Anemia

The Centers for Disease Control and Prevention will be awarding $1.2 million in funding to help states collect data on issues faced by people with sickle cell disease.

Currently, only Georgia and California work with the CDC on the Sickle Cell Data Collection program to gather population-based, comprehensive health information about people with sickle cell disease. The new funding will expand that base to nine states. The money will go toward a 1-year project that will build infrastructure for recipient sites to gather unique data and conduct in-depth analyses in people with sickle cell disease, the CDC noted.

The sites that were awarded funding are Duke University, Durham, N.C.; Georgia State University, Atlanta; the Indiana Hemophilia and Thrombosis Center in Indianapolis; the Michigan Department of Health & Human Services; the Minnesota Department of Health; the Public Health Institute in Oakland, Calif.; the University of Alabama at Birmingham; the University of Tennessee Health Science Center in Memphis; and the Virginia Department of Health.

“Data is vital to informing new treatments and clinical care that will improve the lives of people affected by sickle cell disease. This new funding expands CDC’s partner network across the country which will accelerate efforts to ensure sickle cell patients live longer and healthier lives,” said CDC Director Robert R. Redfield, MD.

Find the full press release on the CDC website.

[email protected]

The Centers for Disease Control and Prevention will be awarding $1.2 million in funding to help states collect data on issues faced by people with sickle cell disease.

Currently, only Georgia and California work with the CDC on the Sickle Cell Data Collection program to gather population-based, comprehensive health information about people with sickle cell disease. The new funding will expand that base to nine states. The money will go toward a 1-year project that will build infrastructure for recipient sites to gather unique data and conduct in-depth analyses in people with sickle cell disease, the CDC noted.

The sites that were awarded funding are Duke University, Durham, N.C.; Georgia State University, Atlanta; the Indiana Hemophilia and Thrombosis Center in Indianapolis; the Michigan Department of Health & Human Services; the Minnesota Department of Health; the Public Health Institute in Oakland, Calif.; the University of Alabama at Birmingham; the University of Tennessee Health Science Center in Memphis; and the Virginia Department of Health.

“Data is vital to informing new treatments and clinical care that will improve the lives of people affected by sickle cell disease. This new funding expands CDC’s partner network across the country which will accelerate efforts to ensure sickle cell patients live longer and healthier lives,” said CDC Director Robert R. Redfield, MD.

Find the full press release on the CDC website.

[email protected]

The Centers for Disease Control and Prevention will be awarding $1.2 million in funding to help states collect data on issues faced by people with sickle cell disease.

Currently, only Georgia and California work with the CDC on the Sickle Cell Data Collection program to gather population-based, comprehensive health information about people with sickle cell disease. The new funding will expand that base to nine states. The money will go toward a 1-year project that will build infrastructure for recipient sites to gather unique data and conduct in-depth analyses in people with sickle cell disease, the CDC noted.

The sites that were awarded funding are Duke University, Durham, N.C.; Georgia State University, Atlanta; the Indiana Hemophilia and Thrombosis Center in Indianapolis; the Michigan Department of Health & Human Services; the Minnesota Department of Health; the Public Health Institute in Oakland, Calif.; the University of Alabama at Birmingham; the University of Tennessee Health Science Center in Memphis; and the Virginia Department of Health.

“Data is vital to informing new treatments and clinical care that will improve the lives of people affected by sickle cell disease. This new funding expands CDC’s partner network across the country which will accelerate efforts to ensure sickle cell patients live longer and healthier lives,” said CDC Director Robert R. Redfield, MD.

Find the full press release on the CDC website.

[email protected]

Early results indicate experimental gene therapies could illicit a cure for sickle cell disease (SCD), but many barriers to access remain, namely cost, experts reported during a recent webinar sponsored by the National Heart, Lung, and Blood Institute.

Pogonic/Getty Images

At present, allogeneic hematopoietic stem cell transplant remains the only curative therapy available for patients with SCD. Newer transplant techniques include the use of mobilized blood stem cells, where stem cells are collected from the circulation using blood cell growth factors, explained Mark Walters, MD, of UCSF Benioff Children’s Hospital Oakland in California.

The most promising experimental gene therapies currently undergoing clinical development are gene-addition and gene-editing therapies, he said. Another technique, in vivo gene editing to correct the sickle mutation, is also being investigated, but has not yet reached clinical development.
 

Gene-addition therapy

Gene-addition therapy is a technique where a fetal hemoglobin (HbF) or anti-sickling beta-hemoglobin gene is inserted into a hematopoietic stem cell to illicit a curative effect. In this technique, the corrective gene is harvested from a patient’s own blood stem cells.

In patients with SCD, when HbF levels are elevated, the likelihood of sickling is reduced, resulting in a milder form of disease. As a result, raising HbF levels is a therapeutic target that forms the basis of several ongoing clinical studies.

The technique involves packaging an HbF rescue gene into a viral vector and coincubating the vector with a patient’s own blood stem cells. Subsequently, the corrected stem cells are injected back into the patient to produce higher levels of HbF.

The ongoing phase 1/2 HGB-206 clinical study is evaluating this technique in patients aged 12-50 years with severe SCD in multiple centers throughout Europe and the United States.

In those treated thus far, initial results appear promising, Dr. Walters reported, with one patient experiencing a rise in Hb levels from 10.7 g/dL at 3 months to 15.0 g/dL at 15 months follow-up.

Dr. Walters also reported that some of these patients no longer exhibit any signs or symptoms of SCD, such as anemia or painful adverse events. While these initial findings are compelling, whether these benefits will be maintained is still unknown.

“While it’s too early to call this a cure, if [these results] could be extended for 5, 10, or 15 years, I think everyone would agree that this would be a cure,” he said.

This technique could be universally available, he said, since a patient’s own blood stem cells are used. Other complications, such as graft-versus-host disease (GVHD) or immune-related reactions, are negated with this form of therapy, he said.

Recent evidence has demonstrated that only about 20% of donor stem cells need to be corrected to illicit a very strong effect. This principle is now being applied in gene-editing techniques, as correcting every gene in every stem cell would be very challenging, Dr. Walters explained.
 

Gene editing

Another technique being investigated in SCD is gene editing, in which the fetal hemoglobin gene is “reawakened,” or other techniques are used to correct the sickle gene directly, such as CRISPR-Cas9 technology, Dr. Walters said.

In this technique, the Cas9 protein makes a cut and repairs an individual’s genomic DNA by inserting a strand of corrected donor DNA. The novel technology would allow for targeted genome editing that is specific to the SCD patient.

Currently, this experimental therapy is being investigated in preclinical studies. Dr. Walters said that he and his colleagues hope to begin enrolling patients in clinical trials within the next 1-2 years.

But while some gene therapies have been approved in other disorders, such as spinal muscle atrophy, a limiting factor to widespread availability is cost. Despite promising initial results in SCD, the affordability of future gene therapies will be a key factor to universal access, Dr. Walters said.
 

The Cure Sickle Cell Initiative

Traci Mondoro, PhD, chief of the Translational Blood Science and Resources Branch at NHLBI, explained that the NHLBI has funded a large proportion of the research that has formed the basis of several genetically based clinical studies.

One of the primary goals of the Cure Sickle Cell Initiative is to bridge the gap between new research and the SCD community. Their aim is to improve access for patients to participate in genetically based studies to advance cures.

The comprehensive approach is intended to fill in existing gaps by funding breakthrough research in both academic and private settings.

By establishing partnerships with key stakeholders, institutions, and patient groups, Dr. Mondoro said they hope to increase patient participation in clinical trials involving curative therapies. In the future, they also intend to establish a large body of evidence to provide adequate safety data to study these therapies in pediatric populations.

Dr. Walters and Dr. Mondoro did not provide information on financial disclosures.

Early results indicate experimental gene therapies could illicit a cure for sickle cell disease (SCD), but many barriers to access remain, namely cost, experts reported during a recent webinar sponsored by the National Heart, Lung, and Blood Institute.

Pogonic/Getty Images

At present, allogeneic hematopoietic stem cell transplant remains the only curative therapy available for patients with SCD. Newer transplant techniques include the use of mobilized blood stem cells, where stem cells are collected from the circulation using blood cell growth factors, explained Mark Walters, MD, of UCSF Benioff Children’s Hospital Oakland in California.

The most promising experimental gene therapies currently undergoing clinical development are gene-addition and gene-editing therapies, he said. Another technique, in vivo gene editing to correct the sickle mutation, is also being investigated, but has not yet reached clinical development.
 

Gene-addition therapy

Gene-addition therapy is a technique where a fetal hemoglobin (HbF) or anti-sickling beta-hemoglobin gene is inserted into a hematopoietic stem cell to illicit a curative effect. In this technique, the corrective gene is harvested from a patient’s own blood stem cells.

In patients with SCD, when HbF levels are elevated, the likelihood of sickling is reduced, resulting in a milder form of disease. As a result, raising HbF levels is a therapeutic target that forms the basis of several ongoing clinical studies.

The technique involves packaging an HbF rescue gene into a viral vector and coincubating the vector with a patient’s own blood stem cells. Subsequently, the corrected stem cells are injected back into the patient to produce higher levels of HbF.

The ongoing phase 1/2 HGB-206 clinical study is evaluating this technique in patients aged 12-50 years with severe SCD in multiple centers throughout Europe and the United States.

In those treated thus far, initial results appear promising, Dr. Walters reported, with one patient experiencing a rise in Hb levels from 10.7 g/dL at 3 months to 15.0 g/dL at 15 months follow-up.

Dr. Walters also reported that some of these patients no longer exhibit any signs or symptoms of SCD, such as anemia or painful adverse events. While these initial findings are compelling, whether these benefits will be maintained is still unknown.

“While it’s too early to call this a cure, if [these results] could be extended for 5, 10, or 15 years, I think everyone would agree that this would be a cure,” he said.

This technique could be universally available, he said, since a patient’s own blood stem cells are used. Other complications, such as graft-versus-host disease (GVHD) or immune-related reactions, are negated with this form of therapy, he said.

Recent evidence has demonstrated that only about 20% of donor stem cells need to be corrected to illicit a very strong effect. This principle is now being applied in gene-editing techniques, as correcting every gene in every stem cell would be very challenging, Dr. Walters explained.
 

Gene editing

Another technique being investigated in SCD is gene editing, in which the fetal hemoglobin gene is “reawakened,” or other techniques are used to correct the sickle gene directly, such as CRISPR-Cas9 technology, Dr. Walters said.

In this technique, the Cas9 protein makes a cut and repairs an individual’s genomic DNA by inserting a strand of corrected donor DNA. The novel technology would allow for targeted genome editing that is specific to the SCD patient.

Currently, this experimental therapy is being investigated in preclinical studies. Dr. Walters said that he and his colleagues hope to begin enrolling patients in clinical trials within the next 1-2 years.

But while some gene therapies have been approved in other disorders, such as spinal muscle atrophy, a limiting factor to widespread availability is cost. Despite promising initial results in SCD, the affordability of future gene therapies will be a key factor to universal access, Dr. Walters said.
 

The Cure Sickle Cell Initiative

Traci Mondoro, PhD, chief of the Translational Blood Science and Resources Branch at NHLBI, explained that the NHLBI has funded a large proportion of the research that has formed the basis of several genetically based clinical studies.

One of the primary goals of the Cure Sickle Cell Initiative is to bridge the gap between new research and the SCD community. Their aim is to improve access for patients to participate in genetically based studies to advance cures.

The comprehensive approach is intended to fill in existing gaps by funding breakthrough research in both academic and private settings.

By establishing partnerships with key stakeholders, institutions, and patient groups, Dr. Mondoro said they hope to increase patient participation in clinical trials involving curative therapies. In the future, they also intend to establish a large body of evidence to provide adequate safety data to study these therapies in pediatric populations.

Dr. Walters and Dr. Mondoro did not provide information on financial disclosures.

Early results indicate experimental gene therapies could illicit a cure for sickle cell disease (SCD), but many barriers to access remain, namely cost, experts reported during a recent webinar sponsored by the National Heart, Lung, and Blood Institute.

Pogonic/Getty Images

At present, allogeneic hematopoietic stem cell transplant remains the only curative therapy available for patients with SCD. Newer transplant techniques include the use of mobilized blood stem cells, where stem cells are collected from the circulation using blood cell growth factors, explained Mark Walters, MD, of UCSF Benioff Children’s Hospital Oakland in California.

The most promising experimental gene therapies currently undergoing clinical development are gene-addition and gene-editing therapies, he said. Another technique, in vivo gene editing to correct the sickle mutation, is also being investigated, but has not yet reached clinical development.
 

Gene-addition therapy

Gene-addition therapy is a technique where a fetal hemoglobin (HbF) or anti-sickling beta-hemoglobin gene is inserted into a hematopoietic stem cell to illicit a curative effect. In this technique, the corrective gene is harvested from a patient’s own blood stem cells.

In patients with SCD, when HbF levels are elevated, the likelihood of sickling is reduced, resulting in a milder form of disease. As a result, raising HbF levels is a therapeutic target that forms the basis of several ongoing clinical studies.

The technique involves packaging an HbF rescue gene into a viral vector and coincubating the vector with a patient’s own blood stem cells. Subsequently, the corrected stem cells are injected back into the patient to produce higher levels of HbF.

The ongoing phase 1/2 HGB-206 clinical study is evaluating this technique in patients aged 12-50 years with severe SCD in multiple centers throughout Europe and the United States.

In those treated thus far, initial results appear promising, Dr. Walters reported, with one patient experiencing a rise in Hb levels from 10.7 g/dL at 3 months to 15.0 g/dL at 15 months follow-up.

Dr. Walters also reported that some of these patients no longer exhibit any signs or symptoms of SCD, such as anemia or painful adverse events. While these initial findings are compelling, whether these benefits will be maintained is still unknown.

“While it’s too early to call this a cure, if [these results] could be extended for 5, 10, or 15 years, I think everyone would agree that this would be a cure,” he said.

This technique could be universally available, he said, since a patient’s own blood stem cells are used. Other complications, such as graft-versus-host disease (GVHD) or immune-related reactions, are negated with this form of therapy, he said.

Recent evidence has demonstrated that only about 20% of donor stem cells need to be corrected to illicit a very strong effect. This principle is now being applied in gene-editing techniques, as correcting every gene in every stem cell would be very challenging, Dr. Walters explained.
 

Gene editing

Another technique being investigated in SCD is gene editing, in which the fetal hemoglobin gene is “reawakened,” or other techniques are used to correct the sickle gene directly, such as CRISPR-Cas9 technology, Dr. Walters said.

In this technique, the Cas9 protein makes a cut and repairs an individual’s genomic DNA by inserting a strand of corrected donor DNA. The novel technology would allow for targeted genome editing that is specific to the SCD patient.

Currently, this experimental therapy is being investigated in preclinical studies. Dr. Walters said that he and his colleagues hope to begin enrolling patients in clinical trials within the next 1-2 years.

But while some gene therapies have been approved in other disorders, such as spinal muscle atrophy, a limiting factor to widespread availability is cost. Despite promising initial results in SCD, the affordability of future gene therapies will be a key factor to universal access, Dr. Walters said.
 

The Cure Sickle Cell Initiative

Traci Mondoro, PhD, chief of the Translational Blood Science and Resources Branch at NHLBI, explained that the NHLBI has funded a large proportion of the research that has formed the basis of several genetically based clinical studies.

One of the primary goals of the Cure Sickle Cell Initiative is to bridge the gap between new research and the SCD community. Their aim is to improve access for patients to participate in genetically based studies to advance cures.

The comprehensive approach is intended to fill in existing gaps by funding breakthrough research in both academic and private settings.

By establishing partnerships with key stakeholders, institutions, and patient groups, Dr. Mondoro said they hope to increase patient participation in clinical trials involving curative therapies. In the future, they also intend to establish a large body of evidence to provide adequate safety data to study these therapies in pediatric populations.

Dr. Walters and Dr. Mondoro did not provide information on financial disclosures.

A new report by members of the Lancet Commission on Malaria Eradication has called for ending malaria in Africa within a generation, specifically aiming at the year 2050.

Courtesy NIAID

The Lancet Commission on Malaria Eradication is a joint endeavor between The Lancet and the University of California, San Francisco, and was convened in 2017 to consider the feasibility and affordability of malaria eradication, as well as to identify priority actions for the achievement of the goal. Eradication was considered “a necessary one given the never-ending struggle against drug and insecticide resistance and the social and economic costs associated with a failure to eradicate.”

Between 2000 and 2017, the worldwide annual incidence of malaria declined by 36%, and the annual death rate declined by 60%, according to the report. In 2007, Bill and Melinda Gates proposed that controlling malaria was not enough and complete eradication was the only scientifically and ethically defensible objective. This goal was adopted by the World Health Organization and other interested parties, and by 2015, global strategies and a potential timeline for eradication were developed.

“Global progress has stalled since 2015 and the malaria community is now at a critical moment, faced with a decision to either temper its ambitions as it did in 1969 or recommit to an eradication goal,” according to the report.

In the report, the authors used new modeling analysis to estimate plausible scenarios for the distribution and intensity of malaria in 2030 and 2050. Socioeconomic and environmental trends, together with enhanced access to high-quality diagnosis, treatment, and vector control, could lead to a “world largely free of malaria” by 2050, but with pockets of low-level transmission persisting across a belt of Africa.

Current statistics lend weight to the promise of eventual eradication, according to the report.

Between 2000 and 2017, 20 countries – constituting about one-fifth of the 106 malaria-endemic countries in 2000 – eliminated malaria transmission within their borders, reporting zero indigenous malaria cases for at least 1 year. However, this was counterbalanced by the fact that between 2015 and 2017, 55 countries had an increase in cases, and 38 countries had an increase in deaths.

“The good news is that 38 countries had incidences of fewer than ten cases per 1,000 population in 2017, with 25 countries reporting fewer than one case per 1,000 population. The same 38 countries reported just 5% of total malaria deaths. Nearly all of these low-burden countries are actively working towards national and regional elimination goals of 2030 or earlier,” according to the report.

The analysis undertaken for the report consisted of the following four steps:

1. Development of a machine-learning model to capture associations between malaria endemicity data and a wide range of socioeconomic and environmental geospatial covariates.

2. Mapping of covariate estimates to the years 2030 and 2050 on the basis of projected global trends.

3. Application of the associations learned in the first step to projected covariates generated in the second step to estimate the possible future global landscape of malaria endemicity.

4. Use of a mathematical transmission model to explore the potential effect of differing levels of malaria interventions.

The report indicates that an annual spending of $6 billion or more is required, while the current global expenditure is approximately $4.3 billion. An additional investment of $2 billion per year is necessary, with a quarter of the funds coming from increased development assistance from external donors and the rest from government health spending in malaria-endemic countries, according to the report.

However, other areas of concern remain, including the current lack of effective and widely deployable outdoor biting technologies, though these are expected to be available within the next decade, according to the report.

In terms of the modeling used in the report, the authors noted that past performance does not “capture the effect of mass drug administration or mass chemoprevention because these interventions are either relatively new or have yet to be applied widely. These underestimates might be counteracted by the absence of drug or insecticide resistance from our projections,which result in overly optimistic estimates for the continued efficacy of current tools.”

The commission was launched in October 2017 by the Global Health Group at the University of California, San Francisco. The commission built on the 2010 Lancet Malaria Elimination Series, “which evaluated the operational, technical, and financial requirements for malaria elimination and helped shape and build early support for the eradication agenda,” according to the report.

[email protected]

SOURCE: Feachem RGA et al. Lancet. 2019 Sept 8. doi: 10.1016/S0140-6736(19)31139-0.


 

A new report by members of the Lancet Commission on Malaria Eradication has called for ending malaria in Africa within a generation, specifically aiming at the year 2050.

Courtesy NIAID

The Lancet Commission on Malaria Eradication is a joint endeavor between The Lancet and the University of California, San Francisco, and was convened in 2017 to consider the feasibility and affordability of malaria eradication, as well as to identify priority actions for the achievement of the goal. Eradication was considered “a necessary one given the never-ending struggle against drug and insecticide resistance and the social and economic costs associated with a failure to eradicate.”

Between 2000 and 2017, the worldwide annual incidence of malaria declined by 36%, and the annual death rate declined by 60%, according to the report. In 2007, Bill and Melinda Gates proposed that controlling malaria was not enough and complete eradication was the only scientifically and ethically defensible objective. This goal was adopted by the World Health Organization and other interested parties, and by 2015, global strategies and a potential timeline for eradication were developed.

“Global progress has stalled since 2015 and the malaria community is now at a critical moment, faced with a decision to either temper its ambitions as it did in 1969 or recommit to an eradication goal,” according to the report.

In the report, the authors used new modeling analysis to estimate plausible scenarios for the distribution and intensity of malaria in 2030 and 2050. Socioeconomic and environmental trends, together with enhanced access to high-quality diagnosis, treatment, and vector control, could lead to a “world largely free of malaria” by 2050, but with pockets of low-level transmission persisting across a belt of Africa.

Current statistics lend weight to the promise of eventual eradication, according to the report.

Between 2000 and 2017, 20 countries – constituting about one-fifth of the 106 malaria-endemic countries in 2000 – eliminated malaria transmission within their borders, reporting zero indigenous malaria cases for at least 1 year. However, this was counterbalanced by the fact that between 2015 and 2017, 55 countries had an increase in cases, and 38 countries had an increase in deaths.

“The good news is that 38 countries had incidences of fewer than ten cases per 1,000 population in 2017, with 25 countries reporting fewer than one case per 1,000 population. The same 38 countries reported just 5% of total malaria deaths. Nearly all of these low-burden countries are actively working towards national and regional elimination goals of 2030 or earlier,” according to the report.

The analysis undertaken for the report consisted of the following four steps:

1. Development of a machine-learning model to capture associations between malaria endemicity data and a wide range of socioeconomic and environmental geospatial covariates.

2. Mapping of covariate estimates to the years 2030 and 2050 on the basis of projected global trends.

3. Application of the associations learned in the first step to projected covariates generated in the second step to estimate the possible future global landscape of malaria endemicity.

4. Use of a mathematical transmission model to explore the potential effect of differing levels of malaria interventions.

The report indicates that an annual spending of $6 billion or more is required, while the current global expenditure is approximately $4.3 billion. An additional investment of $2 billion per year is necessary, with a quarter of the funds coming from increased development assistance from external donors and the rest from government health spending in malaria-endemic countries, according to the report.

However, other areas of concern remain, including the current lack of effective and widely deployable outdoor biting technologies, though these are expected to be available within the next decade, according to the report.

In terms of the modeling used in the report, the authors noted that past performance does not “capture the effect of mass drug administration or mass chemoprevention because these interventions are either relatively new or have yet to be applied widely. These underestimates might be counteracted by the absence of drug or insecticide resistance from our projections,which result in overly optimistic estimates for the continued efficacy of current tools.”

The commission was launched in October 2017 by the Global Health Group at the University of California, San Francisco. The commission built on the 2010 Lancet Malaria Elimination Series, “which evaluated the operational, technical, and financial requirements for malaria elimination and helped shape and build early support for the eradication agenda,” according to the report.

[email protected]

SOURCE: Feachem RGA et al. Lancet. 2019 Sept 8. doi: 10.1016/S0140-6736(19)31139-0.


 

A new report by members of the Lancet Commission on Malaria Eradication has called for ending malaria in Africa within a generation, specifically aiming at the year 2050.

Courtesy NIAID

The Lancet Commission on Malaria Eradication is a joint endeavor between The Lancet and the University of California, San Francisco, and was convened in 2017 to consider the feasibility and affordability of malaria eradication, as well as to identify priority actions for the achievement of the goal. Eradication was considered “a necessary one given the never-ending struggle against drug and insecticide resistance and the social and economic costs associated with a failure to eradicate.”

Between 2000 and 2017, the worldwide annual incidence of malaria declined by 36%, and the annual death rate declined by 60%, according to the report. In 2007, Bill and Melinda Gates proposed that controlling malaria was not enough and complete eradication was the only scientifically and ethically defensible objective. This goal was adopted by the World Health Organization and other interested parties, and by 2015, global strategies and a potential timeline for eradication were developed.

“Global progress has stalled since 2015 and the malaria community is now at a critical moment, faced with a decision to either temper its ambitions as it did in 1969 or recommit to an eradication goal,” according to the report.

In the report, the authors used new modeling analysis to estimate plausible scenarios for the distribution and intensity of malaria in 2030 and 2050. Socioeconomic and environmental trends, together with enhanced access to high-quality diagnosis, treatment, and vector control, could lead to a “world largely free of malaria” by 2050, but with pockets of low-level transmission persisting across a belt of Africa.

Current statistics lend weight to the promise of eventual eradication, according to the report.

Between 2000 and 2017, 20 countries – constituting about one-fifth of the 106 malaria-endemic countries in 2000 – eliminated malaria transmission within their borders, reporting zero indigenous malaria cases for at least 1 year. However, this was counterbalanced by the fact that between 2015 and 2017, 55 countries had an increase in cases, and 38 countries had an increase in deaths.

“The good news is that 38 countries had incidences of fewer than ten cases per 1,000 population in 2017, with 25 countries reporting fewer than one case per 1,000 population. The same 38 countries reported just 5% of total malaria deaths. Nearly all of these low-burden countries are actively working towards national and regional elimination goals of 2030 or earlier,” according to the report.

The analysis undertaken for the report consisted of the following four steps:

1. Development of a machine-learning model to capture associations between malaria endemicity data and a wide range of socioeconomic and environmental geospatial covariates.

2. Mapping of covariate estimates to the years 2030 and 2050 on the basis of projected global trends.

3. Application of the associations learned in the first step to projected covariates generated in the second step to estimate the possible future global landscape of malaria endemicity.

4. Use of a mathematical transmission model to explore the potential effect of differing levels of malaria interventions.

The report indicates that an annual spending of $6 billion or more is required, while the current global expenditure is approximately $4.3 billion. An additional investment of $2 billion per year is necessary, with a quarter of the funds coming from increased development assistance from external donors and the rest from government health spending in malaria-endemic countries, according to the report.

However, other areas of concern remain, including the current lack of effective and widely deployable outdoor biting technologies, though these are expected to be available within the next decade, according to the report.

In terms of the modeling used in the report, the authors noted that past performance does not “capture the effect of mass drug administration or mass chemoprevention because these interventions are either relatively new or have yet to be applied widely. These underestimates might be counteracted by the absence of drug or insecticide resistance from our projections,which result in overly optimistic estimates for the continued efficacy of current tools.”

The commission was launched in October 2017 by the Global Health Group at the University of California, San Francisco. The commission built on the 2010 Lancet Malaria Elimination Series, “which evaluated the operational, technical, and financial requirements for malaria elimination and helped shape and build early support for the eradication agenda,” according to the report.

[email protected]

SOURCE: Feachem RGA et al. Lancet. 2019 Sept 8. doi: 10.1016/S0140-6736(19)31139-0.


 

Researchers are leading several programs designed to serve the sickle cell community in the United States and sub-Saharan Africa, officials at the National Heart, Lung, and Blood Institute (NHLBI) said during a recent webinar.

Dr_Microbe/Thinkstock

One program based in the United States is focused on building a registry for patients with sickle cell disease (SCD) and conducting studies designed to improve SCD care. Another program involves building “an information-sharing network and patient-powered registry” in the United States.

The programs in sub-Saharan Africa were designed to establish a database of SCD patients, optimize the use of hydroxyurea in children with SCD, and aid genomic studies of SCD.

W. Keith Hoots, MD, director of the Division of Blood Diseases and Resources at NHLBI, began the webinar with an overview of the programs in sub-Saharan Africa. He described four programs with sites in nine countries (Angola, Cameroon, Democratic Republic of Congo, Ghana, Kenya, Nigeria, South Africa, Tanzania, and Uganda).

SPARCO and SADaCC

Dr. Hoots outlined the scope the Sickle Pan-African Research Consortium (SPARCO) and the Sickle Africa Data Coordinating Center (SADaCC), both part of the Sickle In Africa consortium.

A major goal of SPARCO and SADaCC is to create a Research Electronic Data Capture database that encompasses SCD patients in sub-Saharan Africa. As of April 2019, the database included 6,578 patients. The target is 13,000 patients.

Other goals of SPARCO and SADaCC are to “harmonize” SCD phenotype definitions and ontologies, create clinical guidelines for SCD management in sub-Saharan Africa, plan future cohort studies, and develop programs for newborn screening, infection prevention, and increased use of hydroxyurea.

“So far, they’re well along in establishing a registry and a database system,” Dr. Hoots said. “They’ve agreed on the database elements, phenotype definitions, and ontologies, they’ve developed some regionally appropriate clinical management guidelines, and they’ve begun skills development on the ground at all respective sites.”

REACH

Another program Dr. Hoots discussed is Realizing Effectiveness Across Continents With Hydroxyurea (REACH), a phase 1/2 pilot study of hydroxyurea in children (aged 1-10 years) with SCD in sub-Saharan Africa.

The goals of REACH are to determine the optimal dose of hydroxyurea in this population; teach African physicians how to administer hydroxyurea; assess the safety, feasibility, and benefits of hydroxyurea; study variability in response to hydroxyurea; gather data for the Research Electronic Data Capture database; and establish a research infrastructure for future collaborations.

Results from more than 600 children enrolled in REACH were presented at the 2018 annual meeting of the American Society of Hematology and simultaneously published in the New England Journal of Medicine (N Engl J Med. 2019 Jan 10; 380[2]:121-31).

SickleGenAfrica

SickleGenAfrica is part of the H3Africa consortium and aims to “build capacity for genomic research in Africa,” Dr. Hoots said.

Under this program, researchers will conduct three studies to test the hypothesis that genetic variation affects the defense against hemolysis and organ damage in patients with SCD. The researchers will study existing cohorts of SCD patients including children and adults.

Other goals of SickleGenAfrica are to establish a molecular hematology and sickle cell mouse core, an SCD biorepository core, a bioinformatics core, and an administrative core for the coordination of activities. The program will also be used to train “future science leaders” in SCD research, Dr. Hoots said.
 

SCDIC

Cheryl Anne Boyce, PhD, chief of the Implementation Science Branch at the Center for Translation Research and Implementation Science at NHLBI, discussed the United States–based Sickle Cell Disease Implementation Consortium (SCDIC).

“The goals of the consortium are to develop a registry in collaboration with other centers and the NHLBI, as well as a needs-based community assessment of the barriers to care for subjects with sickle cell disease,” Dr. Boyce said. “We also wanted to design implementation research studies that address the identified barriers to care.”

Dr. Boyce said the SCDIC’s registry is open to patients aged 15-45 years who have a confirmed SCD diagnosis, speak English, and are able to consent to and complete a survey. The registry has enrolled almost 2,400 patients from eight centers over 18 months.

The SCDIC has also performed a needs assessment that prompted the development of three implementation research studies. The first study involves using mobile health interventions to, ideally, increase patient adherence to hydroxyurea and improve provider knowledge of hydroxyurea.

With the second study, researchers aim to improve the care of SCD patients in the emergency department by using an inpatient portal. The goals of the third study are to establish a standard definition for unaffiliated patients, conduct a needs assessment for this group, and develop an intervention that can provide these patients with guideline-based SCD care.

Get Connected

Kim Smith-Whitley, MD, director of the Comprehensive Sickle Cell Center at the Children’s Hospital of Philadelphia and a board member of the Sickle Cell Disease Association of America (SCDAA), described Get Connected, “an information-sharing network and patient-powered registry” created by SCDAA.

Dr. Smith-Whitley said one purpose of Get Connected is to provide a network that facilitates “the distribution of information related to clinical care, research, health services, health policy, and advocacy.”

The network is open to families living with SCD and sickle cell trait, SCDAA member organizations, health care providers, clinical researchers, and community-based organizations.

Get Connected also includes a registry for SCD patients that stores information on their diagnosis and treatment, as well as online communities that can be used to share information and provide psychosocial support.

Thus far, Get Connected has enrolled 6,329 individuals. This includes 5,100 children and adults with SCD, 652 children and adults with sickle cell trait, and 577 nonpatients.

The webinar presenters did not disclose any conflicts of interest.

[email protected]

Researchers are leading several programs designed to serve the sickle cell community in the United States and sub-Saharan Africa, officials at the National Heart, Lung, and Blood Institute (NHLBI) said during a recent webinar.

Dr_Microbe/Thinkstock

One program based in the United States is focused on building a registry for patients with sickle cell disease (SCD) and conducting studies designed to improve SCD care. Another program involves building “an information-sharing network and patient-powered registry” in the United States.

The programs in sub-Saharan Africa were designed to establish a database of SCD patients, optimize the use of hydroxyurea in children with SCD, and aid genomic studies of SCD.

W. Keith Hoots, MD, director of the Division of Blood Diseases and Resources at NHLBI, began the webinar with an overview of the programs in sub-Saharan Africa. He described four programs with sites in nine countries (Angola, Cameroon, Democratic Republic of Congo, Ghana, Kenya, Nigeria, South Africa, Tanzania, and Uganda).

SPARCO and SADaCC

Dr. Hoots outlined the scope the Sickle Pan-African Research Consortium (SPARCO) and the Sickle Africa Data Coordinating Center (SADaCC), both part of the Sickle In Africa consortium.

A major goal of SPARCO and SADaCC is to create a Research Electronic Data Capture database that encompasses SCD patients in sub-Saharan Africa. As of April 2019, the database included 6,578 patients. The target is 13,000 patients.

Other goals of SPARCO and SADaCC are to “harmonize” SCD phenotype definitions and ontologies, create clinical guidelines for SCD management in sub-Saharan Africa, plan future cohort studies, and develop programs for newborn screening, infection prevention, and increased use of hydroxyurea.

“So far, they’re well along in establishing a registry and a database system,” Dr. Hoots said. “They’ve agreed on the database elements, phenotype definitions, and ontologies, they’ve developed some regionally appropriate clinical management guidelines, and they’ve begun skills development on the ground at all respective sites.”

REACH

Another program Dr. Hoots discussed is Realizing Effectiveness Across Continents With Hydroxyurea (REACH), a phase 1/2 pilot study of hydroxyurea in children (aged 1-10 years) with SCD in sub-Saharan Africa.

The goals of REACH are to determine the optimal dose of hydroxyurea in this population; teach African physicians how to administer hydroxyurea; assess the safety, feasibility, and benefits of hydroxyurea; study variability in response to hydroxyurea; gather data for the Research Electronic Data Capture database; and establish a research infrastructure for future collaborations.

Results from more than 600 children enrolled in REACH were presented at the 2018 annual meeting of the American Society of Hematology and simultaneously published in the New England Journal of Medicine (N Engl J Med. 2019 Jan 10; 380[2]:121-31).

SickleGenAfrica

SickleGenAfrica is part of the H3Africa consortium and aims to “build capacity for genomic research in Africa,” Dr. Hoots said.

Under this program, researchers will conduct three studies to test the hypothesis that genetic variation affects the defense against hemolysis and organ damage in patients with SCD. The researchers will study existing cohorts of SCD patients including children and adults.

Other goals of SickleGenAfrica are to establish a molecular hematology and sickle cell mouse core, an SCD biorepository core, a bioinformatics core, and an administrative core for the coordination of activities. The program will also be used to train “future science leaders” in SCD research, Dr. Hoots said.
 

SCDIC

Cheryl Anne Boyce, PhD, chief of the Implementation Science Branch at the Center for Translation Research and Implementation Science at NHLBI, discussed the United States–based Sickle Cell Disease Implementation Consortium (SCDIC).

“The goals of the consortium are to develop a registry in collaboration with other centers and the NHLBI, as well as a needs-based community assessment of the barriers to care for subjects with sickle cell disease,” Dr. Boyce said. “We also wanted to design implementation research studies that address the identified barriers to care.”

Dr. Boyce said the SCDIC’s registry is open to patients aged 15-45 years who have a confirmed SCD diagnosis, speak English, and are able to consent to and complete a survey. The registry has enrolled almost 2,400 patients from eight centers over 18 months.

The SCDIC has also performed a needs assessment that prompted the development of three implementation research studies. The first study involves using mobile health interventions to, ideally, increase patient adherence to hydroxyurea and improve provider knowledge of hydroxyurea.

With the second study, researchers aim to improve the care of SCD patients in the emergency department by using an inpatient portal. The goals of the third study are to establish a standard definition for unaffiliated patients, conduct a needs assessment for this group, and develop an intervention that can provide these patients with guideline-based SCD care.

Get Connected

Kim Smith-Whitley, MD, director of the Comprehensive Sickle Cell Center at the Children’s Hospital of Philadelphia and a board member of the Sickle Cell Disease Association of America (SCDAA), described Get Connected, “an information-sharing network and patient-powered registry” created by SCDAA.

Dr. Smith-Whitley said one purpose of Get Connected is to provide a network that facilitates “the distribution of information related to clinical care, research, health services, health policy, and advocacy.”

The network is open to families living with SCD and sickle cell trait, SCDAA member organizations, health care providers, clinical researchers, and community-based organizations.

Get Connected also includes a registry for SCD patients that stores information on their diagnosis and treatment, as well as online communities that can be used to share information and provide psychosocial support.

Thus far, Get Connected has enrolled 6,329 individuals. This includes 5,100 children and adults with SCD, 652 children and adults with sickle cell trait, and 577 nonpatients.

The webinar presenters did not disclose any conflicts of interest.

[email protected]

Researchers are leading several programs designed to serve the sickle cell community in the United States and sub-Saharan Africa, officials at the National Heart, Lung, and Blood Institute (NHLBI) said during a recent webinar.

Dr_Microbe/Thinkstock

One program based in the United States is focused on building a registry for patients with sickle cell disease (SCD) and conducting studies designed to improve SCD care. Another program involves building “an information-sharing network and patient-powered registry” in the United States.

The programs in sub-Saharan Africa were designed to establish a database of SCD patients, optimize the use of hydroxyurea in children with SCD, and aid genomic studies of SCD.

W. Keith Hoots, MD, director of the Division of Blood Diseases and Resources at NHLBI, began the webinar with an overview of the programs in sub-Saharan Africa. He described four programs with sites in nine countries (Angola, Cameroon, Democratic Republic of Congo, Ghana, Kenya, Nigeria, South Africa, Tanzania, and Uganda).

SPARCO and SADaCC

Dr. Hoots outlined the scope the Sickle Pan-African Research Consortium (SPARCO) and the Sickle Africa Data Coordinating Center (SADaCC), both part of the Sickle In Africa consortium.

A major goal of SPARCO and SADaCC is to create a Research Electronic Data Capture database that encompasses SCD patients in sub-Saharan Africa. As of April 2019, the database included 6,578 patients. The target is 13,000 patients.

Other goals of SPARCO and SADaCC are to “harmonize” SCD phenotype definitions and ontologies, create clinical guidelines for SCD management in sub-Saharan Africa, plan future cohort studies, and develop programs for newborn screening, infection prevention, and increased use of hydroxyurea.

“So far, they’re well along in establishing a registry and a database system,” Dr. Hoots said. “They’ve agreed on the database elements, phenotype definitions, and ontologies, they’ve developed some regionally appropriate clinical management guidelines, and they’ve begun skills development on the ground at all respective sites.”

REACH

Another program Dr. Hoots discussed is Realizing Effectiveness Across Continents With Hydroxyurea (REACH), a phase 1/2 pilot study of hydroxyurea in children (aged 1-10 years) with SCD in sub-Saharan Africa.

The goals of REACH are to determine the optimal dose of hydroxyurea in this population; teach African physicians how to administer hydroxyurea; assess the safety, feasibility, and benefits of hydroxyurea; study variability in response to hydroxyurea; gather data for the Research Electronic Data Capture database; and establish a research infrastructure for future collaborations.

Results from more than 600 children enrolled in REACH were presented at the 2018 annual meeting of the American Society of Hematology and simultaneously published in the New England Journal of Medicine (N Engl J Med. 2019 Jan 10; 380[2]:121-31).

SickleGenAfrica

SickleGenAfrica is part of the H3Africa consortium and aims to “build capacity for genomic research in Africa,” Dr. Hoots said.

Under this program, researchers will conduct three studies to test the hypothesis that genetic variation affects the defense against hemolysis and organ damage in patients with SCD. The researchers will study existing cohorts of SCD patients including children and adults.

Other goals of SickleGenAfrica are to establish a molecular hematology and sickle cell mouse core, an SCD biorepository core, a bioinformatics core, and an administrative core for the coordination of activities. The program will also be used to train “future science leaders” in SCD research, Dr. Hoots said.
 

SCDIC

Cheryl Anne Boyce, PhD, chief of the Implementation Science Branch at the Center for Translation Research and Implementation Science at NHLBI, discussed the United States–based Sickle Cell Disease Implementation Consortium (SCDIC).

“The goals of the consortium are to develop a registry in collaboration with other centers and the NHLBI, as well as a needs-based community assessment of the barriers to care for subjects with sickle cell disease,” Dr. Boyce said. “We also wanted to design implementation research studies that address the identified barriers to care.”

Dr. Boyce said the SCDIC’s registry is open to patients aged 15-45 years who have a confirmed SCD diagnosis, speak English, and are able to consent to and complete a survey. The registry has enrolled almost 2,400 patients from eight centers over 18 months.

The SCDIC has also performed a needs assessment that prompted the development of three implementation research studies. The first study involves using mobile health interventions to, ideally, increase patient adherence to hydroxyurea and improve provider knowledge of hydroxyurea.

With the second study, researchers aim to improve the care of SCD patients in the emergency department by using an inpatient portal. The goals of the third study are to establish a standard definition for unaffiliated patients, conduct a needs assessment for this group, and develop an intervention that can provide these patients with guideline-based SCD care.

Get Connected

Kim Smith-Whitley, MD, director of the Comprehensive Sickle Cell Center at the Children’s Hospital of Philadelphia and a board member of the Sickle Cell Disease Association of America (SCDAA), described Get Connected, “an information-sharing network and patient-powered registry” created by SCDAA.

Dr. Smith-Whitley said one purpose of Get Connected is to provide a network that facilitates “the distribution of information related to clinical care, research, health services, health policy, and advocacy.”

The network is open to families living with SCD and sickle cell trait, SCDAA member organizations, health care providers, clinical researchers, and community-based organizations.

Get Connected also includes a registry for SCD patients that stores information on their diagnosis and treatment, as well as online communities that can be used to share information and provide psychosocial support.

Thus far, Get Connected has enrolled 6,329 individuals. This includes 5,100 children and adults with SCD, 652 children and adults with sickle cell trait, and 577 nonpatients.

The webinar presenters did not disclose any conflicts of interest.

[email protected]

Mitapivat showed positive safety and efficacy outcomes in patients with pyruvate kinase deficiency, according to results from a phase 2 trial.

After 24 weeks of treatment, the therapy was associated with a rapid rise in hemoglobin levels in 50% of study participants, while the majority of toxicities reported were transient and low grade.

“The primary objective of this study was to assess the safety and side-effect profile of mitapivat administration in patients with pyruvate kinase deficiency,” wrote Rachael F. Grace, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, and coinvestigators. The findings were published in the New England Journal of Medicine.

The uncontrolled study included 52 adults with pyruvate kinase deficiency who were not undergoing regular transfusions.

The median age at baseline was 34 years (range, 18-61 years), 62% of patients were male, and the median baseline hemoglobin level was 8.9 g/dL (range, 6.5-12.3 g/dL). In addition, 73% and 83% of patients had previously undergone cholecystectomy and splenectomy, respectively.

Study patients received oral mitapivat at 50 mg or 300 mg twice weekly for a total of 24 weeks. Eligible participants were subsequently enrolled into an extension phase that continued to monitor safety.

At 24 weeks, the team reported that 26 patients – 50% – experienced a greater than 1.0-g/dL rise in hemoglobin levels, with a maximum mean increase of 3.4 g/dL (range, 1.1-5.8 g/dL). The first rise of greater than 1.0 g/dL was observed after a median duration of 10 days (range, 7-187 days).

Of the 26 patients, 20 had an increase from baseline of more than 1.0 g/dL at more than half of the assessment during the core study period. That met the definition for hemoglobin response, according to the researchers.

“The hemoglobin response was maintained in the 19 patients who were continuing to be treated in the extension phase, all of whom had at least 21.6 months of treatment,” they wrote.

With respect to safety, the majority of adverse events were of low severity (grade 1-2) and transient in nature, with most resolving within 7 days. The most frequently reported toxicities in the core period and extension phase were headache (46%), insomnia (42%), and nausea (40%). The most serious reported toxicities were pharyngitis (4%) and hemolytic anemia (4%).

“Patient-reported quality of life was not assessed in this phase 2 safety study, although such outcome measures are being evaluated in the ongoing phase 3 trials,” Dr. Grace and colleagues wrote. “This study establishes proof of concept for a molecular therapy targeting the underlying enzymatic defect of a hereditary enzymopathy,” they concluded.

Agios Pharmaceuticals funded the study. Dr. Grace reported research funding from and consulting for Agios, and several authors reported employment, consulting, or research funding with the company.
 

SOURCE: Grace RF et al. N Engl J Med. 2019;381:933-44.

Mitapivat showed positive safety and efficacy outcomes in patients with pyruvate kinase deficiency, according to results from a phase 2 trial.

After 24 weeks of treatment, the therapy was associated with a rapid rise in hemoglobin levels in 50% of study participants, while the majority of toxicities reported were transient and low grade.

“The primary objective of this study was to assess the safety and side-effect profile of mitapivat administration in patients with pyruvate kinase deficiency,” wrote Rachael F. Grace, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, and coinvestigators. The findings were published in the New England Journal of Medicine.

The uncontrolled study included 52 adults with pyruvate kinase deficiency who were not undergoing regular transfusions.

The median age at baseline was 34 years (range, 18-61 years), 62% of patients were male, and the median baseline hemoglobin level was 8.9 g/dL (range, 6.5-12.3 g/dL). In addition, 73% and 83% of patients had previously undergone cholecystectomy and splenectomy, respectively.

Study patients received oral mitapivat at 50 mg or 300 mg twice weekly for a total of 24 weeks. Eligible participants were subsequently enrolled into an extension phase that continued to monitor safety.

At 24 weeks, the team reported that 26 patients – 50% – experienced a greater than 1.0-g/dL rise in hemoglobin levels, with a maximum mean increase of 3.4 g/dL (range, 1.1-5.8 g/dL). The first rise of greater than 1.0 g/dL was observed after a median duration of 10 days (range, 7-187 days).

Of the 26 patients, 20 had an increase from baseline of more than 1.0 g/dL at more than half of the assessment during the core study period. That met the definition for hemoglobin response, according to the researchers.

“The hemoglobin response was maintained in the 19 patients who were continuing to be treated in the extension phase, all of whom had at least 21.6 months of treatment,” they wrote.

With respect to safety, the majority of adverse events were of low severity (grade 1-2) and transient in nature, with most resolving within 7 days. The most frequently reported toxicities in the core period and extension phase were headache (46%), insomnia (42%), and nausea (40%). The most serious reported toxicities were pharyngitis (4%) and hemolytic anemia (4%).

“Patient-reported quality of life was not assessed in this phase 2 safety study, although such outcome measures are being evaluated in the ongoing phase 3 trials,” Dr. Grace and colleagues wrote. “This study establishes proof of concept for a molecular therapy targeting the underlying enzymatic defect of a hereditary enzymopathy,” they concluded.

Agios Pharmaceuticals funded the study. Dr. Grace reported research funding from and consulting for Agios, and several authors reported employment, consulting, or research funding with the company.
 

SOURCE: Grace RF et al. N Engl J Med. 2019;381:933-44.

Mitapivat showed positive safety and efficacy outcomes in patients with pyruvate kinase deficiency, according to results from a phase 2 trial.

After 24 weeks of treatment, the therapy was associated with a rapid rise in hemoglobin levels in 50% of study participants, while the majority of toxicities reported were transient and low grade.

“The primary objective of this study was to assess the safety and side-effect profile of mitapivat administration in patients with pyruvate kinase deficiency,” wrote Rachael F. Grace, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, and coinvestigators. The findings were published in the New England Journal of Medicine.

The uncontrolled study included 52 adults with pyruvate kinase deficiency who were not undergoing regular transfusions.

The median age at baseline was 34 years (range, 18-61 years), 62% of patients were male, and the median baseline hemoglobin level was 8.9 g/dL (range, 6.5-12.3 g/dL). In addition, 73% and 83% of patients had previously undergone cholecystectomy and splenectomy, respectively.

Study patients received oral mitapivat at 50 mg or 300 mg twice weekly for a total of 24 weeks. Eligible participants were subsequently enrolled into an extension phase that continued to monitor safety.

At 24 weeks, the team reported that 26 patients – 50% – experienced a greater than 1.0-g/dL rise in hemoglobin levels, with a maximum mean increase of 3.4 g/dL (range, 1.1-5.8 g/dL). The first rise of greater than 1.0 g/dL was observed after a median duration of 10 days (range, 7-187 days).

Of the 26 patients, 20 had an increase from baseline of more than 1.0 g/dL at more than half of the assessment during the core study period. That met the definition for hemoglobin response, according to the researchers.

“The hemoglobin response was maintained in the 19 patients who were continuing to be treated in the extension phase, all of whom had at least 21.6 months of treatment,” they wrote.

With respect to safety, the majority of adverse events were of low severity (grade 1-2) and transient in nature, with most resolving within 7 days. The most frequently reported toxicities in the core period and extension phase were headache (46%), insomnia (42%), and nausea (40%). The most serious reported toxicities were pharyngitis (4%) and hemolytic anemia (4%).

“Patient-reported quality of life was not assessed in this phase 2 safety study, although such outcome measures are being evaluated in the ongoing phase 3 trials,” Dr. Grace and colleagues wrote. “This study establishes proof of concept for a molecular therapy targeting the underlying enzymatic defect of a hereditary enzymopathy,” they concluded.

Agios Pharmaceuticals funded the study. Dr. Grace reported research funding from and consulting for Agios, and several authors reported employment, consulting, or research funding with the company.
 

SOURCE: Grace RF et al. N Engl J Med. 2019;381:933-44.

Combination quercetin and desferrioxamine could decrease iron overload in patients with transfusion-dependent beta-thalassemia major, according to a randomized clinical study.

Over the course of treatment, quercetin was well tolerated and no major complications were reported. The findings highlight the potential of quercetin to lower ferritin levels in patients with thalassemia major.

“Quercetin is a member of flavone family that mainly exists in apples, onions, tea, red wines, and berries,” wrote Zohreh Sajadi Hezaveh of Iran University of Medical Sciences in Tehran and colleagues. The findings of the study were published in Complementary Therapies in Medicine.

The researchers conducted a randomized, double-blind trial of 84 patients with thalassemia major. Of those enrolled, 71 patients were included in the final analysis.

Study patients were randomly assigned to receive either oral quercetin 500 mg daily or placebo for a total of 12 weeks. At baseline, all patients received desferrioxamine monotherapy. All participants were enrolled in the single-center study from April 2017 to March 2018. The team measured several inflammatory and iron-related markers during the study.

In comparison with placebo, combined therapy significantly improved high sensitivity C-reactive protein (P = .046), ferritin (P = .043), serum iron (P = .036), transferrin (P = .045), and transferrin saturation (P = .008), but not tumor necrosis factor–alpha (P = .310) or total iron-binding capacity (P = .734).

With respect to ferritin levels, a significant decrease was observed in the quercetin group, while patients in the placebo group had a marginal increase in levels.

“Insignificant results for [tumor necrosis factor–alpha] prevents us from making definitive comments [about inflammation],” the researchers wrote.

One key limitation of the study was the significant loss to follow-up seen in the placebo group. As a result, the generalizability of the findings may be limited.

“These results need to be confirmed by studies with larger sample size, longer follow-up period, and different doses of quercetin,” the researchers concluded.

The study was funded by the Iran University of Medical Sciences. The authors reported having no conflicts of interest.

SOURCE: Sajadi Hezaveh Z et al. Complement Ther Med. 2019;46:24-8.

Combination quercetin and desferrioxamine could decrease iron overload in patients with transfusion-dependent beta-thalassemia major, according to a randomized clinical study.

Over the course of treatment, quercetin was well tolerated and no major complications were reported. The findings highlight the potential of quercetin to lower ferritin levels in patients with thalassemia major.

“Quercetin is a member of flavone family that mainly exists in apples, onions, tea, red wines, and berries,” wrote Zohreh Sajadi Hezaveh of Iran University of Medical Sciences in Tehran and colleagues. The findings of the study were published in Complementary Therapies in Medicine.

The researchers conducted a randomized, double-blind trial of 84 patients with thalassemia major. Of those enrolled, 71 patients were included in the final analysis.

Study patients were randomly assigned to receive either oral quercetin 500 mg daily or placebo for a total of 12 weeks. At baseline, all patients received desferrioxamine monotherapy. All participants were enrolled in the single-center study from April 2017 to March 2018. The team measured several inflammatory and iron-related markers during the study.

In comparison with placebo, combined therapy significantly improved high sensitivity C-reactive protein (P = .046), ferritin (P = .043), serum iron (P = .036), transferrin (P = .045), and transferrin saturation (P = .008), but not tumor necrosis factor–alpha (P = .310) or total iron-binding capacity (P = .734).

With respect to ferritin levels, a significant decrease was observed in the quercetin group, while patients in the placebo group had a marginal increase in levels.

“Insignificant results for [tumor necrosis factor–alpha] prevents us from making definitive comments [about inflammation],” the researchers wrote.

One key limitation of the study was the significant loss to follow-up seen in the placebo group. As a result, the generalizability of the findings may be limited.

“These results need to be confirmed by studies with larger sample size, longer follow-up period, and different doses of quercetin,” the researchers concluded.

The study was funded by the Iran University of Medical Sciences. The authors reported having no conflicts of interest.

SOURCE: Sajadi Hezaveh Z et al. Complement Ther Med. 2019;46:24-8.

Combination quercetin and desferrioxamine could decrease iron overload in patients with transfusion-dependent beta-thalassemia major, according to a randomized clinical study.

Over the course of treatment, quercetin was well tolerated and no major complications were reported. The findings highlight the potential of quercetin to lower ferritin levels in patients with thalassemia major.

“Quercetin is a member of flavone family that mainly exists in apples, onions, tea, red wines, and berries,” wrote Zohreh Sajadi Hezaveh of Iran University of Medical Sciences in Tehran and colleagues. The findings of the study were published in Complementary Therapies in Medicine.

The researchers conducted a randomized, double-blind trial of 84 patients with thalassemia major. Of those enrolled, 71 patients were included in the final analysis.

Study patients were randomly assigned to receive either oral quercetin 500 mg daily or placebo for a total of 12 weeks. At baseline, all patients received desferrioxamine monotherapy. All participants were enrolled in the single-center study from April 2017 to March 2018. The team measured several inflammatory and iron-related markers during the study.

In comparison with placebo, combined therapy significantly improved high sensitivity C-reactive protein (P = .046), ferritin (P = .043), serum iron (P = .036), transferrin (P = .045), and transferrin saturation (P = .008), but not tumor necrosis factor–alpha (P = .310) or total iron-binding capacity (P = .734).

With respect to ferritin levels, a significant decrease was observed in the quercetin group, while patients in the placebo group had a marginal increase in levels.

“Insignificant results for [tumor necrosis factor–alpha] prevents us from making definitive comments [about inflammation],” the researchers wrote.

One key limitation of the study was the significant loss to follow-up seen in the placebo group. As a result, the generalizability of the findings may be limited.

“These results need to be confirmed by studies with larger sample size, longer follow-up period, and different doses of quercetin,” the researchers concluded.

The study was funded by the Iran University of Medical Sciences. The authors reported having no conflicts of interest.

SOURCE: Sajadi Hezaveh Z et al. Complement Ther Med. 2019;46:24-8.

Deferasirox plus deferoxamine is more effective than deferasirox alone for treating iron overload in patients with thalassemia major, according to a single-center study.

Over the course of 1 year of treatment, deferasirox plus deferoxamine significantly increased myocardial T2* and significantly reduced serum ferritin, whereas deferasirox alone had no significant effect on either endpoint. Neither treatment had a significant effect on hepatic iron.

Deferasirox plus deferoxamine caused a significantly greater increase in alanine aminotransferase, aspartate aminotransferase, and bilirubin. Other adverse events were similar between the treatment groups.

Aziz Eghbali, MD, of Arak (Iran) University of Medical Sciences and colleagues described this study in Transfusion and Apheresis Science.

The team conducted a randomized, double-blind trial of patients with thalassemia major. Of the 62 patients enrolled, 55 were randomized and evaluable. At baseline, the mean patient age was 24.5 years, and 67.3% were female.

The patients were randomized to receive oral deferasirox at 30 mg/kg daily either alone (n = 27) or with subcutaneous deferoxamine at 50 mg/kg for 5 days a week (n = 28). In both groups, patients received treatment for 12 months.

There were no significant differences between the groups in baseline characteristics such as myocardial or hepatic iron, transfusion volume, or white blood cell and platelet counts.

Results

The study’s primary endpoints were changes in myocardial T2* and hepatic T2* from baseline to 12 months. Changes in serum ferritin and adverse events were secondary endpoints.

Myocardial T2* decreased slightly in the monotherapy group, from 23.3 plus or minus 7.4 ms at baseline to 22.1 plus or minus 6.9 ms at 12 months (P = .3) but increased significantly in the combination group, from 23.1 plus or minus 7.5 ms to 27.1 plus or minus 7.0 ms (P less than .05). The difference between the groups was significant (P = .01).

There was no significant change in hepatic iron in either group. Hepatic T2* was 7.0 plus or minus 5.6 ms at baseline and 7.0 plus or minus 5.3 ms at 12 months in the monotherapy group (P = .7). In the combination group, hepatic T2* increased from 9.8 plus or minus 8.8 ms to 10.2 plus or minus 8.2 ms (P = .5). The between-group difference was not significant (P = .094).

Serum ferritin decreased from 1,390 plus or minus 816 mcg/ml to 1,085 plus or minus 919 mcg/mL in the monotherapy group (P = .06) and from 1,446 plus or minus 987 mcg/mL to 737 plus or minus 459 mcg/mL in the combination group (P less than .01). The between-group difference was significant (P = .001).

Increases in alanine aminotransferase, aspartate aminotransferase, and bilirubin were significantly greater in the combination group than in the monotherapy group (P less than .05 for all). Combination therapy also prompted an increase in alkaline phosphatase, but this was not significantly greater than in the monotherapy group (P = .3).

Blood urea nitrogen levels increased in both groups, but levels remained within the normal range. There were no increases in serum creatinine in either group.

Rates of mild gastrointestinal adverse events were similar in the monotherapy and combination groups (40% and 39%, respectively), as were rates of transient skin rashes (18% and 14%, respectively).

There were no deaths, and none of the patients stopped treatment because of severe adverse events.

This study was supported by Arak University of Medical Sciences. The researchers reported having no conflicts of interest.

[email protected]

SOURCE: Eghbali A et al. Transfus Apher Sci. 2019 Aug;58(4):429-33.
 

Deferasirox plus deferoxamine is more effective than deferasirox alone for treating iron overload in patients with thalassemia major, according to a single-center study.

Over the course of 1 year of treatment, deferasirox plus deferoxamine significantly increased myocardial T2* and significantly reduced serum ferritin, whereas deferasirox alone had no significant effect on either endpoint. Neither treatment had a significant effect on hepatic iron.

Deferasirox plus deferoxamine caused a significantly greater increase in alanine aminotransferase, aspartate aminotransferase, and bilirubin. Other adverse events were similar between the treatment groups.

Aziz Eghbali, MD, of Arak (Iran) University of Medical Sciences and colleagues described this study in Transfusion and Apheresis Science.

The team conducted a randomized, double-blind trial of patients with thalassemia major. Of the 62 patients enrolled, 55 were randomized and evaluable. At baseline, the mean patient age was 24.5 years, and 67.3% were female.

The patients were randomized to receive oral deferasirox at 30 mg/kg daily either alone (n = 27) or with subcutaneous deferoxamine at 50 mg/kg for 5 days a week (n = 28). In both groups, patients received treatment for 12 months.

There were no significant differences between the groups in baseline characteristics such as myocardial or hepatic iron, transfusion volume, or white blood cell and platelet counts.

Results

The study’s primary endpoints were changes in myocardial T2* and hepatic T2* from baseline to 12 months. Changes in serum ferritin and adverse events were secondary endpoints.

Myocardial T2* decreased slightly in the monotherapy group, from 23.3 plus or minus 7.4 ms at baseline to 22.1 plus or minus 6.9 ms at 12 months (P = .3) but increased significantly in the combination group, from 23.1 plus or minus 7.5 ms to 27.1 plus or minus 7.0 ms (P less than .05). The difference between the groups was significant (P = .01).

There was no significant change in hepatic iron in either group. Hepatic T2* was 7.0 plus or minus 5.6 ms at baseline and 7.0 plus or minus 5.3 ms at 12 months in the monotherapy group (P = .7). In the combination group, hepatic T2* increased from 9.8 plus or minus 8.8 ms to 10.2 plus or minus 8.2 ms (P = .5). The between-group difference was not significant (P = .094).

Serum ferritin decreased from 1,390 plus or minus 816 mcg/ml to 1,085 plus or minus 919 mcg/mL in the monotherapy group (P = .06) and from 1,446 plus or minus 987 mcg/mL to 737 plus or minus 459 mcg/mL in the combination group (P less than .01). The between-group difference was significant (P = .001).

Increases in alanine aminotransferase, aspartate aminotransferase, and bilirubin were significantly greater in the combination group than in the monotherapy group (P less than .05 for all). Combination therapy also prompted an increase in alkaline phosphatase, but this was not significantly greater than in the monotherapy group (P = .3).

Blood urea nitrogen levels increased in both groups, but levels remained within the normal range. There were no increases in serum creatinine in either group.

Rates of mild gastrointestinal adverse events were similar in the monotherapy and combination groups (40% and 39%, respectively), as were rates of transient skin rashes (18% and 14%, respectively).

There were no deaths, and none of the patients stopped treatment because of severe adverse events.

This study was supported by Arak University of Medical Sciences. The researchers reported having no conflicts of interest.

[email protected]

SOURCE: Eghbali A et al. Transfus Apher Sci. 2019 Aug;58(4):429-33.
 

Deferasirox plus deferoxamine is more effective than deferasirox alone for treating iron overload in patients with thalassemia major, according to a single-center study.

Over the course of 1 year of treatment, deferasirox plus deferoxamine significantly increased myocardial T2* and significantly reduced serum ferritin, whereas deferasirox alone had no significant effect on either endpoint. Neither treatment had a significant effect on hepatic iron.

Deferasirox plus deferoxamine caused a significantly greater increase in alanine aminotransferase, aspartate aminotransferase, and bilirubin. Other adverse events were similar between the treatment groups.

Aziz Eghbali, MD, of Arak (Iran) University of Medical Sciences and colleagues described this study in Transfusion and Apheresis Science.

The team conducted a randomized, double-blind trial of patients with thalassemia major. Of the 62 patients enrolled, 55 were randomized and evaluable. At baseline, the mean patient age was 24.5 years, and 67.3% were female.

The patients were randomized to receive oral deferasirox at 30 mg/kg daily either alone (n = 27) or with subcutaneous deferoxamine at 50 mg/kg for 5 days a week (n = 28). In both groups, patients received treatment for 12 months.

There were no significant differences between the groups in baseline characteristics such as myocardial or hepatic iron, transfusion volume, or white blood cell and platelet counts.

Results

The study’s primary endpoints were changes in myocardial T2* and hepatic T2* from baseline to 12 months. Changes in serum ferritin and adverse events were secondary endpoints.

Myocardial T2* decreased slightly in the monotherapy group, from 23.3 plus or minus 7.4 ms at baseline to 22.1 plus or minus 6.9 ms at 12 months (P = .3) but increased significantly in the combination group, from 23.1 plus or minus 7.5 ms to 27.1 plus or minus 7.0 ms (P less than .05). The difference between the groups was significant (P = .01).

There was no significant change in hepatic iron in either group. Hepatic T2* was 7.0 plus or minus 5.6 ms at baseline and 7.0 plus or minus 5.3 ms at 12 months in the monotherapy group (P = .7). In the combination group, hepatic T2* increased from 9.8 plus or minus 8.8 ms to 10.2 plus or minus 8.2 ms (P = .5). The between-group difference was not significant (P = .094).

Serum ferritin decreased from 1,390 plus or minus 816 mcg/ml to 1,085 plus or minus 919 mcg/mL in the monotherapy group (P = .06) and from 1,446 plus or minus 987 mcg/mL to 737 plus or minus 459 mcg/mL in the combination group (P less than .01). The between-group difference was significant (P = .001).

Increases in alanine aminotransferase, aspartate aminotransferase, and bilirubin were significantly greater in the combination group than in the monotherapy group (P less than .05 for all). Combination therapy also prompted an increase in alkaline phosphatase, but this was not significantly greater than in the monotherapy group (P = .3).

Blood urea nitrogen levels increased in both groups, but levels remained within the normal range. There were no increases in serum creatinine in either group.

Rates of mild gastrointestinal adverse events were similar in the monotherapy and combination groups (40% and 39%, respectively), as were rates of transient skin rashes (18% and 14%, respectively).

There were no deaths, and none of the patients stopped treatment because of severe adverse events.

This study was supported by Arak University of Medical Sciences. The researchers reported having no conflicts of interest.

[email protected]

SOURCE: Eghbali A et al. Transfus Apher Sci. 2019 Aug;58(4):429-33.
 

Trial results suggest African children with uncomplicated, severe anemia may not require immediate blood transfusion, and the volume of transfusion may only matter in the context of fever.

roobcio/Thinkstock

The TRACT trial showed no significant differences in 28-day mortality or other clinical outcomes between children who received immediate transfusions and those who did not.

Similarly, there was no significant difference in 28-day mortality among children who received transfusions of 20 mL/kg and those who received transfusions of 30 mL/kg. There was evidence to suggest a higher transfusion volume may benefit children without fevers, but this was an exploratory endpoint. The findings were published in the New England Journal of Medicine.

These results suggest “there is no credible reason to transfuse immediately or to transfuse a higher volume of blood, at least in pediatric populations in regions such as these two sub-Saharan countries [Uganda and Malawi],” Julie R. Ingelfinger, MD, of Massachusetts General Hospital in Boston, wrote in an accompanying editorial, also published in the New England Journal of Medicine (2019;381:475-6).

“The possible effect of higher volume transfusion in patients with fever may trigger additional and potentially useful studies,” she added.

Immediate transfusion

One goal of the TRACT trial was to determine if blood transfusion is the best treatment for children with severe anemia. With this in mind, Kathryn Maitland, MD, PhD, of Imperial College London and colleagues evaluated 1,565 Ugandan and Malawian children with uncomplicated, severe anemia. The patients’ median age was 26 months, and 984 (62.9%) had malaria.

The children were randomized to immediate transfusion (n = 778) or no immediate transfusion (n = 787). Children who did not have an immediate transfusion (control group) could receive a transfusion if they exhibited new signs of clinical severity or had their hemoglobin decrease to below 4 g/dL.

All children in the immediate-transfusion group received a transfusion, as did 386 (49.0%) in the control group. The median time to transfusion was 1.3 hours in the immediate group and 24.9 hours in the control group. The mean total blood volume transfused per child was 314 plus or minus 228 mL and 142 plus or minus 224, respectively. The follow-up period was 180 days, and 4.5% of patients (n = 71) were lost to follow-up.

The researchers found no significant difference between the treatment groups with regard to mortality, other clinical outcomes, or the cost of care.

The 28-day mortality rate was 0.9% in the immediate-transfusion group and 1.7% in the control group (hazard ratio, 0.54; 95% confidence interval, 0.22-1.36; P = .19). The 180-day mortality was 4.5% and 6.0%, respectively (HR, 0.75; 95% CI, 0.48-1.15).
 

Transfusion volume

To assess the effects of transfusion volume, Dr. Maitland and colleagues evaluated 3,196 Ugandan and Malawian children with severe anemia. The median age of the children was 37 months, and 2,050 (64.1%) had malaria.

The children received a transfusion of 30 mL/kg (n = 1,592) or 20 mL/kg (n = 1,596) at a median of 1.2 hours after randomization. Some children – 197 in the 30-mL/kg group and 300 in the 20-mL/kg group – received additional transfusions. The mean volume of total blood transfused per child was 475 plus or minus 385 mL, and 353 plus or minus 348 mL, respectively.

Overall, there was no significant between-group difference with regard to mortality. The 28-day mortality rate was 3.4% in the 30 mL/kg group and 4.5% in the 20 mL/kg group (HR = 0.76; 95% CI, 0.54 to 1.08; P = .12).

However, the 28-day mortality rate did differ according to the presence of fever at screening. The mortality rate was lower in the 30 mL/kg group for children without fevers (HR = 0.43; 95% CI, 0.27 to 0.69) but higher in the 30 mL/kg group for febrile children (HR = 1.91; 95% CI, 1.04 to 3.49).

For other outcomes, including readmissions and serious adverse events, the researchers found no significant between-group differences.

This trial was supported by a grant from the United Kingdom Medical Research Council through a concordat with the Department for International Development. One researcher has a Wellcome Senior Research Fellowship, and another is a National Institute for Health Research Senior Investigator. Dr. Ingelfinger is a deputy editor at the New England Journal of Medicine. No other relevant conflicts of interest were reported.

[email protected]

SOURCES: Maitland K et al. N Engl J Med. 2019;381:407-19. Maitland K et al. N Engl J Med. 2019;381:420-31.


 

Trial results suggest African children with uncomplicated, severe anemia may not require immediate blood transfusion, and the volume of transfusion may only matter in the context of fever.

roobcio/Thinkstock

The TRACT trial showed no significant differences in 28-day mortality or other clinical outcomes between children who received immediate transfusions and those who did not.

Similarly, there was no significant difference in 28-day mortality among children who received transfusions of 20 mL/kg and those who received transfusions of 30 mL/kg. There was evidence to suggest a higher transfusion volume may benefit children without fevers, but this was an exploratory endpoint. The findings were published in the New England Journal of Medicine.

These results suggest “there is no credible reason to transfuse immediately or to transfuse a higher volume of blood, at least in pediatric populations in regions such as these two sub-Saharan countries [Uganda and Malawi],” Julie R. Ingelfinger, MD, of Massachusetts General Hospital in Boston, wrote in an accompanying editorial, also published in the New England Journal of Medicine (2019;381:475-6).

“The possible effect of higher volume transfusion in patients with fever may trigger additional and potentially useful studies,” she added.

Immediate transfusion

One goal of the TRACT trial was to determine if blood transfusion is the best treatment for children with severe anemia. With this in mind, Kathryn Maitland, MD, PhD, of Imperial College London and colleagues evaluated 1,565 Ugandan and Malawian children with uncomplicated, severe anemia. The patients’ median age was 26 months, and 984 (62.9%) had malaria.

The children were randomized to immediate transfusion (n = 778) or no immediate transfusion (n = 787). Children who did not have an immediate transfusion (control group) could receive a transfusion if they exhibited new signs of clinical severity or had their hemoglobin decrease to below 4 g/dL.

All children in the immediate-transfusion group received a transfusion, as did 386 (49.0%) in the control group. The median time to transfusion was 1.3 hours in the immediate group and 24.9 hours in the control group. The mean total blood volume transfused per child was 314 plus or minus 228 mL and 142 plus or minus 224, respectively. The follow-up period was 180 days, and 4.5% of patients (n = 71) were lost to follow-up.

The researchers found no significant difference between the treatment groups with regard to mortality, other clinical outcomes, or the cost of care.

The 28-day mortality rate was 0.9% in the immediate-transfusion group and 1.7% in the control group (hazard ratio, 0.54; 95% confidence interval, 0.22-1.36; P = .19). The 180-day mortality was 4.5% and 6.0%, respectively (HR, 0.75; 95% CI, 0.48-1.15).
 

Transfusion volume

To assess the effects of transfusion volume, Dr. Maitland and colleagues evaluated 3,196 Ugandan and Malawian children with severe anemia. The median age of the children was 37 months, and 2,050 (64.1%) had malaria.

The children received a transfusion of 30 mL/kg (n = 1,592) or 20 mL/kg (n = 1,596) at a median of 1.2 hours after randomization. Some children – 197 in the 30-mL/kg group and 300 in the 20-mL/kg group – received additional transfusions. The mean volume of total blood transfused per child was 475 plus or minus 385 mL, and 353 plus or minus 348 mL, respectively.

Overall, there was no significant between-group difference with regard to mortality. The 28-day mortality rate was 3.4% in the 30 mL/kg group and 4.5% in the 20 mL/kg group (HR = 0.76; 95% CI, 0.54 to 1.08; P = .12).

However, the 28-day mortality rate did differ according to the presence of fever at screening. The mortality rate was lower in the 30 mL/kg group for children without fevers (HR = 0.43; 95% CI, 0.27 to 0.69) but higher in the 30 mL/kg group for febrile children (HR = 1.91; 95% CI, 1.04 to 3.49).

For other outcomes, including readmissions and serious adverse events, the researchers found no significant between-group differences.

This trial was supported by a grant from the United Kingdom Medical Research Council through a concordat with the Department for International Development. One researcher has a Wellcome Senior Research Fellowship, and another is a National Institute for Health Research Senior Investigator. Dr. Ingelfinger is a deputy editor at the New England Journal of Medicine. No other relevant conflicts of interest were reported.

[email protected]

SOURCES: Maitland K et al. N Engl J Med. 2019;381:407-19. Maitland K et al. N Engl J Med. 2019;381:420-31.


 

Trial results suggest African children with uncomplicated, severe anemia may not require immediate blood transfusion, and the volume of transfusion may only matter in the context of fever.

roobcio/Thinkstock

The TRACT trial showed no significant differences in 28-day mortality or other clinical outcomes between children who received immediate transfusions and those who did not.

Similarly, there was no significant difference in 28-day mortality among children who received transfusions of 20 mL/kg and those who received transfusions of 30 mL/kg. There was evidence to suggest a higher transfusion volume may benefit children without fevers, but this was an exploratory endpoint. The findings were published in the New England Journal of Medicine.

These results suggest “there is no credible reason to transfuse immediately or to transfuse a higher volume of blood, at least in pediatric populations in regions such as these two sub-Saharan countries [Uganda and Malawi],” Julie R. Ingelfinger, MD, of Massachusetts General Hospital in Boston, wrote in an accompanying editorial, also published in the New England Journal of Medicine (2019;381:475-6).

“The possible effect of higher volume transfusion in patients with fever may trigger additional and potentially useful studies,” she added.

Immediate transfusion

One goal of the TRACT trial was to determine if blood transfusion is the best treatment for children with severe anemia. With this in mind, Kathryn Maitland, MD, PhD, of Imperial College London and colleagues evaluated 1,565 Ugandan and Malawian children with uncomplicated, severe anemia. The patients’ median age was 26 months, and 984 (62.9%) had malaria.

The children were randomized to immediate transfusion (n = 778) or no immediate transfusion (n = 787). Children who did not have an immediate transfusion (control group) could receive a transfusion if they exhibited new signs of clinical severity or had their hemoglobin decrease to below 4 g/dL.

All children in the immediate-transfusion group received a transfusion, as did 386 (49.0%) in the control group. The median time to transfusion was 1.3 hours in the immediate group and 24.9 hours in the control group. The mean total blood volume transfused per child was 314 plus or minus 228 mL and 142 plus or minus 224, respectively. The follow-up period was 180 days, and 4.5% of patients (n = 71) were lost to follow-up.

The researchers found no significant difference between the treatment groups with regard to mortality, other clinical outcomes, or the cost of care.

The 28-day mortality rate was 0.9% in the immediate-transfusion group and 1.7% in the control group (hazard ratio, 0.54; 95% confidence interval, 0.22-1.36; P = .19). The 180-day mortality was 4.5% and 6.0%, respectively (HR, 0.75; 95% CI, 0.48-1.15).
 

Transfusion volume

To assess the effects of transfusion volume, Dr. Maitland and colleagues evaluated 3,196 Ugandan and Malawian children with severe anemia. The median age of the children was 37 months, and 2,050 (64.1%) had malaria.

The children received a transfusion of 30 mL/kg (n = 1,592) or 20 mL/kg (n = 1,596) at a median of 1.2 hours after randomization. Some children – 197 in the 30-mL/kg group and 300 in the 20-mL/kg group – received additional transfusions. The mean volume of total blood transfused per child was 475 plus or minus 385 mL, and 353 plus or minus 348 mL, respectively.

Overall, there was no significant between-group difference with regard to mortality. The 28-day mortality rate was 3.4% in the 30 mL/kg group and 4.5% in the 20 mL/kg group (HR = 0.76; 95% CI, 0.54 to 1.08; P = .12).

However, the 28-day mortality rate did differ according to the presence of fever at screening. The mortality rate was lower in the 30 mL/kg group for children without fevers (HR = 0.43; 95% CI, 0.27 to 0.69) but higher in the 30 mL/kg group for febrile children (HR = 1.91; 95% CI, 1.04 to 3.49).

For other outcomes, including readmissions and serious adverse events, the researchers found no significant between-group differences.

This trial was supported by a grant from the United Kingdom Medical Research Council through a concordat with the Department for International Development. One researcher has a Wellcome Senior Research Fellowship, and another is a National Institute for Health Research Senior Investigator. Dr. Ingelfinger is a deputy editor at the New England Journal of Medicine. No other relevant conflicts of interest were reported.

[email protected]

SOURCES: Maitland K et al. N Engl J Med. 2019;381:407-19. Maitland K et al. N Engl J Med. 2019;381:420-31.


 

Adults with low levels of hemoglobin and adults with high levels of hemoglobin have an increased risk of developing dementia over 12 years of follow-up, compared with adults with midrange levels, according to a population-based study in the Netherlands.

This U-shaped association “may relate to differences in white matter integrity and cerebral perfusion,” the researchers wrote in Neurology.

Ton Everaers, Erasmus Medical Center

“With around 10% of people over age 65 having anemia in the Americas and Europe and up to 45% in African and southeast Asian countries, these results could have important implications for the burden of dementia,” said study author M. Arfan Ikram, MD, PhD, in a news release. Dr. Ikram is a professor of epidemiology at Erasmus Medical Center in Rotterdam, the Netherlands.

Prior studies have found that low hemoglobin levels are associated with adverse health outcomes, such as coronary heart disease, stroke, and mortality, but data about the relationship between hemoglobin levels and dementia risk have been limited.

A population-based cohort study

To examine the long-term association of hemoglobin levels and anemia with risk of dementia, Dr. Ikram and coauthors analyzed data from the Rotterdam Study, an ongoing population-based cohort study in the Netherlands that started in 1990. Their analysis included data from 12,305 participants without dementia who had serum hemoglobin measured at baseline (mean age, 64.6 years; 57.7% women).

During a mean follow-up of 12.1 years, 1,520 participants developed dementia, 1,194 of whom had Alzheimer’s disease.

“Both low and high hemoglobin levels were associated with increased dementia risk,” the authors wrote. Compared with participants in the middle quintile of hemoglobin levels (8.57-8.99 mmol/L), participants in the lowest quintile (less than 8.11 mmol/L) had a hazard ratio of dementia of 1.29, and participants in the highest quintile (greater than 9.40 mmol/L) had an HR of 1.20.

About 6% of the participants had anemia – that is, a hemoglobin level of less than 8.1 mmol/L for men and less than 7.5 mmol/L for women. Anemia was associated with a 34% increased risk of dementia and a 41% increased risk of Alzheimer’s disease.

Of the 745 people with anemia, 128 developed dementia, compared with 1,392 of the 11,560 people who did not have anemia (17% vs. 12%).

A U-shaped association

The researchers also examined hemoglobin in relation to vascular brain disease, structural connectivity, and global cerebral perfusion among 5,267 participants without dementia who had brain MRI. White matter hyperintensity volume and hemoglobin had a U-shaped association, similar to that for dementia and hemoglobin. In addition, hemoglobin inversely correlated to cerebral perfusion.

The results remained consistent after adjustment for factors such as smoking, high blood pressure, high cholesterol, and alcohol use.

A limitation of the study is that the participants lived in the Netherlands and were primarily of European descent, so the results may not apply to other populations, the authors wrote.

Dr. Ikram noted that the study does not prove that low or high hemoglobin levels cause dementia. “More research is needed to determine whether hemoglobin levels play a direct role in this increased risk or whether these associations can be explained by underlying issues or other vascular or metabolic changes.”

The study was supported by the Netherlands Cardiovascular Research Initiative; Erasmus Medical Centre; Erasmus University Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly; Netherlands Genomic Initiative; Dutch Ministry of Education, Culture, and Science; Dutch Ministry of Health, Welfare, and Sports; European Commission; Municipality of Rotterdam; Netherlands Consortium for Healthy Aging; and Dutch Heart Foundation. The authors reported no relevant disclosures.

[email protected]

SOURCE: Ikram MA et al. Neurology. 2019 Jul 31. doi: 10.1212/WNL.0000000000008003.

Adults with low levels of hemoglobin and adults with high levels of hemoglobin have an increased risk of developing dementia over 12 years of follow-up, compared with adults with midrange levels, according to a population-based study in the Netherlands.

This U-shaped association “may relate to differences in white matter integrity and cerebral perfusion,” the researchers wrote in Neurology.

Ton Everaers, Erasmus Medical Center

“With around 10% of people over age 65 having anemia in the Americas and Europe and up to 45% in African and southeast Asian countries, these results could have important implications for the burden of dementia,” said study author M. Arfan Ikram, MD, PhD, in a news release. Dr. Ikram is a professor of epidemiology at Erasmus Medical Center in Rotterdam, the Netherlands.

Prior studies have found that low hemoglobin levels are associated with adverse health outcomes, such as coronary heart disease, stroke, and mortality, but data about the relationship between hemoglobin levels and dementia risk have been limited.

A population-based cohort study

To examine the long-term association of hemoglobin levels and anemia with risk of dementia, Dr. Ikram and coauthors analyzed data from the Rotterdam Study, an ongoing population-based cohort study in the Netherlands that started in 1990. Their analysis included data from 12,305 participants without dementia who had serum hemoglobin measured at baseline (mean age, 64.6 years; 57.7% women).

During a mean follow-up of 12.1 years, 1,520 participants developed dementia, 1,194 of whom had Alzheimer’s disease.

“Both low and high hemoglobin levels were associated with increased dementia risk,” the authors wrote. Compared with participants in the middle quintile of hemoglobin levels (8.57-8.99 mmol/L), participants in the lowest quintile (less than 8.11 mmol/L) had a hazard ratio of dementia of 1.29, and participants in the highest quintile (greater than 9.40 mmol/L) had an HR of 1.20.

About 6% of the participants had anemia – that is, a hemoglobin level of less than 8.1 mmol/L for men and less than 7.5 mmol/L for women. Anemia was associated with a 34% increased risk of dementia and a 41% increased risk of Alzheimer’s disease.

Of the 745 people with anemia, 128 developed dementia, compared with 1,392 of the 11,560 people who did not have anemia (17% vs. 12%).

A U-shaped association

The researchers also examined hemoglobin in relation to vascular brain disease, structural connectivity, and global cerebral perfusion among 5,267 participants without dementia who had brain MRI. White matter hyperintensity volume and hemoglobin had a U-shaped association, similar to that for dementia and hemoglobin. In addition, hemoglobin inversely correlated to cerebral perfusion.

The results remained consistent after adjustment for factors such as smoking, high blood pressure, high cholesterol, and alcohol use.

A limitation of the study is that the participants lived in the Netherlands and were primarily of European descent, so the results may not apply to other populations, the authors wrote.

Dr. Ikram noted that the study does not prove that low or high hemoglobin levels cause dementia. “More research is needed to determine whether hemoglobin levels play a direct role in this increased risk or whether these associations can be explained by underlying issues or other vascular or metabolic changes.”

The study was supported by the Netherlands Cardiovascular Research Initiative; Erasmus Medical Centre; Erasmus University Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly; Netherlands Genomic Initiative; Dutch Ministry of Education, Culture, and Science; Dutch Ministry of Health, Welfare, and Sports; European Commission; Municipality of Rotterdam; Netherlands Consortium for Healthy Aging; and Dutch Heart Foundation. The authors reported no relevant disclosures.

[email protected]

SOURCE: Ikram MA et al. Neurology. 2019 Jul 31. doi: 10.1212/WNL.0000000000008003.

Adults with low levels of hemoglobin and adults with high levels of hemoglobin have an increased risk of developing dementia over 12 years of follow-up, compared with adults with midrange levels, according to a population-based study in the Netherlands.

This U-shaped association “may relate to differences in white matter integrity and cerebral perfusion,” the researchers wrote in Neurology.

Ton Everaers, Erasmus Medical Center

“With around 10% of people over age 65 having anemia in the Americas and Europe and up to 45% in African and southeast Asian countries, these results could have important implications for the burden of dementia,” said study author M. Arfan Ikram, MD, PhD, in a news release. Dr. Ikram is a professor of epidemiology at Erasmus Medical Center in Rotterdam, the Netherlands.

Prior studies have found that low hemoglobin levels are associated with adverse health outcomes, such as coronary heart disease, stroke, and mortality, but data about the relationship between hemoglobin levels and dementia risk have been limited.

A population-based cohort study

To examine the long-term association of hemoglobin levels and anemia with risk of dementia, Dr. Ikram and coauthors analyzed data from the Rotterdam Study, an ongoing population-based cohort study in the Netherlands that started in 1990. Their analysis included data from 12,305 participants without dementia who had serum hemoglobin measured at baseline (mean age, 64.6 years; 57.7% women).

During a mean follow-up of 12.1 years, 1,520 participants developed dementia, 1,194 of whom had Alzheimer’s disease.

“Both low and high hemoglobin levels were associated with increased dementia risk,” the authors wrote. Compared with participants in the middle quintile of hemoglobin levels (8.57-8.99 mmol/L), participants in the lowest quintile (less than 8.11 mmol/L) had a hazard ratio of dementia of 1.29, and participants in the highest quintile (greater than 9.40 mmol/L) had an HR of 1.20.

About 6% of the participants had anemia – that is, a hemoglobin level of less than 8.1 mmol/L for men and less than 7.5 mmol/L for women. Anemia was associated with a 34% increased risk of dementia and a 41% increased risk of Alzheimer’s disease.

Of the 745 people with anemia, 128 developed dementia, compared with 1,392 of the 11,560 people who did not have anemia (17% vs. 12%).

A U-shaped association

The researchers also examined hemoglobin in relation to vascular brain disease, structural connectivity, and global cerebral perfusion among 5,267 participants without dementia who had brain MRI. White matter hyperintensity volume and hemoglobin had a U-shaped association, similar to that for dementia and hemoglobin. In addition, hemoglobin inversely correlated to cerebral perfusion.

The results remained consistent after adjustment for factors such as smoking, high blood pressure, high cholesterol, and alcohol use.

A limitation of the study is that the participants lived in the Netherlands and were primarily of European descent, so the results may not apply to other populations, the authors wrote.

Dr. Ikram noted that the study does not prove that low or high hemoglobin levels cause dementia. “More research is needed to determine whether hemoglobin levels play a direct role in this increased risk or whether these associations can be explained by underlying issues or other vascular or metabolic changes.”

The study was supported by the Netherlands Cardiovascular Research Initiative; Erasmus Medical Centre; Erasmus University Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly; Netherlands Genomic Initiative; Dutch Ministry of Education, Culture, and Science; Dutch Ministry of Health, Welfare, and Sports; European Commission; Municipality of Rotterdam; Netherlands Consortium for Healthy Aging; and Dutch Heart Foundation. The authors reported no relevant disclosures.

[email protected]

SOURCE: Ikram MA et al. Neurology. 2019 Jul 31. doi: 10.1212/WNL.0000000000008003.

FORT LAUDERDALE, FLA. — A dedicated, 24-hour, 7-day-a-week sickle cell inpatient observation unit staffed by a multidisciplinary care team significantly reduced inpatient admissions and emergency department visits per patient, according to an analysis of a Philadelphia program.

“These findings confirm the need for an individualized approach to treatment,” Sanaa Rizk, MD, director of the hereditary anemia program at Thomas Jefferson University Hospital, Philadelphia, said at the annual meeting of the Foundation for Sickle Cell Disease Research. “The potential strength of a multidisciplinary approach and personalized interventions toward high-utilizing subpopulations may offer the greatest impact.”

The study evaluated what Dr. Rizk called “the second clinical transformation” in care of sickle cell disease patients, which Thomas Jefferson University implemented in 2015. The comprehensive sickle cell center first opened in 2003, and the first transformation in November 2013 consisted of opening a four-bed sickle cell day unit to treat uncomplicated sickle cell vaso-occlusive crises with personalized pain treatment protocols (including IV fluids and opioids). It was staffed by a nurse practitioner, medical assistant, and two registered nurses from 8 a.m. to 5 p.m.

The second transformation transferred care to the inpatient observation unit on the hospital floor with access to 12 patient beds. A sickle cell nurse practitioner sees patients for same-day appointments, conducts sick visits, performs outreach, and handles follow-up with patients. The rest of the multidisciplinary team includes hospitalists, hematologists, internists, and a social worker who performs weekly inpatient rounds and meets monthly with ED leaders and pharmacists.

With the first transformation, ED visits per patient fell from 3.67 to 2.14 a year (P less than .001), and inpatient admissions per patient fell from 1.33 to 0.63 (P less than .0001), Dr. Rizk reported.

The second transformation reduced those per-patient rates even further, to 0.47 ED visits (P less than .01) and 0.29 inpatient admissions (P less than .001), she said.

“The expansion of the service reduced admissions and ED use significantly,” Dr. Rizk said.

She added that a subanalysis of the high-utilizer subgroup showed a decrease in average total medical charges by approximately $100,000/patient per year.

Dr. Rizk reported having no relevant financial disclosures.

SOURCE: Rizk S et al. FSCDR 2019, Abstract JSCDH-D-19-00049.

FORT LAUDERDALE, FLA. — A dedicated, 24-hour, 7-day-a-week sickle cell inpatient observation unit staffed by a multidisciplinary care team significantly reduced inpatient admissions and emergency department visits per patient, according to an analysis of a Philadelphia program.

“These findings confirm the need for an individualized approach to treatment,” Sanaa Rizk, MD, director of the hereditary anemia program at Thomas Jefferson University Hospital, Philadelphia, said at the annual meeting of the Foundation for Sickle Cell Disease Research. “The potential strength of a multidisciplinary approach and personalized interventions toward high-utilizing subpopulations may offer the greatest impact.”

The study evaluated what Dr. Rizk called “the second clinical transformation” in care of sickle cell disease patients, which Thomas Jefferson University implemented in 2015. The comprehensive sickle cell center first opened in 2003, and the first transformation in November 2013 consisted of opening a four-bed sickle cell day unit to treat uncomplicated sickle cell vaso-occlusive crises with personalized pain treatment protocols (including IV fluids and opioids). It was staffed by a nurse practitioner, medical assistant, and two registered nurses from 8 a.m. to 5 p.m.

The second transformation transferred care to the inpatient observation unit on the hospital floor with access to 12 patient beds. A sickle cell nurse practitioner sees patients for same-day appointments, conducts sick visits, performs outreach, and handles follow-up with patients. The rest of the multidisciplinary team includes hospitalists, hematologists, internists, and a social worker who performs weekly inpatient rounds and meets monthly with ED leaders and pharmacists.

With the first transformation, ED visits per patient fell from 3.67 to 2.14 a year (P less than .001), and inpatient admissions per patient fell from 1.33 to 0.63 (P less than .0001), Dr. Rizk reported.

The second transformation reduced those per-patient rates even further, to 0.47 ED visits (P less than .01) and 0.29 inpatient admissions (P less than .001), she said.

“The expansion of the service reduced admissions and ED use significantly,” Dr. Rizk said.

She added that a subanalysis of the high-utilizer subgroup showed a decrease in average total medical charges by approximately $100,000/patient per year.

Dr. Rizk reported having no relevant financial disclosures.

SOURCE: Rizk S et al. FSCDR 2019, Abstract JSCDH-D-19-00049.

FORT LAUDERDALE, FLA. — A dedicated, 24-hour, 7-day-a-week sickle cell inpatient observation unit staffed by a multidisciplinary care team significantly reduced inpatient admissions and emergency department visits per patient, according to an analysis of a Philadelphia program.

“These findings confirm the need for an individualized approach to treatment,” Sanaa Rizk, MD, director of the hereditary anemia program at Thomas Jefferson University Hospital, Philadelphia, said at the annual meeting of the Foundation for Sickle Cell Disease Research. “The potential strength of a multidisciplinary approach and personalized interventions toward high-utilizing subpopulations may offer the greatest impact.”

The study evaluated what Dr. Rizk called “the second clinical transformation” in care of sickle cell disease patients, which Thomas Jefferson University implemented in 2015. The comprehensive sickle cell center first opened in 2003, and the first transformation in November 2013 consisted of opening a four-bed sickle cell day unit to treat uncomplicated sickle cell vaso-occlusive crises with personalized pain treatment protocols (including IV fluids and opioids). It was staffed by a nurse practitioner, medical assistant, and two registered nurses from 8 a.m. to 5 p.m.

The second transformation transferred care to the inpatient observation unit on the hospital floor with access to 12 patient beds. A sickle cell nurse practitioner sees patients for same-day appointments, conducts sick visits, performs outreach, and handles follow-up with patients. The rest of the multidisciplinary team includes hospitalists, hematologists, internists, and a social worker who performs weekly inpatient rounds and meets monthly with ED leaders and pharmacists.

With the first transformation, ED visits per patient fell from 3.67 to 2.14 a year (P less than .001), and inpatient admissions per patient fell from 1.33 to 0.63 (P less than .0001), Dr. Rizk reported.

The second transformation reduced those per-patient rates even further, to 0.47 ED visits (P less than .01) and 0.29 inpatient admissions (P less than .001), she said.

“The expansion of the service reduced admissions and ED use significantly,” Dr. Rizk said.

She added that a subanalysis of the high-utilizer subgroup showed a decrease in average total medical charges by approximately $100,000/patient per year.

Dr. Rizk reported having no relevant financial disclosures.

SOURCE: Rizk S et al. FSCDR 2019, Abstract JSCDH-D-19-00049.