Related Issues

Mother and child

Photo by Vera Kratochvil

A new study indicates that many young adult female cancer survivors do not receive adequate information about their fertility as part of their survivorship care, despite having concerns about their ability to bear children in the future.

The research, published in Cancer, suggests a need for better resources to support cancer survivors in making informed decisions about their reproductive options after they complete treatment.

To conduct this study, Catherine Benedict, PhD, of North Shore-Long Island Jewish Medical Center in Manhasset, New York, and her colleagues asked female cancer survivors to complete a web-based, anonymous survey.

There were 346 participants. They had an average age of 29.9 and had completed treatment an average of 4.9 years earlier.

The investigators focused on a subgroup of 179 women with uncertain fertility status who had not previously undergone or attempted fertility preservation, either before or after their cancer treatment, and who either wanted future children or were unsure.

Many of these women said they did not have enough information concerning their risk of infertility (58%), risk of early menopause (60%), options to assess their fertility (62%), options to preserve their fertility (51%), or options for alternative family building (43%).

The women’s greatest reproductive concerns were potential fertility problems and the health of a future child. Sixty-four percent of the women said they were concerned about not being able to have children (or more children), and 59% were worried about passing the risk of cancer on to their future children.

Only 13% of women said they were well informed about options for preserving fertility, and 74% were unclear about their personal values regarding fertility preservation.

Seventy percent of the women said they hadn’t received enough advice on fertility preservation, and 35% said they didn’t have enough support to make a decision about fertility preservation.

The investigators found a significant association between greater unmet information needs and higher levels of decisional conflict about fertility preservation (P<0.001).

On the other hand, having undergone a fertility evaluation after treatment was associated with lower decisional conflict (P=0.02).

The investigators said these findings establish the need for support services to help young female cancer survivors make decisions about fertility preservation and family-building as part of survivorship care.

The literature has largely focused on the clinical and support needs of women making fertility decisions before their treatment begins, but most patients do not preserve their fertility before treatment for a number of reasons, despite wanting children in the future.

“The potential loss of fertility has been described in the literature as being almost as painful, if not more so, than the cancer diagnosis itself,” Dr Benedict said.

“Failure to provide information and address concerns with respect to fertility-related decisions may have lasting consequences for young women who hope to move on from their cancer experience to achieve important life goals such as having children. For women at risk for early menopause, delaying fertility-related decisions may cause them to miss their narrowed window of opportunity to preserve their fertility, if desired.”

Mother and child

Photo by Vera Kratochvil

A new study indicates that many young adult female cancer survivors do not receive adequate information about their fertility as part of their survivorship care, despite having concerns about their ability to bear children in the future.

The research, published in Cancer, suggests a need for better resources to support cancer survivors in making informed decisions about their reproductive options after they complete treatment.

To conduct this study, Catherine Benedict, PhD, of North Shore-Long Island Jewish Medical Center in Manhasset, New York, and her colleagues asked female cancer survivors to complete a web-based, anonymous survey.

There were 346 participants. They had an average age of 29.9 and had completed treatment an average of 4.9 years earlier.

The investigators focused on a subgroup of 179 women with uncertain fertility status who had not previously undergone or attempted fertility preservation, either before or after their cancer treatment, and who either wanted future children or were unsure.

Many of these women said they did not have enough information concerning their risk of infertility (58%), risk of early menopause (60%), options to assess their fertility (62%), options to preserve their fertility (51%), or options for alternative family building (43%).

The women’s greatest reproductive concerns were potential fertility problems and the health of a future child. Sixty-four percent of the women said they were concerned about not being able to have children (or more children), and 59% were worried about passing the risk of cancer on to their future children.

Only 13% of women said they were well informed about options for preserving fertility, and 74% were unclear about their personal values regarding fertility preservation.

Seventy percent of the women said they hadn’t received enough advice on fertility preservation, and 35% said they didn’t have enough support to make a decision about fertility preservation.

The investigators found a significant association between greater unmet information needs and higher levels of decisional conflict about fertility preservation (P<0.001).

On the other hand, having undergone a fertility evaluation after treatment was associated with lower decisional conflict (P=0.02).

The investigators said these findings establish the need for support services to help young female cancer survivors make decisions about fertility preservation and family-building as part of survivorship care.

The literature has largely focused on the clinical and support needs of women making fertility decisions before their treatment begins, but most patients do not preserve their fertility before treatment for a number of reasons, despite wanting children in the future.

“The potential loss of fertility has been described in the literature as being almost as painful, if not more so, than the cancer diagnosis itself,” Dr Benedict said.

“Failure to provide information and address concerns with respect to fertility-related decisions may have lasting consequences for young women who hope to move on from their cancer experience to achieve important life goals such as having children. For women at risk for early menopause, delaying fertility-related decisions may cause them to miss their narrowed window of opportunity to preserve their fertility, if desired.”

Mother and child

Photo by Vera Kratochvil

A new study indicates that many young adult female cancer survivors do not receive adequate information about their fertility as part of their survivorship care, despite having concerns about their ability to bear children in the future.

The research, published in Cancer, suggests a need for better resources to support cancer survivors in making informed decisions about their reproductive options after they complete treatment.

To conduct this study, Catherine Benedict, PhD, of North Shore-Long Island Jewish Medical Center in Manhasset, New York, and her colleagues asked female cancer survivors to complete a web-based, anonymous survey.

There were 346 participants. They had an average age of 29.9 and had completed treatment an average of 4.9 years earlier.

The investigators focused on a subgroup of 179 women with uncertain fertility status who had not previously undergone or attempted fertility preservation, either before or after their cancer treatment, and who either wanted future children or were unsure.

Many of these women said they did not have enough information concerning their risk of infertility (58%), risk of early menopause (60%), options to assess their fertility (62%), options to preserve their fertility (51%), or options for alternative family building (43%).

The women’s greatest reproductive concerns were potential fertility problems and the health of a future child. Sixty-four percent of the women said they were concerned about not being able to have children (or more children), and 59% were worried about passing the risk of cancer on to their future children.

Only 13% of women said they were well informed about options for preserving fertility, and 74% were unclear about their personal values regarding fertility preservation.

Seventy percent of the women said they hadn’t received enough advice on fertility preservation, and 35% said they didn’t have enough support to make a decision about fertility preservation.

The investigators found a significant association between greater unmet information needs and higher levels of decisional conflict about fertility preservation (P<0.001).

On the other hand, having undergone a fertility evaluation after treatment was associated with lower decisional conflict (P=0.02).

The investigators said these findings establish the need for support services to help young female cancer survivors make decisions about fertility preservation and family-building as part of survivorship care.

The literature has largely focused on the clinical and support needs of women making fertility decisions before their treatment begins, but most patients do not preserve their fertility before treatment for a number of reasons, despite wanting children in the future.

“The potential loss of fertility has been described in the literature as being almost as painful, if not more so, than the cancer diagnosis itself,” Dr Benedict said.

“Failure to provide information and address concerns with respect to fertility-related decisions may have lasting consequences for young women who hope to move on from their cancer experience to achieve important life goals such as having children. For women at risk for early menopause, delaying fertility-related decisions may cause them to miss their narrowed window of opportunity to preserve their fertility, if desired.”

Injectable drugs

Photo by Bill Branson

A new drug-making technique could reduce the risk of hemolysis, thrombosis, and other serious side effects that can occur with injectable drugs, according to researchers.

The team used the technique to remove potentially harmful additives—surfactants—from 12 common injectable drugs.

Jonathan F. Lovell, PhD, of University at Buffalo in New York, and his colleagues described the technique in Nature Communications.

Pharmaceutical companies use surfactants to dissolve a medicine into a liquid solution, making it suitable for injection. Unfortunately, solutions loaded with surfactants and other nonessential ingredients may increase the risk of thrombosis, hemolysis, anaphylactic shock, and other side effects.

Researchers have tried to address this problem in two ways, each with varying degrees of success.

Some have taken the “top-down” approach, in which they shrink drug particles to nanoscale sizes to eliminate excess additives. While promising, the method doesn’t work well with injectable medicine because the drug particles are still too large to safely inject.

Other researchers have worked from the “bottom up,” using nanotechnology to build new drugs from scratch. This can yield the desired results, but developing new drug formulations takes years, and drugs are coupled with new additives that can produce new side effects.

The technique described in Nature Communications differs from both of these approaches.

Dr Lovell and his colleagues dissolved 12 drugs—vitamin K1, cyclosporine, cabazitaxel, and others—one at a time into a surfactant called Pluronic. Then, by lowering the solution’s temperature to 4° C, they were able to remove the excess Pluronic via a membrane.

The end result was drugs that contain 100 to 1000 times less excess additives.

“For the drugs we looked at, this is as close as anyone has gotten to introducing pure, injectable medicine into the body,” Dr Lovell said. “Essentially, it’s a new way to package drugs.”

The findings are significant, he said, because they show that many injectable drug formulations may be improved through an easy-to-adopt process. He and his colleagues are now working to refine the method further.

Injectable drugs

Photo by Bill Branson

A new drug-making technique could reduce the risk of hemolysis, thrombosis, and other serious side effects that can occur with injectable drugs, according to researchers.

The team used the technique to remove potentially harmful additives—surfactants—from 12 common injectable drugs.

Jonathan F. Lovell, PhD, of University at Buffalo in New York, and his colleagues described the technique in Nature Communications.

Pharmaceutical companies use surfactants to dissolve a medicine into a liquid solution, making it suitable for injection. Unfortunately, solutions loaded with surfactants and other nonessential ingredients may increase the risk of thrombosis, hemolysis, anaphylactic shock, and other side effects.

Researchers have tried to address this problem in two ways, each with varying degrees of success.

Some have taken the “top-down” approach, in which they shrink drug particles to nanoscale sizes to eliminate excess additives. While promising, the method doesn’t work well with injectable medicine because the drug particles are still too large to safely inject.

Other researchers have worked from the “bottom up,” using nanotechnology to build new drugs from scratch. This can yield the desired results, but developing new drug formulations takes years, and drugs are coupled with new additives that can produce new side effects.

The technique described in Nature Communications differs from both of these approaches.

Dr Lovell and his colleagues dissolved 12 drugs—vitamin K1, cyclosporine, cabazitaxel, and others—one at a time into a surfactant called Pluronic. Then, by lowering the solution’s temperature to 4° C, they were able to remove the excess Pluronic via a membrane.

The end result was drugs that contain 100 to 1000 times less excess additives.

“For the drugs we looked at, this is as close as anyone has gotten to introducing pure, injectable medicine into the body,” Dr Lovell said. “Essentially, it’s a new way to package drugs.”

The findings are significant, he said, because they show that many injectable drug formulations may be improved through an easy-to-adopt process. He and his colleagues are now working to refine the method further.

Injectable drugs

Photo by Bill Branson

A new drug-making technique could reduce the risk of hemolysis, thrombosis, and other serious side effects that can occur with injectable drugs, according to researchers.

The team used the technique to remove potentially harmful additives—surfactants—from 12 common injectable drugs.

Jonathan F. Lovell, PhD, of University at Buffalo in New York, and his colleagues described the technique in Nature Communications.

Pharmaceutical companies use surfactants to dissolve a medicine into a liquid solution, making it suitable for injection. Unfortunately, solutions loaded with surfactants and other nonessential ingredients may increase the risk of thrombosis, hemolysis, anaphylactic shock, and other side effects.

Researchers have tried to address this problem in two ways, each with varying degrees of success.

Some have taken the “top-down” approach, in which they shrink drug particles to nanoscale sizes to eliminate excess additives. While promising, the method doesn’t work well with injectable medicine because the drug particles are still too large to safely inject.

Other researchers have worked from the “bottom up,” using nanotechnology to build new drugs from scratch. This can yield the desired results, but developing new drug formulations takes years, and drugs are coupled with new additives that can produce new side effects.

The technique described in Nature Communications differs from both of these approaches.

Dr Lovell and his colleagues dissolved 12 drugs—vitamin K1, cyclosporine, cabazitaxel, and others—one at a time into a surfactant called Pluronic. Then, by lowering the solution’s temperature to 4° C, they were able to remove the excess Pluronic via a membrane.

The end result was drugs that contain 100 to 1000 times less excess additives.

“For the drugs we looked at, this is as close as anyone has gotten to introducing pure, injectable medicine into the body,” Dr Lovell said. “Essentially, it’s a new way to package drugs.”

The findings are significant, he said, because they show that many injectable drug formulations may be improved through an easy-to-adopt process. He and his colleagues are now working to refine the method further.

Lab mouse

Researchers say they have discovered a mutation in a subline of C57BL/6 mice that could compromise results from previous studies.

“We found an unexpected mutation with potentially important consequences in strains of mice that had been separately engineered in labs in California and Japan,” said Shiv Pillai, MD, PhD, of The Ragon Institute of MGH, MIT and Harvard in Cambridge, Massachusetts.

“[W]e traced the problem to a subline of B6 mice from one specific company that have been sold in Asia, North America, Europe, and Israel. We have notified this company—Harlan Laboratories, which is now part of Envigo—of our findings, and they have been very responsive and will use approaches we have provided to check all of their colonies.”

Dr Pillai and his colleagues described their discovery of the mutation in Cell Reports.

The team noted that, in immunological studies, mutant mice are backcrossed for many generations into B6 mice so that all genes other than the mutant gene are derived from the B6 strain. This allows the comparison of data from laboratories in different parts of the world and simplifies creating mice with mutations in several genes.

A 2009 study out of Dr Pillai’s lab showed that 2 strains of mice engineered to lack the Siae or Cmah genes—both of which code for enzymes involved with sialic acid proteins—also had significant defects in the development of B cells, which were assumed to be the result of the knockout genes.

However, when Siae-deficient mice were further backcrossed with a different group of C57BL/6 mice, the result was a strain of Siae-knockout mice that did not have the B-cell development defects. A newly engineered strain of mice with a different Siae mutation also had normal B-cell development.

Detailed genetic sequencing of the first knockout line revealed a previously unsuspected mutation in a gene called Dock2, located on a chromosome 11, instead of chromosome 9 where Siae is located.

The same mutation was previously reported in 2 colonies of a different knockout mouse developed in Japan.

Dr Pillai’s team also found the Dock2 mutation in a completely different group of mice from the University of California, San Diego—where their Siae-mutant strain had been developed—and realized that 3 different engineered strains with the same unwanted mutation had probably acquired it from a common source. The team eventually traced it back to a subline of C57BL/6 mice from Harlan/Envigo.

Since most research papers using C57BL/6 mice or other such “background” strains do not indicate the specific subline, the researchers said they have no way of knowing how many studies might be affected by their findings.

But they hope the publication of these results will alert other research teams to the potential need to review their results.

“While embryonic stem cells from C57BL/6 mice have recently become available, which allows the generation of knockout strains with less backcrossing, B6 mice are used for many different kinds of experiments, including as controls,” Dr Pillai said.

“Researchers who have used them need to re-genotype the mice to look for the Dock2 mutation and, if they find it, check to see whether their results are preserved if the Dock2 mutation is bred out.”

Lab mouse

Researchers say they have discovered a mutation in a subline of C57BL/6 mice that could compromise results from previous studies.

“We found an unexpected mutation with potentially important consequences in strains of mice that had been separately engineered in labs in California and Japan,” said Shiv Pillai, MD, PhD, of The Ragon Institute of MGH, MIT and Harvard in Cambridge, Massachusetts.

“[W]e traced the problem to a subline of B6 mice from one specific company that have been sold in Asia, North America, Europe, and Israel. We have notified this company—Harlan Laboratories, which is now part of Envigo—of our findings, and they have been very responsive and will use approaches we have provided to check all of their colonies.”

Dr Pillai and his colleagues described their discovery of the mutation in Cell Reports.

The team noted that, in immunological studies, mutant mice are backcrossed for many generations into B6 mice so that all genes other than the mutant gene are derived from the B6 strain. This allows the comparison of data from laboratories in different parts of the world and simplifies creating mice with mutations in several genes.

A 2009 study out of Dr Pillai’s lab showed that 2 strains of mice engineered to lack the Siae or Cmah genes—both of which code for enzymes involved with sialic acid proteins—also had significant defects in the development of B cells, which were assumed to be the result of the knockout genes.

However, when Siae-deficient mice were further backcrossed with a different group of C57BL/6 mice, the result was a strain of Siae-knockout mice that did not have the B-cell development defects. A newly engineered strain of mice with a different Siae mutation also had normal B-cell development.

Detailed genetic sequencing of the first knockout line revealed a previously unsuspected mutation in a gene called Dock2, located on a chromosome 11, instead of chromosome 9 where Siae is located.

The same mutation was previously reported in 2 colonies of a different knockout mouse developed in Japan.

Dr Pillai’s team also found the Dock2 mutation in a completely different group of mice from the University of California, San Diego—where their Siae-mutant strain had been developed—and realized that 3 different engineered strains with the same unwanted mutation had probably acquired it from a common source. The team eventually traced it back to a subline of C57BL/6 mice from Harlan/Envigo.

Since most research papers using C57BL/6 mice or other such “background” strains do not indicate the specific subline, the researchers said they have no way of knowing how many studies might be affected by their findings.

But they hope the publication of these results will alert other research teams to the potential need to review their results.

“While embryonic stem cells from C57BL/6 mice have recently become available, which allows the generation of knockout strains with less backcrossing, B6 mice are used for many different kinds of experiments, including as controls,” Dr Pillai said.

“Researchers who have used them need to re-genotype the mice to look for the Dock2 mutation and, if they find it, check to see whether their results are preserved if the Dock2 mutation is bred out.”

Lab mouse

Researchers say they have discovered a mutation in a subline of C57BL/6 mice that could compromise results from previous studies.

“We found an unexpected mutation with potentially important consequences in strains of mice that had been separately engineered in labs in California and Japan,” said Shiv Pillai, MD, PhD, of The Ragon Institute of MGH, MIT and Harvard in Cambridge, Massachusetts.

“[W]e traced the problem to a subline of B6 mice from one specific company that have been sold in Asia, North America, Europe, and Israel. We have notified this company—Harlan Laboratories, which is now part of Envigo—of our findings, and they have been very responsive and will use approaches we have provided to check all of their colonies.”

Dr Pillai and his colleagues described their discovery of the mutation in Cell Reports.

The team noted that, in immunological studies, mutant mice are backcrossed for many generations into B6 mice so that all genes other than the mutant gene are derived from the B6 strain. This allows the comparison of data from laboratories in different parts of the world and simplifies creating mice with mutations in several genes.

A 2009 study out of Dr Pillai’s lab showed that 2 strains of mice engineered to lack the Siae or Cmah genes—both of which code for enzymes involved with sialic acid proteins—also had significant defects in the development of B cells, which were assumed to be the result of the knockout genes.

However, when Siae-deficient mice were further backcrossed with a different group of C57BL/6 mice, the result was a strain of Siae-knockout mice that did not have the B-cell development defects. A newly engineered strain of mice with a different Siae mutation also had normal B-cell development.

Detailed genetic sequencing of the first knockout line revealed a previously unsuspected mutation in a gene called Dock2, located on a chromosome 11, instead of chromosome 9 where Siae is located.

The same mutation was previously reported in 2 colonies of a different knockout mouse developed in Japan.

Dr Pillai’s team also found the Dock2 mutation in a completely different group of mice from the University of California, San Diego—where their Siae-mutant strain had been developed—and realized that 3 different engineered strains with the same unwanted mutation had probably acquired it from a common source. The team eventually traced it back to a subline of C57BL/6 mice from Harlan/Envigo.

Since most research papers using C57BL/6 mice or other such “background” strains do not indicate the specific subline, the researchers said they have no way of knowing how many studies might be affected by their findings.

But they hope the publication of these results will alert other research teams to the potential need to review their results.

“While embryonic stem cells from C57BL/6 mice have recently become available, which allows the generation of knockout strains with less backcrossing, B6 mice are used for many different kinds of experiments, including as controls,” Dr Pillai said.

“Researchers who have used them need to re-genotype the mice to look for the Dock2 mutation and, if they find it, check to see whether their results are preserved if the Dock2 mutation is bred out.”

Human Tregs

Image by Kathryn T. Iacono

A new approach to cancer immunotherapy may avoid some of the shortcomings associated with other methods, according to researchers.

The group found that eliminating a key protein in regulatory T cells (Tregs) makes them so unstable that they become effector T cells (Teff) and begin to attack the cancer.

And this conversion from Treg to Teff occurs only in the inflammatory conditions that prevail within many tumors.

As a result, Tregs embedded in normal tissue throughout the body continue to have a restraining effect on their local Teffs, protecting healthy organs and tissues from attack.

The researchers said this raises the prospect of therapies that concentrate the immune system’s firepower on tumors without producing residual damage and harmful side effects.

“Many current approaches to immunotherapy involve depleting or blocking Tregs in order to shift the balance toward Teff cells,” said Harvey Cantor, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

“This, however, runs the risk of triggering an autoimmune response in which the Teff cells attack normal as well as malignant tissue. The key to our approach is that it singles out the Tregs inside a tumor for conversion, leaving Tregs elsewhere in the body unchanged.”

Dr Cantor and his colleagues described the approach in PNAS.

The study builds on research published last year in Science. That study showed that Tregs maintain their immune-suppressive properties under inflammatory conditions as long as they have high enough levels of a protein called Helios. Depriving Tregs of sufficient Helios caused them to lose that stability and turn into Teff cells.

The new study explored whether this convertibility could be harnessed for therapeutic purposes in cancers.

The first set of experiments involved mice engineered to lack Helios in their Tregs. When the animals were injected with melanoma or colon cancer cells, they developed tumors far more slowly than animals with normal Tregs.

“Inspection of the animals’ tumor tissue showed an unstable set of T regulatory cells, many of which had converted into Teffs,” said Hye-Jung Kim, PhD, also of the Dana-Farber Cancer Institute.

The researchers then explored whether stanching Helios production in tumor-dwelling Tregs could have the same effect. They tested several antibodies that bind to key receptors on Tregs and cause a downturn in Helios production.

The team chose an antibody that worked well, DTA-1, and tested it in mice with Treg-laden tumors. When they analyzed the tumor tissue, it was clear that DTA-1 had triggered conversion of Tregs to Teffs.

“This represents a next stage in cancer immunotherapy,” Dr Cantor said. “We now have a very specific, targeted way of inducing a T-effector-cell attack on cancer while lowering the risk of adverse effects on healthy tissue. The next step will be to organize a clinical trial using this approach in patients.”

Human Tregs

Image by Kathryn T. Iacono

A new approach to cancer immunotherapy may avoid some of the shortcomings associated with other methods, according to researchers.

The group found that eliminating a key protein in regulatory T cells (Tregs) makes them so unstable that they become effector T cells (Teff) and begin to attack the cancer.

And this conversion from Treg to Teff occurs only in the inflammatory conditions that prevail within many tumors.

As a result, Tregs embedded in normal tissue throughout the body continue to have a restraining effect on their local Teffs, protecting healthy organs and tissues from attack.

The researchers said this raises the prospect of therapies that concentrate the immune system’s firepower on tumors without producing residual damage and harmful side effects.

“Many current approaches to immunotherapy involve depleting or blocking Tregs in order to shift the balance toward Teff cells,” said Harvey Cantor, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

“This, however, runs the risk of triggering an autoimmune response in which the Teff cells attack normal as well as malignant tissue. The key to our approach is that it singles out the Tregs inside a tumor for conversion, leaving Tregs elsewhere in the body unchanged.”

Dr Cantor and his colleagues described the approach in PNAS.

The study builds on research published last year in Science. That study showed that Tregs maintain their immune-suppressive properties under inflammatory conditions as long as they have high enough levels of a protein called Helios. Depriving Tregs of sufficient Helios caused them to lose that stability and turn into Teff cells.

The new study explored whether this convertibility could be harnessed for therapeutic purposes in cancers.

The first set of experiments involved mice engineered to lack Helios in their Tregs. When the animals were injected with melanoma or colon cancer cells, they developed tumors far more slowly than animals with normal Tregs.

“Inspection of the animals’ tumor tissue showed an unstable set of T regulatory cells, many of which had converted into Teffs,” said Hye-Jung Kim, PhD, also of the Dana-Farber Cancer Institute.

The researchers then explored whether stanching Helios production in tumor-dwelling Tregs could have the same effect. They tested several antibodies that bind to key receptors on Tregs and cause a downturn in Helios production.

The team chose an antibody that worked well, DTA-1, and tested it in mice with Treg-laden tumors. When they analyzed the tumor tissue, it was clear that DTA-1 had triggered conversion of Tregs to Teffs.

“This represents a next stage in cancer immunotherapy,” Dr Cantor said. “We now have a very specific, targeted way of inducing a T-effector-cell attack on cancer while lowering the risk of adverse effects on healthy tissue. The next step will be to organize a clinical trial using this approach in patients.”

Human Tregs

Image by Kathryn T. Iacono

A new approach to cancer immunotherapy may avoid some of the shortcomings associated with other methods, according to researchers.

The group found that eliminating a key protein in regulatory T cells (Tregs) makes them so unstable that they become effector T cells (Teff) and begin to attack the cancer.

And this conversion from Treg to Teff occurs only in the inflammatory conditions that prevail within many tumors.

As a result, Tregs embedded in normal tissue throughout the body continue to have a restraining effect on their local Teffs, protecting healthy organs and tissues from attack.

The researchers said this raises the prospect of therapies that concentrate the immune system’s firepower on tumors without producing residual damage and harmful side effects.

“Many current approaches to immunotherapy involve depleting or blocking Tregs in order to shift the balance toward Teff cells,” said Harvey Cantor, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

“This, however, runs the risk of triggering an autoimmune response in which the Teff cells attack normal as well as malignant tissue. The key to our approach is that it singles out the Tregs inside a tumor for conversion, leaving Tregs elsewhere in the body unchanged.”

Dr Cantor and his colleagues described the approach in PNAS.

The study builds on research published last year in Science. That study showed that Tregs maintain their immune-suppressive properties under inflammatory conditions as long as they have high enough levels of a protein called Helios. Depriving Tregs of sufficient Helios caused them to lose that stability and turn into Teff cells.

The new study explored whether this convertibility could be harnessed for therapeutic purposes in cancers.

The first set of experiments involved mice engineered to lack Helios in their Tregs. When the animals were injected with melanoma or colon cancer cells, they developed tumors far more slowly than animals with normal Tregs.

“Inspection of the animals’ tumor tissue showed an unstable set of T regulatory cells, many of which had converted into Teffs,” said Hye-Jung Kim, PhD, also of the Dana-Farber Cancer Institute.

The researchers then explored whether stanching Helios production in tumor-dwelling Tregs could have the same effect. They tested several antibodies that bind to key receptors on Tregs and cause a downturn in Helios production.

The team chose an antibody that worked well, DTA-1, and tested it in mice with Treg-laden tumors. When they analyzed the tumor tissue, it was clear that DTA-1 had triggered conversion of Tregs to Teffs.

“This represents a next stage in cancer immunotherapy,” Dr Cantor said. “We now have a very specific, targeted way of inducing a T-effector-cell attack on cancer while lowering the risk of adverse effects on healthy tissue. The next step will be to organize a clinical trial using this approach in patients.”

Aedes aegypti mosquito

Photo courtesy of

Muhammad Mahdi Karim

The US Centers for Disease Control and Prevention (CDC) has announced that US states and territories can now apply for funds to fight Zika locally.

The agency said more than $85 million in redirected funds identified by the Department of Health and Human Services is being made available to support efforts to protect Americans from Zika infection and associated adverse health outcomes.

“These funds will allow states and territories to continue implementation of their Zika preparedness plans but are not enough to support a comprehensive Zika response and can only temporarily address what is needed,” said Stephen C. Redd, MD, director of the CDC’s Office of Public Health Preparedness and Response.

“Without the full amount of requested emergency supplemental funding, many activities that need to start now are being delayed or may have to be stopped within months.”

The more than $85 million in funds includes the more $60 million reported earlier this year (Funding opportunity number CDC-RFA-CK14-1401CONTPPHF16) as well as another $25 million that was just announced (Funding opportunity number CDC-RFA-TP16-1602).

Earlier this year, states and cities participating in the Epidemiology and Lab Capacity program became eligible for more than $60 million in funds to:

• Build laboratory capacity
• Enhance epidemiological surveillance and investigation
• Improve mosquito control and monitoring
• Keep blood supplies safe
• Contribute data to the US Zika Pregnancy registry.

Applications for these funds are due May 27, 2016, and will be disbursed during the summer.

Under the latest announcement, $25 million in FY 2016 preparedness and response funding will go to 53 states, cities, and territories at risk for outbreaks of Zika virus infection.‎

Recipients will receive funds based on the geographic locations of the two mosquitoes known to transmit Zika virus (Aedes aegypti and Aedes albopictus), history of mosquito-borne disease outbreaks, and size of population.

The funds are intended to strengthen incident management and emergency operations coordination, information management and sharing, and community recovery and resilience.

State, local, and territorial health officials can use the funds to identify and investigate a possible outbreak of Zika virus disease in their communities, coordinate a comprehensive response across all levels of government and non-governmental partners (including the healthcare sector), and identify and connect to community services families affected by Zika virus disease.

Applications for the funds are due June 13, 2016. Funds will be disbursed during the summer and remain available through July 2017.

Zika virus disease is caused by the Zika virus, which is spread to people primarily through the bite of infected Aedes aegypti and Aedes albopictus mosquitoes, though Aedes aegypti are more likely to spread Zika. Sexual transmission and transmission via blood transfusion have been documented as well.

There is currently no vaccine or treatment for Zika. The most common symptoms of Zika are fever, rash, joint pain, and conjunctivitis. In previous outbreaks, the illness has typically been mild, with symptoms lasting for several days to a week after a person is bitten by an infected mosquito.

Zika virus infection in pregnant women is a cause of microcephaly and other severe fetal brain defects. Zika has also been linked to Guillain-Barré syndrome.

Aedes aegypti mosquito

Photo courtesy of

Muhammad Mahdi Karim

The US Centers for Disease Control and Prevention (CDC) has announced that US states and territories can now apply for funds to fight Zika locally.

The agency said more than $85 million in redirected funds identified by the Department of Health and Human Services is being made available to support efforts to protect Americans from Zika infection and associated adverse health outcomes.

“These funds will allow states and territories to continue implementation of their Zika preparedness plans but are not enough to support a comprehensive Zika response and can only temporarily address what is needed,” said Stephen C. Redd, MD, director of the CDC’s Office of Public Health Preparedness and Response.

“Without the full amount of requested emergency supplemental funding, many activities that need to start now are being delayed or may have to be stopped within months.”

The more than $85 million in funds includes the more $60 million reported earlier this year (Funding opportunity number CDC-RFA-CK14-1401CONTPPHF16) as well as another $25 million that was just announced (Funding opportunity number CDC-RFA-TP16-1602).

Earlier this year, states and cities participating in the Epidemiology and Lab Capacity program became eligible for more than $60 million in funds to:

• Build laboratory capacity
• Enhance epidemiological surveillance and investigation
• Improve mosquito control and monitoring
• Keep blood supplies safe
• Contribute data to the US Zika Pregnancy registry.

Applications for these funds are due May 27, 2016, and will be disbursed during the summer.

Under the latest announcement, $25 million in FY 2016 preparedness and response funding will go to 53 states, cities, and territories at risk for outbreaks of Zika virus infection.‎

Recipients will receive funds based on the geographic locations of the two mosquitoes known to transmit Zika virus (Aedes aegypti and Aedes albopictus), history of mosquito-borne disease outbreaks, and size of population.

The funds are intended to strengthen incident management and emergency operations coordination, information management and sharing, and community recovery and resilience.

State, local, and territorial health officials can use the funds to identify and investigate a possible outbreak of Zika virus disease in their communities, coordinate a comprehensive response across all levels of government and non-governmental partners (including the healthcare sector), and identify and connect to community services families affected by Zika virus disease.

Applications for the funds are due June 13, 2016. Funds will be disbursed during the summer and remain available through July 2017.

Zika virus disease is caused by the Zika virus, which is spread to people primarily through the bite of infected Aedes aegypti and Aedes albopictus mosquitoes, though Aedes aegypti are more likely to spread Zika. Sexual transmission and transmission via blood transfusion have been documented as well.

There is currently no vaccine or treatment for Zika. The most common symptoms of Zika are fever, rash, joint pain, and conjunctivitis. In previous outbreaks, the illness has typically been mild, with symptoms lasting for several days to a week after a person is bitten by an infected mosquito.

Zika virus infection in pregnant women is a cause of microcephaly and other severe fetal brain defects. Zika has also been linked to Guillain-Barré syndrome.

Aedes aegypti mosquito

Photo courtesy of

Muhammad Mahdi Karim

The US Centers for Disease Control and Prevention (CDC) has announced that US states and territories can now apply for funds to fight Zika locally.

The agency said more than $85 million in redirected funds identified by the Department of Health and Human Services is being made available to support efforts to protect Americans from Zika infection and associated adverse health outcomes.

“These funds will allow states and territories to continue implementation of their Zika preparedness plans but are not enough to support a comprehensive Zika response and can only temporarily address what is needed,” said Stephen C. Redd, MD, director of the CDC’s Office of Public Health Preparedness and Response.

“Without the full amount of requested emergency supplemental funding, many activities that need to start now are being delayed or may have to be stopped within months.”

The more than $85 million in funds includes the more $60 million reported earlier this year (Funding opportunity number CDC-RFA-CK14-1401CONTPPHF16) as well as another $25 million that was just announced (Funding opportunity number CDC-RFA-TP16-1602).

Earlier this year, states and cities participating in the Epidemiology and Lab Capacity program became eligible for more than $60 million in funds to:

• Build laboratory capacity
• Enhance epidemiological surveillance and investigation
• Improve mosquito control and monitoring
• Keep blood supplies safe
• Contribute data to the US Zika Pregnancy registry.

Applications for these funds are due May 27, 2016, and will be disbursed during the summer.

Under the latest announcement, $25 million in FY 2016 preparedness and response funding will go to 53 states, cities, and territories at risk for outbreaks of Zika virus infection.‎

Recipients will receive funds based on the geographic locations of the two mosquitoes known to transmit Zika virus (Aedes aegypti and Aedes albopictus), history of mosquito-borne disease outbreaks, and size of population.

The funds are intended to strengthen incident management and emergency operations coordination, information management and sharing, and community recovery and resilience.

State, local, and territorial health officials can use the funds to identify and investigate a possible outbreak of Zika virus disease in their communities, coordinate a comprehensive response across all levels of government and non-governmental partners (including the healthcare sector), and identify and connect to community services families affected by Zika virus disease.

Applications for the funds are due June 13, 2016. Funds will be disbursed during the summer and remain available through July 2017.

Zika virus disease is caused by the Zika virus, which is spread to people primarily through the bite of infected Aedes aegypti and Aedes albopictus mosquitoes, though Aedes aegypti are more likely to spread Zika. Sexual transmission and transmission via blood transfusion have been documented as well.

There is currently no vaccine or treatment for Zika. The most common symptoms of Zika are fever, rash, joint pain, and conjunctivitis. In previous outbreaks, the illness has typically been mild, with symptoms lasting for several days to a week after a person is bitten by an infected mosquito.

Zika virus infection in pregnant women is a cause of microcephaly and other severe fetal brain defects. Zika has also been linked to Guillain-Barré syndrome.

Urine sample

The US Centers for Disease Control and Prevention (CDC) has released an interim guidance for testing urine for the Zika virus.

The agency noted that, in most patients, Zika virus RNA is unlikely to be detected in serum after the first week of illness.

However, recent reports have suggested that Zika virus RNA can be detected in urine for at least 2 weeks after the onset of symptoms.

Therefore, the CDC recommends that real-time reverse transcription–polymerase chain reaction (rRT-PCR) be performed on urine collected less than 14 days after the onset of symptoms in patients with suspected Zika virus.

The agency said further investigation is needed to determine the utility of rRT-PCR on urine specimens collected at 14 days or beyond.

The CDC also recommends that urine testing be performed in conjunction with serum testing for specimens collected less than 7 days after symptom onset. The agency said its recommendations for testing serum and other clinical specimens for Zika virus have not changed.

At present, the CDC’s Trioplex rRT-PCR assay is the only diagnostic tool authorized by the US Food and Drug Administration to test urine for Zika virus.

Urine sample

The US Centers for Disease Control and Prevention (CDC) has released an interim guidance for testing urine for the Zika virus.

The agency noted that, in most patients, Zika virus RNA is unlikely to be detected in serum after the first week of illness.

However, recent reports have suggested that Zika virus RNA can be detected in urine for at least 2 weeks after the onset of symptoms.

Therefore, the CDC recommends that real-time reverse transcription–polymerase chain reaction (rRT-PCR) be performed on urine collected less than 14 days after the onset of symptoms in patients with suspected Zika virus.

The agency said further investigation is needed to determine the utility of rRT-PCR on urine specimens collected at 14 days or beyond.

The CDC also recommends that urine testing be performed in conjunction with serum testing for specimens collected less than 7 days after symptom onset. The agency said its recommendations for testing serum and other clinical specimens for Zika virus have not changed.

At present, the CDC’s Trioplex rRT-PCR assay is the only diagnostic tool authorized by the US Food and Drug Administration to test urine for Zika virus.

Urine sample

The US Centers for Disease Control and Prevention (CDC) has released an interim guidance for testing urine for the Zika virus.

The agency noted that, in most patients, Zika virus RNA is unlikely to be detected in serum after the first week of illness.

However, recent reports have suggested that Zika virus RNA can be detected in urine for at least 2 weeks after the onset of symptoms.

Therefore, the CDC recommends that real-time reverse transcription–polymerase chain reaction (rRT-PCR) be performed on urine collected less than 14 days after the onset of symptoms in patients with suspected Zika virus.

The agency said further investigation is needed to determine the utility of rRT-PCR on urine specimens collected at 14 days or beyond.

The CDC also recommends that urine testing be performed in conjunction with serum testing for specimens collected less than 7 days after symptom onset. The agency said its recommendations for testing serum and other clinical specimens for Zika virus have not changed.

At present, the CDC’s Trioplex rRT-PCR assay is the only diagnostic tool authorized by the US Food and Drug Administration to test urine for Zika virus.

Endothelial cells

Image courtesy of NIH

Chronic exposure to proton pump inhibitors (PPIs) accelerates biological aging in human endothelial cells, according to preclinical research.

Investigators said this finding, published in Circulation Research, supports recent epidemiological and retrospective studies that revealed associations between the long-term use of PPIs and an increased risk of heart attack, renal failure, and dementia.

“When we exposed human endothelial cells over a period of time to these PPIs, we observed accelerated aging of the cells,” said John P. Cooke, MD, PhD, of the Houston Methodist Research Institute in Texas.

“The PPIs also reduce acidity in lysosomes of the endothelial cell. The lysosomes are like cellular garbage disposals and need acid to work properly. We observed cellular garbage accumulating in the endothelial cells, which sped up the aging process.”

Dr Cooke suspects this may be the unifying mechanism that explains the increased risk of heart attack, renal failure, and dementia observed in long-term PPI users.

“These drugs do not seem to adversely affect the heart and blood vessels when taken for a few weeks,” he said. “However, we urgently need studies to assess the impact of long-term use of these drugs on vascular health in a broad patient population. We also need to consider if these drugs should be so accessible without medical supervision.”

Dr Cooke and his colleagues noted that, while PPIs like esomeprazole (Nexium) were shown to affect vascular aging, H2 blockers like ranitidine (Zantac) did not adversely affect the endothelium.

Therefore, other approaches to long-term treatment that should be considered for gastroesophageal reflux disease include H2 antagonists, lifestyle modifications, and, in severe cases, surgical approaches.

The investigators also pointed out that this study had some limitations. Although two different PPIs were tested, only one of these, esomeprazole, is commercially available.

In addition, the study did not show how PPIs actually impair the lysosome’s ability to produce enough acid to clear waste.

Finally, since this study was conducted in a laboratory setting, it did not show whether PPIs act in the same way within the human body as they do in vitro.

Endothelial cells

Image courtesy of NIH

Chronic exposure to proton pump inhibitors (PPIs) accelerates biological aging in human endothelial cells, according to preclinical research.

Investigators said this finding, published in Circulation Research, supports recent epidemiological and retrospective studies that revealed associations between the long-term use of PPIs and an increased risk of heart attack, renal failure, and dementia.

“When we exposed human endothelial cells over a period of time to these PPIs, we observed accelerated aging of the cells,” said John P. Cooke, MD, PhD, of the Houston Methodist Research Institute in Texas.

“The PPIs also reduce acidity in lysosomes of the endothelial cell. The lysosomes are like cellular garbage disposals and need acid to work properly. We observed cellular garbage accumulating in the endothelial cells, which sped up the aging process.”

Dr Cooke suspects this may be the unifying mechanism that explains the increased risk of heart attack, renal failure, and dementia observed in long-term PPI users.

“These drugs do not seem to adversely affect the heart and blood vessels when taken for a few weeks,” he said. “However, we urgently need studies to assess the impact of long-term use of these drugs on vascular health in a broad patient population. We also need to consider if these drugs should be so accessible without medical supervision.”

Dr Cooke and his colleagues noted that, while PPIs like esomeprazole (Nexium) were shown to affect vascular aging, H2 blockers like ranitidine (Zantac) did not adversely affect the endothelium.

Therefore, other approaches to long-term treatment that should be considered for gastroesophageal reflux disease include H2 antagonists, lifestyle modifications, and, in severe cases, surgical approaches.

The investigators also pointed out that this study had some limitations. Although two different PPIs were tested, only one of these, esomeprazole, is commercially available.

In addition, the study did not show how PPIs actually impair the lysosome’s ability to produce enough acid to clear waste.

Finally, since this study was conducted in a laboratory setting, it did not show whether PPIs act in the same way within the human body as they do in vitro.

Endothelial cells

Image courtesy of NIH

Chronic exposure to proton pump inhibitors (PPIs) accelerates biological aging in human endothelial cells, according to preclinical research.

Investigators said this finding, published in Circulation Research, supports recent epidemiological and retrospective studies that revealed associations between the long-term use of PPIs and an increased risk of heart attack, renal failure, and dementia.

“When we exposed human endothelial cells over a period of time to these PPIs, we observed accelerated aging of the cells,” said John P. Cooke, MD, PhD, of the Houston Methodist Research Institute in Texas.

“The PPIs also reduce acidity in lysosomes of the endothelial cell. The lysosomes are like cellular garbage disposals and need acid to work properly. We observed cellular garbage accumulating in the endothelial cells, which sped up the aging process.”

Dr Cooke suspects this may be the unifying mechanism that explains the increased risk of heart attack, renal failure, and dementia observed in long-term PPI users.

“These drugs do not seem to adversely affect the heart and blood vessels when taken for a few weeks,” he said. “However, we urgently need studies to assess the impact of long-term use of these drugs on vascular health in a broad patient population. We also need to consider if these drugs should be so accessible without medical supervision.”

Dr Cooke and his colleagues noted that, while PPIs like esomeprazole (Nexium) were shown to affect vascular aging, H2 blockers like ranitidine (Zantac) did not adversely affect the endothelium.

Therefore, other approaches to long-term treatment that should be considered for gastroesophageal reflux disease include H2 antagonists, lifestyle modifications, and, in severe cases, surgical approaches.

The investigators also pointed out that this study had some limitations. Although two different PPIs were tested, only one of these, esomeprazole, is commercially available.

In addition, the study did not show how PPIs actually impair the lysosome’s ability to produce enough acid to clear waste.

Finally, since this study was conducted in a laboratory setting, it did not show whether PPIs act in the same way within the human body as they do in vitro.

Blood samples

Photo by Graham Colm

A new technique provides a way to keep blood samples stable for long periods at high temperatures, according to research published in PNAS.

Investigators found they could keep blood samples stable for nearly 3 months at temperatures as high as 113 degrees F by encapsulating them in air-dried silk protein.

The team believes this technique could have broad applications for clinical care and research.

“This approach should facilitate outpatient blood collection for disease screening and monitoring, particularly for underserved populations, and also serve needs of researchers and clinicians without access to centralized testing facilities,” said study author David L. Kaplan, PhD, of the Department of Biomedical Engineering at Tufts University in Medford, Massachusetts.

For this approach, Dr Kaplan and his colleagues mixed a solution or a powder of purified silk fibroin protein extracted from silkworm cocoons with blood or plasma and air-dried the mixture.

The air-dried silk films were stored at temperatures between 22 and 45 degrees C (71.6 to 113 degrees F). At set intervals, the researchers recovered the encapsulated blood samples by dissolving the films in water and analyzed them.

“We found that biomarkers could be successfully analyzed even after storage for 84 days at temperatures up to 113 degrees F,” said study author Jonathan A. Kluge, PhD, formerly of Tufts University but now at Vaxess Technologies in Cambridge, Massachusetts.

“Encapsulation of samples in silk provided better protection than the traditional approach of drying on paper, especially at these elevated temperatures, which a shipment might encounter during overseas or summer transport.”

The investigators noted that the silk-based technique requires accurate starting volumes of the blood or other specimens to be known, and salts or other buffers are needed to reconstitute samples for accurate testing of certain markers.

Blood samples

Photo by Graham Colm

A new technique provides a way to keep blood samples stable for long periods at high temperatures, according to research published in PNAS.

Investigators found they could keep blood samples stable for nearly 3 months at temperatures as high as 113 degrees F by encapsulating them in air-dried silk protein.

The team believes this technique could have broad applications for clinical care and research.

“This approach should facilitate outpatient blood collection for disease screening and monitoring, particularly for underserved populations, and also serve needs of researchers and clinicians without access to centralized testing facilities,” said study author David L. Kaplan, PhD, of the Department of Biomedical Engineering at Tufts University in Medford, Massachusetts.

For this approach, Dr Kaplan and his colleagues mixed a solution or a powder of purified silk fibroin protein extracted from silkworm cocoons with blood or plasma and air-dried the mixture.

The air-dried silk films were stored at temperatures between 22 and 45 degrees C (71.6 to 113 degrees F). At set intervals, the researchers recovered the encapsulated blood samples by dissolving the films in water and analyzed them.

“We found that biomarkers could be successfully analyzed even after storage for 84 days at temperatures up to 113 degrees F,” said study author Jonathan A. Kluge, PhD, formerly of Tufts University but now at Vaxess Technologies in Cambridge, Massachusetts.

“Encapsulation of samples in silk provided better protection than the traditional approach of drying on paper, especially at these elevated temperatures, which a shipment might encounter during overseas or summer transport.”

The investigators noted that the silk-based technique requires accurate starting volumes of the blood or other specimens to be known, and salts or other buffers are needed to reconstitute samples for accurate testing of certain markers.

Blood samples

Photo by Graham Colm

A new technique provides a way to keep blood samples stable for long periods at high temperatures, according to research published in PNAS.

Investigators found they could keep blood samples stable for nearly 3 months at temperatures as high as 113 degrees F by encapsulating them in air-dried silk protein.

The team believes this technique could have broad applications for clinical care and research.

“This approach should facilitate outpatient blood collection for disease screening and monitoring, particularly for underserved populations, and also serve needs of researchers and clinicians without access to centralized testing facilities,” said study author David L. Kaplan, PhD, of the Department of Biomedical Engineering at Tufts University in Medford, Massachusetts.

For this approach, Dr Kaplan and his colleagues mixed a solution or a powder of purified silk fibroin protein extracted from silkworm cocoons with blood or plasma and air-dried the mixture.

The air-dried silk films were stored at temperatures between 22 and 45 degrees C (71.6 to 113 degrees F). At set intervals, the researchers recovered the encapsulated blood samples by dissolving the films in water and analyzed them.

“We found that biomarkers could be successfully analyzed even after storage for 84 days at temperatures up to 113 degrees F,” said study author Jonathan A. Kluge, PhD, formerly of Tufts University but now at Vaxess Technologies in Cambridge, Massachusetts.

“Encapsulation of samples in silk provided better protection than the traditional approach of drying on paper, especially at these elevated temperatures, which a shipment might encounter during overseas or summer transport.”

The investigators noted that the silk-based technique requires accurate starting volumes of the blood or other specimens to be known, and salts or other buffers are needed to reconstitute samples for accurate testing of certain markers.

Doctor and patient

Photo courtesy of NIH

Changing the default prescription settings in the electronic health record (EHR) can increase the prescribing rates of generic drugs, according to a study published in JAMA Internal Medicine.

The study showed an increase in generic prescribing rates from 75% to 98% when prescriptions were defaulted to a generic medication (if available) in the EHR.

To order the brand name drug, physicians had to opt out by checking a box labelled “dispense as written.”

The study, which builds upon previous research, indicates that the manner in which default options are designed and implemented can influence physician behavior.

“Many of the decisions physicians make are shifting from pen and paper to digital platforms, like the electronic health record, yet there lacks sufficient evidence on how to design choice architecture within these environments to improve healthcare value and outcomes,” said study author Mitesh S. Patel, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

“Our results demonstrate that default options are a powerful tool for influencing physician behaviors but that they have to be well-designed to achieve the intended goals.”

For the study, Dr Patel and his colleagues tracked prescribing rates of oral medications for 10 common medical conditions across the University of Pennsylvania Health System.

Rather than changing prescription default settings to display generic names instead of brand names—a change that previously resulted in a 5% change in prescribing habits—in the new study, an opt-out checkbox was used.

When a physician prescribed a drug for a patient, the EHR would default to an equivalent generic. However, the physician could still prescribe the brand name when warranted by selecting the “dispense as written” checkbox.

The researchers compared prescribing rates between the pre-intervention period (January 2014 to October 2014) and the post-intervention period (December 2014 to June 2015).

The results showed that, during the pre-intervention period, generic drugs were prescribed 75.3% of the time, compared to 98.4% of the time during the post-intervention period (P<0.001).

The researchers said this indicates that, for most drugs, physicians specified the brand name should be prescribed only 2% of the time.

The exception to the trend was when physicians prescribed Synthroid for patients with thyroid conditions, as this brand name drug is known to have different hormone levels than its generic version, levothyroxine. In this case, physicians opted out and selected the brand name 22% of the time.

“Studies examining these seemingly minute details point to the importance of design when implementing defaults, which is something that could in result in a significant savings for patients and health systems, and hasn’t previously been examined closely in a healthcare setting,” said study author C. William Hanson, MD, of the Perelman School of Medicine.

“If a simple, low-cost change like adding an opt-out check box to prescription settings can make such a significant impact, there are likely other refinements that can be made just as easily that will also result in cost savings for patients and health systems. It’s a valuable area of research to continue exploring.”

Doctor and patient

Photo courtesy of NIH

Changing the default prescription settings in the electronic health record (EHR) can increase the prescribing rates of generic drugs, according to a study published in JAMA Internal Medicine.

The study showed an increase in generic prescribing rates from 75% to 98% when prescriptions were defaulted to a generic medication (if available) in the EHR.

To order the brand name drug, physicians had to opt out by checking a box labelled “dispense as written.”

The study, which builds upon previous research, indicates that the manner in which default options are designed and implemented can influence physician behavior.

“Many of the decisions physicians make are shifting from pen and paper to digital platforms, like the electronic health record, yet there lacks sufficient evidence on how to design choice architecture within these environments to improve healthcare value and outcomes,” said study author Mitesh S. Patel, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

“Our results demonstrate that default options are a powerful tool for influencing physician behaviors but that they have to be well-designed to achieve the intended goals.”

For the study, Dr Patel and his colleagues tracked prescribing rates of oral medications for 10 common medical conditions across the University of Pennsylvania Health System.

Rather than changing prescription default settings to display generic names instead of brand names—a change that previously resulted in a 5% change in prescribing habits—in the new study, an opt-out checkbox was used.

When a physician prescribed a drug for a patient, the EHR would default to an equivalent generic. However, the physician could still prescribe the brand name when warranted by selecting the “dispense as written” checkbox.

The researchers compared prescribing rates between the pre-intervention period (January 2014 to October 2014) and the post-intervention period (December 2014 to June 2015).

The results showed that, during the pre-intervention period, generic drugs were prescribed 75.3% of the time, compared to 98.4% of the time during the post-intervention period (P<0.001).

The researchers said this indicates that, for most drugs, physicians specified the brand name should be prescribed only 2% of the time.

The exception to the trend was when physicians prescribed Synthroid for patients with thyroid conditions, as this brand name drug is known to have different hormone levels than its generic version, levothyroxine. In this case, physicians opted out and selected the brand name 22% of the time.

“Studies examining these seemingly minute details point to the importance of design when implementing defaults, which is something that could in result in a significant savings for patients and health systems, and hasn’t previously been examined closely in a healthcare setting,” said study author C. William Hanson, MD, of the Perelman School of Medicine.

“If a simple, low-cost change like adding an opt-out check box to prescription settings can make such a significant impact, there are likely other refinements that can be made just as easily that will also result in cost savings for patients and health systems. It’s a valuable area of research to continue exploring.”

Doctor and patient

Photo courtesy of NIH

Changing the default prescription settings in the electronic health record (EHR) can increase the prescribing rates of generic drugs, according to a study published in JAMA Internal Medicine.

The study showed an increase in generic prescribing rates from 75% to 98% when prescriptions were defaulted to a generic medication (if available) in the EHR.

To order the brand name drug, physicians had to opt out by checking a box labelled “dispense as written.”

The study, which builds upon previous research, indicates that the manner in which default options are designed and implemented can influence physician behavior.

“Many of the decisions physicians make are shifting from pen and paper to digital platforms, like the electronic health record, yet there lacks sufficient evidence on how to design choice architecture within these environments to improve healthcare value and outcomes,” said study author Mitesh S. Patel, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

“Our results demonstrate that default options are a powerful tool for influencing physician behaviors but that they have to be well-designed to achieve the intended goals.”

For the study, Dr Patel and his colleagues tracked prescribing rates of oral medications for 10 common medical conditions across the University of Pennsylvania Health System.

Rather than changing prescription default settings to display generic names instead of brand names—a change that previously resulted in a 5% change in prescribing habits—in the new study, an opt-out checkbox was used.

When a physician prescribed a drug for a patient, the EHR would default to an equivalent generic. However, the physician could still prescribe the brand name when warranted by selecting the “dispense as written” checkbox.

The researchers compared prescribing rates between the pre-intervention period (January 2014 to October 2014) and the post-intervention period (December 2014 to June 2015).

The results showed that, during the pre-intervention period, generic drugs were prescribed 75.3% of the time, compared to 98.4% of the time during the post-intervention period (P<0.001).

The researchers said this indicates that, for most drugs, physicians specified the brand name should be prescribed only 2% of the time.

The exception to the trend was when physicians prescribed Synthroid for patients with thyroid conditions, as this brand name drug is known to have different hormone levels than its generic version, levothyroxine. In this case, physicians opted out and selected the brand name 22% of the time.

“Studies examining these seemingly minute details point to the importance of design when implementing defaults, which is something that could in result in a significant savings for patients and health systems, and hasn’t previously been examined closely in a healthcare setting,” said study author C. William Hanson, MD, of the Perelman School of Medicine.

“If a simple, low-cost change like adding an opt-out check box to prescription settings can make such a significant impact, there are likely other refinements that can be made just as easily that will also result in cost savings for patients and health systems. It’s a valuable area of research to continue exploring.”

Malaria-carrying mosquito

Photo by James Gathany

An experimental vaccine can protect some healthy adults from malaria infection long-term, according to a phase 1 study.

Researchers tested the vaccine, PfSPZ, by exposing malaria-naïve adults to mosquitoes infected with the parasite Plasmodium falciparum.

Six of the 11 subjects who received PfSPZ at the optimal dose and schedule were free of malaria parasites after they were exposed to the mosquitoes at 21 weeks after immunization.

Five of these subjects were still free of malaria parasites after they were exposed to the mosquitoes at 59 weeks after immunization.

In addition, the researchers said the vaccine was well-tolerated.

“It is now clear that administering the PfSPZ vaccine intravenously confers long-term, sterile protection in a small number of subjects, which has not been achieved with other current vaccine approaches,” said Robert A. Seder, MD, of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.

“Based on the favorable safety profile, we’re testing higher doses in larger trials to see if even greater protection can be achieved long-term against other P falciparum strains different than the vaccine strain.”

Dr Seder and his colleagues reported the results of the current trial in Nature Medicine.

The PfSPZ vaccine was developed and produced by Sanaria Inc., with support from several Small Business Innovation Research awards from the National Institute of Allergy and Infectious Diseases.

The PfSPZ vaccine is composed of live but weakened P falciparum sporozoites. Previous research showed the vaccine to be protective 3 weeks after immunization.

In this trial, researchers assessed if protection could last for 5 months to a year. The trial enrolled 101 healthy adults, ages 18 to 45, who had never had malaria.

Fifty-seven subjects were scheduled to receive the PfSPZ vaccine, and 32 were not vaccinated. Vaccine recipients were divided into several groups to assess the roles of the route of administration, dose, and number of immunizations in conferring short- and long-term protection against malaria.

To evaluate how well the PfSPZ vaccine prevented malaria infection, all subjects were exposed at varying times to the bites of mosquitoes carrying the same P falciparum strain from which the PfSPZ vaccine was derived—a process known as controlled human malaria infection (CHMI).

Fifty-five subjects completed all their scheduled vaccinations, and 52 of these subjects underwent at least 1 CHMI.

Safety

Seventy-two percent of the vaccinated subjects (n=41) did not have any solicited adverse events at the injection site after any vaccination. Twenty-six percent (n=15) had mild symptoms (pain and redness), and 1 patient (2%) had a moderate symptom (pain).

Fifty-six percent of vaccinated subjects (n=32) did not have solicited systemic adverse events.

Thirty-three percent (n=19) had mild systemic symptoms (malaise, myalgia, headache, chills, nausea, temperature, and joint pain), and 11% (n=6) had moderate systemic symptoms (malaise, myalgia, headache, chills, nausea, and joint pain).

There were no serious adverse events attributed to vaccination.

Efficacy

The researchers found the efficacy of the PfSPZ vaccine depended on the dose given, the number of vaccinations received, and the route of administration. A higher dose, a higher number of doses, and intravenous (IV) administration were all associated with increased efficacy.

The estimated vaccine efficacy against CHMI at 3 weeks after immunization was 24% with 3 doses of 2.7×10⁵ PfSPZ IV, compared to 73% with 4 doses of 2.7×10⁵ PfSPZ IV.

The estimated vaccine efficacy against CHMI at 21 weeks was 25% with 4 or 5 doses of 1.35×10⁵ PfSPZ IV, compared to 55% with 4 doses of 2.7×10⁵ PfSPZ IV.

In other words, after 4 immunizations with PfSPZ at 2.7×10⁵ IV, 6 of 11 (55%) vaccinated subjects remained without parasitemia following CHMI at 21 weeks after immunization.

Five of the subjects without parasitemia underwent CHMI again at 59 weeks, and none developed parasitemia.

Based on these results, the researchers hypothesize that further increasing the dose of PfSPZ will increase the magnitude and durability of efficacy. They said ongoing studies using 4.5×10⁵ to 2.7×10⁶ PfSPZ per dose are assessing this for homologous CHMI, heterologous CHMI, and natural exposure in all age groups.

Malaria-carrying mosquito

Photo by James Gathany

An experimental vaccine can protect some healthy adults from malaria infection long-term, according to a phase 1 study.

Researchers tested the vaccine, PfSPZ, by exposing malaria-naïve adults to mosquitoes infected with the parasite Plasmodium falciparum.

Six of the 11 subjects who received PfSPZ at the optimal dose and schedule were free of malaria parasites after they were exposed to the mosquitoes at 21 weeks after immunization.

Five of these subjects were still free of malaria parasites after they were exposed to the mosquitoes at 59 weeks after immunization.

In addition, the researchers said the vaccine was well-tolerated.

“It is now clear that administering the PfSPZ vaccine intravenously confers long-term, sterile protection in a small number of subjects, which has not been achieved with other current vaccine approaches,” said Robert A. Seder, MD, of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.

“Based on the favorable safety profile, we’re testing higher doses in larger trials to see if even greater protection can be achieved long-term against other P falciparum strains different than the vaccine strain.”

Dr Seder and his colleagues reported the results of the current trial in Nature Medicine.

The PfSPZ vaccine was developed and produced by Sanaria Inc., with support from several Small Business Innovation Research awards from the National Institute of Allergy and Infectious Diseases.

The PfSPZ vaccine is composed of live but weakened P falciparum sporozoites. Previous research showed the vaccine to be protective 3 weeks after immunization.

In this trial, researchers assessed if protection could last for 5 months to a year. The trial enrolled 101 healthy adults, ages 18 to 45, who had never had malaria.

Fifty-seven subjects were scheduled to receive the PfSPZ vaccine, and 32 were not vaccinated. Vaccine recipients were divided into several groups to assess the roles of the route of administration, dose, and number of immunizations in conferring short- and long-term protection against malaria.

To evaluate how well the PfSPZ vaccine prevented malaria infection, all subjects were exposed at varying times to the bites of mosquitoes carrying the same P falciparum strain from which the PfSPZ vaccine was derived—a process known as controlled human malaria infection (CHMI).

Fifty-five subjects completed all their scheduled vaccinations, and 52 of these subjects underwent at least 1 CHMI.

Safety

Seventy-two percent of the vaccinated subjects (n=41) did not have any solicited adverse events at the injection site after any vaccination. Twenty-six percent (n=15) had mild symptoms (pain and redness), and 1 patient (2%) had a moderate symptom (pain).

Fifty-six percent of vaccinated subjects (n=32) did not have solicited systemic adverse events.

Thirty-three percent (n=19) had mild systemic symptoms (malaise, myalgia, headache, chills, nausea, temperature, and joint pain), and 11% (n=6) had moderate systemic symptoms (malaise, myalgia, headache, chills, nausea, and joint pain).

There were no serious adverse events attributed to vaccination.

Efficacy

The researchers found the efficacy of the PfSPZ vaccine depended on the dose given, the number of vaccinations received, and the route of administration. A higher dose, a higher number of doses, and intravenous (IV) administration were all associated with increased efficacy.

The estimated vaccine efficacy against CHMI at 3 weeks after immunization was 24% with 3 doses of 2.7×10⁵ PfSPZ IV, compared to 73% with 4 doses of 2.7×10⁵ PfSPZ IV.

The estimated vaccine efficacy against CHMI at 21 weeks was 25% with 4 or 5 doses of 1.35×10⁵ PfSPZ IV, compared to 55% with 4 doses of 2.7×10⁵ PfSPZ IV.

In other words, after 4 immunizations with PfSPZ at 2.7×10⁵ IV, 6 of 11 (55%) vaccinated subjects remained without parasitemia following CHMI at 21 weeks after immunization.

Five of the subjects without parasitemia underwent CHMI again at 59 weeks, and none developed parasitemia.

Based on these results, the researchers hypothesize that further increasing the dose of PfSPZ will increase the magnitude and durability of efficacy. They said ongoing studies using 4.5×10⁵ to 2.7×10⁶ PfSPZ per dose are assessing this for homologous CHMI, heterologous CHMI, and natural exposure in all age groups.

Malaria-carrying mosquito

Photo by James Gathany

An experimental vaccine can protect some healthy adults from malaria infection long-term, according to a phase 1 study.

Researchers tested the vaccine, PfSPZ, by exposing malaria-naïve adults to mosquitoes infected with the parasite Plasmodium falciparum.

Six of the 11 subjects who received PfSPZ at the optimal dose and schedule were free of malaria parasites after they were exposed to the mosquitoes at 21 weeks after immunization.

Five of these subjects were still free of malaria parasites after they were exposed to the mosquitoes at 59 weeks after immunization.

In addition, the researchers said the vaccine was well-tolerated.

“It is now clear that administering the PfSPZ vaccine intravenously confers long-term, sterile protection in a small number of subjects, which has not been achieved with other current vaccine approaches,” said Robert A. Seder, MD, of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.

“Based on the favorable safety profile, we’re testing higher doses in larger trials to see if even greater protection can be achieved long-term against other P falciparum strains different than the vaccine strain.”

Dr Seder and his colleagues reported the results of the current trial in Nature Medicine.

The PfSPZ vaccine was developed and produced by Sanaria Inc., with support from several Small Business Innovation Research awards from the National Institute of Allergy and Infectious Diseases.

The PfSPZ vaccine is composed of live but weakened P falciparum sporozoites. Previous research showed the vaccine to be protective 3 weeks after immunization.

In this trial, researchers assessed if protection could last for 5 months to a year. The trial enrolled 101 healthy adults, ages 18 to 45, who had never had malaria.

Fifty-seven subjects were scheduled to receive the PfSPZ vaccine, and 32 were not vaccinated. Vaccine recipients were divided into several groups to assess the roles of the route of administration, dose, and number of immunizations in conferring short- and long-term protection against malaria.

To evaluate how well the PfSPZ vaccine prevented malaria infection, all subjects were exposed at varying times to the bites of mosquitoes carrying the same P falciparum strain from which the PfSPZ vaccine was derived—a process known as controlled human malaria infection (CHMI).

Fifty-five subjects completed all their scheduled vaccinations, and 52 of these subjects underwent at least 1 CHMI.

Safety

Seventy-two percent of the vaccinated subjects (n=41) did not have any solicited adverse events at the injection site after any vaccination. Twenty-six percent (n=15) had mild symptoms (pain and redness), and 1 patient (2%) had a moderate symptom (pain).

Fifty-six percent of vaccinated subjects (n=32) did not have solicited systemic adverse events.

Thirty-three percent (n=19) had mild systemic symptoms (malaise, myalgia, headache, chills, nausea, temperature, and joint pain), and 11% (n=6) had moderate systemic symptoms (malaise, myalgia, headache, chills, nausea, and joint pain).

There were no serious adverse events attributed to vaccination.

Efficacy

The researchers found the efficacy of the PfSPZ vaccine depended on the dose given, the number of vaccinations received, and the route of administration. A higher dose, a higher number of doses, and intravenous (IV) administration were all associated with increased efficacy.

The estimated vaccine efficacy against CHMI at 3 weeks after immunization was 24% with 3 doses of 2.7×10⁵ PfSPZ IV, compared to 73% with 4 doses of 2.7×10⁵ PfSPZ IV.

The estimated vaccine efficacy against CHMI at 21 weeks was 25% with 4 or 5 doses of 1.35×10⁵ PfSPZ IV, compared to 55% with 4 doses of 2.7×10⁵ PfSPZ IV.

In other words, after 4 immunizations with PfSPZ at 2.7×10⁵ IV, 6 of 11 (55%) vaccinated subjects remained without parasitemia following CHMI at 21 weeks after immunization.

Five of the subjects without parasitemia underwent CHMI again at 59 weeks, and none developed parasitemia.

Based on these results, the researchers hypothesize that further increasing the dose of PfSPZ will increase the magnitude and durability of efficacy. They said ongoing studies using 4.5×10⁵ to 2.7×10⁶ PfSPZ per dose are assessing this for homologous CHMI, heterologous CHMI, and natural exposure in all age groups.