Platelets for transfusion

Scientists say they’ve discovered a way to create a potentially inexhaustible supply of functional platelets.

The researchers used human induced pluripotent stem cells (iPSCs) to create immortalized megakaryocyte progenitor cell lines (imMKCLs). And by manipulating the cell lines, the team produced platelets.

These imMKCL-derived platelets were functional, although not as functional as donor-derived platelets.

On the other hand, the imMKCL-derived cells offer an advantage over donated platelets—namely, the imMKCLs can be expanded in culture for up to 5 months, even after cryopreservation.

“[W]e established a method to achieve the long-term self-replication of megakaryocyte progenitors as an immortalized cell line, which could eventually contribute to large-scale cultivation and production of platelets,” said senior study author Koji Eto, MD, PhD, of Kyoto University and the University of Tokyo in Japan.

He and his colleagues believe this work, published in Cell Stem Cell, could eventually help us eliminate platelet shortages. The supply of donated platelets, which have a short shelf-life and must be kept at room temperature, is often insufficient to meet clinical needs.

With that in mind, Dr Eto’s team set out to create large quantities of functional platelets. They first generated stable imMKCLs from iPSC-derived hematopoietic progenitors.

They accomplished this by inducing overexpression of BMI1 and BCL-XL to suppress senescence and apoptosis. They also induced constrained overexpression of c-MYC to promote proliferation, as they found too-high c-MYC expression led to caspase-dependent MKCL apoptosis.

When the researchers turned off expression of c-MYC, BMI1, and BCL-XL, they saw an increase in CD42b+ platelet yield from the imMKCLs and upregulated CD42b expression in CD41a+ platelets. They noted that expression of CD42b is required for clotting initiation and bacterial clearance in vivo.

The team then conducted in vitro and in vivo experiments to test the functionality of their platelets. Most of the in vitro functional parameters indicated that imMKCL-derived platelets produced less robust responses than donor platelets.

But the imMKCL-derived platelets were functional enough to be useful and produced promising results in vivo. In mouse models of thrombocytopenia, the imMKCL-derived platelets contributed to thrombi development better than human endogenous pooled platelets.

Platelets for transfusion

Scientists say they’ve discovered a way to create a potentially inexhaustible supply of functional platelets.

The researchers used human induced pluripotent stem cells (iPSCs) to create immortalized megakaryocyte progenitor cell lines (imMKCLs). And by manipulating the cell lines, the team produced platelets.

These imMKCL-derived platelets were functional, although not as functional as donor-derived platelets.

On the other hand, the imMKCL-derived cells offer an advantage over donated platelets—namely, the imMKCLs can be expanded in culture for up to 5 months, even after cryopreservation.

“[W]e established a method to achieve the long-term self-replication of megakaryocyte progenitors as an immortalized cell line, which could eventually contribute to large-scale cultivation and production of platelets,” said senior study author Koji Eto, MD, PhD, of Kyoto University and the University of Tokyo in Japan.

He and his colleagues believe this work, published in Cell Stem Cell, could eventually help us eliminate platelet shortages. The supply of donated platelets, which have a short shelf-life and must be kept at room temperature, is often insufficient to meet clinical needs.

With that in mind, Dr Eto’s team set out to create large quantities of functional platelets. They first generated stable imMKCLs from iPSC-derived hematopoietic progenitors.

They accomplished this by inducing overexpression of BMI1 and BCL-XL to suppress senescence and apoptosis. They also induced constrained overexpression of c-MYC to promote proliferation, as they found too-high c-MYC expression led to caspase-dependent MKCL apoptosis.

When the researchers turned off expression of c-MYC, BMI1, and BCL-XL, they saw an increase in CD42b+ platelet yield from the imMKCLs and upregulated CD42b expression in CD41a+ platelets. They noted that expression of CD42b is required for clotting initiation and bacterial clearance in vivo.

The team then conducted in vitro and in vivo experiments to test the functionality of their platelets. Most of the in vitro functional parameters indicated that imMKCL-derived platelets produced less robust responses than donor platelets.

But the imMKCL-derived platelets were functional enough to be useful and produced promising results in vivo. In mouse models of thrombocytopenia, the imMKCL-derived platelets contributed to thrombi development better than human endogenous pooled platelets.

Platelets for transfusion

Scientists say they’ve discovered a way to create a potentially inexhaustible supply of functional platelets.

The researchers used human induced pluripotent stem cells (iPSCs) to create immortalized megakaryocyte progenitor cell lines (imMKCLs). And by manipulating the cell lines, the team produced platelets.

These imMKCL-derived platelets were functional, although not as functional as donor-derived platelets.

On the other hand, the imMKCL-derived cells offer an advantage over donated platelets—namely, the imMKCLs can be expanded in culture for up to 5 months, even after cryopreservation.

“[W]e established a method to achieve the long-term self-replication of megakaryocyte progenitors as an immortalized cell line, which could eventually contribute to large-scale cultivation and production of platelets,” said senior study author Koji Eto, MD, PhD, of Kyoto University and the University of Tokyo in Japan.

He and his colleagues believe this work, published in Cell Stem Cell, could eventually help us eliminate platelet shortages. The supply of donated platelets, which have a short shelf-life and must be kept at room temperature, is often insufficient to meet clinical needs.

With that in mind, Dr Eto’s team set out to create large quantities of functional platelets. They first generated stable imMKCLs from iPSC-derived hematopoietic progenitors.

They accomplished this by inducing overexpression of BMI1 and BCL-XL to suppress senescence and apoptosis. They also induced constrained overexpression of c-MYC to promote proliferation, as they found too-high c-MYC expression led to caspase-dependent MKCL apoptosis.

When the researchers turned off expression of c-MYC, BMI1, and BCL-XL, they saw an increase in CD42b+ platelet yield from the imMKCLs and upregulated CD42b expression in CD41a+ platelets. They noted that expression of CD42b is required for clotting initiation and bacterial clearance in vivo.

The team then conducted in vitro and in vivo experiments to test the functionality of their platelets. Most of the in vitro functional parameters indicated that imMKCL-derived platelets produced less robust responses than donor platelets.

But the imMKCL-derived platelets were functional enough to be useful and produced promising results in vivo. In mouse models of thrombocytopenia, the imMKCL-derived platelets contributed to thrombi development better than human endogenous pooled platelets.

Drug in vials

Credit: Bill Branson

The US Food and Drug Administration (FDA) has granted full approval of omacetaxine mepesuccinate (Synribo) for the treatment of chronic myeloid leukemia (CML).

The drug received accelerated approval in October 2012 to treat adults with chronic phase (CP) or accelerated phase (AP) CML who were resistant to or could not tolerate 2 or more tyrosine kinase inhibitors (TKIs).

But additional clinical trial data were required before the FDA could grant the drug full approval.

Now, the agency has granted that approval based on the final analysis of two phase 2 trials.

The original approval of omacetaxine mepesuccinate was based on an analysis of combined data subsets from these trials. The pooled analysis included patients who had received 2 or more approved TKIs and, at a minimum, had evidence of resistance or intolerance to dasatinib and/or nilotinib.

Forty-seven percent of patients with CP CML and 63% of patients with AP CML had failed treatment with 3 TKIs—imatinib, dasatinib, and nilotinib. The majority of patients had also received other treatments, including hydroxyurea, interferon, and cytarabine.

Among CP patients, 18% (14/76) achieved a major cytogenetic response (MCyR). The mean time to MCyR onset was 3.5 months, and the median duration of MCyR was 12.5 months.

Among AP Patients, 14% (5/35) achieved a major hematologic response (MaHR). The mean time to MaHR onset was 2.3 months, and the median duration of MaHR was 4.7 months.

The most common adverse events for AP and CP patients (occurring in 20% or more) were thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, and lymphopenia.

Omacetaxine mepesuccinate is the first protein synthesis inhibitor for CML. Although the drug’s mechanism of action is not fully understood, it is known to prevent the production of Bcr-Abl and Mcl-1, which help drive CML.

For more details on omacetaxine mepesuccinate, see the full prescribing information.

Drug in vials

Credit: Bill Branson

The US Food and Drug Administration (FDA) has granted full approval of omacetaxine mepesuccinate (Synribo) for the treatment of chronic myeloid leukemia (CML).

The drug received accelerated approval in October 2012 to treat adults with chronic phase (CP) or accelerated phase (AP) CML who were resistant to or could not tolerate 2 or more tyrosine kinase inhibitors (TKIs).

But additional clinical trial data were required before the FDA could grant the drug full approval.

Now, the agency has granted that approval based on the final analysis of two phase 2 trials.

The original approval of omacetaxine mepesuccinate was based on an analysis of combined data subsets from these trials. The pooled analysis included patients who had received 2 or more approved TKIs and, at a minimum, had evidence of resistance or intolerance to dasatinib and/or nilotinib.

Forty-seven percent of patients with CP CML and 63% of patients with AP CML had failed treatment with 3 TKIs—imatinib, dasatinib, and nilotinib. The majority of patients had also received other treatments, including hydroxyurea, interferon, and cytarabine.

Among CP patients, 18% (14/76) achieved a major cytogenetic response (MCyR). The mean time to MCyR onset was 3.5 months, and the median duration of MCyR was 12.5 months.

Among AP Patients, 14% (5/35) achieved a major hematologic response (MaHR). The mean time to MaHR onset was 2.3 months, and the median duration of MaHR was 4.7 months.

The most common adverse events for AP and CP patients (occurring in 20% or more) were thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, and lymphopenia.

Omacetaxine mepesuccinate is the first protein synthesis inhibitor for CML. Although the drug’s mechanism of action is not fully understood, it is known to prevent the production of Bcr-Abl and Mcl-1, which help drive CML.

For more details on omacetaxine mepesuccinate, see the full prescribing information.

Drug in vials

Credit: Bill Branson

The US Food and Drug Administration (FDA) has granted full approval of omacetaxine mepesuccinate (Synribo) for the treatment of chronic myeloid leukemia (CML).

The drug received accelerated approval in October 2012 to treat adults with chronic phase (CP) or accelerated phase (AP) CML who were resistant to or could not tolerate 2 or more tyrosine kinase inhibitors (TKIs).

But additional clinical trial data were required before the FDA could grant the drug full approval.

Now, the agency has granted that approval based on the final analysis of two phase 2 trials.

The original approval of omacetaxine mepesuccinate was based on an analysis of combined data subsets from these trials. The pooled analysis included patients who had received 2 or more approved TKIs and, at a minimum, had evidence of resistance or intolerance to dasatinib and/or nilotinib.

Forty-seven percent of patients with CP CML and 63% of patients with AP CML had failed treatment with 3 TKIs—imatinib, dasatinib, and nilotinib. The majority of patients had also received other treatments, including hydroxyurea, interferon, and cytarabine.

Among CP patients, 18% (14/76) achieved a major cytogenetic response (MCyR). The mean time to MCyR onset was 3.5 months, and the median duration of MCyR was 12.5 months.

Among AP Patients, 14% (5/35) achieved a major hematologic response (MaHR). The mean time to MaHR onset was 2.3 months, and the median duration of MaHR was 4.7 months.

The most common adverse events for AP and CP patients (occurring in 20% or more) were thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, and lymphopenia.

Omacetaxine mepesuccinate is the first protein synthesis inhibitor for CML. Although the drug’s mechanism of action is not fully understood, it is known to prevent the production of Bcr-Abl and Mcl-1, which help drive CML.

For more details on omacetaxine mepesuccinate, see the full prescribing information.

Thrombus

Credit: Andre E.X. Brown

The US Food and Drug Administration (FDA) has again decided not to approve the anticoagulant rivaroxaban (Xarelto) for use in patients with acute coronary syndromes (ACS).

The drug’s developers are seeking approval of rivaroxaban to reduce the risk of secondary cardiovascular events—heart attack, stroke, or death—and to reduce the risk of stent thrombosis in ACS patients.

For both indications, the drug would be given in combination with standard antiplatelet therapy.

This is not the first time the FDA has decided against approving rivaroxaban for use in ACS patients. The agency rejected the drug as prophylaxis for cardiovascular events in June 2012 and March 2013. And the drug was denied approval for stent thrombosis in June 2013.

Nevertheless, it seems the companies developing rivaroxaban—Janssen Research & Development, LLC and Bayer HealthCare—plan to continue pursuing approvals for these indications.

“We remain committed to providing patients who have suffered from acute coronary syndrome with additional protection against stent thrombosis and secondary, life-threatening cardiovascular events,” said Paul Burton, MD, PhD, Vice President, Clinical Development, Janssen Research & Development.

“We are evaluating the contents of the [FDA’s complete response] letters and will determine the appropriate next steps.”

Both applications for expanding rivaroxaban use were based on results from the phase 3 ATLAS ACS 2 TIMI 51 trial, which were published in NEJM in November 2011.

The study showed that rivaroxaban, when given in combination with standard antiplatelet therapy, reduced the composite endpoint of cardiovascular death, myocardial infarction, and stroke in ACS patients, compared to placebo. But rivaroxaban also increased the risk of major bleeding and intracranial hemorrhage.

In past evaluations of rivaroxaban, the FDA and its advisors expressed concerns about data from this trial, particularly the risk of bleeding associated with rivaroxaban and some gaps in trial data.

Although Janssen submitted the missing data, the FDA still had reservations about rivaroxaban’s safety and efficacy in ACS patients. The FDA recently suggested the company limit the proposed duration of rivaroxaban treatment, as the drug might be safer and more effective when given for a shorter period.

So Janssen changed the suggested treatment duration to 90 days. But last month, an FDA advisory committee still recommended against expanding the drug’s indication. And the agency seems to have taken that recommendation to heart.

Rivaroxaban is currently FDA-approved to treat patients with venous thromboembolism (VTE) and to reduce the risk of VTE recurrence following an initial 6-month treatment for acute VTE. The drug is also approved for use as thromboprophylaxis for patients with non-valvular atrial fibrillation, those who have undergone knee replacement surgery, and patients who have had hip replacement surgery.

Thrombus

Credit: Andre E.X. Brown

The US Food and Drug Administration (FDA) has again decided not to approve the anticoagulant rivaroxaban (Xarelto) for use in patients with acute coronary syndromes (ACS).

The drug’s developers are seeking approval of rivaroxaban to reduce the risk of secondary cardiovascular events—heart attack, stroke, or death—and to reduce the risk of stent thrombosis in ACS patients.

For both indications, the drug would be given in combination with standard antiplatelet therapy.

This is not the first time the FDA has decided against approving rivaroxaban for use in ACS patients. The agency rejected the drug as prophylaxis for cardiovascular events in June 2012 and March 2013. And the drug was denied approval for stent thrombosis in June 2013.

Nevertheless, it seems the companies developing rivaroxaban—Janssen Research & Development, LLC and Bayer HealthCare—plan to continue pursuing approvals for these indications.

“We remain committed to providing patients who have suffered from acute coronary syndrome with additional protection against stent thrombosis and secondary, life-threatening cardiovascular events,” said Paul Burton, MD, PhD, Vice President, Clinical Development, Janssen Research & Development.

“We are evaluating the contents of the [FDA’s complete response] letters and will determine the appropriate next steps.”

Both applications for expanding rivaroxaban use were based on results from the phase 3 ATLAS ACS 2 TIMI 51 trial, which were published in NEJM in November 2011.

The study showed that rivaroxaban, when given in combination with standard antiplatelet therapy, reduced the composite endpoint of cardiovascular death, myocardial infarction, and stroke in ACS patients, compared to placebo. But rivaroxaban also increased the risk of major bleeding and intracranial hemorrhage.

In past evaluations of rivaroxaban, the FDA and its advisors expressed concerns about data from this trial, particularly the risk of bleeding associated with rivaroxaban and some gaps in trial data.

Although Janssen submitted the missing data, the FDA still had reservations about rivaroxaban’s safety and efficacy in ACS patients. The FDA recently suggested the company limit the proposed duration of rivaroxaban treatment, as the drug might be safer and more effective when given for a shorter period.

So Janssen changed the suggested treatment duration to 90 days. But last month, an FDA advisory committee still recommended against expanding the drug’s indication. And the agency seems to have taken that recommendation to heart.

Rivaroxaban is currently FDA-approved to treat patients with venous thromboembolism (VTE) and to reduce the risk of VTE recurrence following an initial 6-month treatment for acute VTE. The drug is also approved for use as thromboprophylaxis for patients with non-valvular atrial fibrillation, those who have undergone knee replacement surgery, and patients who have had hip replacement surgery.

Thrombus

Credit: Andre E.X. Brown

The US Food and Drug Administration (FDA) has again decided not to approve the anticoagulant rivaroxaban (Xarelto) for use in patients with acute coronary syndromes (ACS).

The drug’s developers are seeking approval of rivaroxaban to reduce the risk of secondary cardiovascular events—heart attack, stroke, or death—and to reduce the risk of stent thrombosis in ACS patients.

For both indications, the drug would be given in combination with standard antiplatelet therapy.

This is not the first time the FDA has decided against approving rivaroxaban for use in ACS patients. The agency rejected the drug as prophylaxis for cardiovascular events in June 2012 and March 2013. And the drug was denied approval for stent thrombosis in June 2013.

Nevertheless, it seems the companies developing rivaroxaban—Janssen Research & Development, LLC and Bayer HealthCare—plan to continue pursuing approvals for these indications.

“We remain committed to providing patients who have suffered from acute coronary syndrome with additional protection against stent thrombosis and secondary, life-threatening cardiovascular events,” said Paul Burton, MD, PhD, Vice President, Clinical Development, Janssen Research & Development.

“We are evaluating the contents of the [FDA’s complete response] letters and will determine the appropriate next steps.”

Both applications for expanding rivaroxaban use were based on results from the phase 3 ATLAS ACS 2 TIMI 51 trial, which were published in NEJM in November 2011.

The study showed that rivaroxaban, when given in combination with standard antiplatelet therapy, reduced the composite endpoint of cardiovascular death, myocardial infarction, and stroke in ACS patients, compared to placebo. But rivaroxaban also increased the risk of major bleeding and intracranial hemorrhage.

In past evaluations of rivaroxaban, the FDA and its advisors expressed concerns about data from this trial, particularly the risk of bleeding associated with rivaroxaban and some gaps in trial data.

Although Janssen submitted the missing data, the FDA still had reservations about rivaroxaban’s safety and efficacy in ACS patients. The FDA recently suggested the company limit the proposed duration of rivaroxaban treatment, as the drug might be safer and more effective when given for a shorter period.

So Janssen changed the suggested treatment duration to 90 days. But last month, an FDA advisory committee still recommended against expanding the drug’s indication. And the agency seems to have taken that recommendation to heart.

Rivaroxaban is currently FDA-approved to treat patients with venous thromboembolism (VTE) and to reduce the risk of VTE recurrence following an initial 6-month treatment for acute VTE. The drug is also approved for use as thromboprophylaxis for patients with non-valvular atrial fibrillation, those who have undergone knee replacement surgery, and patients who have had hip replacement surgery.

When I was a little girl, I enjoyed watching the Brady Bunch on television. For those of you under the age of 30, who may not be familiar with this hit series, Mrs. Brady, played by Florence Henderson, was a stay-at-home mother with six kids, three of her own and three of her husband’s by a prior marriage. Somehow, the house was always immaculate, the kids were always well kept, and she always managed to be level-headed, warm, and nurturing (but Alice, the housekeeper, helped a lot).

Fast forward a few decades. Now women frequently are the primary breadwinners, often working outside the home and then even more when they return after work, tethered to a computer or with smartphone in hand. This is the new work-life balance equation for many of us.

©photo168/iStockphoto

My husband and I are currently seeking to adopt a little girl in the foster care system. If we are successful in 2014, this will be our second adoption in 5 years. Anyone who has ever added to their family this way can attest to the hurdles, stumbling blocks, and utter frustration the journey can hold. In the last 8 months, I have seen thousands of photos of waiting children and found only one child in our self-defined age group (4 or younger) who does not have major developmental or physical challenges. There are over 15 other families who have also inquired about her.

I used to feel guilty that I flipped through the pictures of special-needs children quickly, but when I think about my reality as a full-time hospitalist and a mother, I know I cannot provide a special-needs child with the attention she needs. If I have a patient in the ER with unstable angina and a child at home in the midst of a seizure, I cannot exactly call into work for "family reasons." How idyllic would it be for a physician to adopt a sick child, bringing her into a home already endowed with medical expertise? On its face, and to outsiders, it would be perfect. But I have to be realistic about what I can and cannot handle, and about what choice is caring and considerate to both patients and my existing family.

While I await that life-changing call from a social worker somewhere, who has seen my family profile and thinks we would be a perfect fit for a child in her caseload, I am working toward the future. I have a glimpse of what it will be like with two small children and a demanding job, and it has the potential to be chaotic, hair-raising, and overwhelming, but it can also be calm, joyous, and well organized. I realized it is okay to say, "I can’t do this by myself." Cooking, shopping, washing, homework, tantrums, beepers, ... oh my!

I have no relatives who can help make life more manageable, but I have figured out a few things I can do. In addition to a housekeeper, I decided to enlist the help of a personal assistant – who happens to also be my hairdresser and friend – whom I can pay by the hour ($25) to do a variety of tasks around the house and run errands here and there. A few hours here and there will make a huge difference in my peace of mind. I cannot yet rule out an au pair or live-in nanny, but we are not quite ready to share our space with anyone outside our family. I am thankful, of course, that this is even an option for my household financially.

Whether you are a soon-to-be mom or dad, you too may want to think out of the box about ways to trade a hectic, disorganized life for one far more peaceful and serene, even if it comes with a price tag. What works for me may not work for you, but there is a potential solution for us all. We may just have to search hard and pay for it.

Thoughts? E-mail me at [email protected].

Dr. Hester is a hospitalist with Baltimore-Washington Medical Center who has a passion for empowering patients to partner in their health care. She is the creator of the Patient Whiz, a patient-engagement app for iOS.

When I was a little girl, I enjoyed watching the Brady Bunch on television. For those of you under the age of 30, who may not be familiar with this hit series, Mrs. Brady, played by Florence Henderson, was a stay-at-home mother with six kids, three of her own and three of her husband’s by a prior marriage. Somehow, the house was always immaculate, the kids were always well kept, and she always managed to be level-headed, warm, and nurturing (but Alice, the housekeeper, helped a lot).

Fast forward a few decades. Now women frequently are the primary breadwinners, often working outside the home and then even more when they return after work, tethered to a computer or with smartphone in hand. This is the new work-life balance equation for many of us.

©photo168/iStockphoto

My husband and I are currently seeking to adopt a little girl in the foster care system. If we are successful in 2014, this will be our second adoption in 5 years. Anyone who has ever added to their family this way can attest to the hurdles, stumbling blocks, and utter frustration the journey can hold. In the last 8 months, I have seen thousands of photos of waiting children and found only one child in our self-defined age group (4 or younger) who does not have major developmental or physical challenges. There are over 15 other families who have also inquired about her.

I used to feel guilty that I flipped through the pictures of special-needs children quickly, but when I think about my reality as a full-time hospitalist and a mother, I know I cannot provide a special-needs child with the attention she needs. If I have a patient in the ER with unstable angina and a child at home in the midst of a seizure, I cannot exactly call into work for "family reasons." How idyllic would it be for a physician to adopt a sick child, bringing her into a home already endowed with medical expertise? On its face, and to outsiders, it would be perfect. But I have to be realistic about what I can and cannot handle, and about what choice is caring and considerate to both patients and my existing family.

While I await that life-changing call from a social worker somewhere, who has seen my family profile and thinks we would be a perfect fit for a child in her caseload, I am working toward the future. I have a glimpse of what it will be like with two small children and a demanding job, and it has the potential to be chaotic, hair-raising, and overwhelming, but it can also be calm, joyous, and well organized. I realized it is okay to say, "I can’t do this by myself." Cooking, shopping, washing, homework, tantrums, beepers, ... oh my!

I have no relatives who can help make life more manageable, but I have figured out a few things I can do. In addition to a housekeeper, I decided to enlist the help of a personal assistant – who happens to also be my hairdresser and friend – whom I can pay by the hour ($25) to do a variety of tasks around the house and run errands here and there. A few hours here and there will make a huge difference in my peace of mind. I cannot yet rule out an au pair or live-in nanny, but we are not quite ready to share our space with anyone outside our family. I am thankful, of course, that this is even an option for my household financially.

Whether you are a soon-to-be mom or dad, you too may want to think out of the box about ways to trade a hectic, disorganized life for one far more peaceful and serene, even if it comes with a price tag. What works for me may not work for you, but there is a potential solution for us all. We may just have to search hard and pay for it.

Thoughts? E-mail me at [email protected].

Dr. Hester is a hospitalist with Baltimore-Washington Medical Center who has a passion for empowering patients to partner in their health care. She is the creator of the Patient Whiz, a patient-engagement app for iOS.

When I was a little girl, I enjoyed watching the Brady Bunch on television. For those of you under the age of 30, who may not be familiar with this hit series, Mrs. Brady, played by Florence Henderson, was a stay-at-home mother with six kids, three of her own and three of her husband’s by a prior marriage. Somehow, the house was always immaculate, the kids were always well kept, and she always managed to be level-headed, warm, and nurturing (but Alice, the housekeeper, helped a lot).

Fast forward a few decades. Now women frequently are the primary breadwinners, often working outside the home and then even more when they return after work, tethered to a computer or with smartphone in hand. This is the new work-life balance equation for many of us.

©photo168/iStockphoto

My husband and I are currently seeking to adopt a little girl in the foster care system. If we are successful in 2014, this will be our second adoption in 5 years. Anyone who has ever added to their family this way can attest to the hurdles, stumbling blocks, and utter frustration the journey can hold. In the last 8 months, I have seen thousands of photos of waiting children and found only one child in our self-defined age group (4 or younger) who does not have major developmental or physical challenges. There are over 15 other families who have also inquired about her.

I used to feel guilty that I flipped through the pictures of special-needs children quickly, but when I think about my reality as a full-time hospitalist and a mother, I know I cannot provide a special-needs child with the attention she needs. If I have a patient in the ER with unstable angina and a child at home in the midst of a seizure, I cannot exactly call into work for "family reasons." How idyllic would it be for a physician to adopt a sick child, bringing her into a home already endowed with medical expertise? On its face, and to outsiders, it would be perfect. But I have to be realistic about what I can and cannot handle, and about what choice is caring and considerate to both patients and my existing family.

While I await that life-changing call from a social worker somewhere, who has seen my family profile and thinks we would be a perfect fit for a child in her caseload, I am working toward the future. I have a glimpse of what it will be like with two small children and a demanding job, and it has the potential to be chaotic, hair-raising, and overwhelming, but it can also be calm, joyous, and well organized. I realized it is okay to say, "I can’t do this by myself." Cooking, shopping, washing, homework, tantrums, beepers, ... oh my!

I have no relatives who can help make life more manageable, but I have figured out a few things I can do. In addition to a housekeeper, I decided to enlist the help of a personal assistant – who happens to also be my hairdresser and friend – whom I can pay by the hour ($25) to do a variety of tasks around the house and run errands here and there. A few hours here and there will make a huge difference in my peace of mind. I cannot yet rule out an au pair or live-in nanny, but we are not quite ready to share our space with anyone outside our family. I am thankful, of course, that this is even an option for my household financially.

Whether you are a soon-to-be mom or dad, you too may want to think out of the box about ways to trade a hectic, disorganized life for one far more peaceful and serene, even if it comes with a price tag. What works for me may not work for you, but there is a potential solution for us all. We may just have to search hard and pay for it.

Thoughts? E-mail me at [email protected].

Dr. Hester is a hospitalist with Baltimore-Washington Medical Center who has a passion for empowering patients to partner in their health care. She is the creator of the Patient Whiz, a patient-engagement app for iOS.

SAN FRANCISCO – Updated guidelines from the American Diabetes Association open the door to using a two-step approach to gestational diabetes screening.

Screening is still recommended for undiagnosed type 2 diabetes at the first prenatal visit in those with risk factors, and for gestational diabetes mellitus (GDM) between weeks 24 and 28 of gestation.

What’s changed in the 2014 Standards of Medical Care in Diabetes (Diabetes Care 2014;37(suppl 1):S14-80) is how that screening is accomplished, Dr. Richard W. Grant, chair of the ADA professional practice committee, said at the annual advanced postgraduate course held by the American Diabetes Association.

In prior years, the ADA adopted the International Association of Diabetes and Pregnancy Study Groups (IADPSG) 2009 recommendation that a 2-hour, 75-gram oral glucose tolerance test (OGTT) be performed the morning after a fast of at least an 8 hours.

A two-step approach was added this year to reflect the 2013 National Institutes of Health Consensus Guidelines recommendation for a 1-hour, 50-gram glucose tolerance screening test followed by a fasting OGTT on another day, if the test is abnormal.

One-step vs. two-step approach

"The issues for these two approaches are the sensitivity with which you can diagnose GDM and the difficulty in implementing these two approaches," said Dr. Grant, a research scientist with Kaiser Permanente Northern California, Oakland.

The one-step approach tends to be more sensitive and diagnoses a broader range of GDM, but it may be a barrier to screening because it requires the patient to fast for 8 hours, he said. Though the one-step approach allows for a diagnosis of GDM within the context of a single office visit, critics also argue its tight diagnostic glucose cut points could dramatically increase the prevalence of GDM from about 5%-6% to 15%-20%, and bring added health care costs and interventions without clear evidence of improved outcomes.

On the other hand, the two-step approach may be more palatable to women because it avoids the up-front fasting requirement, but it could miss GDM in women with an abnormal screen who fail to return for a second visit.

"The bottom line is we need to make sure we do gestational diabetes screening, whichever method we use," Dr. Grant said. "What’s more important is that all women in early pregnancy get screened."

During a discussion following the presentation, a Canadian attendee said similar recommendations released last fall in Canada allowing two screening methods, albeit with different diagnostic thresholds, have resulted in confusion, particularly among referring obstetricians and endocrinologists.

Dr. Grant said there shouldn’t be confusion surrounding the new option as long as recommendations are consistent within an institution.

"I don’t think it’s actually going to make people change what they’re doing currently," he said in an interview. "There’s not a good reason to jump from one to another if you’ve already chosen an approach."

In a separate interview, Dr. R. Harsha Rao, with the Center for Diabetes and Endocrinology at the University of Pittsburgh, said he can see the rationale for the one-step method, but that the two-step approach is almost implanted in the DNA of American obstetricians and that this behavior pattern will be difficult to change for practical reasons alone.

"Patients don’t like 75 grams of Glucola; it’s an awful-tasting substance," he said. "I’ve had patients tell me they felt like [vomiting] when they got the 75-gram Glucola load, and as it is, ‘I’m pregnant and already feeling nauseated.’ "

In addition, there’s the added stress of waiting for a second appointment and a definitive diagnosis for women who screen positive.

The ADA’s bimodal approach to gestational screening reflects an overarching theme of individualized care for diabetes in the 2014 standards. The guidelines are updated annually and this year they contain 232 recommendations, of which 52% are based on high level A or B evidence.

Individualized diabetes care

"One of the themes that comes out in looking at the data very carefully is that you can’t have a one-size-fits-all approach," Dr. Grant observed.

To that end, the guidelines maintain an earlier recommendation raising the systolic blood pressure target goal for hypertension to 140 mm Hg, but also allow a target goal of less than 130 mm Hg in certain populations, such as younger patients.

Dr. Grant observed that the ADA’s position was confirmed by the U.S. Preventive Services Task Force’s recent endorsement of GDM screening using the two-step approach.

"The USPSTF said that the two-step method is an accurate approach, which is what the ADA also says," he remarked.

Based on the recently revised 2013 ADA nutrition position paper (described in the next section below), the guidelines also encourage individualized dietary approaches rather recommending one particular diet over another, Dr. Grant said.

Other revisions include:

• Clarification that the hemoglobin A_1c test is just one of three methods to diagnose diabetes in asymptomatic patients, along with the fasting plasma glucose or 75-gram, 2-hour OGTT;

• An expanded chapter on neuropathy screening and treatment, including B level evidentiary support to test for distal symmetric polyneuropathy;

• Added emphasis on the need to ask patients about symptomatic and asymptomatic hypoglycemia and perform ongoing assessments of cognitive function; and

• Added emphasis on a patient-centered communication style that assesses literacy, but also the often overlooked issue of numeracy.

"It’s really quite impressive how many patients don’t get numbers, but we as physicians speak in numbers," Dr. Grant said.

The recent controversial 2013 American College of Cardiology/American Heart Association cholesterol guideline could not be reviewed in time to for this year’s guidelines, but it will be something to keep an eye out for next year.

ADA dodges dietary dogma

Highlights of the American Diabetes Association’s nutrition recommendations, updated in late 2013, and also presented at the meeting by Patti Urbanski, M.Ed., a member of the ADA Nutrition Recommendations Writing Group Committee, include:

• Select an "eating pattern" based on an individual’s personal and cultural preferences; literacy and numeracy; readiness; and ability to change, because no one dietary plan – be it the Mediterranean, low-carb, or DASH (Dietary Approaches to Stop Hypertension) diet – is best.

• In the absence of evidence supporting an ideal percentage of calories from carbohydrates, protein, or fat for all patients with diabetes, macronutrient distribution should be based on individualized assessment of current eating patterns, preferences, and goals.

• Reduce energy intake/carbohydrate portions and number of servings per meal, as indicated by individual assessment.

• Early referral to registered dietitians and nutritionists for nutrition therapy.

• First-ever call to avoid sugar-sweetened beverages.

• Continued support to limit sodium intake to 2,300 mg/day, as recommended for the general population, with lower sodium targets an option for those with comorbid hypertension.

• Routine supplementation with oxidants, such as vitamin E and C and carotene, is not advised, nor is routine use of micronutrients such as chromium, magnesium, and vitamin D to improve glycemic control.

Dr. Grant disclosed no conflicts of interest.

[email protected]

SAN FRANCISCO – Updated guidelines from the American Diabetes Association open the door to using a two-step approach to gestational diabetes screening.

Screening is still recommended for undiagnosed type 2 diabetes at the first prenatal visit in those with risk factors, and for gestational diabetes mellitus (GDM) between weeks 24 and 28 of gestation.

What’s changed in the 2014 Standards of Medical Care in Diabetes (Diabetes Care 2014;37(suppl 1):S14-80) is how that screening is accomplished, Dr. Richard W. Grant, chair of the ADA professional practice committee, said at the annual advanced postgraduate course held by the American Diabetes Association.

In prior years, the ADA adopted the International Association of Diabetes and Pregnancy Study Groups (IADPSG) 2009 recommendation that a 2-hour, 75-gram oral glucose tolerance test (OGTT) be performed the morning after a fast of at least an 8 hours.

A two-step approach was added this year to reflect the 2013 National Institutes of Health Consensus Guidelines recommendation for a 1-hour, 50-gram glucose tolerance screening test followed by a fasting OGTT on another day, if the test is abnormal.

One-step vs. two-step approach

"The issues for these two approaches are the sensitivity with which you can diagnose GDM and the difficulty in implementing these two approaches," said Dr. Grant, a research scientist with Kaiser Permanente Northern California, Oakland.

The one-step approach tends to be more sensitive and diagnoses a broader range of GDM, but it may be a barrier to screening because it requires the patient to fast for 8 hours, he said. Though the one-step approach allows for a diagnosis of GDM within the context of a single office visit, critics also argue its tight diagnostic glucose cut points could dramatically increase the prevalence of GDM from about 5%-6% to 15%-20%, and bring added health care costs and interventions without clear evidence of improved outcomes.

On the other hand, the two-step approach may be more palatable to women because it avoids the up-front fasting requirement, but it could miss GDM in women with an abnormal screen who fail to return for a second visit.

"The bottom line is we need to make sure we do gestational diabetes screening, whichever method we use," Dr. Grant said. "What’s more important is that all women in early pregnancy get screened."

During a discussion following the presentation, a Canadian attendee said similar recommendations released last fall in Canada allowing two screening methods, albeit with different diagnostic thresholds, have resulted in confusion, particularly among referring obstetricians and endocrinologists.

Dr. Grant said there shouldn’t be confusion surrounding the new option as long as recommendations are consistent within an institution.

"I don’t think it’s actually going to make people change what they’re doing currently," he said in an interview. "There’s not a good reason to jump from one to another if you’ve already chosen an approach."

In a separate interview, Dr. R. Harsha Rao, with the Center for Diabetes and Endocrinology at the University of Pittsburgh, said he can see the rationale for the one-step method, but that the two-step approach is almost implanted in the DNA of American obstetricians and that this behavior pattern will be difficult to change for practical reasons alone.

"Patients don’t like 75 grams of Glucola; it’s an awful-tasting substance," he said. "I’ve had patients tell me they felt like [vomiting] when they got the 75-gram Glucola load, and as it is, ‘I’m pregnant and already feeling nauseated.’ "

In addition, there’s the added stress of waiting for a second appointment and a definitive diagnosis for women who screen positive.

The ADA’s bimodal approach to gestational screening reflects an overarching theme of individualized care for diabetes in the 2014 standards. The guidelines are updated annually and this year they contain 232 recommendations, of which 52% are based on high level A or B evidence.

Individualized diabetes care

"One of the themes that comes out in looking at the data very carefully is that you can’t have a one-size-fits-all approach," Dr. Grant observed.

To that end, the guidelines maintain an earlier recommendation raising the systolic blood pressure target goal for hypertension to 140 mm Hg, but also allow a target goal of less than 130 mm Hg in certain populations, such as younger patients.

Dr. Grant observed that the ADA’s position was confirmed by the U.S. Preventive Services Task Force’s recent endorsement of GDM screening using the two-step approach.

"The USPSTF said that the two-step method is an accurate approach, which is what the ADA also says," he remarked.

Based on the recently revised 2013 ADA nutrition position paper (described in the next section below), the guidelines also encourage individualized dietary approaches rather recommending one particular diet over another, Dr. Grant said.

Other revisions include:

• Clarification that the hemoglobin A_1c test is just one of three methods to diagnose diabetes in asymptomatic patients, along with the fasting plasma glucose or 75-gram, 2-hour OGTT;

• An expanded chapter on neuropathy screening and treatment, including B level evidentiary support to test for distal symmetric polyneuropathy;

• Added emphasis on the need to ask patients about symptomatic and asymptomatic hypoglycemia and perform ongoing assessments of cognitive function; and

• Added emphasis on a patient-centered communication style that assesses literacy, but also the often overlooked issue of numeracy.

"It’s really quite impressive how many patients don’t get numbers, but we as physicians speak in numbers," Dr. Grant said.

The recent controversial 2013 American College of Cardiology/American Heart Association cholesterol guideline could not be reviewed in time to for this year’s guidelines, but it will be something to keep an eye out for next year.

ADA dodges dietary dogma

Highlights of the American Diabetes Association’s nutrition recommendations, updated in late 2013, and also presented at the meeting by Patti Urbanski, M.Ed., a member of the ADA Nutrition Recommendations Writing Group Committee, include:

• Select an "eating pattern" based on an individual’s personal and cultural preferences; literacy and numeracy; readiness; and ability to change, because no one dietary plan – be it the Mediterranean, low-carb, or DASH (Dietary Approaches to Stop Hypertension) diet – is best.

• In the absence of evidence supporting an ideal percentage of calories from carbohydrates, protein, or fat for all patients with diabetes, macronutrient distribution should be based on individualized assessment of current eating patterns, preferences, and goals.

• Reduce energy intake/carbohydrate portions and number of servings per meal, as indicated by individual assessment.

• Early referral to registered dietitians and nutritionists for nutrition therapy.

• First-ever call to avoid sugar-sweetened beverages.

• Continued support to limit sodium intake to 2,300 mg/day, as recommended for the general population, with lower sodium targets an option for those with comorbid hypertension.

• Routine supplementation with oxidants, such as vitamin E and C and carotene, is not advised, nor is routine use of micronutrients such as chromium, magnesium, and vitamin D to improve glycemic control.

Dr. Grant disclosed no conflicts of interest.

[email protected]

SAN FRANCISCO – Updated guidelines from the American Diabetes Association open the door to using a two-step approach to gestational diabetes screening.

Screening is still recommended for undiagnosed type 2 diabetes at the first prenatal visit in those with risk factors, and for gestational diabetes mellitus (GDM) between weeks 24 and 28 of gestation.

What’s changed in the 2014 Standards of Medical Care in Diabetes (Diabetes Care 2014;37(suppl 1):S14-80) is how that screening is accomplished, Dr. Richard W. Grant, chair of the ADA professional practice committee, said at the annual advanced postgraduate course held by the American Diabetes Association.

In prior years, the ADA adopted the International Association of Diabetes and Pregnancy Study Groups (IADPSG) 2009 recommendation that a 2-hour, 75-gram oral glucose tolerance test (OGTT) be performed the morning after a fast of at least an 8 hours.

A two-step approach was added this year to reflect the 2013 National Institutes of Health Consensus Guidelines recommendation for a 1-hour, 50-gram glucose tolerance screening test followed by a fasting OGTT on another day, if the test is abnormal.

One-step vs. two-step approach

"The issues for these two approaches are the sensitivity with which you can diagnose GDM and the difficulty in implementing these two approaches," said Dr. Grant, a research scientist with Kaiser Permanente Northern California, Oakland.

The one-step approach tends to be more sensitive and diagnoses a broader range of GDM, but it may be a barrier to screening because it requires the patient to fast for 8 hours, he said. Though the one-step approach allows for a diagnosis of GDM within the context of a single office visit, critics also argue its tight diagnostic glucose cut points could dramatically increase the prevalence of GDM from about 5%-6% to 15%-20%, and bring added health care costs and interventions without clear evidence of improved outcomes.

On the other hand, the two-step approach may be more palatable to women because it avoids the up-front fasting requirement, but it could miss GDM in women with an abnormal screen who fail to return for a second visit.

"The bottom line is we need to make sure we do gestational diabetes screening, whichever method we use," Dr. Grant said. "What’s more important is that all women in early pregnancy get screened."

During a discussion following the presentation, a Canadian attendee said similar recommendations released last fall in Canada allowing two screening methods, albeit with different diagnostic thresholds, have resulted in confusion, particularly among referring obstetricians and endocrinologists.

Dr. Grant said there shouldn’t be confusion surrounding the new option as long as recommendations are consistent within an institution.

"I don’t think it’s actually going to make people change what they’re doing currently," he said in an interview. "There’s not a good reason to jump from one to another if you’ve already chosen an approach."

In a separate interview, Dr. R. Harsha Rao, with the Center for Diabetes and Endocrinology at the University of Pittsburgh, said he can see the rationale for the one-step method, but that the two-step approach is almost implanted in the DNA of American obstetricians and that this behavior pattern will be difficult to change for practical reasons alone.

"Patients don’t like 75 grams of Glucola; it’s an awful-tasting substance," he said. "I’ve had patients tell me they felt like [vomiting] when they got the 75-gram Glucola load, and as it is, ‘I’m pregnant and already feeling nauseated.’ "

In addition, there’s the added stress of waiting for a second appointment and a definitive diagnosis for women who screen positive.

The ADA’s bimodal approach to gestational screening reflects an overarching theme of individualized care for diabetes in the 2014 standards. The guidelines are updated annually and this year they contain 232 recommendations, of which 52% are based on high level A or B evidence.

Individualized diabetes care

"One of the themes that comes out in looking at the data very carefully is that you can’t have a one-size-fits-all approach," Dr. Grant observed.

To that end, the guidelines maintain an earlier recommendation raising the systolic blood pressure target goal for hypertension to 140 mm Hg, but also allow a target goal of less than 130 mm Hg in certain populations, such as younger patients.

Dr. Grant observed that the ADA’s position was confirmed by the U.S. Preventive Services Task Force’s recent endorsement of GDM screening using the two-step approach.

"The USPSTF said that the two-step method is an accurate approach, which is what the ADA also says," he remarked.

Based on the recently revised 2013 ADA nutrition position paper (described in the next section below), the guidelines also encourage individualized dietary approaches rather recommending one particular diet over another, Dr. Grant said.

Other revisions include:

• Clarification that the hemoglobin A_1c test is just one of three methods to diagnose diabetes in asymptomatic patients, along with the fasting plasma glucose or 75-gram, 2-hour OGTT;

• An expanded chapter on neuropathy screening and treatment, including B level evidentiary support to test for distal symmetric polyneuropathy;

• Added emphasis on the need to ask patients about symptomatic and asymptomatic hypoglycemia and perform ongoing assessments of cognitive function; and

• Added emphasis on a patient-centered communication style that assesses literacy, but also the often overlooked issue of numeracy.

"It’s really quite impressive how many patients don’t get numbers, but we as physicians speak in numbers," Dr. Grant said.

The recent controversial 2013 American College of Cardiology/American Heart Association cholesterol guideline could not be reviewed in time to for this year’s guidelines, but it will be something to keep an eye out for next year.

ADA dodges dietary dogma

Highlights of the American Diabetes Association’s nutrition recommendations, updated in late 2013, and also presented at the meeting by Patti Urbanski, M.Ed., a member of the ADA Nutrition Recommendations Writing Group Committee, include:

• Select an "eating pattern" based on an individual’s personal and cultural preferences; literacy and numeracy; readiness; and ability to change, because no one dietary plan – be it the Mediterranean, low-carb, or DASH (Dietary Approaches to Stop Hypertension) diet – is best.

• In the absence of evidence supporting an ideal percentage of calories from carbohydrates, protein, or fat for all patients with diabetes, macronutrient distribution should be based on individualized assessment of current eating patterns, preferences, and goals.

• Reduce energy intake/carbohydrate portions and number of servings per meal, as indicated by individual assessment.

• Early referral to registered dietitians and nutritionists for nutrition therapy.

• First-ever call to avoid sugar-sweetened beverages.

• Continued support to limit sodium intake to 2,300 mg/day, as recommended for the general population, with lower sodium targets an option for those with comorbid hypertension.

• Routine supplementation with oxidants, such as vitamin E and C and carotene, is not advised, nor is routine use of micronutrients such as chromium, magnesium, and vitamin D to improve glycemic control.

Dr. Grant disclosed no conflicts of interest.

[email protected]

Pregnant woman

Credit: Nina Matthews

SAN DIEGO—A woman’s risk of thrombosis remains significantly elevated for 12 weeks after delivering a baby, according to research presented at the International Stroke Conference 2014.

The study suggested that pregnant and postpartum women have a low absolute risk of experiencing thrombotic events.

However, their risk is nearly 11 times higher than normal for the first 6 weeks after delivery. And they have roughly twice the normal risk of thrombosis in the following 6 weeks.

Hooman Kamel, MD, of Weill Cornell Medical College in New York, presented these findings at the meeting as abstract 216.*

Dr Kamel and his colleagues had analyzed data on 1,687,930 women who were admitted for labor and delivery at California hospitals from 2005 through 2010.

The researchers compared the risk of thrombosis during sequential 6-week periods after delivery to the same 6-week period 1 year later (0-6 weeks, 7-12 weeks, 13-18 weeks, and 19-24 weeks).

In all, 1015 women had a thrombotic event after delivery, including 720 cases of venous thromboembolism, 248 strokes, and 47 cases of myocardial infarction.

In the first 6 weeks after delivery, a woman’s risk of thrombosis was 10.8 times higher than normal. There were 24.4 thrombotic events per 100,000 deliveries in the first 6 weeks after delivery, compared to 2.3 events during the same period 1 year later.

From week 7 to 12 after delivery, the risk of thrombosis was 2.2 times higher than normal. There were 5.6 thrombotic events per 100,000 deliveries in the 7 to 12 weeks after delivery, compared to 2.6 events during the same period 1 year later.

The risk of thrombosis was 1.4 times higher than normal from 13 to 18 weeks after delivery, although this was not a significant increase. And by weeks 19 through 24, the risk of thrombosis had returned to normal.

“While rare, blood clots are a serious cause of disability and death in pregnant and postpartum women . . . ,” Dr Kamel said. “Clinicians should consider our results when caring for high-risk postpartum patients, such as those with previous clots, or postpartum patients with symptoms concerning for thrombosis.”

*Information in the abstract differs from that presented at the meeting.

Pregnant woman

Credit: Nina Matthews

SAN DIEGO—A woman’s risk of thrombosis remains significantly elevated for 12 weeks after delivering a baby, according to research presented at the International Stroke Conference 2014.

The study suggested that pregnant and postpartum women have a low absolute risk of experiencing thrombotic events.

However, their risk is nearly 11 times higher than normal for the first 6 weeks after delivery. And they have roughly twice the normal risk of thrombosis in the following 6 weeks.

Hooman Kamel, MD, of Weill Cornell Medical College in New York, presented these findings at the meeting as abstract 216.*

Dr Kamel and his colleagues had analyzed data on 1,687,930 women who were admitted for labor and delivery at California hospitals from 2005 through 2010.

The researchers compared the risk of thrombosis during sequential 6-week periods after delivery to the same 6-week period 1 year later (0-6 weeks, 7-12 weeks, 13-18 weeks, and 19-24 weeks).

In all, 1015 women had a thrombotic event after delivery, including 720 cases of venous thromboembolism, 248 strokes, and 47 cases of myocardial infarction.

In the first 6 weeks after delivery, a woman’s risk of thrombosis was 10.8 times higher than normal. There were 24.4 thrombotic events per 100,000 deliveries in the first 6 weeks after delivery, compared to 2.3 events during the same period 1 year later.

From week 7 to 12 after delivery, the risk of thrombosis was 2.2 times higher than normal. There were 5.6 thrombotic events per 100,000 deliveries in the 7 to 12 weeks after delivery, compared to 2.6 events during the same period 1 year later.

The risk of thrombosis was 1.4 times higher than normal from 13 to 18 weeks after delivery, although this was not a significant increase. And by weeks 19 through 24, the risk of thrombosis had returned to normal.

“While rare, blood clots are a serious cause of disability and death in pregnant and postpartum women . . . ,” Dr Kamel said. “Clinicians should consider our results when caring for high-risk postpartum patients, such as those with previous clots, or postpartum patients with symptoms concerning for thrombosis.”

*Information in the abstract differs from that presented at the meeting.

Pregnant woman

Credit: Nina Matthews

SAN DIEGO—A woman’s risk of thrombosis remains significantly elevated for 12 weeks after delivering a baby, according to research presented at the International Stroke Conference 2014.

The study suggested that pregnant and postpartum women have a low absolute risk of experiencing thrombotic events.

However, their risk is nearly 11 times higher than normal for the first 6 weeks after delivery. And they have roughly twice the normal risk of thrombosis in the following 6 weeks.

Hooman Kamel, MD, of Weill Cornell Medical College in New York, presented these findings at the meeting as abstract 216.*

Dr Kamel and his colleagues had analyzed data on 1,687,930 women who were admitted for labor and delivery at California hospitals from 2005 through 2010.

The researchers compared the risk of thrombosis during sequential 6-week periods after delivery to the same 6-week period 1 year later (0-6 weeks, 7-12 weeks, 13-18 weeks, and 19-24 weeks).

In all, 1015 women had a thrombotic event after delivery, including 720 cases of venous thromboembolism, 248 strokes, and 47 cases of myocardial infarction.

In the first 6 weeks after delivery, a woman’s risk of thrombosis was 10.8 times higher than normal. There were 24.4 thrombotic events per 100,000 deliveries in the first 6 weeks after delivery, compared to 2.3 events during the same period 1 year later.

From week 7 to 12 after delivery, the risk of thrombosis was 2.2 times higher than normal. There were 5.6 thrombotic events per 100,000 deliveries in the 7 to 12 weeks after delivery, compared to 2.6 events during the same period 1 year later.

The risk of thrombosis was 1.4 times higher than normal from 13 to 18 weeks after delivery, although this was not a significant increase. And by weeks 19 through 24, the risk of thrombosis had returned to normal.

“While rare, blood clots are a serious cause of disability and death in pregnant and postpartum women . . . ,” Dr Kamel said. “Clinicians should consider our results when caring for high-risk postpartum patients, such as those with previous clots, or postpartum patients with symptoms concerning for thrombosis.”

*Information in the abstract differs from that presented at the meeting.

Drug release in a cancer cell

Credit: PNAS

New findings suggest drugs can effectively fight K-Ras-mutant cancers—if they have a little help.

Experiments in human cancer cells showed that K-Ras-mutant tumor growth was highly dependent on the cells’ constant need to check and mend their DNA.

However, inhibiting the activity of H-Ras and N-Ras prevented the DNA damage response. And this made the cells more vulnerable to treatment.

“Our finding suggests that K-Ras cancers can be made more susceptible to existing therapies by interfering with their DNA repair mechanisms,” said Dafna Bar-Sagi, PhD, of the New York University School of Medicine.

“What some researchers have described as therapeutic ‘mission impossible’ may now become a ‘mission doable.’”

Dr Bar-Sagi and her colleagues reported this discovery in Cancer Cell.

The group’s research began with experiments to determine how Ras signaling leads to the uncontrolled growth of cancer cells. The team found that downregulation of wild-type H-Ras and N-Ras in mutant K-Ras cells caused the buildup of damaged DNA and slowed cell growth.

In the absence of H-Ras and N-Ras, K-Ras-mutant cancer cells failed to repair their DNA at the G2 phase of cell division. And this defect was caused by failure to properly activate Chk1.

With this in mind, the researchers decided to test the effects of H-Ras or N-Ras knockdown on treatment with DNA-damaging agents.

Knockdown of H-Ras or N-Ras sensitized K-Ras-mutant cancer cells to SN38 and oxaliplatin in vitro. But the same effect did not occur when H-Ras or N-Ras was knocked down in K-Ras-wild-type cancer cells.

K-Ras-mutant cancer cells were also sensitive to treatment with the Chk1/Chk2 inhibitor AZD7726 when H-Ras or N-Ras was knocked down in vitro.

To further support these findings, the researchers conducted experiments in mice with K-Ras-mutant tumors. Mice with H-Ras knockdown experienced tumor growth similar to controls.

But when the mice with H-Ras-suppressed tumors received the chemotherapy drug irinotecan, they experienced tumor regression that lasted up to 18 days post-treatment. On the other hand, mice without H-Ras suppression experienced modest tumor growth after treatment with irinotecan.

“Discovering more about how these different forms of Ras act on one another—including how they control DNA damage repair at Chk1 in combination with chemotherapy—could help us design drugs that greatly stall disease progression,” said study author Elda Grabocka, PhD, also of the New York University School of Medicine.

The researchers are now planning additional experiments on the biological interdependency of Ras proteins and what other chemotherapies might be involved in slowing cancer growth. Their goal is to map the Ras signaling pathways and identify as many therapeutic targets as possible.

Drug release in a cancer cell

Credit: PNAS

New findings suggest drugs can effectively fight K-Ras-mutant cancers—if they have a little help.

Experiments in human cancer cells showed that K-Ras-mutant tumor growth was highly dependent on the cells’ constant need to check and mend their DNA.

However, inhibiting the activity of H-Ras and N-Ras prevented the DNA damage response. And this made the cells more vulnerable to treatment.

“Our finding suggests that K-Ras cancers can be made more susceptible to existing therapies by interfering with their DNA repair mechanisms,” said Dafna Bar-Sagi, PhD, of the New York University School of Medicine.

“What some researchers have described as therapeutic ‘mission impossible’ may now become a ‘mission doable.’”

Dr Bar-Sagi and her colleagues reported this discovery in Cancer Cell.

The group’s research began with experiments to determine how Ras signaling leads to the uncontrolled growth of cancer cells. The team found that downregulation of wild-type H-Ras and N-Ras in mutant K-Ras cells caused the buildup of damaged DNA and slowed cell growth.

In the absence of H-Ras and N-Ras, K-Ras-mutant cancer cells failed to repair their DNA at the G2 phase of cell division. And this defect was caused by failure to properly activate Chk1.

With this in mind, the researchers decided to test the effects of H-Ras or N-Ras knockdown on treatment with DNA-damaging agents.

Knockdown of H-Ras or N-Ras sensitized K-Ras-mutant cancer cells to SN38 and oxaliplatin in vitro. But the same effect did not occur when H-Ras or N-Ras was knocked down in K-Ras-wild-type cancer cells.

K-Ras-mutant cancer cells were also sensitive to treatment with the Chk1/Chk2 inhibitor AZD7726 when H-Ras or N-Ras was knocked down in vitro.

To further support these findings, the researchers conducted experiments in mice with K-Ras-mutant tumors. Mice with H-Ras knockdown experienced tumor growth similar to controls.

But when the mice with H-Ras-suppressed tumors received the chemotherapy drug irinotecan, they experienced tumor regression that lasted up to 18 days post-treatment. On the other hand, mice without H-Ras suppression experienced modest tumor growth after treatment with irinotecan.

“Discovering more about how these different forms of Ras act on one another—including how they control DNA damage repair at Chk1 in combination with chemotherapy—could help us design drugs that greatly stall disease progression,” said study author Elda Grabocka, PhD, also of the New York University School of Medicine.

The researchers are now planning additional experiments on the biological interdependency of Ras proteins and what other chemotherapies might be involved in slowing cancer growth. Their goal is to map the Ras signaling pathways and identify as many therapeutic targets as possible.

Drug release in a cancer cell

Credit: PNAS

New findings suggest drugs can effectively fight K-Ras-mutant cancers—if they have a little help.

Experiments in human cancer cells showed that K-Ras-mutant tumor growth was highly dependent on the cells’ constant need to check and mend their DNA.

However, inhibiting the activity of H-Ras and N-Ras prevented the DNA damage response. And this made the cells more vulnerable to treatment.

“Our finding suggests that K-Ras cancers can be made more susceptible to existing therapies by interfering with their DNA repair mechanisms,” said Dafna Bar-Sagi, PhD, of the New York University School of Medicine.

“What some researchers have described as therapeutic ‘mission impossible’ may now become a ‘mission doable.’”

Dr Bar-Sagi and her colleagues reported this discovery in Cancer Cell.

The group’s research began with experiments to determine how Ras signaling leads to the uncontrolled growth of cancer cells. The team found that downregulation of wild-type H-Ras and N-Ras in mutant K-Ras cells caused the buildup of damaged DNA and slowed cell growth.

In the absence of H-Ras and N-Ras, K-Ras-mutant cancer cells failed to repair their DNA at the G2 phase of cell division. And this defect was caused by failure to properly activate Chk1.

With this in mind, the researchers decided to test the effects of H-Ras or N-Ras knockdown on treatment with DNA-damaging agents.

Knockdown of H-Ras or N-Ras sensitized K-Ras-mutant cancer cells to SN38 and oxaliplatin in vitro. But the same effect did not occur when H-Ras or N-Ras was knocked down in K-Ras-wild-type cancer cells.

K-Ras-mutant cancer cells were also sensitive to treatment with the Chk1/Chk2 inhibitor AZD7726 when H-Ras or N-Ras was knocked down in vitro.

To further support these findings, the researchers conducted experiments in mice with K-Ras-mutant tumors. Mice with H-Ras knockdown experienced tumor growth similar to controls.

But when the mice with H-Ras-suppressed tumors received the chemotherapy drug irinotecan, they experienced tumor regression that lasted up to 18 days post-treatment. On the other hand, mice without H-Ras suppression experienced modest tumor growth after treatment with irinotecan.

“Discovering more about how these different forms of Ras act on one another—including how they control DNA damage repair at Chk1 in combination with chemotherapy—could help us design drugs that greatly stall disease progression,” said study author Elda Grabocka, PhD, also of the New York University School of Medicine.

The researchers are now planning additional experiments on the biological interdependency of Ras proteins and what other chemotherapies might be involved in slowing cancer growth. Their goal is to map the Ras signaling pathways and identify as many therapeutic targets as possible.

Cancer patient receives therapy

Credit: Rhoda Baer

The first reported outbreak of Tsukamurella species bloodstream infections was due to improper handling of intravenous saline, according to a report published in Infection Control and Hospital Epidemiology.

From September 2011 to May 2012, 15 immunocompromised patients treated at an outpatient oncology clinic in West Virginia developed infections with Tsukamurella, which are gram-positive bacteria that rarely cause disease in humans.

All patients had received a cancer diagnosis and had an indwelling central line, although central line types varied.

A case-control study revealed that the only risk factor for developing Tsukamurella infection was the receipt of a saline flush in September or October 2011, when clinic staff were using a common-source bag of saline.

Investigations by the West Virginia Bureau of Public Health (WVBPH) and the Centers for Disease Control and Prevention (CDC) uncovered several lapses in infection control procedures relating to the care of long-term intravenous catheters and preparation of chemotherapy for patients at the clinic.

However, these investigations also suggested that saline flush syringes were the likely source of infection.

So the WVBPH and the CDC recommended the clinic institute several changes to its infection prevention and control practices, including using pre-packaged, manufactured saline flushes.

After the clinic changed this practice, Tsukamurella bloodstream infections stopped occurring, further supporting the saline flush as the source of infection.

“This outbreak illustrates the need for outpatient clinics to follow proper infection control guidelines and medication preparation practices to minimize the risk of infection for patients with weakened immune systems,” said lead study author Isaac See, MD, of the CDC.

To that end, the CDC has developed a basic infection control plan tailored to outpatient oncology facilities.

The plan outlines policies and procedures needed to meet minimal requirements for patient safety, including the proper use and handling of injectable medications and correct procedures for assessing central lines.

Cancer patient receives therapy

Credit: Rhoda Baer

The first reported outbreak of Tsukamurella species bloodstream infections was due to improper handling of intravenous saline, according to a report published in Infection Control and Hospital Epidemiology.

From September 2011 to May 2012, 15 immunocompromised patients treated at an outpatient oncology clinic in West Virginia developed infections with Tsukamurella, which are gram-positive bacteria that rarely cause disease in humans.

All patients had received a cancer diagnosis and had an indwelling central line, although central line types varied.

A case-control study revealed that the only risk factor for developing Tsukamurella infection was the receipt of a saline flush in September or October 2011, when clinic staff were using a common-source bag of saline.

Investigations by the West Virginia Bureau of Public Health (WVBPH) and the Centers for Disease Control and Prevention (CDC) uncovered several lapses in infection control procedures relating to the care of long-term intravenous catheters and preparation of chemotherapy for patients at the clinic.

However, these investigations also suggested that saline flush syringes were the likely source of infection.

So the WVBPH and the CDC recommended the clinic institute several changes to its infection prevention and control practices, including using pre-packaged, manufactured saline flushes.

After the clinic changed this practice, Tsukamurella bloodstream infections stopped occurring, further supporting the saline flush as the source of infection.

“This outbreak illustrates the need for outpatient clinics to follow proper infection control guidelines and medication preparation practices to minimize the risk of infection for patients with weakened immune systems,” said lead study author Isaac See, MD, of the CDC.

To that end, the CDC has developed a basic infection control plan tailored to outpatient oncology facilities.

The plan outlines policies and procedures needed to meet minimal requirements for patient safety, including the proper use and handling of injectable medications and correct procedures for assessing central lines.

Cancer patient receives therapy

Credit: Rhoda Baer

The first reported outbreak of Tsukamurella species bloodstream infections was due to improper handling of intravenous saline, according to a report published in Infection Control and Hospital Epidemiology.

From September 2011 to May 2012, 15 immunocompromised patients treated at an outpatient oncology clinic in West Virginia developed infections with Tsukamurella, which are gram-positive bacteria that rarely cause disease in humans.

All patients had received a cancer diagnosis and had an indwelling central line, although central line types varied.

A case-control study revealed that the only risk factor for developing Tsukamurella infection was the receipt of a saline flush in September or October 2011, when clinic staff were using a common-source bag of saline.

Investigations by the West Virginia Bureau of Public Health (WVBPH) and the Centers for Disease Control and Prevention (CDC) uncovered several lapses in infection control procedures relating to the care of long-term intravenous catheters and preparation of chemotherapy for patients at the clinic.

However, these investigations also suggested that saline flush syringes were the likely source of infection.

So the WVBPH and the CDC recommended the clinic institute several changes to its infection prevention and control practices, including using pre-packaged, manufactured saline flushes.

After the clinic changed this practice, Tsukamurella bloodstream infections stopped occurring, further supporting the saline flush as the source of infection.

“This outbreak illustrates the need for outpatient clinics to follow proper infection control guidelines and medication preparation practices to minimize the risk of infection for patients with weakened immune systems,” said lead study author Isaac See, MD, of the CDC.

To that end, the CDC has developed a basic infection control plan tailored to outpatient oncology facilities.

The plan outlines policies and procedures needed to meet minimal requirements for patient safety, including the proper use and handling of injectable medications and correct procedures for assessing central lines.