Photo courtesy of Janssen

NEW YORK, NY—The 4-year follow-up of the RESONATE trial suggests ibrutinib may provide long-term efficacy in previously treated patients with chronic lymphocytic leukemia (CLL).

The median progression-free survival (PFS) has not yet been reached in this trial, regardless of high-risk cytogenetics, according to Jennifer Brown, MD, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

She presented the update at Lymphoma & Myeloma 2017. The follow-up study was awarded the best clinical CLL abstract of the meeting.

In the phase 3 RESONATE study, investigators compared ibrutinib—the first-in-class, once-daily, oral inhibitor of Bruton tyrosine kinase—to ofatumumab in previously treated CLL/small lymphocytic lymphoma (SLL).

The primary analysis showed ibrutinib significantly improved survival, with a 78% reduction in the risk of progression and a 57% reduction in the risk of death.

The phase 3 trial randomized 195 CLL/SLL patients to oral ibrutinib at 420 mg once daily and 196 patients to intravenous ofatumumab at an initial dose of 300 mg followed by 2000 mg for 11 doses over 24 weeks.

One hundred thirty-three patients progressed on ofatumumab and crossed over to receive once-daily ibrutinib.

Patient characteristics

In each arm, the median patient age was 67, more than half of patients had an ECOG status of 1, and more than half had advanced-stage disease.

High-risk genetic abnormalities were common, Dr Brown said, with deletion 11q in a third of patients in the ibrutinib arm and 31% in the ofatumumab arm. Another third in each arm had deletion 17p, while 51% in the ibrutinib arm and 46% in the ofatumumab arm had TP53 mutation.

About a quarter of the patients in each arm had complex karyotype, and 73% and 63% in the ibrutinib and ofatumumab arms, respectively, were IGHV-unmutated.

Survival

Ibrutinib significantly extended PFS compared with ofatumumab. At a median follow-up for ibrutinib of 44 months (range, 0.33 – 53), ibrutinib led to an 87% reduction in the risk of progression or death. The 3-year PFS rate was 59% with ibrutinib and 3% with ofatumumab.

Ibrutinib conferred a benefit in PFS across all baseline patient characteristics.

Among ibrutinib-treated patients, the 3-year PFS was 53% for patients with deletion 17p, 66% for those with deletion 11q but not deletion 17p, and 58% for those with neither abnormality.

Dr Brown noted how closely complex karyotype associates with high-risk cytogenetics. Forty-two percent of patients with 17p deletion had a complex karyotype, as did 23% of patients with 11q deletion and 15% of patients with neither 17p nor 11q deletion.

For IGHV-mutation status, Dr Brown said there is no difference in PFS with this degree of follow-up.

In terms of TP53 mutation status, Dr Brown pointed out a trend toward a worse PFS in those patients with the mutation.

“We actually looked by individual p53 mutation versus 17p deletion, versus both, versus neither, in the 2-year follow-up paper and found that p53 with 17p, both abnormalities, did have worse PFS than neither,” she said.

“This may require further follow-up because we do know that most 17p patients also have a p53 mutation, particularly in the relapsed setting.”

As expected, Dr Brown said, those patients with more than 2 prior therapies had a worse PFS compared to patients with 2 or fewer prior therapies.

Multivariate analysis demonstrated that more than 2 prior lines of therapy or an elevated ß2 microglobulin were associated with decreased PFS with ibrutinib.

When the investigators adjusted the overall survival data for cross-over, ibrutinib was projected to continue the overall survival benefit compared with ofatumumab, with a hazard ratio of 0.37.

Response rates

Dr Brown noted that, early on, there’s quite a significant rate of partial response with lymphocytosis observed in patients on ibrutinib.

This “diminishes dramatically,” she said, but about 5% of patients at 3 and 4 years still have ongoing lymphocytosis.

“Similarly, initially, there’s a very low rate of complete remission, which has risen steadily to 9% at this follow-up,” she said.

And the overall response rate is 91%.

Treatment exposure and toxicity

The median duration of ibrutinib treatment is 41 months, and 46% of patients continue on treatment. Twenty-seven percent of patients discontinued due to progression, and 12% because of adverse events (AEs).

Of the 53 patients who discontinued therapy, 14 had transformation as their primary reason, 9 with diffuse large B-cell lymphoma, 3 with Hodgkin disease, and 2 with prolymphocytic lymphoma.

The most frequent AEs leading to discontinuation included pneumonia (n=3), anemia (n=2), thrombocytopenia (n=2), diarrhea (n=2), and anal incontinence (n=2).

AEs leading to discontinuation decreased over time—6% in year 0 to 1 and 4% in years 2 to 3.

“The most frequent cumulative AEs are similar to what we’ve seen in most prior studies,” Dr Brown said, including diarrhea, fatigue, and cough.

In terms of grade 3 or higher AEs, about a quarter of patients had neutropenia, 17% had pneumonia, and 8% had hypertension.

Six percent of patients had major hemorrhage, and all-grade atrial fibrillation occurred in 11% of patients.

“Now, many of the grade 3 and higher AEs did decline over time during the study,” Dr Brown noted. “You can see this is quite evident for neutropenia as well as pneumonia, and all infections declined from year 1 to subsequent years.”

Hypertension, in contrast, has been fairly steady over the later years, she said, and atrial fibrillation is highest in the first 6 months but then continues at a low rate thereafter.

The investigators believe these long-term results demonstrate that ibrutinib is tolerable and continues to show sustained efficacy in previously treated and high-genomic-risk patients with CLL. In addition, no long-term safety signals have emerged.

This study was sponsored by Pharmacyclics, LLC, an AbbVie company.

Photo courtesy of Janssen

NEW YORK, NY—The 4-year follow-up of the RESONATE trial suggests ibrutinib may provide long-term efficacy in previously treated patients with chronic lymphocytic leukemia (CLL).

The median progression-free survival (PFS) has not yet been reached in this trial, regardless of high-risk cytogenetics, according to Jennifer Brown, MD, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

She presented the update at Lymphoma & Myeloma 2017. The follow-up study was awarded the best clinical CLL abstract of the meeting.

In the phase 3 RESONATE study, investigators compared ibrutinib—the first-in-class, once-daily, oral inhibitor of Bruton tyrosine kinase—to ofatumumab in previously treated CLL/small lymphocytic lymphoma (SLL).

The primary analysis showed ibrutinib significantly improved survival, with a 78% reduction in the risk of progression and a 57% reduction in the risk of death.

The phase 3 trial randomized 195 CLL/SLL patients to oral ibrutinib at 420 mg once daily and 196 patients to intravenous ofatumumab at an initial dose of 300 mg followed by 2000 mg for 11 doses over 24 weeks.

One hundred thirty-three patients progressed on ofatumumab and crossed over to receive once-daily ibrutinib.

Patient characteristics

In each arm, the median patient age was 67, more than half of patients had an ECOG status of 1, and more than half had advanced-stage disease.

High-risk genetic abnormalities were common, Dr Brown said, with deletion 11q in a third of patients in the ibrutinib arm and 31% in the ofatumumab arm. Another third in each arm had deletion 17p, while 51% in the ibrutinib arm and 46% in the ofatumumab arm had TP53 mutation.

About a quarter of the patients in each arm had complex karyotype, and 73% and 63% in the ibrutinib and ofatumumab arms, respectively, were IGHV-unmutated.

Survival

Ibrutinib significantly extended PFS compared with ofatumumab. At a median follow-up for ibrutinib of 44 months (range, 0.33 – 53), ibrutinib led to an 87% reduction in the risk of progression or death. The 3-year PFS rate was 59% with ibrutinib and 3% with ofatumumab.

Ibrutinib conferred a benefit in PFS across all baseline patient characteristics.

Among ibrutinib-treated patients, the 3-year PFS was 53% for patients with deletion 17p, 66% for those with deletion 11q but not deletion 17p, and 58% for those with neither abnormality.

Dr Brown noted how closely complex karyotype associates with high-risk cytogenetics. Forty-two percent of patients with 17p deletion had a complex karyotype, as did 23% of patients with 11q deletion and 15% of patients with neither 17p nor 11q deletion.

For IGHV-mutation status, Dr Brown said there is no difference in PFS with this degree of follow-up.

In terms of TP53 mutation status, Dr Brown pointed out a trend toward a worse PFS in those patients with the mutation.

“We actually looked by individual p53 mutation versus 17p deletion, versus both, versus neither, in the 2-year follow-up paper and found that p53 with 17p, both abnormalities, did have worse PFS than neither,” she said.

“This may require further follow-up because we do know that most 17p patients also have a p53 mutation, particularly in the relapsed setting.”

As expected, Dr Brown said, those patients with more than 2 prior therapies had a worse PFS compared to patients with 2 or fewer prior therapies.

Multivariate analysis demonstrated that more than 2 prior lines of therapy or an elevated ß2 microglobulin were associated with decreased PFS with ibrutinib.

When the investigators adjusted the overall survival data for cross-over, ibrutinib was projected to continue the overall survival benefit compared with ofatumumab, with a hazard ratio of 0.37.

Response rates

Dr Brown noted that, early on, there’s quite a significant rate of partial response with lymphocytosis observed in patients on ibrutinib.

This “diminishes dramatically,” she said, but about 5% of patients at 3 and 4 years still have ongoing lymphocytosis.

“Similarly, initially, there’s a very low rate of complete remission, which has risen steadily to 9% at this follow-up,” she said.

And the overall response rate is 91%.

Treatment exposure and toxicity

The median duration of ibrutinib treatment is 41 months, and 46% of patients continue on treatment. Twenty-seven percent of patients discontinued due to progression, and 12% because of adverse events (AEs).

Of the 53 patients who discontinued therapy, 14 had transformation as their primary reason, 9 with diffuse large B-cell lymphoma, 3 with Hodgkin disease, and 2 with prolymphocytic lymphoma.

The most frequent AEs leading to discontinuation included pneumonia (n=3), anemia (n=2), thrombocytopenia (n=2), diarrhea (n=2), and anal incontinence (n=2).

AEs leading to discontinuation decreased over time—6% in year 0 to 1 and 4% in years 2 to 3.

“The most frequent cumulative AEs are similar to what we’ve seen in most prior studies,” Dr Brown said, including diarrhea, fatigue, and cough.

In terms of grade 3 or higher AEs, about a quarter of patients had neutropenia, 17% had pneumonia, and 8% had hypertension.

Six percent of patients had major hemorrhage, and all-grade atrial fibrillation occurred in 11% of patients.

“Now, many of the grade 3 and higher AEs did decline over time during the study,” Dr Brown noted. “You can see this is quite evident for neutropenia as well as pneumonia, and all infections declined from year 1 to subsequent years.”

Hypertension, in contrast, has been fairly steady over the later years, she said, and atrial fibrillation is highest in the first 6 months but then continues at a low rate thereafter.

The investigators believe these long-term results demonstrate that ibrutinib is tolerable and continues to show sustained efficacy in previously treated and high-genomic-risk patients with CLL. In addition, no long-term safety signals have emerged.

This study was sponsored by Pharmacyclics, LLC, an AbbVie company.

Photo courtesy of Janssen

NEW YORK, NY—The 4-year follow-up of the RESONATE trial suggests ibrutinib may provide long-term efficacy in previously treated patients with chronic lymphocytic leukemia (CLL).

The median progression-free survival (PFS) has not yet been reached in this trial, regardless of high-risk cytogenetics, according to Jennifer Brown, MD, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

She presented the update at Lymphoma & Myeloma 2017. The follow-up study was awarded the best clinical CLL abstract of the meeting.

In the phase 3 RESONATE study, investigators compared ibrutinib—the first-in-class, once-daily, oral inhibitor of Bruton tyrosine kinase—to ofatumumab in previously treated CLL/small lymphocytic lymphoma (SLL).

The primary analysis showed ibrutinib significantly improved survival, with a 78% reduction in the risk of progression and a 57% reduction in the risk of death.

The phase 3 trial randomized 195 CLL/SLL patients to oral ibrutinib at 420 mg once daily and 196 patients to intravenous ofatumumab at an initial dose of 300 mg followed by 2000 mg for 11 doses over 24 weeks.

One hundred thirty-three patients progressed on ofatumumab and crossed over to receive once-daily ibrutinib.

Patient characteristics

In each arm, the median patient age was 67, more than half of patients had an ECOG status of 1, and more than half had advanced-stage disease.

High-risk genetic abnormalities were common, Dr Brown said, with deletion 11q in a third of patients in the ibrutinib arm and 31% in the ofatumumab arm. Another third in each arm had deletion 17p, while 51% in the ibrutinib arm and 46% in the ofatumumab arm had TP53 mutation.

About a quarter of the patients in each arm had complex karyotype, and 73% and 63% in the ibrutinib and ofatumumab arms, respectively, were IGHV-unmutated.

Survival

Ibrutinib significantly extended PFS compared with ofatumumab. At a median follow-up for ibrutinib of 44 months (range, 0.33 – 53), ibrutinib led to an 87% reduction in the risk of progression or death. The 3-year PFS rate was 59% with ibrutinib and 3% with ofatumumab.

Ibrutinib conferred a benefit in PFS across all baseline patient characteristics.

Among ibrutinib-treated patients, the 3-year PFS was 53% for patients with deletion 17p, 66% for those with deletion 11q but not deletion 17p, and 58% for those with neither abnormality.

Dr Brown noted how closely complex karyotype associates with high-risk cytogenetics. Forty-two percent of patients with 17p deletion had a complex karyotype, as did 23% of patients with 11q deletion and 15% of patients with neither 17p nor 11q deletion.

For IGHV-mutation status, Dr Brown said there is no difference in PFS with this degree of follow-up.

In terms of TP53 mutation status, Dr Brown pointed out a trend toward a worse PFS in those patients with the mutation.

“We actually looked by individual p53 mutation versus 17p deletion, versus both, versus neither, in the 2-year follow-up paper and found that p53 with 17p, both abnormalities, did have worse PFS than neither,” she said.

“This may require further follow-up because we do know that most 17p patients also have a p53 mutation, particularly in the relapsed setting.”

As expected, Dr Brown said, those patients with more than 2 prior therapies had a worse PFS compared to patients with 2 or fewer prior therapies.

Multivariate analysis demonstrated that more than 2 prior lines of therapy or an elevated ß2 microglobulin were associated with decreased PFS with ibrutinib.

When the investigators adjusted the overall survival data for cross-over, ibrutinib was projected to continue the overall survival benefit compared with ofatumumab, with a hazard ratio of 0.37.

Response rates

Dr Brown noted that, early on, there’s quite a significant rate of partial response with lymphocytosis observed in patients on ibrutinib.

This “diminishes dramatically,” she said, but about 5% of patients at 3 and 4 years still have ongoing lymphocytosis.

“Similarly, initially, there’s a very low rate of complete remission, which has risen steadily to 9% at this follow-up,” she said.

And the overall response rate is 91%.

Treatment exposure and toxicity

The median duration of ibrutinib treatment is 41 months, and 46% of patients continue on treatment. Twenty-seven percent of patients discontinued due to progression, and 12% because of adverse events (AEs).

Of the 53 patients who discontinued therapy, 14 had transformation as their primary reason, 9 with diffuse large B-cell lymphoma, 3 with Hodgkin disease, and 2 with prolymphocytic lymphoma.

The most frequent AEs leading to discontinuation included pneumonia (n=3), anemia (n=2), thrombocytopenia (n=2), diarrhea (n=2), and anal incontinence (n=2).

AEs leading to discontinuation decreased over time—6% in year 0 to 1 and 4% in years 2 to 3.

“The most frequent cumulative AEs are similar to what we’ve seen in most prior studies,” Dr Brown said, including diarrhea, fatigue, and cough.

In terms of grade 3 or higher AEs, about a quarter of patients had neutropenia, 17% had pneumonia, and 8% had hypertension.

Six percent of patients had major hemorrhage, and all-grade atrial fibrillation occurred in 11% of patients.

“Now, many of the grade 3 and higher AEs did decline over time during the study,” Dr Brown noted. “You can see this is quite evident for neutropenia as well as pneumonia, and all infections declined from year 1 to subsequent years.”

Hypertension, in contrast, has been fairly steady over the later years, she said, and atrial fibrillation is highest in the first 6 months but then continues at a low rate thereafter.

The investigators believe these long-term results demonstrate that ibrutinib is tolerable and continues to show sustained efficacy in previously treated and high-genomic-risk patients with CLL. In addition, no long-term safety signals have emerged.

This study was sponsored by Pharmacyclics, LLC, an AbbVie company.

Red and white blood cells

The US Food and Drug Administration (FDA) has expanded the approved use of the XW-100 Automated Hematology Analyzer.

The analyzer can now be used at non-traditional laboratory sites by non-medical personnel.

The XW-100 Automated Hematology Analyzer is intended for use in patients age 2 and older who require a whole blood cell count and white blood cell differential.

Test results can be used with other clinical and laboratory findings to provide early alerts of patients with serious conditions, such as severe anemia and agranulocytosis, who require additional testing.

The XW-100 Automated Hematology Analyzer is not intended to diagnose or monitor patients with primary and/or secondary hematologic diseases.

The device works by using a blood sample to classify and quantify 12 hematology parameters, which provides patients with a blood component profile as part of their overall health assessment.

Expanded clearance

The FDA granted the XW-100 Automated Hematology Analyzer a waiver under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). The waiver allows the device to be used by a variety of non-traditional laboratory sites, including physicians’ offices, clinics, or other types of healthcare facilities with a CLIA Certificate of Waiver.

The XW-100 Automated Hematology Analyzer was reviewed through the dual submission pathway, a streamlined regulatory pathway for 510(k) marketing clearance and CLIA Waiver by Application.

A 510(k) notification is a premarket submission made by device manufacturers to the FDA to demonstrate that the new device is substantially equivalent to a legally marketed predicate device.

The XW-100 Automated Hematology Analyzer was originally cleared through the 510(k) pathway in 2015 for use at the patient’s point-of-care.

To support the use of this device in CLIA-waived settings with non-medical personnel, the analyzer is now accompanied by simple instructions for operator actions when results are flagged or outside of a specified range.

To further ensure accurate testing in this setting and to eliminate results that are most susceptible to inaccuracy or require additional testing, the number of hematology parameters has been reduced to 12.

The FDA found this modified version of the XW-100 Automated Hematology Analyzer to be substantially equivalent to the 2015 model.

In addition, data submitted by Sysmex America, Inc. (the company marketing the analyzer) demonstrated ease of use and a low risk of false results when the modified XW-100 Automated Hematology Analyzer was used by untrained operators.

The FDA reviewed data from a study conducted on 582 samples collected from patients ages 2 to 92.

In this study, researchers compared XW-100 Automated Hematology Analyzer results collected by non-medical personnel in CLIA-waived settings to results from a hematology analyzer in an accredited clinical laboratory.

Results showed that, by following the manufacturer’s instructions for use, accurate testing can be effectively conducted by untrained personnel.

Red and white blood cells

The US Food and Drug Administration (FDA) has expanded the approved use of the XW-100 Automated Hematology Analyzer.

The analyzer can now be used at non-traditional laboratory sites by non-medical personnel.

The XW-100 Automated Hematology Analyzer is intended for use in patients age 2 and older who require a whole blood cell count and white blood cell differential.

Test results can be used with other clinical and laboratory findings to provide early alerts of patients with serious conditions, such as severe anemia and agranulocytosis, who require additional testing.

The XW-100 Automated Hematology Analyzer is not intended to diagnose or monitor patients with primary and/or secondary hematologic diseases.

The device works by using a blood sample to classify and quantify 12 hematology parameters, which provides patients with a blood component profile as part of their overall health assessment.

Expanded clearance

The FDA granted the XW-100 Automated Hematology Analyzer a waiver under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). The waiver allows the device to be used by a variety of non-traditional laboratory sites, including physicians’ offices, clinics, or other types of healthcare facilities with a CLIA Certificate of Waiver.

The XW-100 Automated Hematology Analyzer was reviewed through the dual submission pathway, a streamlined regulatory pathway for 510(k) marketing clearance and CLIA Waiver by Application.

A 510(k) notification is a premarket submission made by device manufacturers to the FDA to demonstrate that the new device is substantially equivalent to a legally marketed predicate device.

The XW-100 Automated Hematology Analyzer was originally cleared through the 510(k) pathway in 2015 for use at the patient’s point-of-care.

To support the use of this device in CLIA-waived settings with non-medical personnel, the analyzer is now accompanied by simple instructions for operator actions when results are flagged or outside of a specified range.

To further ensure accurate testing in this setting and to eliminate results that are most susceptible to inaccuracy or require additional testing, the number of hematology parameters has been reduced to 12.

The FDA found this modified version of the XW-100 Automated Hematology Analyzer to be substantially equivalent to the 2015 model.

In addition, data submitted by Sysmex America, Inc. (the company marketing the analyzer) demonstrated ease of use and a low risk of false results when the modified XW-100 Automated Hematology Analyzer was used by untrained operators.

The FDA reviewed data from a study conducted on 582 samples collected from patients ages 2 to 92.

In this study, researchers compared XW-100 Automated Hematology Analyzer results collected by non-medical personnel in CLIA-waived settings to results from a hematology analyzer in an accredited clinical laboratory.

Results showed that, by following the manufacturer’s instructions for use, accurate testing can be effectively conducted by untrained personnel.

Red and white blood cells

The US Food and Drug Administration (FDA) has expanded the approved use of the XW-100 Automated Hematology Analyzer.

The analyzer can now be used at non-traditional laboratory sites by non-medical personnel.

The XW-100 Automated Hematology Analyzer is intended for use in patients age 2 and older who require a whole blood cell count and white blood cell differential.

Test results can be used with other clinical and laboratory findings to provide early alerts of patients with serious conditions, such as severe anemia and agranulocytosis, who require additional testing.

The XW-100 Automated Hematology Analyzer is not intended to diagnose or monitor patients with primary and/or secondary hematologic diseases.

The device works by using a blood sample to classify and quantify 12 hematology parameters, which provides patients with a blood component profile as part of their overall health assessment.

Expanded clearance

The FDA granted the XW-100 Automated Hematology Analyzer a waiver under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). The waiver allows the device to be used by a variety of non-traditional laboratory sites, including physicians’ offices, clinics, or other types of healthcare facilities with a CLIA Certificate of Waiver.

The XW-100 Automated Hematology Analyzer was reviewed through the dual submission pathway, a streamlined regulatory pathway for 510(k) marketing clearance and CLIA Waiver by Application.

A 510(k) notification is a premarket submission made by device manufacturers to the FDA to demonstrate that the new device is substantially equivalent to a legally marketed predicate device.

The XW-100 Automated Hematology Analyzer was originally cleared through the 510(k) pathway in 2015 for use at the patient’s point-of-care.

To support the use of this device in CLIA-waived settings with non-medical personnel, the analyzer is now accompanied by simple instructions for operator actions when results are flagged or outside of a specified range.

To further ensure accurate testing in this setting and to eliminate results that are most susceptible to inaccuracy or require additional testing, the number of hematology parameters has been reduced to 12.

The FDA found this modified version of the XW-100 Automated Hematology Analyzer to be substantially equivalent to the 2015 model.

In addition, data submitted by Sysmex America, Inc. (the company marketing the analyzer) demonstrated ease of use and a low risk of false results when the modified XW-100 Automated Hematology Analyzer was used by untrained operators.

The FDA reviewed data from a study conducted on 582 samples collected from patients ages 2 to 92.

In this study, researchers compared XW-100 Automated Hematology Analyzer results collected by non-medical personnel in CLIA-waived settings to results from a hematology analyzer in an accredited clinical laboratory.

Results showed that, by following the manufacturer’s instructions for use, accurate testing can be effectively conducted by untrained personnel.

Photo by Rhoda Baer

SAN DIEGO—New research suggests an intervention can improve psychosocial health in adolescents and young adults (AYAs) living with cancer.

The intervention, Promoting Resilience in Stress Management (PRISM), is designed to help patients manage stress, set goals, and change their perspective.

Overall, PRISM improved resilience, enhanced quality of life, increased hope, and lowered distress and depression in the patients studied.

Abby R. Rosenberg, MD, of Seattle Children’s Research Institute in Seattle, Washington, presented these results at the 2017 Palliative and Supportive Care in Oncology Symposium (abstract 176*).

“The experience of cancer is stressful in all realms, but we tend to focus more on physical symptoms than the equally important social and emotional challenges,” Dr Rosenberg said.

“This is particularly true for adolescents and young adults who already struggle with normal developmental changes. When you throw cancer into the mix, it can become much harder.”

With this in mind, Dr Rosenberg and her colleagues tested PRISM in AYAs with cancer. The trial included 99 English-speaking patients, ages 12 to 25, who were diagnosed with new or newly recurrent cancer.

The patients were randomized to receive PRISM (n=49) plus standard psychosocial supportive care or standard care alone (n=50). Standard care at Seattle Children’s Research Institute includes a dedicated social worker and access to psychologists, child-life specialists, and other experts in AYA oncology care, as needed.

PRISM targets 4 topics:

• Managing stress with skills based on mindfulness and relaxation
• Setting goals that are specific and realistic, as well as planning for roadblocks
• Positive reframing, or recognizing and replacing negative self-talk
• Making meaning, or identifying benefits, gratitude, purpose, and legacy.

Each of the 4 topics were discussed with patients in separate, one-on-one sessions with a trained research associate. The sessions lasted 30 minutes to an hour. Patients also received boosters and worksheets for practicing the skills discussed in the meetings.

After all 4 sessions had been completed, patients could participate in an optional family meeting. During this meeting, patients could discuss with their family members which aspects of PRISM worked.

Results

Patients completed surveys at study enrollment, 2 months, 4 months, and 6 months. There were 74 participants who were still alive and well enough to complete the 6-month survey—36 in the PRISM group and 38 in the control group.

At the 6-month mark, PRISM was associated with (sometimes significant) improvements in resilience (P=0.02), generic quality of life (P=0.08), cancer-specific quality of life (P=0.01), hope (P=0.34), and distress (P=0.03). (P values are for absolute difference from baseline to 6 months.)

In addition, the incidence of depression at 6 months was lower in the PRISM group than the control group—6% and 21%, respectively (odds ratio=0.09, 95% CI 0.01, 1.09).

All but 4 of the PRISM recipients chose to participate in the family meeting following their one-on-one sessions.

“We included the family meeting because teens told us they wanted to share with their parents, and parents told us they wanted to know what their children had learned,” Dr Rosenberg said. “While the specific impact of this meeting is yet to be determined, we hope it will guide families so that there is continued support of teen or young adult patients.”

Now, Dr Rosenberg and her colleagues would like to test PRISM in other patient populations.

“We need to include a much larger cultural demographic in future studies,” Dr Rosenberg noted. “Beyond that, we also need to determine if this type of intervention could translate to other centers where usual care may not be as comprehensive as what we have here.”

*Some data in the abstract differ from the presentation.

Photo by Rhoda Baer

SAN DIEGO—New research suggests an intervention can improve psychosocial health in adolescents and young adults (AYAs) living with cancer.

The intervention, Promoting Resilience in Stress Management (PRISM), is designed to help patients manage stress, set goals, and change their perspective.

Overall, PRISM improved resilience, enhanced quality of life, increased hope, and lowered distress and depression in the patients studied.

Abby R. Rosenberg, MD, of Seattle Children’s Research Institute in Seattle, Washington, presented these results at the 2017 Palliative and Supportive Care in Oncology Symposium (abstract 176*).

“The experience of cancer is stressful in all realms, but we tend to focus more on physical symptoms than the equally important social and emotional challenges,” Dr Rosenberg said.

“This is particularly true for adolescents and young adults who already struggle with normal developmental changes. When you throw cancer into the mix, it can become much harder.”

With this in mind, Dr Rosenberg and her colleagues tested PRISM in AYAs with cancer. The trial included 99 English-speaking patients, ages 12 to 25, who were diagnosed with new or newly recurrent cancer.

The patients were randomized to receive PRISM (n=49) plus standard psychosocial supportive care or standard care alone (n=50). Standard care at Seattle Children’s Research Institute includes a dedicated social worker and access to psychologists, child-life specialists, and other experts in AYA oncology care, as needed.

PRISM targets 4 topics:

• Managing stress with skills based on mindfulness and relaxation
• Setting goals that are specific and realistic, as well as planning for roadblocks
• Positive reframing, or recognizing and replacing negative self-talk
• Making meaning, or identifying benefits, gratitude, purpose, and legacy.

Each of the 4 topics were discussed with patients in separate, one-on-one sessions with a trained research associate. The sessions lasted 30 minutes to an hour. Patients also received boosters and worksheets for practicing the skills discussed in the meetings.

After all 4 sessions had been completed, patients could participate in an optional family meeting. During this meeting, patients could discuss with their family members which aspects of PRISM worked.

Results

Patients completed surveys at study enrollment, 2 months, 4 months, and 6 months. There were 74 participants who were still alive and well enough to complete the 6-month survey—36 in the PRISM group and 38 in the control group.

At the 6-month mark, PRISM was associated with (sometimes significant) improvements in resilience (P=0.02), generic quality of life (P=0.08), cancer-specific quality of life (P=0.01), hope (P=0.34), and distress (P=0.03). (P values are for absolute difference from baseline to 6 months.)

In addition, the incidence of depression at 6 months was lower in the PRISM group than the control group—6% and 21%, respectively (odds ratio=0.09, 95% CI 0.01, 1.09).

All but 4 of the PRISM recipients chose to participate in the family meeting following their one-on-one sessions.

“We included the family meeting because teens told us they wanted to share with their parents, and parents told us they wanted to know what their children had learned,” Dr Rosenberg said. “While the specific impact of this meeting is yet to be determined, we hope it will guide families so that there is continued support of teen or young adult patients.”

Now, Dr Rosenberg and her colleagues would like to test PRISM in other patient populations.

“We need to include a much larger cultural demographic in future studies,” Dr Rosenberg noted. “Beyond that, we also need to determine if this type of intervention could translate to other centers where usual care may not be as comprehensive as what we have here.”

*Some data in the abstract differ from the presentation.

Photo by Rhoda Baer

SAN DIEGO—New research suggests an intervention can improve psychosocial health in adolescents and young adults (AYAs) living with cancer.

The intervention, Promoting Resilience in Stress Management (PRISM), is designed to help patients manage stress, set goals, and change their perspective.

Overall, PRISM improved resilience, enhanced quality of life, increased hope, and lowered distress and depression in the patients studied.

Abby R. Rosenberg, MD, of Seattle Children’s Research Institute in Seattle, Washington, presented these results at the 2017 Palliative and Supportive Care in Oncology Symposium (abstract 176*).

“The experience of cancer is stressful in all realms, but we tend to focus more on physical symptoms than the equally important social and emotional challenges,” Dr Rosenberg said.

“This is particularly true for adolescents and young adults who already struggle with normal developmental changes. When you throw cancer into the mix, it can become much harder.”

With this in mind, Dr Rosenberg and her colleagues tested PRISM in AYAs with cancer. The trial included 99 English-speaking patients, ages 12 to 25, who were diagnosed with new or newly recurrent cancer.

The patients were randomized to receive PRISM (n=49) plus standard psychosocial supportive care or standard care alone (n=50). Standard care at Seattle Children’s Research Institute includes a dedicated social worker and access to psychologists, child-life specialists, and other experts in AYA oncology care, as needed.

PRISM targets 4 topics:

• Managing stress with skills based on mindfulness and relaxation
• Setting goals that are specific and realistic, as well as planning for roadblocks
• Positive reframing, or recognizing and replacing negative self-talk
• Making meaning, or identifying benefits, gratitude, purpose, and legacy.

Each of the 4 topics were discussed with patients in separate, one-on-one sessions with a trained research associate. The sessions lasted 30 minutes to an hour. Patients also received boosters and worksheets for practicing the skills discussed in the meetings.

After all 4 sessions had been completed, patients could participate in an optional family meeting. During this meeting, patients could discuss with their family members which aspects of PRISM worked.

Results

Patients completed surveys at study enrollment, 2 months, 4 months, and 6 months. There were 74 participants who were still alive and well enough to complete the 6-month survey—36 in the PRISM group and 38 in the control group.

At the 6-month mark, PRISM was associated with (sometimes significant) improvements in resilience (P=0.02), generic quality of life (P=0.08), cancer-specific quality of life (P=0.01), hope (P=0.34), and distress (P=0.03). (P values are for absolute difference from baseline to 6 months.)

In addition, the incidence of depression at 6 months was lower in the PRISM group than the control group—6% and 21%, respectively (odds ratio=0.09, 95% CI 0.01, 1.09).

All but 4 of the PRISM recipients chose to participate in the family meeting following their one-on-one sessions.

“We included the family meeting because teens told us they wanted to share with their parents, and parents told us they wanted to know what their children had learned,” Dr Rosenberg said. “While the specific impact of this meeting is yet to be determined, we hope it will guide families so that there is continued support of teen or young adult patients.”

Now, Dr Rosenberg and her colleagues would like to test PRISM in other patient populations.

“We need to include a much larger cultural demographic in future studies,” Dr Rosenberg noted. “Beyond that, we also need to determine if this type of intervention could translate to other centers where usual care may not be as comprehensive as what we have here.”

*Some data in the abstract differ from the presentation.

Clinical question: What is the national frequency of interhospital transfers, and are there any patient or hospital factors that predict these transfers?

Background: Interhospital patient transfers may be due to the need for a specialized service, but the factors and patterns have not been well studied.

Clinical question: What is the national frequency of interhospital transfers, and are there any patient or hospital factors that predict these transfers?

Background: Interhospital patient transfers may be due to the need for a specialized service, but the factors and patterns have not been well studied.

Clinical question: What is the national frequency of interhospital transfers, and are there any patient or hospital factors that predict these transfers?

Background: Interhospital patient transfers may be due to the need for a specialized service, but the factors and patterns have not been well studied.

With new technology available to aid patients, diabetes management in the 21st century is moving beyond metformin. Among these advances are insulin pumps, which are not just for the young and tech-savvy. In fact, in 2016, the American Diabetes Association (ADA) revised their Standards in Medical Care to recommend patients 65 and older continue to use their insulin pumps and continuous glucose monitoring devices (CGMs), rather than forego technology for more traditional treatment options.¹

Insulin pumps enhance or mimic the role of the pancreas by providing a background, or basal, rate of insulin, as well as boluses for food or glucose corrections. A small catheter is inserted under the skin—in the same areas used for injections (eg, arm, thigh, abdomen)—to release ­insulin.²

While the benefits of technology cannot always be quantified, there are data to suggest insulin pumps can reduce A1C by 1.1% in patients with type 2 diabetes. In tandem with CGMs, insulin pumps have been shown to be cost effective in those with a history of severe hypoglycemia.^3,4

Q When should patients consider using an insulin pump?

Patients with type 1 or type 2 diabetes can benefit from an insulin pump. In particular, they can be useful for patients who

Are tired of multiple daily injections. Insulin is still bolused at mealtime—just electronically.

Require a tailored approach. Multiple basal settings can be programmed to reflect activity and work level; some patients need more insulin on active days and less on sedentary days.

Have an on-the-go lifestyle. Insulin pumps replace multiple daily injections, as noted, which helps when patients miss manual injections due to accessibility issues.

Value discretion. Those who wear restrictive uniforms for work or simply desire privacy may benefit from an insulin pump model that can bolus via remote control, without physical access to the pump.

Have found other treatments suboptimal. Some insurers allow patients to try a pump before a decision is made.

Experience hypoglycemia unawareness. Some pumps work with CGMs to suspend insulin delivery with a low glucose level; proper use of a pump can help to restore patient awareness of their condition.

Are sensitive to insulin. Select pumps can deliver insulin at a rate of one-hundredth of a unit at a time.

Experience the dawn phenomenon or Somogyi effect. Patients with high early-morning glucose levels can adjust their rates to combat hyperglycemia, and those with overnight lows and rebounding hyperglycemia can adjust their basal rates or nighttime snacking settings to prevent this occurrence.

Q Who would be an ideal candidate?

Motivated patients who want to attain glycemic control and adhere to the recommendations of their care team are ideally suited to insulin pump use. Insurance companies want to ensure patient safety, so before approving coverage for an insulin pump, they may require patients to demonstrate their willingness to adjust their lifestyle, work with their diabetes educator and/or provider team, and test routinely in the weeks or months leading up to the final decision—all expected behavior while using pump therapy.

Q How do you initiate insulin pump therapy?

With any new treatment, clear communication is key. Patients should schedule specific appointments with their provider and diabetes team to know what is expected from both parties during this process.

Pump selection should be individualized choice, depending on the patient’s goals, lifestyle, and a thorough review of the pros and cons of each pump. When a selection has been made, patients can begin testing—at least four times daily, before meals and at bedtime, as required by most insurers. Representatives from the pump’s manufacturer can be a helpful resource for questions about the particular pump, as well as a liaison to the insurance company if clarifications are needed.

Each practice is different, but once insurance coverage is determined, the patient may be asked to review his/her food log with the team. Those who count carbohydrates may be assessed for their ability to accurately measure and record this information, since it improves the accuracy of insulin boluses and effectiveness of treatment. Patients who do not count carbs should be advised of alternative options, such as capping meals at a certain carbohydrate amount (eg, 60 to 75 g, based on labels) or carbohydrate exchanges (eg, if a typical serving size is 15 g, patients may have 3 servings per meal).

The comfort level of the practice and the care team, as well as the patient, may influence how pump therapy is initiated. Some care teams may decide to do a trial run with saline for safety, to ensure the patient is using the pump properly before advancing to insulin.

Q What are some features to consider when selecting a pump?

The practical reality is that individual practices and providers are unlikely to offer every possible insulin pump; a practice may not have the software needed to download data from every type of pump. Patients must be comfortable with their choice of pump—but so must providers. A clinician may be more familiar and/or comfortable with a particular pump (or pumps), based in part on his/her relationship with the manufacturer. If the provider feels sufficiently educated, he or she is better equipped to advise the patient on usage.

Some of the insulin pumps available in the United States are described in the table.^5-11 Note that there are many common features, such as 24-hour toll-free assistance hotlines; child button lockouts; full training; temporary basal rate options; programmable reminders; downloadable glucose data; low insulin warnings; low battery warnings; and user-set active insulin times. Other features vary and may influence a patient’s choice of pump. These include color vs black-and-white screen (which can impact patients with impaired vision); tubeless versus insulin tubes; insulin cartridge size; compatibility and integration with CGMs; various degrees of water resistance; and hypoglycemia suspension.¹²

Q Does insurance cover insulin pumps?

Insurance coverage varies and may be offered on a case-by-case basis. Also, some insurers have preferred insulin pumps just as they have a preferred formulary.

Some insurance companies may require patients to use multiple daily injections for at least six months prior to pump approval. Prior authorization for a pump trial (of a specific duration) may be required; after trial completion, another prior authorization may be needed before approval is granted. During the trial, the patient will need to demonstrate competency in self-management with the pump, motivation to continue use, and commitment to making dietary and lifestyle changes. Some insurers may want to see A1C lowered to less than 7%, although this stipulation may be assessed by case, particularly in patients with risk factors for poor glycemic control (eg, recurrent hypoglycemia, severe hypoglycemic episode, dawn phenomenon, large glycemic excursions, or pregnancy). Others will require patients to complete a comprehensive diabetes education program within two years prior to pump initiation.^13,14

For Medicare-qualified patients, pump supplies may not be covered; they may have to rely on supplemental insurance or switch therapies if insulin pump usage is not financially feasible. Under “original Medicare,” patients pay 20% of the Medicare-approved amount after the part B deductible for pump equipment (which is categorized as durable medical equipment). Medicare does pay for 80% of the insulin cost, but coverage can differ by case.¹⁵

Q What are CGMs, and are they required?

CGMs are small, external devices that sample glucose from the interstitial fluid using an electrode under the skin. The electrode transmits information to a display device, which can alert patients of patient-specific glucose values: if a high or low glucose value is reached; if the glucose value is predicted to change; or the rate of glucose value change.

CGMs do not completely replace testing glucose levels, as they typically need to be calibrated two or more times throughout the day (though upcoming technology may reduce that to one or no calibrations). During calibration, patients manually check their glucose levels and enter readings into the CGM to ensure accuracy.

CGMs are not required, but they can enhance a patient’s insulin pump experience. Some CGMs “talk” directly with insulin pumps, so users do not have to manually input glucose levels. However, while there is even a CGM on the market that allows insulin dosing without a finger-prick, most sensors encourage patients to dose insulin based on manual glucose readings rather than CGM readings. A notable exception is a CGM “talking” to an insulin pump with a safety feature that can temporarily shut off the pump if low glucose levels are detected or predicted.^16-18

Q What are the latest advances in insulin pumps?

In September 2016, the FDA approved Medtronic’s hybrid closed-loop system for use by patients (ages 14 and older) with type 1 diabetes who use 8 U or more of insulin daily. This new insulin pump system, which uses a CGM, is sometimes referred to as an “artificial pancreas.” It tracks glucose levels every five minutes, increasing or decreasing basal insulin rates according to a glucose-based algorithm (though users still bolus at mealtimes by entering carbohydrates and calibrating their sensor).^19,20 Approval was based on results from a study of patients ages 14 to 75 with type 1 diabetes, which showed a reduction in A1C from 7.4% to 6.9%, without severe hypoglycemia or diabetic ketoacidosis. The percentage of patients in target range (defined as 70-180 mg/dL) increased from 66.7% at baseline to 72.2% at the end of the study.²¹ Medtronic officially launched the device in June 2017.

Other manufacturers are not far behind. Tandem is currently participating in an NIH-funded International Diabetes Closed Loop (IDCL) Trial of combined technology from Tandem Diabetes Care, Dexcom, and TypeZero (a software company). The company projects a launch date of late 2018 for their product.²²

Editor’s Note: At press time, Animas had announced that it will be discontinuing its insulin pumps in the United States. More information, including a transition plan for patients, is available at www.animaspatientsupport.com.

With new technology available to aid patients, diabetes management in the 21st century is moving beyond metformin. Among these advances are insulin pumps, which are not just for the young and tech-savvy. In fact, in 2016, the American Diabetes Association (ADA) revised their Standards in Medical Care to recommend patients 65 and older continue to use their insulin pumps and continuous glucose monitoring devices (CGMs), rather than forego technology for more traditional treatment options.¹

Insulin pumps enhance or mimic the role of the pancreas by providing a background, or basal, rate of insulin, as well as boluses for food or glucose corrections. A small catheter is inserted under the skin—in the same areas used for injections (eg, arm, thigh, abdomen)—to release ­insulin.²

While the benefits of technology cannot always be quantified, there are data to suggest insulin pumps can reduce A1C by 1.1% in patients with type 2 diabetes. In tandem with CGMs, insulin pumps have been shown to be cost effective in those with a history of severe hypoglycemia.^3,4

Q When should patients consider using an insulin pump?

Patients with type 1 or type 2 diabetes can benefit from an insulin pump. In particular, they can be useful for patients who

Are tired of multiple daily injections. Insulin is still bolused at mealtime—just electronically.

Require a tailored approach. Multiple basal settings can be programmed to reflect activity and work level; some patients need more insulin on active days and less on sedentary days.

Have an on-the-go lifestyle. Insulin pumps replace multiple daily injections, as noted, which helps when patients miss manual injections due to accessibility issues.

Value discretion. Those who wear restrictive uniforms for work or simply desire privacy may benefit from an insulin pump model that can bolus via remote control, without physical access to the pump.

Have found other treatments suboptimal. Some insurers allow patients to try a pump before a decision is made.

Experience hypoglycemia unawareness. Some pumps work with CGMs to suspend insulin delivery with a low glucose level; proper use of a pump can help to restore patient awareness of their condition.

Are sensitive to insulin. Select pumps can deliver insulin at a rate of one-hundredth of a unit at a time.

Experience the dawn phenomenon or Somogyi effect. Patients with high early-morning glucose levels can adjust their rates to combat hyperglycemia, and those with overnight lows and rebounding hyperglycemia can adjust their basal rates or nighttime snacking settings to prevent this occurrence.

Q Who would be an ideal candidate?

Motivated patients who want to attain glycemic control and adhere to the recommendations of their care team are ideally suited to insulin pump use. Insurance companies want to ensure patient safety, so before approving coverage for an insulin pump, they may require patients to demonstrate their willingness to adjust their lifestyle, work with their diabetes educator and/or provider team, and test routinely in the weeks or months leading up to the final decision—all expected behavior while using pump therapy.

Q How do you initiate insulin pump therapy?

With any new treatment, clear communication is key. Patients should schedule specific appointments with their provider and diabetes team to know what is expected from both parties during this process.

Pump selection should be individualized choice, depending on the patient’s goals, lifestyle, and a thorough review of the pros and cons of each pump. When a selection has been made, patients can begin testing—at least four times daily, before meals and at bedtime, as required by most insurers. Representatives from the pump’s manufacturer can be a helpful resource for questions about the particular pump, as well as a liaison to the insurance company if clarifications are needed.

Each practice is different, but once insurance coverage is determined, the patient may be asked to review his/her food log with the team. Those who count carbohydrates may be assessed for their ability to accurately measure and record this information, since it improves the accuracy of insulin boluses and effectiveness of treatment. Patients who do not count carbs should be advised of alternative options, such as capping meals at a certain carbohydrate amount (eg, 60 to 75 g, based on labels) or carbohydrate exchanges (eg, if a typical serving size is 15 g, patients may have 3 servings per meal).

The comfort level of the practice and the care team, as well as the patient, may influence how pump therapy is initiated. Some care teams may decide to do a trial run with saline for safety, to ensure the patient is using the pump properly before advancing to insulin.

Q What are some features to consider when selecting a pump?

The practical reality is that individual practices and providers are unlikely to offer every possible insulin pump; a practice may not have the software needed to download data from every type of pump. Patients must be comfortable with their choice of pump—but so must providers. A clinician may be more familiar and/or comfortable with a particular pump (or pumps), based in part on his/her relationship with the manufacturer. If the provider feels sufficiently educated, he or she is better equipped to advise the patient on usage.

Some of the insulin pumps available in the United States are described in the table.^5-11 Note that there are many common features, such as 24-hour toll-free assistance hotlines; child button lockouts; full training; temporary basal rate options; programmable reminders; downloadable glucose data; low insulin warnings; low battery warnings; and user-set active insulin times. Other features vary and may influence a patient’s choice of pump. These include color vs black-and-white screen (which can impact patients with impaired vision); tubeless versus insulin tubes; insulin cartridge size; compatibility and integration with CGMs; various degrees of water resistance; and hypoglycemia suspension.¹²

Q Does insurance cover insulin pumps?

Insurance coverage varies and may be offered on a case-by-case basis. Also, some insurers have preferred insulin pumps just as they have a preferred formulary.

Some insurance companies may require patients to use multiple daily injections for at least six months prior to pump approval. Prior authorization for a pump trial (of a specific duration) may be required; after trial completion, another prior authorization may be needed before approval is granted. During the trial, the patient will need to demonstrate competency in self-management with the pump, motivation to continue use, and commitment to making dietary and lifestyle changes. Some insurers may want to see A1C lowered to less than 7%, although this stipulation may be assessed by case, particularly in patients with risk factors for poor glycemic control (eg, recurrent hypoglycemia, severe hypoglycemic episode, dawn phenomenon, large glycemic excursions, or pregnancy). Others will require patients to complete a comprehensive diabetes education program within two years prior to pump initiation.^13,14

For Medicare-qualified patients, pump supplies may not be covered; they may have to rely on supplemental insurance or switch therapies if insulin pump usage is not financially feasible. Under “original Medicare,” patients pay 20% of the Medicare-approved amount after the part B deductible for pump equipment (which is categorized as durable medical equipment). Medicare does pay for 80% of the insulin cost, but coverage can differ by case.¹⁵

Q What are CGMs, and are they required?

CGMs are small, external devices that sample glucose from the interstitial fluid using an electrode under the skin. The electrode transmits information to a display device, which can alert patients of patient-specific glucose values: if a high or low glucose value is reached; if the glucose value is predicted to change; or the rate of glucose value change.

CGMs do not completely replace testing glucose levels, as they typically need to be calibrated two or more times throughout the day (though upcoming technology may reduce that to one or no calibrations). During calibration, patients manually check their glucose levels and enter readings into the CGM to ensure accuracy.

CGMs are not required, but they can enhance a patient’s insulin pump experience. Some CGMs “talk” directly with insulin pumps, so users do not have to manually input glucose levels. However, while there is even a CGM on the market that allows insulin dosing without a finger-prick, most sensors encourage patients to dose insulin based on manual glucose readings rather than CGM readings. A notable exception is a CGM “talking” to an insulin pump with a safety feature that can temporarily shut off the pump if low glucose levels are detected or predicted.^16-18

Q What are the latest advances in insulin pumps?

In September 2016, the FDA approved Medtronic’s hybrid closed-loop system for use by patients (ages 14 and older) with type 1 diabetes who use 8 U or more of insulin daily. This new insulin pump system, which uses a CGM, is sometimes referred to as an “artificial pancreas.” It tracks glucose levels every five minutes, increasing or decreasing basal insulin rates according to a glucose-based algorithm (though users still bolus at mealtimes by entering carbohydrates and calibrating their sensor).^19,20 Approval was based on results from a study of patients ages 14 to 75 with type 1 diabetes, which showed a reduction in A1C from 7.4% to 6.9%, without severe hypoglycemia or diabetic ketoacidosis. The percentage of patients in target range (defined as 70-180 mg/dL) increased from 66.7% at baseline to 72.2% at the end of the study.²¹ Medtronic officially launched the device in June 2017.

Other manufacturers are not far behind. Tandem is currently participating in an NIH-funded International Diabetes Closed Loop (IDCL) Trial of combined technology from Tandem Diabetes Care, Dexcom, and TypeZero (a software company). The company projects a launch date of late 2018 for their product.²²

Editor’s Note: At press time, Animas had announced that it will be discontinuing its insulin pumps in the United States. More information, including a transition plan for patients, is available at www.animaspatientsupport.com.

With new technology available to aid patients, diabetes management in the 21st century is moving beyond metformin. Among these advances are insulin pumps, which are not just for the young and tech-savvy. In fact, in 2016, the American Diabetes Association (ADA) revised their Standards in Medical Care to recommend patients 65 and older continue to use their insulin pumps and continuous glucose monitoring devices (CGMs), rather than forego technology for more traditional treatment options.¹

Insulin pumps enhance or mimic the role of the pancreas by providing a background, or basal, rate of insulin, as well as boluses for food or glucose corrections. A small catheter is inserted under the skin—in the same areas used for injections (eg, arm, thigh, abdomen)—to release ­insulin.²

While the benefits of technology cannot always be quantified, there are data to suggest insulin pumps can reduce A1C by 1.1% in patients with type 2 diabetes. In tandem with CGMs, insulin pumps have been shown to be cost effective in those with a history of severe hypoglycemia.^3,4

Q When should patients consider using an insulin pump?

Patients with type 1 or type 2 diabetes can benefit from an insulin pump. In particular, they can be useful for patients who

Are tired of multiple daily injections. Insulin is still bolused at mealtime—just electronically.

Require a tailored approach. Multiple basal settings can be programmed to reflect activity and work level; some patients need more insulin on active days and less on sedentary days.

Have an on-the-go lifestyle. Insulin pumps replace multiple daily injections, as noted, which helps when patients miss manual injections due to accessibility issues.

Value discretion. Those who wear restrictive uniforms for work or simply desire privacy may benefit from an insulin pump model that can bolus via remote control, without physical access to the pump.

Have found other treatments suboptimal. Some insurers allow patients to try a pump before a decision is made.

Experience hypoglycemia unawareness. Some pumps work with CGMs to suspend insulin delivery with a low glucose level; proper use of a pump can help to restore patient awareness of their condition.

Are sensitive to insulin. Select pumps can deliver insulin at a rate of one-hundredth of a unit at a time.

Experience the dawn phenomenon or Somogyi effect. Patients with high early-morning glucose levels can adjust their rates to combat hyperglycemia, and those with overnight lows and rebounding hyperglycemia can adjust their basal rates or nighttime snacking settings to prevent this occurrence.

Q Who would be an ideal candidate?

Motivated patients who want to attain glycemic control and adhere to the recommendations of their care team are ideally suited to insulin pump use. Insurance companies want to ensure patient safety, so before approving coverage for an insulin pump, they may require patients to demonstrate their willingness to adjust their lifestyle, work with their diabetes educator and/or provider team, and test routinely in the weeks or months leading up to the final decision—all expected behavior while using pump therapy.

Q How do you initiate insulin pump therapy?

With any new treatment, clear communication is key. Patients should schedule specific appointments with their provider and diabetes team to know what is expected from both parties during this process.

Pump selection should be individualized choice, depending on the patient’s goals, lifestyle, and a thorough review of the pros and cons of each pump. When a selection has been made, patients can begin testing—at least four times daily, before meals and at bedtime, as required by most insurers. Representatives from the pump’s manufacturer can be a helpful resource for questions about the particular pump, as well as a liaison to the insurance company if clarifications are needed.

Each practice is different, but once insurance coverage is determined, the patient may be asked to review his/her food log with the team. Those who count carbohydrates may be assessed for their ability to accurately measure and record this information, since it improves the accuracy of insulin boluses and effectiveness of treatment. Patients who do not count carbs should be advised of alternative options, such as capping meals at a certain carbohydrate amount (eg, 60 to 75 g, based on labels) or carbohydrate exchanges (eg, if a typical serving size is 15 g, patients may have 3 servings per meal).

The comfort level of the practice and the care team, as well as the patient, may influence how pump therapy is initiated. Some care teams may decide to do a trial run with saline for safety, to ensure the patient is using the pump properly before advancing to insulin.

Q What are some features to consider when selecting a pump?

The practical reality is that individual practices and providers are unlikely to offer every possible insulin pump; a practice may not have the software needed to download data from every type of pump. Patients must be comfortable with their choice of pump—but so must providers. A clinician may be more familiar and/or comfortable with a particular pump (or pumps), based in part on his/her relationship with the manufacturer. If the provider feels sufficiently educated, he or she is better equipped to advise the patient on usage.

Some of the insulin pumps available in the United States are described in the table.^5-11 Note that there are many common features, such as 24-hour toll-free assistance hotlines; child button lockouts; full training; temporary basal rate options; programmable reminders; downloadable glucose data; low insulin warnings; low battery warnings; and user-set active insulin times. Other features vary and may influence a patient’s choice of pump. These include color vs black-and-white screen (which can impact patients with impaired vision); tubeless versus insulin tubes; insulin cartridge size; compatibility and integration with CGMs; various degrees of water resistance; and hypoglycemia suspension.¹²

Q Does insurance cover insulin pumps?

Insurance coverage varies and may be offered on a case-by-case basis. Also, some insurers have preferred insulin pumps just as they have a preferred formulary.

Some insurance companies may require patients to use multiple daily injections for at least six months prior to pump approval. Prior authorization for a pump trial (of a specific duration) may be required; after trial completion, another prior authorization may be needed before approval is granted. During the trial, the patient will need to demonstrate competency in self-management with the pump, motivation to continue use, and commitment to making dietary and lifestyle changes. Some insurers may want to see A1C lowered to less than 7%, although this stipulation may be assessed by case, particularly in patients with risk factors for poor glycemic control (eg, recurrent hypoglycemia, severe hypoglycemic episode, dawn phenomenon, large glycemic excursions, or pregnancy). Others will require patients to complete a comprehensive diabetes education program within two years prior to pump initiation.^13,14

For Medicare-qualified patients, pump supplies may not be covered; they may have to rely on supplemental insurance or switch therapies if insulin pump usage is not financially feasible. Under “original Medicare,” patients pay 20% of the Medicare-approved amount after the part B deductible for pump equipment (which is categorized as durable medical equipment). Medicare does pay for 80% of the insulin cost, but coverage can differ by case.¹⁵

Q What are CGMs, and are they required?

CGMs are small, external devices that sample glucose from the interstitial fluid using an electrode under the skin. The electrode transmits information to a display device, which can alert patients of patient-specific glucose values: if a high or low glucose value is reached; if the glucose value is predicted to change; or the rate of glucose value change.

CGMs do not completely replace testing glucose levels, as they typically need to be calibrated two or more times throughout the day (though upcoming technology may reduce that to one or no calibrations). During calibration, patients manually check their glucose levels and enter readings into the CGM to ensure accuracy.

CGMs are not required, but they can enhance a patient’s insulin pump experience. Some CGMs “talk” directly with insulin pumps, so users do not have to manually input glucose levels. However, while there is even a CGM on the market that allows insulin dosing without a finger-prick, most sensors encourage patients to dose insulin based on manual glucose readings rather than CGM readings. A notable exception is a CGM “talking” to an insulin pump with a safety feature that can temporarily shut off the pump if low glucose levels are detected or predicted.^16-18

Q What are the latest advances in insulin pumps?

In September 2016, the FDA approved Medtronic’s hybrid closed-loop system for use by patients (ages 14 and older) with type 1 diabetes who use 8 U or more of insulin daily. This new insulin pump system, which uses a CGM, is sometimes referred to as an “artificial pancreas.” It tracks glucose levels every five minutes, increasing or decreasing basal insulin rates according to a glucose-based algorithm (though users still bolus at mealtimes by entering carbohydrates and calibrating their sensor).^19,20 Approval was based on results from a study of patients ages 14 to 75 with type 1 diabetes, which showed a reduction in A1C from 7.4% to 6.9%, without severe hypoglycemia or diabetic ketoacidosis. The percentage of patients in target range (defined as 70-180 mg/dL) increased from 66.7% at baseline to 72.2% at the end of the study.²¹ Medtronic officially launched the device in June 2017.

Other manufacturers are not far behind. Tandem is currently participating in an NIH-funded International Diabetes Closed Loop (IDCL) Trial of combined technology from Tandem Diabetes Care, Dexcom, and TypeZero (a software company). The company projects a launch date of late 2018 for their product.²²

Editor’s Note: At press time, Animas had announced that it will be discontinuing its insulin pumps in the United States. More information, including a transition plan for patients, is available at www.animaspatientsupport.com.

GENEVA – Apremilast showed substantial efficacy for patients with truly moderate psoriasis as defined by an involved body surface area of 5%-10% in the first-of-its-kind UNVEIL trial, Bruce Strober, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Patients with moderate psoriasis constitute a very large and underserved population, said Dr. Strober, professor and chair of the department of dermatology at the University of Connecticut, Farmington. “I would say the moderate psoriasis group defined by 5%-10% psoriasis-involved body surface area represents a gray area in our treatment. Often, people with this degree of psoriasis receive no treatment or are relegated to topical monotherapy, yet unfortunately do not respond to those treatments. Nevertheless, clinical trials for systemic therapies, including biologics, exclude this population solely because they’re under 10% involved body surface area,” he noted.

[email protected]

GENEVA – Apremilast showed substantial efficacy for patients with truly moderate psoriasis as defined by an involved body surface area of 5%-10% in the first-of-its-kind UNVEIL trial, Bruce Strober, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Patients with moderate psoriasis constitute a very large and underserved population, said Dr. Strober, professor and chair of the department of dermatology at the University of Connecticut, Farmington. “I would say the moderate psoriasis group defined by 5%-10% psoriasis-involved body surface area represents a gray area in our treatment. Often, people with this degree of psoriasis receive no treatment or are relegated to topical monotherapy, yet unfortunately do not respond to those treatments. Nevertheless, clinical trials for systemic therapies, including biologics, exclude this population solely because they’re under 10% involved body surface area,” he noted.

[email protected]

GENEVA – Apremilast showed substantial efficacy for patients with truly moderate psoriasis as defined by an involved body surface area of 5%-10% in the first-of-its-kind UNVEIL trial, Bruce Strober, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Patients with moderate psoriasis constitute a very large and underserved population, said Dr. Strober, professor and chair of the department of dermatology at the University of Connecticut, Farmington. “I would say the moderate psoriasis group defined by 5%-10% psoriasis-involved body surface area represents a gray area in our treatment. Often, people with this degree of psoriasis receive no treatment or are relegated to topical monotherapy, yet unfortunately do not respond to those treatments. Nevertheless, clinical trials for systemic therapies, including biologics, exclude this population solely because they’re under 10% involved body surface area,” he noted.

[email protected]

The Diagnosis: Isomorphic Psoriasis

Tattooing has become an increasingly popular trend among young people. Currently, there are no guidelines in the United States regulating the production of tattoo ink and pigments.¹ Henna tattooing, a form of temporary skin painting, also has risks of allergic contact dermatitis from paraphenylenediamine dye.² Complications following tattoo application include an allergic contact dermatitis to tattoo pigments, infection, granulomatous and lichenoid reactions, and skin disease localized to the tattooed area.³

Localized dermatosis arising in a traumatized area, or the Koebner phenomenon, was first described by Heinrich Koebner in 1877.⁴ He described the formation of psoriasiform lesions at the site of cutaneous trauma.⁵ These isomorphic lesions can occur in 25% of patients with psoriasis after trauma to the skin such as tattooing.⁶ Other dermatologic diseases that can present as an isomorphic response to tattooing include lichen planus, Darier disease, vitiligo, and autoimmune bullous disease.^3,5,6

Various causes of trauma such as burns, insect bites, physical trauma, and needle trauma have been shown to produce new psoriatic lesions.⁶ The time period from trauma to formation of psoriasiform lesions usually ranges from 10 to 20 days; however, an initial reaction can occur as early as 3 days or as long as 2 years after trauma.⁴ Although the pathophysiology of the isomorphic response is not well known, it has been shown that nerve growth factor has a role. Raychaudhuri et al⁷ demonstrated the upregulation of nerve growth factor in the development of a psoriatic lesion, influencing keratinocyte proliferation, angiogenesis, and T-cell activation. 

Physical trauma such as tattooing has been shown to cause an isomorphic response in psoriasis. We describe a case of isomorphic psoriasis in a patient after tattoo application. Our patient had a several-month history of well-controlled psoriasis prior to obtaining the new tattoo. Several days after receiving the tattoo, the patient reported an increase in psoriatic lesions, including at the site of the tattoo. The trauma causing the isomorphic response could have been either a response to the tattoo pigment or needle injury to the skin.⁶

Psoriasis and isomorphic lesions can be treated with topical corticosteroids as well as systemic and biologic agents. Our patient was treated with triamcinolone cream with good response.⁸

The Diagnosis: Isomorphic Psoriasis

Tattooing has become an increasingly popular trend among young people. Currently, there are no guidelines in the United States regulating the production of tattoo ink and pigments.¹ Henna tattooing, a form of temporary skin painting, also has risks of allergic contact dermatitis from paraphenylenediamine dye.² Complications following tattoo application include an allergic contact dermatitis to tattoo pigments, infection, granulomatous and lichenoid reactions, and skin disease localized to the tattooed area.³

Localized dermatosis arising in a traumatized area, or the Koebner phenomenon, was first described by Heinrich Koebner in 1877.⁴ He described the formation of psoriasiform lesions at the site of cutaneous trauma.⁵ These isomorphic lesions can occur in 25% of patients with psoriasis after trauma to the skin such as tattooing.⁶ Other dermatologic diseases that can present as an isomorphic response to tattooing include lichen planus, Darier disease, vitiligo, and autoimmune bullous disease.^3,5,6

Various causes of trauma such as burns, insect bites, physical trauma, and needle trauma have been shown to produce new psoriatic lesions.⁶ The time period from trauma to formation of psoriasiform lesions usually ranges from 10 to 20 days; however, an initial reaction can occur as early as 3 days or as long as 2 years after trauma.⁴ Although the pathophysiology of the isomorphic response is not well known, it has been shown that nerve growth factor has a role. Raychaudhuri et al⁷ demonstrated the upregulation of nerve growth factor in the development of a psoriatic lesion, influencing keratinocyte proliferation, angiogenesis, and T-cell activation. 

Physical trauma such as tattooing has been shown to cause an isomorphic response in psoriasis. We describe a case of isomorphic psoriasis in a patient after tattoo application. Our patient had a several-month history of well-controlled psoriasis prior to obtaining the new tattoo. Several days after receiving the tattoo, the patient reported an increase in psoriatic lesions, including at the site of the tattoo. The trauma causing the isomorphic response could have been either a response to the tattoo pigment or needle injury to the skin.⁶

Psoriasis and isomorphic lesions can be treated with topical corticosteroids as well as systemic and biologic agents. Our patient was treated with triamcinolone cream with good response.⁸

The Diagnosis: Isomorphic Psoriasis

Tattooing has become an increasingly popular trend among young people. Currently, there are no guidelines in the United States regulating the production of tattoo ink and pigments.¹ Henna tattooing, a form of temporary skin painting, also has risks of allergic contact dermatitis from paraphenylenediamine dye.² Complications following tattoo application include an allergic contact dermatitis to tattoo pigments, infection, granulomatous and lichenoid reactions, and skin disease localized to the tattooed area.³

Localized dermatosis arising in a traumatized area, or the Koebner phenomenon, was first described by Heinrich Koebner in 1877.⁴ He described the formation of psoriasiform lesions at the site of cutaneous trauma.⁵ These isomorphic lesions can occur in 25% of patients with psoriasis after trauma to the skin such as tattooing.⁶ Other dermatologic diseases that can present as an isomorphic response to tattooing include lichen planus, Darier disease, vitiligo, and autoimmune bullous disease.^3,5,6

Various causes of trauma such as burns, insect bites, physical trauma, and needle trauma have been shown to produce new psoriatic lesions.⁶ The time period from trauma to formation of psoriasiform lesions usually ranges from 10 to 20 days; however, an initial reaction can occur as early as 3 days or as long as 2 years after trauma.⁴ Although the pathophysiology of the isomorphic response is not well known, it has been shown that nerve growth factor has a role. Raychaudhuri et al⁷ demonstrated the upregulation of nerve growth factor in the development of a psoriatic lesion, influencing keratinocyte proliferation, angiogenesis, and T-cell activation. 

Physical trauma such as tattooing has been shown to cause an isomorphic response in psoriasis. We describe a case of isomorphic psoriasis in a patient after tattoo application. Our patient had a several-month history of well-controlled psoriasis prior to obtaining the new tattoo. Several days after receiving the tattoo, the patient reported an increase in psoriatic lesions, including at the site of the tattoo. The trauma causing the isomorphic response could have been either a response to the tattoo pigment or needle injury to the skin.⁶

Psoriasis and isomorphic lesions can be treated with topical corticosteroids as well as systemic and biologic agents. Our patient was treated with triamcinolone cream with good response.⁸

VICTORIA, B.C. – Ultrasound risk criteria for adults are no match for the training, skill, and gut instinct of an experienced radiologist when evaluating pediatric thyroid nodules, results of a retrospective cohort study reported at the annual meeting of the American Thyroid Association suggest.

“In 2015, the ATA commissioned a pediatric task force that developed valuable guidelines specific to our pediatric patients. These guidelines recommend performing an FNA [fine-needle aspiration biopsy] in any nodule with a concerning clinical history or a concerning ultrasound feature,” commented first author Ana L. Creo, MD, a pediatric endocrinology fellow at the Mayo Clinic in Rochester, Minn.

Study details

The investigators studied pediatric patients (mean age, 15.5 years) with thyroid nodules who underwent initial ultrasound at the Mayo Clinic during 1996-2015, had at least a year of follow-up, and for whom histology or cytology results were available. Those with a known genetic tumor syndrome or a history of radiation exposure were excluded.

Two blinded radiologists assessed nodule ultrasound features using the Thyroid Imaging and Reporting Data System (TIRADS) (J Am Coll Radiol. 2015;12[12 Pt A]:1272-9) and then rendered their overall impression: malignant, indeterminate, or benign.

Next, an independent reviewer assigned each nodule an ATA adult risk category (Thyroid. 2016;26:1-133): high, intermediate, low, or very low suspicion.

Finally, both measures were compared against the reference standard of the nodule’s histology or cytology results.

Ultimately, 34% of the patients had malignant nodules, Dr. Creo reported. “This is likely quite a bit elevated from the true prevalence due to our intentional study design requiring follow-up, likely excluding some patients with benign nodules,” she commented.

Patients with benign and malignant nodules did not differ significantly on any of a variety of sociodemographic and clinical factors, such as family history and mode of detection.

For comparison of sensitivity, the investigators combined the ATA risk categories of high and intermediate suspicion and combined the overall radiologists’ impression of malignant and indeterminate. “We felt this best answered the practical clinical question of how many malignant nodules would be missed if FNA was not performed, assuming FNA would typically be performed if the ATA risk stratification was high or intermediate or if the radiologist’s overall impression was malignant or indeterminate,” Dr. Creo explained.

Results here showed that the ATA risk stratification and the radiologists’ overall impression had the same high sensitivity of 90%.

For comparison of specificity, the investigators compared the ATA risk category of high suspicion with the radiologists’ overall impression of malignant.

Results showed that the overall impression had specificity of 80%, whereas the risk category had a specificity of only about 52%. Findings were similar when analyses instead used ATA high suspicion and intermediate suspicion combined.

“The key ultrasound characteristics that drove the diagnosis included having a solid component, calcifications, irregular margins, and hypoechogenicity – all similar to those seen in pediatric studies and similar to those in adult studies as well,” Dr. Creo noted.

Compared with benign nodules, malignant nodules significantly more often had a greater than 75% solid component (84% vs. 64%; P = .01), contained calcifications (60% vs. 18%; P less than .0001), had irregular margins (70% vs. 46%; P = .0073), and were hypoechogenic (74% vs. 51%; P = .0073). Notably, size and presence of halo did not differ significantly.

“Our study adds to previous work in that it had a relatively large pediatric sample size, used strict inclusion criteria with at least a year of follow-up to increase the validity of the diagnosis, and had precise definitions of the ultrasound features,” concluded Dr. Creo, who disclosed that she had no relevant conflicts of interest.

At the same time, the study had limitations, such as its use of a referral population, likely loss to follow-up of some patients with benign nodules, and possible clustering effect. “Lastly, we had the benefit of extremely experienced pediatric radiologists, and their overall diagnostic accuracy may not universally apply across all radiologists,” she said.

VICTORIA, B.C. – Ultrasound risk criteria for adults are no match for the training, skill, and gut instinct of an experienced radiologist when evaluating pediatric thyroid nodules, results of a retrospective cohort study reported at the annual meeting of the American Thyroid Association suggest.

“In 2015, the ATA commissioned a pediatric task force that developed valuable guidelines specific to our pediatric patients. These guidelines recommend performing an FNA [fine-needle aspiration biopsy] in any nodule with a concerning clinical history or a concerning ultrasound feature,” commented first author Ana L. Creo, MD, a pediatric endocrinology fellow at the Mayo Clinic in Rochester, Minn.

Study details

The investigators studied pediatric patients (mean age, 15.5 years) with thyroid nodules who underwent initial ultrasound at the Mayo Clinic during 1996-2015, had at least a year of follow-up, and for whom histology or cytology results were available. Those with a known genetic tumor syndrome or a history of radiation exposure were excluded.

Two blinded radiologists assessed nodule ultrasound features using the Thyroid Imaging and Reporting Data System (TIRADS) (J Am Coll Radiol. 2015;12[12 Pt A]:1272-9) and then rendered their overall impression: malignant, indeterminate, or benign.

Next, an independent reviewer assigned each nodule an ATA adult risk category (Thyroid. 2016;26:1-133): high, intermediate, low, or very low suspicion.

Finally, both measures were compared against the reference standard of the nodule’s histology or cytology results.

Ultimately, 34% of the patients had malignant nodules, Dr. Creo reported. “This is likely quite a bit elevated from the true prevalence due to our intentional study design requiring follow-up, likely excluding some patients with benign nodules,” she commented.

Patients with benign and malignant nodules did not differ significantly on any of a variety of sociodemographic and clinical factors, such as family history and mode of detection.

For comparison of sensitivity, the investigators combined the ATA risk categories of high and intermediate suspicion and combined the overall radiologists’ impression of malignant and indeterminate. “We felt this best answered the practical clinical question of how many malignant nodules would be missed if FNA was not performed, assuming FNA would typically be performed if the ATA risk stratification was high or intermediate or if the radiologist’s overall impression was malignant or indeterminate,” Dr. Creo explained.

Results here showed that the ATA risk stratification and the radiologists’ overall impression had the same high sensitivity of 90%.

For comparison of specificity, the investigators compared the ATA risk category of high suspicion with the radiologists’ overall impression of malignant.

Results showed that the overall impression had specificity of 80%, whereas the risk category had a specificity of only about 52%. Findings were similar when analyses instead used ATA high suspicion and intermediate suspicion combined.

“The key ultrasound characteristics that drove the diagnosis included having a solid component, calcifications, irregular margins, and hypoechogenicity – all similar to those seen in pediatric studies and similar to those in adult studies as well,” Dr. Creo noted.

Compared with benign nodules, malignant nodules significantly more often had a greater than 75% solid component (84% vs. 64%; P = .01), contained calcifications (60% vs. 18%; P less than .0001), had irregular margins (70% vs. 46%; P = .0073), and were hypoechogenic (74% vs. 51%; P = .0073). Notably, size and presence of halo did not differ significantly.

“Our study adds to previous work in that it had a relatively large pediatric sample size, used strict inclusion criteria with at least a year of follow-up to increase the validity of the diagnosis, and had precise definitions of the ultrasound features,” concluded Dr. Creo, who disclosed that she had no relevant conflicts of interest.

At the same time, the study had limitations, such as its use of a referral population, likely loss to follow-up of some patients with benign nodules, and possible clustering effect. “Lastly, we had the benefit of extremely experienced pediatric radiologists, and their overall diagnostic accuracy may not universally apply across all radiologists,” she said.

VICTORIA, B.C. – Ultrasound risk criteria for adults are no match for the training, skill, and gut instinct of an experienced radiologist when evaluating pediatric thyroid nodules, results of a retrospective cohort study reported at the annual meeting of the American Thyroid Association suggest.

“In 2015, the ATA commissioned a pediatric task force that developed valuable guidelines specific to our pediatric patients. These guidelines recommend performing an FNA [fine-needle aspiration biopsy] in any nodule with a concerning clinical history or a concerning ultrasound feature,” commented first author Ana L. Creo, MD, a pediatric endocrinology fellow at the Mayo Clinic in Rochester, Minn.

Study details

The investigators studied pediatric patients (mean age, 15.5 years) with thyroid nodules who underwent initial ultrasound at the Mayo Clinic during 1996-2015, had at least a year of follow-up, and for whom histology or cytology results were available. Those with a known genetic tumor syndrome or a history of radiation exposure were excluded.

Two blinded radiologists assessed nodule ultrasound features using the Thyroid Imaging and Reporting Data System (TIRADS) (J Am Coll Radiol. 2015;12[12 Pt A]:1272-9) and then rendered their overall impression: malignant, indeterminate, or benign.

Next, an independent reviewer assigned each nodule an ATA adult risk category (Thyroid. 2016;26:1-133): high, intermediate, low, or very low suspicion.

Finally, both measures were compared against the reference standard of the nodule’s histology or cytology results.

Ultimately, 34% of the patients had malignant nodules, Dr. Creo reported. “This is likely quite a bit elevated from the true prevalence due to our intentional study design requiring follow-up, likely excluding some patients with benign nodules,” she commented.

Patients with benign and malignant nodules did not differ significantly on any of a variety of sociodemographic and clinical factors, such as family history and mode of detection.

For comparison of sensitivity, the investigators combined the ATA risk categories of high and intermediate suspicion and combined the overall radiologists’ impression of malignant and indeterminate. “We felt this best answered the practical clinical question of how many malignant nodules would be missed if FNA was not performed, assuming FNA would typically be performed if the ATA risk stratification was high or intermediate or if the radiologist’s overall impression was malignant or indeterminate,” Dr. Creo explained.

Results here showed that the ATA risk stratification and the radiologists’ overall impression had the same high sensitivity of 90%.

For comparison of specificity, the investigators compared the ATA risk category of high suspicion with the radiologists’ overall impression of malignant.

Results showed that the overall impression had specificity of 80%, whereas the risk category had a specificity of only about 52%. Findings were similar when analyses instead used ATA high suspicion and intermediate suspicion combined.

“The key ultrasound characteristics that drove the diagnosis included having a solid component, calcifications, irregular margins, and hypoechogenicity – all similar to those seen in pediatric studies and similar to those in adult studies as well,” Dr. Creo noted.

Compared with benign nodules, malignant nodules significantly more often had a greater than 75% solid component (84% vs. 64%; P = .01), contained calcifications (60% vs. 18%; P less than .0001), had irregular margins (70% vs. 46%; P = .0073), and were hypoechogenic (74% vs. 51%; P = .0073). Notably, size and presence of halo did not differ significantly.

“Our study adds to previous work in that it had a relatively large pediatric sample size, used strict inclusion criteria with at least a year of follow-up to increase the validity of the diagnosis, and had precise definitions of the ultrasound features,” concluded Dr. Creo, who disclosed that she had no relevant conflicts of interest.

At the same time, the study had limitations, such as its use of a referral population, likely loss to follow-up of some patients with benign nodules, and possible clustering effect. “Lastly, we had the benefit of extremely experienced pediatric radiologists, and their overall diagnostic accuracy may not universally apply across all radiologists,” she said.

SAN DIEGO – Among patients with systemic lupus erythematosus, a low level of vitamin D is associated with an increased risk of end-stage renal disease and total organ damage, results from a single-center cohort study showed.

“We had previously proved that vitamin D supplementation helped lupus activity,” lead study author Michelle Petri, MD, MPH, said in an interview in advance of the annual meeting of the American College of Rheumatology. “Now, we prove that it specifically helps renal activity as measured by the urine protein. By helping to reduce urine protein, it helps to prevent permanent renal damage and end-stage renal disease.”

[email protected]

SAN DIEGO – Among patients with systemic lupus erythematosus, a low level of vitamin D is associated with an increased risk of end-stage renal disease and total organ damage, results from a single-center cohort study showed.

“We had previously proved that vitamin D supplementation helped lupus activity,” lead study author Michelle Petri, MD, MPH, said in an interview in advance of the annual meeting of the American College of Rheumatology. “Now, we prove that it specifically helps renal activity as measured by the urine protein. By helping to reduce urine protein, it helps to prevent permanent renal damage and end-stage renal disease.”

[email protected]

SAN DIEGO – Among patients with systemic lupus erythematosus, a low level of vitamin D is associated with an increased risk of end-stage renal disease and total organ damage, results from a single-center cohort study showed.

“We had previously proved that vitamin D supplementation helped lupus activity,” lead study author Michelle Petri, MD, MPH, said in an interview in advance of the annual meeting of the American College of Rheumatology. “Now, we prove that it specifically helps renal activity as measured by the urine protein. By helping to reduce urine protein, it helps to prevent permanent renal damage and end-stage renal disease.”

[email protected]

The Food and Drug Administration has approved vemurafenib for adults with Erdheim-Chester disease (ECD) with the BRAF V600 mutation.

The kinase inhibitor – marketed as Zelboraf – was approved on Nov. 6. It is the first approved treatment for ECD and is already on the market as a treatment for patients with unresectable or metastatic melanoma with BRAF V600E mutation.

The FDA expedited approval of the drug under the Priority Review and Breakthrough Therapy programs. The drug also received an orphan status designation, which makes the sponsor eligible for incentives such as tax credits for clinical testing.

The agency based its approval on results from 22 patients with BRAF-V600-mutation positive ECD. Half of the patients (11) experienced a partial reduction in tumor size and 1 patient experienced a complete response, according to the FDA. Initial results from the phase 2, open-label VE-BASKET study were published in 2015 (N Engl J Med. 2015 Aug 20;373[8]:726-36).

Common side effects of vemurafenib include arthralgias, maculopapular rash, alopecia, fatigue, prolonged QT interval, and papilloma. Severe side effects include development of new cancers, growth of tumors in patients with BRAF wild-type melanoma, anaphylaxis and DRESS syndrome, severe skin reactions, heart abnormalities, hepatotoxicity, photosensitivity, uveitis, radiation sensitization and radiation recall, and Dupuytren’s contracture and plantar fascial fibromatosis. The drug is also considered teratogenic and women should be advised to use contraception while taking it, according to the FDA.

The full prescribing information is available at zelboraf.com.

[email protected]

On Twitter @maryellenny

The Food and Drug Administration has approved vemurafenib for adults with Erdheim-Chester disease (ECD) with the BRAF V600 mutation.

The kinase inhibitor – marketed as Zelboraf – was approved on Nov. 6. It is the first approved treatment for ECD and is already on the market as a treatment for patients with unresectable or metastatic melanoma with BRAF V600E mutation.

The FDA expedited approval of the drug under the Priority Review and Breakthrough Therapy programs. The drug also received an orphan status designation, which makes the sponsor eligible for incentives such as tax credits for clinical testing.

The agency based its approval on results from 22 patients with BRAF-V600-mutation positive ECD. Half of the patients (11) experienced a partial reduction in tumor size and 1 patient experienced a complete response, according to the FDA. Initial results from the phase 2, open-label VE-BASKET study were published in 2015 (N Engl J Med. 2015 Aug 20;373[8]:726-36).

Common side effects of vemurafenib include arthralgias, maculopapular rash, alopecia, fatigue, prolonged QT interval, and papilloma. Severe side effects include development of new cancers, growth of tumors in patients with BRAF wild-type melanoma, anaphylaxis and DRESS syndrome, severe skin reactions, heart abnormalities, hepatotoxicity, photosensitivity, uveitis, radiation sensitization and radiation recall, and Dupuytren’s contracture and plantar fascial fibromatosis. The drug is also considered teratogenic and women should be advised to use contraception while taking it, according to the FDA.

The full prescribing information is available at zelboraf.com.

[email protected]

On Twitter @maryellenny

The Food and Drug Administration has approved vemurafenib for adults with Erdheim-Chester disease (ECD) with the BRAF V600 mutation.

The kinase inhibitor – marketed as Zelboraf – was approved on Nov. 6. It is the first approved treatment for ECD and is already on the market as a treatment for patients with unresectable or metastatic melanoma with BRAF V600E mutation.

The FDA expedited approval of the drug under the Priority Review and Breakthrough Therapy programs. The drug also received an orphan status designation, which makes the sponsor eligible for incentives such as tax credits for clinical testing.

The agency based its approval on results from 22 patients with BRAF-V600-mutation positive ECD. Half of the patients (11) experienced a partial reduction in tumor size and 1 patient experienced a complete response, according to the FDA. Initial results from the phase 2, open-label VE-BASKET study were published in 2015 (N Engl J Med. 2015 Aug 20;373[8]:726-36).

Common side effects of vemurafenib include arthralgias, maculopapular rash, alopecia, fatigue, prolonged QT interval, and papilloma. Severe side effects include development of new cancers, growth of tumors in patients with BRAF wild-type melanoma, anaphylaxis and DRESS syndrome, severe skin reactions, heart abnormalities, hepatotoxicity, photosensitivity, uveitis, radiation sensitization and radiation recall, and Dupuytren’s contracture and plantar fascial fibromatosis. The drug is also considered teratogenic and women should be advised to use contraception while taking it, according to the FDA.

The full prescribing information is available at zelboraf.com.

[email protected]

On Twitter @maryellenny