Treatment with the anti-PD-L1 cancer immunotherapy atezolizumab produced a durable clinical benefit in patients with metastatic triple-negative breast cancer who responded to treatment, according to results from a phase I study.

Overall survival (OS) rates were 41% at 1 year and 22% at both year 2 and year 3. Patients with PD-L1 on 5% or more of tumor-infiltrating immune cells (IC2/3) achieved even better clinical outcomes: Their OS rates at 1, 2, and 3 years were 45%, 28%, and 28%.

The findings from this early phase I trial, which were presented at the annual meeting of the American Association for Cancer Research, also demonstrated that response rates were higher in the first-line setting, and an exploratory biomarker analysis suggested that higher CD8 T cell and tumor-infiltrating lymphocyte counts also contributed to a better response.

“We have no targeted therapy at the moment for triple-negative breast cancer,” said study lead author Dr. Peter Schmid, director of the St. Bartholomew’s Breast Centre at St. Bartholomew’s Hospital and Barts Cancer Institute in London, during a media briefing. “The treatment we have is chemotherapy, and most patients develop resistance relatively quickly.”

Dr. Schmid noted that the median survival for these patients is still relatively short – about 9-12 months – so, the data from this trial need to be seen in that context.

“On the other hand, triple-negative breast cancer is probably the best subtype of breast cancer in terms of selecting patients for immune therapy,” said Dr. Schmid. “This is based on a high degree of genetic instability, a high rate of mutations, higher levels of PD-L1 expression, and tumor infiltrating lymphocytes inside the tumor.”

Atezolizumab is a humanized monoclonal antibody that disrupts the PD pathway, inhibits the binding of PD-L1 to PD-1 and B7.1, and, in doing so, restores tumor-specific T-cell immunity.

In this study, Dr Schmid and colleagues recruited patients with metastatic triple-negative breast cancer to one of the expansion cohorts of a phase I trial. A total of 112 patients were evaluable for response. Of this group, 19 received atezolizumab as first-line treatment, and 93 had received at least two lines of prior therapy.

Atezolizumab was administered every 3 weeks at 15 mg/kg or 20 mg/kg, and the level of PD-L1 expression on tumor-infiltrating immune cells was evaluated. The primary endpoint of the study was safety, with overall response rate, duration of response, and progression-free survival as key secondary endpoints.

The 1- and 2-year overall survival rates for responders were 100%, but that dropped to 33% and 11%, respectively, for nonresponders. Of the 11 responders, 5 received atezolizumab as first-line therapy, while 9 had high PD-L1 expression (IC2/3).

For patients who received atezolizumab in the first-line setting, 1-year overall survival was 63%, and 2-year overall survival was 47%. The rates were lower for second-line and beyond; 37% and 18%, respectively.

For IC2/3 patients, 1-year overall survival was 45%, compared with 37% for those with low to no PD-L1 expression (IC0/1).

Only 11% of patients experienced treatment-related grade 3 or greater adverse events, and side effects led to treatment discontinuation in 3% of patients.

A key message was that the duration of response had a median of 21 months, and that is significant in this disease setting, explained Dr. Schmid. Another important point was that “overall survival was significantly longer that what we see with chemotherapy.”

Genentech funded the study. Dr Schmid’s spouse is a consultant to Roche/Genentech.

Treatment with the anti-PD-L1 cancer immunotherapy atezolizumab produced a durable clinical benefit in patients with metastatic triple-negative breast cancer who responded to treatment, according to results from a phase I study.

Overall survival (OS) rates were 41% at 1 year and 22% at both year 2 and year 3. Patients with PD-L1 on 5% or more of tumor-infiltrating immune cells (IC2/3) achieved even better clinical outcomes: Their OS rates at 1, 2, and 3 years were 45%, 28%, and 28%.

The findings from this early phase I trial, which were presented at the annual meeting of the American Association for Cancer Research, also demonstrated that response rates were higher in the first-line setting, and an exploratory biomarker analysis suggested that higher CD8 T cell and tumor-infiltrating lymphocyte counts also contributed to a better response.

“We have no targeted therapy at the moment for triple-negative breast cancer,” said study lead author Dr. Peter Schmid, director of the St. Bartholomew’s Breast Centre at St. Bartholomew’s Hospital and Barts Cancer Institute in London, during a media briefing. “The treatment we have is chemotherapy, and most patients develop resistance relatively quickly.”

Dr. Schmid noted that the median survival for these patients is still relatively short – about 9-12 months – so, the data from this trial need to be seen in that context.

“On the other hand, triple-negative breast cancer is probably the best subtype of breast cancer in terms of selecting patients for immune therapy,” said Dr. Schmid. “This is based on a high degree of genetic instability, a high rate of mutations, higher levels of PD-L1 expression, and tumor infiltrating lymphocytes inside the tumor.”

Atezolizumab is a humanized monoclonal antibody that disrupts the PD pathway, inhibits the binding of PD-L1 to PD-1 and B7.1, and, in doing so, restores tumor-specific T-cell immunity.

In this study, Dr Schmid and colleagues recruited patients with metastatic triple-negative breast cancer to one of the expansion cohorts of a phase I trial. A total of 112 patients were evaluable for response. Of this group, 19 received atezolizumab as first-line treatment, and 93 had received at least two lines of prior therapy.

Atezolizumab was administered every 3 weeks at 15 mg/kg or 20 mg/kg, and the level of PD-L1 expression on tumor-infiltrating immune cells was evaluated. The primary endpoint of the study was safety, with overall response rate, duration of response, and progression-free survival as key secondary endpoints.

The 1- and 2-year overall survival rates for responders were 100%, but that dropped to 33% and 11%, respectively, for nonresponders. Of the 11 responders, 5 received atezolizumab as first-line therapy, while 9 had high PD-L1 expression (IC2/3).

For patients who received atezolizumab in the first-line setting, 1-year overall survival was 63%, and 2-year overall survival was 47%. The rates were lower for second-line and beyond; 37% and 18%, respectively.

For IC2/3 patients, 1-year overall survival was 45%, compared with 37% for those with low to no PD-L1 expression (IC0/1).

Only 11% of patients experienced treatment-related grade 3 or greater adverse events, and side effects led to treatment discontinuation in 3% of patients.

A key message was that the duration of response had a median of 21 months, and that is significant in this disease setting, explained Dr. Schmid. Another important point was that “overall survival was significantly longer that what we see with chemotherapy.”

Genentech funded the study. Dr Schmid’s spouse is a consultant to Roche/Genentech.

Treatment with the anti-PD-L1 cancer immunotherapy atezolizumab produced a durable clinical benefit in patients with metastatic triple-negative breast cancer who responded to treatment, according to results from a phase I study.

Overall survival (OS) rates were 41% at 1 year and 22% at both year 2 and year 3. Patients with PD-L1 on 5% or more of tumor-infiltrating immune cells (IC2/3) achieved even better clinical outcomes: Their OS rates at 1, 2, and 3 years were 45%, 28%, and 28%.

The findings from this early phase I trial, which were presented at the annual meeting of the American Association for Cancer Research, also demonstrated that response rates were higher in the first-line setting, and an exploratory biomarker analysis suggested that higher CD8 T cell and tumor-infiltrating lymphocyte counts also contributed to a better response.

“We have no targeted therapy at the moment for triple-negative breast cancer,” said study lead author Dr. Peter Schmid, director of the St. Bartholomew’s Breast Centre at St. Bartholomew’s Hospital and Barts Cancer Institute in London, during a media briefing. “The treatment we have is chemotherapy, and most patients develop resistance relatively quickly.”

Dr. Schmid noted that the median survival for these patients is still relatively short – about 9-12 months – so, the data from this trial need to be seen in that context.

“On the other hand, triple-negative breast cancer is probably the best subtype of breast cancer in terms of selecting patients for immune therapy,” said Dr. Schmid. “This is based on a high degree of genetic instability, a high rate of mutations, higher levels of PD-L1 expression, and tumor infiltrating lymphocytes inside the tumor.”

Atezolizumab is a humanized monoclonal antibody that disrupts the PD pathway, inhibits the binding of PD-L1 to PD-1 and B7.1, and, in doing so, restores tumor-specific T-cell immunity.

In this study, Dr Schmid and colleagues recruited patients with metastatic triple-negative breast cancer to one of the expansion cohorts of a phase I trial. A total of 112 patients were evaluable for response. Of this group, 19 received atezolizumab as first-line treatment, and 93 had received at least two lines of prior therapy.

Atezolizumab was administered every 3 weeks at 15 mg/kg or 20 mg/kg, and the level of PD-L1 expression on tumor-infiltrating immune cells was evaluated. The primary endpoint of the study was safety, with overall response rate, duration of response, and progression-free survival as key secondary endpoints.

The 1- and 2-year overall survival rates for responders were 100%, but that dropped to 33% and 11%, respectively, for nonresponders. Of the 11 responders, 5 received atezolizumab as first-line therapy, while 9 had high PD-L1 expression (IC2/3).

For patients who received atezolizumab in the first-line setting, 1-year overall survival was 63%, and 2-year overall survival was 47%. The rates were lower for second-line and beyond; 37% and 18%, respectively.

For IC2/3 patients, 1-year overall survival was 45%, compared with 37% for those with low to no PD-L1 expression (IC0/1).

Only 11% of patients experienced treatment-related grade 3 or greater adverse events, and side effects led to treatment discontinuation in 3% of patients.

A key message was that the duration of response had a median of 21 months, and that is significant in this disease setting, explained Dr. Schmid. Another important point was that “overall survival was significantly longer that what we see with chemotherapy.”

Genentech funded the study. Dr Schmid’s spouse is a consultant to Roche/Genentech.

ORLANDO – About 80% of children with growth disorders will attain their expected normal adult height if adequately treated with growth hormone, a large observational study has determined.

Somatropin recombinant human growth hormone seemed most effective for patients with growth hormone deficiency, idiopathic short stature, and for those who were born small for gestational age. Patients who had Turner syndrome or a homeobox-deficiency gene didn’t do quite as well, although most did still improve their final height.

The Genetics and Neuroendocrinology of Short Stature International Study (GENESIS) followed more than 22,000 children who were treated in 30 countries from 1999 to 2015.

All of the patients were treated with somatropin recombinant human growth hormone (Humatrope). Eli Lilly, which makes the medication, sponsored the study and presented the results during a poster session at the annual meeting of the Endocrine Society. Representatives at the poster declined to discuss results with the media during the open session.

“The results speak for themselves,” said Cheri Deal, MD, PhD, of the University of Montreal, Quebec, one of the presenting authors. “It’s an incredible story.”

The GENESIS cohort comprised more than 22,000 children who were treated for a variety of growth disorders at 827 international sites.

Subanalyses have been published, but this is the first release of the data on 5,076 patients with full follow-up. Most of the patients (61%) received the medication for growth hormone deficiency. Other indications were Turner syndrome (14%), idiopathic short stature (11%), short-stature homeobox-containing gene deficiency (3%), small for gestational age (5%), and chronic renal insufficiency (0.3%). Other diagnoses, plus unknown causes, made up the remainder of the diagnoses.

The investigators, led by Christopher J. Child, PhD, an Eli Lilly scientist, split the cohort into diagnostic groups and treatment subgroups: those who attained normal adult height, those who attained normal adult height with at least 4 years of treatment, and those who gained normal adult height who started treatment at younger than 10 years of age.

At baseline, those with growth hormone deficiency were a mean of 11 years old; their height was a mean of 2.4 standard deviations (SDS) below normal. They received a mean of 6 years of treatment; 86% achieved a normal adult height, with an overall gain of 1.39 SDS. Those who started somatropin before age 10 years made bigger gains. The final height gain was 1.78 SDS after a mean of 9.5 years of treatment.

At baseline, those with idiopathic short stature were a mean of 12 years old; their mean height was 2.3 SDS below normal. They received a mean of 4.7 years of treatment; 82% achieved normal height, with a gain of 1.1 SDS. Starting somatropin at a younger age (mean 8 years) improved outcomes slightly, with a final height gain of 1.6 SDS after 8 years of treatment.

Patients with Turner syndrome were a mean of 10 years when they started treatment; their mean height was 2.65 SDS below normal. They received a mean of 6.4 years of treatment; 66% achieved normal adult height, with a mean height gain of 0.95 SDS. Early treatment didn’t alter outcomes much in this group. After a mean of 8.5 years of treatment, 65% achieved normal height, with a height gain of 0.84 SDS.

Patients with a short-stature homeobox-containing gene deficiency were a mean of 11 years when they started treatment. At that time, their height was a mean of 2.36 SDS below normal. They were treated for a mean of 4.7 years; 76% achieved a normal adult height, with a mean gain of 0.86 SDS. Early treatment did improve outcomes a bit. After a mean treatment time of 7 years, 78% gained normal adult height, with a height gain of 0.84 SDS.

Children who were small for gestational age started treatment when they were a mean of 10.5 years. At that time, their mean height was 2.57 SDS below normal. They were treated for a mean of 5.4 years; 78% attained a normal adult height, with a mean gain of 1.1 SDS. Early treatment improved outcomes. After a mean treatment time of 7.8 years, 81% achieved normal adult height, with a mean gain of 1.41 SDS.

The less-robust gains seen in the children with genetically influenced growth disorders “wasn’t unexpected” and is in line with what has been observed in a number of clinical trials, the investigators said.

Eli Lilly manufactures the somatropin product used in the study, and it sponsored the study. Dr. Child is an employee of the company. Dr. Deal did not have any financial disclosures.

[email protected]

On Twitter @Alz_gal

ORLANDO – About 80% of children with growth disorders will attain their expected normal adult height if adequately treated with growth hormone, a large observational study has determined.

Somatropin recombinant human growth hormone seemed most effective for patients with growth hormone deficiency, idiopathic short stature, and for those who were born small for gestational age. Patients who had Turner syndrome or a homeobox-deficiency gene didn’t do quite as well, although most did still improve their final height.

The Genetics and Neuroendocrinology of Short Stature International Study (GENESIS) followed more than 22,000 children who were treated in 30 countries from 1999 to 2015.

All of the patients were treated with somatropin recombinant human growth hormone (Humatrope). Eli Lilly, which makes the medication, sponsored the study and presented the results during a poster session at the annual meeting of the Endocrine Society. Representatives at the poster declined to discuss results with the media during the open session.

“The results speak for themselves,” said Cheri Deal, MD, PhD, of the University of Montreal, Quebec, one of the presenting authors. “It’s an incredible story.”

The GENESIS cohort comprised more than 22,000 children who were treated for a variety of growth disorders at 827 international sites.

Subanalyses have been published, but this is the first release of the data on 5,076 patients with full follow-up. Most of the patients (61%) received the medication for growth hormone deficiency. Other indications were Turner syndrome (14%), idiopathic short stature (11%), short-stature homeobox-containing gene deficiency (3%), small for gestational age (5%), and chronic renal insufficiency (0.3%). Other diagnoses, plus unknown causes, made up the remainder of the diagnoses.

The investigators, led by Christopher J. Child, PhD, an Eli Lilly scientist, split the cohort into diagnostic groups and treatment subgroups: those who attained normal adult height, those who attained normal adult height with at least 4 years of treatment, and those who gained normal adult height who started treatment at younger than 10 years of age.

At baseline, those with growth hormone deficiency were a mean of 11 years old; their height was a mean of 2.4 standard deviations (SDS) below normal. They received a mean of 6 years of treatment; 86% achieved a normal adult height, with an overall gain of 1.39 SDS. Those who started somatropin before age 10 years made bigger gains. The final height gain was 1.78 SDS after a mean of 9.5 years of treatment.

At baseline, those with idiopathic short stature were a mean of 12 years old; their mean height was 2.3 SDS below normal. They received a mean of 4.7 years of treatment; 82% achieved normal height, with a gain of 1.1 SDS. Starting somatropin at a younger age (mean 8 years) improved outcomes slightly, with a final height gain of 1.6 SDS after 8 years of treatment.

Patients with Turner syndrome were a mean of 10 years when they started treatment; their mean height was 2.65 SDS below normal. They received a mean of 6.4 years of treatment; 66% achieved normal adult height, with a mean height gain of 0.95 SDS. Early treatment didn’t alter outcomes much in this group. After a mean of 8.5 years of treatment, 65% achieved normal height, with a height gain of 0.84 SDS.

Patients with a short-stature homeobox-containing gene deficiency were a mean of 11 years when they started treatment. At that time, their height was a mean of 2.36 SDS below normal. They were treated for a mean of 4.7 years; 76% achieved a normal adult height, with a mean gain of 0.86 SDS. Early treatment did improve outcomes a bit. After a mean treatment time of 7 years, 78% gained normal adult height, with a height gain of 0.84 SDS.

Children who were small for gestational age started treatment when they were a mean of 10.5 years. At that time, their mean height was 2.57 SDS below normal. They were treated for a mean of 5.4 years; 78% attained a normal adult height, with a mean gain of 1.1 SDS. Early treatment improved outcomes. After a mean treatment time of 7.8 years, 81% achieved normal adult height, with a mean gain of 1.41 SDS.

The less-robust gains seen in the children with genetically influenced growth disorders “wasn’t unexpected” and is in line with what has been observed in a number of clinical trials, the investigators said.

Eli Lilly manufactures the somatropin product used in the study, and it sponsored the study. Dr. Child is an employee of the company. Dr. Deal did not have any financial disclosures.

[email protected]

On Twitter @Alz_gal

ORLANDO – About 80% of children with growth disorders will attain their expected normal adult height if adequately treated with growth hormone, a large observational study has determined.

Somatropin recombinant human growth hormone seemed most effective for patients with growth hormone deficiency, idiopathic short stature, and for those who were born small for gestational age. Patients who had Turner syndrome or a homeobox-deficiency gene didn’t do quite as well, although most did still improve their final height.

The Genetics and Neuroendocrinology of Short Stature International Study (GENESIS) followed more than 22,000 children who were treated in 30 countries from 1999 to 2015.

All of the patients were treated with somatropin recombinant human growth hormone (Humatrope). Eli Lilly, which makes the medication, sponsored the study and presented the results during a poster session at the annual meeting of the Endocrine Society. Representatives at the poster declined to discuss results with the media during the open session.

“The results speak for themselves,” said Cheri Deal, MD, PhD, of the University of Montreal, Quebec, one of the presenting authors. “It’s an incredible story.”

The GENESIS cohort comprised more than 22,000 children who were treated for a variety of growth disorders at 827 international sites.

Subanalyses have been published, but this is the first release of the data on 5,076 patients with full follow-up. Most of the patients (61%) received the medication for growth hormone deficiency. Other indications were Turner syndrome (14%), idiopathic short stature (11%), short-stature homeobox-containing gene deficiency (3%), small for gestational age (5%), and chronic renal insufficiency (0.3%). Other diagnoses, plus unknown causes, made up the remainder of the diagnoses.

The investigators, led by Christopher J. Child, PhD, an Eli Lilly scientist, split the cohort into diagnostic groups and treatment subgroups: those who attained normal adult height, those who attained normal adult height with at least 4 years of treatment, and those who gained normal adult height who started treatment at younger than 10 years of age.

At baseline, those with growth hormone deficiency were a mean of 11 years old; their height was a mean of 2.4 standard deviations (SDS) below normal. They received a mean of 6 years of treatment; 86% achieved a normal adult height, with an overall gain of 1.39 SDS. Those who started somatropin before age 10 years made bigger gains. The final height gain was 1.78 SDS after a mean of 9.5 years of treatment.

At baseline, those with idiopathic short stature were a mean of 12 years old; their mean height was 2.3 SDS below normal. They received a mean of 4.7 years of treatment; 82% achieved normal height, with a gain of 1.1 SDS. Starting somatropin at a younger age (mean 8 years) improved outcomes slightly, with a final height gain of 1.6 SDS after 8 years of treatment.

Patients with Turner syndrome were a mean of 10 years when they started treatment; their mean height was 2.65 SDS below normal. They received a mean of 6.4 years of treatment; 66% achieved normal adult height, with a mean height gain of 0.95 SDS. Early treatment didn’t alter outcomes much in this group. After a mean of 8.5 years of treatment, 65% achieved normal height, with a height gain of 0.84 SDS.

Patients with a short-stature homeobox-containing gene deficiency were a mean of 11 years when they started treatment. At that time, their height was a mean of 2.36 SDS below normal. They were treated for a mean of 4.7 years; 76% achieved a normal adult height, with a mean gain of 0.86 SDS. Early treatment did improve outcomes a bit. After a mean treatment time of 7 years, 78% gained normal adult height, with a height gain of 0.84 SDS.

Children who were small for gestational age started treatment when they were a mean of 10.5 years. At that time, their mean height was 2.57 SDS below normal. They were treated for a mean of 5.4 years; 78% attained a normal adult height, with a mean gain of 1.1 SDS. Early treatment improved outcomes. After a mean treatment time of 7.8 years, 81% achieved normal adult height, with a mean gain of 1.41 SDS.

The less-robust gains seen in the children with genetically influenced growth disorders “wasn’t unexpected” and is in line with what has been observed in a number of clinical trials, the investigators said.

Eli Lilly manufactures the somatropin product used in the study, and it sponsored the study. Dr. Child is an employee of the company. Dr. Deal did not have any financial disclosures.

[email protected]

On Twitter @Alz_gal

SAN DIEGO – Incorporating pharmacists into primary care offices has the potential to significantly impact patient care and save health care costs, according to Hae Mi Choe, PharmD.

Drug-related morbidity in the United States costs an estimated $290 billion annually, or about 13% of total health care expenditures, said Dr. Choe, associate dean at the University of Michigan College of Pharmacy and director of pharmacy innovations and partnerships at the University of Michigan Medical Group, Ann Arbor.

[email protected]

SAN DIEGO – Incorporating pharmacists into primary care offices has the potential to significantly impact patient care and save health care costs, according to Hae Mi Choe, PharmD.

Drug-related morbidity in the United States costs an estimated $290 billion annually, or about 13% of total health care expenditures, said Dr. Choe, associate dean at the University of Michigan College of Pharmacy and director of pharmacy innovations and partnerships at the University of Michigan Medical Group, Ann Arbor.

[email protected]

SAN DIEGO – Incorporating pharmacists into primary care offices has the potential to significantly impact patient care and save health care costs, according to Hae Mi Choe, PharmD.

Drug-related morbidity in the United States costs an estimated $290 billion annually, or about 13% of total health care expenditures, said Dr. Choe, associate dean at the University of Michigan College of Pharmacy and director of pharmacy innovations and partnerships at the University of Michigan Medical Group, Ann Arbor.

[email protected]

NEW YORK – The success that tyrosine kinase inhibitors have had in prolonging life and producing deep hematologic and molecular remissions in patients with chronic myeloid leukemia has led to an unexpected bonus for young women living with the disease: an opportunity to safely become pregnant and mother a child.

The approach is not yet routine and poses a level of risk to both the mother and fetus, especially because tyrosine kinase inhibitors (TKIs) are teratogenic. But with careful planning, close gestational monitoring, and with support from skilled obstetricians, the scenario of a successful pregnancy in women with chronic myeloid leukemia (CML) has now played out several dozen times at a handful of U.S. centers, Mrinal S. Patnaik, MD, said in a talk at the conference held by Imedex.

“We make it clear that this is experimental and is associated with risk, and we share the data [from case reports]; but if the woman wants to go forward,” a protocol now exists “to successfully get them to pregnancy,” said Dr. Patnaik, a hematologist oncologist at the Mayo Clinic in Rochester, Minn.

At Mayo alone, upwards of 20 women with CML have been successfully shepherded through pregnancy, he said in a video interview.

The prospect for a planned pregnancy is reserved for women with their CML well controlled for at least 2 years using a TKI, most often imatinib (Gleevec). In addition to being under complete hematologic control, the candidate patient must also show a deep molecular response, which means a blood level of the BRC-ABL tyrosine kinase that drives CML at least 4 or 4.5 logs (10,000-50,000-fold) below pretreatment levels or molecularly undetectable.

The patient then monitors her ovulatory cycle and stops her medication at the time of ovulation, attempts conception, and then monitors whether pregnancy has actually started. If it has, she needs to stay off her TKI regimen through at least the first 18 weeks of gestation, although an even longer drug holiday is preferred. If not, she resumes the medication and repeats the process later if she wants.

Once the women is pregnant and remains off her TKI regimen Dr. Patnaik and his associates closely follow the woman for signs of a molecular or hematologic relapse, although the latter are unusual. If a resurgence of CML stem cells occurs, the woman receives treatment with pegylated interferon-alpha, which is safe during pregnancy. When possible, TKI treatment remains on hold into the breast-feeding period.

During pregnancy and delivery, the patient requires careful and regular follow-up by a maternal-fetal medicine specialist and has an ongoing risk for high platelet counts causing placental blood clots, fetuses that are small for gestational age, preterm labor, premature rupture of membranes, and other complications.

“These are manageable with good obstetrical care,” Dr. Patnaik said. “We have developed a good system to work out the obstetrical complications.

“By and large we can be successful, but it requires a lot of monitoring and a lot of patient compliance with regular follow-ups,” he stressed.

In a video interview at the meeting, Dr. Patnaik discussed the approach he takes with his patients.

[email protected]

On Twitter @mitchelzoler

NEW YORK – The success that tyrosine kinase inhibitors have had in prolonging life and producing deep hematologic and molecular remissions in patients with chronic myeloid leukemia has led to an unexpected bonus for young women living with the disease: an opportunity to safely become pregnant and mother a child.

The approach is not yet routine and poses a level of risk to both the mother and fetus, especially because tyrosine kinase inhibitors (TKIs) are teratogenic. But with careful planning, close gestational monitoring, and with support from skilled obstetricians, the scenario of a successful pregnancy in women with chronic myeloid leukemia (CML) has now played out several dozen times at a handful of U.S. centers, Mrinal S. Patnaik, MD, said in a talk at the conference held by Imedex.

“We make it clear that this is experimental and is associated with risk, and we share the data [from case reports]; but if the woman wants to go forward,” a protocol now exists “to successfully get them to pregnancy,” said Dr. Patnaik, a hematologist oncologist at the Mayo Clinic in Rochester, Minn.

At Mayo alone, upwards of 20 women with CML have been successfully shepherded through pregnancy, he said in a video interview.

The prospect for a planned pregnancy is reserved for women with their CML well controlled for at least 2 years using a TKI, most often imatinib (Gleevec). In addition to being under complete hematologic control, the candidate patient must also show a deep molecular response, which means a blood level of the BRC-ABL tyrosine kinase that drives CML at least 4 or 4.5 logs (10,000-50,000-fold) below pretreatment levels or molecularly undetectable.

The patient then monitors her ovulatory cycle and stops her medication at the time of ovulation, attempts conception, and then monitors whether pregnancy has actually started. If it has, she needs to stay off her TKI regimen through at least the first 18 weeks of gestation, although an even longer drug holiday is preferred. If not, she resumes the medication and repeats the process later if she wants.

Once the women is pregnant and remains off her TKI regimen Dr. Patnaik and his associates closely follow the woman for signs of a molecular or hematologic relapse, although the latter are unusual. If a resurgence of CML stem cells occurs, the woman receives treatment with pegylated interferon-alpha, which is safe during pregnancy. When possible, TKI treatment remains on hold into the breast-feeding period.

During pregnancy and delivery, the patient requires careful and regular follow-up by a maternal-fetal medicine specialist and has an ongoing risk for high platelet counts causing placental blood clots, fetuses that are small for gestational age, preterm labor, premature rupture of membranes, and other complications.

“These are manageable with good obstetrical care,” Dr. Patnaik said. “We have developed a good system to work out the obstetrical complications.

“By and large we can be successful, but it requires a lot of monitoring and a lot of patient compliance with regular follow-ups,” he stressed.

In a video interview at the meeting, Dr. Patnaik discussed the approach he takes with his patients.

[email protected]

On Twitter @mitchelzoler

NEW YORK – The success that tyrosine kinase inhibitors have had in prolonging life and producing deep hematologic and molecular remissions in patients with chronic myeloid leukemia has led to an unexpected bonus for young women living with the disease: an opportunity to safely become pregnant and mother a child.

The approach is not yet routine and poses a level of risk to both the mother and fetus, especially because tyrosine kinase inhibitors (TKIs) are teratogenic. But with careful planning, close gestational monitoring, and with support from skilled obstetricians, the scenario of a successful pregnancy in women with chronic myeloid leukemia (CML) has now played out several dozen times at a handful of U.S. centers, Mrinal S. Patnaik, MD, said in a talk at the conference held by Imedex.

“We make it clear that this is experimental and is associated with risk, and we share the data [from case reports]; but if the woman wants to go forward,” a protocol now exists “to successfully get them to pregnancy,” said Dr. Patnaik, a hematologist oncologist at the Mayo Clinic in Rochester, Minn.

At Mayo alone, upwards of 20 women with CML have been successfully shepherded through pregnancy, he said in a video interview.

The prospect for a planned pregnancy is reserved for women with their CML well controlled for at least 2 years using a TKI, most often imatinib (Gleevec). In addition to being under complete hematologic control, the candidate patient must also show a deep molecular response, which means a blood level of the BRC-ABL tyrosine kinase that drives CML at least 4 or 4.5 logs (10,000-50,000-fold) below pretreatment levels or molecularly undetectable.

The patient then monitors her ovulatory cycle and stops her medication at the time of ovulation, attempts conception, and then monitors whether pregnancy has actually started. If it has, she needs to stay off her TKI regimen through at least the first 18 weeks of gestation, although an even longer drug holiday is preferred. If not, she resumes the medication and repeats the process later if she wants.

Once the women is pregnant and remains off her TKI regimen Dr. Patnaik and his associates closely follow the woman for signs of a molecular or hematologic relapse, although the latter are unusual. If a resurgence of CML stem cells occurs, the woman receives treatment with pegylated interferon-alpha, which is safe during pregnancy. When possible, TKI treatment remains on hold into the breast-feeding period.

During pregnancy and delivery, the patient requires careful and regular follow-up by a maternal-fetal medicine specialist and has an ongoing risk for high platelet counts causing placental blood clots, fetuses that are small for gestational age, preterm labor, premature rupture of membranes, and other complications.

“These are manageable with good obstetrical care,” Dr. Patnaik said. “We have developed a good system to work out the obstetrical complications.

“By and large we can be successful, but it requires a lot of monitoring and a lot of patient compliance with regular follow-ups,” he stressed.

In a video interview at the meeting, Dr. Patnaik discussed the approach he takes with his patients.

[email protected]

On Twitter @mitchelzoler

SNOWMASS, COLO. – Think very carefully before extending the duration of dual antiplatelet therapy beyond 6 months in drug-eluting stent recipients with stable ischemic heart disease, Patrick T. O’Gara, MD, advised at the Annual Cardiovascular Conference at Snowmass.

Six months of dual antiplatelet therapy (DAPT) in this setting received a Class I recommendation in the 2016 American College of Cardiology/American Heart Association guideline focused update on DAPT duration (J Am Coll Cardiol. 2016 Sep 6;68[10]:1082-115). That’s a departure from previous guidelines, which recommended 12 months of DAPT. The shortened DAPT duration of 6 months is consistent with European Society of Cardiology recommendations.

In contrast, extending DAPT beyond the 6-month mark garnered a relatively weak Class IIb recommendation in the ACC/AHA focused update, meaning it “could be considered,” noted Dr. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.

Considerable enthusiasm for extending DAPT well beyond 6 months after drug-eluting stent implantation has been generated in some quarters by the positive results of the PEGASUS TIMI 54 trial. But Dr. O’Gara and the other members of the guideline writing committee had reservations about the study, which together with other concerning evidence led to the weak Class IIb recommendation.

PEGASUS TIMI 54 included 21,162 patients with stable ischemic heart disease 1-3 years after a myocardial infarction who were randomized to low-dose aspirin plus either placebo or ticagrelor (Brilinta) at 60 mg or 90 mg b.i.d. and followed prospectively for a median of 33 months (N Engl J Med. 2015 May 7;372[19]:1791-800).

The primary efficacy endpoint, a composite of cardiovascular death, MI, or stroke, occurred in 9.0% of placebo-treated patients, compared with 7.8% of patients on either ticagrelor regimen, for a statistically significant 15% relative risk reduction in the DAPT group.

But there is more to the study than first meets the eye.

“I think what we as practitioners sometimes lose track of is that the investigators in this particular trial were very careful to enroll patients with stable ischemic heart disease who were at high risk of ischemic events over the next 3-5 years,” Dr. O’Gara noted. “These were patients who were generally older, patients with diabetes, chronic kidney disease, multivessel coronary disease, or who had had a second MI.”

Thus, the deck was stacked in favor of obtaining a result showing maximum efficacy. Yet, for every 10,000 patients treated with ticagrelor at 90 mg b.i.d., there were only 40 fewer cardiovascular events per year, compared with placebo. And that came at a cost of 41 more TIMI major bleeding events.

“That’s a wash at 90 mg,” the cardiologist said.

At 60 mg b.i.d. – the dose ultimately approved by the Food and Drug Administration – there were 42 fewer primary cardiovascular events per year per 10,000 treated patients, a benefit that came at the expense of 31 more TIMI major bleeding events.

“These are really razor thin margins, and I would encourage you to make a risk-benefit assessment of the trade-off between ischemia and bleeding in your decision-making,” Dr. O’Gara said.

The ACC/AHA guideline writing committee also took into account a meta-analysis of six randomized clinical trials totaling more than 33,000 high-risk patients post-MI who were assigned to more than 1 year of DAPT or aspirin alone. Extended DAPT brought a 22% reduction in the relative risk of major adverse cardiovascular events, but this was accompanied with a 73% increase in the risk of major bleeding (Eur Heart J. 2016 Jan 21;37[4]:390-9).

Turning to DAPT duration post-PCI in patients with an acute coronary syndrome, Dr. O’Gara noted that the 2016 ACC/AHA guideline focused update gave a Class I indication for 12 months of DAPT in recipients of a drug-eluting stent, but a weaker IIb recommendation for consideration of extending DAPT beyond that point – provided the patient was not at high bleeding risk and didn’t have significant bleeding during the first 12 months on DAPT.

“I think there’s a lot of individual and institutional variation with respect to this kind of decision-making, and I don’t think our guidelines are meant to be proscriptive, because our patients are quite nuanced,” the cardiologist observed.

The question physicians always have to ask in considering extended DAPT is, “How many ischemic events am I going to prevent at the expense of how many bleeding events?”

The investigators in the landmark DAPT study of extended therapy have analyzed their data in a fashion that has enabled them to develop a risk scoring system, known as the DAPT prediction rule, which is readily calculated based on factors including age, presence of diabetes, heart failure, and the size of the treated vessel.

For patients with a high DAPT score, assignment to an additional 18 months of DAPT after the initial 12 months of dual therapy was associated with a net 1.67% reduction in adverse events – both ischemic and bleeding – compared with the rate in patients who stopped DAPT at 12 months. For those with a low DAPT score, extended dual antiplatelet therapy resulted in a 1.03% net increase in adverse events (JAMA. 2016 Apr 26;315[16]:1735-49).

“I should warn you that the discriminatory power of this particular score is relatively modest,” Dr. O’Gara noted. “The C-statistic is not higher than about 0.7. But I do think that the DAPT score meets the sniff test biologically and clinically. It’s a real good first step. I do think this particular score needs to be validated externally in other populations going forward.”

Dr. O’Gara reported having no financial conflicts of interest.

[email protected]

SNOWMASS, COLO. – Think very carefully before extending the duration of dual antiplatelet therapy beyond 6 months in drug-eluting stent recipients with stable ischemic heart disease, Patrick T. O’Gara, MD, advised at the Annual Cardiovascular Conference at Snowmass.

Six months of dual antiplatelet therapy (DAPT) in this setting received a Class I recommendation in the 2016 American College of Cardiology/American Heart Association guideline focused update on DAPT duration (J Am Coll Cardiol. 2016 Sep 6;68[10]:1082-115). That’s a departure from previous guidelines, which recommended 12 months of DAPT. The shortened DAPT duration of 6 months is consistent with European Society of Cardiology recommendations.

In contrast, extending DAPT beyond the 6-month mark garnered a relatively weak Class IIb recommendation in the ACC/AHA focused update, meaning it “could be considered,” noted Dr. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.

Considerable enthusiasm for extending DAPT well beyond 6 months after drug-eluting stent implantation has been generated in some quarters by the positive results of the PEGASUS TIMI 54 trial. But Dr. O’Gara and the other members of the guideline writing committee had reservations about the study, which together with other concerning evidence led to the weak Class IIb recommendation.

PEGASUS TIMI 54 included 21,162 patients with stable ischemic heart disease 1-3 years after a myocardial infarction who were randomized to low-dose aspirin plus either placebo or ticagrelor (Brilinta) at 60 mg or 90 mg b.i.d. and followed prospectively for a median of 33 months (N Engl J Med. 2015 May 7;372[19]:1791-800).

The primary efficacy endpoint, a composite of cardiovascular death, MI, or stroke, occurred in 9.0% of placebo-treated patients, compared with 7.8% of patients on either ticagrelor regimen, for a statistically significant 15% relative risk reduction in the DAPT group.

But there is more to the study than first meets the eye.

“I think what we as practitioners sometimes lose track of is that the investigators in this particular trial were very careful to enroll patients with stable ischemic heart disease who were at high risk of ischemic events over the next 3-5 years,” Dr. O’Gara noted. “These were patients who were generally older, patients with diabetes, chronic kidney disease, multivessel coronary disease, or who had had a second MI.”

Thus, the deck was stacked in favor of obtaining a result showing maximum efficacy. Yet, for every 10,000 patients treated with ticagrelor at 90 mg b.i.d., there were only 40 fewer cardiovascular events per year, compared with placebo. And that came at a cost of 41 more TIMI major bleeding events.

“That’s a wash at 90 mg,” the cardiologist said.

At 60 mg b.i.d. – the dose ultimately approved by the Food and Drug Administration – there were 42 fewer primary cardiovascular events per year per 10,000 treated patients, a benefit that came at the expense of 31 more TIMI major bleeding events.

“These are really razor thin margins, and I would encourage you to make a risk-benefit assessment of the trade-off between ischemia and bleeding in your decision-making,” Dr. O’Gara said.

The ACC/AHA guideline writing committee also took into account a meta-analysis of six randomized clinical trials totaling more than 33,000 high-risk patients post-MI who were assigned to more than 1 year of DAPT or aspirin alone. Extended DAPT brought a 22% reduction in the relative risk of major adverse cardiovascular events, but this was accompanied with a 73% increase in the risk of major bleeding (Eur Heart J. 2016 Jan 21;37[4]:390-9).

Turning to DAPT duration post-PCI in patients with an acute coronary syndrome, Dr. O’Gara noted that the 2016 ACC/AHA guideline focused update gave a Class I indication for 12 months of DAPT in recipients of a drug-eluting stent, but a weaker IIb recommendation for consideration of extending DAPT beyond that point – provided the patient was not at high bleeding risk and didn’t have significant bleeding during the first 12 months on DAPT.

“I think there’s a lot of individual and institutional variation with respect to this kind of decision-making, and I don’t think our guidelines are meant to be proscriptive, because our patients are quite nuanced,” the cardiologist observed.

The question physicians always have to ask in considering extended DAPT is, “How many ischemic events am I going to prevent at the expense of how many bleeding events?”

The investigators in the landmark DAPT study of extended therapy have analyzed their data in a fashion that has enabled them to develop a risk scoring system, known as the DAPT prediction rule, which is readily calculated based on factors including age, presence of diabetes, heart failure, and the size of the treated vessel.

For patients with a high DAPT score, assignment to an additional 18 months of DAPT after the initial 12 months of dual therapy was associated with a net 1.67% reduction in adverse events – both ischemic and bleeding – compared with the rate in patients who stopped DAPT at 12 months. For those with a low DAPT score, extended dual antiplatelet therapy resulted in a 1.03% net increase in adverse events (JAMA. 2016 Apr 26;315[16]:1735-49).

“I should warn you that the discriminatory power of this particular score is relatively modest,” Dr. O’Gara noted. “The C-statistic is not higher than about 0.7. But I do think that the DAPT score meets the sniff test biologically and clinically. It’s a real good first step. I do think this particular score needs to be validated externally in other populations going forward.”

Dr. O’Gara reported having no financial conflicts of interest.

[email protected]

SNOWMASS, COLO. – Think very carefully before extending the duration of dual antiplatelet therapy beyond 6 months in drug-eluting stent recipients with stable ischemic heart disease, Patrick T. O’Gara, MD, advised at the Annual Cardiovascular Conference at Snowmass.

Six months of dual antiplatelet therapy (DAPT) in this setting received a Class I recommendation in the 2016 American College of Cardiology/American Heart Association guideline focused update on DAPT duration (J Am Coll Cardiol. 2016 Sep 6;68[10]:1082-115). That’s a departure from previous guidelines, which recommended 12 months of DAPT. The shortened DAPT duration of 6 months is consistent with European Society of Cardiology recommendations.

In contrast, extending DAPT beyond the 6-month mark garnered a relatively weak Class IIb recommendation in the ACC/AHA focused update, meaning it “could be considered,” noted Dr. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.

Considerable enthusiasm for extending DAPT well beyond 6 months after drug-eluting stent implantation has been generated in some quarters by the positive results of the PEGASUS TIMI 54 trial. But Dr. O’Gara and the other members of the guideline writing committee had reservations about the study, which together with other concerning evidence led to the weak Class IIb recommendation.

PEGASUS TIMI 54 included 21,162 patients with stable ischemic heart disease 1-3 years after a myocardial infarction who were randomized to low-dose aspirin plus either placebo or ticagrelor (Brilinta) at 60 mg or 90 mg b.i.d. and followed prospectively for a median of 33 months (N Engl J Med. 2015 May 7;372[19]:1791-800).

The primary efficacy endpoint, a composite of cardiovascular death, MI, or stroke, occurred in 9.0% of placebo-treated patients, compared with 7.8% of patients on either ticagrelor regimen, for a statistically significant 15% relative risk reduction in the DAPT group.

But there is more to the study than first meets the eye.

“I think what we as practitioners sometimes lose track of is that the investigators in this particular trial were very careful to enroll patients with stable ischemic heart disease who were at high risk of ischemic events over the next 3-5 years,” Dr. O’Gara noted. “These were patients who were generally older, patients with diabetes, chronic kidney disease, multivessel coronary disease, or who had had a second MI.”

Thus, the deck was stacked in favor of obtaining a result showing maximum efficacy. Yet, for every 10,000 patients treated with ticagrelor at 90 mg b.i.d., there were only 40 fewer cardiovascular events per year, compared with placebo. And that came at a cost of 41 more TIMI major bleeding events.

“That’s a wash at 90 mg,” the cardiologist said.

At 60 mg b.i.d. – the dose ultimately approved by the Food and Drug Administration – there were 42 fewer primary cardiovascular events per year per 10,000 treated patients, a benefit that came at the expense of 31 more TIMI major bleeding events.

“These are really razor thin margins, and I would encourage you to make a risk-benefit assessment of the trade-off between ischemia and bleeding in your decision-making,” Dr. O’Gara said.

The ACC/AHA guideline writing committee also took into account a meta-analysis of six randomized clinical trials totaling more than 33,000 high-risk patients post-MI who were assigned to more than 1 year of DAPT or aspirin alone. Extended DAPT brought a 22% reduction in the relative risk of major adverse cardiovascular events, but this was accompanied with a 73% increase in the risk of major bleeding (Eur Heart J. 2016 Jan 21;37[4]:390-9).

Turning to DAPT duration post-PCI in patients with an acute coronary syndrome, Dr. O’Gara noted that the 2016 ACC/AHA guideline focused update gave a Class I indication for 12 months of DAPT in recipients of a drug-eluting stent, but a weaker IIb recommendation for consideration of extending DAPT beyond that point – provided the patient was not at high bleeding risk and didn’t have significant bleeding during the first 12 months on DAPT.

“I think there’s a lot of individual and institutional variation with respect to this kind of decision-making, and I don’t think our guidelines are meant to be proscriptive, because our patients are quite nuanced,” the cardiologist observed.

The question physicians always have to ask in considering extended DAPT is, “How many ischemic events am I going to prevent at the expense of how many bleeding events?”

The investigators in the landmark DAPT study of extended therapy have analyzed their data in a fashion that has enabled them to develop a risk scoring system, known as the DAPT prediction rule, which is readily calculated based on factors including age, presence of diabetes, heart failure, and the size of the treated vessel.

For patients with a high DAPT score, assignment to an additional 18 months of DAPT after the initial 12 months of dual therapy was associated with a net 1.67% reduction in adverse events – both ischemic and bleeding – compared with the rate in patients who stopped DAPT at 12 months. For those with a low DAPT score, extended dual antiplatelet therapy resulted in a 1.03% net increase in adverse events (JAMA. 2016 Apr 26;315[16]:1735-49).

“I should warn you that the discriminatory power of this particular score is relatively modest,” Dr. O’Gara noted. “The C-statistic is not higher than about 0.7. But I do think that the DAPT score meets the sniff test biologically and clinically. It’s a real good first step. I do think this particular score needs to be validated externally in other populations going forward.”

Dr. O’Gara reported having no financial conflicts of interest.

[email protected]

Having or having had a parent in jail appears to be a risk factor for adolescent mental health problems, a Minnesota study found.

In a study of 122,180 children from the 8th, 9th, and 11th grades drawn from the 2013 Minnesota Student Survey, parental incarceration was strongly associated with higher rates of mental health problems such as internalizing, self-injury, suicidal ideation, and suicidal attempts. Children of currently incarcerated parents were two and a half to four times as likely to experience these mental health problems, and children of formerly incarcerated parents were roughly twice as likely to experience them, compared with children whose parents had not been jailed, said Laurel Davis, PhD, and Rebecca J. Shlafer, PhD, MPH, of the department of pediatrics at the University of Minnesota, Minneapolis.

For youth with currently incarcerated parents, almost half reported moderate symptoms of internalizing, and more than one-third reported at least one purposeful self-injury. However, only 30% reported any type of treatment for a mental health concern, the researchers said.

Parental closeness was protective against negative mental health outcomes, they noted. “Children of incarcerated parents are a vulnerable population and they should continue to be the targets of intervention efforts aiming to buttress their personal and social resources, including strong relationships with caregivers.”

Studies suggest that an estimated 1.9 million U.S. children have a parent in a state or federal prison, and millions more have a parent in county jails.

In Minnesota alone, 2,500 young people who had a parent in jail or whose parent had been in jail reported attempting suicide, and more than 5,000 children of incarcerated or formerly incarcerated parents had reported purposely having injured themselves in the last year. “This represents an enormous challenge to our systems of care,” said Dr. Davis and Dr. Shlafer. “Identifying and intervening with these youth should be a priority with governments and social service organizations.”

Read more at the Journal of Adolescence (2017;54:120-34).

[email protected]

Having or having had a parent in jail appears to be a risk factor for adolescent mental health problems, a Minnesota study found.

In a study of 122,180 children from the 8th, 9th, and 11th grades drawn from the 2013 Minnesota Student Survey, parental incarceration was strongly associated with higher rates of mental health problems such as internalizing, self-injury, suicidal ideation, and suicidal attempts. Children of currently incarcerated parents were two and a half to four times as likely to experience these mental health problems, and children of formerly incarcerated parents were roughly twice as likely to experience them, compared with children whose parents had not been jailed, said Laurel Davis, PhD, and Rebecca J. Shlafer, PhD, MPH, of the department of pediatrics at the University of Minnesota, Minneapolis.

For youth with currently incarcerated parents, almost half reported moderate symptoms of internalizing, and more than one-third reported at least one purposeful self-injury. However, only 30% reported any type of treatment for a mental health concern, the researchers said.

Parental closeness was protective against negative mental health outcomes, they noted. “Children of incarcerated parents are a vulnerable population and they should continue to be the targets of intervention efforts aiming to buttress their personal and social resources, including strong relationships with caregivers.”

Studies suggest that an estimated 1.9 million U.S. children have a parent in a state or federal prison, and millions more have a parent in county jails.

In Minnesota alone, 2,500 young people who had a parent in jail or whose parent had been in jail reported attempting suicide, and more than 5,000 children of incarcerated or formerly incarcerated parents had reported purposely having injured themselves in the last year. “This represents an enormous challenge to our systems of care,” said Dr. Davis and Dr. Shlafer. “Identifying and intervening with these youth should be a priority with governments and social service organizations.”

Read more at the Journal of Adolescence (2017;54:120-34).

[email protected]

Having or having had a parent in jail appears to be a risk factor for adolescent mental health problems, a Minnesota study found.

In a study of 122,180 children from the 8th, 9th, and 11th grades drawn from the 2013 Minnesota Student Survey, parental incarceration was strongly associated with higher rates of mental health problems such as internalizing, self-injury, suicidal ideation, and suicidal attempts. Children of currently incarcerated parents were two and a half to four times as likely to experience these mental health problems, and children of formerly incarcerated parents were roughly twice as likely to experience them, compared with children whose parents had not been jailed, said Laurel Davis, PhD, and Rebecca J. Shlafer, PhD, MPH, of the department of pediatrics at the University of Minnesota, Minneapolis.

For youth with currently incarcerated parents, almost half reported moderate symptoms of internalizing, and more than one-third reported at least one purposeful self-injury. However, only 30% reported any type of treatment for a mental health concern, the researchers said.

Parental closeness was protective against negative mental health outcomes, they noted. “Children of incarcerated parents are a vulnerable population and they should continue to be the targets of intervention efforts aiming to buttress their personal and social resources, including strong relationships with caregivers.”

Studies suggest that an estimated 1.9 million U.S. children have a parent in a state or federal prison, and millions more have a parent in county jails.

In Minnesota alone, 2,500 young people who had a parent in jail or whose parent had been in jail reported attempting suicide, and more than 5,000 children of incarcerated or formerly incarcerated parents had reported purposely having injured themselves in the last year. “This represents an enormous challenge to our systems of care,” said Dr. Davis and Dr. Shlafer. “Identifying and intervening with these youth should be a priority with governments and social service organizations.”

Read more at the Journal of Adolescence (2017;54:120-34).

[email protected]

Red blood cells

Researchers say they have discovered a new mechanism through which globin genes are expressed.

Their discovery, described in Cell Research, indicates that cellular stress is needed for the production of hemoglobin.

“Surprisingly, we have revealed an entirely new mechanism through which hemoglobin gene expression is regulated by stress,” said study author Raymond Kaempfer, PhD, of the Hebrew University of Jerusalem in Israel.

“An intracellular signal, essential for coping with stress, is absolutely necessary to allow for hemoglobin production. That stress signal is activated by the hemoglobin gene itself. Although we have long known that this signal strongly inhibits protein synthesis in general, during hemoglobin gene expression, it first plays its indispensable, positive role before being turned off promptly to allow for massive hemoglobin formation needed for breathing.”

To produce a globin protein molecule, the DNA of the globin gene is first transcribed into a long RNA molecule from which internal segments must be spliced out to generate the RNA template for protein synthesis in the red cell.

The researchers found that, for each of the adult and fetal globin genes, the splicing of its RNA is strictly controlled by an intracellular stress signal.

The signal, which has been known for a long time, involves an enzyme called PKR. This enzyme remains silent unless it is activated by a specific RNA structure thought to occur only in RNA made by viruses.

What the researchers discovered is that the long RNAs transcribed from the globin genes each contain a short intrinsic RNA element that is capable of strongly activating PKR.

Unless the PKR enzyme is activated in this manner, the long RNA cannot be spliced to form the mature RNA template for globin protein synthesis.

Once activated, PKR will place a phosphate onto a key initiation factor needed for the synthesis of all proteins, called eIF2-alpha. That, in turn, leads to inactivation of eIF2-alpha, resulting in a block in protein synthesis. This process is essential for coping with stress.

The researchers discovered that, once activated, PKR must phosphorylate eIF2-alpha, and that phosphorylated eIF2-alpha is essential to form the machinery needed to splice globin RNA.

In the splicing process, removal of an internal RNA segment causes the mature RNA product to refold such that it no longer will activate PKR. This allows for unimpeded synthesis on this RNA of the essential globin protein chains at maximal rates, which allows for effective oxygen breathing.

In other words, the ability to activate PKR remains transient, serving solely to enable splicing.

Thus, the researchers have demonstrated a novel, positive role for PKR activation and eIF2-alpha phosphorylation in human globin RNA splicing, in contrast to the long-standing negative role of this intracellular stress response in protein synthesis.

The realization that stress is essential may have implications for how we understand hemoglobin expression.

“What this boils down to is that, even at the cellular level, stress and the ability to mount a stress response are essential to our survival,” Dr Kaempfer said. “We have long known this in relation to other biological processes, and now we see that it is at play even for the tiny molecules that carry oxygen in our blood.”

Red blood cells

Researchers say they have discovered a new mechanism through which globin genes are expressed.

Their discovery, described in Cell Research, indicates that cellular stress is needed for the production of hemoglobin.

“Surprisingly, we have revealed an entirely new mechanism through which hemoglobin gene expression is regulated by stress,” said study author Raymond Kaempfer, PhD, of the Hebrew University of Jerusalem in Israel.

“An intracellular signal, essential for coping with stress, is absolutely necessary to allow for hemoglobin production. That stress signal is activated by the hemoglobin gene itself. Although we have long known that this signal strongly inhibits protein synthesis in general, during hemoglobin gene expression, it first plays its indispensable, positive role before being turned off promptly to allow for massive hemoglobin formation needed for breathing.”

To produce a globin protein molecule, the DNA of the globin gene is first transcribed into a long RNA molecule from which internal segments must be spliced out to generate the RNA template for protein synthesis in the red cell.

The researchers found that, for each of the adult and fetal globin genes, the splicing of its RNA is strictly controlled by an intracellular stress signal.

The signal, which has been known for a long time, involves an enzyme called PKR. This enzyme remains silent unless it is activated by a specific RNA structure thought to occur only in RNA made by viruses.

What the researchers discovered is that the long RNAs transcribed from the globin genes each contain a short intrinsic RNA element that is capable of strongly activating PKR.

Unless the PKR enzyme is activated in this manner, the long RNA cannot be spliced to form the mature RNA template for globin protein synthesis.

Once activated, PKR will place a phosphate onto a key initiation factor needed for the synthesis of all proteins, called eIF2-alpha. That, in turn, leads to inactivation of eIF2-alpha, resulting in a block in protein synthesis. This process is essential for coping with stress.

The researchers discovered that, once activated, PKR must phosphorylate eIF2-alpha, and that phosphorylated eIF2-alpha is essential to form the machinery needed to splice globin RNA.

In the splicing process, removal of an internal RNA segment causes the mature RNA product to refold such that it no longer will activate PKR. This allows for unimpeded synthesis on this RNA of the essential globin protein chains at maximal rates, which allows for effective oxygen breathing.

In other words, the ability to activate PKR remains transient, serving solely to enable splicing.

Thus, the researchers have demonstrated a novel, positive role for PKR activation and eIF2-alpha phosphorylation in human globin RNA splicing, in contrast to the long-standing negative role of this intracellular stress response in protein synthesis.

The realization that stress is essential may have implications for how we understand hemoglobin expression.

“What this boils down to is that, even at the cellular level, stress and the ability to mount a stress response are essential to our survival,” Dr Kaempfer said. “We have long known this in relation to other biological processes, and now we see that it is at play even for the tiny molecules that carry oxygen in our blood.”

Red blood cells

Researchers say they have discovered a new mechanism through which globin genes are expressed.

Their discovery, described in Cell Research, indicates that cellular stress is needed for the production of hemoglobin.

“Surprisingly, we have revealed an entirely new mechanism through which hemoglobin gene expression is regulated by stress,” said study author Raymond Kaempfer, PhD, of the Hebrew University of Jerusalem in Israel.

“An intracellular signal, essential for coping with stress, is absolutely necessary to allow for hemoglobin production. That stress signal is activated by the hemoglobin gene itself. Although we have long known that this signal strongly inhibits protein synthesis in general, during hemoglobin gene expression, it first plays its indispensable, positive role before being turned off promptly to allow for massive hemoglobin formation needed for breathing.”

To produce a globin protein molecule, the DNA of the globin gene is first transcribed into a long RNA molecule from which internal segments must be spliced out to generate the RNA template for protein synthesis in the red cell.

The researchers found that, for each of the adult and fetal globin genes, the splicing of its RNA is strictly controlled by an intracellular stress signal.

The signal, which has been known for a long time, involves an enzyme called PKR. This enzyme remains silent unless it is activated by a specific RNA structure thought to occur only in RNA made by viruses.

What the researchers discovered is that the long RNAs transcribed from the globin genes each contain a short intrinsic RNA element that is capable of strongly activating PKR.

Unless the PKR enzyme is activated in this manner, the long RNA cannot be spliced to form the mature RNA template for globin protein synthesis.

Once activated, PKR will place a phosphate onto a key initiation factor needed for the synthesis of all proteins, called eIF2-alpha. That, in turn, leads to inactivation of eIF2-alpha, resulting in a block in protein synthesis. This process is essential for coping with stress.

The researchers discovered that, once activated, PKR must phosphorylate eIF2-alpha, and that phosphorylated eIF2-alpha is essential to form the machinery needed to splice globin RNA.

In the splicing process, removal of an internal RNA segment causes the mature RNA product to refold such that it no longer will activate PKR. This allows for unimpeded synthesis on this RNA of the essential globin protein chains at maximal rates, which allows for effective oxygen breathing.

In other words, the ability to activate PKR remains transient, serving solely to enable splicing.

Thus, the researchers have demonstrated a novel, positive role for PKR activation and eIF2-alpha phosphorylation in human globin RNA splicing, in contrast to the long-standing negative role of this intracellular stress response in protein synthesis.

The realization that stress is essential may have implications for how we understand hemoglobin expression.

“What this boils down to is that, even at the cellular level, stress and the ability to mount a stress response are essential to our survival,” Dr Kaempfer said. “We have long known this in relation to other biological processes, and now we see that it is at play even for the tiny molecules that carry oxygen in our blood.”

Lifetime headaches appear to be closely associated with lifetime suicide attempts among older patients, a study of 1,965 community-dwelling participants aged 65 years and older suggests.

The results hold “even after adjusting for various confounding variables such as depression,” reported Raffaella Calati, PhD, of Inserm U1061 – Hôpital La Colombière in Montpellier, France, and her associates.

bbbrrn/Thinkstock

[email protected]

On Twitter @ginalhenderson

Lifetime headaches appear to be closely associated with lifetime suicide attempts among older patients, a study of 1,965 community-dwelling participants aged 65 years and older suggests.

The results hold “even after adjusting for various confounding variables such as depression,” reported Raffaella Calati, PhD, of Inserm U1061 – Hôpital La Colombière in Montpellier, France, and her associates.

bbbrrn/Thinkstock

[email protected]

On Twitter @ginalhenderson

Lifetime headaches appear to be closely associated with lifetime suicide attempts among older patients, a study of 1,965 community-dwelling participants aged 65 years and older suggests.

The results hold “even after adjusting for various confounding variables such as depression,” reported Raffaella Calati, PhD, of Inserm U1061 – Hôpital La Colombière in Montpellier, France, and her associates.

bbbrrn/Thinkstock

[email protected]

On Twitter @ginalhenderson

San Diego – A 22-year-old Minnesota patient with schizophrenia tried to “catch ’em all” during last year’s Pokémon Go craze, and he ended up landing something even more important: motivation to get outside and meet people.

That’s the word from clinicians who report that the game dramatically transformed the young man’s life, coaxing him to leave his house, chat with other players, and even stop worrying so much about his movement disorder.

Could Pokémon Go become a treatment for people with mental illness who need motivation to leave their homes? It’s not clear, and the decline of the Pokémon Go phenomenon may make it difficult for researchers to find out, at least until another version sweeps the nation.

The Minnesota clinicians want to study the idea; they also want to know why it seems – based on a tiny sample – that patients with schizophrenia may have trouble tolerating the “augmented reality” built into the game.

San Diego – A 22-year-old Minnesota patient with schizophrenia tried to “catch ’em all” during last year’s Pokémon Go craze, and he ended up landing something even more important: motivation to get outside and meet people.

That’s the word from clinicians who report that the game dramatically transformed the young man’s life, coaxing him to leave his house, chat with other players, and even stop worrying so much about his movement disorder.

Could Pokémon Go become a treatment for people with mental illness who need motivation to leave their homes? It’s not clear, and the decline of the Pokémon Go phenomenon may make it difficult for researchers to find out, at least until another version sweeps the nation.

The Minnesota clinicians want to study the idea; they also want to know why it seems – based on a tiny sample – that patients with schizophrenia may have trouble tolerating the “augmented reality” built into the game.

San Diego – A 22-year-old Minnesota patient with schizophrenia tried to “catch ’em all” during last year’s Pokémon Go craze, and he ended up landing something even more important: motivation to get outside and meet people.

That’s the word from clinicians who report that the game dramatically transformed the young man’s life, coaxing him to leave his house, chat with other players, and even stop worrying so much about his movement disorder.

Could Pokémon Go become a treatment for people with mental illness who need motivation to leave their homes? It’s not clear, and the decline of the Pokémon Go phenomenon may make it difficult for researchers to find out, at least until another version sweeps the nation.

The Minnesota clinicians want to study the idea; they also want to know why it seems – based on a tiny sample – that patients with schizophrenia may have trouble tolerating the “augmented reality” built into the game.

SNOWMASS, COLO. – Mounting evidence attests to the value of noninvasive measurement of coronary flow reserve as a means of classifying cardiovascular risk in patients with stable coronary artery disease (CAD) more accurately than is possible via coronary angiography or measurement of fractional flow reserve, Marcelo F. Di Carli, MD, reported at the Annual Cardiovascular Conference at Snowmass.

“We use CFR [coronary flow reserve] as a way to exclude coronary disease. It’s a good practical measure of multivessel ischemic CAD. When the CFR is normal, you can with high confidence exclude the possibility of high-risk CAD,” according to Dr. Di Carli, executive director of the cardiovascular imaging program and chief of the division of nuclear medicine and molecular imaging at Brigham and Women’s Hospital, Boston.

Bruce Jancin/Frontline Medical News

[email protected]

SNOWMASS, COLO. – Mounting evidence attests to the value of noninvasive measurement of coronary flow reserve as a means of classifying cardiovascular risk in patients with stable coronary artery disease (CAD) more accurately than is possible via coronary angiography or measurement of fractional flow reserve, Marcelo F. Di Carli, MD, reported at the Annual Cardiovascular Conference at Snowmass.

“We use CFR [coronary flow reserve] as a way to exclude coronary disease. It’s a good practical measure of multivessel ischemic CAD. When the CFR is normal, you can with high confidence exclude the possibility of high-risk CAD,” according to Dr. Di Carli, executive director of the cardiovascular imaging program and chief of the division of nuclear medicine and molecular imaging at Brigham and Women’s Hospital, Boston.

Bruce Jancin/Frontline Medical News

[email protected]

SNOWMASS, COLO. – Mounting evidence attests to the value of noninvasive measurement of coronary flow reserve as a means of classifying cardiovascular risk in patients with stable coronary artery disease (CAD) more accurately than is possible via coronary angiography or measurement of fractional flow reserve, Marcelo F. Di Carli, MD, reported at the Annual Cardiovascular Conference at Snowmass.

“We use CFR [coronary flow reserve] as a way to exclude coronary disease. It’s a good practical measure of multivessel ischemic CAD. When the CFR is normal, you can with high confidence exclude the possibility of high-risk CAD,” according to Dr. Di Carli, executive director of the cardiovascular imaging program and chief of the division of nuclear medicine and molecular imaging at Brigham and Women’s Hospital, Boston.

Bruce Jancin/Frontline Medical News

[email protected]