Katie Lennon

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 ).

[email protected]

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 ).

[email protected]

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 ).

[email protected]

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).

[email protected]

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).

[email protected]

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).

[email protected]

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.

[email protected]

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.

[email protected]

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.

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Osamu Corp. announced that it has voluntarily recalled frozen yellow tuna from a processing plant in Indonesia after 62 people become infected with Salmonella Paratyphi B variant L(+) tartrate(+) bacteria in the United States, according to the Centers for Disease Control and Prevention

“Epidemiologic and laboratory findings indicate that frozen tuna is the likely source of the infections,” with most of the victims having reported eating sushi made from raw tuna in the week prior to becoming sick, stated the CDC.

© oleksajewicz/Thinkstock

Symptoms of the disease typically include diarrhea, fever, and abdominal cramps 12-72 hours after an exposure. Of those infected during this outbreak, 11 were hospitalized and none died, according to the CDC.

Cases of this outbreak have been reported from 11 states, with illness onset dates having begun in March. The two most recent victims became infected with the bacteria after the CDC’s July 15 update on the outbreak.

Osamu has recalled the following:

• All frozen yellowfin tuna (loin, saku, chunk, slice, and ground market forms) sold to restaurants and grocery stories throughout the United States from May 9, 2014, to July 9, 2015. Affected products can be identified by four-digit purchase order numbers 8563 through 8599 located on each product carton box.

• One lot of frozen yellowfin tuna chunk meat distributed to AFC Corp. for use in sushi franchises in grocery stores throughout the United States from May 20, 2015, to May 26, 2015, after the Minnesota Department of Health and the Department of Agriculture isolated the outbreak strain from samples of unopened frozen raw tuna collected from a Minnesota grocery store where an ill person in this outbreak reported eating tuna sushi. The affected lot can be identified by lot number 68568.

The CDC instructs restaurants and retailers who do not know the lot number of frozen tuna in their freezers to contact the distributor and to avoid serving or selling any tuna unless they are certain it has not been recalled.

Restaurants and retailers can reach Osamu at 1-310-849-8881, Monday through Friday from 8:00 a.m. to 5:00 p.m., PDT.

The CDC advises consumers that raw fish or raw shellfish should to be consumed by anyone at high risk for serious food-borne illness, including children under 5 years, adults older than 65 years, pregnant women, and anyone with a weakened immune system.

[email protected]

Osamu Corp. announced that it has voluntarily recalled frozen yellow tuna from a processing plant in Indonesia after 62 people become infected with Salmonella Paratyphi B variant L(+) tartrate(+) bacteria in the United States, according to the Centers for Disease Control and Prevention

“Epidemiologic and laboratory findings indicate that frozen tuna is the likely source of the infections,” with most of the victims having reported eating sushi made from raw tuna in the week prior to becoming sick, stated the CDC.

© oleksajewicz/Thinkstock

Symptoms of the disease typically include diarrhea, fever, and abdominal cramps 12-72 hours after an exposure. Of those infected during this outbreak, 11 were hospitalized and none died, according to the CDC.

Cases of this outbreak have been reported from 11 states, with illness onset dates having begun in March. The two most recent victims became infected with the bacteria after the CDC’s July 15 update on the outbreak.

Osamu has recalled the following:

• All frozen yellowfin tuna (loin, saku, chunk, slice, and ground market forms) sold to restaurants and grocery stories throughout the United States from May 9, 2014, to July 9, 2015. Affected products can be identified by four-digit purchase order numbers 8563 through 8599 located on each product carton box.

• One lot of frozen yellowfin tuna chunk meat distributed to AFC Corp. for use in sushi franchises in grocery stores throughout the United States from May 20, 2015, to May 26, 2015, after the Minnesota Department of Health and the Department of Agriculture isolated the outbreak strain from samples of unopened frozen raw tuna collected from a Minnesota grocery store where an ill person in this outbreak reported eating tuna sushi. The affected lot can be identified by lot number 68568.

The CDC instructs restaurants and retailers who do not know the lot number of frozen tuna in their freezers to contact the distributor and to avoid serving or selling any tuna unless they are certain it has not been recalled.

Restaurants and retailers can reach Osamu at 1-310-849-8881, Monday through Friday from 8:00 a.m. to 5:00 p.m., PDT.

The CDC advises consumers that raw fish or raw shellfish should to be consumed by anyone at high risk for serious food-borne illness, including children under 5 years, adults older than 65 years, pregnant women, and anyone with a weakened immune system.

[email protected]

Osamu Corp. announced that it has voluntarily recalled frozen yellow tuna from a processing plant in Indonesia after 62 people become infected with Salmonella Paratyphi B variant L(+) tartrate(+) bacteria in the United States, according to the Centers for Disease Control and Prevention

“Epidemiologic and laboratory findings indicate that frozen tuna is the likely source of the infections,” with most of the victims having reported eating sushi made from raw tuna in the week prior to becoming sick, stated the CDC.

© oleksajewicz/Thinkstock

Symptoms of the disease typically include diarrhea, fever, and abdominal cramps 12-72 hours after an exposure. Of those infected during this outbreak, 11 were hospitalized and none died, according to the CDC.

Cases of this outbreak have been reported from 11 states, with illness onset dates having begun in March. The two most recent victims became infected with the bacteria after the CDC’s July 15 update on the outbreak.

Osamu has recalled the following:

• All frozen yellowfin tuna (loin, saku, chunk, slice, and ground market forms) sold to restaurants and grocery stories throughout the United States from May 9, 2014, to July 9, 2015. Affected products can be identified by four-digit purchase order numbers 8563 through 8599 located on each product carton box.

• One lot of frozen yellowfin tuna chunk meat distributed to AFC Corp. for use in sushi franchises in grocery stores throughout the United States from May 20, 2015, to May 26, 2015, after the Minnesota Department of Health and the Department of Agriculture isolated the outbreak strain from samples of unopened frozen raw tuna collected from a Minnesota grocery store where an ill person in this outbreak reported eating tuna sushi. The affected lot can be identified by lot number 68568.

The CDC instructs restaurants and retailers who do not know the lot number of frozen tuna in their freezers to contact the distributor and to avoid serving or selling any tuna unless they are certain it has not been recalled.

Restaurants and retailers can reach Osamu at 1-310-849-8881, Monday through Friday from 8:00 a.m. to 5:00 p.m., PDT.

The CDC advises consumers that raw fish or raw shellfish should to be consumed by anyone at high risk for serious food-borne illness, including children under 5 years, adults older than 65 years, pregnant women, and anyone with a weakened immune system.

[email protected]

Drinking sugar-sweetened beverages is associated with a greater incidence of type 2 diabetes, independent of obesity, according to a systematic review and meta-analysis.

The researchers analyzed data from prospective design studies that assessed the consumption of beverages and incident type 2 diabetes, recruited adults free of diabetes, and followed study participants for at least 2 years. The data came from 17 cohorts comprising 38,253 cases of type 2 diabetes over 10,126,756 person-years. Using risk estimates, sampling weights, and population size, the researchers estimated the absolute number of incidents of type 2 diabetes over 10 years, the number of incidents of type 2 diabetes attributable to consumption of sugar-sweetened beverages, and the proportion of the disease incidents attributable to drinking of sugar-sweetened beverages. These estimations assumed causality and no change in individuals’ characteristics over time.

©Lori Martin/Fotolia.com

Higher consumption of sugar-sweetened beverages by one serving per day was associated with an 18% greater incidence of type 2 diabetes (95% confidence interval, 8.8%-28%; I² [for heterogeneity] = 89%), before adjustment for adiposity. When adjusted for potential mediation and confounding by adiposity, the association was weakened to a 13% greater incidence of the disease.

Associations between drinking of artificially sweetened beverages and fruit juice were also found, but findings for artificially sweetened beverages were likely affected by publication bias and residual confounding; for fruit juice, the positive association was not stable and sensitive to study design.

“Under assumption of causality for the association of consumption of sugar-sweetened beverages with incident type 2 diabetes, we provided efficacy estimates that over 10 years two million type 2 diabetes events in the U.S. and 80,000 in the U.K. would be related to consumption of sugar-sweetened beverages,” according to Dr. Fumiaki Imamura of the University of Cambridge School of Clinical Medicine, and his colleagues.

“Future work should seek to improve precision of evidence and characterize efficacy and effectiveness of policy interventions for different populations,” according to the researchers.

Read the full study in the BMJ (doi:10.1136/bmj.h3576).

[email protected]

Drinking sugar-sweetened beverages is associated with a greater incidence of type 2 diabetes, independent of obesity, according to a systematic review and meta-analysis.

The researchers analyzed data from prospective design studies that assessed the consumption of beverages and incident type 2 diabetes, recruited adults free of diabetes, and followed study participants for at least 2 years. The data came from 17 cohorts comprising 38,253 cases of type 2 diabetes over 10,126,756 person-years. Using risk estimates, sampling weights, and population size, the researchers estimated the absolute number of incidents of type 2 diabetes over 10 years, the number of incidents of type 2 diabetes attributable to consumption of sugar-sweetened beverages, and the proportion of the disease incidents attributable to drinking of sugar-sweetened beverages. These estimations assumed causality and no change in individuals’ characteristics over time.

©Lori Martin/Fotolia.com

Higher consumption of sugar-sweetened beverages by one serving per day was associated with an 18% greater incidence of type 2 diabetes (95% confidence interval, 8.8%-28%; I² [for heterogeneity] = 89%), before adjustment for adiposity. When adjusted for potential mediation and confounding by adiposity, the association was weakened to a 13% greater incidence of the disease.

Associations between drinking of artificially sweetened beverages and fruit juice were also found, but findings for artificially sweetened beverages were likely affected by publication bias and residual confounding; for fruit juice, the positive association was not stable and sensitive to study design.

“Under assumption of causality for the association of consumption of sugar-sweetened beverages with incident type 2 diabetes, we provided efficacy estimates that over 10 years two million type 2 diabetes events in the U.S. and 80,000 in the U.K. would be related to consumption of sugar-sweetened beverages,” according to Dr. Fumiaki Imamura of the University of Cambridge School of Clinical Medicine, and his colleagues.

“Future work should seek to improve precision of evidence and characterize efficacy and effectiveness of policy interventions for different populations,” according to the researchers.

Read the full study in the BMJ (doi:10.1136/bmj.h3576).

[email protected]

Drinking sugar-sweetened beverages is associated with a greater incidence of type 2 diabetes, independent of obesity, according to a systematic review and meta-analysis.

The researchers analyzed data from prospective design studies that assessed the consumption of beverages and incident type 2 diabetes, recruited adults free of diabetes, and followed study participants for at least 2 years. The data came from 17 cohorts comprising 38,253 cases of type 2 diabetes over 10,126,756 person-years. Using risk estimates, sampling weights, and population size, the researchers estimated the absolute number of incidents of type 2 diabetes over 10 years, the number of incidents of type 2 diabetes attributable to consumption of sugar-sweetened beverages, and the proportion of the disease incidents attributable to drinking of sugar-sweetened beverages. These estimations assumed causality and no change in individuals’ characteristics over time.

©Lori Martin/Fotolia.com

Higher consumption of sugar-sweetened beverages by one serving per day was associated with an 18% greater incidence of type 2 diabetes (95% confidence interval, 8.8%-28%; I² [for heterogeneity] = 89%), before adjustment for adiposity. When adjusted for potential mediation and confounding by adiposity, the association was weakened to a 13% greater incidence of the disease.

Associations between drinking of artificially sweetened beverages and fruit juice were also found, but findings for artificially sweetened beverages were likely affected by publication bias and residual confounding; for fruit juice, the positive association was not stable and sensitive to study design.

“Under assumption of causality for the association of consumption of sugar-sweetened beverages with incident type 2 diabetes, we provided efficacy estimates that over 10 years two million type 2 diabetes events in the U.S. and 80,000 in the U.K. would be related to consumption of sugar-sweetened beverages,” according to Dr. Fumiaki Imamura of the University of Cambridge School of Clinical Medicine, and his colleagues.

“Future work should seek to improve precision of evidence and characterize efficacy and effectiveness of policy interventions for different populations,” according to the researchers.

Read the full study in the BMJ (doi:10.1136/bmj.h3576).

[email protected]