An elevated rate of autism traits was seen among a cohort of children exposed to antiepileptic drugs (AEDs) in utero. Study findings were reported in the July Epilepsia. “The most important determinant of association with autistic traits was higher doses of sodium valproate exposure,” said Amanda G. Wood, PhD, MPsych, a Senior Lecturer in the School of Psychology at the University of Birmingham in the United Kingdom.

While the use of valproate in women who may become pregnant is generally avoided, there are insufficient data regarding the risk of autism spectrum disorders with low-dose valproate. “If this risk is no greater than with other AEDs, it may enable women with genetic generalized epilepsy to retain optimal seizure control as well as minimize harm to their unborn child,” Dr. Wood said.

Dr. Wood and colleagues conducted a prospective cohort study in children exposed to anticonvulsants during pregnancy, with all assessments conducted by examiners who were blinded to drug-exposure status. Participants were 105 Australian children ages 6 to 8 who were recruited through the Australian Pregnancy Register for Women on Antiepileptic Medication. Maternal epilepsy, pregnancy, and medical history data were obtained prospectively. Autism traits were assessed using the Childhood Autism Rating Scale (CARS).

Among the cohort, 11 children (10.5%) had elevated CARS scores, and this proportion was substantially higher than the estimated prevalence of autism spectrum disorders in age-matched children nationally or internationally. Linear regression analysis showed that the mean valproate dose during pregnancy was a significant predictor of CARS scores after controlling for polytherapy, mean carbamazepine dose, folic acid use, seizures during pregnancy, tobacco and marijuana use, maternal IQ, and socioeconomic status.

Children who had in utero exposure to valproate were most likely to have elevated CARS scores, with 7.7% of the valproate monotherapy group and 46.7% of the valproate polytherapy group displaying autism spectrum disorder symptoms. The dose of valproate taken during pregnancy was found to be an independent risk factor for elevated CARS scores, whereas polytherapy was not. “CARS scores were not elevated in children exposed to polytherapy without valproate, suggesting that valproate, or valproate dose, rather than polytherapy per se, is the critical determinant of the relationship,” the researchers said.

—Glenn S. Williams

An elevated rate of autism traits was seen among a cohort of children exposed to antiepileptic drugs (AEDs) in utero. Study findings were reported in the July Epilepsia. “The most important determinant of association with autistic traits was higher doses of sodium valproate exposure,” said Amanda G. Wood, PhD, MPsych, a Senior Lecturer in the School of Psychology at the University of Birmingham in the United Kingdom.

While the use of valproate in women who may become pregnant is generally avoided, there are insufficient data regarding the risk of autism spectrum disorders with low-dose valproate. “If this risk is no greater than with other AEDs, it may enable women with genetic generalized epilepsy to retain optimal seizure control as well as minimize harm to their unborn child,” Dr. Wood said.

Dr. Wood and colleagues conducted a prospective cohort study in children exposed to anticonvulsants during pregnancy, with all assessments conducted by examiners who were blinded to drug-exposure status. Participants were 105 Australian children ages 6 to 8 who were recruited through the Australian Pregnancy Register for Women on Antiepileptic Medication. Maternal epilepsy, pregnancy, and medical history data were obtained prospectively. Autism traits were assessed using the Childhood Autism Rating Scale (CARS).

Among the cohort, 11 children (10.5%) had elevated CARS scores, and this proportion was substantially higher than the estimated prevalence of autism spectrum disorders in age-matched children nationally or internationally. Linear regression analysis showed that the mean valproate dose during pregnancy was a significant predictor of CARS scores after controlling for polytherapy, mean carbamazepine dose, folic acid use, seizures during pregnancy, tobacco and marijuana use, maternal IQ, and socioeconomic status.

Children who had in utero exposure to valproate were most likely to have elevated CARS scores, with 7.7% of the valproate monotherapy group and 46.7% of the valproate polytherapy group displaying autism spectrum disorder symptoms. The dose of valproate taken during pregnancy was found to be an independent risk factor for elevated CARS scores, whereas polytherapy was not. “CARS scores were not elevated in children exposed to polytherapy without valproate, suggesting that valproate, or valproate dose, rather than polytherapy per se, is the critical determinant of the relationship,” the researchers said.

—Glenn S. Williams

An elevated rate of autism traits was seen among a cohort of children exposed to antiepileptic drugs (AEDs) in utero. Study findings were reported in the July Epilepsia. “The most important determinant of association with autistic traits was higher doses of sodium valproate exposure,” said Amanda G. Wood, PhD, MPsych, a Senior Lecturer in the School of Psychology at the University of Birmingham in the United Kingdom.

While the use of valproate in women who may become pregnant is generally avoided, there are insufficient data regarding the risk of autism spectrum disorders with low-dose valproate. “If this risk is no greater than with other AEDs, it may enable women with genetic generalized epilepsy to retain optimal seizure control as well as minimize harm to their unborn child,” Dr. Wood said.

Dr. Wood and colleagues conducted a prospective cohort study in children exposed to anticonvulsants during pregnancy, with all assessments conducted by examiners who were blinded to drug-exposure status. Participants were 105 Australian children ages 6 to 8 who were recruited through the Australian Pregnancy Register for Women on Antiepileptic Medication. Maternal epilepsy, pregnancy, and medical history data were obtained prospectively. Autism traits were assessed using the Childhood Autism Rating Scale (CARS).

Among the cohort, 11 children (10.5%) had elevated CARS scores, and this proportion was substantially higher than the estimated prevalence of autism spectrum disorders in age-matched children nationally or internationally. Linear regression analysis showed that the mean valproate dose during pregnancy was a significant predictor of CARS scores after controlling for polytherapy, mean carbamazepine dose, folic acid use, seizures during pregnancy, tobacco and marijuana use, maternal IQ, and socioeconomic status.

Children who had in utero exposure to valproate were most likely to have elevated CARS scores, with 7.7% of the valproate monotherapy group and 46.7% of the valproate polytherapy group displaying autism spectrum disorder symptoms. The dose of valproate taken during pregnancy was found to be an independent risk factor for elevated CARS scores, whereas polytherapy was not. “CARS scores were not elevated in children exposed to polytherapy without valproate, suggesting that valproate, or valproate dose, rather than polytherapy per se, is the critical determinant of the relationship,” the researchers said.

—Glenn S. Williams

Platelets (blue) in a thrombus

Image by Andre E.X. Brown

Preclinical research appears to explain how the body can quickly replenish platelets that are lost during infection.

Investigators discovered an “emergency backup system” in mice that bypasses the known pathway of hematopoietic stem cell (HSC) differentiation so that platelet numbers can be restored rapidly.

Marieke Essers, PhD, of The German Cancer Research Center (Deutsches Krebsforschungszentrum) in Heidelberg, Germany, and her colleagues described this phenomenon in Cell Stem Cell.

The team discovered a small cell population within the HSC compartment that induces differentiation in megakaryocytes.

These quiescent stem cells—dubbed stem-like megakaryocyte-committed progenitors (SL-MkPs)—do not provide the normal supply of platelets but serve as a backup in case of emergency.

When quiescent, SL-MkPs express few proteins. In the event of an acute infection, SL-MkPs are aroused from their quiescent state by interferon α, express the typical megakaryocyte proteins, and are rapidly differentiated into advanced precursor cells.

This quickly replaces the platelets that were lost as a result of the infection.

This emergency backup system bypasses the lengthy process of normal HSC differentiation, thereby ensuring that any life-threatening loss of platelets is compensated for quickly.

However, the investigators found that repeat infections can result in the reservoir of SL-MkPs being depleted.

Platelets (blue) in a thrombus

Image by Andre E.X. Brown

Preclinical research appears to explain how the body can quickly replenish platelets that are lost during infection.

Investigators discovered an “emergency backup system” in mice that bypasses the known pathway of hematopoietic stem cell (HSC) differentiation so that platelet numbers can be restored rapidly.

Marieke Essers, PhD, of The German Cancer Research Center (Deutsches Krebsforschungszentrum) in Heidelberg, Germany, and her colleagues described this phenomenon in Cell Stem Cell.

The team discovered a small cell population within the HSC compartment that induces differentiation in megakaryocytes.

These quiescent stem cells—dubbed stem-like megakaryocyte-committed progenitors (SL-MkPs)—do not provide the normal supply of platelets but serve as a backup in case of emergency.

When quiescent, SL-MkPs express few proteins. In the event of an acute infection, SL-MkPs are aroused from their quiescent state by interferon α, express the typical megakaryocyte proteins, and are rapidly differentiated into advanced precursor cells.

This quickly replaces the platelets that were lost as a result of the infection.

This emergency backup system bypasses the lengthy process of normal HSC differentiation, thereby ensuring that any life-threatening loss of platelets is compensated for quickly.

However, the investigators found that repeat infections can result in the reservoir of SL-MkPs being depleted.

Platelets (blue) in a thrombus

Image by Andre E.X. Brown

Preclinical research appears to explain how the body can quickly replenish platelets that are lost during infection.

Investigators discovered an “emergency backup system” in mice that bypasses the known pathway of hematopoietic stem cell (HSC) differentiation so that platelet numbers can be restored rapidly.

Marieke Essers, PhD, of The German Cancer Research Center (Deutsches Krebsforschungszentrum) in Heidelberg, Germany, and her colleagues described this phenomenon in Cell Stem Cell.

The team discovered a small cell population within the HSC compartment that induces differentiation in megakaryocytes.

These quiescent stem cells—dubbed stem-like megakaryocyte-committed progenitors (SL-MkPs)—do not provide the normal supply of platelets but serve as a backup in case of emergency.

When quiescent, SL-MkPs express few proteins. In the event of an acute infection, SL-MkPs are aroused from their quiescent state by interferon α, express the typical megakaryocyte proteins, and are rapidly differentiated into advanced precursor cells.

This quickly replaces the platelets that were lost as a result of the infection.

This emergency backup system bypasses the lengthy process of normal HSC differentiation, thereby ensuring that any life-threatening loss of platelets is compensated for quickly.

However, the investigators found that repeat infections can result in the reservoir of SL-MkPs being depleted.

Syrian hamster

Using an animal model they developed, researchers have identified a pathway that inhibits replication of the adenovirus.

The team generated a new strain of Syrian hamster, a model in which human adenovirus replicates and causes illness similar to that observed in humans.

Experiments with this model suggested the Type I interferon pathway plays a key role in inhibiting adenovirus replication.

“[L]ike many other viruses, adenovirus can replicate at will when a patient’s immune system is suppressed,” said William Wold, PhD, of Saint Louis University in Missouri.

“Adenovirus can become very dangerous, such as for a child who is undergoing a bone marrow transplant to treat leukemia.”

Previously, Dr Wold led a research team that identified the Syrian hamster as an appropriate animal model to study adenovirus because species C human adenoviruses replicate in these animals.

For the current study, which was published in PLOS Pathogens, Dr Wold and his colleagues conducted experiments with a new Syrian hamster strain. In these animals, the STAT2 gene was functionally knocked out by site-specific gene targeting.

The researchers found that STAT2-knockout hamsters were extremely sensitive to infection with type 5 human adenovirus (Ad5).

The team infected both STAT2-knockout hamsters and wild-type controls with Ad5. Knockout hamsters had 100 to 1000 times the viral load of controls.

The knockout hamsters also had pathology characteristic of advanced adenovirus infection—yellow, mottled livers and enlarged gall bladders—whereas controls did not.

The adaptive immune response to Ad5 remained intact in the STAT2-knockout hamsters, as surviving animals were able to clear the virus.

However, the Type 1 interferon response was hampered in these animals. Knocking out STAT2 disrupted the Type 1 interferon pathway by interrupting the cascade of cell signaling.

The researchers said their findings suggest the disrupted Type I interferon pathway contributed to the increased Ad5 replication in the STAT2-knockout hamsters.

“Besides providing an insight into adenovirus infection in humans, our results are also interesting from the perspective of the animal model,” Dr Wold said. “The STAT2-knockout Syrian hamster may also be an important animal model for studying other viral infections, including Ebola, hanta, and dengue viruses.”

The model was created by Zhongde Wang, PhD, and his colleagues at Utah State University in Logan, Utah. Dr Wang’s lab is the first to develop gene-targeting technologies in the Syrian hamster.

“The success we achieved in conducting gene-targeting in the Syrian hamster has provided the opportunity to create models for many of the human diseases for which there are either no existent animal models or severe limitations in the available animal models,” Dr Wang said.

Syrian hamster

Using an animal model they developed, researchers have identified a pathway that inhibits replication of the adenovirus.

The team generated a new strain of Syrian hamster, a model in which human adenovirus replicates and causes illness similar to that observed in humans.

Experiments with this model suggested the Type I interferon pathway plays a key role in inhibiting adenovirus replication.

“[L]ike many other viruses, adenovirus can replicate at will when a patient’s immune system is suppressed,” said William Wold, PhD, of Saint Louis University in Missouri.

“Adenovirus can become very dangerous, such as for a child who is undergoing a bone marrow transplant to treat leukemia.”

Previously, Dr Wold led a research team that identified the Syrian hamster as an appropriate animal model to study adenovirus because species C human adenoviruses replicate in these animals.

For the current study, which was published in PLOS Pathogens, Dr Wold and his colleagues conducted experiments with a new Syrian hamster strain. In these animals, the STAT2 gene was functionally knocked out by site-specific gene targeting.

The researchers found that STAT2-knockout hamsters were extremely sensitive to infection with type 5 human adenovirus (Ad5).

The team infected both STAT2-knockout hamsters and wild-type controls with Ad5. Knockout hamsters had 100 to 1000 times the viral load of controls.

The knockout hamsters also had pathology characteristic of advanced adenovirus infection—yellow, mottled livers and enlarged gall bladders—whereas controls did not.

The adaptive immune response to Ad5 remained intact in the STAT2-knockout hamsters, as surviving animals were able to clear the virus.

However, the Type 1 interferon response was hampered in these animals. Knocking out STAT2 disrupted the Type 1 interferon pathway by interrupting the cascade of cell signaling.

The researchers said their findings suggest the disrupted Type I interferon pathway contributed to the increased Ad5 replication in the STAT2-knockout hamsters.

“Besides providing an insight into adenovirus infection in humans, our results are also interesting from the perspective of the animal model,” Dr Wold said. “The STAT2-knockout Syrian hamster may also be an important animal model for studying other viral infections, including Ebola, hanta, and dengue viruses.”

The model was created by Zhongde Wang, PhD, and his colleagues at Utah State University in Logan, Utah. Dr Wang’s lab is the first to develop gene-targeting technologies in the Syrian hamster.

“The success we achieved in conducting gene-targeting in the Syrian hamster has provided the opportunity to create models for many of the human diseases for which there are either no existent animal models or severe limitations in the available animal models,” Dr Wang said.

Syrian hamster

Using an animal model they developed, researchers have identified a pathway that inhibits replication of the adenovirus.

The team generated a new strain of Syrian hamster, a model in which human adenovirus replicates and causes illness similar to that observed in humans.

Experiments with this model suggested the Type I interferon pathway plays a key role in inhibiting adenovirus replication.

“[L]ike many other viruses, adenovirus can replicate at will when a patient’s immune system is suppressed,” said William Wold, PhD, of Saint Louis University in Missouri.

“Adenovirus can become very dangerous, such as for a child who is undergoing a bone marrow transplant to treat leukemia.”

Previously, Dr Wold led a research team that identified the Syrian hamster as an appropriate animal model to study adenovirus because species C human adenoviruses replicate in these animals.

For the current study, which was published in PLOS Pathogens, Dr Wold and his colleagues conducted experiments with a new Syrian hamster strain. In these animals, the STAT2 gene was functionally knocked out by site-specific gene targeting.

The researchers found that STAT2-knockout hamsters were extremely sensitive to infection with type 5 human adenovirus (Ad5).

The team infected both STAT2-knockout hamsters and wild-type controls with Ad5. Knockout hamsters had 100 to 1000 times the viral load of controls.

The knockout hamsters also had pathology characteristic of advanced adenovirus infection—yellow, mottled livers and enlarged gall bladders—whereas controls did not.

The adaptive immune response to Ad5 remained intact in the STAT2-knockout hamsters, as surviving animals were able to clear the virus.

However, the Type 1 interferon response was hampered in these animals. Knocking out STAT2 disrupted the Type 1 interferon pathway by interrupting the cascade of cell signaling.

The researchers said their findings suggest the disrupted Type I interferon pathway contributed to the increased Ad5 replication in the STAT2-knockout hamsters.

“Besides providing an insight into adenovirus infection in humans, our results are also interesting from the perspective of the animal model,” Dr Wold said. “The STAT2-knockout Syrian hamster may also be an important animal model for studying other viral infections, including Ebola, hanta, and dengue viruses.”

The model was created by Zhongde Wang, PhD, and his colleagues at Utah State University in Logan, Utah. Dr Wang’s lab is the first to develop gene-targeting technologies in the Syrian hamster.

“The success we achieved in conducting gene-targeting in the Syrian hamster has provided the opportunity to create models for many of the human diseases for which there are either no existent animal models or severe limitations in the available animal models,” Dr Wang said.

Treatment with high doses of antimetabolites followed by rituximab plus high-dose sequential chemoimmunotherapy and autologous stem-cell transplantation was feasible and effective in a multicenter phase II study of 38 patients with aggressive B-cell lymphoma and secondary central nervous system involvement.

The patients, aged 18 to 70 years with Eastern Cooperative Oncology Group performance status of 3 or less at enrollment, were treated with high doses of methotrexate and cytarabine, followed by rituximab plus high-dose sequential chemoimmunotherapy (R-HDS) consisting of cylcophosphamide, cytarabine, and etoposide supported by autologous stem-cell transplantation in eligible patients.

Courtesy Wikimedia Commons/Nephron/ Creative Commons License

Toxicity was typically manageable, but 30 treatment courses were complicated by grade 3 or 4 febrile neutropenia and/or infections; 4 patients died because of toxicity, Dr. Andres J. M. Ferreri of San Raffaele Scientific Institute, Milan, Italy and colleagues reported online Aug. 17 in the Journal of Clinical Oncology.

The complete response rate was 63% (24 patients), and 17 patients remained relapse free at a median follow-up of 48 months, with a 2-year event-free survival rate of 50%, and a 5-year survival rate of 41%, the investigators said (J Clin Oncol. 2015 Aug 17. doi: 10.1200/JCO.2015.61.1236).

This novel radiotherapy-free regimen, developed based on encouraging outcomes with antimetabolites in patients with primary CNS lymphoma and with R-HDS in relapsed aggressive lymphoma, appears safe and effective in the setting of secondary CNS lymphoma (SCNSL).

“We propose this strategy as the standard of care for patients with SCNSL and as a comparison control regimen for future trials,” they concluded.

Dr. Ferreri reported having no disclosures. One co-author, Dr. Federico Caligaris-Cappio, reported serving in a consulting or advisory role for Janssen and Pharmacyclics.

[email protected]

Treatment with high doses of antimetabolites followed by rituximab plus high-dose sequential chemoimmunotherapy and autologous stem-cell transplantation was feasible and effective in a multicenter phase II study of 38 patients with aggressive B-cell lymphoma and secondary central nervous system involvement.

The patients, aged 18 to 70 years with Eastern Cooperative Oncology Group performance status of 3 or less at enrollment, were treated with high doses of methotrexate and cytarabine, followed by rituximab plus high-dose sequential chemoimmunotherapy (R-HDS) consisting of cylcophosphamide, cytarabine, and etoposide supported by autologous stem-cell transplantation in eligible patients.

Courtesy Wikimedia Commons/Nephron/ Creative Commons License

Toxicity was typically manageable, but 30 treatment courses were complicated by grade 3 or 4 febrile neutropenia and/or infections; 4 patients died because of toxicity, Dr. Andres J. M. Ferreri of San Raffaele Scientific Institute, Milan, Italy and colleagues reported online Aug. 17 in the Journal of Clinical Oncology.

The complete response rate was 63% (24 patients), and 17 patients remained relapse free at a median follow-up of 48 months, with a 2-year event-free survival rate of 50%, and a 5-year survival rate of 41%, the investigators said (J Clin Oncol. 2015 Aug 17. doi: 10.1200/JCO.2015.61.1236).

This novel radiotherapy-free regimen, developed based on encouraging outcomes with antimetabolites in patients with primary CNS lymphoma and with R-HDS in relapsed aggressive lymphoma, appears safe and effective in the setting of secondary CNS lymphoma (SCNSL).

“We propose this strategy as the standard of care for patients with SCNSL and as a comparison control regimen for future trials,” they concluded.

Dr. Ferreri reported having no disclosures. One co-author, Dr. Federico Caligaris-Cappio, reported serving in a consulting or advisory role for Janssen and Pharmacyclics.

[email protected]

Treatment with high doses of antimetabolites followed by rituximab plus high-dose sequential chemoimmunotherapy and autologous stem-cell transplantation was feasible and effective in a multicenter phase II study of 38 patients with aggressive B-cell lymphoma and secondary central nervous system involvement.

The patients, aged 18 to 70 years with Eastern Cooperative Oncology Group performance status of 3 or less at enrollment, were treated with high doses of methotrexate and cytarabine, followed by rituximab plus high-dose sequential chemoimmunotherapy (R-HDS) consisting of cylcophosphamide, cytarabine, and etoposide supported by autologous stem-cell transplantation in eligible patients.

Courtesy Wikimedia Commons/Nephron/ Creative Commons License

Toxicity was typically manageable, but 30 treatment courses were complicated by grade 3 or 4 febrile neutropenia and/or infections; 4 patients died because of toxicity, Dr. Andres J. M. Ferreri of San Raffaele Scientific Institute, Milan, Italy and colleagues reported online Aug. 17 in the Journal of Clinical Oncology.

The complete response rate was 63% (24 patients), and 17 patients remained relapse free at a median follow-up of 48 months, with a 2-year event-free survival rate of 50%, and a 5-year survival rate of 41%, the investigators said (J Clin Oncol. 2015 Aug 17. doi: 10.1200/JCO.2015.61.1236).

This novel radiotherapy-free regimen, developed based on encouraging outcomes with antimetabolites in patients with primary CNS lymphoma and with R-HDS in relapsed aggressive lymphoma, appears safe and effective in the setting of secondary CNS lymphoma (SCNSL).

“We propose this strategy as the standard of care for patients with SCNSL and as a comparison control regimen for future trials,” they concluded.

Dr. Ferreri reported having no disclosures. One co-author, Dr. Federico Caligaris-Cappio, reported serving in a consulting or advisory role for Janssen and Pharmacyclics.

[email protected]

Blood sample collection

Photo by Juan D. Alfonso

A new study indicates that coagulation tests are an unreliable means for measuring the risk of internal bleeding in patients taking the factor Xa inhibitors rivaroxaban and apixaban.

For most patients who experienced internal bleeding in this study, results of coagulation tests were normal.

Prothrombin time (PT), partial thromboplastin time (PTT), and international normalized ratios (INRs) were elevated in a minority of patients treated with rivaroxaban and none of the patients treated with apixaban.

Henry Spiller, of the Central Ohio Poison Center at Nationwide Children’s Hospital in Columbus, Ohio, and his colleagues conducted this retrospective study and reported the results in Annals of Emergency Medicine.

The study included data on 223 patients from more than 800 hospitals and 8 regional poison centers covering 9 states. The patients’ mean age was 60, and 56% were female. Nine percent of patients (n=20) were children younger than 12.

Eighty-nine percent of patients had taken rivaroxaban (n=198), and 11% had taken apixaban (n=25). The mean dose of rivaroxaban (reported in 182 patients) was 64.5 mg (range, 15 mg to 1200 mg). And the mean dose of apixaban (reported in 21 patients) was 9.6 mg (range, 2.5 mg to 20 mg).

For rivaroxaban, PT was measured in 49 patients (25%) and elevated in 7. PTT was measured in 49 patients (25%) and elevated in 5. And INR was measured in 61 patients (31%) and elevated in 13.

For apixaban, PT and PTT were both measured in 6 patients (24%) and elevated in none. INR was measured in 5 patients (20%) and elevated in none.

Cases of bleeding

Bleeding was reported in 15 patients (7%)—11 on rivaroxaban and 4 on apixaban. The sites of bleeding were gastrointestinal (n=8), oral (n=2), nose (n=1), bruising (n=1), urine (n=1), and subdural (n=1).

All bleeds occurred in adults who were taking the anticoagulants long-term. Twelve bleeds were considered adverse drug reactions, 2 were therapeutic error, and the reason was unknown in 1 case.

Coagulation test results were normal in most patients with bleeding. PT and PTT were both normal in 5 of 6 patients tested (83%), and INR was normal in 5 of 9 patients tested (55%).

PT and PTT were elevated in 1 of 4 patients treated with rivaroxaban and none of the patients treated with apixaban. The INR was elevated in 5 of 8 patients treated with rivaroxaban and none of the patients treated with apixaban.

The researchers said these results suggest that, without specific clarification of methodology and reagent use, PT, PTT, and INR may not reliably predict the risk of bleeding after rivaroxaban or apixaban ingestion.

“One way to overcome the variation in these tests is to use anti-factor Xa chromogenic assays to measure Xa plasma concentrations,” Spiller said.

“However, these are not widely available, and a potential drawback with measuring anti-factor Xa concentrations and plasma rivaroxaban and apixaban concentrations is that the turnaround time for results may be too long to guide a treatment plan.”

Blood sample collection

Photo by Juan D. Alfonso

A new study indicates that coagulation tests are an unreliable means for measuring the risk of internal bleeding in patients taking the factor Xa inhibitors rivaroxaban and apixaban.

For most patients who experienced internal bleeding in this study, results of coagulation tests were normal.

Prothrombin time (PT), partial thromboplastin time (PTT), and international normalized ratios (INRs) were elevated in a minority of patients treated with rivaroxaban and none of the patients treated with apixaban.

Henry Spiller, of the Central Ohio Poison Center at Nationwide Children’s Hospital in Columbus, Ohio, and his colleagues conducted this retrospective study and reported the results in Annals of Emergency Medicine.

The study included data on 223 patients from more than 800 hospitals and 8 regional poison centers covering 9 states. The patients’ mean age was 60, and 56% were female. Nine percent of patients (n=20) were children younger than 12.

Eighty-nine percent of patients had taken rivaroxaban (n=198), and 11% had taken apixaban (n=25). The mean dose of rivaroxaban (reported in 182 patients) was 64.5 mg (range, 15 mg to 1200 mg). And the mean dose of apixaban (reported in 21 patients) was 9.6 mg (range, 2.5 mg to 20 mg).

For rivaroxaban, PT was measured in 49 patients (25%) and elevated in 7. PTT was measured in 49 patients (25%) and elevated in 5. And INR was measured in 61 patients (31%) and elevated in 13.

For apixaban, PT and PTT were both measured in 6 patients (24%) and elevated in none. INR was measured in 5 patients (20%) and elevated in none.

Cases of bleeding

Bleeding was reported in 15 patients (7%)—11 on rivaroxaban and 4 on apixaban. The sites of bleeding were gastrointestinal (n=8), oral (n=2), nose (n=1), bruising (n=1), urine (n=1), and subdural (n=1).

All bleeds occurred in adults who were taking the anticoagulants long-term. Twelve bleeds were considered adverse drug reactions, 2 were therapeutic error, and the reason was unknown in 1 case.

Coagulation test results were normal in most patients with bleeding. PT and PTT were both normal in 5 of 6 patients tested (83%), and INR was normal in 5 of 9 patients tested (55%).

PT and PTT were elevated in 1 of 4 patients treated with rivaroxaban and none of the patients treated with apixaban. The INR was elevated in 5 of 8 patients treated with rivaroxaban and none of the patients treated with apixaban.

The researchers said these results suggest that, without specific clarification of methodology and reagent use, PT, PTT, and INR may not reliably predict the risk of bleeding after rivaroxaban or apixaban ingestion.

“One way to overcome the variation in these tests is to use anti-factor Xa chromogenic assays to measure Xa plasma concentrations,” Spiller said.

“However, these are not widely available, and a potential drawback with measuring anti-factor Xa concentrations and plasma rivaroxaban and apixaban concentrations is that the turnaround time for results may be too long to guide a treatment plan.”

Blood sample collection

Photo by Juan D. Alfonso

A new study indicates that coagulation tests are an unreliable means for measuring the risk of internal bleeding in patients taking the factor Xa inhibitors rivaroxaban and apixaban.

For most patients who experienced internal bleeding in this study, results of coagulation tests were normal.

Prothrombin time (PT), partial thromboplastin time (PTT), and international normalized ratios (INRs) were elevated in a minority of patients treated with rivaroxaban and none of the patients treated with apixaban.

Henry Spiller, of the Central Ohio Poison Center at Nationwide Children’s Hospital in Columbus, Ohio, and his colleagues conducted this retrospective study and reported the results in Annals of Emergency Medicine.

The study included data on 223 patients from more than 800 hospitals and 8 regional poison centers covering 9 states. The patients’ mean age was 60, and 56% were female. Nine percent of patients (n=20) were children younger than 12.

Eighty-nine percent of patients had taken rivaroxaban (n=198), and 11% had taken apixaban (n=25). The mean dose of rivaroxaban (reported in 182 patients) was 64.5 mg (range, 15 mg to 1200 mg). And the mean dose of apixaban (reported in 21 patients) was 9.6 mg (range, 2.5 mg to 20 mg).

For rivaroxaban, PT was measured in 49 patients (25%) and elevated in 7. PTT was measured in 49 patients (25%) and elevated in 5. And INR was measured in 61 patients (31%) and elevated in 13.

For apixaban, PT and PTT were both measured in 6 patients (24%) and elevated in none. INR was measured in 5 patients (20%) and elevated in none.

Cases of bleeding

Bleeding was reported in 15 patients (7%)—11 on rivaroxaban and 4 on apixaban. The sites of bleeding were gastrointestinal (n=8), oral (n=2), nose (n=1), bruising (n=1), urine (n=1), and subdural (n=1).

All bleeds occurred in adults who were taking the anticoagulants long-term. Twelve bleeds were considered adverse drug reactions, 2 were therapeutic error, and the reason was unknown in 1 case.

Coagulation test results were normal in most patients with bleeding. PT and PTT were both normal in 5 of 6 patients tested (83%), and INR was normal in 5 of 9 patients tested (55%).

PT and PTT were elevated in 1 of 4 patients treated with rivaroxaban and none of the patients treated with apixaban. The INR was elevated in 5 of 8 patients treated with rivaroxaban and none of the patients treated with apixaban.

The researchers said these results suggest that, without specific clarification of methodology and reagent use, PT, PTT, and INR may not reliably predict the risk of bleeding after rivaroxaban or apixaban ingestion.

“One way to overcome the variation in these tests is to use anti-factor Xa chromogenic assays to measure Xa plasma concentrations,” Spiller said.

“However, these are not widely available, and a potential drawback with measuring anti-factor Xa concentrations and plasma rivaroxaban and apixaban concentrations is that the turnaround time for results may be too long to guide a treatment plan.”

The Food and Drug Administration has issued a Drug Safety Communication warning for the potential for severe allergic reactions, shingles, and severe eye injuries from incorrect application of Picato (ingenol mebutate), a topical gel used to treat actinic keratosis.

Picato’s manufacurer, Leo Pharma Inc., will be required to change the drug’s labeling to reflect the risk for these adverse events and provide more information about safe application of Picato gel.

In the data summary accompanying the announcement, the FDA noted that some of the incorrect use of Picato gel was related either to inaccurate prescribing or dispensing. Adverse events reported were associated with incorrect application of Picato gel, which is to be used on no more than 25 cm² of skin at a time, and for no more than 3 consecutive days.

Some of the adverse events reports describe mixing Picato with other products, occluding the skin after applying Picato gel, washing it off before the recommended 6 hours, or applying at bedtime.

Additionally, some adverse events occurred when the stronger 0.05% formulation, intended for use on the extremities and trunk, was applied to the face. Facial actinic keratoses are to be treated with the 0.015% formulation.

Adverse events described included severe allergic reactions ranging from significant contact dermatitis to anaphylaxis. Reactivation of herpes zoster was also reported; some of these cases were associated with applying Picato gel to a larger-than-recommended area, or with using an incorrect dose strength.

Another class of adverse events involved accidental transfer of Picato gel, often to the eyes. This occurred even after handwashing. In addition to eyelid swelling and irritation, cases of chemical conjunctivitis and corneal ulceration were reported. Lips, tongue, and rectum were other areas affected by accidental transfer of Picato gel.

[email protected]

On Twitter @karioakes

The Food and Drug Administration has issued a Drug Safety Communication warning for the potential for severe allergic reactions, shingles, and severe eye injuries from incorrect application of Picato (ingenol mebutate), a topical gel used to treat actinic keratosis.

Picato’s manufacurer, Leo Pharma Inc., will be required to change the drug’s labeling to reflect the risk for these adverse events and provide more information about safe application of Picato gel.

In the data summary accompanying the announcement, the FDA noted that some of the incorrect use of Picato gel was related either to inaccurate prescribing or dispensing. Adverse events reported were associated with incorrect application of Picato gel, which is to be used on no more than 25 cm² of skin at a time, and for no more than 3 consecutive days.

Some of the adverse events reports describe mixing Picato with other products, occluding the skin after applying Picato gel, washing it off before the recommended 6 hours, or applying at bedtime.

Additionally, some adverse events occurred when the stronger 0.05% formulation, intended for use on the extremities and trunk, was applied to the face. Facial actinic keratoses are to be treated with the 0.015% formulation.

Adverse events described included severe allergic reactions ranging from significant contact dermatitis to anaphylaxis. Reactivation of herpes zoster was also reported; some of these cases were associated with applying Picato gel to a larger-than-recommended area, or with using an incorrect dose strength.

Another class of adverse events involved accidental transfer of Picato gel, often to the eyes. This occurred even after handwashing. In addition to eyelid swelling and irritation, cases of chemical conjunctivitis and corneal ulceration were reported. Lips, tongue, and rectum were other areas affected by accidental transfer of Picato gel.

[email protected]

On Twitter @karioakes

The Food and Drug Administration has issued a Drug Safety Communication warning for the potential for severe allergic reactions, shingles, and severe eye injuries from incorrect application of Picato (ingenol mebutate), a topical gel used to treat actinic keratosis.

Picato’s manufacurer, Leo Pharma Inc., will be required to change the drug’s labeling to reflect the risk for these adverse events and provide more information about safe application of Picato gel.

In the data summary accompanying the announcement, the FDA noted that some of the incorrect use of Picato gel was related either to inaccurate prescribing or dispensing. Adverse events reported were associated with incorrect application of Picato gel, which is to be used on no more than 25 cm² of skin at a time, and for no more than 3 consecutive days.

Some of the adverse events reports describe mixing Picato with other products, occluding the skin after applying Picato gel, washing it off before the recommended 6 hours, or applying at bedtime.

Additionally, some adverse events occurred when the stronger 0.05% formulation, intended for use on the extremities and trunk, was applied to the face. Facial actinic keratoses are to be treated with the 0.015% formulation.

Adverse events described included severe allergic reactions ranging from significant contact dermatitis to anaphylaxis. Reactivation of herpes zoster was also reported; some of these cases were associated with applying Picato gel to a larger-than-recommended area, or with using an incorrect dose strength.

Another class of adverse events involved accidental transfer of Picato gel, often to the eyes. This occurred even after handwashing. In addition to eyelid swelling and irritation, cases of chemical conjunctivitis and corneal ulceration were reported. Lips, tongue, and rectum were other areas affected by accidental transfer of Picato gel.

[email protected]

On Twitter @karioakes

“Teach residents…really? You want to add yet another time-consuming responsibility to my already hectic schedule?” Residency. The mere mention of the word conjures up chilling memories of 3 am codes, 20-30 hour zombie shifts, and anxiety and stress levels that we never knew before and, fortunately, have not known since. That was a time in life many of us want to put in the deepest recesses of our minds, never to emerge again.

But, on the other hand, there were a lot of good things about our residency training that we should probably never forget, such as the humility with which we approached patient care. At that time in our lives we gladly acknowledged we did not know everything and we were eager to research each and every condition to get a firm handle on what we could and should do to help our patients get better.

Fast forward a decade or two. Now many of us have spouses, children, aging parents, mortgages, and retirement accounts we are feverishly trying to fund. There never seems to be enough time to finish even the most fundamental responsibilities. Not to mention now there are national initiatives, mandatory rules, and sometimes frightening regulations in place that dramatically impact how we practice medicine and sometimes make us feel more like automatons than the physicians we dreamed of becoming when we first applied to medical school years ago.

With all of our current and future responsibilities, how can the average hospitalist embrace young physicians and pour himself into their lives? Or, perhaps the question is better asked, how can we not? None of us morphed from a green medical school graduate to a knowledgeable, well-respected physician without a great deal of hand holding (and sometimes hand wringing), encouragement and investment of time from our teaching attendings. But even if you are hesitant to invest the time and energy to teach resident physicians should you have the opportunity. Keep in mind, in 2015 we are not only teaching them, they are teaching us too!

Young physicians are overflowing with technological knowledge that many of us have never been exposed to, knowledge that can help escalate our own skill sets. They bring fresh ideas, novel approaches to patient care, and frequently, cutting edge medical innovations from the universities from which come.

So, if you are ever asked to teach our future colleagues, remember: you may very well find that the time you invest benefits you as much, if not more, than it does them.

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].

“Teach residents…really? You want to add yet another time-consuming responsibility to my already hectic schedule?” Residency. The mere mention of the word conjures up chilling memories of 3 am codes, 20-30 hour zombie shifts, and anxiety and stress levels that we never knew before and, fortunately, have not known since. That was a time in life many of us want to put in the deepest recesses of our minds, never to emerge again.

But, on the other hand, there were a lot of good things about our residency training that we should probably never forget, such as the humility with which we approached patient care. At that time in our lives we gladly acknowledged we did not know everything and we were eager to research each and every condition to get a firm handle on what we could and should do to help our patients get better.

Fast forward a decade or two. Now many of us have spouses, children, aging parents, mortgages, and retirement accounts we are feverishly trying to fund. There never seems to be enough time to finish even the most fundamental responsibilities. Not to mention now there are national initiatives, mandatory rules, and sometimes frightening regulations in place that dramatically impact how we practice medicine and sometimes make us feel more like automatons than the physicians we dreamed of becoming when we first applied to medical school years ago.

With all of our current and future responsibilities, how can the average hospitalist embrace young physicians and pour himself into their lives? Or, perhaps the question is better asked, how can we not? None of us morphed from a green medical school graduate to a knowledgeable, well-respected physician without a great deal of hand holding (and sometimes hand wringing), encouragement and investment of time from our teaching attendings. But even if you are hesitant to invest the time and energy to teach resident physicians should you have the opportunity. Keep in mind, in 2015 we are not only teaching them, they are teaching us too!

Young physicians are overflowing with technological knowledge that many of us have never been exposed to, knowledge that can help escalate our own skill sets. They bring fresh ideas, novel approaches to patient care, and frequently, cutting edge medical innovations from the universities from which come.

So, if you are ever asked to teach our future colleagues, remember: you may very well find that the time you invest benefits you as much, if not more, than it does them.

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].

“Teach residents…really? You want to add yet another time-consuming responsibility to my already hectic schedule?” Residency. The mere mention of the word conjures up chilling memories of 3 am codes, 20-30 hour zombie shifts, and anxiety and stress levels that we never knew before and, fortunately, have not known since. That was a time in life many of us want to put in the deepest recesses of our minds, never to emerge again.

But, on the other hand, there were a lot of good things about our residency training that we should probably never forget, such as the humility with which we approached patient care. At that time in our lives we gladly acknowledged we did not know everything and we were eager to research each and every condition to get a firm handle on what we could and should do to help our patients get better.

Fast forward a decade or two. Now many of us have spouses, children, aging parents, mortgages, and retirement accounts we are feverishly trying to fund. There never seems to be enough time to finish even the most fundamental responsibilities. Not to mention now there are national initiatives, mandatory rules, and sometimes frightening regulations in place that dramatically impact how we practice medicine and sometimes make us feel more like automatons than the physicians we dreamed of becoming when we first applied to medical school years ago.

With all of our current and future responsibilities, how can the average hospitalist embrace young physicians and pour himself into their lives? Or, perhaps the question is better asked, how can we not? None of us morphed from a green medical school graduate to a knowledgeable, well-respected physician without a great deal of hand holding (and sometimes hand wringing), encouragement and investment of time from our teaching attendings. But even if you are hesitant to invest the time and energy to teach resident physicians should you have the opportunity. Keep in mind, in 2015 we are not only teaching them, they are teaching us too!

Young physicians are overflowing with technological knowledge that many of us have never been exposed to, knowledge that can help escalate our own skill sets. They bring fresh ideas, novel approaches to patient care, and frequently, cutting edge medical innovations from the universities from which come.

So, if you are ever asked to teach our future colleagues, remember: you may very well find that the time you invest benefits you as much, if not more, than it does them.

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].

Doctor and patient

in the intensive care unit

Results of an anonymous survey suggest healthcare professionals in the US may not consistently follow recommendations for preventing bloodstream infections in patients with arterial catheters.

Of the roughly 1000 critical care clinicians surveyed, fewer than half said they comply with the current Centers for Disease Control and Prevention (CDC) guidelines, which recommend the use of limited barrier precautions during arterial catheter insertion.

This includes sterile gloves, a surgical cap, a surgical mask, and a small sterile drape.

“Barrier precautions are employed inconsistently by critical care clinicians across the nation, and such individuals underestimate the infection risks posed by arterial catheters,” said Leonard A. Mermel, DO, of Rhode Island Hospital in Providence.

He and his colleagues reported these findings in Critical Care Medicine.

The researchers sent an anonymous, web-based survey to 11,361 physicians, nurse practitioners, physician assistants, respiratory therapists, and registered nurses who receive emails from the Society of Critical Care Medicine.

There were 1265 responses (an 11% response rate) and 1029 eligible participants after exclusions.

Of the eligible respondents, 44% said they used CDC-recommended barrier precautions during arterial catheter insertion, and 15% said they use full barrier precautions.

However, 39% of respondents said they would support mandatory use of full barrier precautions during arterial catheter insertion.

“There appears to be a significant deviation from clinical guidelines regarding a very commonly performed procedure in critically ill patients,” said study author Andrew Levinson, MD, also of Rhode Island Hospital.

“Bloodstream infections are largely preventable, and if the survey results mirror the clinical practice in the US, there’s work to be done in reducing risk of such infections.”

The survey also indicated that respondents underestimate the risk of bloodstream infections associated with arterial catheters. The respondents’ mean estimate of infection incidence was 0.3 per 1000 catheter-days, and the median estimate was 0.1 per 1000 catheter-days.

However, Dr Mermel and his colleagues said recent studies have suggested the incidence of bloodstream infections associated with arterial catheters in the US is 0.9 to 3.4 per 1000 catheter-days.

Doctor and patient

in the intensive care unit

Results of an anonymous survey suggest healthcare professionals in the US may not consistently follow recommendations for preventing bloodstream infections in patients with arterial catheters.

Of the roughly 1000 critical care clinicians surveyed, fewer than half said they comply with the current Centers for Disease Control and Prevention (CDC) guidelines, which recommend the use of limited barrier precautions during arterial catheter insertion.

This includes sterile gloves, a surgical cap, a surgical mask, and a small sterile drape.

“Barrier precautions are employed inconsistently by critical care clinicians across the nation, and such individuals underestimate the infection risks posed by arterial catheters,” said Leonard A. Mermel, DO, of Rhode Island Hospital in Providence.

He and his colleagues reported these findings in Critical Care Medicine.

The researchers sent an anonymous, web-based survey to 11,361 physicians, nurse practitioners, physician assistants, respiratory therapists, and registered nurses who receive emails from the Society of Critical Care Medicine.

There were 1265 responses (an 11% response rate) and 1029 eligible participants after exclusions.

Of the eligible respondents, 44% said they used CDC-recommended barrier precautions during arterial catheter insertion, and 15% said they use full barrier precautions.

However, 39% of respondents said they would support mandatory use of full barrier precautions during arterial catheter insertion.

“There appears to be a significant deviation from clinical guidelines regarding a very commonly performed procedure in critically ill patients,” said study author Andrew Levinson, MD, also of Rhode Island Hospital.

“Bloodstream infections are largely preventable, and if the survey results mirror the clinical practice in the US, there’s work to be done in reducing risk of such infections.”

The survey also indicated that respondents underestimate the risk of bloodstream infections associated with arterial catheters. The respondents’ mean estimate of infection incidence was 0.3 per 1000 catheter-days, and the median estimate was 0.1 per 1000 catheter-days.

However, Dr Mermel and his colleagues said recent studies have suggested the incidence of bloodstream infections associated with arterial catheters in the US is 0.9 to 3.4 per 1000 catheter-days.

Doctor and patient

in the intensive care unit

Results of an anonymous survey suggest healthcare professionals in the US may not consistently follow recommendations for preventing bloodstream infections in patients with arterial catheters.

Of the roughly 1000 critical care clinicians surveyed, fewer than half said they comply with the current Centers for Disease Control and Prevention (CDC) guidelines, which recommend the use of limited barrier precautions during arterial catheter insertion.

This includes sterile gloves, a surgical cap, a surgical mask, and a small sterile drape.

“Barrier precautions are employed inconsistently by critical care clinicians across the nation, and such individuals underestimate the infection risks posed by arterial catheters,” said Leonard A. Mermel, DO, of Rhode Island Hospital in Providence.

He and his colleagues reported these findings in Critical Care Medicine.

The researchers sent an anonymous, web-based survey to 11,361 physicians, nurse practitioners, physician assistants, respiratory therapists, and registered nurses who receive emails from the Society of Critical Care Medicine.

There were 1265 responses (an 11% response rate) and 1029 eligible participants after exclusions.

Of the eligible respondents, 44% said they used CDC-recommended barrier precautions during arterial catheter insertion, and 15% said they use full barrier precautions.

However, 39% of respondents said they would support mandatory use of full barrier precautions during arterial catheter insertion.

“There appears to be a significant deviation from clinical guidelines regarding a very commonly performed procedure in critically ill patients,” said study author Andrew Levinson, MD, also of Rhode Island Hospital.

“Bloodstream infections are largely preventable, and if the survey results mirror the clinical practice in the US, there’s work to be done in reducing risk of such infections.”

The survey also indicated that respondents underestimate the risk of bloodstream infections associated with arterial catheters. The respondents’ mean estimate of infection incidence was 0.3 per 1000 catheter-days, and the median estimate was 0.1 per 1000 catheter-days.

However, Dr Mermel and his colleagues said recent studies have suggested the incidence of bloodstream infections associated with arterial catheters in the US is 0.9 to 3.4 per 1000 catheter-days.

NEW YORK – For treating actinic keratoses appearing over large or disseminated surface areas, daylight is often a better strategy than artificial light is for activating photodynamic therapy (PDT), according to an update on strategies at the summer meeting of the American Academy of Dermatology.

The evidence that daylight is at least as effective as artificial light for grade 1 and 2 actinic keratoses has created a “really exciting new opportunity” for those with disseminated disease, according to Dr. Emily J. Fisher, director of Mohs surgery at Mercy Health Physicians, Cincinnati, Ohio. This approach is not only a more efficient way to treat large or multiple areas of skin, but it is better tolerated, further facilitating treatment of bigger surface areas.

Moreover, for physicians not currently equipped with blue or red artificial light, daylight activation “is a great way to incorporate PDT into your practice,” Dr. Fisher added. She suggested that PDT, which has been associated with clearance rates exceeding 70% with a single treatment in many studies, appears to be at least as effective as the topical treatments that are employed more often, such as 5-fluorouracil (5-FU) or imiquimod.

When comparing efficacy across studies, “PDT seems to have a higher response than [does] our topical treatments,” but Dr. Fisher cautioned that there are no high-quality, head-to-head comparisons, so there is no definitive evidence of the superiority of one over the other.

However, in patients with multiple actinic keratoses spread over a substantial area of the skin or who have lesions in more than one anatomical site, daylight PDT is a practical approach now widely used in Europe and several other parts of the world, according to Dr. Fisher. She reported that five randomized trials have demonstrated that daylight PDT is effective.

Most aspects of daylight PDT are the same as conventional PDT, according to Dr. Fisher. The skin is first prepared by removing scales and crusts to improve penetration of the photodynamic agent, whether aminolevulinate acid (ALA) or methyl aminolevulinate (MAL). Prior to light exposure, the occlusion time with the photodynamic agent is the same 3 hours. Also, light exposure in both cases should begin within 30 minutes, which may be a consideration for those depending on daylight.

“Patients really should not go indoors or into shade for more than 5 minutes at a time,” Dr. Fisher reported. The problem is that the activity of the intracellular photosensitizing chemicals can build up without light exposure, producing pain and reducing the tolerability of the treatment.

Consensus guidelines have been published for daylight PDT in Australia (J Eur Acad Dermatol Venereol. 2012 Jun;26[6]:673-9.). According to Dr. Fisher, the guidelines recommend a light intensity of greater than 130 W/m², which is a dose provided by sunlight within the continental United States but not at distant points from the equator, such as Alaska. The guidelines also specify that sun exposure take place with a minimum temperature of 10° C. Dr. Fisher said that activity is diminished at lower temperatures.

“After 2 hours of exposure, patients should wash off the ALA and avoid further exposure for about 48 hours,” said Dr. Fisher, who recommended chemical sunscreens on areas of the skin not being treated.

“I think that over the next few years, this is going to have a big place in patient treatment. It is more convenient and better tolerated,” Dr. Fisher reported. She said that several modifications with the potential to enhance efficacy, such as pretreatment with retinoids or employing 5-FU after PDT, are strategies that have shown promise in small studies and may prove to be helpful through expanded clinical investigation.

NEW YORK – For treating actinic keratoses appearing over large or disseminated surface areas, daylight is often a better strategy than artificial light is for activating photodynamic therapy (PDT), according to an update on strategies at the summer meeting of the American Academy of Dermatology.

The evidence that daylight is at least as effective as artificial light for grade 1 and 2 actinic keratoses has created a “really exciting new opportunity” for those with disseminated disease, according to Dr. Emily J. Fisher, director of Mohs surgery at Mercy Health Physicians, Cincinnati, Ohio. This approach is not only a more efficient way to treat large or multiple areas of skin, but it is better tolerated, further facilitating treatment of bigger surface areas.

Moreover, for physicians not currently equipped with blue or red artificial light, daylight activation “is a great way to incorporate PDT into your practice,” Dr. Fisher added. She suggested that PDT, which has been associated with clearance rates exceeding 70% with a single treatment in many studies, appears to be at least as effective as the topical treatments that are employed more often, such as 5-fluorouracil (5-FU) or imiquimod.

When comparing efficacy across studies, “PDT seems to have a higher response than [does] our topical treatments,” but Dr. Fisher cautioned that there are no high-quality, head-to-head comparisons, so there is no definitive evidence of the superiority of one over the other.

However, in patients with multiple actinic keratoses spread over a substantial area of the skin or who have lesions in more than one anatomical site, daylight PDT is a practical approach now widely used in Europe and several other parts of the world, according to Dr. Fisher. She reported that five randomized trials have demonstrated that daylight PDT is effective.

Most aspects of daylight PDT are the same as conventional PDT, according to Dr. Fisher. The skin is first prepared by removing scales and crusts to improve penetration of the photodynamic agent, whether aminolevulinate acid (ALA) or methyl aminolevulinate (MAL). Prior to light exposure, the occlusion time with the photodynamic agent is the same 3 hours. Also, light exposure in both cases should begin within 30 minutes, which may be a consideration for those depending on daylight.

“Patients really should not go indoors or into shade for more than 5 minutes at a time,” Dr. Fisher reported. The problem is that the activity of the intracellular photosensitizing chemicals can build up without light exposure, producing pain and reducing the tolerability of the treatment.

Consensus guidelines have been published for daylight PDT in Australia (J Eur Acad Dermatol Venereol. 2012 Jun;26[6]:673-9.). According to Dr. Fisher, the guidelines recommend a light intensity of greater than 130 W/m², which is a dose provided by sunlight within the continental United States but not at distant points from the equator, such as Alaska. The guidelines also specify that sun exposure take place with a minimum temperature of 10° C. Dr. Fisher said that activity is diminished at lower temperatures.

“After 2 hours of exposure, patients should wash off the ALA and avoid further exposure for about 48 hours,” said Dr. Fisher, who recommended chemical sunscreens on areas of the skin not being treated.

“I think that over the next few years, this is going to have a big place in patient treatment. It is more convenient and better tolerated,” Dr. Fisher reported. She said that several modifications with the potential to enhance efficacy, such as pretreatment with retinoids or employing 5-FU after PDT, are strategies that have shown promise in small studies and may prove to be helpful through expanded clinical investigation.

NEW YORK – For treating actinic keratoses appearing over large or disseminated surface areas, daylight is often a better strategy than artificial light is for activating photodynamic therapy (PDT), according to an update on strategies at the summer meeting of the American Academy of Dermatology.

The evidence that daylight is at least as effective as artificial light for grade 1 and 2 actinic keratoses has created a “really exciting new opportunity” for those with disseminated disease, according to Dr. Emily J. Fisher, director of Mohs surgery at Mercy Health Physicians, Cincinnati, Ohio. This approach is not only a more efficient way to treat large or multiple areas of skin, but it is better tolerated, further facilitating treatment of bigger surface areas.

Moreover, for physicians not currently equipped with blue or red artificial light, daylight activation “is a great way to incorporate PDT into your practice,” Dr. Fisher added. She suggested that PDT, which has been associated with clearance rates exceeding 70% with a single treatment in many studies, appears to be at least as effective as the topical treatments that are employed more often, such as 5-fluorouracil (5-FU) or imiquimod.

When comparing efficacy across studies, “PDT seems to have a higher response than [does] our topical treatments,” but Dr. Fisher cautioned that there are no high-quality, head-to-head comparisons, so there is no definitive evidence of the superiority of one over the other.

However, in patients with multiple actinic keratoses spread over a substantial area of the skin or who have lesions in more than one anatomical site, daylight PDT is a practical approach now widely used in Europe and several other parts of the world, according to Dr. Fisher. She reported that five randomized trials have demonstrated that daylight PDT is effective.

Most aspects of daylight PDT are the same as conventional PDT, according to Dr. Fisher. The skin is first prepared by removing scales and crusts to improve penetration of the photodynamic agent, whether aminolevulinate acid (ALA) or methyl aminolevulinate (MAL). Prior to light exposure, the occlusion time with the photodynamic agent is the same 3 hours. Also, light exposure in both cases should begin within 30 minutes, which may be a consideration for those depending on daylight.

“Patients really should not go indoors or into shade for more than 5 minutes at a time,” Dr. Fisher reported. The problem is that the activity of the intracellular photosensitizing chemicals can build up without light exposure, producing pain and reducing the tolerability of the treatment.

Consensus guidelines have been published for daylight PDT in Australia (J Eur Acad Dermatol Venereol. 2012 Jun;26[6]:673-9.). According to Dr. Fisher, the guidelines recommend a light intensity of greater than 130 W/m², which is a dose provided by sunlight within the continental United States but not at distant points from the equator, such as Alaska. The guidelines also specify that sun exposure take place with a minimum temperature of 10° C. Dr. Fisher said that activity is diminished at lower temperatures.

“After 2 hours of exposure, patients should wash off the ALA and avoid further exposure for about 48 hours,” said Dr. Fisher, who recommended chemical sunscreens on areas of the skin not being treated.

“I think that over the next few years, this is going to have a big place in patient treatment. It is more convenient and better tolerated,” Dr. Fisher reported. She said that several modifications with the potential to enhance efficacy, such as pretreatment with retinoids or employing 5-FU after PDT, are strategies that have shown promise in small studies and may prove to be helpful through expanded clinical investigation.

There’s a lot of information out there about heart disease and how to prevent it, but there’s a lot of misinformation out there as well, and it’s important to get the facts straight when it comes to your heart, according to a Harvard Heart Letter report.

While it may seem logical to limit physical activity if you have a heart problem, in nearly all cases, a person with heart disease can benefit from regular, moderate amounts of exercise. And while it may also make sense to eat a very-low-fat diet, it is really only saturated fat that is harmful to the heart. A diet rich in unsaturated fat from foods such as fish, olive oil, and low-fat dairy products actually reduces the risk of heart disease.

© Stockbyte/Thinkstock

Cholesterol-lowering drugs reduce cholesterol produced by the liver; they do not reduce cholesterol you get from food, so taking such a drug is not a free pass to continue eating fatty food. Along those lines, even if you take a drug to manage diabetes, the disease still can cause heart disease.

While it is true that women under the age of 60 years are significantly less likely to get heart disease than are men, this disparity disappears over the age of 60, and by age 80 years, women are slightly more likely to have heart disease. It is also true that quitting smoking has immediate benefits, even if you’ve been smoking for years. Heart attack risk drops by 50% after 1 year being tobacco free, and the increased risk disappears entirely after 10 years.

A small heart attack may not do much damage – it may be barely noticeable. But any heart attack is indicative of a big problem. While surgical procedures such as stenting or bypasses do a lot for managing symptoms, they do not fix the problem, and life changes are still recommended.

For more information about heart disease myths, visit the Harvard Medical School website.

[email protected]

There’s a lot of information out there about heart disease and how to prevent it, but there’s a lot of misinformation out there as well, and it’s important to get the facts straight when it comes to your heart, according to a Harvard Heart Letter report.

While it may seem logical to limit physical activity if you have a heart problem, in nearly all cases, a person with heart disease can benefit from regular, moderate amounts of exercise. And while it may also make sense to eat a very-low-fat diet, it is really only saturated fat that is harmful to the heart. A diet rich in unsaturated fat from foods such as fish, olive oil, and low-fat dairy products actually reduces the risk of heart disease.

© Stockbyte/Thinkstock

Cholesterol-lowering drugs reduce cholesterol produced by the liver; they do not reduce cholesterol you get from food, so taking such a drug is not a free pass to continue eating fatty food. Along those lines, even if you take a drug to manage diabetes, the disease still can cause heart disease.

While it is true that women under the age of 60 years are significantly less likely to get heart disease than are men, this disparity disappears over the age of 60, and by age 80 years, women are slightly more likely to have heart disease. It is also true that quitting smoking has immediate benefits, even if you’ve been smoking for years. Heart attack risk drops by 50% after 1 year being tobacco free, and the increased risk disappears entirely after 10 years.

A small heart attack may not do much damage – it may be barely noticeable. But any heart attack is indicative of a big problem. While surgical procedures such as stenting or bypasses do a lot for managing symptoms, they do not fix the problem, and life changes are still recommended.

For more information about heart disease myths, visit the Harvard Medical School website.

[email protected]

There’s a lot of information out there about heart disease and how to prevent it, but there’s a lot of misinformation out there as well, and it’s important to get the facts straight when it comes to your heart, according to a Harvard Heart Letter report.

While it may seem logical to limit physical activity if you have a heart problem, in nearly all cases, a person with heart disease can benefit from regular, moderate amounts of exercise. And while it may also make sense to eat a very-low-fat diet, it is really only saturated fat that is harmful to the heart. A diet rich in unsaturated fat from foods such as fish, olive oil, and low-fat dairy products actually reduces the risk of heart disease.

© Stockbyte/Thinkstock

Cholesterol-lowering drugs reduce cholesterol produced by the liver; they do not reduce cholesterol you get from food, so taking such a drug is not a free pass to continue eating fatty food. Along those lines, even if you take a drug to manage diabetes, the disease still can cause heart disease.

While it is true that women under the age of 60 years are significantly less likely to get heart disease than are men, this disparity disappears over the age of 60, and by age 80 years, women are slightly more likely to have heart disease. It is also true that quitting smoking has immediate benefits, even if you’ve been smoking for years. Heart attack risk drops by 50% after 1 year being tobacco free, and the increased risk disappears entirely after 10 years.

A small heart attack may not do much damage – it may be barely noticeable. But any heart attack is indicative of a big problem. While surgical procedures such as stenting or bypasses do a lot for managing symptoms, they do not fix the problem, and life changes are still recommended.

For more information about heart disease myths, visit the Harvard Medical School website.

[email protected]