advisory Committee and hepatologist at Weill Cornell Medical College, New York, said. “If we can enhance patient access to treatment, we know we will improve health outcomes. However, it is too early to tell if this innovation will be a success. At the end of the day, the number of additional patients cured will determine if this was the right approach.”

Visit the AGA GI Patient Center for information to share with your patients about hepatitis C at https://www.gastro.org/practice-guidance/gi-patient-center/topic/hepatitis-c-hcv

[email protected]

Louisiana physicians who treat Medicaid patients for hepatitis C will see less administrative burden under an arrangement approved by the Centers for Medicare & Medicaid Services.

Dynamic Graphics/Thinkstockphotos

Beginning July 15, physicians will no longer have to seek prior authorization or preauthorization to prescribe the authorized generic version of Epclusa (sofosbuvir/velpatasvir) to any Medicaid patient with hepatitis C. There will be no forms to file.

The change comes as part of a supplemental rebate agreement approved June 26 by CMS. That same day, Louisiana announced a deal with Asegua Therapeutics, a wholly owned subsidiary of Epclusa maker Gilead, that essentially caps the annual cost to the state for treating hepatitis C in incarcerated patients and Medicaid recipients.

State officials estimate about 39,000 Louisianans fit those criteria; the goal of the program is to cure at least 31,000 of them by the time the 5-year agreement expires.

“This new model has the potential to save many lives and improve the health of our citizens,” Louisiana Gov. John Bel Edwards (D) said in a statement. “Asegua was willing to come to the table to work with us to help Louisiana residents and we are pleased to initiate this 5-year partnership. Ultimately our goal is to eliminate this disease in Louisiana, and we have taken a big step forward in that effort.”

The agreement was designed to change very little in terms of the mechanics of how Medicaid managed care organizations, which cover most of the state’s Medicaid population and handle coverage and claims. The biggest change is that, when a spending cap is reached, Asegua will rebate 100% excess costs to the state. Louisiana officials did not disclose what the annual financial caps were as part of the agreement.

“We really thought it was important to leave the system – as much as possible – intact because we think that is going to make us most successful,” Alex Billioux, MD, of the Louisiana Department of Health said in an interview. “We think it leverages existing patient relationships and existing [Medicaid managed care organization] care management responsibilities.”

He added that, by keeping current processes unchanged, “it takes what is an otherwise very complicated arrangement with the state and makes it a little simpler.”

Patients will see no change in terms of copayments for the approved generic topping out at $3 depending on income level as they would have prior to the agreement. The biggest difference for them is that “people who couldn’t be treated are now going to have access to those prescriptions,” Dr. Billioux said.

Some cautious optimism surrounds this kind of arrangement and the potential effect it can have on the affected population.

“Innovation geared to improve access to hepatitis C treatment is critical, particularly in areas like Louisiana where treatment rates for Medicaid patients have been very low,” Robert Brown, MD, member of the American Liver Foundation’s National Medical Advisory Committee and hepatologist at Weill Cornell Medical College, New York, said. “If we can enhance patient access to treatment, we know we will improve health outcomes. However, it is too early to tell if this innovation will be a success. At the end of the day, the number of additional patients cured will determine if this was the right approach.”

Visit the AGA GI Patient Center for information to share with your patients about hepatitis C at https://www.gastro.org/practice-guidance/gi-patient-center/topic/hepatitis-c-hcv

[email protected]

Louisiana physicians who treat Medicaid patients for hepatitis C will see less administrative burden under an arrangement approved by the Centers for Medicare & Medicaid Services.

Dynamic Graphics/Thinkstockphotos

Beginning July 15, physicians will no longer have to seek prior authorization or preauthorization to prescribe the authorized generic version of Epclusa (sofosbuvir/velpatasvir) to any Medicaid patient with hepatitis C. There will be no forms to file.

The change comes as part of a supplemental rebate agreement approved June 26 by CMS. That same day, Louisiana announced a deal with Asegua Therapeutics, a wholly owned subsidiary of Epclusa maker Gilead, that essentially caps the annual cost to the state for treating hepatitis C in incarcerated patients and Medicaid recipients.

State officials estimate about 39,000 Louisianans fit those criteria; the goal of the program is to cure at least 31,000 of them by the time the 5-year agreement expires.

“This new model has the potential to save many lives and improve the health of our citizens,” Louisiana Gov. John Bel Edwards (D) said in a statement. “Asegua was willing to come to the table to work with us to help Louisiana residents and we are pleased to initiate this 5-year partnership. Ultimately our goal is to eliminate this disease in Louisiana, and we have taken a big step forward in that effort.”

The agreement was designed to change very little in terms of the mechanics of how Medicaid managed care organizations, which cover most of the state’s Medicaid population and handle coverage and claims. The biggest change is that, when a spending cap is reached, Asegua will rebate 100% excess costs to the state. Louisiana officials did not disclose what the annual financial caps were as part of the agreement.

“We really thought it was important to leave the system – as much as possible – intact because we think that is going to make us most successful,” Alex Billioux, MD, of the Louisiana Department of Health said in an interview. “We think it leverages existing patient relationships and existing [Medicaid managed care organization] care management responsibilities.”

He added that, by keeping current processes unchanged, “it takes what is an otherwise very complicated arrangement with the state and makes it a little simpler.”

Patients will see no change in terms of copayments for the approved generic topping out at $3 depending on income level as they would have prior to the agreement. The biggest difference for them is that “people who couldn’t be treated are now going to have access to those prescriptions,” Dr. Billioux said.

Some cautious optimism surrounds this kind of arrangement and the potential effect it can have on the affected population.

“Innovation geared to improve access to hepatitis C treatment is critical, particularly in areas like Louisiana where treatment rates for Medicaid patients have been very low,” Robert Brown, MD, member of the American Liver Foundation’s National Medical Advisory Committee and hepatologist at Weill Cornell Medical College, New York, said. “If we can enhance patient access to treatment, we know we will improve health outcomes. However, it is too early to tell if this innovation will be a success. At the end of the day, the number of additional patients cured will determine if this was the right approach.”

Visit the AGA GI Patient Center for information to share with your patients about hepatitis C at https://www.gastro.org/practice-guidance/gi-patient-center/topic/hepatitis-c-hcv

[email protected]

On June 10, 2019, a rainy, foggy day, there was a news flash that a plane had crashed into a building in the middle of New York City. I first saw this notification on my iPhone and my immediate thought was: Could this be a redo of Sept. 11?

U.S. Army Corps of Engineers file photo

I was especially concerned because I knew the area fairly well, in that a clinic I had worked in for more than 10 years was only a few blocks away. However, my memory bank brought me back to that day almost 18 years ago when, from a hospital window, many of us doctors, nurses, social workers, and patients saw the fire in the north tower and then saw the second plane crash into the south tower of the World Trade Center. Once we all knew what happened, we spent that night at the hospital awaiting the arrival of people in need of care. Unfortunately, very few arrived.

On this past June day, before anyone really knew the facts, what we heard and saw on TV was buildings being evacuated in midtown Manhattan, people running and moving in all directions with police officers directing people and diverting traffic, firemen entering the building, and EMT first responders in place. What mayhem!

Gov. Andrew Cuomo got to the scene very quickly and assured us that the incident did not appear to be a terrorist attack. Furthermore, he thoughtfully pointed out, we in New York City all seem to have a version or a form of posttraumatic stress disorder taking us back to Sept. 11, 2001. From my point of view, Gov. Cuomo could not have been more correct in his short, televised talk to a nervous public. The incident, and the governor’s reaction to it, started me thinking about how easily triggered the memories and flashbacks of PTSD can be.

It became clear very soon that a pilot had lost control of the helicopter on that foggy, rainy June day and had tried to make an emergency landing on the roof of a Manhattan high-rise. The roof landing did not go well; the helicopter crashed on the roof; and the lone pilot died.

As it turned out, mental health care workers treated many PTSD sufferers at the Bellevue and Mount Sinai hospital programs set up after Sept. 11, including those who were part of the rescue as well as the clean-up. In addition, it appears that many who witnessed the disaster also were vulnerable to PTSD and were additionally treated in various programs. I have seen and interviewed many of those people over the last 10 years.

PTSD is defined mainly in terms of experiencing a traumatic event during a man-made or natural disaster: torture, assaults, the tragedies of war, or any event that causes physical or psychological injury. According to research, it can occur right after the event or years later. Besides those major traumatic events, I’ve seen PTSD occur from much lesser traumas; much depends on how individuals process what is happening around them. For example, in some people, I’ve seen PTSD occur after job loss, where identity and persona are lost and the brain experiences the psychological shock consistent with more dangerously threatening aspects of PTSD. I’ve seen dog bites, auto accidents, even “fender benders” and emotional break-ups bring out the symptoms of PTSD (J Adv Nurs. 2005 Oct;52[1]:22-30). Luckily, in most of those cases, treatment or time itself can heal the problems.

Going back to that June day, for a few brief moments, my memory was jogged back to Sept. 11. A few people I spoke with about the event last month also reported being taken back to that fateful day (Am Psychol. 2011 Sep;66[6]:429-46).

For some experiencing PTSD, flashbacks to the physically threatening or psychologically shocking event occur as opposed to memory alone. During a flashback, the person actually relives the experience as if it were in the present. Flashbacks are quite different from recall alone. In my experience, the flashback is not unlike age regression, where an individual actually relives an event as opposed to having a memory of an event.

PTSD is a serious emotional problem, and I believe that much of it is undiagnosed in society – partly because we tend to look for the disorder after major traumatic events, such as physical and psychological effects of war or disaster, man-made and natural disasters, as well as assaults and torture. As we know in medicine and mental health care, there are certain vulnerabilities to some disorders. I believe that, whether through education, environment, or genetics, we have vulnerabilities to PTSD (Brain Behav Immun. 2013 May;30:12-21); (Clin Psychol Rev. 2012 Nov;32[7]:630-41), not only from major disastrous physical and psychological shocks but less obvious events in life that might create the same clinical picture we see in more traditional cases of PTSD.

Some PTSD survivors will improve and get better with time. Others do well after getting treatments with interventions such as cognitive-behavioral therapy (CBT) and prolonged exposure therapy, both of which are fairly short term in many instances. Medication management might be helpful for some, but I believe it should be combined with CBT or exposure therapy – or at least some form of talk therapy. An ongoing relationship with a supportive therapist or friends and family is extremely important, in order to keep PTSD survivors from isolating and endlessly “living in their heads” as they relive the experience and face the multiple symptom complexes of PTSD.
 

Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including CBT and guided imagery. He recently published a book called “Find Freedom Fast” (New York: Kettlehole Publishing, 2018).

On June 10, 2019, a rainy, foggy day, there was a news flash that a plane had crashed into a building in the middle of New York City. I first saw this notification on my iPhone and my immediate thought was: Could this be a redo of Sept. 11?

U.S. Army Corps of Engineers file photo

I was especially concerned because I knew the area fairly well, in that a clinic I had worked in for more than 10 years was only a few blocks away. However, my memory bank brought me back to that day almost 18 years ago when, from a hospital window, many of us doctors, nurses, social workers, and patients saw the fire in the north tower and then saw the second plane crash into the south tower of the World Trade Center. Once we all knew what happened, we spent that night at the hospital awaiting the arrival of people in need of care. Unfortunately, very few arrived.

On this past June day, before anyone really knew the facts, what we heard and saw on TV was buildings being evacuated in midtown Manhattan, people running and moving in all directions with police officers directing people and diverting traffic, firemen entering the building, and EMT first responders in place. What mayhem!

Gov. Andrew Cuomo got to the scene very quickly and assured us that the incident did not appear to be a terrorist attack. Furthermore, he thoughtfully pointed out, we in New York City all seem to have a version or a form of posttraumatic stress disorder taking us back to Sept. 11, 2001. From my point of view, Gov. Cuomo could not have been more correct in his short, televised talk to a nervous public. The incident, and the governor’s reaction to it, started me thinking about how easily triggered the memories and flashbacks of PTSD can be.

It became clear very soon that a pilot had lost control of the helicopter on that foggy, rainy June day and had tried to make an emergency landing on the roof of a Manhattan high-rise. The roof landing did not go well; the helicopter crashed on the roof; and the lone pilot died.

As it turned out, mental health care workers treated many PTSD sufferers at the Bellevue and Mount Sinai hospital programs set up after Sept. 11, including those who were part of the rescue as well as the clean-up. In addition, it appears that many who witnessed the disaster also were vulnerable to PTSD and were additionally treated in various programs. I have seen and interviewed many of those people over the last 10 years.

PTSD is defined mainly in terms of experiencing a traumatic event during a man-made or natural disaster: torture, assaults, the tragedies of war, or any event that causes physical or psychological injury. According to research, it can occur right after the event or years later. Besides those major traumatic events, I’ve seen PTSD occur from much lesser traumas; much depends on how individuals process what is happening around them. For example, in some people, I’ve seen PTSD occur after job loss, where identity and persona are lost and the brain experiences the psychological shock consistent with more dangerously threatening aspects of PTSD. I’ve seen dog bites, auto accidents, even “fender benders” and emotional break-ups bring out the symptoms of PTSD (J Adv Nurs. 2005 Oct;52[1]:22-30). Luckily, in most of those cases, treatment or time itself can heal the problems.

Going back to that June day, for a few brief moments, my memory was jogged back to Sept. 11. A few people I spoke with about the event last month also reported being taken back to that fateful day (Am Psychol. 2011 Sep;66[6]:429-46).

For some experiencing PTSD, flashbacks to the physically threatening or psychologically shocking event occur as opposed to memory alone. During a flashback, the person actually relives the experience as if it were in the present. Flashbacks are quite different from recall alone. In my experience, the flashback is not unlike age regression, where an individual actually relives an event as opposed to having a memory of an event.

PTSD is a serious emotional problem, and I believe that much of it is undiagnosed in society – partly because we tend to look for the disorder after major traumatic events, such as physical and psychological effects of war or disaster, man-made and natural disasters, as well as assaults and torture. As we know in medicine and mental health care, there are certain vulnerabilities to some disorders. I believe that, whether through education, environment, or genetics, we have vulnerabilities to PTSD (Brain Behav Immun. 2013 May;30:12-21); (Clin Psychol Rev. 2012 Nov;32[7]:630-41), not only from major disastrous physical and psychological shocks but less obvious events in life that might create the same clinical picture we see in more traditional cases of PTSD.

Some PTSD survivors will improve and get better with time. Others do well after getting treatments with interventions such as cognitive-behavioral therapy (CBT) and prolonged exposure therapy, both of which are fairly short term in many instances. Medication management might be helpful for some, but I believe it should be combined with CBT or exposure therapy – or at least some form of talk therapy. An ongoing relationship with a supportive therapist or friends and family is extremely important, in order to keep PTSD survivors from isolating and endlessly “living in their heads” as they relive the experience and face the multiple symptom complexes of PTSD.
 

Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including CBT and guided imagery. He recently published a book called “Find Freedom Fast” (New York: Kettlehole Publishing, 2018).

On June 10, 2019, a rainy, foggy day, there was a news flash that a plane had crashed into a building in the middle of New York City. I first saw this notification on my iPhone and my immediate thought was: Could this be a redo of Sept. 11?

U.S. Army Corps of Engineers file photo

I was especially concerned because I knew the area fairly well, in that a clinic I had worked in for more than 10 years was only a few blocks away. However, my memory bank brought me back to that day almost 18 years ago when, from a hospital window, many of us doctors, nurses, social workers, and patients saw the fire in the north tower and then saw the second plane crash into the south tower of the World Trade Center. Once we all knew what happened, we spent that night at the hospital awaiting the arrival of people in need of care. Unfortunately, very few arrived.

On this past June day, before anyone really knew the facts, what we heard and saw on TV was buildings being evacuated in midtown Manhattan, people running and moving in all directions with police officers directing people and diverting traffic, firemen entering the building, and EMT first responders in place. What mayhem!

Gov. Andrew Cuomo got to the scene very quickly and assured us that the incident did not appear to be a terrorist attack. Furthermore, he thoughtfully pointed out, we in New York City all seem to have a version or a form of posttraumatic stress disorder taking us back to Sept. 11, 2001. From my point of view, Gov. Cuomo could not have been more correct in his short, televised talk to a nervous public. The incident, and the governor’s reaction to it, started me thinking about how easily triggered the memories and flashbacks of PTSD can be.

It became clear very soon that a pilot had lost control of the helicopter on that foggy, rainy June day and had tried to make an emergency landing on the roof of a Manhattan high-rise. The roof landing did not go well; the helicopter crashed on the roof; and the lone pilot died.

As it turned out, mental health care workers treated many PTSD sufferers at the Bellevue and Mount Sinai hospital programs set up after Sept. 11, including those who were part of the rescue as well as the clean-up. In addition, it appears that many who witnessed the disaster also were vulnerable to PTSD and were additionally treated in various programs. I have seen and interviewed many of those people over the last 10 years.

PTSD is defined mainly in terms of experiencing a traumatic event during a man-made or natural disaster: torture, assaults, the tragedies of war, or any event that causes physical or psychological injury. According to research, it can occur right after the event or years later. Besides those major traumatic events, I’ve seen PTSD occur from much lesser traumas; much depends on how individuals process what is happening around them. For example, in some people, I’ve seen PTSD occur after job loss, where identity and persona are lost and the brain experiences the psychological shock consistent with more dangerously threatening aspects of PTSD. I’ve seen dog bites, auto accidents, even “fender benders” and emotional break-ups bring out the symptoms of PTSD (J Adv Nurs. 2005 Oct;52[1]:22-30). Luckily, in most of those cases, treatment or time itself can heal the problems.

Going back to that June day, for a few brief moments, my memory was jogged back to Sept. 11. A few people I spoke with about the event last month also reported being taken back to that fateful day (Am Psychol. 2011 Sep;66[6]:429-46).

For some experiencing PTSD, flashbacks to the physically threatening or psychologically shocking event occur as opposed to memory alone. During a flashback, the person actually relives the experience as if it were in the present. Flashbacks are quite different from recall alone. In my experience, the flashback is not unlike age regression, where an individual actually relives an event as opposed to having a memory of an event.

PTSD is a serious emotional problem, and I believe that much of it is undiagnosed in society – partly because we tend to look for the disorder after major traumatic events, such as physical and psychological effects of war or disaster, man-made and natural disasters, as well as assaults and torture. As we know in medicine and mental health care, there are certain vulnerabilities to some disorders. I believe that, whether through education, environment, or genetics, we have vulnerabilities to PTSD (Brain Behav Immun. 2013 May;30:12-21); (Clin Psychol Rev. 2012 Nov;32[7]:630-41), not only from major disastrous physical and psychological shocks but less obvious events in life that might create the same clinical picture we see in more traditional cases of PTSD.

Some PTSD survivors will improve and get better with time. Others do well after getting treatments with interventions such as cognitive-behavioral therapy (CBT) and prolonged exposure therapy, both of which are fairly short term in many instances. Medication management might be helpful for some, but I believe it should be combined with CBT or exposure therapy – or at least some form of talk therapy. An ongoing relationship with a supportive therapist or friends and family is extremely important, in order to keep PTSD survivors from isolating and endlessly “living in their heads” as they relive the experience and face the multiple symptom complexes of PTSD.
 

Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including CBT and guided imagery. He recently published a book called “Find Freedom Fast” (New York: Kettlehole Publishing, 2018).

Being in stressful situations is part of being a hospitalist. During a hospitalist’s work shift, one of the key determinants of stress is adequate staffing. With use of survey data from 569 hospital medicine groups (HMGs) across the nation, one of the topics examined in the 2018 State of Hospital Medicine Report is how HMGs cope with unfilled hospitalist physician positions.

The survey presented five options for covering unfilled hospitalist physician positions: use of locum tenens, use of moonlighters, use of voluntary extra shifts by the HMG’s existing hospitalists, use of required extra shifts, and leaving some shifts uncovered. Recipients were instructed to select all options that applied, so totals exceeded 100%. The data is organized according to HMGs that serve adults only, children only, and both adults and children.

For all three types of HMGs, the most common tactic to fill coverage gaps is through voluntary extra shifts by existing clinicians, reportedly used by 70.3% of HMGs that cover adults only, 66.7% by those that cover children only, and 76.9% by those that cover both adults and children. Data for adults-only HMGs was further broken down by geographic region, academic status, teaching status, group size, and employment model. Among adults-only HMGs, there is a direct correlation between group size and having members voluntarily work extra shifts, with 91.1% of groups with 30 or more full-time equivalent positions employing this tactic.

For HMGs that cover adults only and those that cover children only, the second most common tactic is to use moonlighters (57.4% and 53.3% respectively), while use of moonlighters is the third most commonly employed surveyed tactic for HMGs that cover both adults and children (53.8%).

HMGs that serve both adults and children were much more likely to utilize locum tenens to cover unfilled positions (69.2%) than were groups that serve adults only (44.0%) or children only (26.7%). The variability in the use of locum tenens is likely because of the willingness and/or ability of the respective groups to afford this option because it is generally the most expensive option of those surveyed.

Requiring that members of the group work extra shifts is the least popular staffing method among adults-only HMGs (10.0%) and HMGs serving both children and adults (7.7%). This strategy is unpopular, especially when there is little advance warning. Surprisingly, 40.0% of HMGs that see children only require members to work extra shifts to cover unfilled slots. This could be because pediatric HMGs are often smaller, and it would be more difficult to absorb the work if the shift is left uncovered. In fact, many pediatric HMGs staff with only one clinician at a time, so there may be no option besides requiring someone else in the group to come in and work.Of the options surveyed, perhaps the most uncomfortable for those hospitalist physicians on duty is to leave some shifts uncovered. The rapid growth and development of the specialty of hospital medicine has made it difficult for HMGs to continuously hire qualified hospitalists fast enough to meet demand. The survey found 46.2% of HMGs that serve both adults and children and 31.4% of groups that serve adults only have employed the staffing model of going short-staffed for at least some shifts. HMGs serving children-only are much less likely to go short-staffed (20.0%).

I work with a large HMG that has more than 70 members, and when it has been short-staffed, it tries to ensure a full complement of evening and night staff as the top priority because these shifts are typically more stressful. Since we have more hospitalist capacity during the day to absorb the loss of a physician, we pull staff from their daytime rounding schedules to execute this strategy. While going short-staffed is not ideal, this option has worked for many groups out of sheer necessity.

Dr. Stephan is a hospitalist at Allina Health’s Abbott Northwestern Hospital in Minneapolis and is a member of the SHM Practice Analysis Committee.

Being in stressful situations is part of being a hospitalist. During a hospitalist’s work shift, one of the key determinants of stress is adequate staffing. With use of survey data from 569 hospital medicine groups (HMGs) across the nation, one of the topics examined in the 2018 State of Hospital Medicine Report is how HMGs cope with unfilled hospitalist physician positions.

The survey presented five options for covering unfilled hospitalist physician positions: use of locum tenens, use of moonlighters, use of voluntary extra shifts by the HMG’s existing hospitalists, use of required extra shifts, and leaving some shifts uncovered. Recipients were instructed to select all options that applied, so totals exceeded 100%. The data is organized according to HMGs that serve adults only, children only, and both adults and children.

For all three types of HMGs, the most common tactic to fill coverage gaps is through voluntary extra shifts by existing clinicians, reportedly used by 70.3% of HMGs that cover adults only, 66.7% by those that cover children only, and 76.9% by those that cover both adults and children. Data for adults-only HMGs was further broken down by geographic region, academic status, teaching status, group size, and employment model. Among adults-only HMGs, there is a direct correlation between group size and having members voluntarily work extra shifts, with 91.1% of groups with 30 or more full-time equivalent positions employing this tactic.

For HMGs that cover adults only and those that cover children only, the second most common tactic is to use moonlighters (57.4% and 53.3% respectively), while use of moonlighters is the third most commonly employed surveyed tactic for HMGs that cover both adults and children (53.8%).

HMGs that serve both adults and children were much more likely to utilize locum tenens to cover unfilled positions (69.2%) than were groups that serve adults only (44.0%) or children only (26.7%). The variability in the use of locum tenens is likely because of the willingness and/or ability of the respective groups to afford this option because it is generally the most expensive option of those surveyed.

Requiring that members of the group work extra shifts is the least popular staffing method among adults-only HMGs (10.0%) and HMGs serving both children and adults (7.7%). This strategy is unpopular, especially when there is little advance warning. Surprisingly, 40.0% of HMGs that see children only require members to work extra shifts to cover unfilled slots. This could be because pediatric HMGs are often smaller, and it would be more difficult to absorb the work if the shift is left uncovered. In fact, many pediatric HMGs staff with only one clinician at a time, so there may be no option besides requiring someone else in the group to come in and work.Of the options surveyed, perhaps the most uncomfortable for those hospitalist physicians on duty is to leave some shifts uncovered. The rapid growth and development of the specialty of hospital medicine has made it difficult for HMGs to continuously hire qualified hospitalists fast enough to meet demand. The survey found 46.2% of HMGs that serve both adults and children and 31.4% of groups that serve adults only have employed the staffing model of going short-staffed for at least some shifts. HMGs serving children-only are much less likely to go short-staffed (20.0%).

I work with a large HMG that has more than 70 members, and when it has been short-staffed, it tries to ensure a full complement of evening and night staff as the top priority because these shifts are typically more stressful. Since we have more hospitalist capacity during the day to absorb the loss of a physician, we pull staff from their daytime rounding schedules to execute this strategy. While going short-staffed is not ideal, this option has worked for many groups out of sheer necessity.

Dr. Stephan is a hospitalist at Allina Health’s Abbott Northwestern Hospital in Minneapolis and is a member of the SHM Practice Analysis Committee.

Being in stressful situations is part of being a hospitalist. During a hospitalist’s work shift, one of the key determinants of stress is adequate staffing. With use of survey data from 569 hospital medicine groups (HMGs) across the nation, one of the topics examined in the 2018 State of Hospital Medicine Report is how HMGs cope with unfilled hospitalist physician positions.

The survey presented five options for covering unfilled hospitalist physician positions: use of locum tenens, use of moonlighters, use of voluntary extra shifts by the HMG’s existing hospitalists, use of required extra shifts, and leaving some shifts uncovered. Recipients were instructed to select all options that applied, so totals exceeded 100%. The data is organized according to HMGs that serve adults only, children only, and both adults and children.

For all three types of HMGs, the most common tactic to fill coverage gaps is through voluntary extra shifts by existing clinicians, reportedly used by 70.3% of HMGs that cover adults only, 66.7% by those that cover children only, and 76.9% by those that cover both adults and children. Data for adults-only HMGs was further broken down by geographic region, academic status, teaching status, group size, and employment model. Among adults-only HMGs, there is a direct correlation between group size and having members voluntarily work extra shifts, with 91.1% of groups with 30 or more full-time equivalent positions employing this tactic.

For HMGs that cover adults only and those that cover children only, the second most common tactic is to use moonlighters (57.4% and 53.3% respectively), while use of moonlighters is the third most commonly employed surveyed tactic for HMGs that cover both adults and children (53.8%).

HMGs that serve both adults and children were much more likely to utilize locum tenens to cover unfilled positions (69.2%) than were groups that serve adults only (44.0%) or children only (26.7%). The variability in the use of locum tenens is likely because of the willingness and/or ability of the respective groups to afford this option because it is generally the most expensive option of those surveyed.

Requiring that members of the group work extra shifts is the least popular staffing method among adults-only HMGs (10.0%) and HMGs serving both children and adults (7.7%). This strategy is unpopular, especially when there is little advance warning. Surprisingly, 40.0% of HMGs that see children only require members to work extra shifts to cover unfilled slots. This could be because pediatric HMGs are often smaller, and it would be more difficult to absorb the work if the shift is left uncovered. In fact, many pediatric HMGs staff with only one clinician at a time, so there may be no option besides requiring someone else in the group to come in and work.Of the options surveyed, perhaps the most uncomfortable for those hospitalist physicians on duty is to leave some shifts uncovered. The rapid growth and development of the specialty of hospital medicine has made it difficult for HMGs to continuously hire qualified hospitalists fast enough to meet demand. The survey found 46.2% of HMGs that serve both adults and children and 31.4% of groups that serve adults only have employed the staffing model of going short-staffed for at least some shifts. HMGs serving children-only are much less likely to go short-staffed (20.0%).

I work with a large HMG that has more than 70 members, and when it has been short-staffed, it tries to ensure a full complement of evening and night staff as the top priority because these shifts are typically more stressful. Since we have more hospitalist capacity during the day to absorb the loss of a physician, we pull staff from their daytime rounding schedules to execute this strategy. While going short-staffed is not ideal, this option has worked for many groups out of sheer necessity.

Dr. Stephan is a hospitalist at Allina Health’s Abbott Northwestern Hospital in Minneapolis and is a member of the SHM Practice Analysis Committee.

A manualized cognitive-behavioral therapy (CBT) program that combines group and individual interventions might effectively treat Internet and computer game addiction in men, results of a multicenter randomized trial suggest.

In the study, Klaus Wölfling, PhD, and colleagues randomized 143 men (mean age, 26.2 years) with Internet addiction (IA), which was defined as a score greater than 13 on the Assessment of Internet and Computer Game Addiction Self-Report (AICA-S). The men were recruited at four outpatient clinics in Germany and Austria from Jan. 24, 2012, to June 14, 2017. The primary endpoint of remission, defined as a score of less than 7 on the AICA-S, was achieved by 50 patients (69.4%) in the treatment arm, compared with 17 patients (23.9%) of the wait-list control arm. The greatest declines in AICA-S scores were seen by midtreatment, but mean scores continued at similar levels through follow-up. The study was published in JAMA Psychiatry (2019 Jul 10. doi: 10.1001/jamapsychiatry.2019.1676).

Dr. Wölfling and colleagues chose to limit the scope of the study to male participants because they represent most of those affected by IA; however, the authors admitted this limits the results’ generalizability. They also noted that many of the patients were ambivalent toward treatment, which is a core characteristic of patients affected by IA. Recruitment was slow, so the investigators had to evaluate a smaller number of participants than planned, although they felt their analyses were still statistically powerful enough to detect difference in endpoints. The authors also noted that, although they tried to control for comorbidities, which are often associated with IA, they had to define exclusion criteria for certain conditions such as major depression and some personality disorders.

IA was included in the DSM-5 in 2013 as a condition warranting further research, the authors of this study noted. More recently, it was “introduced as a new diagnosis in the International Classification of Diseases, 11th Revision, in the section Disorders Due to Substance Use or Addictive Behaviors.” This trial’s manualized CBT treatment, then, “might be used as a benchmark as a nonpharmacologic intervention and serve as a treatment as usual condition in upcoming trials,” they concluded.

[email protected]

A manualized cognitive-behavioral therapy (CBT) program that combines group and individual interventions might effectively treat Internet and computer game addiction in men, results of a multicenter randomized trial suggest.

In the study, Klaus Wölfling, PhD, and colleagues randomized 143 men (mean age, 26.2 years) with Internet addiction (IA), which was defined as a score greater than 13 on the Assessment of Internet and Computer Game Addiction Self-Report (AICA-S). The men were recruited at four outpatient clinics in Germany and Austria from Jan. 24, 2012, to June 14, 2017. The primary endpoint of remission, defined as a score of less than 7 on the AICA-S, was achieved by 50 patients (69.4%) in the treatment arm, compared with 17 patients (23.9%) of the wait-list control arm. The greatest declines in AICA-S scores were seen by midtreatment, but mean scores continued at similar levels through follow-up. The study was published in JAMA Psychiatry (2019 Jul 10. doi: 10.1001/jamapsychiatry.2019.1676).

Dr. Wölfling and colleagues chose to limit the scope of the study to male participants because they represent most of those affected by IA; however, the authors admitted this limits the results’ generalizability. They also noted that many of the patients were ambivalent toward treatment, which is a core characteristic of patients affected by IA. Recruitment was slow, so the investigators had to evaluate a smaller number of participants than planned, although they felt their analyses were still statistically powerful enough to detect difference in endpoints. The authors also noted that, although they tried to control for comorbidities, which are often associated with IA, they had to define exclusion criteria for certain conditions such as major depression and some personality disorders.

IA was included in the DSM-5 in 2013 as a condition warranting further research, the authors of this study noted. More recently, it was “introduced as a new diagnosis in the International Classification of Diseases, 11th Revision, in the section Disorders Due to Substance Use or Addictive Behaviors.” This trial’s manualized CBT treatment, then, “might be used as a benchmark as a nonpharmacologic intervention and serve as a treatment as usual condition in upcoming trials,” they concluded.

[email protected]

A manualized cognitive-behavioral therapy (CBT) program that combines group and individual interventions might effectively treat Internet and computer game addiction in men, results of a multicenter randomized trial suggest.

In the study, Klaus Wölfling, PhD, and colleagues randomized 143 men (mean age, 26.2 years) with Internet addiction (IA), which was defined as a score greater than 13 on the Assessment of Internet and Computer Game Addiction Self-Report (AICA-S). The men were recruited at four outpatient clinics in Germany and Austria from Jan. 24, 2012, to June 14, 2017. The primary endpoint of remission, defined as a score of less than 7 on the AICA-S, was achieved by 50 patients (69.4%) in the treatment arm, compared with 17 patients (23.9%) of the wait-list control arm. The greatest declines in AICA-S scores were seen by midtreatment, but mean scores continued at similar levels through follow-up. The study was published in JAMA Psychiatry (2019 Jul 10. doi: 10.1001/jamapsychiatry.2019.1676).

Dr. Wölfling and colleagues chose to limit the scope of the study to male participants because they represent most of those affected by IA; however, the authors admitted this limits the results’ generalizability. They also noted that many of the patients were ambivalent toward treatment, which is a core characteristic of patients affected by IA. Recruitment was slow, so the investigators had to evaluate a smaller number of participants than planned, although they felt their analyses were still statistically powerful enough to detect difference in endpoints. The authors also noted that, although they tried to control for comorbidities, which are often associated with IA, they had to define exclusion criteria for certain conditions such as major depression and some personality disorders.

IA was included in the DSM-5 in 2013 as a condition warranting further research, the authors of this study noted. More recently, it was “introduced as a new diagnosis in the International Classification of Diseases, 11th Revision, in the section Disorders Due to Substance Use or Addictive Behaviors.” This trial’s manualized CBT treatment, then, “might be used as a benchmark as a nonpharmacologic intervention and serve as a treatment as usual condition in upcoming trials,” they concluded.

[email protected]

MILAN – A novel topical nonsteroidal treatment for psoriasis showed sufficient efficacy in phase 2b clinical trials to proceed to phase 3 studies, with improvements in severity, pain, and burning in adults with mild to moderate psoriasis.

At the end of 12 weeks of treatment, 29% of patients receiving the medication – which targets nerve pathways – experienced a decrease of at least 2 grades on the 5-point Investigator’s Global Assessment (IGA) scale, compared with 13% of those receiving the topical vehicle only (P = .036). A similar proportion of patients achieved 75% improvement on the Psoriasis Area and Severity Index (PASI-75)compared with those on vehicle alone (27% versus 13%; P = .045).

These findings were seen only with the less concentrated formulation of pegcantratinib, known as SNA-120 in the clinical trial program, said Paul F. Lizzul, MD, PhD, presenting the findings during a late-breaking abstract session at the World Congress of Dermatology.

Pruritus severity also dropped by about 60%, but the decrease did not differ significantly from the change seen with vehicle alone, said Dr. Lizzul, chief medical officer for Sienna Biopharmaceuticals, Westlake Village, Calif., which funded the study. He and his coinvestigators found this “interesting, surprising, and different from what we had seen previously,” he said. “We think a few things happened here,” including intensive querying on itch by means of daily diaries, a different approach than had been taken in the investigator’s earlier SNA-120 trials. “We think in this way we probably biased patients’ expectations, altering reporting on this subjective measure,” he added.

“There’s been really a lack of innovation in the topical world in developing nonsteroidal therapies for the majority of patients who are treated with topicals, said Dr. Lizzul. Keratinocytes within psoriatic plaques are known to have elevated levels of nerve growth factor (NGF), he explained. Together with tropomyosin receptor kinase A (TrkA), NGF is implicated in the pathogenesis of psoriasis; it stimulates keratinocyte hyperproliferation, is a factor in neurogenic inflammation, and contributes to pruritus. Upregulation of TrkA expression is seen in nerve fibers within pruritic psoriasis plaques as well, said Dr. Lizzul, senior author of the study. (The first author was Kristina Callis Duffin, MD, cochair of the dermatology department at the University of Utah, Salt Lake City.)

In fact, the pruritus that plagues many psoriasis patients, said Dr. Lizzul, may “serve as a clinical biomarker for elevated NGF/TrkA expression.” And certain clinical phenomena observed in psoriasis, such as the Koebner phenomenon and plaque resolution along the path of damaged nerves, provide other clues. “Clearly, astute clinicians going back many, many years have recognized the very important role that nerves and neuropeptides play in psoriasis,” he added.

SNA-120 targets NGF TrKA activity, and “achieves high local drug concentration in the skin, with low systemic availability,” he said.

The randomized, double-blind, vehicle-controlled study enrolled 208 adults with mild to moderate psoriasis (scores of 2 or 3 on the IGA), with pruritus of at least moderate intensity (5 or higher on a 10-point itch numeric rating scale, or I-NRS). The mean age of the patients was 50 years, and about half were male. Most (84%-90% across study arms) were white. At baseline, the mean I-NRS was 7.3-7.4, and the mean PASI score at baseline ranged from 5.9 to 6.5.


Patients were randomized to receive SNA-120 twice daily at either 0.05% (70 patients) or 0.5% (69 patients) in an ointment formulation, or vehicle alone twice daily (69 patients). Efficacy was tracked by measuring decrease in IGA by one or two grades, the number of patients achieving PASI-50 and PASI-75, reduction in itch, and a composite of a decrease of at least 2 grades on the IGA and having clear or almost clear skin.

The investigators also tracked reduction in burning and pain as measured on a 10-point numeric rating scale. Though itch scores didn’t differ significantly from reductions seen with the topical vehicle alone, pain and burning were both reduced significantly compared with vehicle by week 12 of the study (P = .033 for pain; P = .043 for burning).

All improvements were seen only with the lower dose, not the 0.5% dose of SNA-120, noted Dr. Lizzul, adding: “This is not necessarily surprising in the world of kinase inhibitors, where you can see these J-shaped or inverse dose-response curves.”

In addition to recording adverse events, the researchers assessed safety by obtaining laboratory values and electrocardiograms. Plasma SNA-120 levels at study weeks 2, 4, and 8 were obtained for pharmacokinetic analysis. Systemic uptake was virtually nil, and the safety profile overall was good, said Dr. Lizzul.

Next steps are phase 3 clinical trials that will evaluate global improvement as well as pain, burning, and itch in psoriasis, he noted.

Dr. Lizzul is an employee of Sienna Biopharmaceuticals, which is developing SNA-120.

[email protected]

MILAN – A novel topical nonsteroidal treatment for psoriasis showed sufficient efficacy in phase 2b clinical trials to proceed to phase 3 studies, with improvements in severity, pain, and burning in adults with mild to moderate psoriasis.

At the end of 12 weeks of treatment, 29% of patients receiving the medication – which targets nerve pathways – experienced a decrease of at least 2 grades on the 5-point Investigator’s Global Assessment (IGA) scale, compared with 13% of those receiving the topical vehicle only (P = .036). A similar proportion of patients achieved 75% improvement on the Psoriasis Area and Severity Index (PASI-75)compared with those on vehicle alone (27% versus 13%; P = .045).

These findings were seen only with the less concentrated formulation of pegcantratinib, known as SNA-120 in the clinical trial program, said Paul F. Lizzul, MD, PhD, presenting the findings during a late-breaking abstract session at the World Congress of Dermatology.

Pruritus severity also dropped by about 60%, but the decrease did not differ significantly from the change seen with vehicle alone, said Dr. Lizzul, chief medical officer for Sienna Biopharmaceuticals, Westlake Village, Calif., which funded the study. He and his coinvestigators found this “interesting, surprising, and different from what we had seen previously,” he said. “We think a few things happened here,” including intensive querying on itch by means of daily diaries, a different approach than had been taken in the investigator’s earlier SNA-120 trials. “We think in this way we probably biased patients’ expectations, altering reporting on this subjective measure,” he added.

“There’s been really a lack of innovation in the topical world in developing nonsteroidal therapies for the majority of patients who are treated with topicals, said Dr. Lizzul. Keratinocytes within psoriatic plaques are known to have elevated levels of nerve growth factor (NGF), he explained. Together with tropomyosin receptor kinase A (TrkA), NGF is implicated in the pathogenesis of psoriasis; it stimulates keratinocyte hyperproliferation, is a factor in neurogenic inflammation, and contributes to pruritus. Upregulation of TrkA expression is seen in nerve fibers within pruritic psoriasis plaques as well, said Dr. Lizzul, senior author of the study. (The first author was Kristina Callis Duffin, MD, cochair of the dermatology department at the University of Utah, Salt Lake City.)

In fact, the pruritus that plagues many psoriasis patients, said Dr. Lizzul, may “serve as a clinical biomarker for elevated NGF/TrkA expression.” And certain clinical phenomena observed in psoriasis, such as the Koebner phenomenon and plaque resolution along the path of damaged nerves, provide other clues. “Clearly, astute clinicians going back many, many years have recognized the very important role that nerves and neuropeptides play in psoriasis,” he added.

SNA-120 targets NGF TrKA activity, and “achieves high local drug concentration in the skin, with low systemic availability,” he said.

The randomized, double-blind, vehicle-controlled study enrolled 208 adults with mild to moderate psoriasis (scores of 2 or 3 on the IGA), with pruritus of at least moderate intensity (5 or higher on a 10-point itch numeric rating scale, or I-NRS). The mean age of the patients was 50 years, and about half were male. Most (84%-90% across study arms) were white. At baseline, the mean I-NRS was 7.3-7.4, and the mean PASI score at baseline ranged from 5.9 to 6.5.


Patients were randomized to receive SNA-120 twice daily at either 0.05% (70 patients) or 0.5% (69 patients) in an ointment formulation, or vehicle alone twice daily (69 patients). Efficacy was tracked by measuring decrease in IGA by one or two grades, the number of patients achieving PASI-50 and PASI-75, reduction in itch, and a composite of a decrease of at least 2 grades on the IGA and having clear or almost clear skin.

The investigators also tracked reduction in burning and pain as measured on a 10-point numeric rating scale. Though itch scores didn’t differ significantly from reductions seen with the topical vehicle alone, pain and burning were both reduced significantly compared with vehicle by week 12 of the study (P = .033 for pain; P = .043 for burning).

All improvements were seen only with the lower dose, not the 0.5% dose of SNA-120, noted Dr. Lizzul, adding: “This is not necessarily surprising in the world of kinase inhibitors, where you can see these J-shaped or inverse dose-response curves.”

In addition to recording adverse events, the researchers assessed safety by obtaining laboratory values and electrocardiograms. Plasma SNA-120 levels at study weeks 2, 4, and 8 were obtained for pharmacokinetic analysis. Systemic uptake was virtually nil, and the safety profile overall was good, said Dr. Lizzul.

Next steps are phase 3 clinical trials that will evaluate global improvement as well as pain, burning, and itch in psoriasis, he noted.

Dr. Lizzul is an employee of Sienna Biopharmaceuticals, which is developing SNA-120.

[email protected]

MILAN – A novel topical nonsteroidal treatment for psoriasis showed sufficient efficacy in phase 2b clinical trials to proceed to phase 3 studies, with improvements in severity, pain, and burning in adults with mild to moderate psoriasis.

At the end of 12 weeks of treatment, 29% of patients receiving the medication – which targets nerve pathways – experienced a decrease of at least 2 grades on the 5-point Investigator’s Global Assessment (IGA) scale, compared with 13% of those receiving the topical vehicle only (P = .036). A similar proportion of patients achieved 75% improvement on the Psoriasis Area and Severity Index (PASI-75)compared with those on vehicle alone (27% versus 13%; P = .045).

These findings were seen only with the less concentrated formulation of pegcantratinib, known as SNA-120 in the clinical trial program, said Paul F. Lizzul, MD, PhD, presenting the findings during a late-breaking abstract session at the World Congress of Dermatology.

Pruritus severity also dropped by about 60%, but the decrease did not differ significantly from the change seen with vehicle alone, said Dr. Lizzul, chief medical officer for Sienna Biopharmaceuticals, Westlake Village, Calif., which funded the study. He and his coinvestigators found this “interesting, surprising, and different from what we had seen previously,” he said. “We think a few things happened here,” including intensive querying on itch by means of daily diaries, a different approach than had been taken in the investigator’s earlier SNA-120 trials. “We think in this way we probably biased patients’ expectations, altering reporting on this subjective measure,” he added.

“There’s been really a lack of innovation in the topical world in developing nonsteroidal therapies for the majority of patients who are treated with topicals, said Dr. Lizzul. Keratinocytes within psoriatic plaques are known to have elevated levels of nerve growth factor (NGF), he explained. Together with tropomyosin receptor kinase A (TrkA), NGF is implicated in the pathogenesis of psoriasis; it stimulates keratinocyte hyperproliferation, is a factor in neurogenic inflammation, and contributes to pruritus. Upregulation of TrkA expression is seen in nerve fibers within pruritic psoriasis plaques as well, said Dr. Lizzul, senior author of the study. (The first author was Kristina Callis Duffin, MD, cochair of the dermatology department at the University of Utah, Salt Lake City.)

In fact, the pruritus that plagues many psoriasis patients, said Dr. Lizzul, may “serve as a clinical biomarker for elevated NGF/TrkA expression.” And certain clinical phenomena observed in psoriasis, such as the Koebner phenomenon and plaque resolution along the path of damaged nerves, provide other clues. “Clearly, astute clinicians going back many, many years have recognized the very important role that nerves and neuropeptides play in psoriasis,” he added.

SNA-120 targets NGF TrKA activity, and “achieves high local drug concentration in the skin, with low systemic availability,” he said.

The randomized, double-blind, vehicle-controlled study enrolled 208 adults with mild to moderate psoriasis (scores of 2 or 3 on the IGA), with pruritus of at least moderate intensity (5 or higher on a 10-point itch numeric rating scale, or I-NRS). The mean age of the patients was 50 years, and about half were male. Most (84%-90% across study arms) were white. At baseline, the mean I-NRS was 7.3-7.4, and the mean PASI score at baseline ranged from 5.9 to 6.5.


Patients were randomized to receive SNA-120 twice daily at either 0.05% (70 patients) or 0.5% (69 patients) in an ointment formulation, or vehicle alone twice daily (69 patients). Efficacy was tracked by measuring decrease in IGA by one or two grades, the number of patients achieving PASI-50 and PASI-75, reduction in itch, and a composite of a decrease of at least 2 grades on the IGA and having clear or almost clear skin.

The investigators also tracked reduction in burning and pain as measured on a 10-point numeric rating scale. Though itch scores didn’t differ significantly from reductions seen with the topical vehicle alone, pain and burning were both reduced significantly compared with vehicle by week 12 of the study (P = .033 for pain; P = .043 for burning).

All improvements were seen only with the lower dose, not the 0.5% dose of SNA-120, noted Dr. Lizzul, adding: “This is not necessarily surprising in the world of kinase inhibitors, where you can see these J-shaped or inverse dose-response curves.”

In addition to recording adverse events, the researchers assessed safety by obtaining laboratory values and electrocardiograms. Plasma SNA-120 levels at study weeks 2, 4, and 8 were obtained for pharmacokinetic analysis. Systemic uptake was virtually nil, and the safety profile overall was good, said Dr. Lizzul.

Next steps are phase 3 clinical trials that will evaluate global improvement as well as pain, burning, and itch in psoriasis, he noted.

Dr. Lizzul is an employee of Sienna Biopharmaceuticals, which is developing SNA-120.

[email protected]