BOSTON – Between 15% and 30% of children with moderate to severe atopic dermatitis also have food allergies, but the allergies are a trigger for AD in only a small subset of patients, according to Mercedes E. Gonzalez, MD.

In most cases, allergy testing is not indicated, she said at the American Academy of Dermatology summer meeting.

©Julián Rovagnati/Fotolia.com

She described a scenario involving a parent who is concerned that a food allergy is causing her child’s AD. The child has had no hives, no lip swelling, and no other signs of immediate hypersensitivity. In such a case, the best approach is to treat with topical therapies and follow the patient clinically.

“Allergy testing independent of history is not recommended,” she said.

However, in cases involving a significant concern about food allergy, such as the presence of hives or urticaria, or when the child has severe dermatitis that is not improving with optimized topical therapies, an assessment can be undertaken, said Dr. Gonzalez of the University of Miami.

She recommended limited food allergy testing – for common culprits such as cow’s milk, eggs, wheat, soy, and peanuts – in children younger than age 5 years with moderate to severe AD, if the AD persists despite optimized topical treatment and/or a history of immediate and reproducible reaction after ingestion of a specific food.

Food elimination diets based solely on the findings of food allergy test results are not recommended for managing AD, she noted.

If a patient has true immunoglobulin E–mediated allergy they should practice avoidance to prevent potential serious health sequelae, Dr. Gonzalez said.

When testing is done, keep in mind that skin prick tests and serum-specific IgE levels have high negative predictive values above 95%, but low specificity and positive predictive values of 40%-60%, she pointed out. Positive tests should be verified with a food elimination diet or oral food challenge.

Also, most children develop tolerance to the foods over time and should be retested, Dr. Gonzalez said.

Early peanut introduction advised in infants with AD

There is no need to delay the introduction of peanuts into the diet of an infant at high risk for atopic dermatitis, Dr. Gonzalez said.

A 2015 consensus communication from the American Academy of Pediatrics and numerous other organizations, including the American Academy of Allergy, Asthma & Immunology and the Society of Pediatric Dermatology, offering interim guidance on the topic calls for introduction of peanut products into the diets of high-risk infants in countries where peanut allergy is present, she said.

High-risk infants were defined in the study as those with egg allergy and/or severe eczema.

The guidance, which the AAP “endorses and accepts as its policy” pending more formal guidelines currently in development, was based largely on findings from the LEAP (Learn Early About Peanut Allergy) trial – a 5-year randomized, controlled trial of 640 high-risk infants aged 4-11 months. The trial showed that 17.2% of infants who avoided peanuts had peanut allergy at 5 years, compared with 3.2% of those with peanut consumption three times weekly, a relative risk reduction of 81% (N Engl J Med. 2015; 372:803-13).

In infants with egg allergy or severe eczema, an evaluation by an allergist or dermatologist familiar with the guidance may be warranted to assist in implementing the suggestions, Dr. Gonzalez said.

Dr. Gonzalez reported receiving honoraria for serving as a speaker and/or advisory board member for Pierre Fabre Dermatologie, Anacor Pharmaceuticals, Encore Dermatology, and PuraCap Pharmaceutical.

[email protected]

BOSTON – Between 15% and 30% of children with moderate to severe atopic dermatitis also have food allergies, but the allergies are a trigger for AD in only a small subset of patients, according to Mercedes E. Gonzalez, MD.

In most cases, allergy testing is not indicated, she said at the American Academy of Dermatology summer meeting.

©Julián Rovagnati/Fotolia.com

She described a scenario involving a parent who is concerned that a food allergy is causing her child’s AD. The child has had no hives, no lip swelling, and no other signs of immediate hypersensitivity. In such a case, the best approach is to treat with topical therapies and follow the patient clinically.

“Allergy testing independent of history is not recommended,” she said.

However, in cases involving a significant concern about food allergy, such as the presence of hives or urticaria, or when the child has severe dermatitis that is not improving with optimized topical therapies, an assessment can be undertaken, said Dr. Gonzalez of the University of Miami.

She recommended limited food allergy testing – for common culprits such as cow’s milk, eggs, wheat, soy, and peanuts – in children younger than age 5 years with moderate to severe AD, if the AD persists despite optimized topical treatment and/or a history of immediate and reproducible reaction after ingestion of a specific food.

Food elimination diets based solely on the findings of food allergy test results are not recommended for managing AD, she noted.

If a patient has true immunoglobulin E–mediated allergy they should practice avoidance to prevent potential serious health sequelae, Dr. Gonzalez said.

When testing is done, keep in mind that skin prick tests and serum-specific IgE levels have high negative predictive values above 95%, but low specificity and positive predictive values of 40%-60%, she pointed out. Positive tests should be verified with a food elimination diet or oral food challenge.

Also, most children develop tolerance to the foods over time and should be retested, Dr. Gonzalez said.

Early peanut introduction advised in infants with AD

There is no need to delay the introduction of peanuts into the diet of an infant at high risk for atopic dermatitis, Dr. Gonzalez said.

A 2015 consensus communication from the American Academy of Pediatrics and numerous other organizations, including the American Academy of Allergy, Asthma & Immunology and the Society of Pediatric Dermatology, offering interim guidance on the topic calls for introduction of peanut products into the diets of high-risk infants in countries where peanut allergy is present, she said.

High-risk infants were defined in the study as those with egg allergy and/or severe eczema.

The guidance, which the AAP “endorses and accepts as its policy” pending more formal guidelines currently in development, was based largely on findings from the LEAP (Learn Early About Peanut Allergy) trial – a 5-year randomized, controlled trial of 640 high-risk infants aged 4-11 months. The trial showed that 17.2% of infants who avoided peanuts had peanut allergy at 5 years, compared with 3.2% of those with peanut consumption three times weekly, a relative risk reduction of 81% (N Engl J Med. 2015; 372:803-13).

In infants with egg allergy or severe eczema, an evaluation by an allergist or dermatologist familiar with the guidance may be warranted to assist in implementing the suggestions, Dr. Gonzalez said.

Dr. Gonzalez reported receiving honoraria for serving as a speaker and/or advisory board member for Pierre Fabre Dermatologie, Anacor Pharmaceuticals, Encore Dermatology, and PuraCap Pharmaceutical.

[email protected]

BOSTON – Between 15% and 30% of children with moderate to severe atopic dermatitis also have food allergies, but the allergies are a trigger for AD in only a small subset of patients, according to Mercedes E. Gonzalez, MD.

In most cases, allergy testing is not indicated, she said at the American Academy of Dermatology summer meeting.

©Julián Rovagnati/Fotolia.com

She described a scenario involving a parent who is concerned that a food allergy is causing her child’s AD. The child has had no hives, no lip swelling, and no other signs of immediate hypersensitivity. In such a case, the best approach is to treat with topical therapies and follow the patient clinically.

“Allergy testing independent of history is not recommended,” she said.

However, in cases involving a significant concern about food allergy, such as the presence of hives or urticaria, or when the child has severe dermatitis that is not improving with optimized topical therapies, an assessment can be undertaken, said Dr. Gonzalez of the University of Miami.

She recommended limited food allergy testing – for common culprits such as cow’s milk, eggs, wheat, soy, and peanuts – in children younger than age 5 years with moderate to severe AD, if the AD persists despite optimized topical treatment and/or a history of immediate and reproducible reaction after ingestion of a specific food.

Food elimination diets based solely on the findings of food allergy test results are not recommended for managing AD, she noted.

If a patient has true immunoglobulin E–mediated allergy they should practice avoidance to prevent potential serious health sequelae, Dr. Gonzalez said.

When testing is done, keep in mind that skin prick tests and serum-specific IgE levels have high negative predictive values above 95%, but low specificity and positive predictive values of 40%-60%, she pointed out. Positive tests should be verified with a food elimination diet or oral food challenge.

Also, most children develop tolerance to the foods over time and should be retested, Dr. Gonzalez said.

Early peanut introduction advised in infants with AD

There is no need to delay the introduction of peanuts into the diet of an infant at high risk for atopic dermatitis, Dr. Gonzalez said.

A 2015 consensus communication from the American Academy of Pediatrics and numerous other organizations, including the American Academy of Allergy, Asthma & Immunology and the Society of Pediatric Dermatology, offering interim guidance on the topic calls for introduction of peanut products into the diets of high-risk infants in countries where peanut allergy is present, she said.

High-risk infants were defined in the study as those with egg allergy and/or severe eczema.

The guidance, which the AAP “endorses and accepts as its policy” pending more formal guidelines currently in development, was based largely on findings from the LEAP (Learn Early About Peanut Allergy) trial – a 5-year randomized, controlled trial of 640 high-risk infants aged 4-11 months. The trial showed that 17.2% of infants who avoided peanuts had peanut allergy at 5 years, compared with 3.2% of those with peanut consumption three times weekly, a relative risk reduction of 81% (N Engl J Med. 2015; 372:803-13).

In infants with egg allergy or severe eczema, an evaluation by an allergist or dermatologist familiar with the guidance may be warranted to assist in implementing the suggestions, Dr. Gonzalez said.

Dr. Gonzalez reported receiving honoraria for serving as a speaker and/or advisory board member for Pierre Fabre Dermatologie, Anacor Pharmaceuticals, Encore Dermatology, and PuraCap Pharmaceutical.

[email protected]

Health Canada has approved ixazomib (Ninlaro) for use in combination with lenalidomide and dexamethasone for the treatment of adults with relapsed/refractory multiple myeloma.

The U.S. Food and Drug Administration approved ixazomib in November 2015 for patients with relapsed/refractory multiple myeloma, based on data from TOURMALINE-MM1 that showed extended progression-free survival with a manageable safety profile.

VladimirSorokin/Thinkstock

“The approval of Ninlaro offers a much-needed new option for Canadian patients with multiple myeloma who have received at least one prior therapy. Its oral delivery may help multiple myeloma patients overcome some of the logistical burdens they may face with current therapies, which are typically administered in-clinic or in-hospital requiring significant travel and time constraints,” said Donna Reece, M.D., professor and director of the program for multiple myeloma and related diseases in the department of medical oncology and haematology at Princess Margaret Hospital/University of Toronto.

Ninlaro is marketed by Takeda. Click here to read the press release.

[email protected]

Health Canada has approved ixazomib (Ninlaro) for use in combination with lenalidomide and dexamethasone for the treatment of adults with relapsed/refractory multiple myeloma.

The U.S. Food and Drug Administration approved ixazomib in November 2015 for patients with relapsed/refractory multiple myeloma, based on data from TOURMALINE-MM1 that showed extended progression-free survival with a manageable safety profile.

VladimirSorokin/Thinkstock

“The approval of Ninlaro offers a much-needed new option for Canadian patients with multiple myeloma who have received at least one prior therapy. Its oral delivery may help multiple myeloma patients overcome some of the logistical burdens they may face with current therapies, which are typically administered in-clinic or in-hospital requiring significant travel and time constraints,” said Donna Reece, M.D., professor and director of the program for multiple myeloma and related diseases in the department of medical oncology and haematology at Princess Margaret Hospital/University of Toronto.

Ninlaro is marketed by Takeda. Click here to read the press release.

[email protected]

Health Canada has approved ixazomib (Ninlaro) for use in combination with lenalidomide and dexamethasone for the treatment of adults with relapsed/refractory multiple myeloma.

The U.S. Food and Drug Administration approved ixazomib in November 2015 for patients with relapsed/refractory multiple myeloma, based on data from TOURMALINE-MM1 that showed extended progression-free survival with a manageable safety profile.

VladimirSorokin/Thinkstock

“The approval of Ninlaro offers a much-needed new option for Canadian patients with multiple myeloma who have received at least one prior therapy. Its oral delivery may help multiple myeloma patients overcome some of the logistical burdens they may face with current therapies, which are typically administered in-clinic or in-hospital requiring significant travel and time constraints,” said Donna Reece, M.D., professor and director of the program for multiple myeloma and related diseases in the department of medical oncology and haematology at Princess Margaret Hospital/University of Toronto.

Ninlaro is marketed by Takeda. Click here to read the press release.

[email protected]

Current treatment strategies for chronic hepatitis B virus (HBV) infection seek to suppress viral replication by blocking HBV reverse transcription. When circulating HBV viremia is suppressed, clinical outcomes improve, with slowing of fibrosis and reduced rates of hepatocellular carcinoma. However, when treatment is discontinued, viral replication typically rebounds. This is because nucleos(t)ide (NUC) therapy has no effect on existing HBV cccDNA (covalently closed circular DNA) reservoirs.

A functional cure is defined as the absence of HBV DNA and hepatitis B surface antigen (HBsAg), in the absence of antiviral therapy, with or without the development of protective hepatitis B surface antibody (HBsAb). However, rates of viral clearance are extremely low after therapy with IFN and NUC analogs. Strategies to control HBV replication, purge covalently closed circular DNA (cccDNA) reservoirs, and develop long-lasting protective immunity in patients with chronic HBV infection are desperately needed to achieve a functional cure.

Current investigational approaches to curing HBV fall into two different strategies: targeting the virus directly or manipulating the host immune response to aid in clearance.

Targeting the virus

One of the challenges of treating HBV is the stability of HBV DNA inside infected hepatocytes; supercoiled and sequestered in the host cell nucleus, HBV cccDNA is protected from cellular DNA-sensing machinery. Hepatocytes infected with HBV have a long half-life, serving as a reservoir for HBV reactivation. In addition to preventing, inactivating, or disrupting cccDNA, investigational approaches to target the virus also focus on blocking specific steps in viral replication, including viral transcription, entry into uninfected hepatocytes, capsid assembly, and antigen secretion.

Gene therapy approaches, including zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), clustered regularly interspaced palindromic repeat (CRISP-R) applications, and RNA interference (RNAi) technology may be able to inactivate target cccDNA, silencing or disrupting this viral reservoir.

Various investigational drugs are being studied for their ability to interfere with viral entry, encapsidation, or antigen release. Specific interactions between viral membrane proteins and cellular receptors are attractive targets for blocking HBV entry into host cells. Agents that interfere with assembly of the virus particle may prevent the production of infectious virus. Some innovative therapeutic strategies also seek to block the secretion of HBsAg; chronic exposure to HBsAg can lead to T-cell exhaustion, so this strategy may allow the host to develop a more effective anti-HBV adaptive immune response.

Manipulating host response

The second major strategy of novel HBV therapies involves mediating the host response, reversing immune exhaustion, selectively activating innate and/or adaptive immunity through therapeutic vaccination or passive transfer in order to produce a more effective response that results in viral clearance.

The innate immune response, the first line of defense against viral infections, is activated when toll-like receptors (TLRs) on the surface of innate immune cells are engaged, but TLR signaling is downregulated in chronic HBV infection. Stimulating innate immune cells by activating TLRs may accelerate HBV-specific immune reconstitution and help clear HBV in chronically infected individuals. Likewise, blocking the interaction of PD-1 with its ligands (PD-L1/2) may improve the antiviral function of exhausted T cells.

Reversing immune exhaustion will not work if there are no HBV-specific T cells present. Studies have pointed to the clonal deletion of HBV-specific CD8+ T cells as a mechanism of HBV persistence. T-cell responses may be “trained” to recognize infected cells by expressing HBV-specific chimeric antigen receptors (CARs), which are synthetic engineered receptors that can engage cell-surface molecules.

Therapeutic vaccination additionally presents a promising strategy to address HBV-specific T-cell exhaustion by inducing a potent CD4 T-cell response and counteracting immune tolerance against HBV antigens. Yeast-based vaccines, adenovirus vector and engineered vesicular stomatitis virus vectors have shown to be promising platforms that may be capable of eliciting a functional adaptive immune response in patients with chronic HBV, but their use is often limited by preexisting host immunity.

In summary, current therapies for HBV rarely clear or cure infection. A two-pronged approach of targeting viral and host factors may offer the best chance to reverse the immune tolerance, T-cell exhaustion, and persistent viral reservoir associated with chronic HBV infection.

Rebecca Lee is a second-year medical student at the University of Maryland School of Medicine. Eleanor Wilson, MD, is assistant professor in the Institute of Human Virology at the University of Maryland School of Medicine. Shyam Kottilil, MBBS, PhD, is professor of medicine in the Institute of Human Virology at the University of Maryland School of Medicine.

Current treatment strategies for chronic hepatitis B virus (HBV) infection seek to suppress viral replication by blocking HBV reverse transcription. When circulating HBV viremia is suppressed, clinical outcomes improve, with slowing of fibrosis and reduced rates of hepatocellular carcinoma. However, when treatment is discontinued, viral replication typically rebounds. This is because nucleos(t)ide (NUC) therapy has no effect on existing HBV cccDNA (covalently closed circular DNA) reservoirs.

A functional cure is defined as the absence of HBV DNA and hepatitis B surface antigen (HBsAg), in the absence of antiviral therapy, with or without the development of protective hepatitis B surface antibody (HBsAb). However, rates of viral clearance are extremely low after therapy with IFN and NUC analogs. Strategies to control HBV replication, purge covalently closed circular DNA (cccDNA) reservoirs, and develop long-lasting protective immunity in patients with chronic HBV infection are desperately needed to achieve a functional cure.

Current investigational approaches to curing HBV fall into two different strategies: targeting the virus directly or manipulating the host immune response to aid in clearance.

Targeting the virus

One of the challenges of treating HBV is the stability of HBV DNA inside infected hepatocytes; supercoiled and sequestered in the host cell nucleus, HBV cccDNA is protected from cellular DNA-sensing machinery. Hepatocytes infected with HBV have a long half-life, serving as a reservoir for HBV reactivation. In addition to preventing, inactivating, or disrupting cccDNA, investigational approaches to target the virus also focus on blocking specific steps in viral replication, including viral transcription, entry into uninfected hepatocytes, capsid assembly, and antigen secretion.

Gene therapy approaches, including zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), clustered regularly interspaced palindromic repeat (CRISP-R) applications, and RNA interference (RNAi) technology may be able to inactivate target cccDNA, silencing or disrupting this viral reservoir.

Various investigational drugs are being studied for their ability to interfere with viral entry, encapsidation, or antigen release. Specific interactions between viral membrane proteins and cellular receptors are attractive targets for blocking HBV entry into host cells. Agents that interfere with assembly of the virus particle may prevent the production of infectious virus. Some innovative therapeutic strategies also seek to block the secretion of HBsAg; chronic exposure to HBsAg can lead to T-cell exhaustion, so this strategy may allow the host to develop a more effective anti-HBV adaptive immune response.

Manipulating host response

The second major strategy of novel HBV therapies involves mediating the host response, reversing immune exhaustion, selectively activating innate and/or adaptive immunity through therapeutic vaccination or passive transfer in order to produce a more effective response that results in viral clearance.

The innate immune response, the first line of defense against viral infections, is activated when toll-like receptors (TLRs) on the surface of innate immune cells are engaged, but TLR signaling is downregulated in chronic HBV infection. Stimulating innate immune cells by activating TLRs may accelerate HBV-specific immune reconstitution and help clear HBV in chronically infected individuals. Likewise, blocking the interaction of PD-1 with its ligands (PD-L1/2) may improve the antiviral function of exhausted T cells.

Reversing immune exhaustion will not work if there are no HBV-specific T cells present. Studies have pointed to the clonal deletion of HBV-specific CD8+ T cells as a mechanism of HBV persistence. T-cell responses may be “trained” to recognize infected cells by expressing HBV-specific chimeric antigen receptors (CARs), which are synthetic engineered receptors that can engage cell-surface molecules.

Therapeutic vaccination additionally presents a promising strategy to address HBV-specific T-cell exhaustion by inducing a potent CD4 T-cell response and counteracting immune tolerance against HBV antigens. Yeast-based vaccines, adenovirus vector and engineered vesicular stomatitis virus vectors have shown to be promising platforms that may be capable of eliciting a functional adaptive immune response in patients with chronic HBV, but their use is often limited by preexisting host immunity.

In summary, current therapies for HBV rarely clear or cure infection. A two-pronged approach of targeting viral and host factors may offer the best chance to reverse the immune tolerance, T-cell exhaustion, and persistent viral reservoir associated with chronic HBV infection.

Rebecca Lee is a second-year medical student at the University of Maryland School of Medicine. Eleanor Wilson, MD, is assistant professor in the Institute of Human Virology at the University of Maryland School of Medicine. Shyam Kottilil, MBBS, PhD, is professor of medicine in the Institute of Human Virology at the University of Maryland School of Medicine.

Current treatment strategies for chronic hepatitis B virus (HBV) infection seek to suppress viral replication by blocking HBV reverse transcription. When circulating HBV viremia is suppressed, clinical outcomes improve, with slowing of fibrosis and reduced rates of hepatocellular carcinoma. However, when treatment is discontinued, viral replication typically rebounds. This is because nucleos(t)ide (NUC) therapy has no effect on existing HBV cccDNA (covalently closed circular DNA) reservoirs.

A functional cure is defined as the absence of HBV DNA and hepatitis B surface antigen (HBsAg), in the absence of antiviral therapy, with or without the development of protective hepatitis B surface antibody (HBsAb). However, rates of viral clearance are extremely low after therapy with IFN and NUC analogs. Strategies to control HBV replication, purge covalently closed circular DNA (cccDNA) reservoirs, and develop long-lasting protective immunity in patients with chronic HBV infection are desperately needed to achieve a functional cure.

Current investigational approaches to curing HBV fall into two different strategies: targeting the virus directly or manipulating the host immune response to aid in clearance.

Targeting the virus

One of the challenges of treating HBV is the stability of HBV DNA inside infected hepatocytes; supercoiled and sequestered in the host cell nucleus, HBV cccDNA is protected from cellular DNA-sensing machinery. Hepatocytes infected with HBV have a long half-life, serving as a reservoir for HBV reactivation. In addition to preventing, inactivating, or disrupting cccDNA, investigational approaches to target the virus also focus on blocking specific steps in viral replication, including viral transcription, entry into uninfected hepatocytes, capsid assembly, and antigen secretion.

Gene therapy approaches, including zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), clustered regularly interspaced palindromic repeat (CRISP-R) applications, and RNA interference (RNAi) technology may be able to inactivate target cccDNA, silencing or disrupting this viral reservoir.

Various investigational drugs are being studied for their ability to interfere with viral entry, encapsidation, or antigen release. Specific interactions between viral membrane proteins and cellular receptors are attractive targets for blocking HBV entry into host cells. Agents that interfere with assembly of the virus particle may prevent the production of infectious virus. Some innovative therapeutic strategies also seek to block the secretion of HBsAg; chronic exposure to HBsAg can lead to T-cell exhaustion, so this strategy may allow the host to develop a more effective anti-HBV adaptive immune response.

Manipulating host response

The second major strategy of novel HBV therapies involves mediating the host response, reversing immune exhaustion, selectively activating innate and/or adaptive immunity through therapeutic vaccination or passive transfer in order to produce a more effective response that results in viral clearance.

The innate immune response, the first line of defense against viral infections, is activated when toll-like receptors (TLRs) on the surface of innate immune cells are engaged, but TLR signaling is downregulated in chronic HBV infection. Stimulating innate immune cells by activating TLRs may accelerate HBV-specific immune reconstitution and help clear HBV in chronically infected individuals. Likewise, blocking the interaction of PD-1 with its ligands (PD-L1/2) may improve the antiviral function of exhausted T cells.

Reversing immune exhaustion will not work if there are no HBV-specific T cells present. Studies have pointed to the clonal deletion of HBV-specific CD8+ T cells as a mechanism of HBV persistence. T-cell responses may be “trained” to recognize infected cells by expressing HBV-specific chimeric antigen receptors (CARs), which are synthetic engineered receptors that can engage cell-surface molecules.

Therapeutic vaccination additionally presents a promising strategy to address HBV-specific T-cell exhaustion by inducing a potent CD4 T-cell response and counteracting immune tolerance against HBV antigens. Yeast-based vaccines, adenovirus vector and engineered vesicular stomatitis virus vectors have shown to be promising platforms that may be capable of eliciting a functional adaptive immune response in patients with chronic HBV, but their use is often limited by preexisting host immunity.

In summary, current therapies for HBV rarely clear or cure infection. A two-pronged approach of targeting viral and host factors may offer the best chance to reverse the immune tolerance, T-cell exhaustion, and persistent viral reservoir associated with chronic HBV infection.

Rebecca Lee is a second-year medical student at the University of Maryland School of Medicine. Eleanor Wilson, MD, is assistant professor in the Institute of Human Virology at the University of Maryland School of Medicine. Shyam Kottilil, MBBS, PhD, is professor of medicine in the Institute of Human Virology at the University of Maryland School of Medicine.

Nanoparticles (green) help

form clots in injured liver

Image courtesy of Erin Lavik

PHILADELPHIA—Researchers say they have developed nanoparticles that can congregate at sites of injury and speed blood clotting in vitro and in vivo.

The nanoparticles are designed to bind with activated platelets and help them join together to form clots faster.

The nanoparticles have helped stop bleeding and improved animals’ survival in different models of injury, without producing off-target clotting.

“When you have uncontrolled internal bleeding, that’s when these particles could really make a difference,” said Erin B. Lavik, ScD, of the University of Maryland, Baltimore County (UMBC) in Baltimore, Maryland.

“Compared to injuries that aren’t treated with the nanoparticles, we can cut bleeding time in half and reduce total blood loss.”

Dr Lavik discussed this work at the 252nd National Meeting & Exposition of the American Chemical Society.

She and her colleagues have been testing different versions of these nanoparticles for years. They previously reported results with the particles in 2012 and 2014.

The current nanoparticles are made from polylactic acid or polylactic co-glycolic acid. Dr Lavik said that by using the 2 different materials, the researchers can change the temperature at which the nanoparticles melt. Thus far, the team has developed nanoparticles that are stable up to 50° C (122° F).

The nanoparticles have an outer coating of polyethylene glycol and an attached peptide—RGD—that enables them to bind to natural platelets. Dr Lavik said the researchers chose RGD because platelets have receptors for that peptide, it’s ubiquitous in the body, and it wouldn’t alter the chemistry of the nanoparticles.

The researchers have tested the nanoparticles in a femoral injury model, a liver injury model, and blast injury model. The team has also started testing in models of brain and spinal cord injury, but the results are “very preliminary,” according to Dr Lavik.

In the femoral injury model, the nanoparticles halved bleeding time when compared to no treatment. In both the liver injury model and the blast injury model, the nanoparticles stopped bleeding and improved survival.

Dr Lavik said these experiments have shown that the nanoparticles successfully speed clotting, and the clots formed are mechanically robust.

The nanoparticles also clear the body easily. When the particles are bound into a clot, they stay as long as the clot remains. They begin to degrade once the clot does and clear out of the bloodstream quickly.

Dr Lavik said the researchers haven’t seen non-specific clotting with the nanoparticles yet. However, this side effect remains a possibility because the particles are designed to bind to activated platelets, which may not be confined to the site of injury.

One unfortunate side effect occurred with an earlier version of the nanoparticles. They triggered an immune response, activating complement in pig’s blood. However, the researchers were able to modify the particles to reduce complement activation and the accompanying complications.

In future studies, Dr Lavik and her colleagues plan to test whether the new nanoparticles activate complement in human blood. The team also aims to verify that the nanoparticles don’t cause non-specific clotting.

Nanoparticles (green) help

form clots in injured liver

Image courtesy of Erin Lavik

PHILADELPHIA—Researchers say they have developed nanoparticles that can congregate at sites of injury and speed blood clotting in vitro and in vivo.

The nanoparticles are designed to bind with activated platelets and help them join together to form clots faster.

The nanoparticles have helped stop bleeding and improved animals’ survival in different models of injury, without producing off-target clotting.

“When you have uncontrolled internal bleeding, that’s when these particles could really make a difference,” said Erin B. Lavik, ScD, of the University of Maryland, Baltimore County (UMBC) in Baltimore, Maryland.

“Compared to injuries that aren’t treated with the nanoparticles, we can cut bleeding time in half and reduce total blood loss.”

Dr Lavik discussed this work at the 252nd National Meeting & Exposition of the American Chemical Society.

She and her colleagues have been testing different versions of these nanoparticles for years. They previously reported results with the particles in 2012 and 2014.

The current nanoparticles are made from polylactic acid or polylactic co-glycolic acid. Dr Lavik said that by using the 2 different materials, the researchers can change the temperature at which the nanoparticles melt. Thus far, the team has developed nanoparticles that are stable up to 50° C (122° F).

The nanoparticles have an outer coating of polyethylene glycol and an attached peptide—RGD—that enables them to bind to natural platelets. Dr Lavik said the researchers chose RGD because platelets have receptors for that peptide, it’s ubiquitous in the body, and it wouldn’t alter the chemistry of the nanoparticles.

The researchers have tested the nanoparticles in a femoral injury model, a liver injury model, and blast injury model. The team has also started testing in models of brain and spinal cord injury, but the results are “very preliminary,” according to Dr Lavik.

In the femoral injury model, the nanoparticles halved bleeding time when compared to no treatment. In both the liver injury model and the blast injury model, the nanoparticles stopped bleeding and improved survival.

Dr Lavik said these experiments have shown that the nanoparticles successfully speed clotting, and the clots formed are mechanically robust.

The nanoparticles also clear the body easily. When the particles are bound into a clot, they stay as long as the clot remains. They begin to degrade once the clot does and clear out of the bloodstream quickly.

Dr Lavik said the researchers haven’t seen non-specific clotting with the nanoparticles yet. However, this side effect remains a possibility because the particles are designed to bind to activated platelets, which may not be confined to the site of injury.

One unfortunate side effect occurred with an earlier version of the nanoparticles. They triggered an immune response, activating complement in pig’s blood. However, the researchers were able to modify the particles to reduce complement activation and the accompanying complications.

In future studies, Dr Lavik and her colleagues plan to test whether the new nanoparticles activate complement in human blood. The team also aims to verify that the nanoparticles don’t cause non-specific clotting.

Nanoparticles (green) help

form clots in injured liver

Image courtesy of Erin Lavik

PHILADELPHIA—Researchers say they have developed nanoparticles that can congregate at sites of injury and speed blood clotting in vitro and in vivo.

The nanoparticles are designed to bind with activated platelets and help them join together to form clots faster.

The nanoparticles have helped stop bleeding and improved animals’ survival in different models of injury, without producing off-target clotting.

“When you have uncontrolled internal bleeding, that’s when these particles could really make a difference,” said Erin B. Lavik, ScD, of the University of Maryland, Baltimore County (UMBC) in Baltimore, Maryland.

“Compared to injuries that aren’t treated with the nanoparticles, we can cut bleeding time in half and reduce total blood loss.”

Dr Lavik discussed this work at the 252nd National Meeting & Exposition of the American Chemical Society.

She and her colleagues have been testing different versions of these nanoparticles for years. They previously reported results with the particles in 2012 and 2014.

The current nanoparticles are made from polylactic acid or polylactic co-glycolic acid. Dr Lavik said that by using the 2 different materials, the researchers can change the temperature at which the nanoparticles melt. Thus far, the team has developed nanoparticles that are stable up to 50° C (122° F).

The nanoparticles have an outer coating of polyethylene glycol and an attached peptide—RGD—that enables them to bind to natural platelets. Dr Lavik said the researchers chose RGD because platelets have receptors for that peptide, it’s ubiquitous in the body, and it wouldn’t alter the chemistry of the nanoparticles.

The researchers have tested the nanoparticles in a femoral injury model, a liver injury model, and blast injury model. The team has also started testing in models of brain and spinal cord injury, but the results are “very preliminary,” according to Dr Lavik.

In the femoral injury model, the nanoparticles halved bleeding time when compared to no treatment. In both the liver injury model and the blast injury model, the nanoparticles stopped bleeding and improved survival.

Dr Lavik said these experiments have shown that the nanoparticles successfully speed clotting, and the clots formed are mechanically robust.

The nanoparticles also clear the body easily. When the particles are bound into a clot, they stay as long as the clot remains. They begin to degrade once the clot does and clear out of the bloodstream quickly.

Dr Lavik said the researchers haven’t seen non-specific clotting with the nanoparticles yet. However, this side effect remains a possibility because the particles are designed to bind to activated platelets, which may not be confined to the site of injury.

One unfortunate side effect occurred with an earlier version of the nanoparticles. They triggered an immune response, activating complement in pig’s blood. However, the researchers were able to modify the particles to reduce complement activation and the accompanying complications.

In future studies, Dr Lavik and her colleagues plan to test whether the new nanoparticles activate complement in human blood. The team also aims to verify that the nanoparticles don’t cause non-specific clotting.

In early 2014, I decided to use the six state licenses I had obtained as a locum tenens physician to start practicing telemedicine. Since then, I have worked with several telemedicine platforms. I have found that telemedicine companies differ dramatically in their overall ease of use for the provider. Here are my top tips for deciding which telemedicine company to work with.

1. Technology support: Telemedicine is dependent on technology. If it is difficult to get help from tech support, do not credential with the company. Tech support is your lifeline to your patients. Make sure you can get help right away if you are having problems finishing or starting a consult. Companies that send automatic emails saying they will get back to you within 24 hours are the most difficult to work with.
2. Nursing support: All of the telemedicine companies that I have worked with have amazing nurses, but some are overwhelmed with work. Telemedicine nurses are able to connect to your patients via direct callback numbers in a way that you cannot connect. They are able to call in prescriptions to pharmacies if the platform is down or if the patient put in the wrong pharmacy information. Make sure that the company has a nurse that is able to call you back right away. A few telemedicine companies are understaffed with nurses, and it can take hours for a callback. If the key to telemedicine is volume, this is frustrating to deal with.
3. Chief complaints: Many telemedicine companies are moving away from making the “chief complaint” visible to providers before choosing to take the consult. For me, this is a big red flag. It can be as simple as, “I have a cold.” I like this because if I see a patient who says, “I have abdominal pain,” I know to triage them first.
4. Volume: Telemedicine is great for staying connected to outpatient medicine. If you are looking to work on a telemedicine platform for your main source of income, then volume is key. A lot of telemedicine companies will tell you how many calls they get per day; the key question is how many calls they get for the states that you are licensed in and how many providers they have licensed in those states. If you want higher volume, then ask if they will pay for your license in states with higher needs (some will). If you are willing to pay to be licensed in additional states, make sure the volume is high enough to make that extra out-of-pocket cost worth it.
5. Malpractice coverage: Many companies provide malpractice coverage as part of their credentialing package. If they do not, make sure your malpractice coverage covers you for telemedicine.
6. Documentation: Documentation during your telemedicine consult is arguably even more important than in an outpatient visit. Everything is on the phone or by video, so make sure, in the subjective area, that you are quoting what the patient is telling you. You are not able to do a physical exam, so your recommendations will be based on what the patient is saying.

Have fun! Telemedicine has been really enjoyable for me. I like being able to have the time to educate my patients about things like antibiotics. I enjoy the technological aspects and understanding all of the different platforms. Telemedicine gives you a unique opportunity to practice your skills from the comfort of your own home. TH

In early 2014, I decided to use the six state licenses I had obtained as a locum tenens physician to start practicing telemedicine. Since then, I have worked with several telemedicine platforms. I have found that telemedicine companies differ dramatically in their overall ease of use for the provider. Here are my top tips for deciding which telemedicine company to work with.

1. Technology support: Telemedicine is dependent on technology. If it is difficult to get help from tech support, do not credential with the company. Tech support is your lifeline to your patients. Make sure you can get help right away if you are having problems finishing or starting a consult. Companies that send automatic emails saying they will get back to you within 24 hours are the most difficult to work with.
2. Nursing support: All of the telemedicine companies that I have worked with have amazing nurses, but some are overwhelmed with work. Telemedicine nurses are able to connect to your patients via direct callback numbers in a way that you cannot connect. They are able to call in prescriptions to pharmacies if the platform is down or if the patient put in the wrong pharmacy information. Make sure that the company has a nurse that is able to call you back right away. A few telemedicine companies are understaffed with nurses, and it can take hours for a callback. If the key to telemedicine is volume, this is frustrating to deal with.
3. Chief complaints: Many telemedicine companies are moving away from making the “chief complaint” visible to providers before choosing to take the consult. For me, this is a big red flag. It can be as simple as, “I have a cold.” I like this because if I see a patient who says, “I have abdominal pain,” I know to triage them first.
4. Volume: Telemedicine is great for staying connected to outpatient medicine. If you are looking to work on a telemedicine platform for your main source of income, then volume is key. A lot of telemedicine companies will tell you how many calls they get per day; the key question is how many calls they get for the states that you are licensed in and how many providers they have licensed in those states. If you want higher volume, then ask if they will pay for your license in states with higher needs (some will). If you are willing to pay to be licensed in additional states, make sure the volume is high enough to make that extra out-of-pocket cost worth it.
5. Malpractice coverage: Many companies provide malpractice coverage as part of their credentialing package. If they do not, make sure your malpractice coverage covers you for telemedicine.
6. Documentation: Documentation during your telemedicine consult is arguably even more important than in an outpatient visit. Everything is on the phone or by video, so make sure, in the subjective area, that you are quoting what the patient is telling you. You are not able to do a physical exam, so your recommendations will be based on what the patient is saying.

Have fun! Telemedicine has been really enjoyable for me. I like being able to have the time to educate my patients about things like antibiotics. I enjoy the technological aspects and understanding all of the different platforms. Telemedicine gives you a unique opportunity to practice your skills from the comfort of your own home. TH

In early 2014, I decided to use the six state licenses I had obtained as a locum tenens physician to start practicing telemedicine. Since then, I have worked with several telemedicine platforms. I have found that telemedicine companies differ dramatically in their overall ease of use for the provider. Here are my top tips for deciding which telemedicine company to work with.

1. Technology support: Telemedicine is dependent on technology. If it is difficult to get help from tech support, do not credential with the company. Tech support is your lifeline to your patients. Make sure you can get help right away if you are having problems finishing or starting a consult. Companies that send automatic emails saying they will get back to you within 24 hours are the most difficult to work with.
2. Nursing support: All of the telemedicine companies that I have worked with have amazing nurses, but some are overwhelmed with work. Telemedicine nurses are able to connect to your patients via direct callback numbers in a way that you cannot connect. They are able to call in prescriptions to pharmacies if the platform is down or if the patient put in the wrong pharmacy information. Make sure that the company has a nurse that is able to call you back right away. A few telemedicine companies are understaffed with nurses, and it can take hours for a callback. If the key to telemedicine is volume, this is frustrating to deal with.
3. Chief complaints: Many telemedicine companies are moving away from making the “chief complaint” visible to providers before choosing to take the consult. For me, this is a big red flag. It can be as simple as, “I have a cold.” I like this because if I see a patient who says, “I have abdominal pain,” I know to triage them first.
4. Volume: Telemedicine is great for staying connected to outpatient medicine. If you are looking to work on a telemedicine platform for your main source of income, then volume is key. A lot of telemedicine companies will tell you how many calls they get per day; the key question is how many calls they get for the states that you are licensed in and how many providers they have licensed in those states. If you want higher volume, then ask if they will pay for your license in states with higher needs (some will). If you are willing to pay to be licensed in additional states, make sure the volume is high enough to make that extra out-of-pocket cost worth it.
5. Malpractice coverage: Many companies provide malpractice coverage as part of their credentialing package. If they do not, make sure your malpractice coverage covers you for telemedicine.
6. Documentation: Documentation during your telemedicine consult is arguably even more important than in an outpatient visit. Everything is on the phone or by video, so make sure, in the subjective area, that you are quoting what the patient is telling you. You are not able to do a physical exam, so your recommendations will be based on what the patient is saying.

Have fun! Telemedicine has been really enjoyable for me. I like being able to have the time to educate my patients about things like antibiotics. I enjoy the technological aspects and understanding all of the different platforms. Telemedicine gives you a unique opportunity to practice your skills from the comfort of your own home. TH

Massage therapy class

Photo courtesy of Barbara

E. Carver/New York College

of Health Professions

Massage therapy can reduce pain, fatigue, and anxiety in cancer patients, according to a review and meta-analysis published in Pain Medicine.

Massage therapy is commonly used among people seeking pain management, and research has generally supported its use.

However, there has been no published, rigorous review of the available research and evidence for massage therapy’s efficacy for pain populations, especially for cancer populations.

So Courtney Boyd, of the Samueli Institute in Alexandria, Virginia, and her colleagues set out to conduct just such a review.

The team assessed the quality of massage therapy research and evidence for its efficacy in treating pain, function-related quality of life, and health-related quality of life in cancer patients.

The researchers reviewed data from 12 high-quality studies and 4 low-quality studies.

The team said they could not assess health-related quality of life, emotional stress, or activity outcomes because too few of the studies examined these outcomes.

However, the data suggested that massage therapy can effectively reduce pain intensity or severity when compared to no treatment (standardized mean difference [SMD]=-0.20) or active comparators (SMD=-0.55).

Massage therapy also proved effective for reducing fatigue (SMD=-1.06) and anxiety (SMD=-1.24) when compared to active comparators.

Based on these results, the researchers concluded that massage therapy may have beneficial effects in cancer patients, so they should consider it as an option.

However, before definitive clinical conclusions and recommendations can be made at a policy level, specific factors surrounding the massage protocol, as well as selection of appropriate controls and standard outcomes, need to be well-understood.

Massage therapy class

Photo courtesy of Barbara

E. Carver/New York College

of Health Professions

Massage therapy can reduce pain, fatigue, and anxiety in cancer patients, according to a review and meta-analysis published in Pain Medicine.

Massage therapy is commonly used among people seeking pain management, and research has generally supported its use.

However, there has been no published, rigorous review of the available research and evidence for massage therapy’s efficacy for pain populations, especially for cancer populations.

So Courtney Boyd, of the Samueli Institute in Alexandria, Virginia, and her colleagues set out to conduct just such a review.

The team assessed the quality of massage therapy research and evidence for its efficacy in treating pain, function-related quality of life, and health-related quality of life in cancer patients.

The researchers reviewed data from 12 high-quality studies and 4 low-quality studies.

The team said they could not assess health-related quality of life, emotional stress, or activity outcomes because too few of the studies examined these outcomes.

However, the data suggested that massage therapy can effectively reduce pain intensity or severity when compared to no treatment (standardized mean difference [SMD]=-0.20) or active comparators (SMD=-0.55).

Massage therapy also proved effective for reducing fatigue (SMD=-1.06) and anxiety (SMD=-1.24) when compared to active comparators.

Based on these results, the researchers concluded that massage therapy may have beneficial effects in cancer patients, so they should consider it as an option.

However, before definitive clinical conclusions and recommendations can be made at a policy level, specific factors surrounding the massage protocol, as well as selection of appropriate controls and standard outcomes, need to be well-understood.

Massage therapy class

Photo courtesy of Barbara

E. Carver/New York College

of Health Professions

Massage therapy can reduce pain, fatigue, and anxiety in cancer patients, according to a review and meta-analysis published in Pain Medicine.

Massage therapy is commonly used among people seeking pain management, and research has generally supported its use.

However, there has been no published, rigorous review of the available research and evidence for massage therapy’s efficacy for pain populations, especially for cancer populations.

So Courtney Boyd, of the Samueli Institute in Alexandria, Virginia, and her colleagues set out to conduct just such a review.

The team assessed the quality of massage therapy research and evidence for its efficacy in treating pain, function-related quality of life, and health-related quality of life in cancer patients.

The researchers reviewed data from 12 high-quality studies and 4 low-quality studies.

The team said they could not assess health-related quality of life, emotional stress, or activity outcomes because too few of the studies examined these outcomes.

However, the data suggested that massage therapy can effectively reduce pain intensity or severity when compared to no treatment (standardized mean difference [SMD]=-0.20) or active comparators (SMD=-0.55).

Massage therapy also proved effective for reducing fatigue (SMD=-1.06) and anxiety (SMD=-1.24) when compared to active comparators.

Based on these results, the researchers concluded that massage therapy may have beneficial effects in cancer patients, so they should consider it as an option.

However, before definitive clinical conclusions and recommendations can be made at a policy level, specific factors surrounding the massage protocol, as well as selection of appropriate controls and standard outcomes, need to be well-understood.

Dendritic cells in skin

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for SL-401 in the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN).

SL-401 is a targeted therapy directed to the interleukin-3 receptor (IL-3R), which is present in BPDCN and other hematologic malignancies.

SL-401 is composed of human IL-3 coupled to a truncated diphtheria toxin payload that inhibits protein synthesis.

The drug is under development by Stemline Therapeutics, Inc.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Phase 2 trial of SL-401

The breakthrough designation for SL-401 was supported by data from a phase 2 trial of patients with BPDCN or acute myeloid leukemia. Results observed in the BPDCN patients were presented at the 2016 EHA Congress (abstract S812).

The study consists of a lead-in dose-escalation stage (stage 1) and subsequent expansion stage (stage 2). In stage 1, patients received SL-401 as a daily intravenous infusion for up to 5 days (7, 9, 12, or 16 μg/kg/day) every 21 days. In stage 2, patients received SL-401 at the optimal stage 1 dose—12 μg/kg.

At the data cut-off, 18 BPDCN patients had received SL-401 at 7 μg/kg (n=3, stage 1) or 12 μg/kg (n=15, 6 in stage 1, 9 in stage 2).

Fifteen of these patients were evaluable for response. The overall response rate was 87% (13/15). All 10 previously untreated BPDCN patients achieved a response, including 7 complete responses (CRs).

All 8 previously untreated BPDCN patients treated at the optimal dose (12 μg/kg) achieved a response, including 6 CRs. Four of these patients were still on SL-401 and in CR at the data cutoff, and 2 had gone on to stem cell transplant.

The most common treatment-related adverse events in the BPDCN patients were transient transaminase elevation (57%), hypoalbuminemia (40%), and transient thrombocytopenia (15%).

In stage 1, two patients had capillary leak syndrome (CLS)—one grade 5 (7 μg/kg) and one grade 4 (12 μg/kg). After this, safety precautions were implemented to minimize the risk of severe CLS. There have been no cases of severe CLS since then.

Dendritic cells in skin

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for SL-401 in the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN).

SL-401 is a targeted therapy directed to the interleukin-3 receptor (IL-3R), which is present in BPDCN and other hematologic malignancies.

SL-401 is composed of human IL-3 coupled to a truncated diphtheria toxin payload that inhibits protein synthesis.

The drug is under development by Stemline Therapeutics, Inc.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Phase 2 trial of SL-401

The breakthrough designation for SL-401 was supported by data from a phase 2 trial of patients with BPDCN or acute myeloid leukemia. Results observed in the BPDCN patients were presented at the 2016 EHA Congress (abstract S812).

The study consists of a lead-in dose-escalation stage (stage 1) and subsequent expansion stage (stage 2). In stage 1, patients received SL-401 as a daily intravenous infusion for up to 5 days (7, 9, 12, or 16 μg/kg/day) every 21 days. In stage 2, patients received SL-401 at the optimal stage 1 dose—12 μg/kg.

At the data cut-off, 18 BPDCN patients had received SL-401 at 7 μg/kg (n=3, stage 1) or 12 μg/kg (n=15, 6 in stage 1, 9 in stage 2).

Fifteen of these patients were evaluable for response. The overall response rate was 87% (13/15). All 10 previously untreated BPDCN patients achieved a response, including 7 complete responses (CRs).

All 8 previously untreated BPDCN patients treated at the optimal dose (12 μg/kg) achieved a response, including 6 CRs. Four of these patients were still on SL-401 and in CR at the data cutoff, and 2 had gone on to stem cell transplant.

The most common treatment-related adverse events in the BPDCN patients were transient transaminase elevation (57%), hypoalbuminemia (40%), and transient thrombocytopenia (15%).

In stage 1, two patients had capillary leak syndrome (CLS)—one grade 5 (7 μg/kg) and one grade 4 (12 μg/kg). After this, safety precautions were implemented to minimize the risk of severe CLS. There have been no cases of severe CLS since then.

Dendritic cells in skin

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for SL-401 in the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN).

SL-401 is a targeted therapy directed to the interleukin-3 receptor (IL-3R), which is present in BPDCN and other hematologic malignancies.

SL-401 is composed of human IL-3 coupled to a truncated diphtheria toxin payload that inhibits protein synthesis.

The drug is under development by Stemline Therapeutics, Inc.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Phase 2 trial of SL-401

The breakthrough designation for SL-401 was supported by data from a phase 2 trial of patients with BPDCN or acute myeloid leukemia. Results observed in the BPDCN patients were presented at the 2016 EHA Congress (abstract S812).

The study consists of a lead-in dose-escalation stage (stage 1) and subsequent expansion stage (stage 2). In stage 1, patients received SL-401 as a daily intravenous infusion for up to 5 days (7, 9, 12, or 16 μg/kg/day) every 21 days. In stage 2, patients received SL-401 at the optimal stage 1 dose—12 μg/kg.

At the data cut-off, 18 BPDCN patients had received SL-401 at 7 μg/kg (n=3, stage 1) or 12 μg/kg (n=15, 6 in stage 1, 9 in stage 2).

Fifteen of these patients were evaluable for response. The overall response rate was 87% (13/15). All 10 previously untreated BPDCN patients achieved a response, including 7 complete responses (CRs).

All 8 previously untreated BPDCN patients treated at the optimal dose (12 μg/kg) achieved a response, including 6 CRs. Four of these patients were still on SL-401 and in CR at the data cutoff, and 2 had gone on to stem cell transplant.

The most common treatment-related adverse events in the BPDCN patients were transient transaminase elevation (57%), hypoalbuminemia (40%), and transient thrombocytopenia (15%).

In stage 1, two patients had capillary leak syndrome (CLS)—one grade 5 (7 μg/kg) and one grade 4 (12 μg/kg). After this, safety precautions were implemented to minimize the risk of severe CLS. There have been no cases of severe CLS since then.

Prescription medications

Photo courtesy of the CDC

High prescription drug prices in the US have a few causes, according to researchers.

They said causes include the approach the US has taken to granting government-protected monopolies to drug manufacturers, strategies that delay access to generic drugs, and the restriction of price negotiation at a level not observed in other industrialized nations.

The researchers outlined these issues in JAMA.

Aaron S. Kesselheim, MD, of Brigham and Women’s Hospital in Boston, Massachusetts, and his colleagues conducted this research.

The team reviewed the medical and health policy literature from January 2005 to July 2016, looking for articles addressing the sources of drug prices in the US, the justifications and consequences of high prices, and possible solutions.

The researchers found that per-capita prescription drug spending is higher in the US than in all other countries. In 2013, per-capita spending on prescription drugs was $858 in the US, compared with an average of $400 for 19 other industrialized nations.

Dr Kesselheim and his colleagues said prescription drug spending in the US is largely driven by brand-name drug prices that have been increasing in recent years. And drug prices are higher in the US because the US healthcare system allows manufacturers to set their own price for a given product.

In countries with national health insurance systems, on the other hand, a delegated body negotiates drug prices or rejects coverage of products if the price demanded by the manufacturer is excessive in light of the benefit provided. Manufacturers may then decide to offer the drug at a lower price.

The researchers said the most important factor that allows US manufacturers to set high drug prices is market exclusivity. And although cheaper generic drugs can be made available after an exclusivity period has passed, there are strategies for keeping these drugs off the market.

Furthermore, the negotiating power of the payer is constrained by several factors, including the requirement that most government drug payment plans cover nearly all products.

Considering these findings together, Dr Kesselheim and his colleagues said the most realistic short-term strategies to address high drug prices in the US include:

• Enforcing more stringent requirements for market exclusivity rights
• Ensuring timely generic drug availability
• Providing greater opportunities for price negotiation by governmental payers
• Generating more evidence about comparative cost-effectiveness of therapeutic alternatives
• Educating patients, prescribers, payers, and policy makers about these choices.

The researchers said there is little evidence that such policies would hamper innovation. In fact, they might even drive the development of more valuable new therapies rather than rewarding the persistence of older ones.

Prescription medications

Photo courtesy of the CDC

High prescription drug prices in the US have a few causes, according to researchers.

They said causes include the approach the US has taken to granting government-protected monopolies to drug manufacturers, strategies that delay access to generic drugs, and the restriction of price negotiation at a level not observed in other industrialized nations.

The researchers outlined these issues in JAMA.

Aaron S. Kesselheim, MD, of Brigham and Women’s Hospital in Boston, Massachusetts, and his colleagues conducted this research.

The team reviewed the medical and health policy literature from January 2005 to July 2016, looking for articles addressing the sources of drug prices in the US, the justifications and consequences of high prices, and possible solutions.

The researchers found that per-capita prescription drug spending is higher in the US than in all other countries. In 2013, per-capita spending on prescription drugs was $858 in the US, compared with an average of $400 for 19 other industrialized nations.

Dr Kesselheim and his colleagues said prescription drug spending in the US is largely driven by brand-name drug prices that have been increasing in recent years. And drug prices are higher in the US because the US healthcare system allows manufacturers to set their own price for a given product.

In countries with national health insurance systems, on the other hand, a delegated body negotiates drug prices or rejects coverage of products if the price demanded by the manufacturer is excessive in light of the benefit provided. Manufacturers may then decide to offer the drug at a lower price.

The researchers said the most important factor that allows US manufacturers to set high drug prices is market exclusivity. And although cheaper generic drugs can be made available after an exclusivity period has passed, there are strategies for keeping these drugs off the market.

Furthermore, the negotiating power of the payer is constrained by several factors, including the requirement that most government drug payment plans cover nearly all products.

Considering these findings together, Dr Kesselheim and his colleagues said the most realistic short-term strategies to address high drug prices in the US include:

• Enforcing more stringent requirements for market exclusivity rights
• Ensuring timely generic drug availability
• Providing greater opportunities for price negotiation by governmental payers
• Generating more evidence about comparative cost-effectiveness of therapeutic alternatives
• Educating patients, prescribers, payers, and policy makers about these choices.

The researchers said there is little evidence that such policies would hamper innovation. In fact, they might even drive the development of more valuable new therapies rather than rewarding the persistence of older ones.

Prescription medications

Photo courtesy of the CDC

High prescription drug prices in the US have a few causes, according to researchers.

They said causes include the approach the US has taken to granting government-protected monopolies to drug manufacturers, strategies that delay access to generic drugs, and the restriction of price negotiation at a level not observed in other industrialized nations.

The researchers outlined these issues in JAMA.

Aaron S. Kesselheim, MD, of Brigham and Women’s Hospital in Boston, Massachusetts, and his colleagues conducted this research.

The team reviewed the medical and health policy literature from January 2005 to July 2016, looking for articles addressing the sources of drug prices in the US, the justifications and consequences of high prices, and possible solutions.

The researchers found that per-capita prescription drug spending is higher in the US than in all other countries. In 2013, per-capita spending on prescription drugs was $858 in the US, compared with an average of $400 for 19 other industrialized nations.

Dr Kesselheim and his colleagues said prescription drug spending in the US is largely driven by brand-name drug prices that have been increasing in recent years. And drug prices are higher in the US because the US healthcare system allows manufacturers to set their own price for a given product.

In countries with national health insurance systems, on the other hand, a delegated body negotiates drug prices or rejects coverage of products if the price demanded by the manufacturer is excessive in light of the benefit provided. Manufacturers may then decide to offer the drug at a lower price.

The researchers said the most important factor that allows US manufacturers to set high drug prices is market exclusivity. And although cheaper generic drugs can be made available after an exclusivity period has passed, there are strategies for keeping these drugs off the market.

Furthermore, the negotiating power of the payer is constrained by several factors, including the requirement that most government drug payment plans cover nearly all products.

Considering these findings together, Dr Kesselheim and his colleagues said the most realistic short-term strategies to address high drug prices in the US include:

• Enforcing more stringent requirements for market exclusivity rights
• Ensuring timely generic drug availability
• Providing greater opportunities for price negotiation by governmental payers
• Generating more evidence about comparative cost-effectiveness of therapeutic alternatives
• Educating patients, prescribers, payers, and policy makers about these choices.

The researchers said there is little evidence that such policies would hamper innovation. In fact, they might even drive the development of more valuable new therapies rather than rewarding the persistence of older ones.

ANSWERThe correct interpretation includes sinus rhythm with blocked premature atrial complexes, left-axis deviation, and serial changes of an evolving anterior MI.

The presence of a P wave without a QRS between the third and fourth QRS complex represents a blocked premature atrial complex. The fifth QRS complex also indicates a premature atrial complex; however, it is not blocked.

Left-axis deviation is evidenced by the R axis of –82°. The loss of an R wave in V₁, the poor R-wave progression in V₂ and V₃, and the ST-T wave changes are all consistent with an evolving anterior MI.

ANSWERThe correct interpretation includes sinus rhythm with blocked premature atrial complexes, left-axis deviation, and serial changes of an evolving anterior MI.

The presence of a P wave without a QRS between the third and fourth QRS complex represents a blocked premature atrial complex. The fifth QRS complex also indicates a premature atrial complex; however, it is not blocked.

Left-axis deviation is evidenced by the R axis of –82°. The loss of an R wave in V₁, the poor R-wave progression in V₂ and V₃, and the ST-T wave changes are all consistent with an evolving anterior MI.

ANSWERThe correct interpretation includes sinus rhythm with blocked premature atrial complexes, left-axis deviation, and serial changes of an evolving anterior MI.

The presence of a P wave without a QRS between the third and fourth QRS complex represents a blocked premature atrial complex. The fifth QRS complex also indicates a premature atrial complex; however, it is not blocked.

Left-axis deviation is evidenced by the R axis of –82°. The loss of an R wave in V₁, the poor R-wave progression in V₂ and V₃, and the ST-T wave changes are all consistent with an evolving anterior MI.

ANSWER
The correct answer is impetigo (choice “a”). Impetigo is almost always secondary to another condition, such as contact or irritant dermatitis, eczema, or dry skin.

DISCUSSION
Impetigo is a superficial bacterial infection usually caused by a combination of strep and staph organisms. It requires a break in the skin to provide a point of entry for the organisms. In young children, scratching and picking at eczema, along with lip licking, exacerbate the barrier-breaching process.

The organisms that cause impetigo are typically benign, but this was not always the case. Prior to WWI, certain strains of strep were capable of triggering an immune response that resulted in kidney damage. These “nephritogenic” strains of the Streptococcus family caused acute post-streptococcal glomerulonephritis (Bright disease), which, at that time, killed thousands each year. Fortunately, these strains are rare now.

In the pre-antibiotic days, when the average person bathed once a week, impetigo was highly contagious and serious enough that whole households were quarantined because of it.

Today, impetigo, once diagnosed, is relatively simple to manage. Mild cases can be treated with application of mupirocin ointment or cream three times a day. In this particular case, a 10-day course of an oral antibiotic (trimethoprim sulfa) was added, and the rash rapidly cleared.

ANSWER
The correct answer is impetigo (choice “a”). Impetigo is almost always secondary to another condition, such as contact or irritant dermatitis, eczema, or dry skin.

DISCUSSION
Impetigo is a superficial bacterial infection usually caused by a combination of strep and staph organisms. It requires a break in the skin to provide a point of entry for the organisms. In young children, scratching and picking at eczema, along with lip licking, exacerbate the barrier-breaching process.

The organisms that cause impetigo are typically benign, but this was not always the case. Prior to WWI, certain strains of strep were capable of triggering an immune response that resulted in kidney damage. These “nephritogenic” strains of the Streptococcus family caused acute post-streptococcal glomerulonephritis (Bright disease), which, at that time, killed thousands each year. Fortunately, these strains are rare now.

In the pre-antibiotic days, when the average person bathed once a week, impetigo was highly contagious and serious enough that whole households were quarantined because of it.

Today, impetigo, once diagnosed, is relatively simple to manage. Mild cases can be treated with application of mupirocin ointment or cream three times a day. In this particular case, a 10-day course of an oral antibiotic (trimethoprim sulfa) was added, and the rash rapidly cleared.

ANSWER
The correct answer is impetigo (choice “a”). Impetigo is almost always secondary to another condition, such as contact or irritant dermatitis, eczema, or dry skin.

DISCUSSION
Impetigo is a superficial bacterial infection usually caused by a combination of strep and staph organisms. It requires a break in the skin to provide a point of entry for the organisms. In young children, scratching and picking at eczema, along with lip licking, exacerbate the barrier-breaching process.

The organisms that cause impetigo are typically benign, but this was not always the case. Prior to WWI, certain strains of strep were capable of triggering an immune response that resulted in kidney damage. These “nephritogenic” strains of the Streptococcus family caused acute post-streptococcal glomerulonephritis (Bright disease), which, at that time, killed thousands each year. Fortunately, these strains are rare now.

In the pre-antibiotic days, when the average person bathed once a week, impetigo was highly contagious and serious enough that whole households were quarantined because of it.

Today, impetigo, once diagnosed, is relatively simple to manage. Mild cases can be treated with application of mupirocin ointment or cream three times a day. In this particular case, a 10-day course of an oral antibiotic (trimethoprim sulfa) was added, and the rash rapidly cleared.