Katie Lennon

The American College of Cardiology (ACC) will launch two registries to track the outcomes of treatments for atrial fibrillation, the medical society announced today.

The LAAO Registry will capture data on left atrial appendage occlusion procedures to assess real-world procedural indications and outcomes, as well as short- and long-term safety.

The AFib Ablation Registry will assess the prevalence, demographics, acute management, and outcomes of patients undergoing atrial fibrillation ablation procedures. This registry’s data will support the development of evidence-based guidelines and quality metrics for atrial fibrillation treatments that will improve outcomes, according to the ACC.

“With a growing prevalence of atrial fibrillation and growing options for treatment and stroke prevention in AFib patients, the ACC saw a need for real-world data to track and evaluate the use of these new technologies,” said Dr. Kim A. Williams Sr., ACC president.

klennon@frontlinemedcom.com

The American College of Cardiology (ACC) will launch two registries to track the outcomes of treatments for atrial fibrillation, the medical society announced today.

The LAAO Registry will capture data on left atrial appendage occlusion procedures to assess real-world procedural indications and outcomes, as well as short- and long-term safety.

The AFib Ablation Registry will assess the prevalence, demographics, acute management, and outcomes of patients undergoing atrial fibrillation ablation procedures. This registry’s data will support the development of evidence-based guidelines and quality metrics for atrial fibrillation treatments that will improve outcomes, according to the ACC.

“With a growing prevalence of atrial fibrillation and growing options for treatment and stroke prevention in AFib patients, the ACC saw a need for real-world data to track and evaluate the use of these new technologies,” said Dr. Kim A. Williams Sr., ACC president.

klennon@frontlinemedcom.com

The American College of Cardiology (ACC) will launch two registries to track the outcomes of treatments for atrial fibrillation, the medical society announced today.

The LAAO Registry will capture data on left atrial appendage occlusion procedures to assess real-world procedural indications and outcomes, as well as short- and long-term safety.

The AFib Ablation Registry will assess the prevalence, demographics, acute management, and outcomes of patients undergoing atrial fibrillation ablation procedures. This registry’s data will support the development of evidence-based guidelines and quality metrics for atrial fibrillation treatments that will improve outcomes, according to the ACC.

“With a growing prevalence of atrial fibrillation and growing options for treatment and stroke prevention in AFib patients, the ACC saw a need for real-world data to track and evaluate the use of these new technologies,” said Dr. Kim A. Williams Sr., ACC president.

klennon@frontlinemedcom.com

Most middle schools and high schools start their days earlier than the American Academy of Pediatrics (AAP) recommends, according to an analysis of survey responses.

The Centers for Disease Control and Prevention and the U.S. Department of Education conducted the analysis of data from the 2011-2012 Schools and Staffing Survey (SASS). Among an estimated 39,700 public middle and secondary schools and schools that combine middle schoolers and high schoolers, the average school-day start time was 8:03 a.m.

©Trista Weibell/iStockphoto.com

In a policy statement published last year, the AAP recommended that high- and middle-school days begin at 8:30 a.m. or later to enable students to get adequate sleep and improve their health, safety, academic performance, and quality of life.

“Among adolescents, insufficient sleep has been associated with adverse risk behaviors, poor health outcomes, and poor academic performance,” noted Anne G. Wheaton, Ph.D., and her colleagues at the CDC’s National Center for Chronic Disease Prevention and Health Promotion, Atlanta, who conducted the analysis.

Only 17.7% of the schools studied started their days at 8:30 a.m. or later. Schools’ start times varied widely by state. In Hawaii, Mississippi, and Wyoming, no schools started as late at 8:30 a.m., while more than three-quarters of schools in Alaska and North Dakota began school at 8:30 a.m. or later.

“A school system start time policy of 8:30 a.m. or later provides teenage students the opportunity to achieve the 8.5-9.5 hours of sleep recommended by AAP and the 8-10 hours recommended by the National Sleep Foundation,” the researchers wrote.

Read the full study in Morbidity and Mortality Weekly Report.

klennon@frontlinemedcom.com

Most middle schools and high schools start their days earlier than the American Academy of Pediatrics (AAP) recommends, according to an analysis of survey responses.

The Centers for Disease Control and Prevention and the U.S. Department of Education conducted the analysis of data from the 2011-2012 Schools and Staffing Survey (SASS). Among an estimated 39,700 public middle and secondary schools and schools that combine middle schoolers and high schoolers, the average school-day start time was 8:03 a.m.

©Trista Weibell/iStockphoto.com

In a policy statement published last year, the AAP recommended that high- and middle-school days begin at 8:30 a.m. or later to enable students to get adequate sleep and improve their health, safety, academic performance, and quality of life.

“Among adolescents, insufficient sleep has been associated with adverse risk behaviors, poor health outcomes, and poor academic performance,” noted Anne G. Wheaton, Ph.D., and her colleagues at the CDC’s National Center for Chronic Disease Prevention and Health Promotion, Atlanta, who conducted the analysis.

Only 17.7% of the schools studied started their days at 8:30 a.m. or later. Schools’ start times varied widely by state. In Hawaii, Mississippi, and Wyoming, no schools started as late at 8:30 a.m., while more than three-quarters of schools in Alaska and North Dakota began school at 8:30 a.m. or later.

“A school system start time policy of 8:30 a.m. or later provides teenage students the opportunity to achieve the 8.5-9.5 hours of sleep recommended by AAP and the 8-10 hours recommended by the National Sleep Foundation,” the researchers wrote.

Read the full study in Morbidity and Mortality Weekly Report.

klennon@frontlinemedcom.com

Most middle schools and high schools start their days earlier than the American Academy of Pediatrics (AAP) recommends, according to an analysis of survey responses.

The Centers for Disease Control and Prevention and the U.S. Department of Education conducted the analysis of data from the 2011-2012 Schools and Staffing Survey (SASS). Among an estimated 39,700 public middle and secondary schools and schools that combine middle schoolers and high schoolers, the average school-day start time was 8:03 a.m.

©Trista Weibell/iStockphoto.com

In a policy statement published last year, the AAP recommended that high- and middle-school days begin at 8:30 a.m. or later to enable students to get adequate sleep and improve their health, safety, academic performance, and quality of life.

“Among adolescents, insufficient sleep has been associated with adverse risk behaviors, poor health outcomes, and poor academic performance,” noted Anne G. Wheaton, Ph.D., and her colleagues at the CDC’s National Center for Chronic Disease Prevention and Health Promotion, Atlanta, who conducted the analysis.

Only 17.7% of the schools studied started their days at 8:30 a.m. or later. Schools’ start times varied widely by state. In Hawaii, Mississippi, and Wyoming, no schools started as late at 8:30 a.m., while more than three-quarters of schools in Alaska and North Dakota began school at 8:30 a.m. or later.

“A school system start time policy of 8:30 a.m. or later provides teenage students the opportunity to achieve the 8.5-9.5 hours of sleep recommended by AAP and the 8-10 hours recommended by the National Sleep Foundation,” the researchers wrote.

Read the full study in Morbidity and Mortality Weekly Report.

klennon@frontlinemedcom.com

When type 2 diabetes patients skipped breakfast, they had higher levels of glucagon and free fatty acids (FFA), and reduced levels of insulin, C-peptide, and intact glucagonlike peptide-1 (iGLP-1) after meals, compared with when they ate breakfast, according to a randomized, open-label, cross-over-within-subject clinical trial.

A total of 22 overweight or obese people who had type 2 diabetes completed the study. Patients could not be taking GLP-1 analogs, anorectic drugs, steroids, or oral hypoglycemic agents, other than metformin. Seven of the patients had a history of hypertension and were treated with ACE inhibitors and/or calcium antagonists, wrote Dr. Daniela Jakubowicz of the Diabetes Unit in Hospital de Clinicas in Caracas, Venezuela.

At the Diabetes Unit, the patients participated in 2 full days of testing, separated by a washout period of 2-4 weeks. On one of the days, patients consumed three meals, including breakfast. On the other testing day, patients fasted until 1:30 p.m., consuming only lunch and dinner. All patients ate each of their meals during the same scheduled times; all meals contained identical macronutrient content and composition.

©MattZ90/thinkstockimages.com

Areas under the curve of data values for tested measures during an early response interval (0-30 minutes after eating a meal) and 0-180 minutes after eating a meal were calculated by the trapezoidal rule. These calculations were used as an estimate of response to meal consumption.

Plasma levels for glucose, insulin, C-peptide, and iGLP-1 were, respectively, 16.5%, 45%, 50%, and 33% higher before lunch, on the day that patients consumed breakfast, than they were on the day that they skipped breakfast.

The plasma FFA level was 1,787.1% higher for study participants on the day when they fasted until lunch than it was on the day when they ate breakfast. During tests taken 60-180 minutes after consumption of breakfast, patients’ glucagon levels were 12.5% lower than those of patients who fasted before lunch.

On the day that patients skipped breakfast, insulin was 17% lower after lunch and 7.9% lower after dinner, compared with the amounts of insulin found on the day that patients ate breakfast; iGLP-1 was also lower after dinner (16.5%) on the day that patients skipped breakfast.

After lunch and dinner, glucagon levels were 9.7% and 11.5% higher, respectively, on the day that patients refrained from eating breakfast than on the day that patients ate breakfast. Following lunch and dinner on the day that patients skipped breakfast, FFA values were higher (41.1% and 29.6%, respectively).

“We showed that the deleterious effects of breakfast omission triggering hyperglycemic response occurred after lunch and dinner, but the exact duration of this effect is not known,” wrote Dr. Jakubowicz and her colleagues. “In addition, the role of insulin sensitivity, suppression of hepatic glucose production, gastric emptying, and clock gene expression remain undefined.”

Read the full study in Diabetes Care (doi:10.2337/dc15-0761).

When type 2 diabetes patients skipped breakfast, they had higher levels of glucagon and free fatty acids (FFA), and reduced levels of insulin, C-peptide, and intact glucagonlike peptide-1 (iGLP-1) after meals, compared with when they ate breakfast, according to a randomized, open-label, cross-over-within-subject clinical trial.

A total of 22 overweight or obese people who had type 2 diabetes completed the study. Patients could not be taking GLP-1 analogs, anorectic drugs, steroids, or oral hypoglycemic agents, other than metformin. Seven of the patients had a history of hypertension and were treated with ACE inhibitors and/or calcium antagonists, wrote Dr. Daniela Jakubowicz of the Diabetes Unit in Hospital de Clinicas in Caracas, Venezuela.

At the Diabetes Unit, the patients participated in 2 full days of testing, separated by a washout period of 2-4 weeks. On one of the days, patients consumed three meals, including breakfast. On the other testing day, patients fasted until 1:30 p.m., consuming only lunch and dinner. All patients ate each of their meals during the same scheduled times; all meals contained identical macronutrient content and composition.

©MattZ90/thinkstockimages.com

Areas under the curve of data values for tested measures during an early response interval (0-30 minutes after eating a meal) and 0-180 minutes after eating a meal were calculated by the trapezoidal rule. These calculations were used as an estimate of response to meal consumption.

Plasma levels for glucose, insulin, C-peptide, and iGLP-1 were, respectively, 16.5%, 45%, 50%, and 33% higher before lunch, on the day that patients consumed breakfast, than they were on the day that they skipped breakfast.

The plasma FFA level was 1,787.1% higher for study participants on the day when they fasted until lunch than it was on the day when they ate breakfast. During tests taken 60-180 minutes after consumption of breakfast, patients’ glucagon levels were 12.5% lower than those of patients who fasted before lunch.

On the day that patients skipped breakfast, insulin was 17% lower after lunch and 7.9% lower after dinner, compared with the amounts of insulin found on the day that patients ate breakfast; iGLP-1 was also lower after dinner (16.5%) on the day that patients skipped breakfast.

After lunch and dinner, glucagon levels were 9.7% and 11.5% higher, respectively, on the day that patients refrained from eating breakfast than on the day that patients ate breakfast. Following lunch and dinner on the day that patients skipped breakfast, FFA values were higher (41.1% and 29.6%, respectively).

“We showed that the deleterious effects of breakfast omission triggering hyperglycemic response occurred after lunch and dinner, but the exact duration of this effect is not known,” wrote Dr. Jakubowicz and her colleagues. “In addition, the role of insulin sensitivity, suppression of hepatic glucose production, gastric emptying, and clock gene expression remain undefined.”

Read the full study in Diabetes Care (doi:10.2337/dc15-0761).

When type 2 diabetes patients skipped breakfast, they had higher levels of glucagon and free fatty acids (FFA), and reduced levels of insulin, C-peptide, and intact glucagonlike peptide-1 (iGLP-1) after meals, compared with when they ate breakfast, according to a randomized, open-label, cross-over-within-subject clinical trial.

A total of 22 overweight or obese people who had type 2 diabetes completed the study. Patients could not be taking GLP-1 analogs, anorectic drugs, steroids, or oral hypoglycemic agents, other than metformin. Seven of the patients had a history of hypertension and were treated with ACE inhibitors and/or calcium antagonists, wrote Dr. Daniela Jakubowicz of the Diabetes Unit in Hospital de Clinicas in Caracas, Venezuela.

At the Diabetes Unit, the patients participated in 2 full days of testing, separated by a washout period of 2-4 weeks. On one of the days, patients consumed three meals, including breakfast. On the other testing day, patients fasted until 1:30 p.m., consuming only lunch and dinner. All patients ate each of their meals during the same scheduled times; all meals contained identical macronutrient content and composition.

©MattZ90/thinkstockimages.com

Areas under the curve of data values for tested measures during an early response interval (0-30 minutes after eating a meal) and 0-180 minutes after eating a meal were calculated by the trapezoidal rule. These calculations were used as an estimate of response to meal consumption.

Plasma levels for glucose, insulin, C-peptide, and iGLP-1 were, respectively, 16.5%, 45%, 50%, and 33% higher before lunch, on the day that patients consumed breakfast, than they were on the day that they skipped breakfast.

The plasma FFA level was 1,787.1% higher for study participants on the day when they fasted until lunch than it was on the day when they ate breakfast. During tests taken 60-180 minutes after consumption of breakfast, patients’ glucagon levels were 12.5% lower than those of patients who fasted before lunch.

On the day that patients skipped breakfast, insulin was 17% lower after lunch and 7.9% lower after dinner, compared with the amounts of insulin found on the day that patients ate breakfast; iGLP-1 was also lower after dinner (16.5%) on the day that patients skipped breakfast.

After lunch and dinner, glucagon levels were 9.7% and 11.5% higher, respectively, on the day that patients refrained from eating breakfast than on the day that patients ate breakfast. Following lunch and dinner on the day that patients skipped breakfast, FFA values were higher (41.1% and 29.6%, respectively).

“We showed that the deleterious effects of breakfast omission triggering hyperglycemic response occurred after lunch and dinner, but the exact duration of this effect is not known,” wrote Dr. Jakubowicz and her colleagues. “In addition, the role of insulin sensitivity, suppression of hepatic glucose production, gastric emptying, and clock gene expression remain undefined.”

Read the full study in Diabetes Care (doi:10.2337/dc15-0761).

When type 2 diabetes patients skipped breakfast, they had higher levels of glucagon and free fatty acids (FFA), and reduced levels of insulin, C-peptide, and intact glucagonlike peptide-1 (iGLP-1) after meals, compared with when they ate breakfast, according to a randomized, open-label, cross-over-within-subject clinical trial.

A total of 22 overweight or obese people who had type 2 diabetes completed the study. Patients could not be taking GLP-1 analogs, anorectic drugs, steroids, or oral hypoglycemic agents, other than metformin. Seven of the patients had a history of hypertension and were treated with ACE inhibitors and/or calcium antagonists, wrote Dr. Daniela Jakubowicz of the Diabetes Unit in Hospital de Clinicas in Caracas, Venezuela.

At the Diabetes Unit, the patients participated in 2 full days of testing, separated by a washout period of 2-4 weeks. On one of the days, patients consumed three meals, including breakfast. On the other testing day, patients fasted until 1:30 p.m., consuming only lunch and dinner. All patients ate each of their meals during the same scheduled times; all meals contained identical macronutrient content and composition.

©MattZ90/thinkstockimages.com

Areas under the curve of data values for tested measures during an early response interval (0-30 minutes after eating a meal) and 0-180 minutes after eating a meal were calculated by the trapezoidal rule. These calculations were used as an estimate of response to meal consumption.

Plasma levels for glucose, insulin, C-peptide, and iGLP-1 were, respectively, 16.5%, 45%, 50%, and 33% higher before lunch, on the day that patients consumed breakfast, than they were on the day that they skipped breakfast.

The plasma FFA level was 1,787.1% higher for study participants on the day when they fasted until lunch than it was on the day when they ate breakfast. During tests taken 60-180 minutes after consumption of breakfast, patients’ glucagon levels were 12.5% lower than those of patients who fasted before lunch.

On the day that patients skipped breakfast, insulin was 17% lower after lunch and 7.9% lower after dinner, compared with the amounts of insulin found on the day that patients ate breakfast; iGLP-1 was also lower after dinner (16.5%) on the day that patients skipped breakfast.

After lunch and dinner, glucagon levels were 9.7% and 11.5% higher, respectively, on the day that patients refrained from eating breakfast than on the day that patients ate breakfast. Following lunch and dinner on the day that patients skipped breakfast, FFA values were higher (41.1% and 29.6%, respectively).

“We showed that the deleterious effects of breakfast omission triggering hyperglycemic response occurred after lunch and dinner, but the exact duration of this effect is not known,” wrote Dr. Jakubowicz and her colleagues. “In addition, the role of insulin sensitivity, suppression of hepatic glucose production, gastric emptying, and clock gene expression remain undefined.”

Read the full study in Diabetes Care (doi:10.2337/dc15-0761).

klennon@frontlinemedcom.com

When type 2 diabetes patients skipped breakfast, they had higher levels of glucagon and free fatty acids (FFA), and reduced levels of insulin, C-peptide, and intact glucagonlike peptide-1 (iGLP-1) after meals, compared with when they ate breakfast, according to a randomized, open-label, cross-over-within-subject clinical trial.

A total of 22 overweight or obese people who had type 2 diabetes completed the study. Patients could not be taking GLP-1 analogs, anorectic drugs, steroids, or oral hypoglycemic agents, other than metformin. Seven of the patients had a history of hypertension and were treated with ACE inhibitors and/or calcium antagonists, wrote Dr. Daniela Jakubowicz of the Diabetes Unit in Hospital de Clinicas in Caracas, Venezuela.

At the Diabetes Unit, the patients participated in 2 full days of testing, separated by a washout period of 2-4 weeks. On one of the days, patients consumed three meals, including breakfast. On the other testing day, patients fasted until 1:30 p.m., consuming only lunch and dinner. All patients ate each of their meals during the same scheduled times; all meals contained identical macronutrient content and composition.

©MattZ90/thinkstockimages.com

Areas under the curve of data values for tested measures during an early response interval (0-30 minutes after eating a meal) and 0-180 minutes after eating a meal were calculated by the trapezoidal rule. These calculations were used as an estimate of response to meal consumption.

Plasma levels for glucose, insulin, C-peptide, and iGLP-1 were, respectively, 16.5%, 45%, 50%, and 33% higher before lunch, on the day that patients consumed breakfast, than they were on the day that they skipped breakfast.

The plasma FFA level was 1,787.1% higher for study participants on the day when they fasted until lunch than it was on the day when they ate breakfast. During tests taken 60-180 minutes after consumption of breakfast, patients’ glucagon levels were 12.5% lower than those of patients who fasted before lunch.

On the day that patients skipped breakfast, insulin was 17% lower after lunch and 7.9% lower after dinner, compared with the amounts of insulin found on the day that patients ate breakfast; iGLP-1 was also lower after dinner (16.5%) on the day that patients skipped breakfast.

After lunch and dinner, glucagon levels were 9.7% and 11.5% higher, respectively, on the day that patients refrained from eating breakfast than on the day that patients ate breakfast. Following lunch and dinner on the day that patients skipped breakfast, FFA values were higher (41.1% and 29.6%, respectively).

“We showed that the deleterious effects of breakfast omission triggering hyperglycemic response occurred after lunch and dinner, but the exact duration of this effect is not known,” wrote Dr. Jakubowicz and her colleagues. “In addition, the role of insulin sensitivity, suppression of hepatic glucose production, gastric emptying, and clock gene expression remain undefined.”

Read the full study in Diabetes Care (doi:10.2337/dc15-0761).

klennon@frontlinemedcom.com

When type 2 diabetes patients skipped breakfast, they had higher levels of glucagon and free fatty acids (FFA), and reduced levels of insulin, C-peptide, and intact glucagonlike peptide-1 (iGLP-1) after meals, compared with when they ate breakfast, according to a randomized, open-label, cross-over-within-subject clinical trial.

A total of 22 overweight or obese people who had type 2 diabetes completed the study. Patients could not be taking GLP-1 analogs, anorectic drugs, steroids, or oral hypoglycemic agents, other than metformin. Seven of the patients had a history of hypertension and were treated with ACE inhibitors and/or calcium antagonists, wrote Dr. Daniela Jakubowicz of the Diabetes Unit in Hospital de Clinicas in Caracas, Venezuela.

At the Diabetes Unit, the patients participated in 2 full days of testing, separated by a washout period of 2-4 weeks. On one of the days, patients consumed three meals, including breakfast. On the other testing day, patients fasted until 1:30 p.m., consuming only lunch and dinner. All patients ate each of their meals during the same scheduled times; all meals contained identical macronutrient content and composition.

©MattZ90/thinkstockimages.com

Areas under the curve of data values for tested measures during an early response interval (0-30 minutes after eating a meal) and 0-180 minutes after eating a meal were calculated by the trapezoidal rule. These calculations were used as an estimate of response to meal consumption.

Plasma levels for glucose, insulin, C-peptide, and iGLP-1 were, respectively, 16.5%, 45%, 50%, and 33% higher before lunch, on the day that patients consumed breakfast, than they were on the day that they skipped breakfast.

The plasma FFA level was 1,787.1% higher for study participants on the day when they fasted until lunch than it was on the day when they ate breakfast. During tests taken 60-180 minutes after consumption of breakfast, patients’ glucagon levels were 12.5% lower than those of patients who fasted before lunch.

On the day that patients skipped breakfast, insulin was 17% lower after lunch and 7.9% lower after dinner, compared with the amounts of insulin found on the day that patients ate breakfast; iGLP-1 was also lower after dinner (16.5%) on the day that patients skipped breakfast.

After lunch and dinner, glucagon levels were 9.7% and 11.5% higher, respectively, on the day that patients refrained from eating breakfast than on the day that patients ate breakfast. Following lunch and dinner on the day that patients skipped breakfast, FFA values were higher (41.1% and 29.6%, respectively).

“We showed that the deleterious effects of breakfast omission triggering hyperglycemic response occurred after lunch and dinner, but the exact duration of this effect is not known,” wrote Dr. Jakubowicz and her colleagues. “In addition, the role of insulin sensitivity, suppression of hepatic glucose production, gastric emptying, and clock gene expression remain undefined.”

Read the full study in Diabetes Care (doi:10.2337/dc15-0761).

klennon@frontlinemedcom.com

A single dose of an experimental vaccine was up to 100% effective at preventing Ebola infection among those who had come into contact with recently infected individuals, according to interim results of an open-label trial conducted earlier this year in Guinea.

The study, which took place during an Ebola outbreak, included 90 clusters totaling 7,651 people who either had direct contact with someone recently diagnosed with Ebola or had contact with a direct contact. Children and pregnant or breastfeeding women were not eligible for the vaccine, and some study participants refused vaccination.

Consenting and eligible participants in 48 clusters were randomized to receive the vaccine (rVSV-ZEBOV) immediately after randomization; those in the remaining 42 clusters were vaccinated 21 days after randomization. Given that the incubation period of the virus is 10 days, the primary outcome was laboratory-confirmed Ebola infection at least 10 days after randomization to either immediate or delayed vaccination.

None of the 2,014 immediately vaccinated individuals contracted Ebola during that time, while 16 of the 1,0121 adults in the delayed vaccination group became infected, showing vaccine efficacy of 100%, Dr. Ana Maria Henao-Restrepo of the World Health Organization, Geneva, and her colleagues wrote in the Lancet.

At the cluster level, vaccine efficacy was 76% when all individuals – including children and pregnant and lactating women who were not vaccinated – were included. A total of 43 serious adverse events were reported, one of which was deemed directly related to vaccination.

“The interim results of [this trial] suggest that the efficacy of a single injection of rVSV-ZEBOV to prevent Ebola virus disease might be high, that protection can be established quickly, and that the vaccine might be effective at the population level when delivered by ring vaccination ...” the investigators wrote. The trial will be continued.

The results of this research project “will be the subject of intense scientific scrutiny and debate,” but a team under the World Health Organization’s leadership and the GAVI Alliance are ready to respectively support, and fund procurement and deployment of the vaccine, if it gets licensed, according to an editorial.

Read the full study in The Lancet (http://www.thelancet.com/pb/assets/raw/Lancet/pdfs/S0140673615611175.pdf ).

A single dose of an experimental vaccine was up to 100% effective at preventing Ebola infection among those who had come into contact with recently infected individuals, according to interim results of an open-label trial conducted earlier this year in Guinea.

The study, which took place during an Ebola outbreak, included 90 clusters totaling 7,651 people who either had direct contact with someone recently diagnosed with Ebola or had contact with a direct contact. Children and pregnant or breastfeeding women were not eligible for the vaccine, and some study participants refused vaccination.

Consenting and eligible participants in 48 clusters were randomized to receive the vaccine (rVSV-ZEBOV) immediately after randomization; those in the remaining 42 clusters were vaccinated 21 days after randomization. Given that the incubation period of the virus is 10 days, the primary outcome was laboratory-confirmed Ebola infection at least 10 days after randomization to either immediate or delayed vaccination.

None of the 2,014 immediately vaccinated individuals contracted Ebola during that time, while 16 of the 1,0121 adults in the delayed vaccination group became infected, showing vaccine efficacy of 100%, Dr. Ana Maria Henao-Restrepo of the World Health Organization, Geneva, and her colleagues wrote in the Lancet.

At the cluster level, vaccine efficacy was 76% when all individuals – including children and pregnant and lactating women who were not vaccinated – were included. A total of 43 serious adverse events were reported, one of which was deemed directly related to vaccination.

“The interim results of [this trial] suggest that the efficacy of a single injection of rVSV-ZEBOV to prevent Ebola virus disease might be high, that protection can be established quickly, and that the vaccine might be effective at the population level when delivered by ring vaccination ...” the investigators wrote. The trial will be continued.

The results of this research project “will be the subject of intense scientific scrutiny and debate,” but a team under the World Health Organization’s leadership and the GAVI Alliance are ready to respectively support, and fund procurement and deployment of the vaccine, if it gets licensed, according to an editorial.

Read the full study in The Lancet (http://www.thelancet.com/pb/assets/raw/Lancet/pdfs/S0140673615611175.pdf ).

A single dose of an experimental vaccine was up to 100% effective at preventing Ebola infection among those who had come into contact with recently infected individuals, according to interim results of an open-label trial conducted earlier this year in Guinea.

The study, which took place during an Ebola outbreak, included 90 clusters totaling 7,651 people who either had direct contact with someone recently diagnosed with Ebola or had contact with a direct contact. Children and pregnant or breastfeeding women were not eligible for the vaccine, and some study participants refused vaccination.

Consenting and eligible participants in 48 clusters were randomized to receive the vaccine (rVSV-ZEBOV) immediately after randomization; those in the remaining 42 clusters were vaccinated 21 days after randomization. Given that the incubation period of the virus is 10 days, the primary outcome was laboratory-confirmed Ebola infection at least 10 days after randomization to either immediate or delayed vaccination.

None of the 2,014 immediately vaccinated individuals contracted Ebola during that time, while 16 of the 1,0121 adults in the delayed vaccination group became infected, showing vaccine efficacy of 100%, Dr. Ana Maria Henao-Restrepo of the World Health Organization, Geneva, and her colleagues wrote in the Lancet.

At the cluster level, vaccine efficacy was 76% when all individuals – including children and pregnant and lactating women who were not vaccinated – were included. A total of 43 serious adverse events were reported, one of which was deemed directly related to vaccination.

“The interim results of [this trial] suggest that the efficacy of a single injection of rVSV-ZEBOV to prevent Ebola virus disease might be high, that protection can be established quickly, and that the vaccine might be effective at the population level when delivered by ring vaccination ...” the investigators wrote. The trial will be continued.

The results of this research project “will be the subject of intense scientific scrutiny and debate,” but a team under the World Health Organization’s leadership and the GAVI Alliance are ready to respectively support, and fund procurement and deployment of the vaccine, if it gets licensed, according to an editorial.

Read the full study in The Lancet (http://www.thelancet.com/pb/assets/raw/Lancet/pdfs/S0140673615611175.pdf ).

A single dose of an experimental vaccine was up to 100% effective at preventing Ebola infection among those who had come into contact with recently infected individuals, according to interim results of an open-label trial conducted earlier this year in Guinea.

The study, which took place during an Ebola outbreak, included 90 clusters totaling 7,651 people who either had direct contact with someone recently diagnosed with Ebola or had contact with a direct contact. Children and pregnant or breastfeeding women were not eligible for the vaccine, and some study participants refused vaccination.

Consenting and eligible participants in 48 clusters were randomized to receive the vaccine (rVSV-ZEBOV) immediately after randomization; those in the remaining 42 clusters were vaccinated 21 days after randomization. Given that the incubation period of the virus is 10 days, the primary outcome was laboratory-confirmed Ebola infection at least 10 days after randomization to either immediate or delayed vaccination.

None of the 2,014 immediately vaccinated individuals contracted Ebola during that time, while 16 of the 1,0121 adults in the delayed vaccination group became infected, showing vaccine efficacy of 100%, Dr. Ana Maria Henao-Restrepo of the World Health Organization, Geneva, and her colleagues wrote in the Lancet.

At the cluster level, vaccine efficacy was 76% when all individuals – including children and pregnant and lactating women who were not vaccinated – were included. A total of 43 serious adverse events were reported, one of which was deemed directly related to vaccination.

“The interim results of [this trial] suggest that the efficacy of a single injection of rVSV-ZEBOV to prevent Ebola virus disease might be high, that protection can be established quickly, and that the vaccine might be effective at the population level when delivered by ring vaccination ...” the investigators wrote. The trial will be continued.

The results of this research project “will be the subject of intense scientific scrutiny and debate,” but a team under the World Health Organization’s leadership and the GAVI Alliance are ready to respectively support, and fund procurement and deployment of the vaccine, if it gets licensed, according to an editorial.

Read the full study in The Lancet (http://www.thelancet.com/pb/assets/raw/Lancet/pdfs/S0140673615611175.pdf ).

klennon@frontlinemedcom.com

A single dose of an experimental vaccine was up to 100% effective at preventing Ebola infection among those who had come into contact with recently infected individuals, according to interim results of an open-label trial conducted earlier this year in Guinea.

The study, which took place during an Ebola outbreak, included 90 clusters totaling 7,651 people who either had direct contact with someone recently diagnosed with Ebola or had contact with a direct contact. Children and pregnant or breastfeeding women were not eligible for the vaccine, and some study participants refused vaccination.

Consenting and eligible participants in 48 clusters were randomized to receive the vaccine (rVSV-ZEBOV) immediately after randomization; those in the remaining 42 clusters were vaccinated 21 days after randomization. Given that the incubation period of the virus is 10 days, the primary outcome was laboratory-confirmed Ebola infection at least 10 days after randomization to either immediate or delayed vaccination.

None of the 2,014 immediately vaccinated individuals contracted Ebola during that time, while 16 of the 1,0121 adults in the delayed vaccination group became infected, showing vaccine efficacy of 100%, Dr. Ana Maria Henao-Restrepo of the World Health Organization, Geneva, and her colleagues wrote in the Lancet.

At the cluster level, vaccine efficacy was 76% when all individuals – including children and pregnant and lactating women who were not vaccinated – were included. A total of 43 serious adverse events were reported, one of which was deemed directly related to vaccination.

“The interim results of [this trial] suggest that the efficacy of a single injection of rVSV-ZEBOV to prevent Ebola virus disease might be high, that protection can be established quickly, and that the vaccine might be effective at the population level when delivered by ring vaccination ...” the investigators wrote. The trial will be continued.

The results of this research project “will be the subject of intense scientific scrutiny and debate,” but a team under the World Health Organization’s leadership and the GAVI Alliance are ready to respectively support, and fund procurement and deployment of the vaccine, if it gets licensed, according to an editorial.

Read the full study in The Lancet (http://www.thelancet.com/pb/assets/raw/Lancet/pdfs/S0140673615611175.pdf ).

klennon@frontlinemedcom.com

A single dose of an experimental vaccine was up to 100% effective at preventing Ebola infection among those who had come into contact with recently infected individuals, according to interim results of an open-label trial conducted earlier this year in Guinea.

The study, which took place during an Ebola outbreak, included 90 clusters totaling 7,651 people who either had direct contact with someone recently diagnosed with Ebola or had contact with a direct contact. Children and pregnant or breastfeeding women were not eligible for the vaccine, and some study participants refused vaccination.

Consenting and eligible participants in 48 clusters were randomized to receive the vaccine (rVSV-ZEBOV) immediately after randomization; those in the remaining 42 clusters were vaccinated 21 days after randomization. Given that the incubation period of the virus is 10 days, the primary outcome was laboratory-confirmed Ebola infection at least 10 days after randomization to either immediate or delayed vaccination.

None of the 2,014 immediately vaccinated individuals contracted Ebola during that time, while 16 of the 1,0121 adults in the delayed vaccination group became infected, showing vaccine efficacy of 100%, Dr. Ana Maria Henao-Restrepo of the World Health Organization, Geneva, and her colleagues wrote in the Lancet.

At the cluster level, vaccine efficacy was 76% when all individuals – including children and pregnant and lactating women who were not vaccinated – were included. A total of 43 serious adverse events were reported, one of which was deemed directly related to vaccination.

“The interim results of [this trial] suggest that the efficacy of a single injection of rVSV-ZEBOV to prevent Ebola virus disease might be high, that protection can be established quickly, and that the vaccine might be effective at the population level when delivered by ring vaccination ...” the investigators wrote. The trial will be continued.

The results of this research project “will be the subject of intense scientific scrutiny and debate,” but a team under the World Health Organization’s leadership and the GAVI Alliance are ready to respectively support, and fund procurement and deployment of the vaccine, if it gets licensed, according to an editorial.

Read the full study in The Lancet (http://www.thelancet.com/pb/assets/raw/Lancet/pdfs/S0140673615611175.pdf ).

klennon@frontlinemedcom.com

Many doctors have neglected to advise or have misinformed mothers on the proper infant care practices, according to a self-report study of mothers, with an oversampling of black and Hispanics.

“Advice received by mothers from potentially influential sources such as medical professionals, family, and the media represents a potentially important modifiable factor that may influence mothers’ choices about infant care practices,” wrote Dr. Staci R. Eisenberg of Boston Medical Center and her colleagues (Pediatrics 2015 [doi:10.1542/peds.2015-0551]). However, little is known about how regularly these mothers receive such advice and whether the advice given is consistent.

©Travis Manley/Thinkstock

The researchers studied responses to survey questions on mothers’ knowledge of generally accepted practices regarding immunization, breastfeeding, sleep position, sleep location, and pacifier use. The survey probed mothers on what advice they received on caring for their infants and from whom they obtained such suggestions. Thirty-two U.S. hospitals administered the survey to approximately 1,000 mothers of infants aged 2-6 months.

Although survey participants most often reported receiving advice on infant care from doctors, approximately 20% of mothers said that they did not receive advice from doctors on breastfeeding and sleep positions, and more than 50% of survey participants said they received no advice about sleep location or pacifier use.

Incorrect advice on breastfeeding and pacifier use was received by 10%-15% of the mothers.

Additionally, more than 25% of the study’s participants were told to have their babies sleep in positions and locations that were “not consistent with recommendations,” a finding that Dr. Scott Krugman of MedStar Franklin Square Medical Center, Baltimore, and Carolyn J. Crumpsty-Fowler, Ph.D., of the Bloomberg School of Public Health, in Baltimore, said they found concerning in an accompanying editorial (Pediatrics 2015 [doi:10.1542/peds.2015-1826]).

This study “is a wake-up call for all pediatricians,” said Dr. Krugman and Dr. Crumpsty-Fowler. “We can and must do a better job of engaging fully in evidence-informed, culturally appropriate public discourse that transforms social norms about the necessity of providing a safe sleep environment for infants.

The survey participants also said they received advice on infant care practices from birth hospital nurses, family members, and the media. Nurses and doctors provided similar advice on most practices. The mothers report receiving advice from family members about 30%-60% of the time on the subjects surveyed, and “more than 20% of advice about breastfeeding, and roughly two-thirds of advice about sleep position, sleep location, and pacifier use was not consistent with recommendations,” the investigators said.

The media was reported as a source of advice less than half of the time on all practices, with the exception of breastfeeding; approximately 70% of mothers reported receiving advice on breastfeeding from this source, but the advice was inconsistent with “recommended infant care practices” about 20% of the time.

Another of the study’s findings was that black and Hispanic mothers were more likely than white mothers to report receiving advice consistent with generally accepted practices.

“For health care providers, our findings may suggest a need for increased attention not only to the content of advice delivered, but also to message clarity and delivery,” noted Dr. Staci R. Eisenberg and her colleagues. Understanding that advice provided often is “inconsistent with recommendations may help identify important targets for public health efforts to increase adherence.”

Read the full study in Pediatrics (doi:10.1542/peds.2015-0551).

klennon@frontlinemedcom.com

Many doctors have neglected to advise or have misinformed mothers on the proper infant care practices, according to a self-report study of mothers, with an oversampling of black and Hispanics.

“Advice received by mothers from potentially influential sources such as medical professionals, family, and the media represents a potentially important modifiable factor that may influence mothers’ choices about infant care practices,” wrote Dr. Staci R. Eisenberg of Boston Medical Center and her colleagues (Pediatrics 2015 [doi:10.1542/peds.2015-0551]). However, little is known about how regularly these mothers receive such advice and whether the advice given is consistent.

©Travis Manley/Thinkstock

The researchers studied responses to survey questions on mothers’ knowledge of generally accepted practices regarding immunization, breastfeeding, sleep position, sleep location, and pacifier use. The survey probed mothers on what advice they received on caring for their infants and from whom they obtained such suggestions. Thirty-two U.S. hospitals administered the survey to approximately 1,000 mothers of infants aged 2-6 months.

Although survey participants most often reported receiving advice on infant care from doctors, approximately 20% of mothers said that they did not receive advice from doctors on breastfeeding and sleep positions, and more than 50% of survey participants said they received no advice about sleep location or pacifier use.

Incorrect advice on breastfeeding and pacifier use was received by 10%-15% of the mothers.

Additionally, more than 25% of the study’s participants were told to have their babies sleep in positions and locations that were “not consistent with recommendations,” a finding that Dr. Scott Krugman of MedStar Franklin Square Medical Center, Baltimore, and Carolyn J. Crumpsty-Fowler, Ph.D., of the Bloomberg School of Public Health, in Baltimore, said they found concerning in an accompanying editorial (Pediatrics 2015 [doi:10.1542/peds.2015-1826]).

This study “is a wake-up call for all pediatricians,” said Dr. Krugman and Dr. Crumpsty-Fowler. “We can and must do a better job of engaging fully in evidence-informed, culturally appropriate public discourse that transforms social norms about the necessity of providing a safe sleep environment for infants.

The survey participants also said they received advice on infant care practices from birth hospital nurses, family members, and the media. Nurses and doctors provided similar advice on most practices. The mothers report receiving advice from family members about 30%-60% of the time on the subjects surveyed, and “more than 20% of advice about breastfeeding, and roughly two-thirds of advice about sleep position, sleep location, and pacifier use was not consistent with recommendations,” the investigators said.

The media was reported as a source of advice less than half of the time on all practices, with the exception of breastfeeding; approximately 70% of mothers reported receiving advice on breastfeeding from this source, but the advice was inconsistent with “recommended infant care practices” about 20% of the time.

Another of the study’s findings was that black and Hispanic mothers were more likely than white mothers to report receiving advice consistent with generally accepted practices.

“For health care providers, our findings may suggest a need for increased attention not only to the content of advice delivered, but also to message clarity and delivery,” noted Dr. Staci R. Eisenberg and her colleagues. Understanding that advice provided often is “inconsistent with recommendations may help identify important targets for public health efforts to increase adherence.”

Read the full study in Pediatrics (doi:10.1542/peds.2015-0551).

klennon@frontlinemedcom.com

Many doctors have neglected to advise or have misinformed mothers on the proper infant care practices, according to a self-report study of mothers, with an oversampling of black and Hispanics.

“Advice received by mothers from potentially influential sources such as medical professionals, family, and the media represents a potentially important modifiable factor that may influence mothers’ choices about infant care practices,” wrote Dr. Staci R. Eisenberg of Boston Medical Center and her colleagues (Pediatrics 2015 [doi:10.1542/peds.2015-0551]). However, little is known about how regularly these mothers receive such advice and whether the advice given is consistent.

©Travis Manley/Thinkstock

The researchers studied responses to survey questions on mothers’ knowledge of generally accepted practices regarding immunization, breastfeeding, sleep position, sleep location, and pacifier use. The survey probed mothers on what advice they received on caring for their infants and from whom they obtained such suggestions. Thirty-two U.S. hospitals administered the survey to approximately 1,000 mothers of infants aged 2-6 months.

Although survey participants most often reported receiving advice on infant care from doctors, approximately 20% of mothers said that they did not receive advice from doctors on breastfeeding and sleep positions, and more than 50% of survey participants said they received no advice about sleep location or pacifier use.

Incorrect advice on breastfeeding and pacifier use was received by 10%-15% of the mothers.

Additionally, more than 25% of the study’s participants were told to have their babies sleep in positions and locations that were “not consistent with recommendations,” a finding that Dr. Scott Krugman of MedStar Franklin Square Medical Center, Baltimore, and Carolyn J. Crumpsty-Fowler, Ph.D., of the Bloomberg School of Public Health, in Baltimore, said they found concerning in an accompanying editorial (Pediatrics 2015 [doi:10.1542/peds.2015-1826]).

This study “is a wake-up call for all pediatricians,” said Dr. Krugman and Dr. Crumpsty-Fowler. “We can and must do a better job of engaging fully in evidence-informed, culturally appropriate public discourse that transforms social norms about the necessity of providing a safe sleep environment for infants.

The survey participants also said they received advice on infant care practices from birth hospital nurses, family members, and the media. Nurses and doctors provided similar advice on most practices. The mothers report receiving advice from family members about 30%-60% of the time on the subjects surveyed, and “more than 20% of advice about breastfeeding, and roughly two-thirds of advice about sleep position, sleep location, and pacifier use was not consistent with recommendations,” the investigators said.

The media was reported as a source of advice less than half of the time on all practices, with the exception of breastfeeding; approximately 70% of mothers reported receiving advice on breastfeeding from this source, but the advice was inconsistent with “recommended infant care practices” about 20% of the time.

Another of the study’s findings was that black and Hispanic mothers were more likely than white mothers to report receiving advice consistent with generally accepted practices.

“For health care providers, our findings may suggest a need for increased attention not only to the content of advice delivered, but also to message clarity and delivery,” noted Dr. Staci R. Eisenberg and her colleagues. Understanding that advice provided often is “inconsistent with recommendations may help identify important targets for public health efforts to increase adherence.”

Read the full study in Pediatrics (doi:10.1542/peds.2015-0551).

klennon@frontlinemedcom.com

Using deferasirox to induce iron deficiency may improve the symptoms of congenital erythropoietic porphyria.

The findings come from a study of a woman of Alaskan Native descent who was diagnosed as an infant with CEP and had compound heterozygosity for C73R and A104V mutations in uroporphyrinogen III synthase. Her disease complications included chronic hemolysis and severe photosensitivity with scarring, which were managed with sun avoidance and supportive measures including blood transfusions.

With an episode of occult gastrointestinal bleeding, the patient reported a dramatic improvement in photosensitivity and a normalization in urine color. “Markers of hemolysis also improved, with a reduction in lactate dehydrogenase (LDH) level to 138 U/L and a marked reduction in circulating nucleated red blood cells (nRBCs) to 0.2 × 10³ cells/mL. Hemoglobin level increased from 6.9 to 9.4. Reticulocyte count decreased to 55 billion cells/L.”

When the GI bleeding resolved, the patient’s serum ferritin level rose to 208 ng/mL, her photosensitivity worsened, and her urine color darkened. “Similarly, her LDH level increased to 540 U/L, reticulocyte count increased markedly to 163 billion cells/L, and nRBCs increased to 4.3 x 10³ cells/mL.”

The researchers initiated a trial of deferasirox initially dosed at 500 mg daily for several months and then adjusted to 500 mg three times weekly to target a ferritin level range of 10-15 ng/mL. “With deferasirox, [her] serum ferritin level dropped to 16 ng/mL at 2 months and the patient again reported an improvement in her quality of life with reduced photosensitivity.” Also, total urine porphyrins decreased from 108,364 mcg/24 hours before treatment to 5896.3 mcg/24 hours after 4 months. Concurrently, LDH normalized to a level of 135 U/L, reticulocyte count decreased to 47 billion/L, nRBCs remained between 0.14 and 0.68 × 10³ cells/mL, and hemoglobin level remained between 6.8 and 9.0 g/dL without transfusional support.

Upper GI bleeding recurred, however, so deferasirox was discontinued and red blood cell transfusions were administered. “Over the ensuing 2 years, numerous repeat endoscopies showed persistent gastric erosions and ulcerations despite ongoing use of a proton pump inhibitor.” As a result of the ongoing iron losses, ferritin levels remained within normal range and symptoms and laboratory markers of hemolysis were stabilized.

When the GI bleeding resolved, the patient’s lab values and her photosensitivity suddenly worsened.

Although not known to be a complication of congenital erythropoietic porphyria, the patient developed liver disease of unknown etiology and she died at age 35 of complications of liver failure, hepatorenal syndrome, and hemolysis after nearly 3 years of reduced symptom severity “and a considerable improvement in her quality of life,” Dr. Daniel N. Egan of the University of Washington, Seattle, and his colleagues reported in the case study in Blood (2015;126:257-261).

“Microscopic examination of the liver at autopsy demonstrated areas of marked sinusoidal congestion and dilatation containing aggregates of erythroid precursors consistent with diffuse intrasinusoidal extramedullary hematopoiesis. Extensive patchy fibrosis was present, without regenerative nodules or cirrhosis. Importantly, there was no evidence of polarizable material to suggest porphyrin metabolite accumulation.”

The patient’s sister, who had the same disorder, also died “from sudden cardiac death in the setting of pulmonary hypertension.”

The researchers obtained bone marrow cells from both sisters and cultured the cells in 5% plasma and varying ratios of holo-transferrin (holo-Tf) and apo-transferrin (apo-Tf) (Sigma). The level of available iron was 1.52 mcM with 100% apo-Tf and 9.52 mcM with 100% holo-Tf.

“Erythroid cells obtained from the bone marrow of this CEP patient demonstrated improved growth and differentiation in conditions of relative iron deficiency,” the authors wrote. “The percentages of normal cells reaching stages III and IV at culture day 10 progressively decreased from 67.2% to 38.4% when available iron was reduced.”

“Iron restriction likely impedes heme synthesis upstream of uroporphyrinogen III synthase via decreasing 5-aminolevulinate synthase 2 mRNA translation. Because the tricarboxylic acid cycle enzyme aconitase contains a 4Fe-4S cluster, it also is possible that decreased availability of succinyl coenzyme A, a key substrate for the rate-limiting step in heme production, may play a role,” the researchers wrote.

klennon@frontlinemedcom.com

Using deferasirox to induce iron deficiency may improve the symptoms of congenital erythropoietic porphyria.

The findings come from a study of a woman of Alaskan Native descent who was diagnosed as an infant with CEP and had compound heterozygosity for C73R and A104V mutations in uroporphyrinogen III synthase. Her disease complications included chronic hemolysis and severe photosensitivity with scarring, which were managed with sun avoidance and supportive measures including blood transfusions.

With an episode of occult gastrointestinal bleeding, the patient reported a dramatic improvement in photosensitivity and a normalization in urine color. “Markers of hemolysis also improved, with a reduction in lactate dehydrogenase (LDH) level to 138 U/L and a marked reduction in circulating nucleated red blood cells (nRBCs) to 0.2 × 10³ cells/mL. Hemoglobin level increased from 6.9 to 9.4. Reticulocyte count decreased to 55 billion cells/L.”

When the GI bleeding resolved, the patient’s serum ferritin level rose to 208 ng/mL, her photosensitivity worsened, and her urine color darkened. “Similarly, her LDH level increased to 540 U/L, reticulocyte count increased markedly to 163 billion cells/L, and nRBCs increased to 4.3 x 10³ cells/mL.”

The researchers initiated a trial of deferasirox initially dosed at 500 mg daily for several months and then adjusted to 500 mg three times weekly to target a ferritin level range of 10-15 ng/mL. “With deferasirox, [her] serum ferritin level dropped to 16 ng/mL at 2 months and the patient again reported an improvement in her quality of life with reduced photosensitivity.” Also, total urine porphyrins decreased from 108,364 mcg/24 hours before treatment to 5896.3 mcg/24 hours after 4 months. Concurrently, LDH normalized to a level of 135 U/L, reticulocyte count decreased to 47 billion/L, nRBCs remained between 0.14 and 0.68 × 10³ cells/mL, and hemoglobin level remained between 6.8 and 9.0 g/dL without transfusional support.

Upper GI bleeding recurred, however, so deferasirox was discontinued and red blood cell transfusions were administered. “Over the ensuing 2 years, numerous repeat endoscopies showed persistent gastric erosions and ulcerations despite ongoing use of a proton pump inhibitor.” As a result of the ongoing iron losses, ferritin levels remained within normal range and symptoms and laboratory markers of hemolysis were stabilized.

When the GI bleeding resolved, the patient’s lab values and her photosensitivity suddenly worsened.

Although not known to be a complication of congenital erythropoietic porphyria, the patient developed liver disease of unknown etiology and she died at age 35 of complications of liver failure, hepatorenal syndrome, and hemolysis after nearly 3 years of reduced symptom severity “and a considerable improvement in her quality of life,” Dr. Daniel N. Egan of the University of Washington, Seattle, and his colleagues reported in the case study in Blood (2015;126:257-261).

“Microscopic examination of the liver at autopsy demonstrated areas of marked sinusoidal congestion and dilatation containing aggregates of erythroid precursors consistent with diffuse intrasinusoidal extramedullary hematopoiesis. Extensive patchy fibrosis was present, without regenerative nodules or cirrhosis. Importantly, there was no evidence of polarizable material to suggest porphyrin metabolite accumulation.”

The patient’s sister, who had the same disorder, also died “from sudden cardiac death in the setting of pulmonary hypertension.”

The researchers obtained bone marrow cells from both sisters and cultured the cells in 5% plasma and varying ratios of holo-transferrin (holo-Tf) and apo-transferrin (apo-Tf) (Sigma). The level of available iron was 1.52 mcM with 100% apo-Tf and 9.52 mcM with 100% holo-Tf.

“Erythroid cells obtained from the bone marrow of this CEP patient demonstrated improved growth and differentiation in conditions of relative iron deficiency,” the authors wrote. “The percentages of normal cells reaching stages III and IV at culture day 10 progressively decreased from 67.2% to 38.4% when available iron was reduced.”

“Iron restriction likely impedes heme synthesis upstream of uroporphyrinogen III synthase via decreasing 5-aminolevulinate synthase 2 mRNA translation. Because the tricarboxylic acid cycle enzyme aconitase contains a 4Fe-4S cluster, it also is possible that decreased availability of succinyl coenzyme A, a key substrate for the rate-limiting step in heme production, may play a role,” the researchers wrote.

klennon@frontlinemedcom.com

Using deferasirox to induce iron deficiency may improve the symptoms of congenital erythropoietic porphyria.

The findings come from a study of a woman of Alaskan Native descent who was diagnosed as an infant with CEP and had compound heterozygosity for C73R and A104V mutations in uroporphyrinogen III synthase. Her disease complications included chronic hemolysis and severe photosensitivity with scarring, which were managed with sun avoidance and supportive measures including blood transfusions.

With an episode of occult gastrointestinal bleeding, the patient reported a dramatic improvement in photosensitivity and a normalization in urine color. “Markers of hemolysis also improved, with a reduction in lactate dehydrogenase (LDH) level to 138 U/L and a marked reduction in circulating nucleated red blood cells (nRBCs) to 0.2 × 10³ cells/mL. Hemoglobin level increased from 6.9 to 9.4. Reticulocyte count decreased to 55 billion cells/L.”

When the GI bleeding resolved, the patient’s serum ferritin level rose to 208 ng/mL, her photosensitivity worsened, and her urine color darkened. “Similarly, her LDH level increased to 540 U/L, reticulocyte count increased markedly to 163 billion cells/L, and nRBCs increased to 4.3 x 10³ cells/mL.”

The researchers initiated a trial of deferasirox initially dosed at 500 mg daily for several months and then adjusted to 500 mg three times weekly to target a ferritin level range of 10-15 ng/mL. “With deferasirox, [her] serum ferritin level dropped to 16 ng/mL at 2 months and the patient again reported an improvement in her quality of life with reduced photosensitivity.” Also, total urine porphyrins decreased from 108,364 mcg/24 hours before treatment to 5896.3 mcg/24 hours after 4 months. Concurrently, LDH normalized to a level of 135 U/L, reticulocyte count decreased to 47 billion/L, nRBCs remained between 0.14 and 0.68 × 10³ cells/mL, and hemoglobin level remained between 6.8 and 9.0 g/dL without transfusional support.

Upper GI bleeding recurred, however, so deferasirox was discontinued and red blood cell transfusions were administered. “Over the ensuing 2 years, numerous repeat endoscopies showed persistent gastric erosions and ulcerations despite ongoing use of a proton pump inhibitor.” As a result of the ongoing iron losses, ferritin levels remained within normal range and symptoms and laboratory markers of hemolysis were stabilized.

When the GI bleeding resolved, the patient’s lab values and her photosensitivity suddenly worsened.

Although not known to be a complication of congenital erythropoietic porphyria, the patient developed liver disease of unknown etiology and she died at age 35 of complications of liver failure, hepatorenal syndrome, and hemolysis after nearly 3 years of reduced symptom severity “and a considerable improvement in her quality of life,” Dr. Daniel N. Egan of the University of Washington, Seattle, and his colleagues reported in the case study in Blood (2015;126:257-261).

“Microscopic examination of the liver at autopsy demonstrated areas of marked sinusoidal congestion and dilatation containing aggregates of erythroid precursors consistent with diffuse intrasinusoidal extramedullary hematopoiesis. Extensive patchy fibrosis was present, without regenerative nodules or cirrhosis. Importantly, there was no evidence of polarizable material to suggest porphyrin metabolite accumulation.”

The patient’s sister, who had the same disorder, also died “from sudden cardiac death in the setting of pulmonary hypertension.”

The researchers obtained bone marrow cells from both sisters and cultured the cells in 5% plasma and varying ratios of holo-transferrin (holo-Tf) and apo-transferrin (apo-Tf) (Sigma). The level of available iron was 1.52 mcM with 100% apo-Tf and 9.52 mcM with 100% holo-Tf.

“Erythroid cells obtained from the bone marrow of this CEP patient demonstrated improved growth and differentiation in conditions of relative iron deficiency,” the authors wrote. “The percentages of normal cells reaching stages III and IV at culture day 10 progressively decreased from 67.2% to 38.4% when available iron was reduced.”

“Iron restriction likely impedes heme synthesis upstream of uroporphyrinogen III synthase via decreasing 5-aminolevulinate synthase 2 mRNA translation. Because the tricarboxylic acid cycle enzyme aconitase contains a 4Fe-4S cluster, it also is possible that decreased availability of succinyl coenzyme A, a key substrate for the rate-limiting step in heme production, may play a role,” the researchers wrote.

klennon@frontlinemedcom.com